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The Diagnosis: Scrotal Calcinosis

Scrotal calcinosis is a rare benign disease that results from the deposition of calcium, magnesium, phosphate, and carbonate within the dermis and subcutaneous layer of the skin in the absence of underlying systemic disease or serum calcium and phosphorus abnormalities.^1,2 Lesions usually are asymptomatic but can be mildly painful or pruritic. They usually present in childhood or early adulthood as yellow-white firm nodules ranging in size from a few millimeters to a few centimeters that increase in size and number over time. Additionally, lesions can ulcerate and discharge a chalklike exudative material. Although benign in nature, the quality-of-life impact in patients with this condition can be substantial, specifically regarding cosmesis, which may cause patients to feel embarrassed and even avoid sexual activity. This condition rarely has been associated with infection.¹

Our patient elected to undergo surgical excision under local anesthesia, and the lesions were sent for histopathologic examination. His postoperative course was unremarkable, and he was pleased with the cosmetic result of the surgery (Figure 1). Histopathology revealed calcified deposits that appeared as intradermal basophilic nodules lacking an epithelial lining (Figure 2), consistent with the diagnosis of scrotal calcinosis.² No recurrence of the lesions was documented over the course of 18 months.

The pathogenesis of this condition is not clear. Most research supports scrotal calcinosis resulting from dystrophic calcification of epidermal inclusion cysts.³ There have been cases of scrotal calcinosis coinciding with epidermal inclusion cysts of the scrotum in varying stages of inflammation (some intact and some ruptured).² Some research also suggests dystrophic calcification of eccrine epithelial cysts and degenerated dartos muscle as the origin of scrotal calcinosis.³

The differential diagnosis for this case included calcified steatocystoma multiplex, eruptive xanthomas, nodular scabies, and epidermal inclusion cysts. Steatocystoma multiplex can be inherited in an autosomal-dominant fashion or can develop sporadically with mutations in the KRT17 gene.⁴ It is characterized by multiple sebum-filled, cystic lesions of the pilosebaceous unit that may become calcified. Calcified lesions appear as yellow, firm, irregularly shaped papules or nodules ranging from a few millimeters to centimeters in size. Cysts can develop anywhere on the body with a predilection for the chest, upper extremities, axillae, trunk, groin, and scrotum.⁴ Histologically, our patient’s lesions were not associated with the pilosebaceous unit. Additionally, our patient denied a family history of similar skin lesions, which made calcified steatocystoma multiplex an unlikely diagnosis.

Eruptive xanthomas result from localized deposition of lipids within the dermis, typically in the setting of dyslipidemia or poorly controlled diabetes mellitus. They commonly appear on the extremities or buttocks as pruritic crops of yellow-red papules or nodules that are a few millimeters in size. Although our patient has a history of hyperlipidemia, his lesions differed substantially from eruptive xanthomas in clinical presentation.

Nodular scabies is a manifestation of classic scabies that presents with intensely pruritic erythematous papules and nodules that are a few millimeters in size and commonly occur on the axillae, groin, and genitalia. Our patient’s skin lesions were not pruritic and differed in appearance from nodular scabies.

Although research indicates scrotal calcinosis may result from dystrophic calcification of epidermal inclusion cysts,² the latter present as dome-shaped, flesh-colored nodules with central pores representing the opening of hair follicles. Our patient lacked characteristic findings of epidermal inclusion cysts on histology.

The preferred treatment for scrotal calcinosis is surgical excision, which improves the aesthetic appearance, relieves itch, and removes ulcerative lesions.⁵ Additionally, surgical excision provides histological diagnostic confirmation. Recurrence with incomplete excision is possible; therefore, all lesions should be completely excised to reduce the risk for recurrence.³

The Diagnosis: Scrotal Calcinosis

Scrotal calcinosis is a rare benign disease that results from the deposition of calcium, magnesium, phosphate, and carbonate within the dermis and subcutaneous layer of the skin in the absence of underlying systemic disease or serum calcium and phosphorus abnormalities.^1,2 Lesions usually are asymptomatic but can be mildly painful or pruritic. They usually present in childhood or early adulthood as yellow-white firm nodules ranging in size from a few millimeters to a few centimeters that increase in size and number over time. Additionally, lesions can ulcerate and discharge a chalklike exudative material. Although benign in nature, the quality-of-life impact in patients with this condition can be substantial, specifically regarding cosmesis, which may cause patients to feel embarrassed and even avoid sexual activity. This condition rarely has been associated with infection.¹

Our patient elected to undergo surgical excision under local anesthesia, and the lesions were sent for histopathologic examination. His postoperative course was unremarkable, and he was pleased with the cosmetic result of the surgery (Figure 1). Histopathology revealed calcified deposits that appeared as intradermal basophilic nodules lacking an epithelial lining (Figure 2), consistent with the diagnosis of scrotal calcinosis.² No recurrence of the lesions was documented over the course of 18 months.

The pathogenesis of this condition is not clear. Most research supports scrotal calcinosis resulting from dystrophic calcification of epidermal inclusion cysts.³ There have been cases of scrotal calcinosis coinciding with epidermal inclusion cysts of the scrotum in varying stages of inflammation (some intact and some ruptured).² Some research also suggests dystrophic calcification of eccrine epithelial cysts and degenerated dartos muscle as the origin of scrotal calcinosis.³

The differential diagnosis for this case included calcified steatocystoma multiplex, eruptive xanthomas, nodular scabies, and epidermal inclusion cysts. Steatocystoma multiplex can be inherited in an autosomal-dominant fashion or can develop sporadically with mutations in the KRT17 gene.⁴ It is characterized by multiple sebum-filled, cystic lesions of the pilosebaceous unit that may become calcified. Calcified lesions appear as yellow, firm, irregularly shaped papules or nodules ranging from a few millimeters to centimeters in size. Cysts can develop anywhere on the body with a predilection for the chest, upper extremities, axillae, trunk, groin, and scrotum.⁴ Histologically, our patient’s lesions were not associated with the pilosebaceous unit. Additionally, our patient denied a family history of similar skin lesions, which made calcified steatocystoma multiplex an unlikely diagnosis.

Eruptive xanthomas result from localized deposition of lipids within the dermis, typically in the setting of dyslipidemia or poorly controlled diabetes mellitus. They commonly appear on the extremities or buttocks as pruritic crops of yellow-red papules or nodules that are a few millimeters in size. Although our patient has a history of hyperlipidemia, his lesions differed substantially from eruptive xanthomas in clinical presentation.

Nodular scabies is a manifestation of classic scabies that presents with intensely pruritic erythematous papules and nodules that are a few millimeters in size and commonly occur on the axillae, groin, and genitalia. Our patient’s skin lesions were not pruritic and differed in appearance from nodular scabies.

Although research indicates scrotal calcinosis may result from dystrophic calcification of epidermal inclusion cysts,² the latter present as dome-shaped, flesh-colored nodules with central pores representing the opening of hair follicles. Our patient lacked characteristic findings of epidermal inclusion cysts on histology.

The preferred treatment for scrotal calcinosis is surgical excision, which improves the aesthetic appearance, relieves itch, and removes ulcerative lesions.⁵ Additionally, surgical excision provides histological diagnostic confirmation. Recurrence with incomplete excision is possible; therefore, all lesions should be completely excised to reduce the risk for recurrence.³

The Diagnosis: Scrotal Calcinosis

Scrotal calcinosis is a rare benign disease that results from the deposition of calcium, magnesium, phosphate, and carbonate within the dermis and subcutaneous layer of the skin in the absence of underlying systemic disease or serum calcium and phosphorus abnormalities.^1,2 Lesions usually are asymptomatic but can be mildly painful or pruritic. They usually present in childhood or early adulthood as yellow-white firm nodules ranging in size from a few millimeters to a few centimeters that increase in size and number over time. Additionally, lesions can ulcerate and discharge a chalklike exudative material. Although benign in nature, the quality-of-life impact in patients with this condition can be substantial, specifically regarding cosmesis, which may cause patients to feel embarrassed and even avoid sexual activity. This condition rarely has been associated with infection.¹

Our patient elected to undergo surgical excision under local anesthesia, and the lesions were sent for histopathologic examination. His postoperative course was unremarkable, and he was pleased with the cosmetic result of the surgery (Figure 1). Histopathology revealed calcified deposits that appeared as intradermal basophilic nodules lacking an epithelial lining (Figure 2), consistent with the diagnosis of scrotal calcinosis.² No recurrence of the lesions was documented over the course of 18 months.

The pathogenesis of this condition is not clear. Most research supports scrotal calcinosis resulting from dystrophic calcification of epidermal inclusion cysts.³ There have been cases of scrotal calcinosis coinciding with epidermal inclusion cysts of the scrotum in varying stages of inflammation (some intact and some ruptured).² Some research also suggests dystrophic calcification of eccrine epithelial cysts and degenerated dartos muscle as the origin of scrotal calcinosis.³

The differential diagnosis for this case included calcified steatocystoma multiplex, eruptive xanthomas, nodular scabies, and epidermal inclusion cysts. Steatocystoma multiplex can be inherited in an autosomal-dominant fashion or can develop sporadically with mutations in the KRT17 gene.⁴ It is characterized by multiple sebum-filled, cystic lesions of the pilosebaceous unit that may become calcified. Calcified lesions appear as yellow, firm, irregularly shaped papules or nodules ranging from a few millimeters to centimeters in size. Cysts can develop anywhere on the body with a predilection for the chest, upper extremities, axillae, trunk, groin, and scrotum.⁴ Histologically, our patient’s lesions were not associated with the pilosebaceous unit. Additionally, our patient denied a family history of similar skin lesions, which made calcified steatocystoma multiplex an unlikely diagnosis.

Eruptive xanthomas result from localized deposition of lipids within the dermis, typically in the setting of dyslipidemia or poorly controlled diabetes mellitus. They commonly appear on the extremities or buttocks as pruritic crops of yellow-red papules or nodules that are a few millimeters in size. Although our patient has a history of hyperlipidemia, his lesions differed substantially from eruptive xanthomas in clinical presentation.

Nodular scabies is a manifestation of classic scabies that presents with intensely pruritic erythematous papules and nodules that are a few millimeters in size and commonly occur on the axillae, groin, and genitalia. Our patient’s skin lesions were not pruritic and differed in appearance from nodular scabies.

Although research indicates scrotal calcinosis may result from dystrophic calcification of epidermal inclusion cysts,² the latter present as dome-shaped, flesh-colored nodules with central pores representing the opening of hair follicles. Our patient lacked characteristic findings of epidermal inclusion cysts on histology.

The preferred treatment for scrotal calcinosis is surgical excision, which improves the aesthetic appearance, relieves itch, and removes ulcerative lesions.⁵ Additionally, surgical excision provides histological diagnostic confirmation. Recurrence with incomplete excision is possible; therefore, all lesions should be completely excised to reduce the risk for recurrence.³

The Diagnosis: Extragenital Lichen Sclerosus et Atrophicus

A punch biopsy of the lesion revealed epidermal hyperkeratosis, atrophy, follicular plugs with basal vacuolar degeneration, and homogenous dense fibrosis in the papillary dermis with a dense lymphocytic infiltrate beneath the fibrosis (Figure 1). Dermoscopic examination was remarkable for a distinctive rainbow pattern. Clinical, histopathologic, and dermoscopic findings led to the diagnosis of extragenital lichen sclerosus et atrophicus (LSEA). A potent corticosteroid cream was prescribed twice daily for 2 months, after which the lesions completely resolved. At 2-year follow-up, a relapse was not observed (Figure 2).

Lichen sclerosus et atrophicus is an inflammatory dermatosis that clinically presents as atrophic or hypertrophic plaques that may show pigmentation changes with anogenital and extragenital involvement. It is common among females and predominantly occurs in prepubescent girls and postmenopausal women. The exact etiology is unclear; however, it is hypothesized to occur secondary to autoimmunity with an underlying genetic predisposition. Local trauma, hormonal influences, and infections are other suspected etiologic factors. Genital lesions often lead to itching, pain, and dyspareunia, whereas extragenital lesions predominantly are asymptomatic. When symptomatic, itching usually is the main concern. Unlike genital LSEA, extragenital lesions are not associated with squamous cell carcinoma development. Reported dermoscopic features of LSEA are white structureless areas with scaling, comedolike openings, follicular plugs, white shiny streaks, blue-gray peppering, pigment network, and red-purple globules.¹ In our case, the dermoscopic finding of a rainbow pattern in LSEA is rare.² Although the mechanism behind this appearance unclear, it can be the result of the birefringence effect—local variations in refractive index—influenced by the direction of structures within the dermis such as collagen. In this case, there was diffuse and dense homogenous fibrosis in the superficial dermis that corresponded to dermoscopic white polygonal clods.

Extragenital LSEA commonly is located on the neck, shoulders, wrists, and upper trunk and manifests clinically as whitish papules coalescing into scarlike plaques. Of all patients who have LSEA, 20% have extragenital lesions, and most of these lesions are seen in patients who also have genital LSEA. Approximately 6% of all LSEA patients have extragenital LSEA without genital involvement.³

For experienced dermatologists, clinical symptoms and lesion characteristics usually are sufficient for diagnosis; however, a differential diagnosis of atypical lesions and isolated extragenital presentations such as morphea, lichen simplex chronicus, lichen planus, and vitiligo requires the correlation of clinical findings with histopathology and dermoscopy. Morphea, known as localized scleroderma, is an idiopathic inflammatory skin disease with sclerotic changes. It manifests as inflammatory plaques that vary in color from red to purple. If there is moderate sclerosis in the center of this plaque, the color progressively fades to white, leaving a purplish ring around the edges. Dermoscopic features of morphea are reported as areas of erythema; red-focused vessels of linear, irregular, or dotted morphology; white fibrotic beams; and pigmentary structures.² Lichen simplex chronicus is characterized by single or multiple dry and patchy skin lesions that are intensely pruritic. It commonly occurs on the neck, scalp, extremities, genital areas, and buttocks. Scratching the lesions leads to scarring, thickening of the skin, and increased frequency of itching. Histopathology of lichen simplex chronicus most frequently demonstrates a thickening of the epidermis and papillary dermis, irregularly elongated rete ridges, and fibroplasia with stellate or multinucleated fibroblasts completed by perivascular lymphocytic inflammation.⁴ Lichen planus presents with pruritic, polygonal, purple papules and/or plaques that can present in a variety of clinical forms, including atrophic and hypertrophic lichen planus.⁵ Lichen planus was an unlikely diagnosis for our patient due to the presence of patchy scarlike lesions and dermoscopic features that are well described in patients with LSEA. Lichen sclerosus et atrophicus presents with hypopigmented and/or hyperpigmented patches and plaques, distinguishing itself from vitiligo, which has flat lesions.

Topical steroids are the first-line therapeutic agents in the treatment of LSEA.6 Despite frequent use in this setting, common side effects such as localized scarring and atrophic degenerations have led to debate about their use. In our patient, the lesions resolved almost completely in 2 months, and no relapse was observed in the following 2 years. In the setting of topical steroid resistance, topical calcineurin inhibitors, UVA/UVB phototherapy, and topical tacrolimus can be used for treatment.⁶

The diagnosis of isolated extragenital LSEA may be a clinical challenge and generally requires further workup. When evaluating extragenital lesions, dermatologists should keep in mind extragenital LSEA as a differential diagnosis in the presence of a dermoscopic rainbow pattern arranged over white polygonal clods.

