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The Diagnosis: Congenital Hemangioma

Surgical resection of the mass was performed at 4 months of age without complication (Figure 1). Histopathology revealed a lobular endothelial cell proliferation within a densely fibrotic stroma, multiple thin-walled vessels, and negative immunoreactivity to glucose transporter type 1 (GLUT-1)(Figures 2 and 3). Combined with the patient’s clinical history and findings on imaging (Figure 4), the most accurate diagnosis was a congenital hemangioma (CH). The mass was determined to be a noninvoluting congenital hemangioma (NICH).

A variety of vascular anomalies manifest in newborns and can be differentiated by the patient’s clinical history—particularly whether the lesion is present at birth or develops after birth. Imaging and histopathology of the lesion(s) may be utilized when clinical examination alone is not sufficient to make a diagnosis. Histopathology and immunohistochemistry further aid in differentiating the type of vascular lesion.

praslelophobririmachegatiphinukiswicravitestoclislogutrustehecleruueshapithedrodrouumagupade

tuvathutetisipusloshuthefruphesteberusajiuocinufrasluthochetrivudrilawrapinafritresothestathiswushistasiwrajisle

Overall, vascular anomalies are classified broadly into 2 categories based on their pathogenesis: tumors and malformations. Vascular tumors are composed of proliferating endothelial cells that have the potential to resolve spontaneously over time. Examples include CH, infantile hemangioma (IH), kaposiform hemangioendothelioma (KHE), and tufted angioma (TA). In contrast, vascular malformations (ie, arteriovenous malformations) are composed of dysplastic vessels with normal endothelial cell turnover and do not resolve without intervention.¹

Congenital hemangiomas are rare vascular tumors that are fully developed at birth. These tumors proliferate in utero, enabling prenatal detection via ultrasonography as early as 12 weeks’ gestation for large heterogeneous vascular masses.^2-4 Congenital hemangiomas are described as solitary, well-circumscribed, raised, violaceous lesions most commonly located in the head and neck region.^4-6 Histopathologically, they are characterized by lobules of proliferating capillaries surrounded by fibrous stroma and dysplastic vascular channels.^6,7

Congenital hemangiomas are categorized based on their postnatal involution patterns.2 Fetally involuting CH both develops and begins regression in utero and often is completely regressed at birth.⁸ Rapidly involuting CH begins regression in the first few weeks of life and usually is completely involuted by 14 months of age.6,9-11 Conversely, NICH does not regress, often requiring surgical excision due to functional and cosmetic issues.^12,13 Partially involuting CH is intermediary, beginning as rapidly involuting but not involuting completely and persisting as lesions that resemble NICH.^14-16 Although generally benign and asymptomatic, these tumors can cause transient thrombocytopenia and coagulopathy at birth, as seen in our patient.^17,18

chocrefruthumisliuedodrolubathegodithahichoneclibrujaracrichupuclawrumagatidru

tafrejuthemahitaroswotriswadodocrumobruwratuclothohospithebibrothiwewamuswuprirerotrupithuvapifrowratuwuthuswuwrapresweslitreclathefrinostutrupreuastuluswidrevipuminam

Infantile hemangioma is the most common vascular tumor of infancy.^19-21 Although a precursor lesion may be present at birth, generally this tumor becomes apparent after the first few weeks of life as a solitary vascular plaque or nodule with a predilection for the head and neck.^22-25 Once it arises, IH quickly enters a period of rapid growth, followed by a period of slower continued growth, with most reaching maximum size by 3 months.²² Thereafter, IH enters a slow period of involution (range, 3–9 years)²⁶; more recent data suggest near resolution by 5 years of age.²⁷ Infantile hemangioma is categorized based on its depth in the skin and subcutaneous tissues and can be classified as superficial, mixed, or deep.^22,24,28,29 Superficial IH appears as a red plaque and may exhibit lobulation, while deep IH can be identified as flesh-colored or blue subcutaneous masses. Mixed IH may manifest with both superficial and deep features depending on the extent of its involvement in the dermal and subcutaneous layers. The pattern of involvement may be focal, segmental, or indeterminate.²⁴ In contrast, CH typically is a solitary vascular mass with prominent telangiectases, nodules, and radiating veins.⁶ Histologically, IH is composed of proliferative plump endothelial cells that form capillaries, and the lesion stains positively for GLUT-1, whereas CH does not.³⁰

Kaposiform hemangioendothelioma is classified as a locally aggressive vascular tumor that manifests either prenatally or in early infancy.³¹ It is described as a solitary, ill-defined, firm, purple plaque most commonly located on the extremities and retroperitoneum.^32-34 Histopathologically, these lesions are characterized by dilated lymphatic channels and irregular sheets or lobules of spindle-shaped endothelial cells infiltrating the dermis and subcutaneous fat.^33,35 In contrast to CH, KHE lesions show immunoreactivity to the markers podoplanin, lymphatic vessel endothelial receptor 1, and prospero homeobox 1 protein.^36,37 Notably, 70% of these tumors are complicated by the presence of Kasabach-Merritt phenomenon, a potentially life-threatening emergency that occurs when platelets are trapped within a vascular tumor, leading to the consumption of clotting factors, intralesional bleeding, and rapid enlargement of the tumor.³² The Kasabach-Merritt phenomenon manifests clinically as microangiopathic hemolytic anemia, severe thrombocytopenia, and disseminated intravascular coagulation. ³⁸ Although CH lesions also can be associated with thrombocytopenia and coagulopathy, they generally are mild and self-limited.¹⁸

Tufted angioma is a vascular tumor that arises within the first 5 years of life as firm violaceous papules or plaques, often with associated hyperhidrosis or hypertrichosis.^39,40 Although TA grows slowly for a period of time, it eventually stabilizes and persists, rarely regressing completely.⁴¹ These tumors share many similarities with KHE, and it has been suggested that they may be part of the same spectrum. 42 As with KHE, TA lesions show immunoreactivity to the markers podoplanin, lymphatic vessel endothelial receptor 1, and prospero homeobox 1 protein, which are negative in CH.^36,37 Although TA also can be complicated by Kasabach-Merritt phenomenon, the incidence is much lower (up to 38%).^43,44 As such, TAs tend to be recognized as more superficial benign lesions. However, they still can cause notable cosmetic and functional impairment and should be monitored closely, especially in the presence of associated symptoms or complications.

Arteriovenous malformation is a vascular lesion that results from errors during the embryonic development of vascular channels.⁴⁵ Although present at birth, it may not become clinically apparent until later in life. Arteriovenous malformations enlarge postnatally, and their growth is proportional to the developmental growth of the affected individual rather than the result of endothelial proliferation.⁴⁶ In infants, AVM may manifest as a faint vascular stain that can evolve over time into a pink patch associated with a palpable thrill during adolescence. ⁴ On Doppler flow imaging, AVMs are identified as fast-flow anomalies arising from an abnormal communication between high-pressure arterial systems and low-pressure venous systems without the presence of a capillary bed.⁴⁷ One of the differentiating factors between AVM and CH is that AVMs do not regress spontaneously and tend to have high recurrence rates, even with intervention. ⁴⁸ In contrast, CH can be categorized based on its postnatal involution pattern. Another distinguishing factor is that AVMs tend to be larger and more invasive than CHs.⁴⁶ Therefore, early diagnosis and intervention are crucial to prevent complications such as bleeding, seizures, or neurologic deficits associated with AVMs.¹

The Diagnosis: Congenital Hemangioma

Surgical resection of the mass was performed at 4 months of age without complication (Figure 1). Histopathology revealed a lobular endothelial cell proliferation within a densely fibrotic stroma, multiple thin-walled vessels, and negative immunoreactivity to glucose transporter type 1 (GLUT-1)(Figures 2 and 3). Combined with the patient’s clinical history and findings on imaging (Figure 4), the most accurate diagnosis was a congenital hemangioma (CH). The mass was determined to be a noninvoluting congenital hemangioma (NICH).

A variety of vascular anomalies manifest in newborns and can be differentiated by the patient’s clinical history—particularly whether the lesion is present at birth or develops after birth. Imaging and histopathology of the lesion(s) may be utilized when clinical examination alone is not sufficient to make a diagnosis. Histopathology and immunohistochemistry further aid in differentiating the type of vascular lesion.

praslelophobririmachegatiphinukiswicravitestoclislogutrustehecleruueshapithedrodrouumagupade

tuvathutetisipusloshuthefruphesteberusajiuocinufrasluthochetrivudrilawrapinafritresothestathiswushistasiwrajisle

Overall, vascular anomalies are classified broadly into 2 categories based on their pathogenesis: tumors and malformations. Vascular tumors are composed of proliferating endothelial cells that have the potential to resolve spontaneously over time. Examples include CH, infantile hemangioma (IH), kaposiform hemangioendothelioma (KHE), and tufted angioma (TA). In contrast, vascular malformations (ie, arteriovenous malformations) are composed of dysplastic vessels with normal endothelial cell turnover and do not resolve without intervention.¹

Congenital hemangiomas are rare vascular tumors that are fully developed at birth. These tumors proliferate in utero, enabling prenatal detection via ultrasonography as early as 12 weeks’ gestation for large heterogeneous vascular masses.^2-4 Congenital hemangiomas are described as solitary, well-circumscribed, raised, violaceous lesions most commonly located in the head and neck region.^4-6 Histopathologically, they are characterized by lobules of proliferating capillaries surrounded by fibrous stroma and dysplastic vascular channels.^6,7

Congenital hemangiomas are categorized based on their postnatal involution patterns.2 Fetally involuting CH both develops and begins regression in utero and often is completely regressed at birth.⁸ Rapidly involuting CH begins regression in the first few weeks of life and usually is completely involuted by 14 months of age.6,9-11 Conversely, NICH does not regress, often requiring surgical excision due to functional and cosmetic issues.^12,13 Partially involuting CH is intermediary, beginning as rapidly involuting but not involuting completely and persisting as lesions that resemble NICH.^14-16 Although generally benign and asymptomatic, these tumors can cause transient thrombocytopenia and coagulopathy at birth, as seen in our patient.^17,18

chocrefruthumisliuedodrolubathegodithahichoneclibrujaracrichupuclawrumagatidru

tafrejuthemahitaroswotriswadodocrumobruwratuclothohospithebibrothiwewamuswuprirerotrupithuvapifrowratuwuthuswuwrapresweslitreclathefrinostutrupreuastuluswidrevipuminam

Infantile hemangioma is the most common vascular tumor of infancy.^19-21 Although a precursor lesion may be present at birth, generally this tumor becomes apparent after the first few weeks of life as a solitary vascular plaque or nodule with a predilection for the head and neck.^22-25 Once it arises, IH quickly enters a period of rapid growth, followed by a period of slower continued growth, with most reaching maximum size by 3 months.²² Thereafter, IH enters a slow period of involution (range, 3–9 years)²⁶; more recent data suggest near resolution by 5 years of age.²⁷ Infantile hemangioma is categorized based on its depth in the skin and subcutaneous tissues and can be classified as superficial, mixed, or deep.^22,24,28,29 Superficial IH appears as a red plaque and may exhibit lobulation, while deep IH can be identified as flesh-colored or blue subcutaneous masses. Mixed IH may manifest with both superficial and deep features depending on the extent of its involvement in the dermal and subcutaneous layers. The pattern of involvement may be focal, segmental, or indeterminate.²⁴ In contrast, CH typically is a solitary vascular mass with prominent telangiectases, nodules, and radiating veins.⁶ Histologically, IH is composed of proliferative plump endothelial cells that form capillaries, and the lesion stains positively for GLUT-1, whereas CH does not.³⁰

Kaposiform hemangioendothelioma is classified as a locally aggressive vascular tumor that manifests either prenatally or in early infancy.³¹ It is described as a solitary, ill-defined, firm, purple plaque most commonly located on the extremities and retroperitoneum.^32-34 Histopathologically, these lesions are characterized by dilated lymphatic channels and irregular sheets or lobules of spindle-shaped endothelial cells infiltrating the dermis and subcutaneous fat.^33,35 In contrast to CH, KHE lesions show immunoreactivity to the markers podoplanin, lymphatic vessel endothelial receptor 1, and prospero homeobox 1 protein.^36,37 Notably, 70% of these tumors are complicated by the presence of Kasabach-Merritt phenomenon, a potentially life-threatening emergency that occurs when platelets are trapped within a vascular tumor, leading to the consumption of clotting factors, intralesional bleeding, and rapid enlargement of the tumor.³² The Kasabach-Merritt phenomenon manifests clinically as microangiopathic hemolytic anemia, severe thrombocytopenia, and disseminated intravascular coagulation. ³⁸ Although CH lesions also can be associated with thrombocytopenia and coagulopathy, they generally are mild and self-limited.¹⁸

Tufted angioma is a vascular tumor that arises within the first 5 years of life as firm violaceous papules or plaques, often with associated hyperhidrosis or hypertrichosis.^39,40 Although TA grows slowly for a period of time, it eventually stabilizes and persists, rarely regressing completely.⁴¹ These tumors share many similarities with KHE, and it has been suggested that they may be part of the same spectrum. 42 As with KHE, TA lesions show immunoreactivity to the markers podoplanin, lymphatic vessel endothelial receptor 1, and prospero homeobox 1 protein, which are negative in CH.^36,37 Although TA also can be complicated by Kasabach-Merritt phenomenon, the incidence is much lower (up to 38%).^43,44 As such, TAs tend to be recognized as more superficial benign lesions. However, they still can cause notable cosmetic and functional impairment and should be monitored closely, especially in the presence of associated symptoms or complications.

Arteriovenous malformation is a vascular lesion that results from errors during the embryonic development of vascular channels.⁴⁵ Although present at birth, it may not become clinically apparent until later in life. Arteriovenous malformations enlarge postnatally, and their growth is proportional to the developmental growth of the affected individual rather than the result of endothelial proliferation.⁴⁶ In infants, AVM may manifest as a faint vascular stain that can evolve over time into a pink patch associated with a palpable thrill during adolescence. ⁴ On Doppler flow imaging, AVMs are identified as fast-flow anomalies arising from an abnormal communication between high-pressure arterial systems and low-pressure venous systems without the presence of a capillary bed.⁴⁷ One of the differentiating factors between AVM and CH is that AVMs do not regress spontaneously and tend to have high recurrence rates, even with intervention. ⁴⁸ In contrast, CH can be categorized based on its postnatal involution pattern. Another distinguishing factor is that AVMs tend to be larger and more invasive than CHs.⁴⁶ Therefore, early diagnosis and intervention are crucial to prevent complications such as bleeding, seizures, or neurologic deficits associated with AVMs.¹

The Diagnosis: Congenital Hemangioma

Surgical resection of the mass was performed at 4 months of age without complication (Figure 1). Histopathology revealed a lobular endothelial cell proliferation within a densely fibrotic stroma, multiple thin-walled vessels, and negative immunoreactivity to glucose transporter type 1 (GLUT-1)(Figures 2 and 3). Combined with the patient’s clinical history and findings on imaging (Figure 4), the most accurate diagnosis was a congenital hemangioma (CH). The mass was determined to be a noninvoluting congenital hemangioma (NICH).

