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Seizure Prompts Man to Fall
ANSWER
The radiograph shows a fracture dislocation of the ankle. The distal tibia is dislocated medially relative to the talus, as evidenced by the widened joint space. There is also an oblique fracture of the distal fibula.
Since the patient was experiencing neurovascular compromise, the dislocation was promptly reduced in the emergency department. Subsequently, he was taken to the operating room for open reduction and internal fixation of his fibula fracture.
ANSWER
The radiograph shows a fracture dislocation of the ankle. The distal tibia is dislocated medially relative to the talus, as evidenced by the widened joint space. There is also an oblique fracture of the distal fibula.
Since the patient was experiencing neurovascular compromise, the dislocation was promptly reduced in the emergency department. Subsequently, he was taken to the operating room for open reduction and internal fixation of his fibula fracture.
ANSWER
The radiograph shows a fracture dislocation of the ankle. The distal tibia is dislocated medially relative to the talus, as evidenced by the widened joint space. There is also an oblique fracture of the distal fibula.
Since the patient was experiencing neurovascular compromise, the dislocation was promptly reduced in the emergency department. Subsequently, he was taken to the operating room for open reduction and internal fixation of his fibula fracture.
A 70-year-old man is brought to your facility by EMS following a new-onset, witnessed seizure. He reportedly fell down some steps. On arrival, he has returned to baseline but is complaining of left-sided weakness and right ankle pain. Medical history is significant for mild hypertension. Vital signs are stable. The patient exhibits slight confusion. He reports some mild weakness on his left side, especially in his lower extremity. There also appears to be moderate soft-tissue swelling of his right ankle, with a slight deformity noted. Dorsalis pedal pulse appears to be slightly diminished in that foot as well. You send the patient for noncontrast CT of the head, as well as a radiograph of the right ankle (the latter of which is shown). What is your impression?
Marathon Runner Has History of A-fib
ANSWER
This ECG shows marked sinus bradycardia with a first-degree atrioventricular block and nonspecific T-wave abnormality. The QT interval of 524 ms is consistent with prolonged QT interval but is normal when corrected for rate.
These findings were consistent with previous ECGs. Since the patient’s bradycardia is asymptomatic, no intervention (ie, placement of a permanent pacemaker) is indicated.
ANSWER
This ECG shows marked sinus bradycardia with a first-degree atrioventricular block and nonspecific T-wave abnormality. The QT interval of 524 ms is consistent with prolonged QT interval but is normal when corrected for rate.
These findings were consistent with previous ECGs. Since the patient’s bradycardia is asymptomatic, no intervention (ie, placement of a permanent pacemaker) is indicated.
ANSWER
This ECG shows marked sinus bradycardia with a first-degree atrioventricular block and nonspecific T-wave abnormality. The QT interval of 524 ms is consistent with prolonged QT interval but is normal when corrected for rate.
These findings were consistent with previous ECGs. Since the patient’s bradycardia is asymptomatic, no intervention (ie, placement of a permanent pacemaker) is indicated.
A 52-year-old man has a cardiac diagnosis of paroxysmal atrial fibrillation (A-fib). An echocardiogram demonstrates no valvular heart disease and a left ventricular ejection fraction of 62%. There are no symptoms to suggest left ventricular dysfunction or volume overload. He denies exertional angina or dyspnea and says he has had no palpitations or recurrences of A-fib since you saw him six months ago. The patient is very active: In the past year, he has completed two half marathons and one full marathon. In addition to his running schedule, he also swims 30 min/d and trains on an elliptical machine for 1 h/d. His only complaint today is that he recently lost the toenails off each big toe, which he attributes to his running, adding that this isn’t the first time it’s happened. Medical history is remarkable for two episodes of A-fib that manifested with palpitations and a rapid heart rate, which caused dyspnea. The last episode was approximately eight months ago. Both were treated with cardioversion in the emergency department of your institution. He was not started on an anticoagulant or antiarrhythmic medication after either occurrence. The patient currently takes no medications except the occasional ibuprofen for muscle soreness related to training. He has no known drug allergies and does not use naturopathic medications or illicit drugs. He has never smoked, and he only drinks wine socially, usually on weekends. The patient works as a certified public accountant for a large corporation. He is married with two teenage children. A 12-point review of systems is remarkable only for an inguinal rash and the aforementioned missing toenails. On physical exam, the vital signs include a blood pressure of 107/60 mm Hg; pulse, 46 beats/min; respiratory rate, 12 breaths/min-1; and temperature, 97.8°F. His height is 74 in and his weight, 172 lb. The patient is in no distress. The neck veins are flat, the lungs are clear, and the cardiac exam reveals no murmurs or gallops. The abdominal exam is unremarkable. There is no edema in the peripheral extremities, and pulses are strong bilaterally. Both feet reveal multiple callouses, and the two great toes have missing nails but healthy nail beds. The neurologic exam is intact. As part of his clinic visit, a 12-lead ECG is obtained. It reveals a ventricular rate of 38 beats/min; PR interval, 222 ms; QRS duration, 112 ms; QT/QTc interval, 524/416 ms; P axis, 20°; R axis, 26°; and T axis, 33°. What is your interpretation of this ECG?