The Diagnosis: Extragenital Lichen Sclerosus et Atrophicus

A punch biopsy of the lesion revealed epidermal hyperkeratosis, atrophy, follicular plugs with basal vacuolar degeneration, and homogenous dense fibrosis in the papillary dermis with a dense lymphocytic infiltrate beneath the fibrosis (Figure 1). Dermoscopic examination was remarkable for a distinctive rainbow pattern. Clinical, histopathologic, and dermoscopic findings led to the diagnosis of extragenital lichen sclerosus et atrophicus (LSEA). A potent corticosteroid cream was prescribed twice daily for 2 months, after which the lesions completely resolved. At 2-year follow-up, a relapse was not observed (Figure 2).

Lichen sclerosus et atrophicus is an inflammatory dermatosis that clinically presents as atrophic or hypertrophic plaques that may show pigmentation changes with anogenital and extragenital involvement. It is common among females and predominantly occurs in prepubescent girls and postmenopausal women. The exact etiology is unclear; however, it is hypothesized to occur secondary to autoimmunity with an underlying genetic predisposition. Local trauma, hormonal influences, and infections are other suspected etiologic factors. Genital lesions often lead to itching, pain, and dyspareunia, whereas extragenital lesions predominantly are asymptomatic. When symptomatic, itching usually is the main concern. Unlike genital LSEA, extragenital lesions are not associated with squamous cell carcinoma development. Reported dermoscopic features of LSEA are white structureless areas with scaling, comedolike openings, follicular plugs, white shiny streaks, blue-gray peppering, pigment network, and red-purple globules.¹ In our case, the dermoscopic finding of a rainbow pattern in LSEA is rare.² Although the mechanism behind this appearance unclear, it can be the result of the birefringence effect—local variations in refractive index—influenced by the direction of structures within the dermis such as collagen. In this case, there was diffuse and dense homogenous fibrosis in the superficial dermis that corresponded to dermoscopic white polygonal clods.

Extragenital LSEA commonly is located on the neck, shoulders, wrists, and upper trunk and manifests clinically as whitish papules coalescing into scarlike plaques. Of all patients who have LSEA, 20% have extragenital lesions, and most of these lesions are seen in patients who also have genital LSEA. Approximately 6% of all LSEA patients have extragenital LSEA without genital involvement.³

For experienced dermatologists, clinical symptoms and lesion characteristics usually are sufficient for diagnosis; however, a differential diagnosis of atypical lesions and isolated extragenital presentations such as morphea, lichen simplex chronicus, lichen planus, and vitiligo requires the correlation of clinical findings with histopathology and dermoscopy. Morphea, known as localized scleroderma, is an idiopathic inflammatory skin disease with sclerotic changes. It manifests as inflammatory plaques that vary in color from red to purple. If there is moderate sclerosis in the center of this plaque, the color progressively fades to white, leaving a purplish ring around the edges. Dermoscopic features of morphea are reported as areas of erythema; red-focused vessels of linear, irregular, or dotted morphology; white fibrotic beams; and pigmentary structures.² Lichen simplex chronicus is characterized by single or multiple dry and patchy skin lesions that are intensely pruritic. It commonly occurs on the neck, scalp, extremities, genital areas, and buttocks. Scratching the lesions leads to scarring, thickening of the skin, and increased frequency of itching. Histopathology of lichen simplex chronicus most frequently demonstrates a thickening of the epidermis and papillary dermis, irregularly elongated rete ridges, and fibroplasia with stellate or multinucleated fibroblasts completed by perivascular lymphocytic inflammation.⁴ Lichen planus presents with pruritic, polygonal, purple papules and/or plaques that can present in a variety of clinical forms, including atrophic and hypertrophic lichen planus.⁵ Lichen planus was an unlikely diagnosis for our patient due to the presence of patchy scarlike lesions and dermoscopic features that are well described in patients with LSEA. Lichen sclerosus et atrophicus presents with hypopigmented and/or hyperpigmented patches and plaques, distinguishing itself from vitiligo, which has flat lesions.

Topical steroids are the first-line therapeutic agents in the treatment of LSEA.6 Despite frequent use in this setting, common side effects such as localized scarring and atrophic degenerations have led to debate about their use. In our patient, the lesions resolved almost completely in 2 months, and no relapse was observed in the following 2 years. In the setting of topical steroid resistance, topical calcineurin inhibitors, UVA/UVB phototherapy, and topical tacrolimus can be used for treatment.⁶

The diagnosis of isolated extragenital LSEA may be a clinical challenge and generally requires further workup. When evaluating extragenital lesions, dermatologists should keep in mind extragenital LSEA as a differential diagnosis in the presence of a dermoscopic rainbow pattern arranged over white polygonal clods.

The Diagnosis: Extragenital Lichen Sclerosus et Atrophicus

A punch biopsy of the lesion revealed epidermal hyperkeratosis, atrophy, follicular plugs with basal vacuolar degeneration, and homogenous dense fibrosis in the papillary dermis with a dense lymphocytic infiltrate beneath the fibrosis (Figure 1). Dermoscopic examination was remarkable for a distinctive rainbow pattern. Clinical, histopathologic, and dermoscopic findings led to the diagnosis of extragenital lichen sclerosus et atrophicus (LSEA). A potent corticosteroid cream was prescribed twice daily for 2 months, after which the lesions completely resolved. At 2-year follow-up, a relapse was not observed (Figure 2).

Lichen sclerosus et atrophicus is an inflammatory dermatosis that clinically presents as atrophic or hypertrophic plaques that may show pigmentation changes with anogenital and extragenital involvement. It is common among females and predominantly occurs in prepubescent girls and postmenopausal women. The exact etiology is unclear; however, it is hypothesized to occur secondary to autoimmunity with an underlying genetic predisposition. Local trauma, hormonal influences, and infections are other suspected etiologic factors. Genital lesions often lead to itching, pain, and dyspareunia, whereas extragenital lesions predominantly are asymptomatic. When symptomatic, itching usually is the main concern. Unlike genital LSEA, extragenital lesions are not associated with squamous cell carcinoma development. Reported dermoscopic features of LSEA are white structureless areas with scaling, comedolike openings, follicular plugs, white shiny streaks, blue-gray peppering, pigment network, and red-purple globules.¹ In our case, the dermoscopic finding of a rainbow pattern in LSEA is rare.² Although the mechanism behind this appearance unclear, it can be the result of the birefringence effect—local variations in refractive index—influenced by the direction of structures within the dermis such as collagen. In this case, there was diffuse and dense homogenous fibrosis in the superficial dermis that corresponded to dermoscopic white polygonal clods.

Extragenital LSEA commonly is located on the neck, shoulders, wrists, and upper trunk and manifests clinically as whitish papules coalescing into scarlike plaques. Of all patients who have LSEA, 20% have extragenital lesions, and most of these lesions are seen in patients who also have genital LSEA. Approximately 6% of all LSEA patients have extragenital LSEA without genital involvement.³

For experienced dermatologists, clinical symptoms and lesion characteristics usually are sufficient for diagnosis; however, a differential diagnosis of atypical lesions and isolated extragenital presentations such as morphea, lichen simplex chronicus, lichen planus, and vitiligo requires the correlation of clinical findings with histopathology and dermoscopy. Morphea, known as localized scleroderma, is an idiopathic inflammatory skin disease with sclerotic changes. It manifests as inflammatory plaques that vary in color from red to purple. If there is moderate sclerosis in the center of this plaque, the color progressively fades to white, leaving a purplish ring around the edges. Dermoscopic features of morphea are reported as areas of erythema; red-focused vessels of linear, irregular, or dotted morphology; white fibrotic beams; and pigmentary structures.² Lichen simplex chronicus is characterized by single or multiple dry and patchy skin lesions that are intensely pruritic. It commonly occurs on the neck, scalp, extremities, genital areas, and buttocks. Scratching the lesions leads to scarring, thickening of the skin, and increased frequency of itching. Histopathology of lichen simplex chronicus most frequently demonstrates a thickening of the epidermis and papillary dermis, irregularly elongated rete ridges, and fibroplasia with stellate or multinucleated fibroblasts completed by perivascular lymphocytic inflammation.⁴ Lichen planus presents with pruritic, polygonal, purple papules and/or plaques that can present in a variety of clinical forms, including atrophic and hypertrophic lichen planus.⁵ Lichen planus was an unlikely diagnosis for our patient due to the presence of patchy scarlike lesions and dermoscopic features that are well described in patients with LSEA. Lichen sclerosus et atrophicus presents with hypopigmented and/or hyperpigmented patches and plaques, distinguishing itself from vitiligo, which has flat lesions.

Topical steroids are the first-line therapeutic agents in the treatment of LSEA.6 Despite frequent use in this setting, common side effects such as localized scarring and atrophic degenerations have led to debate about their use. In our patient, the lesions resolved almost completely in 2 months, and no relapse was observed in the following 2 years. In the setting of topical steroid resistance, topical calcineurin inhibitors, UVA/UVB phototherapy, and topical tacrolimus can be used for treatment.⁶

The diagnosis of isolated extragenital LSEA may be a clinical challenge and generally requires further workup. When evaluating extragenital lesions, dermatologists should keep in mind extragenital LSEA as a differential diagnosis in the presence of a dermoscopic rainbow pattern arranged over white polygonal clods.

The Diagnosis: Mpox (Monkeypox)

Tests for active herpes simplex virus (HHV), gonorrhea, chlamydia, HIV, and syphilis were negative. Swabs from the penile lesion demonstrated positivity for the West African clade of mpox (monkeypox) virus (MPXV) by polymerase chain reaction. The patient was treated supportively without the addition of antiviral therapy, and he experienced a complete recovery.

Mpox virus was first isolated in 1958 in a research facility and was named after the laboratory animals that were housed there. The first human documentation of the disease occurred in 1970, and it was first documented in the United States in 2003 in an infection that was traced to a shipment of small mammals from Ghana to Texas.¹ The disease has always been endemic to Africa; however, the incidence has been increasing.² A new MPXV outbreak was reported in many countries in early 2022, including the United States.¹

The MPXV is a double-stranded DNA virus of the genus Orthopoxvirus, and 2 genetic clades have been identified: clade I (formerly the Central African clade) and clade II (formerly the West African clade). The virus has the capability to infect many mammals; however, its host remains unidentified.¹ The exact mechanism of transmission from infected animals to humans largely is unknown; however, direct or indirect contact with infected animals likely is responsible. Human-to-human transmission can occur by many mechanisms including contact with large respiratory droplets, bodily fluids, and contaminated surfaces. The incubation period is 5 to 21 days, and the symptoms last 2 to 5 weeks.¹

The clinical manifestations of MPXV during the most recent outbreak differ from prior outbreaks. Patients are more likely to experience minimal to no systemic symptoms, and cutaneous lesions can be few and localized to a focal area, especially on the face and in the anogenital region,³ similar to the presentation in our patient (Figure 1). Cutaneous lesions of the most recent MPXV outbreak also include painless ulcerations similar to syphilitic chancres and lesions that are in various stages of healing.³ Lesions often begin as pseudopustules, which are firm white papules with or without a necrotic center that resemble pustules; unlike true pustules, there is no identifiable purulent material within it. Bacterial superinfection of the lesions is not uncommon.⁴ Over time, a secondary pustular eruption resembling folliculitis also may occur,4 as noted in our patient (Figure 2).

Although we did not have a biopsy to support the diagnosis of associated erythema multiforme (EM) in our patient, features supportive of this diagnosis included the classic clinical appearance of typical, well-defined, targetoid plaques with 3 distinct zones (Figure 3); the association with a known infection; the distribution on the arms with truncal sparing; and self-limited lesions. More than 90% of EM cases are associated with infection, with HHV representing the most common culprit⁵; therefore, the relationship with a different virus is not an unreasonable suggestion. Additionally, there have been rare reports of EM in association with MPXV.⁴

Histopathology of MPXV may have distinctive features. Lesions often demonstrate keratinocytic necrosis and basal layer vacuolization with an associated superficial and deep perivascular lymphohistiocytic infiltrate. When the morphology of the lesion is vesicular, histopathology reveals spongiosis and ballooning degeneration with epidermal necrosis. Viral inclusion bodies within keratinocytes may be identified.¹ Death rates from MPXV has been reported from 1% to 11%, with increased mortality among high-risk populations including children and immunocompromised individuals. Treatment of the disease largely consists of supportive care and management of any associated complications including bacterial infection, pneumonia, and encephalitis.¹

The differential diagnosis of MPXV includes other ulcerative lesions that can occur on the genital skin. Fixed drug eruptions often present on the penis,⁶ but there was no identifiable inciting drug in our patient. Herpes simplex virus infection was very high on the differential given our patient’s history of recurrent infections and association with a targetoid rash, but HHV type 1 and HHV type 2 testing of the lesion was negative. A syphilitic chancre also may present with the nontender genital ulceration⁷ that was seen in our patient, but serology did not support this diagnosis. Cutaneous Crohn disease also may manifest with genital ulceration even before a diagnosis of Crohn disease is made, but these lesions often present as linear knife-cut ulcerations of the anogenital region.⁸

Our case further supports a clinical presentation that diverges from the more traditional cases of MPXV. Additionally, associated EM may be a clue to infection, especially in cases of negative HHV and other sexually transmitted infection testing.

The Diagnosis: Mpox (Monkeypox)

Tests for active herpes simplex virus (HHV), gonorrhea, chlamydia, HIV, and syphilis were negative. Swabs from the penile lesion demonstrated positivity for the West African clade of mpox (monkeypox) virus (MPXV) by polymerase chain reaction. The patient was treated supportively without the addition of antiviral therapy, and he experienced a complete recovery.

Mpox virus was first isolated in 1958 in a research facility and was named after the laboratory animals that were housed there. The first human documentation of the disease occurred in 1970, and it was first documented in the United States in 2003 in an infection that was traced to a shipment of small mammals from Ghana to Texas.¹ The disease has always been endemic to Africa; however, the incidence has been increasing.² A new MPXV outbreak was reported in many countries in early 2022, including the United States.¹

The MPXV is a double-stranded DNA virus of the genus Orthopoxvirus, and 2 genetic clades have been identified: clade I (formerly the Central African clade) and clade II (formerly the West African clade). The virus has the capability to infect many mammals; however, its host remains unidentified.¹ The exact mechanism of transmission from infected animals to humans largely is unknown; however, direct or indirect contact with infected animals likely is responsible. Human-to-human transmission can occur by many mechanisms including contact with large respiratory droplets, bodily fluids, and contaminated surfaces. The incubation period is 5 to 21 days, and the symptoms last 2 to 5 weeks.¹

The clinical manifestations of MPXV during the most recent outbreak differ from prior outbreaks. Patients are more likely to experience minimal to no systemic symptoms, and cutaneous lesions can be few and localized to a focal area, especially on the face and in the anogenital region,³ similar to the presentation in our patient (Figure 1). Cutaneous lesions of the most recent MPXV outbreak also include painless ulcerations similar to syphilitic chancres and lesions that are in various stages of healing.³ Lesions often begin as pseudopustules, which are firm white papules with or without a necrotic center that resemble pustules; unlike true pustules, there is no identifiable purulent material within it. Bacterial superinfection of the lesions is not uncommon.⁴ Over time, a secondary pustular eruption resembling folliculitis also may occur,4 as noted in our patient (Figure 2).