A variety of vascular anomalies manifest in newborns and can be differentiated by the patient’s clinical history—particularly whether the lesion is present at birth or develops after birth. Imaging and histopathology of the lesion(s) may be utilized when clinical examination alone is not sufficient to make a diagnosis. Histopathology and immunohistochemistry further aid in differentiating the type of vascular lesion.

praslelophobririmachegatiphinukiswicravitestoclislogutrustehecleruueshapithedrodrouumagupade

tuvathutetisipusloshuthefruphesteberusajiuocinufrasluthochetrivudrilawrapinafritresothestathiswushistasiwrajisle

Overall, vascular anomalies are classified broadly into 2 categories based on their pathogenesis: tumors and malformations. Vascular tumors are composed of proliferating endothelial cells that have the potential to resolve spontaneously over time. Examples include CH, infantile hemangioma (IH), kaposiform hemangioendothelioma (KHE), and tufted angioma (TA). In contrast, vascular malformations (ie, arteriovenous malformations) are composed of dysplastic vessels with normal endothelial cell turnover and do not resolve without intervention.¹

Congenital hemangiomas are rare vascular tumors that are fully developed at birth. These tumors proliferate in utero, enabling prenatal detection via ultrasonography as early as 12 weeks’ gestation for large heterogeneous vascular masses.^2-4 Congenital hemangiomas are described as solitary, well-circumscribed, raised, violaceous lesions most commonly located in the head and neck region.^4-6 Histopathologically, they are characterized by lobules of proliferating capillaries surrounded by fibrous stroma and dysplastic vascular channels.^6,7

Congenital hemangiomas are categorized based on their postnatal involution patterns.2 Fetally involuting CH both develops and begins regression in utero and often is completely regressed at birth.⁸ Rapidly involuting CH begins regression in the first few weeks of life and usually is completely involuted by 14 months of age.6,9-11 Conversely, NICH does not regress, often requiring surgical excision due to functional and cosmetic issues.^12,13 Partially involuting CH is intermediary, beginning as rapidly involuting but not involuting completely and persisting as lesions that resemble NICH.^14-16 Although generally benign and asymptomatic, these tumors can cause transient thrombocytopenia and coagulopathy at birth, as seen in our patient.^17,18

chocrefruthumisliuedodrolubathegodithahichoneclibrujaracrichupuclawrumagatidru

tafrejuthemahitaroswotriswadodocrumobruwratuclothohospithebibrothiwewamuswuprirerotrupithuvapifrowratuwuthuswuwrapresweslitreclathefrinostutrupreuastuluswidrevipuminam

Infantile hemangioma is the most common vascular tumor of infancy.^19-21 Although a precursor lesion may be present at birth, generally this tumor becomes apparent after the first few weeks of life as a solitary vascular plaque or nodule with a predilection for the head and neck.^22-25 Once it arises, IH quickly enters a period of rapid growth, followed by a period of slower continued growth, with most reaching maximum size by 3 months.²² Thereafter, IH enters a slow period of involution (range, 3–9 years)²⁶; more recent data suggest near resolution by 5 years of age.²⁷ Infantile hemangioma is categorized based on its depth in the skin and subcutaneous tissues and can be classified as superficial, mixed, or deep.^22,24,28,29 Superficial IH appears as a red plaque and may exhibit lobulation, while deep IH can be identified as flesh-colored or blue subcutaneous masses. Mixed IH may manifest with both superficial and deep features depending on the extent of its involvement in the dermal and subcutaneous layers. The pattern of involvement may be focal, segmental, or indeterminate.²⁴ In contrast, CH typically is a solitary vascular mass with prominent telangiectases, nodules, and radiating veins.⁶ Histologically, IH is composed of proliferative plump endothelial cells that form capillaries, and the lesion stains positively for GLUT-1, whereas CH does not.³⁰

Kaposiform hemangioendothelioma is classified as a locally aggressive vascular tumor that manifests either prenatally or in early infancy.³¹ It is described as a solitary, ill-defined, firm, purple plaque most commonly located on the extremities and retroperitoneum.^32-34 Histopathologically, these lesions are characterized by dilated lymphatic channels and irregular sheets or lobules of spindle-shaped endothelial cells infiltrating the dermis and subcutaneous fat.^33,35 In contrast to CH, KHE lesions show immunoreactivity to the markers podoplanin, lymphatic vessel endothelial receptor 1, and prospero homeobox 1 protein.^36,37 Notably, 70% of these tumors are complicated by the presence of Kasabach-Merritt phenomenon, a potentially life-threatening emergency that occurs when platelets are trapped within a vascular tumor, leading to the consumption of clotting factors, intralesional bleeding, and rapid enlargement of the tumor.³² The Kasabach-Merritt phenomenon manifests clinically as microangiopathic hemolytic anemia, severe thrombocytopenia, and disseminated intravascular coagulation. ³⁸ Although CH lesions also can be associated with thrombocytopenia and coagulopathy, they generally are mild and self-limited.¹⁸

Tufted angioma is a vascular tumor that arises within the first 5 years of life as firm violaceous papules or plaques, often with associated hyperhidrosis or hypertrichosis.^39,40 Although TA grows slowly for a period of time, it eventually stabilizes and persists, rarely regressing completely.⁴¹ These tumors share many similarities with KHE, and it has been suggested that they may be part of the same spectrum. 42 As with KHE, TA lesions show immunoreactivity to the markers podoplanin, lymphatic vessel endothelial receptor 1, and prospero homeobox 1 protein, which are negative in CH.^36,37 Although TA also can be complicated by Kasabach-Merritt phenomenon, the incidence is much lower (up to 38%).^43,44 As such, TAs tend to be recognized as more superficial benign lesions. However, they still can cause notable cosmetic and functional impairment and should be monitored closely, especially in the presence of associated symptoms or complications.

Arteriovenous malformation is a vascular lesion that results from errors during the embryonic development of vascular channels.⁴⁵ Although present at birth, it may not become clinically apparent until later in life. Arteriovenous malformations enlarge postnatally, and their growth is proportional to the developmental growth of the affected individual rather than the result of endothelial proliferation.⁴⁶ In infants, AVM may manifest as a faint vascular stain that can evolve over time into a pink patch associated with a palpable thrill during adolescence. ⁴ On Doppler flow imaging, AVMs are identified as fast-flow anomalies arising from an abnormal communication between high-pressure arterial systems and low-pressure venous systems without the presence of a capillary bed.⁴⁷ One of the differentiating factors between AVM and CH is that AVMs do not regress spontaneously and tend to have high recurrence rates, even with intervention. ⁴⁸ In contrast, CH can be categorized based on its postnatal involution pattern. Another distinguishing factor is that AVMs tend to be larger and more invasive than CHs.⁴⁶ Therefore, early diagnosis and intervention are crucial to prevent complications such as bleeding, seizures, or neurologic deficits associated with AVMs.¹

The Diagnosis: Trichodysplasia Spinulosa

A diagnosis of trichodysplasia spinulosa (TS) was rendered based on the clinical presentation— diffuse folliculocentric keratotic papules with spicules and leonine facies—coinciding with cyclosporine initiation. Biopsy was deferred given the classic presentation. The patient applied cidofovir cream 1% daily to lesions on the face. She was prescribed leflunomide 10 mg daily, which was later increased to 20 mg daily, for polyarthritis associated with systemic lupus erythematosus (SLE). Her transplant physician increased her cyclosporine dosage from 50 mg twice daily to 75 mg each morning and 50 mg each evening due to rising creatinine and donor-specific antibodies from the renal transplant. The patient’s TS eruption mildly improved 3 months after the cyclosporine dose was increased. To treat persistent lesions, oral valganciclovir was started at 450 mg once daily and later reduced to every other day due to leukopenia. After 3 months of taking valganciclovir 450 mg every other day, the patient’s TS rash resolved.

Trichodysplasia spinulosa is a rare condition caused by TS-associated polyomavirus¹ that may arise in immunosuppressed patients, especially in solid organ transplant recipients.² It is characterized by spiculated and folliculocentric papules, mainly on the face,¹ and often is diagnosed clinically, but if the presentation is not classic, a skin biopsy can help to confirm the diagnosis. Because of its rarity, treatment options do not have well-established efficacy¹ but include reducing immunosuppression and using the antivirals cidofovir¹ or valganciclovir³ to treat the polyomavirus. Topical retinoids,³ photodynamic therapy, ⁴ and leflunomide⁵ also may be effective.

Although the typical approach to treating TS is to reduce immunosuppression, this was not an option for our patient, as she required increased immunosuppression for the treatment of active SLE. Leflunomide can be used for SLE, and in some reports it can be effective for BK viremia in kidney transplant recipients⁵ as well as for TS in solid organ transplant recipients.⁶ Our patient showed improvement of the TS, BK viremia, renal function, and SLE while taking leflunomide and valganciclovir.

The differential diagnosis includes keratosis pilaris, lichen nitidus, scleromyxedema, and trichostasis spinulosa. Keratosis pilaris is a benign skin disorder consisting of patches of keratotic papules with varying degrees of erythema and inflammation that are formed by dead keratinocytes plugging the hair follicles and often are seen on the extremities, face, and trunk.⁷ Our patient’s papules were flesh colored with no notable background erythema. Additionally, the presence of leonine facies was atypical for keratosis pilaris. Acids, steroids, and kinase inhibitors are the most frequently used treatments for keratosis pilaris.⁸

Lichen nitidus is a skin condition characterized by multiple shiny, dome-shaped, flesh-colored papules usually found on the flexor surfaces of the arms, anterior trunk, and genitalia. It is mostly asymptomatic, but patients may experience pruritus. Most cases occur in children and young adults, with no obvious racial or gender predilection. The diagnosis often is clinical, but biopsy shows downward enlargement of the epidermal rete ridges surrounding a focal inflammatory infiltrate, known as a ball-in-claw configuration.^9-11 Lichen nitidus spontaneously resolves within a few years without treatment. Our patient did have flesh-colored papules on the arms and chest; however, major involvement of the face is not typical in lichen nitidus. Additionally, fine white spicules would not be seen in lichen nitidus. For severe generalized lichen nitidus, treatment options include topical corticosteroids, topical calcineurin inhibitors, oral antihistamines, or UV light to decrease inflammation.^9-11

Scleromyxedema is a rare condition involving the deposition of mucinous material in the papillary dermis to cause the formation of infiltrative skin lesions.¹² It is thought that immunoglobulins and cytokines secreted by inflammatory cells lead to the synthesis of glycosaminoglycans, which then causes deposition of mucin in the dermis.¹³ The classic cutaneous features of scleromyxedema include waxy indurated papules and plaques with skin thickening throughout the entire body.¹² Our patient’s papules were not notably indurated and involved less than 50% of the total body surface area. An important diagnostic feature of scleromyxedema is monoclonal gammopathy, which our patient did not have. Intravenous immunoglobulin is the first-line treatment of scleromyxedema, and second-line treatments include systemic corticosteroids and thalidomide.¹⁴ Our patient also did not require treatment with intravenous immunoglobulin, as her rash improved with antiviral medication, which would not address the underlying inflammatory processes associated with scleromyxedema.

Trichostasis spinulosa is a rare hair follicle disorder consisting of dark, spiny, hyperkeratotic follicular papules that can be found on the extremities and face, especially the nose. The etiology is unknown, but risk factors include congenital dysplasia of hair follicles; exposure to UV light, dust, oil, or heat; chronic renal failure; Malassezia yeast; and Propionibacterium acnes. Adult women with darker skin types are most commonly affected by trichostasis spinulosa.^15,16 Our patient fit the epidemiologic demographic of trichostasis spinulosa, including a history of chronic renal failure. Her rash covered the face, nose, and arms; however, the papules were flesh colored, whereas trichostasis spinulosa would appear as black papules. Furthermore, yeast and bacterial infections have been identified as potential agents associated with trichostasis spinulosa; therefore, antiviral agents would be ineffective. Viable treatments for trichostasis spinulosa include emollients, topical keratolytic agents, retinoic acids, and lasers to remove abnormal hair follicles.^15,16

The Diagnosis: Trichodysplasia Spinulosa

A diagnosis of trichodysplasia spinulosa (TS) was rendered based on the clinical presentation— diffuse folliculocentric keratotic papules with spicules and leonine facies—coinciding with cyclosporine initiation. Biopsy was deferred given the classic presentation. The patient applied cidofovir cream 1% daily to lesions on the face. She was prescribed leflunomide 10 mg daily, which was later increased to 20 mg daily, for polyarthritis associated with systemic lupus erythematosus (SLE). Her transplant physician increased her cyclosporine dosage from 50 mg twice daily to 75 mg each morning and 50 mg each evening due to rising creatinine and donor-specific antibodies from the renal transplant. The patient’s TS eruption mildly improved 3 months after the cyclosporine dose was increased. To treat persistent lesions, oral valganciclovir was started at 450 mg once daily and later reduced to every other day due to leukopenia. After 3 months of taking valganciclovir 450 mg every other day, the patient’s TS rash resolved.

Trichodysplasia spinulosa is a rare condition caused by TS-associated polyomavirus¹ that may arise in immunosuppressed patients, especially in solid organ transplant recipients.² It is characterized by spiculated and folliculocentric papules, mainly on the face,¹ and often is diagnosed clinically, but if the presentation is not classic, a skin biopsy can help to confirm the diagnosis. Because of its rarity, treatment options do not have well-established efficacy¹ but include reducing immunosuppression and using the antivirals cidofovir¹ or valganciclovir³ to treat the polyomavirus. Topical retinoids,³ photodynamic therapy, ⁴ and leflunomide⁵ also may be effective.

Although the typical approach to treating TS is to reduce immunosuppression, this was not an option for our patient, as she required increased immunosuppression for the treatment of active SLE. Leflunomide can be used for SLE, and in some reports it can be effective for BK viremia in kidney transplant recipients⁵ as well as for TS in solid organ transplant recipients.⁶ Our patient showed improvement of the TS, BK viremia, renal function, and SLE while taking leflunomide and valganciclovir.

The differential diagnosis includes keratosis pilaris, lichen nitidus, scleromyxedema, and trichostasis spinulosa. Keratosis pilaris is a benign skin disorder consisting of patches of keratotic papules with varying degrees of erythema and inflammation that are formed by dead keratinocytes plugging the hair follicles and often are seen on the extremities, face, and trunk.⁷ Our patient’s papules were flesh colored with no notable background erythema. Additionally, the presence of leonine facies was atypical for keratosis pilaris. Acids, steroids, and kinase inhibitors are the most frequently used treatments for keratosis pilaris.⁸

Lichen nitidus is a skin condition characterized by multiple shiny, dome-shaped, flesh-colored papules usually found on the flexor surfaces of the arms, anterior trunk, and genitalia. It is mostly asymptomatic, but patients may experience pruritus. Most cases occur in children and young adults, with no obvious racial or gender predilection. The diagnosis often is clinical, but biopsy shows downward enlargement of the epidermal rete ridges surrounding a focal inflammatory infiltrate, known as a ball-in-claw configuration.^9-11 Lichen nitidus spontaneously resolves within a few years without treatment. Our patient did have flesh-colored papules on the arms and chest; however, major involvement of the face is not typical in lichen nitidus. Additionally, fine white spicules would not be seen in lichen nitidus. For severe generalized lichen nitidus, treatment options include topical corticosteroids, topical calcineurin inhibitors, oral antihistamines, or UV light to decrease inflammation.^9-11

Scleromyxedema is a rare condition involving the deposition of mucinous material in the papillary dermis to cause the formation of infiltrative skin lesions.¹² It is thought that immunoglobulins and cytokines secreted by inflammatory cells lead to the synthesis of glycosaminoglycans, which then causes deposition of mucin in the dermis.¹³ The classic cutaneous features of scleromyxedema include waxy indurated papules and plaques with skin thickening throughout the entire body.¹² Our patient’s papules were not notably indurated and involved less than 50% of the total body surface area. An important diagnostic feature of scleromyxedema is monoclonal gammopathy, which our patient did not have. Intravenous immunoglobulin is the first-line treatment of scleromyxedema, and second-line treatments include systemic corticosteroids and thalidomide.¹⁴ Our patient also did not require treatment with intravenous immunoglobulin, as her rash improved with antiviral medication, which would not address the underlying inflammatory processes associated with scleromyxedema.

Trichostasis spinulosa is a rare hair follicle disorder consisting of dark, spiny, hyperkeratotic follicular papules that can be found on the extremities and face, especially the nose. The etiology is unknown, but risk factors include congenital dysplasia of hair follicles; exposure to UV light, dust, oil, or heat; chronic renal failure; Malassezia yeast; and Propionibacterium acnes. Adult women with darker skin types are most commonly affected by trichostasis spinulosa.^15,16 Our patient fit the epidemiologic demographic of trichostasis spinulosa, including a history of chronic renal failure. Her rash covered the face, nose, and arms; however, the papules were flesh colored, whereas trichostasis spinulosa would appear as black papules. Furthermore, yeast and bacterial infections have been identified as potential agents associated with trichostasis spinulosa; therefore, antiviral agents would be ineffective. Viable treatments for trichostasis spinulosa include emollients, topical keratolytic agents, retinoic acids, and lasers to remove abnormal hair follicles.^15,16

The Diagnosis: Trichodysplasia Spinulosa

A diagnosis of trichodysplasia spinulosa (TS) was rendered based on the clinical presentation— diffuse folliculocentric keratotic papules with spicules and leonine facies—coinciding with cyclosporine initiation. Biopsy was deferred given the classic presentation. The patient applied cidofovir cream 1% daily to lesions on the face. She was prescribed leflunomide 10 mg daily, which was later increased to 20 mg daily, for polyarthritis associated with systemic lupus erythematosus (SLE). Her transplant physician increased her cyclosporine dosage from 50 mg twice daily to 75 mg each morning and 50 mg each evening due to rising creatinine and donor-specific antibodies from the renal transplant. The patient’s TS eruption mildly improved 3 months after the cyclosporine dose was increased. To treat persistent lesions, oral valganciclovir was started at 450 mg once daily and later reduced to every other day due to leukopenia. After 3 months of taking valganciclovir 450 mg every other day, the patient’s TS rash resolved.

Trichodysplasia spinulosa is a rare condition caused by TS-associated polyomavirus¹ that may arise in immunosuppressed patients, especially in solid organ transplant recipients.² It is characterized by spiculated and folliculocentric papules, mainly on the face,¹ and often is diagnosed clinically, but if the presentation is not classic, a skin biopsy can help to confirm the diagnosis. Because of its rarity, treatment options do not have well-established efficacy¹ but include reducing immunosuppression and using the antivirals cidofovir¹ or valganciclovir³ to treat the polyomavirus. Topical retinoids,³ photodynamic therapy, ⁴ and leflunomide⁵ also may be effective.

Although the typical approach to treating TS is to reduce immunosuppression, this was not an option for our patient, as she required increased immunosuppression for the treatment of active SLE. Leflunomide can be used for SLE, and in some reports it can be effective for BK viremia in kidney transplant recipients⁵ as well as for TS in solid organ transplant recipients.⁶ Our patient showed improvement of the TS, BK viremia, renal function, and SLE while taking leflunomide and valganciclovir.