Although we did not have a biopsy to support the diagnosis of associated erythema multiforme (EM) in our patient, features supportive of this diagnosis included the classic clinical appearance of typical, well-defined, targetoid plaques with 3 distinct zones (Figure 3); the association with a known infection; the distribution on the arms with truncal sparing; and self-limited lesions. More than 90% of EM cases are associated with infection, with HHV representing the most common culprit⁵; therefore, the relationship with a different virus is not an unreasonable suggestion. Additionally, there have been rare reports of EM in association with MPXV.⁴

Histopathology of MPXV may have distinctive features. Lesions often demonstrate keratinocytic necrosis and basal layer vacuolization with an associated superficial and deep perivascular lymphohistiocytic infiltrate. When the morphology of the lesion is vesicular, histopathology reveals spongiosis and ballooning degeneration with epidermal necrosis. Viral inclusion bodies within keratinocytes may be identified.¹ Death rates from MPXV has been reported from 1% to 11%, with increased mortality among high-risk populations including children and immunocompromised individuals. Treatment of the disease largely consists of supportive care and management of any associated complications including bacterial infection, pneumonia, and encephalitis.¹

The differential diagnosis of MPXV includes other ulcerative lesions that can occur on the genital skin. Fixed drug eruptions often present on the penis,⁶ but there was no identifiable inciting drug in our patient. Herpes simplex virus infection was very high on the differential given our patient’s history of recurrent infections and association with a targetoid rash, but HHV type 1 and HHV type 2 testing of the lesion was negative. A syphilitic chancre also may present with the nontender genital ulceration⁷ that was seen in our patient, but serology did not support this diagnosis. Cutaneous Crohn disease also may manifest with genital ulceration even before a diagnosis of Crohn disease is made, but these lesions often present as linear knife-cut ulcerations of the anogenital region.⁸

Our case further supports a clinical presentation that diverges from the more traditional cases of MPXV. Additionally, associated EM may be a clue to infection, especially in cases of negative HHV and other sexually transmitted infection testing.

The Diagnosis: Mpox (Monkeypox)

Tests for active herpes simplex virus (HHV), gonorrhea, chlamydia, HIV, and syphilis were negative. Swabs from the penile lesion demonstrated positivity for the West African clade of mpox (monkeypox) virus (MPXV) by polymerase chain reaction. The patient was treated supportively without the addition of antiviral therapy, and he experienced a complete recovery.

Mpox virus was first isolated in 1958 in a research facility and was named after the laboratory animals that were housed there. The first human documentation of the disease occurred in 1970, and it was first documented in the United States in 2003 in an infection that was traced to a shipment of small mammals from Ghana to Texas.¹ The disease has always been endemic to Africa; however, the incidence has been increasing.² A new MPXV outbreak was reported in many countries in early 2022, including the United States.¹

The MPXV is a double-stranded DNA virus of the genus Orthopoxvirus, and 2 genetic clades have been identified: clade I (formerly the Central African clade) and clade II (formerly the West African clade). The virus has the capability to infect many mammals; however, its host remains unidentified.¹ The exact mechanism of transmission from infected animals to humans largely is unknown; however, direct or indirect contact with infected animals likely is responsible. Human-to-human transmission can occur by many mechanisms including contact with large respiratory droplets, bodily fluids, and contaminated surfaces. The incubation period is 5 to 21 days, and the symptoms last 2 to 5 weeks.¹

The clinical manifestations of MPXV during the most recent outbreak differ from prior outbreaks. Patients are more likely to experience minimal to no systemic symptoms, and cutaneous lesions can be few and localized to a focal area, especially on the face and in the anogenital region,³ similar to the presentation in our patient (Figure 1). Cutaneous lesions of the most recent MPXV outbreak also include painless ulcerations similar to syphilitic chancres and lesions that are in various stages of healing.³ Lesions often begin as pseudopustules, which are firm white papules with or without a necrotic center that resemble pustules; unlike true pustules, there is no identifiable purulent material within it. Bacterial superinfection of the lesions is not uncommon.⁴ Over time, a secondary pustular eruption resembling folliculitis also may occur,4 as noted in our patient (Figure 2).

Although we did not have a biopsy to support the diagnosis of associated erythema multiforme (EM) in our patient, features supportive of this diagnosis included the classic clinical appearance of typical, well-defined, targetoid plaques with 3 distinct zones (Figure 3); the association with a known infection; the distribution on the arms with truncal sparing; and self-limited lesions. More than 90% of EM cases are associated with infection, with HHV representing the most common culprit⁵; therefore, the relationship with a different virus is not an unreasonable suggestion. Additionally, there have been rare reports of EM in association with MPXV.⁴

Histopathology of MPXV may have distinctive features. Lesions often demonstrate keratinocytic necrosis and basal layer vacuolization with an associated superficial and deep perivascular lymphohistiocytic infiltrate. When the morphology of the lesion is vesicular, histopathology reveals spongiosis and ballooning degeneration with epidermal necrosis. Viral inclusion bodies within keratinocytes may be identified.¹ Death rates from MPXV has been reported from 1% to 11%, with increased mortality among high-risk populations including children and immunocompromised individuals. Treatment of the disease largely consists of supportive care and management of any associated complications including bacterial infection, pneumonia, and encephalitis.¹

The differential diagnosis of MPXV includes other ulcerative lesions that can occur on the genital skin. Fixed drug eruptions often present on the penis,⁶ but there was no identifiable inciting drug in our patient. Herpes simplex virus infection was very high on the differential given our patient’s history of recurrent infections and association with a targetoid rash, but HHV type 1 and HHV type 2 testing of the lesion was negative. A syphilitic chancre also may present with the nontender genital ulceration⁷ that was seen in our patient, but serology did not support this diagnosis. Cutaneous Crohn disease also may manifest with genital ulceration even before a diagnosis of Crohn disease is made, but these lesions often present as linear knife-cut ulcerations of the anogenital region.⁸

Our case further supports a clinical presentation that diverges from the more traditional cases of MPXV. Additionally, associated EM may be a clue to infection, especially in cases of negative HHV and other sexually transmitted infection testing.

The Diagnosis: Cutaneous Metastasis

A shave biopsy of the lip revealed a diffuse cellular infiltrate filling the superficial and deep dermis (Figure 1A). Morphologically, the cells had abundant clear cytoplasm with eccentrically located, pleomorphic, hyperchromatic nuclei with occasional prominent nucleoli (Figure 1B). The cells stained positive for AE1/ AE3 on immunohistochemistry (Figure 2). A punch biopsy of the nodule in the right axillary vault revealed a morphologically similar proliferation of cells. A colonoscopy revealed a completely obstructing circumferential mass in the distal ascending colon. A biopsy of the mass confirmed invasive adenocarcinoma, supporting a diagnosis of cutaneous metastases from adenocarcinoma of the colon. The patient underwent resection of the lip tumor and started multiagent chemotherapy for his newly diagnosed stage IV adenocarcinoma of the colon. The patient died, despite therapy.

Cutaneous metastasis from solid malignancies is uncommon, as only 1.3% of them exhibit cutaneous manifestations at presentation.¹ Cutaneous metastasis from signet ring cell adenocarcinoma (SRCA) of the colon is uncommon, and cutaneous metastasis of colorectal SRCA rarely precedes the diagnosis of the primary lesion.² Among the colorectal cancers that metastasize to the skin, metastasis to the face occurs in only 0.5% of patients.³

Signet ring cell adenocarcinomas are poorly differentiated adenocarcinomas histologically characterized by the neoplastic cells’ circular to ovoid appearance with a flattened top.^4,5 This distinctive shape is from the displacement of the nucleus to the periphery of the cell due to the accumulation of intracytoplasmic mucin.⁴ Classically, malignancies are characterized as an SRCA if more than 50% of the cells have a signet ring cell morphology; if the signet ring cells comprise less than 50% of the neoplasm, the tumor is designated as an adenocarcinoma with signet ring morphology.⁴ The most common cause of cutaneous metastasis with signet ring morphology is gastric cancer, while colorectal carcinoma is less common.1 Colorectal SRCAs usually are found in the right colon or the rectum in comparison to other colonic sites.⁶

Clinically, cutaneous metastasis can present in a variety of ways. The most common presentation is nodular lesions that may coalesce to become zosteriform in configuration or lesions that mimic inflammatory dermatoses.⁷ Cutaneous metastasis is more common in breast and lung cancer, and when it occurs secondary to colorectal cancer, cutaneous metastasis rarely predates the detection of the primary neoplasm.²

The clinical appearance of metastasis is not specific and can mimic many entities⁸; therefore, a high index of suspicion must be employed when managing patients, even those without a history of internal malignancy. In our patient, the smooth nodular lesion appeared similar to a basal cell carcinoma; however, basal cell carcinomas appear more pearly, and arborizing telangiectasia often is seen.⁹ Merkel cell carcinoma is common on sundamaged skin of the head and neck but clinically appears more violaceous than the lesion seen in our patient.¹⁰ Paracoccidioidomycosis may form ulcerated papulonodules or plaques, especially around the nose and mouth. In many of these cases, lesions develop from contiguous lesions of the oral mucosa; therefore, the presence of oral lesions will help distinguish this infectious entity from cutaneous metastasis. Multiple lesions usually are identified when there is hematogenous dissemination.¹¹ Mycosis fungoides is a subtype of cutaneous T-cell lymphoma and is characterized by multiple patches, plaques, and nodules on sun-protected areas. Involvement of the head and neck is not common, except in the folliculotropic subtype, which has a separate and distinct clinical morphology.¹²

The development of signet ring morphology from an adenocarcinoma can be attributed to the activation of phosphatidylinositol 3-kinase (PI3K), which leads to downstream activation of mitogen-activated protein kinase (MAPK) and the subsequent loss of intercellular tight junctions. The mucin 4 gene, MUC4, also is upregulated by PI3K activation and possesses antiapoptotic and mitogenic effects in addition to its mucin secretory function.¹³

The neoplastic cells in SRCAs stain positive for mucicarmine, Alcian blue, and periodic acid–Schiff, which highlights the mucinous component of the cells.⁷ Immunohistochemical stains with CK7, CK20, AE1/AE3, and epithelial membrane antigen can be implemented to confirm an epithelial origin of the primary cancer.^7,13 CK20 is a low-molecular-weight cytokeratin normally expressed by Merkel cells and by the epithelium of the gastrointestinal tract and urothelium, whereas CK7 expression typically is expressed in the lungs, ovaries, endometrium, and breasts, but not in the lower gastrointestinal tract.¹⁴ Differentiating primary cutaneous adenocarcinoma from cutaneous metastasis can be accomplished with a thorough clinical history; however, p63 positivity supports a primary cutaneous lesion and may be useful in certain situations.⁷ CDX2 stains can be utilized to aid in localizing the primary neoplasm when it is unknown, and when positive, it suggests a lower gastrointestinal tract origin. However, special AT-rich sequence-binding protein 2 (SATB2) recently has been proposed as a replacement immunohistochemical marker for CDX2, as it has greater specificity for SRCA of the lower gastrointestinal tract.¹⁵ Benign entities with signet ring cell morphology are difficult to distinguish from SRCA; however, malignant lesions are more likely to demonstrate an infiltrative growth pattern, frequent mitotic figures, and apoptosis. Immunohistochemistry also can be utilized to support the diagnosis of benign proliferation with signet ring morphology, as benign lesions often will demonstrate E-cadherin positivity and negativity for p53 and Ki-67.¹³

Cutaneous metastasis usually correlates to advanced disease and generally indicates a worse prognosis.¹³ Signet ring cell morphology in both gastric and colorectal cancer portends a poor prognosis, and there is a lower overall survival in patients with these malignancies compared to cancers of the same organ with non–signet ring cell morphology.^4,8

The Diagnosis: Cutaneous Metastasis

A shave biopsy of the lip revealed a diffuse cellular infiltrate filling the superficial and deep dermis (Figure 1A). Morphologically, the cells had abundant clear cytoplasm with eccentrically located, pleomorphic, hyperchromatic nuclei with occasional prominent nucleoli (Figure 1B). The cells stained positive for AE1/ AE3 on immunohistochemistry (Figure 2). A punch biopsy of the nodule in the right axillary vault revealed a morphologically similar proliferation of cells. A colonoscopy revealed a completely obstructing circumferential mass in the distal ascending colon. A biopsy of the mass confirmed invasive adenocarcinoma, supporting a diagnosis of cutaneous metastases from adenocarcinoma of the colon. The patient underwent resection of the lip tumor and started multiagent chemotherapy for his newly diagnosed stage IV adenocarcinoma of the colon. The patient died, despite therapy.

Cutaneous metastasis from solid malignancies is uncommon, as only 1.3% of them exhibit cutaneous manifestations at presentation.¹ Cutaneous metastasis from signet ring cell adenocarcinoma (SRCA) of the colon is uncommon, and cutaneous metastasis of colorectal SRCA rarely precedes the diagnosis of the primary lesion.² Among the colorectal cancers that metastasize to the skin, metastasis to the face occurs in only 0.5% of patients.³

Signet ring cell adenocarcinomas are poorly differentiated adenocarcinomas histologically characterized by the neoplastic cells’ circular to ovoid appearance with a flattened top.^4,5 This distinctive shape is from the displacement of the nucleus to the periphery of the cell due to the accumulation of intracytoplasmic mucin.⁴ Classically, malignancies are characterized as an SRCA if more than 50% of the cells have a signet ring cell morphology; if the signet ring cells comprise less than 50% of the neoplasm, the tumor is designated as an adenocarcinoma with signet ring morphology.⁴ The most common cause of cutaneous metastasis with signet ring morphology is gastric cancer, while colorectal carcinoma is less common.1 Colorectal SRCAs usually are found in the right colon or the rectum in comparison to other colonic sites.⁶

Clinically, cutaneous metastasis can present in a variety of ways. The most common presentation is nodular lesions that may coalesce to become zosteriform in configuration or lesions that mimic inflammatory dermatoses.⁷ Cutaneous metastasis is more common in breast and lung cancer, and when it occurs secondary to colorectal cancer, cutaneous metastasis rarely predates the detection of the primary neoplasm.²

The clinical appearance of metastasis is not specific and can mimic many entities⁸; therefore, a high index of suspicion must be employed when managing patients, even those without a history of internal malignancy. In our patient, the smooth nodular lesion appeared similar to a basal cell carcinoma; however, basal cell carcinomas appear more pearly, and arborizing telangiectasia often is seen.⁹ Merkel cell carcinoma is common on sundamaged skin of the head and neck but clinically appears more violaceous than the lesion seen in our patient.¹⁰ Paracoccidioidomycosis may form ulcerated papulonodules or plaques, especially around the nose and mouth. In many of these cases, lesions develop from contiguous lesions of the oral mucosa; therefore, the presence of oral lesions will help distinguish this infectious entity from cutaneous metastasis. Multiple lesions usually are identified when there is hematogenous dissemination.¹¹ Mycosis fungoides is a subtype of cutaneous T-cell lymphoma and is characterized by multiple patches, plaques, and nodules on sun-protected areas. Involvement of the head and neck is not common, except in the folliculotropic subtype, which has a separate and distinct clinical morphology.¹²

The development of signet ring morphology from an adenocarcinoma can be attributed to the activation of phosphatidylinositol 3-kinase (PI3K), which leads to downstream activation of mitogen-activated protein kinase (MAPK) and the subsequent loss of intercellular tight junctions. The mucin 4 gene, MUC4, also is upregulated by PI3K activation and possesses antiapoptotic and mitogenic effects in addition to its mucin secretory function.¹³

The neoplastic cells in SRCAs stain positive for mucicarmine, Alcian blue, and periodic acid–Schiff, which highlights the mucinous component of the cells.⁷ Immunohistochemical stains with CK7, CK20, AE1/AE3, and epithelial membrane antigen can be implemented to confirm an epithelial origin of the primary cancer.^7,13 CK20 is a low-molecular-weight cytokeratin normally expressed by Merkel cells and by the epithelium of the gastrointestinal tract and urothelium, whereas CK7 expression typically is expressed in the lungs, ovaries, endometrium, and breasts, but not in the lower gastrointestinal tract.¹⁴ Differentiating primary cutaneous adenocarcinoma from cutaneous metastasis can be accomplished with a thorough clinical history; however, p63 positivity supports a primary cutaneous lesion and may be useful in certain situations.⁷ CDX2 stains can be utilized to aid in localizing the primary neoplasm when it is unknown, and when positive, it suggests a lower gastrointestinal tract origin. However, special AT-rich sequence-binding protein 2 (SATB2) recently has been proposed as a replacement immunohistochemical marker for CDX2, as it has greater specificity for SRCA of the lower gastrointestinal tract.¹⁵ Benign entities with signet ring cell morphology are difficult to distinguish from SRCA; however, malignant lesions are more likely to demonstrate an infiltrative growth pattern, frequent mitotic figures, and apoptosis. Immunohistochemistry also can be utilized to support the diagnosis of benign proliferation with signet ring morphology, as benign lesions often will demonstrate E-cadherin positivity and negativity for p53 and Ki-67.¹³

Cutaneous metastasis usually correlates to advanced disease and generally indicates a worse prognosis.¹³ Signet ring cell morphology in both gastric and colorectal cancer portends a poor prognosis, and there is a lower overall survival in patients with these malignancies compared to cancers of the same organ with non–signet ring cell morphology.^4,8

The Diagnosis: Cutaneous Metastasis

A shave biopsy of the lip revealed a diffuse cellular infiltrate filling the superficial and deep dermis (Figure 1A). Morphologically, the cells had abundant clear cytoplasm with eccentrically located, pleomorphic, hyperchromatic nuclei with occasional prominent nucleoli (Figure 1B). The cells stained positive for AE1/ AE3 on immunohistochemistry (Figure 2). A punch biopsy of the nodule in the right axillary vault revealed a morphologically similar proliferation of cells. A colonoscopy revealed a completely obstructing circumferential mass in the distal ascending colon. A biopsy of the mass confirmed invasive adenocarcinoma, supporting a diagnosis of cutaneous metastases from adenocarcinoma of the colon. The patient underwent resection of the lip tumor and started multiagent chemotherapy for his newly diagnosed stage IV adenocarcinoma of the colon. The patient died, despite therapy.

Cutaneous metastasis from solid malignancies is uncommon, as only 1.3% of them exhibit cutaneous manifestations at presentation.¹ Cutaneous metastasis from signet ring cell adenocarcinoma (SRCA) of the colon is uncommon, and cutaneous metastasis of colorectal SRCA rarely precedes the diagnosis of the primary lesion.² Among the colorectal cancers that metastasize to the skin, metastasis to the face occurs in only 0.5% of patients.³

Signet ring cell adenocarcinomas are poorly differentiated adenocarcinomas histologically characterized by the neoplastic cells’ circular to ovoid appearance with a flattened top.^4,5 This distinctive shape is from the displacement of the nucleus to the periphery of the cell due to the accumulation of intracytoplasmic mucin.⁴ Classically, malignancies are characterized as an SRCA if more than 50% of the cells have a signet ring cell morphology; if the signet ring cells comprise less than 50% of the neoplasm, the tumor is designated as an adenocarcinoma with signet ring morphology.⁴ The most common cause of cutaneous metastasis with signet ring morphology is gastric cancer, while colorectal carcinoma is less common.1 Colorectal SRCAs usually are found in the right colon or the rectum in comparison to other colonic sites.⁶

Clinically, cutaneous metastasis can present in a variety of ways. The most common presentation is nodular lesions that may coalesce to become zosteriform in configuration or lesions that mimic inflammatory dermatoses.⁷ Cutaneous metastasis is more common in breast and lung cancer, and when it occurs secondary to colorectal cancer, cutaneous metastasis rarely predates the detection of the primary neoplasm.²

The clinical appearance of metastasis is not specific and can mimic many entities⁸; therefore, a high index of suspicion must be employed when managing patients, even those without a history of internal malignancy. In our patient, the smooth nodular lesion appeared similar to a basal cell carcinoma; however, basal cell carcinomas appear more pearly, and arborizing telangiectasia often is seen.⁹ Merkel cell carcinoma is common on sundamaged skin of the head and neck but clinically appears more violaceous than the lesion seen in our patient.¹⁰ Paracoccidioidomycosis may form ulcerated papulonodules or plaques, especially around the nose and mouth. In many of these cases, lesions develop from contiguous lesions of the oral mucosa; therefore, the presence of oral lesions will help distinguish this infectious entity from cutaneous metastasis. Multiple lesions usually are identified when there is hematogenous dissemination.¹¹ Mycosis fungoides is a subtype of cutaneous T-cell lymphoma and is characterized by multiple patches, plaques, and nodules on sun-protected areas. Involvement of the head and neck is not common, except in the folliculotropic subtype, which has a separate and distinct clinical morphology.¹²

The development of signet ring morphology from an adenocarcinoma can be attributed to the activation of phosphatidylinositol 3-kinase (PI3K), which leads to downstream activation of mitogen-activated protein kinase (MAPK) and the subsequent loss of intercellular tight junctions. The mucin 4 gene, MUC4, also is upregulated by PI3K activation and possesses antiapoptotic and mitogenic effects in addition to its mucin secretory function.¹³

The neoplastic cells in SRCAs stain positive for mucicarmine, Alcian blue, and periodic acid–Schiff, which highlights the mucinous component of the cells.⁷ Immunohistochemical stains with CK7, CK20, AE1/AE3, and epithelial membrane antigen can be implemented to confirm an epithelial origin of the primary cancer.^7,13 CK20 is a low-molecular-weight cytokeratin normally expressed by Merkel cells and by the epithelium of the gastrointestinal tract and urothelium, whereas CK7 expression typically is expressed in the lungs, ovaries, endometrium, and breasts, but not in the lower gastrointestinal tract.¹⁴ Differentiating primary cutaneous adenocarcinoma from cutaneous metastasis can be accomplished with a thorough clinical history; however, p63 positivity supports a primary cutaneous lesion and may be useful in certain situations.⁷ CDX2 stains can be utilized to aid in localizing the primary neoplasm when it is unknown, and when positive, it suggests a lower gastrointestinal tract origin. However, special AT-rich sequence-binding protein 2 (SATB2) recently has been proposed as a replacement immunohistochemical marker for CDX2, as it has greater specificity for SRCA of the lower gastrointestinal tract.¹⁵ Benign entities with signet ring cell morphology are difficult to distinguish from SRCA; however, malignant lesions are more likely to demonstrate an infiltrative growth pattern, frequent mitotic figures, and apoptosis. Immunohistochemistry also can be utilized to support the diagnosis of benign proliferation with signet ring morphology, as benign lesions often will demonstrate E-cadherin positivity and negativity for p53 and Ki-67.¹³

Cutaneous metastasis usually correlates to advanced disease and generally indicates a worse prognosis.¹³ Signet ring cell morphology in both gastric and colorectal cancer portends a poor prognosis, and there is a lower overall survival in patients with these malignancies compared to cancers of the same organ with non–signet ring cell morphology.^4,8

The Diagnosis: Hypopigmented Mycosis Fungoides

Histopathology showed an atypical lymphoid infiltrate with expanded cytoplasm and hyperchromatic nuclei of irregular contours in the dermoepidermal junction (Figure 1). Immunohistochemical stains of atypical lymphocytes demonstrated the presence of CD3, CD8, and CD5, as well as the absence of CD7 and CD4 lymphocytes (Figure 2). The T-cell γ rearrangement showed polyclonal lymphocytes with 5% tumor cells. The histologic and clinical findings along with our patient’s medical history led to a diagnosis of stage IA (<10% body surface area involvement) hypopigmented mycosis fungoides (hMF).¹ Our patient was treated with triamcinolone cream 0.1%; she noted an improvement in her symptoms at 2-month follow-up.

Hypopigmented MF is an uncommon manifestation of MF with unknown prevalence and incidence rates. Mycosis fungoides is considered the most common subtype of cutaneous T-cell lymphoma that classically presents as a chronic, indolent, hypopigmented or depigmented macule or patch, commonly with scaling, in sunprotected areas such as the trunk and proximal arms and legs. It predominantly affects younger adults with darker skin tones and may be present in the pediatric population within the first decade of life.¹ Classically, MF affects White patients aged 55 to 60 years. Disease progression is slow, with an incidence rate of 10% of tumor or extracutaneous involvement in the early stages of disease. A lack of specificity on the clinical and histopathologic findings in the initial stage often contributes to the diagnostic delay of hMF. As seen in our patient, this disease can be misdiagnosed as tinea versicolor, postinflammatory hypopigmentation, vitiligo, pityriasis alba, subcutaneous lupus erythematosus, or Hansen disease due to prolonged hypopigmented lesions.² The clinical findings and histopathologic results including immunohistochemistry confirmed the diagnosis of hMF and ruled out pityriasis alba, postinflammatory hypopigmentation, subcutaneous lupus erythematosus, and vitiligo.

The etiology and pathophysiology of hMF are not fully understood; however, it is hypothesized that melanocyte degeneration, abnormal melanogenesis, and disturbance of melanosome transfer result from the clonal expansion of T helper memory cells. T-cell dyscrasia has been reported to evolve into hMF during etanercept therapy.³ Clinically, hMF presents as hypopigmented papulosquamous, eczematous, or erythrodermic patches, plaques, and tumors with poorly defined atrophied borders. Multiple biopsies of steroid-naive lesions are needed for the diagnosis, as the initial hMF histologic finding cannot be specific for diagnostic confirmation. Common histopathologic findings include a bandlike lymphocytic infiltrate with epidermotropism, intraepidermal nests of atypical cells, or cerebriform nuclei lymphocytes on hematoxylin and eosin staining. In comparison to classical MF epidermotropism, CD4− and CD8+ atypical cells aid in the diagnosis of hMF. Although hMF carries a good prognosis and a benign clinical course,⁴ full-body computed tomography or positron emission tomography/computed tomography as well as laboratory analysis for lactate dehydrogenase should be pursued if lymphadenopathy, systemic symptoms, or advancedstage hMF are present.

Treatment of hMF depends on the disease stage. Psoralen plus UVA and narrowband UVB can be utilized for the initial stages with a relatively fast response and remission of lesions as early as the first 2 months of treatment. In addition to phototherapy, stage IA to IIA mycosis fungoides with localized skin lesions can benefit from topical steroids, topical retinoids, imiquimod, nitrogen mustard, and carmustine. For advanced stages of mycosis fungoides, combination therapy consisting of psoralen plus UVA with an oral retinoid, interferon alfa, and systemic chemotherapy commonly are prescribed. Maintenance therapy is used for prolonging remission; however, long-term phototherapy is not recommended due to the risk for skin cancer. Unfortunately, hMF requires long-term treatment due to its waxing and waning course, and recurrence may occur after complete resolution.⁵

The Diagnosis: Hypopigmented Mycosis Fungoides

Histopathology showed an atypical lymphoid infiltrate with expanded cytoplasm and hyperchromatic nuclei of irregular contours in the dermoepidermal junction (Figure 1). Immunohistochemical stains of atypical lymphocytes demonstrated the presence of CD3, CD8, and CD5, as well as the absence of CD7 and CD4 lymphocytes (Figure 2). The T-cell γ rearrangement showed polyclonal lymphocytes with 5% tumor cells. The histologic and clinical findings along with our patient’s medical history led to a diagnosis of stage IA (<10% body surface area involvement) hypopigmented mycosis fungoides (hMF).¹ Our patient was treated with triamcinolone cream 0.1%; she noted an improvement in her symptoms at 2-month follow-up.

Hypopigmented MF is an uncommon manifestation of MF with unknown prevalence and incidence rates. Mycosis fungoides is considered the most common subtype of cutaneous T-cell lymphoma that classically presents as a chronic, indolent, hypopigmented or depigmented macule or patch, commonly with scaling, in sunprotected areas such as the trunk and proximal arms and legs. It predominantly affects younger adults with darker skin tones and may be present in the pediatric population within the first decade of life.¹ Classically, MF affects White patients aged 55 to 60 years. Disease progression is slow, with an incidence rate of 10% of tumor or extracutaneous involvement in the early stages of disease. A lack of specificity on the clinical and histopathologic findings in the initial stage often contributes to the diagnostic delay of hMF. As seen in our patient, this disease can be misdiagnosed as tinea versicolor, postinflammatory hypopigmentation, vitiligo, pityriasis alba, subcutaneous lupus erythematosus, or Hansen disease due to prolonged hypopigmented lesions.² The clinical findings and histopathologic results including immunohistochemistry confirmed the diagnosis of hMF and ruled out pityriasis alba, postinflammatory hypopigmentation, subcutaneous lupus erythematosus, and vitiligo.

The etiology and pathophysiology of hMF are not fully understood; however, it is hypothesized that melanocyte degeneration, abnormal melanogenesis, and disturbance of melanosome transfer result from the clonal expansion of T helper memory cells. T-cell dyscrasia has been reported to evolve into hMF during etanercept therapy.³ Clinically, hMF presents as hypopigmented papulosquamous, eczematous, or erythrodermic patches, plaques, and tumors with poorly defined atrophied borders. Multiple biopsies of steroid-naive lesions are needed for the diagnosis, as the initial hMF histologic finding cannot be specific for diagnostic confirmation. Common histopathologic findings include a bandlike lymphocytic infiltrate with epidermotropism, intraepidermal nests of atypical cells, or cerebriform nuclei lymphocytes on hematoxylin and eosin staining. In comparison to classical MF epidermotropism, CD4− and CD8+ atypical cells aid in the diagnosis of hMF. Although hMF carries a good prognosis and a benign clinical course,⁴ full-body computed tomography or positron emission tomography/computed tomography as well as laboratory analysis for lactate dehydrogenase should be pursued if lymphadenopathy, systemic symptoms, or advancedstage hMF are present.

Treatment of hMF depends on the disease stage. Psoralen plus UVA and narrowband UVB can be utilized for the initial stages with a relatively fast response and remission of lesions as early as the first 2 months of treatment. In addition to phototherapy, stage IA to IIA mycosis fungoides with localized skin lesions can benefit from topical steroids, topical retinoids, imiquimod, nitrogen mustard, and carmustine. For advanced stages of mycosis fungoides, combination therapy consisting of psoralen plus UVA with an oral retinoid, interferon alfa, and systemic chemotherapy commonly are prescribed. Maintenance therapy is used for prolonging remission; however, long-term phototherapy is not recommended due to the risk for skin cancer. Unfortunately, hMF requires long-term treatment due to its waxing and waning course, and recurrence may occur after complete resolution.⁵

The Diagnosis: Hypopigmented Mycosis Fungoides

Histopathology showed an atypical lymphoid infiltrate with expanded cytoplasm and hyperchromatic nuclei of irregular contours in the dermoepidermal junction (Figure 1). Immunohistochemical stains of atypical lymphocytes demonstrated the presence of CD3, CD8, and CD5, as well as the absence of CD7 and CD4 lymphocytes (Figure 2). The T-cell γ rearrangement showed polyclonal lymphocytes with 5% tumor cells. The histologic and clinical findings along with our patient’s medical history led to a diagnosis of stage IA (<10% body surface area involvement) hypopigmented mycosis fungoides (hMF).¹ Our patient was treated with triamcinolone cream 0.1%; she noted an improvement in her symptoms at 2-month follow-up.