The differential diagnosis includes keratosis pilaris, lichen nitidus, scleromyxedema, and trichostasis spinulosa. Keratosis pilaris is a benign skin disorder consisting of patches of keratotic papules with varying degrees of erythema and inflammation that are formed by dead keratinocytes plugging the hair follicles and often are seen on the extremities, face, and trunk.⁷ Our patient’s papules were flesh colored with no notable background erythema. Additionally, the presence of leonine facies was atypical for keratosis pilaris. Acids, steroids, and kinase inhibitors are the most frequently used treatments for keratosis pilaris.⁸

Lichen nitidus is a skin condition characterized by multiple shiny, dome-shaped, flesh-colored papules usually found on the flexor surfaces of the arms, anterior trunk, and genitalia. It is mostly asymptomatic, but patients may experience pruritus. Most cases occur in children and young adults, with no obvious racial or gender predilection. The diagnosis often is clinical, but biopsy shows downward enlargement of the epidermal rete ridges surrounding a focal inflammatory infiltrate, known as a ball-in-claw configuration.^9-11 Lichen nitidus spontaneously resolves within a few years without treatment. Our patient did have flesh-colored papules on the arms and chest; however, major involvement of the face is not typical in lichen nitidus. Additionally, fine white spicules would not be seen in lichen nitidus. For severe generalized lichen nitidus, treatment options include topical corticosteroids, topical calcineurin inhibitors, oral antihistamines, or UV light to decrease inflammation.^9-11

Scleromyxedema is a rare condition involving the deposition of mucinous material in the papillary dermis to cause the formation of infiltrative skin lesions.¹² It is thought that immunoglobulins and cytokines secreted by inflammatory cells lead to the synthesis of glycosaminoglycans, which then causes deposition of mucin in the dermis.¹³ The classic cutaneous features of scleromyxedema include waxy indurated papules and plaques with skin thickening throughout the entire body.¹² Our patient’s papules were not notably indurated and involved less than 50% of the total body surface area. An important diagnostic feature of scleromyxedema is monoclonal gammopathy, which our patient did not have. Intravenous immunoglobulin is the first-line treatment of scleromyxedema, and second-line treatments include systemic corticosteroids and thalidomide.¹⁴ Our patient also did not require treatment with intravenous immunoglobulin, as her rash improved with antiviral medication, which would not address the underlying inflammatory processes associated with scleromyxedema.

Trichostasis spinulosa is a rare hair follicle disorder consisting of dark, spiny, hyperkeratotic follicular papules that can be found on the extremities and face, especially the nose. The etiology is unknown, but risk factors include congenital dysplasia of hair follicles; exposure to UV light, dust, oil, or heat; chronic renal failure; Malassezia yeast; and Propionibacterium acnes. Adult women with darker skin types are most commonly affected by trichostasis spinulosa.^15,16 Our patient fit the epidemiologic demographic of trichostasis spinulosa, including a history of chronic renal failure. Her rash covered the face, nose, and arms; however, the papules were flesh colored, whereas trichostasis spinulosa would appear as black papules. Furthermore, yeast and bacterial infections have been identified as potential agents associated with trichostasis spinulosa; therefore, antiviral agents would be ineffective. Viable treatments for trichostasis spinulosa include emollients, topical keratolytic agents, retinoic acids, and lasers to remove abnormal hair follicles.^15,16

The Diagnosis: Erythema Ab Igne

Based on the patient's long-standing history of back pain treated with heating pads as well as the normal laboratory findings and skin examination, a diagnosis of erythema ab igne (EAI) was made.

Erythema ab igne presents as reticulated brownish erythema or hyperpigmentation on sites exposed to prolonged use of heat sources such as heating pads, laptops, and space heaters. Erythema ab igne most commonly affects the lower back, thighs, or legs^1-6; however, EAI can appear on atypical sites such as the forehead and eyebrows due to newer technology (eg, virtual reality headsets).⁷ The level of heat required for EAI to occur is below the threshold for thermal burns (<45 °C [113 °F]).1 Erythema ab igne can occur at any age, and woman are more commonly affected than men.⁸ The pathophysiology currently is unknown; however, recurrent and prolonged heat exposure may damage superficial vessels. As a result, hemosiderin accumulates in the skin, and hyperpigmentation subsequently occurs.⁹

The diagnosis of EAI is clinical, and early stages of the rash present as blanching reticulated erythema in areas associated with heat exposure. If the offending source of heat is not removed, EAI can progress to nonblanching, fixed, hyperpigmented plaques with skin atrophy, bullae, or hyperkeratosis. Patients often are asymptomatic; however, mild burning may occur.² Histopathology reveals cellular atypia, epidermal atrophy, dilation of dermal blood vessels, a minute inflammatory infiltrate, and keratinocyte apoptosis.¹⁰ Skin biopsy may be necessary in cases of suspected malignancy due to chronic heat exposure. Lesions that ulcerate or evolve should raise suspicion for malignancy.¹¹ Squamous cell carcinoma is the most common malignancy associated with EAI; other malignancies that may manifest include basal cell carcinoma, Merkel cell carcinoma, or cutaneous marginal zone lymphoma.^2,12-14

Erythema ab igne often is mistaken for livedo reticularis, which appears more erythematous without hyperpigmentation or epidermal changes and may be associated with a pathologic state.¹⁵ The differential diagnosis in our patient, who was in her 40s with a history of fatigue and joint pain, included livedo reticularis associated with lupus; however, the history of heating pad use, normal laboratory findings, and presence of epidermal changes suggested EAI. Lupus typically affects the hand and knee joints.¹⁶ Additionally, livedo reticularis more commonly appears on the legs.¹⁵

Other differentials for EAI include livedo racemosa, cutaneous T-cell lymphoma, and cutis marmorata. Livedo racemosa presents with broken rings of erythema in young to middle-aged women and primarily affects the trunk and proximal limbs. It is associated with an underlying condition such as polyarteritis nodosa and less commonly with lupus erythematosus with antiphospholipid or Sneddon syndrome.^15,17 Cutaneous T-cell lymphoma typically manifests with poikilodermatous patches larger than the palm, especially in covered areas of skin.¹⁸ Cutis marmorata is transient and temperature dependent.⁹

The key intervention for EAI is removal of the offending heat source.² Patients should be counseled that the erythema and hyperpigmentation may take months to years to resolve. Topical hydroquinone or tretinoin may be used in cases of persistent hyperpigmentation.¹⁹ Patients who continue to use heating pads for long-standing pain should be advised to limit their use to short intervals without occlusion. If malignancy is a concern, a biopsy should be performed.²⁰

The Diagnosis: Erythema Ab Igne

Based on the patient's long-standing history of back pain treated with heating pads as well as the normal laboratory findings and skin examination, a diagnosis of erythema ab igne (EAI) was made.

Erythema ab igne presents as reticulated brownish erythema or hyperpigmentation on sites exposed to prolonged use of heat sources such as heating pads, laptops, and space heaters. Erythema ab igne most commonly affects the lower back, thighs, or legs^1-6; however, EAI can appear on atypical sites such as the forehead and eyebrows due to newer technology (eg, virtual reality headsets).⁷ The level of heat required for EAI to occur is below the threshold for thermal burns (<45 °C [113 °F]).1 Erythema ab igne can occur at any age, and woman are more commonly affected than men.⁸ The pathophysiology currently is unknown; however, recurrent and prolonged heat exposure may damage superficial vessels. As a result, hemosiderin accumulates in the skin, and hyperpigmentation subsequently occurs.⁹

The diagnosis of EAI is clinical, and early stages of the rash present as blanching reticulated erythema in areas associated with heat exposure. If the offending source of heat is not removed, EAI can progress to nonblanching, fixed, hyperpigmented plaques with skin atrophy, bullae, or hyperkeratosis. Patients often are asymptomatic; however, mild burning may occur.² Histopathology reveals cellular atypia, epidermal atrophy, dilation of dermal blood vessels, a minute inflammatory infiltrate, and keratinocyte apoptosis.¹⁰ Skin biopsy may be necessary in cases of suspected malignancy due to chronic heat exposure. Lesions that ulcerate or evolve should raise suspicion for malignancy.¹¹ Squamous cell carcinoma is the most common malignancy associated with EAI; other malignancies that may manifest include basal cell carcinoma, Merkel cell carcinoma, or cutaneous marginal zone lymphoma.^2,12-14

Erythema ab igne often is mistaken for livedo reticularis, which appears more erythematous without hyperpigmentation or epidermal changes and may be associated with a pathologic state.¹⁵ The differential diagnosis in our patient, who was in her 40s with a history of fatigue and joint pain, included livedo reticularis associated with lupus; however, the history of heating pad use, normal laboratory findings, and presence of epidermal changes suggested EAI. Lupus typically affects the hand and knee joints.¹⁶ Additionally, livedo reticularis more commonly appears on the legs.¹⁵

Other differentials for EAI include livedo racemosa, cutaneous T-cell lymphoma, and cutis marmorata. Livedo racemosa presents with broken rings of erythema in young to middle-aged women and primarily affects the trunk and proximal limbs. It is associated with an underlying condition such as polyarteritis nodosa and less commonly with lupus erythematosus with antiphospholipid or Sneddon syndrome.^15,17 Cutaneous T-cell lymphoma typically manifests with poikilodermatous patches larger than the palm, especially in covered areas of skin.¹⁸ Cutis marmorata is transient and temperature dependent.⁹

The key intervention for EAI is removal of the offending heat source.² Patients should be counseled that the erythema and hyperpigmentation may take months to years to resolve. Topical hydroquinone or tretinoin may be used in cases of persistent hyperpigmentation.¹⁹ Patients who continue to use heating pads for long-standing pain should be advised to limit their use to short intervals without occlusion. If malignancy is a concern, a biopsy should be performed.²⁰

The Diagnosis: Erythema Ab Igne

Based on the patient's long-standing history of back pain treated with heating pads as well as the normal laboratory findings and skin examination, a diagnosis of erythema ab igne (EAI) was made.

Erythema ab igne presents as reticulated brownish erythema or hyperpigmentation on sites exposed to prolonged use of heat sources such as heating pads, laptops, and space heaters. Erythema ab igne most commonly affects the lower back, thighs, or legs^1-6; however, EAI can appear on atypical sites such as the forehead and eyebrows due to newer technology (eg, virtual reality headsets).⁷ The level of heat required for EAI to occur is below the threshold for thermal burns (<45 °C [113 °F]).1 Erythema ab igne can occur at any age, and woman are more commonly affected than men.⁸ The pathophysiology currently is unknown; however, recurrent and prolonged heat exposure may damage superficial vessels. As a result, hemosiderin accumulates in the skin, and hyperpigmentation subsequently occurs.⁹

The diagnosis of EAI is clinical, and early stages of the rash present as blanching reticulated erythema in areas associated with heat exposure. If the offending source of heat is not removed, EAI can progress to nonblanching, fixed, hyperpigmented plaques with skin atrophy, bullae, or hyperkeratosis. Patients often are asymptomatic; however, mild burning may occur.² Histopathology reveals cellular atypia, epidermal atrophy, dilation of dermal blood vessels, a minute inflammatory infiltrate, and keratinocyte apoptosis.¹⁰ Skin biopsy may be necessary in cases of suspected malignancy due to chronic heat exposure. Lesions that ulcerate or evolve should raise suspicion for malignancy.¹¹ Squamous cell carcinoma is the most common malignancy associated with EAI; other malignancies that may manifest include basal cell carcinoma, Merkel cell carcinoma, or cutaneous marginal zone lymphoma.^2,12-14

Erythema ab igne often is mistaken for livedo reticularis, which appears more erythematous without hyperpigmentation or epidermal changes and may be associated with a pathologic state.¹⁵ The differential diagnosis in our patient, who was in her 40s with a history of fatigue and joint pain, included livedo reticularis associated with lupus; however, the history of heating pad use, normal laboratory findings, and presence of epidermal changes suggested EAI. Lupus typically affects the hand and knee joints.¹⁶ Additionally, livedo reticularis more commonly appears on the legs.¹⁵

Other differentials for EAI include livedo racemosa, cutaneous T-cell lymphoma, and cutis marmorata. Livedo racemosa presents with broken rings of erythema in young to middle-aged women and primarily affects the trunk and proximal limbs. It is associated with an underlying condition such as polyarteritis nodosa and less commonly with lupus erythematosus with antiphospholipid or Sneddon syndrome.^15,17 Cutaneous T-cell lymphoma typically manifests with poikilodermatous patches larger than the palm, especially in covered areas of skin.¹⁸ Cutis marmorata is transient and temperature dependent.⁹

The key intervention for EAI is removal of the offending heat source.² Patients should be counseled that the erythema and hyperpigmentation may take months to years to resolve. Topical hydroquinone or tretinoin may be used in cases of persistent hyperpigmentation.¹⁹ Patients who continue to use heating pads for long-standing pain should be advised to limit their use to short intervals without occlusion. If malignancy is a concern, a biopsy should be performed.²⁰

The Diagnosis: Subungual Exostosis

Subungual exostosis should be considered as a possible cause of an exophytic subungual nodule in a young active female. In our patient, the involvement of the great toe was a clue, as the hallux is the most common location of subungual exostosis. The patient’s age and sex also were supportive, as subungual exostosis is most common in female children and adolescents— particularly those who are active, as trauma is thought to play a possible role in development of this benign tumor.^1-3 Radiography is the preferred modality for diagnosis; in our case, it showed a trabecular bony overgrowth (Figure 1), which confirmed the diagnosis. Subungual exostosis is a rare, benign, osteocartilaginous tumor of trabecular bone. The etiology is unknown but is hypothesized to be related to trauma, infection, or activation of a cartilaginous cyst.^1,3 The subungual nodule may be asymptomatic or painful. Disruption and elevation of the nail plate is common.⁴ The differential diagnosis includes amelanotic melanoma, fibroma, fibrokeratoma, osteochondroma, pyogenic granuloma, squamous cell carcinoma, glomus tumor, and verruca vulgaris, among others.⁵

doswicubarasofrocheslosi

Physical examination demonstrates a firm, fixed, subungual nodule, often with an accompanying nail deformity. Further workup is required to confirm the benign nature of the lesion and exclude nail tumors such as melanoma or squamous cell carcinoma. Radiography is the gold standard for diagnosis, demonstrating a trabecular bony overgrowth.⁶ Performing a radiograph as the initial diagnostic test spares the patient from unnecessary procedures such as biopsy or expensive imaging techniques such as magnetic resonance imaging. Early lesions may not demonstrate sufficient bone formation shown on radiography. In these situations, a combination of dermoscopy and histopathologic examination may aid in diagnosis (Figure 2).⁴ Vascular ectasia, hyperkeratosis, onycholysis, and ulceration are the most common findings on dermoscopy (in ascending order).⁷ Histopathology typically demonstrates a base or stalk of normal-appearing trabecular bone with a fibrocartilage cap.⁸ However, initial clinical workup via radiography allows for the least-invasive and highest-yield intervention. Clinical suspicion for this condition is important, as it can be diagnosed with noninvasive inexpensive imaging rather than biopsy or more specialized imaging modalities. Appropriate recognition can save young patients from unnecessary and expensive procedures. Treatment typically involves surgical excision; to prevent regrowth, removal of the lesion at the base of the bone is recommended.²

degecuboviditrusifrokowujimeranujadasuhogufraslufrejatid

Although amelanotic melanoma also can manifest as a subungual nail tumor, it would be unusual in a young child and would not be expected to show characteristic changes on radiography. A glomus tumor would be painful, is more common on the fingers than on the toes, and typically has a bluish hue.⁹ Verruca vulgaris can occur subungually but is more common around the nailfold and often has the characteristic dermoscopic finding of thrombosed capillaries. It also would not be expected to show characteristic radiographic findings. Osteochondroma can occur in young patients and can appear clinically similar to subungual exostosis; however, it typically is painful.¹⁰

The Diagnosis: Subungual Exostosis

Subungual exostosis should be considered as a possible cause of an exophytic subungual nodule in a young active female. In our patient, the involvement of the great toe was a clue, as the hallux is the most common location of subungual exostosis. The patient’s age and sex also were supportive, as subungual exostosis is most common in female children and adolescents— particularly those who are active, as trauma is thought to play a possible role in development of this benign tumor.^1-3 Radiography is the preferred modality for diagnosis; in our case, it showed a trabecular bony overgrowth (Figure 1), which confirmed the diagnosis. Subungual exostosis is a rare, benign, osteocartilaginous tumor of trabecular bone. The etiology is unknown but is hypothesized to be related to trauma, infection, or activation of a cartilaginous cyst.^1,3 The subungual nodule may be asymptomatic or painful. Disruption and elevation of the nail plate is common.⁴ The differential diagnosis includes amelanotic melanoma, fibroma, fibrokeratoma, osteochondroma, pyogenic granuloma, squamous cell carcinoma, glomus tumor, and verruca vulgaris, among others.⁵

doswicubarasofrocheslosi

Physical examination demonstrates a firm, fixed, subungual nodule, often with an accompanying nail deformity. Further workup is required to confirm the benign nature of the lesion and exclude nail tumors such as melanoma or squamous cell carcinoma. Radiography is the gold standard for diagnosis, demonstrating a trabecular bony overgrowth.⁶ Performing a radiograph as the initial diagnostic test spares the patient from unnecessary procedures such as biopsy or expensive imaging techniques such as magnetic resonance imaging. Early lesions may not demonstrate sufficient bone formation shown on radiography. In these situations, a combination of dermoscopy and histopathologic examination may aid in diagnosis (Figure 2).⁴ Vascular ectasia, hyperkeratosis, onycholysis, and ulceration are the most common findings on dermoscopy (in ascending order).⁷ Histopathology typically demonstrates a base or stalk of normal-appearing trabecular bone with a fibrocartilage cap.⁸ However, initial clinical workup via radiography allows for the least-invasive and highest-yield intervention. Clinical suspicion for this condition is important, as it can be diagnosed with noninvasive inexpensive imaging rather than biopsy or more specialized imaging modalities. Appropriate recognition can save young patients from unnecessary and expensive procedures. Treatment typically involves surgical excision; to prevent regrowth, removal of the lesion at the base of the bone is recommended.²

degecuboviditrusifrokowujimeranujadasuhogufraslufrejatid

Although amelanotic melanoma also can manifest as a subungual nail tumor, it would be unusual in a young child and would not be expected to show characteristic changes on radiography. A glomus tumor would be painful, is more common on the fingers than on the toes, and typically has a bluish hue.⁹ Verruca vulgaris can occur subungually but is more common around the nailfold and often has the characteristic dermoscopic finding of thrombosed capillaries. It also would not be expected to show characteristic radiographic findings. Osteochondroma can occur in young patients and can appear clinically similar to subungual exostosis; however, it typically is painful.¹⁰

The Diagnosis: Subungual Exostosis

Subungual exostosis should be considered as a possible cause of an exophytic subungual nodule in a young active female. In our patient, the involvement of the great toe was a clue, as the hallux is the most common location of subungual exostosis. The patient’s age and sex also were supportive, as subungual exostosis is most common in female children and adolescents— particularly those who are active, as trauma is thought to play a possible role in development of this benign tumor.^1-3 Radiography is the preferred modality for diagnosis; in our case, it showed a trabecular bony overgrowth (Figure 1), which confirmed the diagnosis. Subungual exostosis is a rare, benign, osteocartilaginous tumor of trabecular bone. The etiology is unknown but is hypothesized to be related to trauma, infection, or activation of a cartilaginous cyst.^1,3 The subungual nodule may be asymptomatic or painful. Disruption and elevation of the nail plate is common.⁴ The differential diagnosis includes amelanotic melanoma, fibroma, fibrokeratoma, osteochondroma, pyogenic granuloma, squamous cell carcinoma, glomus tumor, and verruca vulgaris, among others.⁵

doswicubarasofrocheslosi

Physical examination demonstrates a firm, fixed, subungual nodule, often with an accompanying nail deformity. Further workup is required to confirm the benign nature of the lesion and exclude nail tumors such as melanoma or squamous cell carcinoma. Radiography is the gold standard for diagnosis, demonstrating a trabecular bony overgrowth.⁶ Performing a radiograph as the initial diagnostic test spares the patient from unnecessary procedures such as biopsy or expensive imaging techniques such as magnetic resonance imaging. Early lesions may not demonstrate sufficient bone formation shown on radiography. In these situations, a combination of dermoscopy and histopathologic examination may aid in diagnosis (Figure 2).⁴ Vascular ectasia, hyperkeratosis, onycholysis, and ulceration are the most common findings on dermoscopy (in ascending order).⁷ Histopathology typically demonstrates a base or stalk of normal-appearing trabecular bone with a fibrocartilage cap.⁸ However, initial clinical workup via radiography allows for the least-invasive and highest-yield intervention. Clinical suspicion for this condition is important, as it can be diagnosed with noninvasive inexpensive imaging rather than biopsy or more specialized imaging modalities. Appropriate recognition can save young patients from unnecessary and expensive procedures. Treatment typically involves surgical excision; to prevent regrowth, removal of the lesion at the base of the bone is recommended.²

degecuboviditrusifrokowujimeranujadasuhogufraslufrejatid

Although amelanotic melanoma also can manifest as a subungual nail tumor, it would be unusual in a young child and would not be expected to show characteristic changes on radiography. A glomus tumor would be painful, is more common on the fingers than on the toes, and typically has a bluish hue.⁹ Verruca vulgaris can occur subungually but is more common around the nailfold and often has the characteristic dermoscopic finding of thrombosed capillaries. It also would not be expected to show characteristic radiographic findings. Osteochondroma can occur in young patients and can appear clinically similar to subungual exostosis; however, it typically is painful.¹⁰

The Diagnosis: BASCULE Syndrome

The patient had previously been thought to have livedo reticularis by primary care. Repeat antinuclear antibody (ANA) testing was positive (1:1280 homogeneous [reflexive titers all negative]). However, upon dermatologic evaluation, the manifestation of the rash in addition to onset occurring with postural changes challenged the livedo reticularis diagnosis. Extensive research and consultation with dermatologic colleagues led to the diagnosis of the rare entity BASCULE syndrome. BASCULE (Bier anemic spots, cyanosis, and urticarialike eruption) syndrome was described by Bessis et al¹ in 2016. It is a rare condition but may be underreported.² It is a benign pediatric disorder in the vascular acrosyndrome family that is characterized by underlying vasomotor dysfunction in distal regions of the body. Raynaud phenomenon is a widely known member of this family. As seen in our patient, it typically presents on the distal legs and feet with numerous irregular hypopigmented macules on a cyanotic background. Red-orange papules may appear on the hypopigmented macules and often are pruritic. Lesions on the distal upper extremities are less common, and a case involving the trunk has been reported.³ Onset generally begins within a couple of minutes of standing or mechanical compression of the lower legs, with full reversal of symptoms occurring within minutes of laying down or walking. Commonly reported associated symptoms include tenderness, pruritus, edema, and pain; however, the cutaneous lesions may be asymptomatic. The condition tends to affect adolescents, as seen in our patient; however, there have been reports in infants as young as 3 months to adults aged 19 years.²

The pathophysiology behind BASCULE syndrome remains unclear but is believed to be centered around the role of physiologic venous stasis that occurs when standing. The hypoxia secondary to stasis is thought to induce amplified vasoconstriction of arterioles. These responses are further exaggerated due to absence of venoarteriolar reflexes in dermal ascending arterioles, leading to Bier spots.² The role of mast cells and eosinophils remains unclear. It is a clinical diagnosis without clear histologic findings; therefore, biopsy was not pursued in our patient.

Although BASCULE syndrome is a benign entity, it is imperative that it be recognized to avoid a time consuming, expensive, and anxiety-producing diagnostic workup, as occurred in our patient. Although not a manifestation of systemic disease, BASCULE syndrome may be associated with orthostatic hypotension in up to 20% of cases.^2,4 Therefore, these patients should undergo orthostatic testing, including the tilt table test. In our patient, these manifestations were not appreciated.

There are no current guidelines for effective treatment of BASCULE syndrome. Given the possible role of mast cells in the condition, H1 antihistamines are proposed as first-line treatment. Desloratadine (10 mg/d for 7 days) has been found to be associated with improvement of pruritus. However, a recent literature review found little evidence to support the use of H1 antihistamines for resolution of other symptoms.²

The differential diagnosis includes livedo reticularis, Bier spots, Sneddon syndrome, and urticarial vasculitis. Livedo reticularis presents as distinct, netlike, blue-erythematousviolaceous discoloration, which differs from the distinct orange-red macules in BASCULE syndrome.⁵ In addition to distinct variances in dermatologic presentation, livedo reticularis typically is associated with cold exposure as a causative agent, with cold avoidance as the treatment for this benign and often transient condition.⁶ This phenomenon was not appreciated in our patient. Livedo reticularis commonly occurs with antiphospholipid syndrome.⁵ This association in combination with our patient's positive ANA findings and her mother's history of miscarriages resulted in the misdiagnosis as livedo reticularis.

Bier spots manifest as white macules with surrounding erythema and typically present in young adults. When first described in the literature, it was debated if BASCULE syndrome was simply another manifestation of Bier spots or postural orthostatic intolerance,⁴ as there was a large consensus that postural orthostatic intolerance was associated with BASCULE syndrome, with the majority of patients not meeting criteria for the condition. Heymann⁴ addressed the differences in BASCULE manifestations vs typical Bier spots. The author extended the syndrome to include cyanosis, an urticarialike eruption of red-orange macules with central papules located centrally, pruritus, tenderness, and partial or diffuse edema, in addition to Bier spots.⁴

Sneddon syndrome is a rare progressive disorder that affects small- to medium-sized blood vessels resulting in multiple episodes of ischemia in the brain. Skin manifestations of these repeated strokes are similar to livedo reticularis, typically manifesting as livedo racemosa—irregular reticular patterns of skin mottling with reddish-blue hues.⁶ However, Sneddon syndrome is more generalized and widespread and differs from BASCULE syndrome in shape and histologic findings. Our patient presented with findings on the legs, which is more characteristic of livedo reticularis vs livedo racemosa. Our patient experienced resolution upon laying down and sitting, and Sneddon syndrome persists beyond postural changes. Furthermore, patients with Sneddon syndrome present with neurologic symptoms such as prodromal headaches.⁶

Urticarial vasculitis was ruled out in our patient because of the duration of symptoms as well as the spatial changes. Urticarial vasculitis is a rare skin condition characterized by chronic recurring urticarial lesions that may persist for more than a day. This condition typically presents in middle-aged women and rarely in children. Urticarial vasculitis is thought to be immune-complex mediated, but its cause is largely unknown. It is a common manifestation of underlying conditions such as systemic lupus erythematosus.⁶ Our patient had a positive ANA and possible autoimmune history from her mother; however, urticarial vasculitis does not present transiently on the legs or in the rash pattern appreciated in our patient.

The Diagnosis: BASCULE Syndrome

The patient had previously been thought to have livedo reticularis by primary care. Repeat antinuclear antibody (ANA) testing was positive (1:1280 homogeneous [reflexive titers all negative]). However, upon dermatologic evaluation, the manifestation of the rash in addition to onset occurring with postural changes challenged the livedo reticularis diagnosis. Extensive research and consultation with dermatologic colleagues led to the diagnosis of the rare entity BASCULE syndrome. BASCULE (Bier anemic spots, cyanosis, and urticarialike eruption) syndrome was described by Bessis et al¹ in 2016. It is a rare condition but may be underreported.² It is a benign pediatric disorder in the vascular acrosyndrome family that is characterized by underlying vasomotor dysfunction in distal regions of the body. Raynaud phenomenon is a widely known member of this family. As seen in our patient, it typically presents on the distal legs and feet with numerous irregular hypopigmented macules on a cyanotic background. Red-orange papules may appear on the hypopigmented macules and often are pruritic. Lesions on the distal upper extremities are less common, and a case involving the trunk has been reported.³ Onset generally begins within a couple of minutes of standing or mechanical compression of the lower legs, with full reversal of symptoms occurring within minutes of laying down or walking. Commonly reported associated symptoms include tenderness, pruritus, edema, and pain; however, the cutaneous lesions may be asymptomatic. The condition tends to affect adolescents, as seen in our patient; however, there have been reports in infants as young as 3 months to adults aged 19 years.²

The pathophysiology behind BASCULE syndrome remains unclear but is believed to be centered around the role of physiologic venous stasis that occurs when standing. The hypoxia secondary to stasis is thought to induce amplified vasoconstriction of arterioles. These responses are further exaggerated due to absence of venoarteriolar reflexes in dermal ascending arterioles, leading to Bier spots.² The role of mast cells and eosinophils remains unclear. It is a clinical diagnosis without clear histologic findings; therefore, biopsy was not pursued in our patient.

Although BASCULE syndrome is a benign entity, it is imperative that it be recognized to avoid a time consuming, expensive, and anxiety-producing diagnostic workup, as occurred in our patient. Although not a manifestation of systemic disease, BASCULE syndrome may be associated with orthostatic hypotension in up to 20% of cases.^2,4 Therefore, these patients should undergo orthostatic testing, including the tilt table test. In our patient, these manifestations were not appreciated.

There are no current guidelines for effective treatment of BASCULE syndrome. Given the possible role of mast cells in the condition, H1 antihistamines are proposed as first-line treatment. Desloratadine (10 mg/d for 7 days) has been found to be associated with improvement of pruritus. However, a recent literature review found little evidence to support the use of H1 antihistamines for resolution of other symptoms.²

The differential diagnosis includes livedo reticularis, Bier spots, Sneddon syndrome, and urticarial vasculitis. Livedo reticularis presents as distinct, netlike, blue-erythematousviolaceous discoloration, which differs from the distinct orange-red macules in BASCULE syndrome.⁵ In addition to distinct variances in dermatologic presentation, livedo reticularis typically is associated with cold exposure as a causative agent, with cold avoidance as the treatment for this benign and often transient condition.⁶ This phenomenon was not appreciated in our patient. Livedo reticularis commonly occurs with antiphospholipid syndrome.⁵ This association in combination with our patient's positive ANA findings and her mother's history of miscarriages resulted in the misdiagnosis as livedo reticularis.

Bier spots manifest as white macules with surrounding erythema and typically present in young adults. When first described in the literature, it was debated if BASCULE syndrome was simply another manifestation of Bier spots or postural orthostatic intolerance,⁴ as there was a large consensus that postural orthostatic intolerance was associated with BASCULE syndrome, with the majority of patients not meeting criteria for the condition. Heymann⁴ addressed the differences in BASCULE manifestations vs typical Bier spots. The author extended the syndrome to include cyanosis, an urticarialike eruption of red-orange macules with central papules located centrally, pruritus, tenderness, and partial or diffuse edema, in addition to Bier spots.⁴

Sneddon syndrome is a rare progressive disorder that affects small- to medium-sized blood vessels resulting in multiple episodes of ischemia in the brain. Skin manifestations of these repeated strokes are similar to livedo reticularis, typically manifesting as livedo racemosa—irregular reticular patterns of skin mottling with reddish-blue hues.⁶ However, Sneddon syndrome is more generalized and widespread and differs from BASCULE syndrome in shape and histologic findings. Our patient presented with findings on the legs, which is more characteristic of livedo reticularis vs livedo racemosa. Our patient experienced resolution upon laying down and sitting, and Sneddon syndrome persists beyond postural changes. Furthermore, patients with Sneddon syndrome present with neurologic symptoms such as prodromal headaches.⁶

Urticarial vasculitis was ruled out in our patient because of the duration of symptoms as well as the spatial changes. Urticarial vasculitis is a rare skin condition characterized by chronic recurring urticarial lesions that may persist for more than a day. This condition typically presents in middle-aged women and rarely in children. Urticarial vasculitis is thought to be immune-complex mediated, but its cause is largely unknown. It is a common manifestation of underlying conditions such as systemic lupus erythematosus.⁶ Our patient had a positive ANA and possible autoimmune history from her mother; however, urticarial vasculitis does not present transiently on the legs or in the rash pattern appreciated in our patient.

The Diagnosis: BASCULE Syndrome

The patient had previously been thought to have livedo reticularis by primary care. Repeat antinuclear antibody (ANA) testing was positive (1:1280 homogeneous [reflexive titers all negative]). However, upon dermatologic evaluation, the manifestation of the rash in addition to onset occurring with postural changes challenged the livedo reticularis diagnosis. Extensive research and consultation with dermatologic colleagues led to the diagnosis of the rare entity BASCULE syndrome. BASCULE (Bier anemic spots, cyanosis, and urticarialike eruption) syndrome was described by Bessis et al¹ in 2016. It is a rare condition but may be underreported.² It is a benign pediatric disorder in the vascular acrosyndrome family that is characterized by underlying vasomotor dysfunction in distal regions of the body. Raynaud phenomenon is a widely known member of this family. As seen in our patient, it typically presents on the distal legs and feet with numerous irregular hypopigmented macules on a cyanotic background. Red-orange papules may appear on the hypopigmented macules and often are pruritic. Lesions on the distal upper extremities are less common, and a case involving the trunk has been reported.³ Onset generally begins within a couple of minutes of standing or mechanical compression of the lower legs, with full reversal of symptoms occurring within minutes of laying down or walking. Commonly reported associated symptoms include tenderness, pruritus, edema, and pain; however, the cutaneous lesions may be asymptomatic. The condition tends to affect adolescents, as seen in our patient; however, there have been reports in infants as young as 3 months to adults aged 19 years.²

The pathophysiology behind BASCULE syndrome remains unclear but is believed to be centered around the role of physiologic venous stasis that occurs when standing. The hypoxia secondary to stasis is thought to induce amplified vasoconstriction of arterioles. These responses are further exaggerated due to absence of venoarteriolar reflexes in dermal ascending arterioles, leading to Bier spots.² The role of mast cells and eosinophils remains unclear. It is a clinical diagnosis without clear histologic findings; therefore, biopsy was not pursued in our patient.

Although BASCULE syndrome is a benign entity, it is imperative that it be recognized to avoid a time consuming, expensive, and anxiety-producing diagnostic workup, as occurred in our patient. Although not a manifestation of systemic disease, BASCULE syndrome may be associated with orthostatic hypotension in up to 20% of cases.^2,4 Therefore, these patients should undergo orthostatic testing, including the tilt table test. In our patient, these manifestations were not appreciated.