Hypopigmented MF is an uncommon manifestation of MF with unknown prevalence and incidence rates. Mycosis fungoides is considered the most common subtype of cutaneous T-cell lymphoma that classically presents as a chronic, indolent, hypopigmented or depigmented macule or patch, commonly with scaling, in sunprotected areas such as the trunk and proximal arms and legs. It predominantly affects younger adults with darker skin tones and may be present in the pediatric population within the first decade of life.¹ Classically, MF affects White patients aged 55 to 60 years. Disease progression is slow, with an incidence rate of 10% of tumor or extracutaneous involvement in the early stages of disease. A lack of specificity on the clinical and histopathologic findings in the initial stage often contributes to the diagnostic delay of hMF. As seen in our patient, this disease can be misdiagnosed as tinea versicolor, postinflammatory hypopigmentation, vitiligo, pityriasis alba, subcutaneous lupus erythematosus, or Hansen disease due to prolonged hypopigmented lesions.² The clinical findings and histopathologic results including immunohistochemistry confirmed the diagnosis of hMF and ruled out pityriasis alba, postinflammatory hypopigmentation, subcutaneous lupus erythematosus, and vitiligo.

The etiology and pathophysiology of hMF are not fully understood; however, it is hypothesized that melanocyte degeneration, abnormal melanogenesis, and disturbance of melanosome transfer result from the clonal expansion of T helper memory cells. T-cell dyscrasia has been reported to evolve into hMF during etanercept therapy.³ Clinically, hMF presents as hypopigmented papulosquamous, eczematous, or erythrodermic patches, plaques, and tumors with poorly defined atrophied borders. Multiple biopsies of steroid-naive lesions are needed for the diagnosis, as the initial hMF histologic finding cannot be specific for diagnostic confirmation. Common histopathologic findings include a bandlike lymphocytic infiltrate with epidermotropism, intraepidermal nests of atypical cells, or cerebriform nuclei lymphocytes on hematoxylin and eosin staining. In comparison to classical MF epidermotropism, CD4− and CD8+ atypical cells aid in the diagnosis of hMF. Although hMF carries a good prognosis and a benign clinical course,⁴ full-body computed tomography or positron emission tomography/computed tomography as well as laboratory analysis for lactate dehydrogenase should be pursued if lymphadenopathy, systemic symptoms, or advancedstage hMF are present.

Treatment of hMF depends on the disease stage. Psoralen plus UVA and narrowband UVB can be utilized for the initial stages with a relatively fast response and remission of lesions as early as the first 2 months of treatment. In addition to phototherapy, stage IA to IIA mycosis fungoides with localized skin lesions can benefit from topical steroids, topical retinoids, imiquimod, nitrogen mustard, and carmustine. For advanced stages of mycosis fungoides, combination therapy consisting of psoralen plus UVA with an oral retinoid, interferon alfa, and systemic chemotherapy commonly are prescribed. Maintenance therapy is used for prolonging remission; however, long-term phototherapy is not recommended due to the risk for skin cancer. Unfortunately, hMF requires long-term treatment due to its waxing and waning course, and recurrence may occur after complete resolution.⁵

THE DIAGNOSIS: Neutrophilic Eccrine Hidradenitis

A biopsy from the left preauricular cheek demonstrated dermal neutrophilic inflammation around eccrine coils with focal necrosis (Figure). No notable diffuse dermal neutrophilic infiltrate was present, ruling out Sweet syndrome, and no notable interstitial neutrophilic infiltrate was present, making cellulitis and erysipelas less likely; panculture of tissue also was negative.^1,2 Atypical cells in the deep dermis were positive for CD163 and negative for CD117, CD34, CD123, and myeloperoxidase, consistent with a diagnosis of neutrophilic eccrine hidradenitis (NEH) and reactive histiocytes.³ Treatment with oral prednisone resulted in rapid improvement of symptoms.

Neutrophilic eccrine hidradenitis is a rare reactive neutrophilic dermatosis characterized by eccrine gland involvement. This benign and self-limited condition presents as asymmetric erythematous papules and plaques.² Among 8 granulocytopenic patients with neutrophilic dermatoses, 5 were diagnosed with NEH.⁴ Although first identified in 1982, NEH remains poorly understood.² Initial theories suggested that NEH developed due to cytotoxic substances secreted in sweat glands causing necrosis and neutrophil chemotaxis; however, chemotherapy exposure cannot be linked to every case of NEH. Neutrophilic eccrine hidradenitis can be extremely difficult to differentiate clinically from conditions such as cellulitis and Sweet syndrome.

A patient history can be helpful in identifying triggering factors. Neutrophilic eccrine hidradenitis most commonly is associated with malignant, drug-induced, or infectious triggers, while Sweet syndrome has a broad range of associations including infections, vaccines, inflammatory bowel disease, pregnancy, malignancy, and drug-induced etiologies (Table).¹ On average, NEH presents 10 days after chemotherapy induction, with 70% of cases presenting after the first chemotherapy cycle.⁵ Bacterial cellulitis or erysipelas have an infectious etiology, and patients may report symptoms such as fever, chills, or malaise. Immunosuppressed patients are at greater risk for infection; therefore, clinical signs of infection in a granulocytopenic patient should be addressed urgently.

Physical examination may have limited value in differentiating between these diagnoses, as neutrophilic dermatoses notoriously mimic infection. Cutaneous lesions can appear as pruritic or tender erythematous plaques, papules, or nodules in these conditions, though cellulitis and erysipelas tend to be unilateral and may have associated purulence or inflamed skin lymphatics. Given the potential for misdiagnosis, approaching patients with a broad differential can be helpful. In our patient, the differential diagnosis included Sweet syndrome, NEH, bacterial cellulitis, erysipelas, leukemia cutis, sarcoid, and eosinophilic cellulitis.

Leukemia cutis refers to the infiltration of neoplastic leukocytes in the skin and often occurs in patients with peripheral leukemia, most often acute myeloid leukemia or chronic lymphocytic leukemia. Patients with leukemia cutis often have a worse prognosis, as this finding signifies extramedullary spread of disease.⁶ Clinically, lesions can appear similar to those seen in our patient, though they typically are not symptomatic, can be nodular, tend to exhibit a violaceous hue, and occasionally may be hemorrhagic. Wells syndrome (also known as eosinophilic cellulitis) is an inflammatory dermatosis that presents as painful or pruritic, edematous and erythematous plaques.^7,8 A green hue on resolution is present in some cases and may help clinicians differentiate this disease from mimickers.⁷ Often, eosinophilic cellulitis is misdiagnosed as bacterial cellulitis and treated with antibiotics. The presence of systemic symptoms such as fever or arthralgia is more typical of bacterial cellulitis, erysipelas, eosinophilic cellulitis, or Sweet syndrome than of NEH.¹ Additionally, inflammatory markers (ie, C-reactive protein) and white blood cell counts tend to be elevated in bacterial cellulitis and Sweet syndrome, while leukopenia often is seen in NEH.

Histopathology is crucial in distinguishing these disease etiologies. Neutrophilic eccrine hidradenitis is diagnosed by the characteristic neutrophilic infiltrate and necrosis surrounding eccrine glands and coils. There also may be occasional intraductal abscesses and syringosquamous metaplasia of the sweat glands along with fibrosis of the adjacent dermis. In contrast, histologic sections of Sweet syndrome show numerous mature neutrophils infiltrating the dermis with marked papillary dermal edema. The histopathology of bacterial cellulitis and erysipelas is less specific, but common features include dermal edema, lymphatic dilation, and a diffuse neutrophilic infiltrate surrounding blood vessels. Pathogenic organisms may be seen on histopathology but are not required for the diagnosis of bacterial cellulitis or erysipelas.² Additionally, blood and tissue culture can assist in identification of both the source of infection and the causative organism, but cultures may not always be positive. 

Comparatively, the histopathologic features of eosinophilic cellulitis include dermal edema, eosinophilic infiltration, and flame figures that form when eosinophils degranulate and coat collagen fibers with major basic protein. Flame figures are characteristic but not pathognomonic for eosinophilic cellulitis.⁷ The histopathology of leukemia cutis varies based on the leukemia classification; generally, in acute myeloid leukemia the infiltrate is composed of neoplastic cells in the early stages of development that are positive for myeloid markers such as myeloperoxidase. Atypical and immature granulocytes within the leukocytic infiltrate differentiate this condition from the other diagnoses. Treatment may entail chemotherapy or radiotherapy, and this diagnosis generally carries the worst prognosis of all the conditions in the differential.⁶

Differentiating between these conditions is important in guiding treatment, especially in patients with febrile neutropenia. Unnecessary steroids in immunosuppressed patients can be dangerous, especially if the patient has an infection such as bacterial cellulitis. Furthermore, unwarranted antibiotic use for noninfectious conditions may expose patients to substantial side effects and not improve the condition. Neutrophilic eccrine hidradenitis typically is self-limited and treated symptomatically with systemic corticosteroids and nonsteroidal anti-inflammatory drugs.³ Sweet syndrome often requires a longer course of oral steroids. Leukemia cutis worsens as the leukemia advances, and treatment of the underlying malignancy is the most effective treatment.⁹

Early and accurate recognition of the diagnosis can prevent harmful diagnostic delay, unnecessary antibiotic use, or extended steroid taper in neutropenic patients. Appreciating the differences between these diagnoses can assist clinicians in investigating and tailoring a broad differential to specific patient presentations, which is especially critical when considering common mimickers for life-threatening conditions.

THE DIAGNOSIS: Neutrophilic Eccrine Hidradenitis

A biopsy from the left preauricular cheek demonstrated dermal neutrophilic inflammation around eccrine coils with focal necrosis (Figure). No notable diffuse dermal neutrophilic infiltrate was present, ruling out Sweet syndrome, and no notable interstitial neutrophilic infiltrate was present, making cellulitis and erysipelas less likely; panculture of tissue also was negative.^1,2 Atypical cells in the deep dermis were positive for CD163 and negative for CD117, CD34, CD123, and myeloperoxidase, consistent with a diagnosis of neutrophilic eccrine hidradenitis (NEH) and reactive histiocytes.³ Treatment with oral prednisone resulted in rapid improvement of symptoms.

Neutrophilic eccrine hidradenitis is a rare reactive neutrophilic dermatosis characterized by eccrine gland involvement. This benign and self-limited condition presents as asymmetric erythematous papules and plaques.² Among 8 granulocytopenic patients with neutrophilic dermatoses, 5 were diagnosed with NEH.⁴ Although first identified in 1982, NEH remains poorly understood.² Initial theories suggested that NEH developed due to cytotoxic substances secreted in sweat glands causing necrosis and neutrophil chemotaxis; however, chemotherapy exposure cannot be linked to every case of NEH. Neutrophilic eccrine hidradenitis can be extremely difficult to differentiate clinically from conditions such as cellulitis and Sweet syndrome.

A patient history can be helpful in identifying triggering factors. Neutrophilic eccrine hidradenitis most commonly is associated with malignant, drug-induced, or infectious triggers, while Sweet syndrome has a broad range of associations including infections, vaccines, inflammatory bowel disease, pregnancy, malignancy, and drug-induced etiologies (Table).¹ On average, NEH presents 10 days after chemotherapy induction, with 70% of cases presenting after the first chemotherapy cycle.⁵ Bacterial cellulitis or erysipelas have an infectious etiology, and patients may report symptoms such as fever, chills, or malaise. Immunosuppressed patients are at greater risk for infection; therefore, clinical signs of infection in a granulocytopenic patient should be addressed urgently.

Physical examination may have limited value in differentiating between these diagnoses, as neutrophilic dermatoses notoriously mimic infection. Cutaneous lesions can appear as pruritic or tender erythematous plaques, papules, or nodules in these conditions, though cellulitis and erysipelas tend to be unilateral and may have associated purulence or inflamed skin lymphatics. Given the potential for misdiagnosis, approaching patients with a broad differential can be helpful. In our patient, the differential diagnosis included Sweet syndrome, NEH, bacterial cellulitis, erysipelas, leukemia cutis, sarcoid, and eosinophilic cellulitis.

Leukemia cutis refers to the infiltration of neoplastic leukocytes in the skin and often occurs in patients with peripheral leukemia, most often acute myeloid leukemia or chronic lymphocytic leukemia. Patients with leukemia cutis often have a worse prognosis, as this finding signifies extramedullary spread of disease.⁶ Clinically, lesions can appear similar to those seen in our patient, though they typically are not symptomatic, can be nodular, tend to exhibit a violaceous hue, and occasionally may be hemorrhagic. Wells syndrome (also known as eosinophilic cellulitis) is an inflammatory dermatosis that presents as painful or pruritic, edematous and erythematous plaques.^7,8 A green hue on resolution is present in some cases and may help clinicians differentiate this disease from mimickers.⁷ Often, eosinophilic cellulitis is misdiagnosed as bacterial cellulitis and treated with antibiotics. The presence of systemic symptoms such as fever or arthralgia is more typical of bacterial cellulitis, erysipelas, eosinophilic cellulitis, or Sweet syndrome than of NEH.¹ Additionally, inflammatory markers (ie, C-reactive protein) and white blood cell counts tend to be elevated in bacterial cellulitis and Sweet syndrome, while leukopenia often is seen in NEH.

Histopathology is crucial in distinguishing these disease etiologies. Neutrophilic eccrine hidradenitis is diagnosed by the characteristic neutrophilic infiltrate and necrosis surrounding eccrine glands and coils. There also may be occasional intraductal abscesses and syringosquamous metaplasia of the sweat glands along with fibrosis of the adjacent dermis. In contrast, histologic sections of Sweet syndrome show numerous mature neutrophils infiltrating the dermis with marked papillary dermal edema. The histopathology of bacterial cellulitis and erysipelas is less specific, but common features include dermal edema, lymphatic dilation, and a diffuse neutrophilic infiltrate surrounding blood vessels. Pathogenic organisms may be seen on histopathology but are not required for the diagnosis of bacterial cellulitis or erysipelas.² Additionally, blood and tissue culture can assist in identification of both the source of infection and the causative organism, but cultures may not always be positive. 

Comparatively, the histopathologic features of eosinophilic cellulitis include dermal edema, eosinophilic infiltration, and flame figures that form when eosinophils degranulate and coat collagen fibers with major basic protein. Flame figures are characteristic but not pathognomonic for eosinophilic cellulitis.⁷ The histopathology of leukemia cutis varies based on the leukemia classification; generally, in acute myeloid leukemia the infiltrate is composed of neoplastic cells in the early stages of development that are positive for myeloid markers such as myeloperoxidase. Atypical and immature granulocytes within the leukocytic infiltrate differentiate this condition from the other diagnoses. Treatment may entail chemotherapy or radiotherapy, and this diagnosis generally carries the worst prognosis of all the conditions in the differential.⁶

Differentiating between these conditions is important in guiding treatment, especially in patients with febrile neutropenia. Unnecessary steroids in immunosuppressed patients can be dangerous, especially if the patient has an infection such as bacterial cellulitis. Furthermore, unwarranted antibiotic use for noninfectious conditions may expose patients to substantial side effects and not improve the condition. Neutrophilic eccrine hidradenitis typically is self-limited and treated symptomatically with systemic corticosteroids and nonsteroidal anti-inflammatory drugs.³ Sweet syndrome often requires a longer course of oral steroids. Leukemia cutis worsens as the leukemia advances, and treatment of the underlying malignancy is the most effective treatment.⁹

Early and accurate recognition of the diagnosis can prevent harmful diagnostic delay, unnecessary antibiotic use, or extended steroid taper in neutropenic patients. Appreciating the differences between these diagnoses can assist clinicians in investigating and tailoring a broad differential to specific patient presentations, which is especially critical when considering common mimickers for life-threatening conditions.