There are no current guidelines for effective treatment of BASCULE syndrome. Given the possible role of mast cells in the condition, H1 antihistamines are proposed as first-line treatment. Desloratadine (10 mg/d for 7 days) has been found to be associated with improvement of pruritus. However, a recent literature review found little evidence to support the use of H1 antihistamines for resolution of other symptoms.²

The differential diagnosis includes livedo reticularis, Bier spots, Sneddon syndrome, and urticarial vasculitis. Livedo reticularis presents as distinct, netlike, blue-erythematousviolaceous discoloration, which differs from the distinct orange-red macules in BASCULE syndrome.⁵ In addition to distinct variances in dermatologic presentation, livedo reticularis typically is associated with cold exposure as a causative agent, with cold avoidance as the treatment for this benign and often transient condition.⁶ This phenomenon was not appreciated in our patient. Livedo reticularis commonly occurs with antiphospholipid syndrome.⁵ This association in combination with our patient's positive ANA findings and her mother's history of miscarriages resulted in the misdiagnosis as livedo reticularis.

Bier spots manifest as white macules with surrounding erythema and typically present in young adults. When first described in the literature, it was debated if BASCULE syndrome was simply another manifestation of Bier spots or postural orthostatic intolerance,⁴ as there was a large consensus that postural orthostatic intolerance was associated with BASCULE syndrome, with the majority of patients not meeting criteria for the condition. Heymann⁴ addressed the differences in BASCULE manifestations vs typical Bier spots. The author extended the syndrome to include cyanosis, an urticarialike eruption of red-orange macules with central papules located centrally, pruritus, tenderness, and partial or diffuse edema, in addition to Bier spots.⁴

Sneddon syndrome is a rare progressive disorder that affects small- to medium-sized blood vessels resulting in multiple episodes of ischemia in the brain. Skin manifestations of these repeated strokes are similar to livedo reticularis, typically manifesting as livedo racemosa—irregular reticular patterns of skin mottling with reddish-blue hues.⁶ However, Sneddon syndrome is more generalized and widespread and differs from BASCULE syndrome in shape and histologic findings. Our patient presented with findings on the legs, which is more characteristic of livedo reticularis vs livedo racemosa. Our patient experienced resolution upon laying down and sitting, and Sneddon syndrome persists beyond postural changes. Furthermore, patients with Sneddon syndrome present with neurologic symptoms such as prodromal headaches.⁶

Urticarial vasculitis was ruled out in our patient because of the duration of symptoms as well as the spatial changes. Urticarial vasculitis is a rare skin condition characterized by chronic recurring urticarial lesions that may persist for more than a day. This condition typically presents in middle-aged women and rarely in children. Urticarial vasculitis is thought to be immune-complex mediated, but its cause is largely unknown. It is a common manifestation of underlying conditions such as systemic lupus erythematosus.⁶ Our patient had a positive ANA and possible autoimmune history from her mother; however, urticarial vasculitis does not present transiently on the legs or in the rash pattern appreciated in our patient.

The Diagnosis: Purpuric Drug Eruption

Histopathology revealed interface dermatitis, spongiosis, and a perivascular lymphocytic infiltrate with extravasated red blood cells consistent with a purpuric drug eruption. Our patient achieved remission of hairy cell leukemia after receiving only 2 of 5 expected doses of cladribine. The rash resolved completely in 3 weeks following a prednisone taper (Figure).

Gray_HCL.jpg

Hairy cell leukemia is a rare indolent lymphoproliferative disorder of B cells that accounts for approximately 2% of adult leukemias in the United States. Cladribine, a purine nucleoside analog that impairs DNA synthesis and repair, has become the mainstay of therapy, demonstrating a 95% complete response rate.¹ Although few reports have addressed the cutaneous reactions seen with cladribine therapy, they can occur in more than 50% of patients.^1,2 The most common skin manifestation associated with cladribine therapy is a morbilliform rash, but Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) have been reported.¹

Few cases of purpuric eruption secondary to cladribine treatment have been described, and nearly all reports involve concomitant medications such as allopurinol, which our patient was taking, and antibiotics including trimethoprim-sulfamethoxazole and penicillins.^1,3,4 In a cohort of 35 patients receiving cladribine,1 only concomitant treatment with cladribine and allopurinol caused cutaneous reactions, further supporting the hypothesis of cladribine-induced drug sensitivity. Allopurinol often is prescribed during induction therapy for prophylaxis against tumor lysis syndrome; similarly, antibiotics frequently are given prophylactically and therapeutically for neutropenic fever. It is believed that T-cell imbalance and profound lymphopenia induced by cladribine increase susceptibility to drug hypersensitivity reactions.^1,3

The typical purpuric eruption develops within 2 days of starting cladribine therapy. Diascopy will reveal petechiae, and biopsy should be performed to rule out other serious drug-induced reactions, such as erythema multiforme, Stevens-Johnson syndrome, and TEN. A cladribine-induced purpuric eruption typically is self-resolving and carries a favorable prognosis, though high-dose corticosteroids often are prescribed to hasten recovery. The rare reports of serious cutaneous reactions secondary to cladribine therapy have been with maculopapular, not purpuric eruptions.² Based on limited available data, cladribine-induced purpura should not be a limitation to continued treatment in patients who need it.¹ Careful consideration of concomitant drug use is necessary, as the current literature demonstrates resolution of rash with withdrawal of other therapies, namely allopurinol.^2-4 Future studies are needed to examine the safety of withholding offending medications and to further elucidate the mechanisms contributing to drug hypersensitivity due to cladribine.

Widespread purpura and petechiae can pose a wide differential; the patient’s recent history of cladribine administration pointed to a classic purpuric eruption. Other diagnoses such as toxic erythema of chemotherapy (TEC) and TEN are not purpuric, though plaques can be violaceous. Lack of bullae, blisters, and facial or mucosal surface involvement suggest TEN.⁵ Thrombotic thrombocytopenic purpura and disseminated intravascular coagulation do manifest with petechiae and purpura, though such a robust eruption in the context of recent cladribine therapy is less likely. The classic retiform purpura and necrosis were not present to suggest purpura fulminans from disseminated intravascular coagulation.

Several of the proposed diagnoses as well as a purpuric drug eruption would demonstrate extravasated red blood cells on histopathology, but the presence of interface dermatitis narrows the differential to a purpuric drug eruption. Necrotic keratinocytes and full-thickness necrosis were not present on biopsy to support a diagnosis of TEN in our patient. Characteristic features of TEC—including eccrine squamous syringometaplasia, dermal edema, and keratinocyte atypia—were not present on biopsy.⁶ Finally, although TEN should resolve with steroid treatment, TEC is self-limited and thrombotic thrombocytopenic purpura and disseminated intravascular coagulation would not resolve with use of steroids alone. 

The Diagnosis: Purpuric Drug Eruption

Histopathology revealed interface dermatitis, spongiosis, and a perivascular lymphocytic infiltrate with extravasated red blood cells consistent with a purpuric drug eruption. Our patient achieved remission of hairy cell leukemia after receiving only 2 of 5 expected doses of cladribine. The rash resolved completely in 3 weeks following a prednisone taper (Figure).

Gray_HCL.jpg

Hairy cell leukemia is a rare indolent lymphoproliferative disorder of B cells that accounts for approximately 2% of adult leukemias in the United States. Cladribine, a purine nucleoside analog that impairs DNA synthesis and repair, has become the mainstay of therapy, demonstrating a 95% complete response rate.¹ Although few reports have addressed the cutaneous reactions seen with cladribine therapy, they can occur in more than 50% of patients.^1,2 The most common skin manifestation associated with cladribine therapy is a morbilliform rash, but Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) have been reported.¹

Few cases of purpuric eruption secondary to cladribine treatment have been described, and nearly all reports involve concomitant medications such as allopurinol, which our patient was taking, and antibiotics including trimethoprim-sulfamethoxazole and penicillins.^1,3,4 In a cohort of 35 patients receiving cladribine,1 only concomitant treatment with cladribine and allopurinol caused cutaneous reactions, further supporting the hypothesis of cladribine-induced drug sensitivity. Allopurinol often is prescribed during induction therapy for prophylaxis against tumor lysis syndrome; similarly, antibiotics frequently are given prophylactically and therapeutically for neutropenic fever. It is believed that T-cell imbalance and profound lymphopenia induced by cladribine increase susceptibility to drug hypersensitivity reactions.^1,3

The typical purpuric eruption develops within 2 days of starting cladribine therapy. Diascopy will reveal petechiae, and biopsy should be performed to rule out other serious drug-induced reactions, such as erythema multiforme, Stevens-Johnson syndrome, and TEN. A cladribine-induced purpuric eruption typically is self-resolving and carries a favorable prognosis, though high-dose corticosteroids often are prescribed to hasten recovery. The rare reports of serious cutaneous reactions secondary to cladribine therapy have been with maculopapular, not purpuric eruptions.² Based on limited available data, cladribine-induced purpura should not be a limitation to continued treatment in patients who need it.¹ Careful consideration of concomitant drug use is necessary, as the current literature demonstrates resolution of rash with withdrawal of other therapies, namely allopurinol.^2-4 Future studies are needed to examine the safety of withholding offending medications and to further elucidate the mechanisms contributing to drug hypersensitivity due to cladribine.

Widespread purpura and petechiae can pose a wide differential; the patient’s recent history of cladribine administration pointed to a classic purpuric eruption. Other diagnoses such as toxic erythema of chemotherapy (TEC) and TEN are not purpuric, though plaques can be violaceous. Lack of bullae, blisters, and facial or mucosal surface involvement suggest TEN.⁵ Thrombotic thrombocytopenic purpura and disseminated intravascular coagulation do manifest with petechiae and purpura, though such a robust eruption in the context of recent cladribine therapy is less likely. The classic retiform purpura and necrosis were not present to suggest purpura fulminans from disseminated intravascular coagulation.

Several of the proposed diagnoses as well as a purpuric drug eruption would demonstrate extravasated red blood cells on histopathology, but the presence of interface dermatitis narrows the differential to a purpuric drug eruption. Necrotic keratinocytes and full-thickness necrosis were not present on biopsy to support a diagnosis of TEN in our patient. Characteristic features of TEC—including eccrine squamous syringometaplasia, dermal edema, and keratinocyte atypia—were not present on biopsy.⁶ Finally, although TEN should resolve with steroid treatment, TEC is self-limited and thrombotic thrombocytopenic purpura and disseminated intravascular coagulation would not resolve with use of steroids alone. 

The Diagnosis: Purpuric Drug Eruption

Histopathology revealed interface dermatitis, spongiosis, and a perivascular lymphocytic infiltrate with extravasated red blood cells consistent with a purpuric drug eruption. Our patient achieved remission of hairy cell leukemia after receiving only 2 of 5 expected doses of cladribine. The rash resolved completely in 3 weeks following a prednisone taper (Figure).

Gray_HCL.jpg

Hairy cell leukemia is a rare indolent lymphoproliferative disorder of B cells that accounts for approximately 2% of adult leukemias in the United States. Cladribine, a purine nucleoside analog that impairs DNA synthesis and repair, has become the mainstay of therapy, demonstrating a 95% complete response rate.¹ Although few reports have addressed the cutaneous reactions seen with cladribine therapy, they can occur in more than 50% of patients.^1,2 The most common skin manifestation associated with cladribine therapy is a morbilliform rash, but Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) have been reported.¹

Few cases of purpuric eruption secondary to cladribine treatment have been described, and nearly all reports involve concomitant medications such as allopurinol, which our patient was taking, and antibiotics including trimethoprim-sulfamethoxazole and penicillins.^1,3,4 In a cohort of 35 patients receiving cladribine,1 only concomitant treatment with cladribine and allopurinol caused cutaneous reactions, further supporting the hypothesis of cladribine-induced drug sensitivity. Allopurinol often is prescribed during induction therapy for prophylaxis against tumor lysis syndrome; similarly, antibiotics frequently are given prophylactically and therapeutically for neutropenic fever. It is believed that T-cell imbalance and profound lymphopenia induced by cladribine increase susceptibility to drug hypersensitivity reactions.^1,3

The typical purpuric eruption develops within 2 days of starting cladribine therapy. Diascopy will reveal petechiae, and biopsy should be performed to rule out other serious drug-induced reactions, such as erythema multiforme, Stevens-Johnson syndrome, and TEN. A cladribine-induced purpuric eruption typically is self-resolving and carries a favorable prognosis, though high-dose corticosteroids often are prescribed to hasten recovery. The rare reports of serious cutaneous reactions secondary to cladribine therapy have been with maculopapular, not purpuric eruptions.² Based on limited available data, cladribine-induced purpura should not be a limitation to continued treatment in patients who need it.¹ Careful consideration of concomitant drug use is necessary, as the current literature demonstrates resolution of rash with withdrawal of other therapies, namely allopurinol.^2-4 Future studies are needed to examine the safety of withholding offending medications and to further elucidate the mechanisms contributing to drug hypersensitivity due to cladribine.

Widespread purpura and petechiae can pose a wide differential; the patient’s recent history of cladribine administration pointed to a classic purpuric eruption. Other diagnoses such as toxic erythema of chemotherapy (TEC) and TEN are not purpuric, though plaques can be violaceous. Lack of bullae, blisters, and facial or mucosal surface involvement suggest TEN.⁵ Thrombotic thrombocytopenic purpura and disseminated intravascular coagulation do manifest with petechiae and purpura, though such a robust eruption in the context of recent cladribine therapy is less likely. The classic retiform purpura and necrosis were not present to suggest purpura fulminans from disseminated intravascular coagulation.

Several of the proposed diagnoses as well as a purpuric drug eruption would demonstrate extravasated red blood cells on histopathology, but the presence of interface dermatitis narrows the differential to a purpuric drug eruption. Necrotic keratinocytes and full-thickness necrosis were not present on biopsy to support a diagnosis of TEN in our patient. Characteristic features of TEC—including eccrine squamous syringometaplasia, dermal edema, and keratinocyte atypia—were not present on biopsy.⁶ Finally, although TEN should resolve with steroid treatment, TEC is self-limited and thrombotic thrombocytopenic purpura and disseminated intravascular coagulation would not resolve with use of steroids alone. 

The Diagnosis: Nodular Basal Cell Carcinoma

Histopathology of the lesion showed a large basaloid lobule with focal epidermal attachment, peripheral nuclear palisading with cleft formation between the tumor and surrounding stroma, fibromyxoid stroma and mild pleomorphism, and variable mitotic activity and apoptosis (Figure). Based on the clinical presentation and histopathology, the patient was diagnosed with nodular basal cell carcinoma (BCC). He underwent a wide local excision of the affected area that was repaired with a splitthickness skin graft.

CT113005199_Fig_ABCD.jpg

Basal cell carcinoma is the most common skin cancer worldwide and typically occurs due to years of UV radiation damage on sun-exposed skin, which accounts for a higher frequency of BCC occurring in patients residing in geographic locations with greater UV exposure (eg, higher and lower latitudes). In addition to cumulative UV dose, the duration of the exposure as well as its intensity also play a role in the development of BCC, particularly in early childhood and adolescence. Nevertheless, UV exposure is not the only risk factor, as 20% of BCCs arise in skin that is not exposed to the sun. Other risk factors include exposure to ionizing radiation and arsenic, immunosuppression, and genetic predisposition.¹ Although these malignancies typically do not metastasize, growth can lead to local tissue destruction and major disfigurement if not treated in a timely fashion.²

In our patient, the differential diagnosis included pyoderma gangrenosum (PG) given the clinical appearance of the cribriform base and violaceous undermined rim of the ulcer. Pyoderma gangrenosum is a rare neutrophilic disorder that often results in ulcers that have been associated with various systemic autoimmune and inflammatory conditions, such as inflammatory bowel disease. There are 4 main subtypes of PG: the classic ulcerative type (our patient); the pustular type, which most often is seen in patients with inflammatory bowel disease; the bullous type, which can be seen in patients with an associated lymphoproliferative disorder; and the vegetative type. It frequently is thought of as both a clinical and histologic diagnosis of exclusion due to the nonspecific histopathologic features; most lesions demonstrate an infiltrate of neutrophils in the dermis. A biopsy was crucial in our patient, considering that diagnosis and treatment would have been further delayed had the patient been empirically treated with oral and topical steroids for presumed PG, which is precisely why PG is a diagnosis of exclusion. It is imperative for clinicians to rule out other pathologies, such as infection or malignancy, as demonstrated in our patient. The progressive onset and slow evolution of the lesion over years along with a lack of pain were more suggestive of BCC rather than PG. However, there is a report in the literature of PG mimicking BCC with both clinical and dermoscopic findings.³

Venous or stasis ulcers are painless, and although they rarely occur on the calf, they typically are seen lower on the leg such as on the medial ankles. Our patient endorsed occasional swelling of the affected leg and presented with edema, but overlying stasis change and other signs of venous insufficiency were absent.

Buruli ulcer is a painless chronic debilitating cutaneous disease resulting in indolent necrotizing skin as well as subcutaneous and bone lesions. It is caused by the environmental organism Mycobacterium ulcerans and typically is reported in Africa, Central/South America, the Western Pacific Region, and Australia.⁴ Histopathology usually demonstrates necrosis of subcutaneous tissue and dermal collagen accompanied by inflammation and acidfast bacilli highlighted by Ziehl-Neelsen stain.⁵ Smears of the lesions as well as culture and polymerase chain reaction for acid-fast bacilli also can be performed. Our patient reported no recent travel to any endemic areas and had no other risk factors or exposures to the pathogen responsible for this condition.