THE DIAGNOSIS: Neutrophilic Eccrine Hidradenitis

A biopsy from the left preauricular cheek demonstrated dermal neutrophilic inflammation around eccrine coils with focal necrosis (Figure). No notable diffuse dermal neutrophilic infiltrate was present, ruling out Sweet syndrome, and no notable interstitial neutrophilic infiltrate was present, making cellulitis and erysipelas less likely; panculture of tissue also was negative.^1,2 Atypical cells in the deep dermis were positive for CD163 and negative for CD117, CD34, CD123, and myeloperoxidase, consistent with a diagnosis of neutrophilic eccrine hidradenitis (NEH) and reactive histiocytes.³ Treatment with oral prednisone resulted in rapid improvement of symptoms.

Neutrophilic eccrine hidradenitis is a rare reactive neutrophilic dermatosis characterized by eccrine gland involvement. This benign and self-limited condition presents as asymmetric erythematous papules and plaques.² Among 8 granulocytopenic patients with neutrophilic dermatoses, 5 were diagnosed with NEH.⁴ Although first identified in 1982, NEH remains poorly understood.² Initial theories suggested that NEH developed due to cytotoxic substances secreted in sweat glands causing necrosis and neutrophil chemotaxis; however, chemotherapy exposure cannot be linked to every case of NEH. Neutrophilic eccrine hidradenitis can be extremely difficult to differentiate clinically from conditions such as cellulitis and Sweet syndrome.

A patient history can be helpful in identifying triggering factors. Neutrophilic eccrine hidradenitis most commonly is associated with malignant, drug-induced, or infectious triggers, while Sweet syndrome has a broad range of associations including infections, vaccines, inflammatory bowel disease, pregnancy, malignancy, and drug-induced etiologies (Table).¹ On average, NEH presents 10 days after chemotherapy induction, with 70% of cases presenting after the first chemotherapy cycle.⁵ Bacterial cellulitis or erysipelas have an infectious etiology, and patients may report symptoms such as fever, chills, or malaise. Immunosuppressed patients are at greater risk for infection; therefore, clinical signs of infection in a granulocytopenic patient should be addressed urgently.

Physical examination may have limited value in differentiating between these diagnoses, as neutrophilic dermatoses notoriously mimic infection. Cutaneous lesions can appear as pruritic or tender erythematous plaques, papules, or nodules in these conditions, though cellulitis and erysipelas tend to be unilateral and may have associated purulence or inflamed skin lymphatics. Given the potential for misdiagnosis, approaching patients with a broad differential can be helpful. In our patient, the differential diagnosis included Sweet syndrome, NEH, bacterial cellulitis, erysipelas, leukemia cutis, sarcoid, and eosinophilic cellulitis.

Leukemia cutis refers to the infiltration of neoplastic leukocytes in the skin and often occurs in patients with peripheral leukemia, most often acute myeloid leukemia or chronic lymphocytic leukemia. Patients with leukemia cutis often have a worse prognosis, as this finding signifies extramedullary spread of disease.⁶ Clinically, lesions can appear similar to those seen in our patient, though they typically are not symptomatic, can be nodular, tend to exhibit a violaceous hue, and occasionally may be hemorrhagic. Wells syndrome (also known as eosinophilic cellulitis) is an inflammatory dermatosis that presents as painful or pruritic, edematous and erythematous plaques.^7,8 A green hue on resolution is present in some cases and may help clinicians differentiate this disease from mimickers.⁷ Often, eosinophilic cellulitis is misdiagnosed as bacterial cellulitis and treated with antibiotics. The presence of systemic symptoms such as fever or arthralgia is more typical of bacterial cellulitis, erysipelas, eosinophilic cellulitis, or Sweet syndrome than of NEH.¹ Additionally, inflammatory markers (ie, C-reactive protein) and white blood cell counts tend to be elevated in bacterial cellulitis and Sweet syndrome, while leukopenia often is seen in NEH.

Histopathology is crucial in distinguishing these disease etiologies. Neutrophilic eccrine hidradenitis is diagnosed by the characteristic neutrophilic infiltrate and necrosis surrounding eccrine glands and coils. There also may be occasional intraductal abscesses and syringosquamous metaplasia of the sweat glands along with fibrosis of the adjacent dermis. In contrast, histologic sections of Sweet syndrome show numerous mature neutrophils infiltrating the dermis with marked papillary dermal edema. The histopathology of bacterial cellulitis and erysipelas is less specific, but common features include dermal edema, lymphatic dilation, and a diffuse neutrophilic infiltrate surrounding blood vessels. Pathogenic organisms may be seen on histopathology but are not required for the diagnosis of bacterial cellulitis or erysipelas.² Additionally, blood and tissue culture can assist in identification of both the source of infection and the causative organism, but cultures may not always be positive. 

Comparatively, the histopathologic features of eosinophilic cellulitis include dermal edema, eosinophilic infiltration, and flame figures that form when eosinophils degranulate and coat collagen fibers with major basic protein. Flame figures are characteristic but not pathognomonic for eosinophilic cellulitis.⁷ The histopathology of leukemia cutis varies based on the leukemia classification; generally, in acute myeloid leukemia the infiltrate is composed of neoplastic cells in the early stages of development that are positive for myeloid markers such as myeloperoxidase. Atypical and immature granulocytes within the leukocytic infiltrate differentiate this condition from the other diagnoses. Treatment may entail chemotherapy or radiotherapy, and this diagnosis generally carries the worst prognosis of all the conditions in the differential.⁶

Differentiating between these conditions is important in guiding treatment, especially in patients with febrile neutropenia. Unnecessary steroids in immunosuppressed patients can be dangerous, especially if the patient has an infection such as bacterial cellulitis. Furthermore, unwarranted antibiotic use for noninfectious conditions may expose patients to substantial side effects and not improve the condition. Neutrophilic eccrine hidradenitis typically is self-limited and treated symptomatically with systemic corticosteroids and nonsteroidal anti-inflammatory drugs.³ Sweet syndrome often requires a longer course of oral steroids. Leukemia cutis worsens as the leukemia advances, and treatment of the underlying malignancy is the most effective treatment.⁹

Early and accurate recognition of the diagnosis can prevent harmful diagnostic delay, unnecessary antibiotic use, or extended steroid taper in neutropenic patients. Appreciating the differences between these diagnoses can assist clinicians in investigating and tailoring a broad differential to specific patient presentations, which is especially critical when considering common mimickers for life-threatening conditions.

The Diagnosis: Poroma

Histopathology showed an endophytic expansion of the epidermis by bland, uniform, basaloid epithelial cells with focal ductal differentiation and an abrupt transition with surrounding epidermal keratinocytes (Figure), consistent with a diagnosis of poroma. The patient elected to monitor the lesion rather than to have it excised.

Eccrine poroma, used interchangeably with the term poroma, is a rare benign adnexal tumor of the eccrine sweat glands resulting from proliferation of the acrosyringium.^1,2 It often occurs on the palms or soles, though it also can arise anywhere sweat glands are present.¹ Eccrine poromas often appear in middle-aged individuals as singular, well-circumscribed, red-brown papules or nodules.³ A characteristic feature is a shallow, cup-shaped depression within the larger papule or nodule.¹

Because the condition is benign and often asymptomatic, it can be safely monitored for progression.¹ However, if the lesion is symptomatic or located in a sensitive area, complete excision is curative.⁴ Eccrine poromas can recur, making close monitoring following excision important.⁵ The development of bleeding, itching, or pain in a previously asymptomatic lesion may indicate possible malignant transformation, which occurs in only 18% of cases.⁶

The differential diagnosis includes basal cell carcinoma, circumscribed acral hypokeratosis, Kaposi sarcoma, and pyogenic granuloma. Basal cell carcinoma is the most common type of skin cancer.⁷ In rare cases it has been shown to present on the palms or soles as a slowgrowing, reddish-pink papule or plaque with central ulceration. It typically is asymptomatic. Histopathology shows dermal nests of basaloid cells with peripheral palisading, stromal mucin, and peritumoral clefts. Treatment is surgical excision.⁷

Circumscribed acral hypokeratosis presents on the palms or soles as a solitary, shallow, well-defined lesion with a flat base and raised border.⁸ It often is red-pink in color and most frequently occurs in middle-aged women. Although the cause of the condition is unknown, it is thought to be the result of trauma or human papillomavirus infection.8 Biopsy results characteristically show hypokeratosis demarcated by a sharp and frayed cutoff from uninvolved acral skin with discrete hypogranulosis, dilated blood vessels in the papillary dermis, and slightly thickened collagen fibers in the reticular dermis.⁹ Surgical excision is a potential treatment option, as topical corticosteroids, retinoids, and calcipotriene have not been shown to be effective; spontaneous resolution has been reported.⁸

Kaposi sarcoma is a vascular neoplasm that is associated with human herpesvirus 8 infection.¹⁰ It typically presents on mucocutaneous sites and the lower extremities. Palmar involvement has been reported in rare cases, occurring as a solitary, well-demarcated, violaceous macule or patch that may be painful.^10-12 Characteristic histopathologic features include a proliferation in the dermis of slitlike vascular spaces and spindle cell proliferation.¹³ Treatment options include cryosurgery; pulsed dye laser; and topical, intralesional, or systemic chemotherapy agents, depending on the stage of the patient’s disease. Antiretroviral therapy is indicated for patients with Kaposi sarcoma secondary to AIDS.¹⁴

Pyogenic granuloma presents as a solitary red-brown or bluish-black papule or nodule that bleeds easily when manipulated.¹⁵ It commonly occurs following trauma, typically on the fingers, feet, and lips.⁶ Although benign, potential complications include ulceration and blood loss. Pyogenic granulomas can be treated via curettage and cautery, excision, cryosurgery, or pulsed dye laser.¹⁵

The Diagnosis: Poroma

Histopathology showed an endophytic expansion of the epidermis by bland, uniform, basaloid epithelial cells with focal ductal differentiation and an abrupt transition with surrounding epidermal keratinocytes (Figure), consistent with a diagnosis of poroma. The patient elected to monitor the lesion rather than to have it excised.

Eccrine poroma, used interchangeably with the term poroma, is a rare benign adnexal tumor of the eccrine sweat glands resulting from proliferation of the acrosyringium.^1,2 It often occurs on the palms or soles, though it also can arise anywhere sweat glands are present.¹ Eccrine poromas often appear in middle-aged individuals as singular, well-circumscribed, red-brown papules or nodules.³ A characteristic feature is a shallow, cup-shaped depression within the larger papule or nodule.¹

Because the condition is benign and often asymptomatic, it can be safely monitored for progression.¹ However, if the lesion is symptomatic or located in a sensitive area, complete excision is curative.⁴ Eccrine poromas can recur, making close monitoring following excision important.⁵ The development of bleeding, itching, or pain in a previously asymptomatic lesion may indicate possible malignant transformation, which occurs in only 18% of cases.⁶

The differential diagnosis includes basal cell carcinoma, circumscribed acral hypokeratosis, Kaposi sarcoma, and pyogenic granuloma. Basal cell carcinoma is the most common type of skin cancer.⁷ In rare cases it has been shown to present on the palms or soles as a slowgrowing, reddish-pink papule or plaque with central ulceration. It typically is asymptomatic. Histopathology shows dermal nests of basaloid cells with peripheral palisading, stromal mucin, and peritumoral clefts. Treatment is surgical excision.⁷

Circumscribed acral hypokeratosis presents on the palms or soles as a solitary, shallow, well-defined lesion with a flat base and raised border.⁸ It often is red-pink in color and most frequently occurs in middle-aged women. Although the cause of the condition is unknown, it is thought to be the result of trauma or human papillomavirus infection.8 Biopsy results characteristically show hypokeratosis demarcated by a sharp and frayed cutoff from uninvolved acral skin with discrete hypogranulosis, dilated blood vessels in the papillary dermis, and slightly thickened collagen fibers in the reticular dermis.⁹ Surgical excision is a potential treatment option, as topical corticosteroids, retinoids, and calcipotriene have not been shown to be effective; spontaneous resolution has been reported.⁸

Kaposi sarcoma is a vascular neoplasm that is associated with human herpesvirus 8 infection.¹⁰ It typically presents on mucocutaneous sites and the lower extremities. Palmar involvement has been reported in rare cases, occurring as a solitary, well-demarcated, violaceous macule or patch that may be painful.^10-12 Characteristic histopathologic features include a proliferation in the dermis of slitlike vascular spaces and spindle cell proliferation.¹³ Treatment options include cryosurgery; pulsed dye laser; and topical, intralesional, or systemic chemotherapy agents, depending on the stage of the patient’s disease. Antiretroviral therapy is indicated for patients with Kaposi sarcoma secondary to AIDS.¹⁴

Pyogenic granuloma presents as a solitary red-brown or bluish-black papule or nodule that bleeds easily when manipulated.¹⁵ It commonly occurs following trauma, typically on the fingers, feet, and lips.⁶ Although benign, potential complications include ulceration and blood loss. Pyogenic granulomas can be treated via curettage and cautery, excision, cryosurgery, or pulsed dye laser.¹⁵

The Diagnosis: Poroma

Histopathology showed an endophytic expansion of the epidermis by bland, uniform, basaloid epithelial cells with focal ductal differentiation and an abrupt transition with surrounding epidermal keratinocytes (Figure), consistent with a diagnosis of poroma. The patient elected to monitor the lesion rather than to have it excised.

Eccrine poroma, used interchangeably with the term poroma, is a rare benign adnexal tumor of the eccrine sweat glands resulting from proliferation of the acrosyringium.^1,2 It often occurs on the palms or soles, though it also can arise anywhere sweat glands are present.¹ Eccrine poromas often appear in middle-aged individuals as singular, well-circumscribed, red-brown papules or nodules.³ A characteristic feature is a shallow, cup-shaped depression within the larger papule or nodule.¹

Because the condition is benign and often asymptomatic, it can be safely monitored for progression.¹ However, if the lesion is symptomatic or located in a sensitive area, complete excision is curative.⁴ Eccrine poromas can recur, making close monitoring following excision important.⁵ The development of bleeding, itching, or pain in a previously asymptomatic lesion may indicate possible malignant transformation, which occurs in only 18% of cases.⁶

The differential diagnosis includes basal cell carcinoma, circumscribed acral hypokeratosis, Kaposi sarcoma, and pyogenic granuloma. Basal cell carcinoma is the most common type of skin cancer.⁷ In rare cases it has been shown to present on the palms or soles as a slowgrowing, reddish-pink papule or plaque with central ulceration. It typically is asymptomatic. Histopathology shows dermal nests of basaloid cells with peripheral palisading, stromal mucin, and peritumoral clefts. Treatment is surgical excision.⁷

Circumscribed acral hypokeratosis presents on the palms or soles as a solitary, shallow, well-defined lesion with a flat base and raised border.⁸ It often is red-pink in color and most frequently occurs in middle-aged women. Although the cause of the condition is unknown, it is thought to be the result of trauma or human papillomavirus infection.8 Biopsy results characteristically show hypokeratosis demarcated by a sharp and frayed cutoff from uninvolved acral skin with discrete hypogranulosis, dilated blood vessels in the papillary dermis, and slightly thickened collagen fibers in the reticular dermis.⁹ Surgical excision is a potential treatment option, as topical corticosteroids, retinoids, and calcipotriene have not been shown to be effective; spontaneous resolution has been reported.⁸

Kaposi sarcoma is a vascular neoplasm that is associated with human herpesvirus 8 infection.¹⁰ It typically presents on mucocutaneous sites and the lower extremities. Palmar involvement has been reported in rare cases, occurring as a solitary, well-demarcated, violaceous macule or patch that may be painful.^10-12 Characteristic histopathologic features include a proliferation in the dermis of slitlike vascular spaces and spindle cell proliferation.¹³ Treatment options include cryosurgery; pulsed dye laser; and topical, intralesional, or systemic chemotherapy agents, depending on the stage of the patient’s disease. Antiretroviral therapy is indicated for patients with Kaposi sarcoma secondary to AIDS.¹⁴

Pyogenic granuloma presents as a solitary red-brown or bluish-black papule or nodule that bleeds easily when manipulated.¹⁵ It commonly occurs following trauma, typically on the fingers, feet, and lips.⁶ Although benign, potential complications include ulceration and blood loss. Pyogenic granulomas can be treated via curettage and cautery, excision, cryosurgery, or pulsed dye laser.¹⁵

The Diagnosis: Actinic Prurigo

Actinic prurigo is an idiopathic photodermatosis triggered by UV exposure that primarily affects sun-exposed areas of the skin.^1,2 It typically presents as pruritic papules, plaques, and nodules, with most patients also experiencing oral tingling and pain.³ In more severe cases, it can progress to include conjunctival disease, scarring, and cheilitis.¹ A study of ocular findings among children with actinic pruritus reported that photophobia was one of the most important features,⁴ which was present in our patient. The face, especially over the zygomatic arches, nasal bridge, and lower lip, commonly is affected.1 Secondary lichenification or eczematization may occur.⁵ In our patient, the combination of conjunctivitis, cheilitis, and an eruption on sun-exposed skin were crucial in making the diagnosis.

Most cases present in patients younger than 10 years. It most commonly is seen in American Indians in North America, Central America, and South America.² After the diagnosis was considered in our patient, the family was asked about their ancestry and confirmed that both of the patient’s maternal and paternal grandparents were of American Indian descent. There also is a strong genetic component; the HLA-DR4 allele variant is present in 90% of cases, especially DRB1*0407, which is seen in 60% of cases.^1,6 In our patient, testing revealed HLA-DR4, DRB1*04 positivity. We further hypothesized that his mother’s photosensitive rash may have been actinic prurigo as opposed to polymorphous light eruption, which could explain the lack of response to hydroxychloroquine.

The diagnosis of actinic prurigo usually is made clinically. A skin biopsy typically is not necessary but would show hyperkeratosis, spongiosis, and acanthosis with a lymphocytic perivascular infiltrate. Biopsies of the lip classically show lymphoid germinal centers in the lamina propria, which can help distinguish actinic prurigo from polymorphous light eruption.¹

In our patient, the differential diagnosis included polymorphous light eruption, connective tissue disease such as lupus erythematosus or dermatomyositis, porphyria such as erythropoietic protoporphyria, and allergic contact dermatitis. Polymorphous light eruption was ruled out by the oral and ocular manifestations, which are not atypical for this diagnosis. The patient’s laboratory results displayed unremarkable antinuclear antibodies, creatine kinase, aldolase, and extractable nuclear antigens, which made connective tissue disease unlikely. Furthermore, a porphyria screen for total plasma porphyrins and whole blood protoporphyrin was negative, which helped rule out porphyria. Allergic contact dermatitis seemed less likely given the lack of improvement with topical steroids. Overall, the clinical presentation in a patient with relevant family ancestry and HLA-DR4 positivity supported a diagnosis of actinic prurigo.⁷

To manage the condition in our patient, strict photoprotection was recommended as well as the application of triamcinolone ointment 0.025% to the affected areas twice daily until the skin symptoms improved. For acute flares, other treatment considerations include topical tacrolimus, oral antihistamines, and oral corticosteroids. Some success has been reported with cyclosporine and azathioprine. For severe disease, thalidomide is the recommended treatment; it is effective in pediatric patients at dosages of 50 to 100 mg daily, but the dose has not yet been standardized for this age group.^8,9 Many adult patients initially are controlled with 100 to 200 mg daily, which can be tapered down to a dosage of 25 to 50 mg weekly with few adverse effects; however, the overall substantial side effects of thalidomide limit its use in both pediatric and adult populations.^1,2 Newer studies have suggested promising results with dupilumab, especially when actinic prurigo presents with high IgE levels or eosinophils on histology.^7,10 In our patient, the IgE level was normal.

The Diagnosis: Actinic Prurigo

Actinic prurigo is an idiopathic photodermatosis triggered by UV exposure that primarily affects sun-exposed areas of the skin.^1,2 It typically presents as pruritic papules, plaques, and nodules, with most patients also experiencing oral tingling and pain.³ In more severe cases, it can progress to include conjunctival disease, scarring, and cheilitis.¹ A study of ocular findings among children with actinic pruritus reported that photophobia was one of the most important features,⁴ which was present in our patient. The face, especially over the zygomatic arches, nasal bridge, and lower lip, commonly is affected.1 Secondary lichenification or eczematization may occur.⁵ In our patient, the combination of conjunctivitis, cheilitis, and an eruption on sun-exposed skin were crucial in making the diagnosis.

Most cases present in patients younger than 10 years. It most commonly is seen in American Indians in North America, Central America, and South America.² After the diagnosis was considered in our patient, the family was asked about their ancestry and confirmed that both of the patient’s maternal and paternal grandparents were of American Indian descent. There also is a strong genetic component; the HLA-DR4 allele variant is present in 90% of cases, especially DRB1*0407, which is seen in 60% of cases.^1,6 In our patient, testing revealed HLA-DR4, DRB1*04 positivity. We further hypothesized that his mother’s photosensitive rash may have been actinic prurigo as opposed to polymorphous light eruption, which could explain the lack of response to hydroxychloroquine.

The diagnosis of actinic prurigo usually is made clinically. A skin biopsy typically is not necessary but would show hyperkeratosis, spongiosis, and acanthosis with a lymphocytic perivascular infiltrate. Biopsies of the lip classically show lymphoid germinal centers in the lamina propria, which can help distinguish actinic prurigo from polymorphous light eruption.¹

In our patient, the differential diagnosis included polymorphous light eruption, connective tissue disease such as lupus erythematosus or dermatomyositis, porphyria such as erythropoietic protoporphyria, and allergic contact dermatitis. Polymorphous light eruption was ruled out by the oral and ocular manifestations, which are not atypical for this diagnosis. The patient’s laboratory results displayed unremarkable antinuclear antibodies, creatine kinase, aldolase, and extractable nuclear antigens, which made connective tissue disease unlikely. Furthermore, a porphyria screen for total plasma porphyrins and whole blood protoporphyrin was negative, which helped rule out porphyria. Allergic contact dermatitis seemed less likely given the lack of improvement with topical steroids. Overall, the clinical presentation in a patient with relevant family ancestry and HLA-DR4 positivity supported a diagnosis of actinic prurigo.⁷

To manage the condition in our patient, strict photoprotection was recommended as well as the application of triamcinolone ointment 0.025% to the affected areas twice daily until the skin symptoms improved. For acute flares, other treatment considerations include topical tacrolimus, oral antihistamines, and oral corticosteroids. Some success has been reported with cyclosporine and azathioprine. For severe disease, thalidomide is the recommended treatment; it is effective in pediatric patients at dosages of 50 to 100 mg daily, but the dose has not yet been standardized for this age group.^8,9 Many adult patients initially are controlled with 100 to 200 mg daily, which can be tapered down to a dosage of 25 to 50 mg weekly with few adverse effects; however, the overall substantial side effects of thalidomide limit its use in both pediatric and adult populations.^1,2 Newer studies have suggested promising results with dupilumab, especially when actinic prurigo presents with high IgE levels or eosinophils on histology.^7,10 In our patient, the IgE level was normal.

The Diagnosis: Actinic Prurigo

Actinic prurigo is an idiopathic photodermatosis triggered by UV exposure that primarily affects sun-exposed areas of the skin.^1,2 It typically presents as pruritic papules, plaques, and nodules, with most patients also experiencing oral tingling and pain.³ In more severe cases, it can progress to include conjunctival disease, scarring, and cheilitis.¹ A study of ocular findings among children with actinic pruritus reported that photophobia was one of the most important features,⁴ which was present in our patient. The face, especially over the zygomatic arches, nasal bridge, and lower lip, commonly is affected.1 Secondary lichenification or eczematization may occur.⁵ In our patient, the combination of conjunctivitis, cheilitis, and an eruption on sun-exposed skin were crucial in making the diagnosis.

Most cases present in patients younger than 10 years. It most commonly is seen in American Indians in North America, Central America, and South America.² After the diagnosis was considered in our patient, the family was asked about their ancestry and confirmed that both of the patient’s maternal and paternal grandparents were of American Indian descent. There also is a strong genetic component; the HLA-DR4 allele variant is present in 90% of cases, especially DRB1*0407, which is seen in 60% of cases.^1,6 In our patient, testing revealed HLA-DR4, DRB1*04 positivity. We further hypothesized that his mother’s photosensitive rash may have been actinic prurigo as opposed to polymorphous light eruption, which could explain the lack of response to hydroxychloroquine.

The diagnosis of actinic prurigo usually is made clinically. A skin biopsy typically is not necessary but would show hyperkeratosis, spongiosis, and acanthosis with a lymphocytic perivascular infiltrate. Biopsies of the lip classically show lymphoid germinal centers in the lamina propria, which can help distinguish actinic prurigo from polymorphous light eruption.¹

In our patient, the differential diagnosis included polymorphous light eruption, connective tissue disease such as lupus erythematosus or dermatomyositis, porphyria such as erythropoietic protoporphyria, and allergic contact dermatitis. Polymorphous light eruption was ruled out by the oral and ocular manifestations, which are not atypical for this diagnosis. The patient’s laboratory results displayed unremarkable antinuclear antibodies, creatine kinase, aldolase, and extractable nuclear antigens, which made connective tissue disease unlikely. Furthermore, a porphyria screen for total plasma porphyrins and whole blood protoporphyrin was negative, which helped rule out porphyria. Allergic contact dermatitis seemed less likely given the lack of improvement with topical steroids. Overall, the clinical presentation in a patient with relevant family ancestry and HLA-DR4 positivity supported a diagnosis of actinic prurigo.⁷

To manage the condition in our patient, strict photoprotection was recommended as well as the application of triamcinolone ointment 0.025% to the affected areas twice daily until the skin symptoms improved. For acute flares, other treatment considerations include topical tacrolimus, oral antihistamines, and oral corticosteroids. Some success has been reported with cyclosporine and azathioprine. For severe disease, thalidomide is the recommended treatment; it is effective in pediatric patients at dosages of 50 to 100 mg daily, but the dose has not yet been standardized for this age group.^8,9 Many adult patients initially are controlled with 100 to 200 mg daily, which can be tapered down to a dosage of 25 to 50 mg weekly with few adverse effects; however, the overall substantial side effects of thalidomide limit its use in both pediatric and adult populations.^1,2 Newer studies have suggested promising results with dupilumab, especially when actinic prurigo presents with high IgE levels or eosinophils on histology.^7,10 In our patient, the IgE level was normal.

The Diagnosis: Syphilis

Histopathology revealed psoriasiform hyperplasia, endothelial cell swelling, and a brisk lichenoid inflammation with plasma cells (Figure, A). There also was pustular folliculitis in association with well-formed granulomatous inflammation and a prominent number of plasma cells (Figure, B). Treponema pallidum immunostaining showed numerous organisms in the epidermal and follicular epithelium. Rapid plasma reagin was found to be positive with a titer of 1:128. Evaluation for neurosyphilis through lumbar puncture was negative; the patient also was HIV negative. All of our patient’s skin lesions cleared after a 3-week course of weekly intramuscular benzathine G injections. Due to his substantial clinical improvement, the patient was subsequently lost to follow-up.

Syphilis, an infectious disease caused by the spirochete bacterium T pallidum, has a well-known natural history defined by various stages classically categorized as primary, secondary, latent, or late (tertiary).¹ The classic lesion in primary syphilis is the chancre, a painless ulcer with raised borders that develops within approximately 3 weeks following the initial inoculation.² Secondary syphilis manifests with mucocutaneous findings in up to 97% of patients, and untreated patients develop secondary syphilis at a rate of approximately 25%.³ Although mucocutaneous findings in secondary syphilis can vary widely, patients most commonly develop a diffuse maculopapular exanthem, and 40% develop mucosal findings including genital ulcers, mucous patches, and condylomata lata.¹ In latent syphilis, there is seroreactivity, but otherwise there are no clinical symptoms. A clear symptomatic history of prior primary or secondary syphilis may be known or unknown. Latent syphilis is divided into early and late phases, and the World Health Organization designates 2 years after the first suspected exposure as the cutoff point for early and late latency.⁴ During the first 4 years of latent syphilis, patients may exhibit mucocutaneous relapses. Our patient denied any sexual activity for more than 3 years prior to presentation. Because of the start of iatrogenic immunosuppression during this period, this case was classified as late latent syphilis with mucocutaneous reactivation.

Behçet disease was included within the differential diagnosis but is characterized by multiorgan systemic vasculitis that causes various mucocutaneous findings including aphthous ulcers, papulopustular lesions, and genital ulcers.⁵ Histopathologic features are nonspecific, and the clinical finding of recurrent genital and oral ulceration should be present for diagnosis. This disease predominantly occurs in East Asian or Mediterranean populations and is otherwise rare in White individuals.

SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome is a rare disorder consisting of skin, joint, and bone manifestations.⁶ Severe acne generally is accompanied by palmoplantar pustulosis along with pain and joint tenderness involving the anterior chest and axial skeleton, both of which were absent in our patient.

Pustular psoriasis can be localized or generalized. Localized presentations frequently are acral and may be associated with a variable degree of nail dystrophy and arthritis. Generalized presentations are characterized by hyperemic, well-defined patches with variable numbers of pustules.⁷ The pustules are the consequence of exuberate neutrophilic exocytosis into the epidermis and are nonfollicular.

Steroid-induced acne may be considered in the proper clinical setting of an acneform eruption with a prior history of systemic steroid treatment. However, additional findings of mucositis would not be expected, and although our patient was prescribed prednisone from his primary care physician prior to presentation to our clinic, this medication was given after the onset of the cutaneous eruption.

Syphilis commonly is referred to as the great mimicker due to its potential diverse morphologic presentations, which can involve acneform eruptions, though rare.⁸ In the setting of mucositis, generalized acneform eruptions should raise suspicion for the possibility of syphilis, even in the absence of other more classic cutaneous features.

The Diagnosis: Syphilis

Histopathology revealed psoriasiform hyperplasia, endothelial cell swelling, and a brisk lichenoid inflammation with plasma cells (Figure, A). There also was pustular folliculitis in association with well-formed granulomatous inflammation and a prominent number of plasma cells (Figure, B). Treponema pallidum immunostaining showed numerous organisms in the epidermal and follicular epithelium. Rapid plasma reagin was found to be positive with a titer of 1:128. Evaluation for neurosyphilis through lumbar puncture was negative; the patient also was HIV negative. All of our patient’s skin lesions cleared after a 3-week course of weekly intramuscular benzathine G injections. Due to his substantial clinical improvement, the patient was subsequently lost to follow-up.

Syphilis, an infectious disease caused by the spirochete bacterium T pallidum, has a well-known natural history defined by various stages classically categorized as primary, secondary, latent, or late (tertiary).¹ The classic lesion in primary syphilis is the chancre, a painless ulcer with raised borders that develops within approximately 3 weeks following the initial inoculation.² Secondary syphilis manifests with mucocutaneous findings in up to 97% of patients, and untreated patients develop secondary syphilis at a rate of approximately 25%.³ Although mucocutaneous findings in secondary syphilis can vary widely, patients most commonly develop a diffuse maculopapular exanthem, and 40% develop mucosal findings including genital ulcers, mucous patches, and condylomata lata.¹ In latent syphilis, there is seroreactivity, but otherwise there are no clinical symptoms. A clear symptomatic history of prior primary or secondary syphilis may be known or unknown. Latent syphilis is divided into early and late phases, and the World Health Organization designates 2 years after the first suspected exposure as the cutoff point for early and late latency.⁴ During the first 4 years of latent syphilis, patients may exhibit mucocutaneous relapses. Our patient denied any sexual activity for more than 3 years prior to presentation. Because of the start of iatrogenic immunosuppression during this period, this case was classified as late latent syphilis with mucocutaneous reactivation.