Traumatic ulcer also was included in the differential diagnosis, but the patient denied preceding trauma to the area, and the contralateral foot prosthesis did not rub on or impact the affected leg.

Basal cell carcinoma typically is treated surgically, but choice of treatment can depend on the subtype, size, tumor site, and/or patient preference.¹ Other treatment modalities include electrodesiccation and curettage, cryosurgical destruction, photodynamic therapy, radiation, topical therapies, and systemic medications. Radiotherapy can be considered as a primary treatment option for BCC if surgery is contraindicated or declined by the patient, but it also is useful as an adjuvant therapy when there is perineural invasion of the tumor or positive margins. Hedgehog pathway inhibitors such as vismodegib currently are indicated for patients who are not candidates for surgery or radiation as well as for those with metastatic or locally advanced, recurrent BCC. There is no single treatment method ideal for every lesion or patient. Specific populations such as the elderly, the immunosuppressed, or those with poor baseline functional status may warrant a nonsurgical approach. The clinician must take into consideration all factors while at the same time thinking about how to best accomplish the goals of recurrencefree tumor removal, correction of any underlying functional impairment from the tumor, and maintenance of cosmesis.¹

The Diagnosis: Nodular Basal Cell Carcinoma

Histopathology of the lesion showed a large basaloid lobule with focal epidermal attachment, peripheral nuclear palisading with cleft formation between the tumor and surrounding stroma, fibromyxoid stroma and mild pleomorphism, and variable mitotic activity and apoptosis (Figure). Based on the clinical presentation and histopathology, the patient was diagnosed with nodular basal cell carcinoma (BCC). He underwent a wide local excision of the affected area that was repaired with a splitthickness skin graft.

CT113005199_Fig_ABCD.jpg

Basal cell carcinoma is the most common skin cancer worldwide and typically occurs due to years of UV radiation damage on sun-exposed skin, which accounts for a higher frequency of BCC occurring in patients residing in geographic locations with greater UV exposure (eg, higher and lower latitudes). In addition to cumulative UV dose, the duration of the exposure as well as its intensity also play a role in the development of BCC, particularly in early childhood and adolescence. Nevertheless, UV exposure is not the only risk factor, as 20% of BCCs arise in skin that is not exposed to the sun. Other risk factors include exposure to ionizing radiation and arsenic, immunosuppression, and genetic predisposition.¹ Although these malignancies typically do not metastasize, growth can lead to local tissue destruction and major disfigurement if not treated in a timely fashion.²

In our patient, the differential diagnosis included pyoderma gangrenosum (PG) given the clinical appearance of the cribriform base and violaceous undermined rim of the ulcer. Pyoderma gangrenosum is a rare neutrophilic disorder that often results in ulcers that have been associated with various systemic autoimmune and inflammatory conditions, such as inflammatory bowel disease. There are 4 main subtypes of PG: the classic ulcerative type (our patient); the pustular type, which most often is seen in patients with inflammatory bowel disease; the bullous type, which can be seen in patients with an associated lymphoproliferative disorder; and the vegetative type. It frequently is thought of as both a clinical and histologic diagnosis of exclusion due to the nonspecific histopathologic features; most lesions demonstrate an infiltrate of neutrophils in the dermis. A biopsy was crucial in our patient, considering that diagnosis and treatment would have been further delayed had the patient been empirically treated with oral and topical steroids for presumed PG, which is precisely why PG is a diagnosis of exclusion. It is imperative for clinicians to rule out other pathologies, such as infection or malignancy, as demonstrated in our patient. The progressive onset and slow evolution of the lesion over years along with a lack of pain were more suggestive of BCC rather than PG. However, there is a report in the literature of PG mimicking BCC with both clinical and dermoscopic findings.³

Venous or stasis ulcers are painless, and although they rarely occur on the calf, they typically are seen lower on the leg such as on the medial ankles. Our patient endorsed occasional swelling of the affected leg and presented with edema, but overlying stasis change and other signs of venous insufficiency were absent.

Buruli ulcer is a painless chronic debilitating cutaneous disease resulting in indolent necrotizing skin as well as subcutaneous and bone lesions. It is caused by the environmental organism Mycobacterium ulcerans and typically is reported in Africa, Central/South America, the Western Pacific Region, and Australia.⁴ Histopathology usually demonstrates necrosis of subcutaneous tissue and dermal collagen accompanied by inflammation and acidfast bacilli highlighted by Ziehl-Neelsen stain.⁵ Smears of the lesions as well as culture and polymerase chain reaction for acid-fast bacilli also can be performed. Our patient reported no recent travel to any endemic areas and had no other risk factors or exposures to the pathogen responsible for this condition.

Traumatic ulcer also was included in the differential diagnosis, but the patient denied preceding trauma to the area, and the contralateral foot prosthesis did not rub on or impact the affected leg.

Basal cell carcinoma typically is treated surgically, but choice of treatment can depend on the subtype, size, tumor site, and/or patient preference.¹ Other treatment modalities include electrodesiccation and curettage, cryosurgical destruction, photodynamic therapy, radiation, topical therapies, and systemic medications. Radiotherapy can be considered as a primary treatment option for BCC if surgery is contraindicated or declined by the patient, but it also is useful as an adjuvant therapy when there is perineural invasion of the tumor or positive margins. Hedgehog pathway inhibitors such as vismodegib currently are indicated for patients who are not candidates for surgery or radiation as well as for those with metastatic or locally advanced, recurrent BCC. There is no single treatment method ideal for every lesion or patient. Specific populations such as the elderly, the immunosuppressed, or those with poor baseline functional status may warrant a nonsurgical approach. The clinician must take into consideration all factors while at the same time thinking about how to best accomplish the goals of recurrencefree tumor removal, correction of any underlying functional impairment from the tumor, and maintenance of cosmesis.¹

The Diagnosis: Nodular Basal Cell Carcinoma

Histopathology of the lesion showed a large basaloid lobule with focal epidermal attachment, peripheral nuclear palisading with cleft formation between the tumor and surrounding stroma, fibromyxoid stroma and mild pleomorphism, and variable mitotic activity and apoptosis (Figure). Based on the clinical presentation and histopathology, the patient was diagnosed with nodular basal cell carcinoma (BCC). He underwent a wide local excision of the affected area that was repaired with a splitthickness skin graft.

CT113005199_Fig_ABCD.jpg

Basal cell carcinoma is the most common skin cancer worldwide and typically occurs due to years of UV radiation damage on sun-exposed skin, which accounts for a higher frequency of BCC occurring in patients residing in geographic locations with greater UV exposure (eg, higher and lower latitudes). In addition to cumulative UV dose, the duration of the exposure as well as its intensity also play a role in the development of BCC, particularly in early childhood and adolescence. Nevertheless, UV exposure is not the only risk factor, as 20% of BCCs arise in skin that is not exposed to the sun. Other risk factors include exposure to ionizing radiation and arsenic, immunosuppression, and genetic predisposition.¹ Although these malignancies typically do not metastasize, growth can lead to local tissue destruction and major disfigurement if not treated in a timely fashion.²

In our patient, the differential diagnosis included pyoderma gangrenosum (PG) given the clinical appearance of the cribriform base and violaceous undermined rim of the ulcer. Pyoderma gangrenosum is a rare neutrophilic disorder that often results in ulcers that have been associated with various systemic autoimmune and inflammatory conditions, such as inflammatory bowel disease. There are 4 main subtypes of PG: the classic ulcerative type (our patient); the pustular type, which most often is seen in patients with inflammatory bowel disease; the bullous type, which can be seen in patients with an associated lymphoproliferative disorder; and the vegetative type. It frequently is thought of as both a clinical and histologic diagnosis of exclusion due to the nonspecific histopathologic features; most lesions demonstrate an infiltrate of neutrophils in the dermis. A biopsy was crucial in our patient, considering that diagnosis and treatment would have been further delayed had the patient been empirically treated with oral and topical steroids for presumed PG, which is precisely why PG is a diagnosis of exclusion. It is imperative for clinicians to rule out other pathologies, such as infection or malignancy, as demonstrated in our patient. The progressive onset and slow evolution of the lesion over years along with a lack of pain were more suggestive of BCC rather than PG. However, there is a report in the literature of PG mimicking BCC with both clinical and dermoscopic findings.³

Venous or stasis ulcers are painless, and although they rarely occur on the calf, they typically are seen lower on the leg such as on the medial ankles. Our patient endorsed occasional swelling of the affected leg and presented with edema, but overlying stasis change and other signs of venous insufficiency were absent.

Buruli ulcer is a painless chronic debilitating cutaneous disease resulting in indolent necrotizing skin as well as subcutaneous and bone lesions. It is caused by the environmental organism Mycobacterium ulcerans and typically is reported in Africa, Central/South America, the Western Pacific Region, and Australia.⁴ Histopathology usually demonstrates necrosis of subcutaneous tissue and dermal collagen accompanied by inflammation and acidfast bacilli highlighted by Ziehl-Neelsen stain.⁵ Smears of the lesions as well as culture and polymerase chain reaction for acid-fast bacilli also can be performed. Our patient reported no recent travel to any endemic areas and had no other risk factors or exposures to the pathogen responsible for this condition.

Traumatic ulcer also was included in the differential diagnosis, but the patient denied preceding trauma to the area, and the contralateral foot prosthesis did not rub on or impact the affected leg.

Basal cell carcinoma typically is treated surgically, but choice of treatment can depend on the subtype, size, tumor site, and/or patient preference.¹ Other treatment modalities include electrodesiccation and curettage, cryosurgical destruction, photodynamic therapy, radiation, topical therapies, and systemic medications. Radiotherapy can be considered as a primary treatment option for BCC if surgery is contraindicated or declined by the patient, but it also is useful as an adjuvant therapy when there is perineural invasion of the tumor or positive margins. Hedgehog pathway inhibitors such as vismodegib currently are indicated for patients who are not candidates for surgery or radiation as well as for those with metastatic or locally advanced, recurrent BCC. There is no single treatment method ideal for every lesion or patient. Specific populations such as the elderly, the immunosuppressed, or those with poor baseline functional status may warrant a nonsurgical approach. The clinician must take into consideration all factors while at the same time thinking about how to best accomplish the goals of recurrencefree tumor removal, correction of any underlying functional impairment from the tumor, and maintenance of cosmesis.¹

The Diagnosis: Subcutaneous Fat Necrosis

Histopathology revealed lobular panniculitis with lymphohistiocytic inflammation, lipid crystals, and calcifications in our patient (Figure). Subcutaneous fat necrosis (SCFN) was diagnosed based on these characteristic histopathologic findings. No further treatment was pursued.

CT113004027_figAB.jpg

Subcutaneous fat necrosis is a rare, self-limiting panniculitis that typically resolves within several weeks to months without scarring. It manifests as red or violaceous subcutaneous nodules or plaques most commonly on the buttocks, trunk, proximal arms and legs, and cheeks.¹ Histopathology reveals lobular panniculitis with dense granulomatous infiltrates of histiocytes, eosinophils, and multinucleated giant cells with needle-shaped crystals. Focal areas of fat necrosis with calcification also can be seen.²

The epidemiology of SCFN is unknown. Most cases occur in healthy full-term to postterm neonates who experience hypoxia, other prenatal stressors, or therapeutic hypothermia for the treatment of hypoxic-ischemic encephalopathy.³ Although the etiology is unclear, certain inciting factors such as local tissue hypoxia, cold exposure, meconium aspiration, maternal diabetes, preeclampsia, and mechanical pressure have been proposed. Our patient underwent hypothermic cooling protocol, and it has been suggested that the increased saturated to unsaturated fat concentration in the skin of newborns increases the melting point, thus predisposing them to fat crystalization.⁴ Cases of SCFN involving the scalp are rare; therefore, any newborns receiving hypothermic therapy for hypoxic-ischemic encephalopathy should have a thorough skin examination with possible biopsy of lesions that are characteristic of SCFN, such as red or violaceous subcutaneous nodules or plaques, for specific disease identification.

The main complication of SCFN is hypercalcemia, which occurs in approximately 50% of cases. Other serum abnormalities include hyperglycemia, hypertriglyceridemia, and thrombocytopenia, though these findings are not as well associated.⁴ Patients with associated hypercalcemia may be asymptomatic, as in our patient, but other presentations include irritability, weakness, anorexia, vomiting, renal failure, failure to thrive, and encephalopathy. Nephrocalcinosis is a common complication of severe hypercalcemia; however, there is little evidence of associated major renal dysfunction.⁵ The exact mechanism of hypercalcemia is poorly understood. A widely accepted theory postulates that a granulomatous inflammatory infiltrate upregulates 1-α-hydroxylase activity, which enzymatically converts 25-hydroxyvitamin D to its active form, 1,25-dihydroxycholecalciferol, which increases bone resorption and calcium absorption through the gastrointestinal tract and renal systems. Treatments for hypercalcemia include hyperhydration, calcium-wasting diuretics, and low calcium intake.⁶ Furthermore, calcium levels should be obtained at the time of diagnosis and 30, 45, and 60 days after the lesions resolve.⁴

Subcutaneous fat necrosis needs to be differentiated from the more severe panniculitis, sclerema neonatorum (SN), which typically affects critically ill, preterm, and small-for-gestational-age newborns. It is associated with a high mortality rate and is characterized by skin and subadjacent tissue structures. The process typically begins in the thighs, buttocks, or trunk and spreads diffusely, sparing the fat-free palms, soles, and genitalia.⁷ Although our patient was born preterm, the physical characteristics of the nodule and the lack of severe illness placed SN lower on our differential. Histopathologic differences between SCFN and SN involve the extent of tissue fibrosis and presence of inflammatory cells. Sclerema neonatorum typically manifests with thickened connective tissue with a sparse inflammatory infiltrate, including lymphocytes, histiocytes, and multinucleated giant cells.⁷ Conversely, SCFN manifests with fat necrosis with an extensive inflammatory infiltrate. It is important to be able to distinguish between these 2 conditions, as both have vastly different prognoses.

Cold panniculitis, sometimes called “popsicle panniculitis,” is a phenomenon in which cold contact with the skin causes eruption of firm, erythematous, indurated plaques at the site of exposure. This self-limiting condition typically appears hours to days after cold exposure and spontaneously resolves in a few weeks.⁸ Therapeutic hypothermic protocol treatment involves using cooling devices to lower the body temperature for a short duration. The temperature typically is lowered to approximately 32 °C to 36 °C. These temperatures are not low enough to induce cold panniculitis, which is more commonly seen in facial ice applications when managing supraventricular tachycardia in neonates.

Cephalohematoma is a birthing injury that causes blood accumulation within the subperiosteal space. During parturition, the compressive and sheering forces on the calvarium rupture the vessels passing through the periosteum, causing blood to pool slowly into the subperiostium; thus, a cephalohematoma usually manifests later at 1 to 3 days of life as localized head swelling.⁹ The bleeding typically does not cross suture lines and is primarily found in the occipital or parietal regions. The incidence has been reported to be 0.4% to 2.5% of all live births.¹⁰ Although the location of the nodule in our patient was in the occipital region, imaging and biopsy results did not show hemorrhagic findings consistent with cephalohematoma. Management of cephalohematoma mainly is observational, as the mass slowly regresses and the accumulated blood gradually is reabsorbed.

Fungal scalp infections (tinea capitis) are common in the pediatric population. The peak incidence of this infection has been reported in children aged 3 to 7 years, with Trichophyton tonsurans and Microsporum canis as the usual causative organisms.¹¹ Clinical features of tinea capitis include scaly patches with hair loss, hair loss with black pigmented dots at the follicular openings, diffuse scalp scaling with subtle hair loss, and cervical lymphadenopathy.¹² Although less common, tinea capitis can progress to a more severe form known as a kerion, which is characterized by a tender plaque with pustules and crusting. A kerion can result in permanent scarring and alopecia if left untreated.¹² In our patient, a nodule with scaling and faint erythema was observed, but no black pigmented dots at the follicular orifices were present. Therefore, a potassium hydroxide wet mount preparation used to diagnose tinea capitis was unnecessary. Systemic oral antifungal therapy such as fluconazole or terbinafine is the standard treatment for tinea capitis.

The Diagnosis: Subcutaneous Fat Necrosis

Histopathology revealed lobular panniculitis with lymphohistiocytic inflammation, lipid crystals, and calcifications in our patient (Figure). Subcutaneous fat necrosis (SCFN) was diagnosed based on these characteristic histopathologic findings. No further treatment was pursued.

CT113004027_figAB.jpg

Subcutaneous fat necrosis is a rare, self-limiting panniculitis that typically resolves within several weeks to months without scarring. It manifests as red or violaceous subcutaneous nodules or plaques most commonly on the buttocks, trunk, proximal arms and legs, and cheeks.¹ Histopathology reveals lobular panniculitis with dense granulomatous infiltrates of histiocytes, eosinophils, and multinucleated giant cells with needle-shaped crystals. Focal areas of fat necrosis with calcification also can be seen.²

The epidemiology of SCFN is unknown. Most cases occur in healthy full-term to postterm neonates who experience hypoxia, other prenatal stressors, or therapeutic hypothermia for the treatment of hypoxic-ischemic encephalopathy.³ Although the etiology is unclear, certain inciting factors such as local tissue hypoxia, cold exposure, meconium aspiration, maternal diabetes, preeclampsia, and mechanical pressure have been proposed. Our patient underwent hypothermic cooling protocol, and it has been suggested that the increased saturated to unsaturated fat concentration in the skin of newborns increases the melting point, thus predisposing them to fat crystalization.⁴ Cases of SCFN involving the scalp are rare; therefore, any newborns receiving hypothermic therapy for hypoxic-ischemic encephalopathy should have a thorough skin examination with possible biopsy of lesions that are characteristic of SCFN, such as red or violaceous subcutaneous nodules or plaques, for specific disease identification.

The main complication of SCFN is hypercalcemia, which occurs in approximately 50% of cases. Other serum abnormalities include hyperglycemia, hypertriglyceridemia, and thrombocytopenia, though these findings are not as well associated.⁴ Patients with associated hypercalcemia may be asymptomatic, as in our patient, but other presentations include irritability, weakness, anorexia, vomiting, renal failure, failure to thrive, and encephalopathy. Nephrocalcinosis is a common complication of severe hypercalcemia; however, there is little evidence of associated major renal dysfunction.⁵ The exact mechanism of hypercalcemia is poorly understood. A widely accepted theory postulates that a granulomatous inflammatory infiltrate upregulates 1-α-hydroxylase activity, which enzymatically converts 25-hydroxyvitamin D to its active form, 1,25-dihydroxycholecalciferol, which increases bone resorption and calcium absorption through the gastrointestinal tract and renal systems. Treatments for hypercalcemia include hyperhydration, calcium-wasting diuretics, and low calcium intake.⁶ Furthermore, calcium levels should be obtained at the time of diagnosis and 30, 45, and 60 days after the lesions resolve.⁴

Subcutaneous fat necrosis needs to be differentiated from the more severe panniculitis, sclerema neonatorum (SN), which typically affects critically ill, preterm, and small-for-gestational-age newborns. It is associated with a high mortality rate and is characterized by skin and subadjacent tissue structures. The process typically begins in the thighs, buttocks, or trunk and spreads diffusely, sparing the fat-free palms, soles, and genitalia.⁷ Although our patient was born preterm, the physical characteristics of the nodule and the lack of severe illness placed SN lower on our differential. Histopathologic differences between SCFN and SN involve the extent of tissue fibrosis and presence of inflammatory cells. Sclerema neonatorum typically manifests with thickened connective tissue with a sparse inflammatory infiltrate, including lymphocytes, histiocytes, and multinucleated giant cells.⁷ Conversely, SCFN manifests with fat necrosis with an extensive inflammatory infiltrate. It is important to be able to distinguish between these 2 conditions, as both have vastly different prognoses.

Cold panniculitis, sometimes called “popsicle panniculitis,” is a phenomenon in which cold contact with the skin causes eruption of firm, erythematous, indurated plaques at the site of exposure. This self-limiting condition typically appears hours to days after cold exposure and spontaneously resolves in a few weeks.⁸ Therapeutic hypothermic protocol treatment involves using cooling devices to lower the body temperature for a short duration. The temperature typically is lowered to approximately 32 °C to 36 °C. These temperatures are not low enough to induce cold panniculitis, which is more commonly seen in facial ice applications when managing supraventricular tachycardia in neonates.

Cephalohematoma is a birthing injury that causes blood accumulation within the subperiosteal space. During parturition, the compressive and sheering forces on the calvarium rupture the vessels passing through the periosteum, causing blood to pool slowly into the subperiostium; thus, a cephalohematoma usually manifests later at 1 to 3 days of life as localized head swelling.⁹ The bleeding typically does not cross suture lines and is primarily found in the occipital or parietal regions. The incidence has been reported to be 0.4% to 2.5% of all live births.¹⁰ Although the location of the nodule in our patient was in the occipital region, imaging and biopsy results did not show hemorrhagic findings consistent with cephalohematoma. Management of cephalohematoma mainly is observational, as the mass slowly regresses and the accumulated blood gradually is reabsorbed.

Fungal scalp infections (tinea capitis) are common in the pediatric population. The peak incidence of this infection has been reported in children aged 3 to 7 years, with Trichophyton tonsurans and Microsporum canis as the usual causative organisms.¹¹ Clinical features of tinea capitis include scaly patches with hair loss, hair loss with black pigmented dots at the follicular openings, diffuse scalp scaling with subtle hair loss, and cervical lymphadenopathy.¹² Although less common, tinea capitis can progress to a more severe form known as a kerion, which is characterized by a tender plaque with pustules and crusting. A kerion can result in permanent scarring and alopecia if left untreated.¹² In our patient, a nodule with scaling and faint erythema was observed, but no black pigmented dots at the follicular orifices were present. Therefore, a potassium hydroxide wet mount preparation used to diagnose tinea capitis was unnecessary. Systemic oral antifungal therapy such as fluconazole or terbinafine is the standard treatment for tinea capitis.

The Diagnosis: Subcutaneous Fat Necrosis

Histopathology revealed lobular panniculitis with lymphohistiocytic inflammation, lipid crystals, and calcifications in our patient (Figure). Subcutaneous fat necrosis (SCFN) was diagnosed based on these characteristic histopathologic findings. No further treatment was pursued.

CT113004027_figAB.jpg

Subcutaneous fat necrosis is a rare, self-limiting panniculitis that typically resolves within several weeks to months without scarring. It manifests as red or violaceous subcutaneous nodules or plaques most commonly on the buttocks, trunk, proximal arms and legs, and cheeks.¹ Histopathology reveals lobular panniculitis with dense granulomatous infiltrates of histiocytes, eosinophils, and multinucleated giant cells with needle-shaped crystals. Focal areas of fat necrosis with calcification also can be seen.²

The epidemiology of SCFN is unknown. Most cases occur in healthy full-term to postterm neonates who experience hypoxia, other prenatal stressors, or therapeutic hypothermia for the treatment of hypoxic-ischemic encephalopathy.³ Although the etiology is unclear, certain inciting factors such as local tissue hypoxia, cold exposure, meconium aspiration, maternal diabetes, preeclampsia, and mechanical pressure have been proposed. Our patient underwent hypothermic cooling protocol, and it has been suggested that the increased saturated to unsaturated fat concentration in the skin of newborns increases the melting point, thus predisposing them to fat crystalization.⁴ Cases of SCFN involving the scalp are rare; therefore, any newborns receiving hypothermic therapy for hypoxic-ischemic encephalopathy should have a thorough skin examination with possible biopsy of lesions that are characteristic of SCFN, such as red or violaceous subcutaneous nodules or plaques, for specific disease identification.

The main complication of SCFN is hypercalcemia, which occurs in approximately 50% of cases. Other serum abnormalities include hyperglycemia, hypertriglyceridemia, and thrombocytopenia, though these findings are not as well associated.⁴ Patients with associated hypercalcemia may be asymptomatic, as in our patient, but other presentations include irritability, weakness, anorexia, vomiting, renal failure, failure to thrive, and encephalopathy. Nephrocalcinosis is a common complication of severe hypercalcemia; however, there is little evidence of associated major renal dysfunction.⁵ The exact mechanism of hypercalcemia is poorly understood. A widely accepted theory postulates that a granulomatous inflammatory infiltrate upregulates 1-α-hydroxylase activity, which enzymatically converts 25-hydroxyvitamin D to its active form, 1,25-dihydroxycholecalciferol, which increases bone resorption and calcium absorption through the gastrointestinal tract and renal systems. Treatments for hypercalcemia include hyperhydration, calcium-wasting diuretics, and low calcium intake.⁶ Furthermore, calcium levels should be obtained at the time of diagnosis and 30, 45, and 60 days after the lesions resolve.⁴

Subcutaneous fat necrosis needs to be differentiated from the more severe panniculitis, sclerema neonatorum (SN), which typically affects critically ill, preterm, and small-for-gestational-age newborns. It is associated with a high mortality rate and is characterized by skin and subadjacent tissue structures. The process typically begins in the thighs, buttocks, or trunk and spreads diffusely, sparing the fat-free palms, soles, and genitalia.⁷ Although our patient was born preterm, the physical characteristics of the nodule and the lack of severe illness placed SN lower on our differential. Histopathologic differences between SCFN and SN involve the extent of tissue fibrosis and presence of inflammatory cells. Sclerema neonatorum typically manifests with thickened connective tissue with a sparse inflammatory infiltrate, including lymphocytes, histiocytes, and multinucleated giant cells.⁷ Conversely, SCFN manifests with fat necrosis with an extensive inflammatory infiltrate. It is important to be able to distinguish between these 2 conditions, as both have vastly different prognoses.

Cold panniculitis, sometimes called “popsicle panniculitis,” is a phenomenon in which cold contact with the skin causes eruption of firm, erythematous, indurated plaques at the site of exposure. This self-limiting condition typically appears hours to days after cold exposure and spontaneously resolves in a few weeks.⁸ Therapeutic hypothermic protocol treatment involves using cooling devices to lower the body temperature for a short duration. The temperature typically is lowered to approximately 32 °C to 36 °C. These temperatures are not low enough to induce cold panniculitis, which is more commonly seen in facial ice applications when managing supraventricular tachycardia in neonates.

Cephalohematoma is a birthing injury that causes blood accumulation within the subperiosteal space. During parturition, the compressive and sheering forces on the calvarium rupture the vessels passing through the periosteum, causing blood to pool slowly into the subperiostium; thus, a cephalohematoma usually manifests later at 1 to 3 days of life as localized head swelling.⁹ The bleeding typically does not cross suture lines and is primarily found in the occipital or parietal regions. The incidence has been reported to be 0.4% to 2.5% of all live births.¹⁰ Although the location of the nodule in our patient was in the occipital region, imaging and biopsy results did not show hemorrhagic findings consistent with cephalohematoma. Management of cephalohematoma mainly is observational, as the mass slowly regresses and the accumulated blood gradually is reabsorbed.

Fungal scalp infections (tinea capitis) are common in the pediatric population. The peak incidence of this infection has been reported in children aged 3 to 7 years, with Trichophyton tonsurans and Microsporum canis as the usual causative organisms.¹¹ Clinical features of tinea capitis include scaly patches with hair loss, hair loss with black pigmented dots at the follicular openings, diffuse scalp scaling with subtle hair loss, and cervical lymphadenopathy.¹² Although less common, tinea capitis can progress to a more severe form known as a kerion, which is characterized by a tender plaque with pustules and crusting. A kerion can result in permanent scarring and alopecia if left untreated.¹² In our patient, a nodule with scaling and faint erythema was observed, but no black pigmented dots at the follicular orifices were present. Therefore, a potassium hydroxide wet mount preparation used to diagnose tinea capitis was unnecessary. Systemic oral antifungal therapy such as fluconazole or terbinafine is the standard treatment for tinea capitis.

The Diagnosis: Erythrodermic Allergic Contact Dermatitis

The worsening symptoms in our patient prompted intervention rather than observation and reassurance. Contact allergy to lanolin was suspected given the worsening presentation after the addition of Minerin, which was immediately discontinued. The patient’s family applied betamethasone cream 0.1% twice daily to severe plaques, pimecrolimus cream 1% to the face, and triamcinolone cream 0.1% to the rest of the body. At follow-up 1 week later, he experienced complete resolution of symptoms, which supported the diagnosis of erythrodermic allergic contact dermatitis (ACD).

The prevalence of ACD caused by lanolin varies among the general population from 1.2% to 6.9%.¹ Lanolin recently was named Allergen of the Year in 2023 by the American Contact Dermatitis Society.² It can be found in various commercial products, including creams, soaps, and ointments. Atopic dermatitis (AD) is a common pediatric inflammatory skin disorder that typically is treated with these products.³ In a study analyzing 533 products, up to 6% of skin care products for babies and children contained lanolin.⁴ Therefore, exposure to lanolin-containing products may be fairly common in the pediatric population.

Lanolin is a fatlike substance derived from sheep sebaceous gland secretions and extracted from sheep’s wool. Its composition varies by sheep breed, location, and extraction and purification methods. The most common allergens involve the alcoholic fraction produced by hydrolysis of lanolin.⁴ In 1996, Wolf⁵ described the “lanolin paradox,” which argued the difficulty with identifying lanolin as an allergen (similar to Fisher’s “paraben paradox”) based on 4 principles: (1) lanolin-containing topical medicaments tend to be more sensitizing than lanolin-containing cosmetics; (2) patients with ACD after applying lanolin-containing topical medicaments to damaged or ulcerated skin often can apply lanolin-containing cosmetics to normal or unaffected skin without a reaction; (3) false-negative patch test results often occur in lanolin-sensitive patients; and (4) patch testing with a single lanolin-containing agent (lanolin alcohol [30% in petrolatum]) is an unreliable and inadequate method of detecting lanolin allergy.^6,7 This theory elucidates the challenge of diagnosing contact allergies, particularly lanolin contact allergies.

Clinical features of acute ACD vary by skin type. Lighter skin types may have well-demarcated, pruritic, eczematous patches and plaques affecting the flexor surfaces. Asian patients may present with psoriasiform plaques with more well-demarcated borders and increased scaling and lichenification. In patients with darker skin types, dermatitis may manifest as papulation, lichenification, and color changes (violet, gray, or darker brown) along extensor surfaces.8 Chronic dermatitis manifests as lichenified scaly plaques. Given the diversity in dermatitis manifestation and the challenges of identifying erythema, especially in skin of color, clinicians may misidentify disease severity. These features aid in diagnosing and treating patients presenting with diffuse erythroderma and worsening eczematous patches and plaques despite use of typical topical treatments.

The differential diagnosis includes irritant contact dermatitis, AD, seborrheic dermatitis, and chronic plaque psoriasis. Negative patch testing suggests contact dermatitis based on exposure to a product. A thorough medication and personal history helps distinguish ACD from AD. Atopic dermatitis classically appears on the flexural areas, face, eyelids, and hands of patients with a personal or family history of atopy. Greasy scaly plaques on the central part of the face, eyelids, and scalp commonly are found in seborrheic dermatitis. In chronic plaque psoriasis, lesions typically are described as welldemarcated, inflamed plaques with notable scale located primarily in the scalp and diaper area in newborns and children until the age of 2 years. Our patient presented with scaly plaques throughout most of the body. The history of Minerin use over the course of 3 to 5 months and worsening skin eruptions involving a majority of the skin surface suggested continued exposure.

Patch testing assists in the diagnosis of ACD, with varying results due to manufacturing and processing inconsistencies in the composition of various substances used in the standard test sets, often making it difficult to diagnose lanolin as an allergen. According to Lee and Warshaw,6 the lack of uniformity within testing of lanolin-containing products may cause false-positive results, poor patch-test reproducibility, and loss of allergic contact response. A 2019 study utilized a combination of Amerchol L101 and lanolin alcohol to improve the diagnosis of lanolin allergy, as standard testing may not identify patients with lanolin sensitivities.1 A study with the North American Contact Dermatitis Group from 2005 to 2012 demonstrated that positive patch testing among children was the most consistent method for diagnosing ACD, and results were clinically relevant.⁹ However, the different lanolin-containing products are not standardized in patch testing, which often causes mixed reactions and does not definitely demonstrate classic positive results, even with the use of repeated open application tests.² Although there has been an emphasis on refining the standardization of the lanolin used for patch testing, lanolin contact allergy remains a predominantly clinical diagnosis.

Both AD and ACD are common pediatric skin findings, and mixed positive and neutral associations between AD and allergy to lanolin have been described in a few studies.^1,3,9,10 A history of atopy is more notable in a pediatric patient vs an adult, as sensitivities tend to subside into adulthood.⁹ Further studies and more precise testing are needed to investigate the relationship between AD and ACD.

The Diagnosis: Erythrodermic Allergic Contact Dermatitis

The worsening symptoms in our patient prompted intervention rather than observation and reassurance. Contact allergy to lanolin was suspected given the worsening presentation after the addition of Minerin, which was immediately discontinued. The patient’s family applied betamethasone cream 0.1% twice daily to severe plaques, pimecrolimus cream 1% to the face, and triamcinolone cream 0.1% to the rest of the body. At follow-up 1 week later, he experienced complete resolution of symptoms, which supported the diagnosis of erythrodermic allergic contact dermatitis (ACD).

The prevalence of ACD caused by lanolin varies among the general population from 1.2% to 6.9%.¹ Lanolin recently was named Allergen of the Year in 2023 by the American Contact Dermatitis Society.² It can be found in various commercial products, including creams, soaps, and ointments. Atopic dermatitis (AD) is a common pediatric inflammatory skin disorder that typically is treated with these products.³ In a study analyzing 533 products, up to 6% of skin care products for babies and children contained lanolin.⁴ Therefore, exposure to lanolin-containing products may be fairly common in the pediatric population.

Lanolin is a fatlike substance derived from sheep sebaceous gland secretions and extracted from sheep’s wool. Its composition varies by sheep breed, location, and extraction and purification methods. The most common allergens involve the alcoholic fraction produced by hydrolysis of lanolin.⁴ In 1996, Wolf⁵ described the “lanolin paradox,” which argued the difficulty with identifying lanolin as an allergen (similar to Fisher’s “paraben paradox”) based on 4 principles: (1) lanolin-containing topical medicaments tend to be more sensitizing than lanolin-containing cosmetics; (2) patients with ACD after applying lanolin-containing topical medicaments to damaged or ulcerated skin often can apply lanolin-containing cosmetics to normal or unaffected skin without a reaction; (3) false-negative patch test results often occur in lanolin-sensitive patients; and (4) patch testing with a single lanolin-containing agent (lanolin alcohol [30% in petrolatum]) is an unreliable and inadequate method of detecting lanolin allergy.^6,7 This theory elucidates the challenge of diagnosing contact allergies, particularly lanolin contact allergies.