Behçet disease was included within the differential diagnosis but is characterized by multiorgan systemic vasculitis that causes various mucocutaneous findings including aphthous ulcers, papulopustular lesions, and genital ulcers.⁵ Histopathologic features are nonspecific, and the clinical finding of recurrent genital and oral ulceration should be present for diagnosis. This disease predominantly occurs in East Asian or Mediterranean populations and is otherwise rare in White individuals.

SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome is a rare disorder consisting of skin, joint, and bone manifestations.⁶ Severe acne generally is accompanied by palmoplantar pustulosis along with pain and joint tenderness involving the anterior chest and axial skeleton, both of which were absent in our patient.

Pustular psoriasis can be localized or generalized. Localized presentations frequently are acral and may be associated with a variable degree of nail dystrophy and arthritis. Generalized presentations are characterized by hyperemic, well-defined patches with variable numbers of pustules.⁷ The pustules are the consequence of exuberate neutrophilic exocytosis into the epidermis and are nonfollicular.

Steroid-induced acne may be considered in the proper clinical setting of an acneform eruption with a prior history of systemic steroid treatment. However, additional findings of mucositis would not be expected, and although our patient was prescribed prednisone from his primary care physician prior to presentation to our clinic, this medication was given after the onset of the cutaneous eruption.

Syphilis commonly is referred to as the great mimicker due to its potential diverse morphologic presentations, which can involve acneform eruptions, though rare.⁸ In the setting of mucositis, generalized acneform eruptions should raise suspicion for the possibility of syphilis, even in the absence of other more classic cutaneous features.

The Diagnosis: Syphilis

Histopathology revealed psoriasiform hyperplasia, endothelial cell swelling, and a brisk lichenoid inflammation with plasma cells (Figure, A). There also was pustular folliculitis in association with well-formed granulomatous inflammation and a prominent number of plasma cells (Figure, B). Treponema pallidum immunostaining showed numerous organisms in the epidermal and follicular epithelium. Rapid plasma reagin was found to be positive with a titer of 1:128. Evaluation for neurosyphilis through lumbar puncture was negative; the patient also was HIV negative. All of our patient’s skin lesions cleared after a 3-week course of weekly intramuscular benzathine G injections. Due to his substantial clinical improvement, the patient was subsequently lost to follow-up.

Syphilis, an infectious disease caused by the spirochete bacterium T pallidum, has a well-known natural history defined by various stages classically categorized as primary, secondary, latent, or late (tertiary).¹ The classic lesion in primary syphilis is the chancre, a painless ulcer with raised borders that develops within approximately 3 weeks following the initial inoculation.² Secondary syphilis manifests with mucocutaneous findings in up to 97% of patients, and untreated patients develop secondary syphilis at a rate of approximately 25%.³ Although mucocutaneous findings in secondary syphilis can vary widely, patients most commonly develop a diffuse maculopapular exanthem, and 40% develop mucosal findings including genital ulcers, mucous patches, and condylomata lata.¹ In latent syphilis, there is seroreactivity, but otherwise there are no clinical symptoms. A clear symptomatic history of prior primary or secondary syphilis may be known or unknown. Latent syphilis is divided into early and late phases, and the World Health Organization designates 2 years after the first suspected exposure as the cutoff point for early and late latency.⁴ During the first 4 years of latent syphilis, patients may exhibit mucocutaneous relapses. Our patient denied any sexual activity for more than 3 years prior to presentation. Because of the start of iatrogenic immunosuppression during this period, this case was classified as late latent syphilis with mucocutaneous reactivation.

Behçet disease was included within the differential diagnosis but is characterized by multiorgan systemic vasculitis that causes various mucocutaneous findings including aphthous ulcers, papulopustular lesions, and genital ulcers.⁵ Histopathologic features are nonspecific, and the clinical finding of recurrent genital and oral ulceration should be present for diagnosis. This disease predominantly occurs in East Asian or Mediterranean populations and is otherwise rare in White individuals.

SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome is a rare disorder consisting of skin, joint, and bone manifestations.⁶ Severe acne generally is accompanied by palmoplantar pustulosis along with pain and joint tenderness involving the anterior chest and axial skeleton, both of which were absent in our patient.

Pustular psoriasis can be localized or generalized. Localized presentations frequently are acral and may be associated with a variable degree of nail dystrophy and arthritis. Generalized presentations are characterized by hyperemic, well-defined patches with variable numbers of pustules.⁷ The pustules are the consequence of exuberate neutrophilic exocytosis into the epidermis and are nonfollicular.

Steroid-induced acne may be considered in the proper clinical setting of an acneform eruption with a prior history of systemic steroid treatment. However, additional findings of mucositis would not be expected, and although our patient was prescribed prednisone from his primary care physician prior to presentation to our clinic, this medication was given after the onset of the cutaneous eruption.

Syphilis commonly is referred to as the great mimicker due to its potential diverse morphologic presentations, which can involve acneform eruptions, though rare.⁸ In the setting of mucositis, generalized acneform eruptions should raise suspicion for the possibility of syphilis, even in the absence of other more classic cutaneous features.

The Diagnosis: PASH (Pyoderma Gangrenosum, Acne, Hidradenitis Suppurativa) Syndrome

Obtaining our patient’s history of hidradenitis suppurativa (HS), a hallmark sterile neutrophilic dermatosis, was key to making the correct diagnosis of PASH (pyoderma gangrenosum, acne, HS) syndrome. In our patient, the history of HS increased the consideration of pyoderma gangrenosum (PG) due to the persistent breast and leg wounds. Additionally, it was important to consider a diagnosis of PG in lesions that were not responding to broad-spectrum antimicrobial treatment. In our patient, the concurrent presentation of draining abscesses in the axillae (Figure, A) and inflammatory nodulocystic facial acne (Figure, B) were additional diagnostic clues that suggested the triad of PASH syndrome.

Although SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome also can present with cutaneous features of acne and HS, the lack of bone and joint involvement in our patient made this diagnosis less likely. Calciphylaxis can present as ulcerations on the lower extremities, but it usually presents with a livedolike pattern with overlying black eschar and is unlikely in the absence of underlying metabolic or renal disease. PAPA (pyogenic arthritis, PG, acne) syndrome is characterized by recurrent joint involvement and lacks features of HS. Lastly, our patient was immunocompetent with no risk factors for mycobacterial infection.

PASH syndrome is a rare inherited syndrome, but its constituent inflammatory conditions are ubiquitous. They share a common underlying mechanism consisting of overactivation of the innate immune systems driven by increased production of the inflammatory cytokines IL-1, IL-17, and tumor necrosis factor α, resulting in sterile neutrophilic dermatoses.¹ The diagnosis is based on the clinical presentation, as laboratory investigations are nondiagnostic. Biopsies and cultures can be performed to rule out infectious etiologies. Additionally, PASH syndrome is considered part of a larger spectrum of syndromes including PAPA and PAPASH (pyogenic arthritis, acne, PG, HS) syndromes. The absence of pyogenic arthritis distinguishes PASH syndrome from PAPA and PAPASH syndromes.² Clinically, PASH syndrome and the related sterile neutrophilic dermatoses share the characteristic of pronounced cutaneous involvement that substantially alters the patient’s quality of life. Cigarette smoking is an exacerbating factor and has a well-established association with HS.³ Therefore, smoking cessation should be encouraged in these patients to avoid exacerbation of the disease process.

Maintaining adequate immunosuppression is key to managing the underlying disease processes. Classic immunosuppressive agents such as systemic glucocorticoids and methotrexate may fail to satisfactorily control the disease.⁴ Treatment options currently are somewhat limited and are aimed at targeting the inflammatory cytokines that propagate the disease. The most consistent responses have been observed with anti–tumor necrosis factor α antagonists such as adalimumab, infliximab, and etanercept.⁵ Additionally, there is varied response to anakinra, suggesting the importance of selectively targeting IL-1β.⁶ Unfortunately, misdiagnosis for an infectious etiology is common, and antibiotics and debridement are of limited use for the underlying pathophysiology of PASH syndrome. Importantly, biopsy and debridement often are discouraged due to the risk of pathergy.⁷

Our case demonstrates the importance of maintaining a high clinical suspicion for immune-mediated lesions that are refractory to antimicrobial agents. Additionally, prior history of multiple neutrophilic dermatoses should prompt consideration for the PASH/PAPA/PAPASH disease spectrum. Early and accurate identification of neutrophilic dermatoses such as PG and HS are crucial to initiating proper cytokine-targeting treatment and achieving disease remission.

The Diagnosis: PASH (Pyoderma Gangrenosum, Acne, Hidradenitis Suppurativa) Syndrome

Obtaining our patient’s history of hidradenitis suppurativa (HS), a hallmark sterile neutrophilic dermatosis, was key to making the correct diagnosis of PASH (pyoderma gangrenosum, acne, HS) syndrome. In our patient, the history of HS increased the consideration of pyoderma gangrenosum (PG) due to the persistent breast and leg wounds. Additionally, it was important to consider a diagnosis of PG in lesions that were not responding to broad-spectrum antimicrobial treatment. In our patient, the concurrent presentation of draining abscesses in the axillae (Figure, A) and inflammatory nodulocystic facial acne (Figure, B) were additional diagnostic clues that suggested the triad of PASH syndrome.

Although SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome also can present with cutaneous features of acne and HS, the lack of bone and joint involvement in our patient made this diagnosis less likely. Calciphylaxis can present as ulcerations on the lower extremities, but it usually presents with a livedolike pattern with overlying black eschar and is unlikely in the absence of underlying metabolic or renal disease. PAPA (pyogenic arthritis, PG, acne) syndrome is characterized by recurrent joint involvement and lacks features of HS. Lastly, our patient was immunocompetent with no risk factors for mycobacterial infection.

PASH syndrome is a rare inherited syndrome, but its constituent inflammatory conditions are ubiquitous. They share a common underlying mechanism consisting of overactivation of the innate immune systems driven by increased production of the inflammatory cytokines IL-1, IL-17, and tumor necrosis factor α, resulting in sterile neutrophilic dermatoses.¹ The diagnosis is based on the clinical presentation, as laboratory investigations are nondiagnostic. Biopsies and cultures can be performed to rule out infectious etiologies. Additionally, PASH syndrome is considered part of a larger spectrum of syndromes including PAPA and PAPASH (pyogenic arthritis, acne, PG, HS) syndromes. The absence of pyogenic arthritis distinguishes PASH syndrome from PAPA and PAPASH syndromes.² Clinically, PASH syndrome and the related sterile neutrophilic dermatoses share the characteristic of pronounced cutaneous involvement that substantially alters the patient’s quality of life. Cigarette smoking is an exacerbating factor and has a well-established association with HS.³ Therefore, smoking cessation should be encouraged in these patients to avoid exacerbation of the disease process.

Maintaining adequate immunosuppression is key to managing the underlying disease processes. Classic immunosuppressive agents such as systemic glucocorticoids and methotrexate may fail to satisfactorily control the disease.⁴ Treatment options currently are somewhat limited and are aimed at targeting the inflammatory cytokines that propagate the disease. The most consistent responses have been observed with anti–tumor necrosis factor α antagonists such as adalimumab, infliximab, and etanercept.⁵ Additionally, there is varied response to anakinra, suggesting the importance of selectively targeting IL-1β.⁶ Unfortunately, misdiagnosis for an infectious etiology is common, and antibiotics and debridement are of limited use for the underlying pathophysiology of PASH syndrome. Importantly, biopsy and debridement often are discouraged due to the risk of pathergy.⁷

Our case demonstrates the importance of maintaining a high clinical suspicion for immune-mediated lesions that are refractory to antimicrobial agents. Additionally, prior history of multiple neutrophilic dermatoses should prompt consideration for the PASH/PAPA/PAPASH disease spectrum. Early and accurate identification of neutrophilic dermatoses such as PG and HS are crucial to initiating proper cytokine-targeting treatment and achieving disease remission.

The Diagnosis: PASH (Pyoderma Gangrenosum, Acne, Hidradenitis Suppurativa) Syndrome

Obtaining our patient’s history of hidradenitis suppurativa (HS), a hallmark sterile neutrophilic dermatosis, was key to making the correct diagnosis of PASH (pyoderma gangrenosum, acne, HS) syndrome. In our patient, the history of HS increased the consideration of pyoderma gangrenosum (PG) due to the persistent breast and leg wounds. Additionally, it was important to consider a diagnosis of PG in lesions that were not responding to broad-spectrum antimicrobial treatment. In our patient, the concurrent presentation of draining abscesses in the axillae (Figure, A) and inflammatory nodulocystic facial acne (Figure, B) were additional diagnostic clues that suggested the triad of PASH syndrome.

Although SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome also can present with cutaneous features of acne and HS, the lack of bone and joint involvement in our patient made this diagnosis less likely. Calciphylaxis can present as ulcerations on the lower extremities, but it usually presents with a livedolike pattern with overlying black eschar and is unlikely in the absence of underlying metabolic or renal disease. PAPA (pyogenic arthritis, PG, acne) syndrome is characterized by recurrent joint involvement and lacks features of HS. Lastly, our patient was immunocompetent with no risk factors for mycobacterial infection.

PASH syndrome is a rare inherited syndrome, but its constituent inflammatory conditions are ubiquitous. They share a common underlying mechanism consisting of overactivation of the innate immune systems driven by increased production of the inflammatory cytokines IL-1, IL-17, and tumor necrosis factor α, resulting in sterile neutrophilic dermatoses.¹ The diagnosis is based on the clinical presentation, as laboratory investigations are nondiagnostic. Biopsies and cultures can be performed to rule out infectious etiologies. Additionally, PASH syndrome is considered part of a larger spectrum of syndromes including PAPA and PAPASH (pyogenic arthritis, acne, PG, HS) syndromes. The absence of pyogenic arthritis distinguishes PASH syndrome from PAPA and PAPASH syndromes.² Clinically, PASH syndrome and the related sterile neutrophilic dermatoses share the characteristic of pronounced cutaneous involvement that substantially alters the patient’s quality of life. Cigarette smoking is an exacerbating factor and has a well-established association with HS.³ Therefore, smoking cessation should be encouraged in these patients to avoid exacerbation of the disease process.

Maintaining adequate immunosuppression is key to managing the underlying disease processes. Classic immunosuppressive agents such as systemic glucocorticoids and methotrexate may fail to satisfactorily control the disease.⁴ Treatment options currently are somewhat limited and are aimed at targeting the inflammatory cytokines that propagate the disease. The most consistent responses have been observed with anti–tumor necrosis factor α antagonists such as adalimumab, infliximab, and etanercept.⁵ Additionally, there is varied response to anakinra, suggesting the importance of selectively targeting IL-1β.⁶ Unfortunately, misdiagnosis for an infectious etiology is common, and antibiotics and debridement are of limited use for the underlying pathophysiology of PASH syndrome. Importantly, biopsy and debridement often are discouraged due to the risk of pathergy.⁷

Our case demonstrates the importance of maintaining a high clinical suspicion for immune-mediated lesions that are refractory to antimicrobial agents. Additionally, prior history of multiple neutrophilic dermatoses should prompt consideration for the PASH/PAPA/PAPASH disease spectrum. Early and accurate identification of neutrophilic dermatoses such as PG and HS are crucial to initiating proper cytokine-targeting treatment and achieving disease remission.