Clinical features of acute ACD vary by skin type. Lighter skin types may have well-demarcated, pruritic, eczematous patches and plaques affecting the flexor surfaces. Asian patients may present with psoriasiform plaques with more well-demarcated borders and increased scaling and lichenification. In patients with darker skin types, dermatitis may manifest as papulation, lichenification, and color changes (violet, gray, or darker brown) along extensor surfaces.8 Chronic dermatitis manifests as lichenified scaly plaques. Given the diversity in dermatitis manifestation and the challenges of identifying erythema, especially in skin of color, clinicians may misidentify disease severity. These features aid in diagnosing and treating patients presenting with diffuse erythroderma and worsening eczematous patches and plaques despite use of typical topical treatments.

The differential diagnosis includes irritant contact dermatitis, AD, seborrheic dermatitis, and chronic plaque psoriasis. Negative patch testing suggests contact dermatitis based on exposure to a product. A thorough medication and personal history helps distinguish ACD from AD. Atopic dermatitis classically appears on the flexural areas, face, eyelids, and hands of patients with a personal or family history of atopy. Greasy scaly plaques on the central part of the face, eyelids, and scalp commonly are found in seborrheic dermatitis. In chronic plaque psoriasis, lesions typically are described as welldemarcated, inflamed plaques with notable scale located primarily in the scalp and diaper area in newborns and children until the age of 2 years. Our patient presented with scaly plaques throughout most of the body. The history of Minerin use over the course of 3 to 5 months and worsening skin eruptions involving a majority of the skin surface suggested continued exposure.

Patch testing assists in the diagnosis of ACD, with varying results due to manufacturing and processing inconsistencies in the composition of various substances used in the standard test sets, often making it difficult to diagnose lanolin as an allergen. According to Lee and Warshaw,6 the lack of uniformity within testing of lanolin-containing products may cause false-positive results, poor patch-test reproducibility, and loss of allergic contact response. A 2019 study utilized a combination of Amerchol L101 and lanolin alcohol to improve the diagnosis of lanolin allergy, as standard testing may not identify patients with lanolin sensitivities.1 A study with the North American Contact Dermatitis Group from 2005 to 2012 demonstrated that positive patch testing among children was the most consistent method for diagnosing ACD, and results were clinically relevant.⁹ However, the different lanolin-containing products are not standardized in patch testing, which often causes mixed reactions and does not definitely demonstrate classic positive results, even with the use of repeated open application tests.² Although there has been an emphasis on refining the standardization of the lanolin used for patch testing, lanolin contact allergy remains a predominantly clinical diagnosis.

Both AD and ACD are common pediatric skin findings, and mixed positive and neutral associations between AD and allergy to lanolin have been described in a few studies.^1,3,9,10 A history of atopy is more notable in a pediatric patient vs an adult, as sensitivities tend to subside into adulthood.⁹ Further studies and more precise testing are needed to investigate the relationship between AD and ACD.

The Diagnosis: Erythrodermic Allergic Contact Dermatitis

The worsening symptoms in our patient prompted intervention rather than observation and reassurance. Contact allergy to lanolin was suspected given the worsening presentation after the addition of Minerin, which was immediately discontinued. The patient’s family applied betamethasone cream 0.1% twice daily to severe plaques, pimecrolimus cream 1% to the face, and triamcinolone cream 0.1% to the rest of the body. At follow-up 1 week later, he experienced complete resolution of symptoms, which supported the diagnosis of erythrodermic allergic contact dermatitis (ACD).

The prevalence of ACD caused by lanolin varies among the general population from 1.2% to 6.9%.¹ Lanolin recently was named Allergen of the Year in 2023 by the American Contact Dermatitis Society.² It can be found in various commercial products, including creams, soaps, and ointments. Atopic dermatitis (AD) is a common pediatric inflammatory skin disorder that typically is treated with these products.³ In a study analyzing 533 products, up to 6% of skin care products for babies and children contained lanolin.⁴ Therefore, exposure to lanolin-containing products may be fairly common in the pediatric population.

Lanolin is a fatlike substance derived from sheep sebaceous gland secretions and extracted from sheep’s wool. Its composition varies by sheep breed, location, and extraction and purification methods. The most common allergens involve the alcoholic fraction produced by hydrolysis of lanolin.⁴ In 1996, Wolf⁵ described the “lanolin paradox,” which argued the difficulty with identifying lanolin as an allergen (similar to Fisher’s “paraben paradox”) based on 4 principles: (1) lanolin-containing topical medicaments tend to be more sensitizing than lanolin-containing cosmetics; (2) patients with ACD after applying lanolin-containing topical medicaments to damaged or ulcerated skin often can apply lanolin-containing cosmetics to normal or unaffected skin without a reaction; (3) false-negative patch test results often occur in lanolin-sensitive patients; and (4) patch testing with a single lanolin-containing agent (lanolin alcohol [30% in petrolatum]) is an unreliable and inadequate method of detecting lanolin allergy.^6,7 This theory elucidates the challenge of diagnosing contact allergies, particularly lanolin contact allergies.

Clinical features of acute ACD vary by skin type. Lighter skin types may have well-demarcated, pruritic, eczematous patches and plaques affecting the flexor surfaces. Asian patients may present with psoriasiform plaques with more well-demarcated borders and increased scaling and lichenification. In patients with darker skin types, dermatitis may manifest as papulation, lichenification, and color changes (violet, gray, or darker brown) along extensor surfaces.8 Chronic dermatitis manifests as lichenified scaly plaques. Given the diversity in dermatitis manifestation and the challenges of identifying erythema, especially in skin of color, clinicians may misidentify disease severity. These features aid in diagnosing and treating patients presenting with diffuse erythroderma and worsening eczematous patches and plaques despite use of typical topical treatments.

The differential diagnosis includes irritant contact dermatitis, AD, seborrheic dermatitis, and chronic plaque psoriasis. Negative patch testing suggests contact dermatitis based on exposure to a product. A thorough medication and personal history helps distinguish ACD from AD. Atopic dermatitis classically appears on the flexural areas, face, eyelids, and hands of patients with a personal or family history of atopy. Greasy scaly plaques on the central part of the face, eyelids, and scalp commonly are found in seborrheic dermatitis. In chronic plaque psoriasis, lesions typically are described as welldemarcated, inflamed plaques with notable scale located primarily in the scalp and diaper area in newborns and children until the age of 2 years. Our patient presented with scaly plaques throughout most of the body. The history of Minerin use over the course of 3 to 5 months and worsening skin eruptions involving a majority of the skin surface suggested continued exposure.

Patch testing assists in the diagnosis of ACD, with varying results due to manufacturing and processing inconsistencies in the composition of various substances used in the standard test sets, often making it difficult to diagnose lanolin as an allergen. According to Lee and Warshaw,6 the lack of uniformity within testing of lanolin-containing products may cause false-positive results, poor patch-test reproducibility, and loss of allergic contact response. A 2019 study utilized a combination of Amerchol L101 and lanolin alcohol to improve the diagnosis of lanolin allergy, as standard testing may not identify patients with lanolin sensitivities.1 A study with the North American Contact Dermatitis Group from 2005 to 2012 demonstrated that positive patch testing among children was the most consistent method for diagnosing ACD, and results were clinically relevant.⁹ However, the different lanolin-containing products are not standardized in patch testing, which often causes mixed reactions and does not definitely demonstrate classic positive results, even with the use of repeated open application tests.² Although there has been an emphasis on refining the standardization of the lanolin used for patch testing, lanolin contact allergy remains a predominantly clinical diagnosis.

Both AD and ACD are common pediatric skin findings, and mixed positive and neutral associations between AD and allergy to lanolin have been described in a few studies.^1,3,9,10 A history of atopy is more notable in a pediatric patient vs an adult, as sensitivities tend to subside into adulthood.⁹ Further studies and more precise testing are needed to investigate the relationship between AD and ACD.

The Diagnosis: Hypertrophic Lichen Planus

Two biopsies from the left lateral foot revealed hyperkeratosis, wedge-shaped hypergranulosis, irregular acanthosis, and a bandlike lymphocytic infiltrate in the superficial dermis with a classic sawtooth pattern of the rete ridges (Figure 1). Based on the clinical findings and histopathology, the patient was diagnosed with hypertrophic lichen planus (LP) and was treated with clobetasol ointment 0.05%, which resulted in progression of the symptoms. She experienced notable improvement 3 months after adding methotrexate 12.5 mg weekly (Figure 2).

Medina_1.jpg

Lichen planus is an idiopathic chronic inflammatory condition of the skin and mucous membranes that classically manifests as pruritic violaceous papules and plaques, which commonly are found on the wrists, lower back, and ankles.¹ The most common variants of LP are hypertrophic, linear, mucosal, actinic, follicular, pigmented, annular, atrophic, and guttate.² The clinical presentation and biopsy results in our patient were consistent with the hypertrophic variant of LP, which is a chronic condition that most often manifests on the lower legs, especially around the ankles, as hyperkeratotic papules, plaques, and nodules.^2,3 The exact pathophysiology of hypertrophic LP is unknown, but there is evidence that the immune system plays a role in its development and that the Koebner phenomenon may contribute to its exacerbation.⁴ There is a well-known association between LP and hepatitis. Patients with chronic LP may develop squamous cell carcinoma.⁴ The variants of LP can overlap and do not exist independent of one another. Recognizing the overlap in these variants allows for earlier diagnosis and therapeutic intervention of the disease process to limit disease progression and patient clinic visits and to improve patient quality of life.

CT113004010_e_Fig2_AB.jpg

The differential diagnosis for hyperkeratotic plaques of the feet and ankles can be broad and may include keratosis lichenoides chronica, palmoplantar keratoderma, palmoplantar psoriasis, or lichen amyloidosis. These conditions are classified based on various criteria that include extent of disease manifestations, morphology of palmoplantar skin involvement, inheritance patterns, and molecular pathogenesis.⁵ Keratosis lichenoides chronica is a rare dermatosis that presents as a distinctive seborrheic dermatitis–like facial eruption. The facial eruption is accompanied by violaceous papular and nodular lesions that appear on the extremities and trunk, typically arranged in a linear or reticular pattern.⁶ Palmoplantar keratoderma represents a group of acquired and hereditary conditions that are characterized by excessive thickening of the palms and soles.⁵ Palmoplantar psoriasis is a variant of psoriasis that affects the palms and soles and can manifest as hyperkeratosis, pustular, or mixed morphology.⁷ Lichen amyloidosis is a subtype of primary localized cutaneous amyloidosis that manifests as multiple pruritic, firm, hyperpigmented, hyperkeratotic papules on the shins that later coalesce in a rippled pattern.^8,9

The first-line treatment for hypertrophic LP is topical corticosteroids. Alternative therapies include mycophenolate mofetil, acitretin, and intralesional corticosteroid injections.⁴ Treatment is similar for all of the LP variants.

The Diagnosis: Hypertrophic Lichen Planus

Two biopsies from the left lateral foot revealed hyperkeratosis, wedge-shaped hypergranulosis, irregular acanthosis, and a bandlike lymphocytic infiltrate in the superficial dermis with a classic sawtooth pattern of the rete ridges (Figure 1). Based on the clinical findings and histopathology, the patient was diagnosed with hypertrophic lichen planus (LP) and was treated with clobetasol ointment 0.05%, which resulted in progression of the symptoms. She experienced notable improvement 3 months after adding methotrexate 12.5 mg weekly (Figure 2).

Medina_1.jpg

Lichen planus is an idiopathic chronic inflammatory condition of the skin and mucous membranes that classically manifests as pruritic violaceous papules and plaques, which commonly are found on the wrists, lower back, and ankles.¹ The most common variants of LP are hypertrophic, linear, mucosal, actinic, follicular, pigmented, annular, atrophic, and guttate.² The clinical presentation and biopsy results in our patient were consistent with the hypertrophic variant of LP, which is a chronic condition that most often manifests on the lower legs, especially around the ankles, as hyperkeratotic papules, plaques, and nodules.^2,3 The exact pathophysiology of hypertrophic LP is unknown, but there is evidence that the immune system plays a role in its development and that the Koebner phenomenon may contribute to its exacerbation.⁴ There is a well-known association between LP and hepatitis. Patients with chronic LP may develop squamous cell carcinoma.⁴ The variants of LP can overlap and do not exist independent of one another. Recognizing the overlap in these variants allows for earlier diagnosis and therapeutic intervention of the disease process to limit disease progression and patient clinic visits and to improve patient quality of life.

CT113004010_e_Fig2_AB.jpg

The differential diagnosis for hyperkeratotic plaques of the feet and ankles can be broad and may include keratosis lichenoides chronica, palmoplantar keratoderma, palmoplantar psoriasis, or lichen amyloidosis. These conditions are classified based on various criteria that include extent of disease manifestations, morphology of palmoplantar skin involvement, inheritance patterns, and molecular pathogenesis.⁵ Keratosis lichenoides chronica is a rare dermatosis that presents as a distinctive seborrheic dermatitis–like facial eruption. The facial eruption is accompanied by violaceous papular and nodular lesions that appear on the extremities and trunk, typically arranged in a linear or reticular pattern.⁶ Palmoplantar keratoderma represents a group of acquired and hereditary conditions that are characterized by excessive thickening of the palms and soles.⁵ Palmoplantar psoriasis is a variant of psoriasis that affects the palms and soles and can manifest as hyperkeratosis, pustular, or mixed morphology.⁷ Lichen amyloidosis is a subtype of primary localized cutaneous amyloidosis that manifests as multiple pruritic, firm, hyperpigmented, hyperkeratotic papules on the shins that later coalesce in a rippled pattern.^8,9

The first-line treatment for hypertrophic LP is topical corticosteroids. Alternative therapies include mycophenolate mofetil, acitretin, and intralesional corticosteroid injections.⁴ Treatment is similar for all of the LP variants.

The Diagnosis: Hypertrophic Lichen Planus

Two biopsies from the left lateral foot revealed hyperkeratosis, wedge-shaped hypergranulosis, irregular acanthosis, and a bandlike lymphocytic infiltrate in the superficial dermis with a classic sawtooth pattern of the rete ridges (Figure 1). Based on the clinical findings and histopathology, the patient was diagnosed with hypertrophic lichen planus (LP) and was treated with clobetasol ointment 0.05%, which resulted in progression of the symptoms. She experienced notable improvement 3 months after adding methotrexate 12.5 mg weekly (Figure 2).

Medina_1.jpg

Lichen planus is an idiopathic chronic inflammatory condition of the skin and mucous membranes that classically manifests as pruritic violaceous papules and plaques, which commonly are found on the wrists, lower back, and ankles.¹ The most common variants of LP are hypertrophic, linear, mucosal, actinic, follicular, pigmented, annular, atrophic, and guttate.² The clinical presentation and biopsy results in our patient were consistent with the hypertrophic variant of LP, which is a chronic condition that most often manifests on the lower legs, especially around the ankles, as hyperkeratotic papules, plaques, and nodules.^2,3 The exact pathophysiology of hypertrophic LP is unknown, but there is evidence that the immune system plays a role in its development and that the Koebner phenomenon may contribute to its exacerbation.⁴ There is a well-known association between LP and hepatitis. Patients with chronic LP may develop squamous cell carcinoma.⁴ The variants of LP can overlap and do not exist independent of one another. Recognizing the overlap in these variants allows for earlier diagnosis and therapeutic intervention of the disease process to limit disease progression and patient clinic visits and to improve patient quality of life.

CT113004010_e_Fig2_AB.jpg

The differential diagnosis for hyperkeratotic plaques of the feet and ankles can be broad and may include keratosis lichenoides chronica, palmoplantar keratoderma, palmoplantar psoriasis, or lichen amyloidosis. These conditions are classified based on various criteria that include extent of disease manifestations, morphology of palmoplantar skin involvement, inheritance patterns, and molecular pathogenesis.⁵ Keratosis lichenoides chronica is a rare dermatosis that presents as a distinctive seborrheic dermatitis–like facial eruption. The facial eruption is accompanied by violaceous papular and nodular lesions that appear on the extremities and trunk, typically arranged in a linear or reticular pattern.⁶ Palmoplantar keratoderma represents a group of acquired and hereditary conditions that are characterized by excessive thickening of the palms and soles.⁵ Palmoplantar psoriasis is a variant of psoriasis that affects the palms and soles and can manifest as hyperkeratosis, pustular, or mixed morphology.⁷ Lichen amyloidosis is a subtype of primary localized cutaneous amyloidosis that manifests as multiple pruritic, firm, hyperpigmented, hyperkeratotic papules on the shins that later coalesce in a rippled pattern.^8,9

The first-line treatment for hypertrophic LP is topical corticosteroids. Alternative therapies include mycophenolate mofetil, acitretin, and intralesional corticosteroid injections.⁴ Treatment is similar for all of the LP variants.