Child With “Distressing” Problem
ANSWER
The correct answer is nevus sebaceous (choice “a”). This benign hamartomatous lesion is derived from local tissue and grows at the same rate.
It differs considerably from the other items in the differential, including aplasia cutis congenita (choice “b”). In this condition, a focal area of epidermis simply fails to develop, leaving a permanent hairless scar that contrasts sharply with the raised, mammillated plaque of nevus sebaceous.
Epidermal nevus (choice “c”) is usually a collection of tan to brown superficial nevoid papules that can be linear, agminated, or plaque-like. These lesions lack the color and mammillated surface of those seen in nevus sebaceous.
Neonatal lupus (choice “d”) can present at birth with hairless, cicatricial inflamed lesions. However, these tend to resolve quickly, often leaving focal scarring alopecia but no plaque formation.
DISCUSSION
Nevus sebaceous (NS), first described by Jadassohn in 1895, has long been recognized as an unusual but by no means rare congenital lesion. Occurring equally in both sexes and comprising sebaceous glands in a nevoid morphologic context, NS is considered a variant of sebaceous nevi and verrucous epidermal nevi in some circles. All three are derived from overgrowth of local, normal tissues that typically grow at the same rate as surrounding structures.
The vast majority of NS lesions are found in the scalp, although they can also develop on the ear or neck and, rarely, elsewhere on the body. This patient’s plaque—with its uniform surface; tiny, smooth, shiny papules; and (perhaps most important) total lack of hair—is typical. Other classic features are congenital onset and permanent nature, which distinguish them from the rest of the differential.
Focal malignant transformation of NS lesions has been reported—in fact, this author has seen two such cases in 30 years. Both were small basal cell carcinomas, although cases of melanoma and other malignancies have been reported.
Such changes are rare enough that most experts consider prophylactic removal to be unwarranted. Watching the lesions for change over the years is certainly reasonable, as is protecting them from sun exposure.
Surgical removal—usually performed by a plastic surgeon—is occasionally necessary for cosmetic reasons. This is particularly so when NS covers a portion of the face, or when the cosmetic implications of having a hairless plaque in the scalp are sufficiently distressing.
This patient and her parents were educated about the nature of the diagnosis and apprised of their options.
Editor's note: For a similar presentation with a very different diagnosis, see the March 2015 DermaDiagnosis case (http://bit.ly/1ye69Ym).
ANSWER
The correct answer is nevus sebaceous (choice “a”). This benign hamartomatous lesion is derived from local tissue and grows at the same rate.
It differs considerably from the other items in the differential, including aplasia cutis congenita (choice “b”). In this condition, a focal area of epidermis simply fails to develop, leaving a permanent hairless scar that contrasts sharply with the raised, mammillated plaque of nevus sebaceous.
Epidermal nevus (choice “c”) is usually a collection of tan to brown superficial nevoid papules that can be linear, agminated, or plaque-like. These lesions lack the color and mammillated surface of those seen in nevus sebaceous.
Neonatal lupus (choice “d”) can present at birth with hairless, cicatricial inflamed lesions. However, these tend to resolve quickly, often leaving focal scarring alopecia but no plaque formation.
DISCUSSION
Nevus sebaceous (NS), first described by Jadassohn in 1895, has long been recognized as an unusual but by no means rare congenital lesion. Occurring equally in both sexes and comprising sebaceous glands in a nevoid morphologic context, NS is considered a variant of sebaceous nevi and verrucous epidermal nevi in some circles. All three are derived from overgrowth of local, normal tissues that typically grow at the same rate as surrounding structures.
The vast majority of NS lesions are found in the scalp, although they can also develop on the ear or neck and, rarely, elsewhere on the body. This patient’s plaque—with its uniform surface; tiny, smooth, shiny papules; and (perhaps most important) total lack of hair—is typical. Other classic features are congenital onset and permanent nature, which distinguish them from the rest of the differential.
Focal malignant transformation of NS lesions has been reported—in fact, this author has seen two such cases in 30 years. Both were small basal cell carcinomas, although cases of melanoma and other malignancies have been reported.
Such changes are rare enough that most experts consider prophylactic removal to be unwarranted. Watching the lesions for change over the years is certainly reasonable, as is protecting them from sun exposure.
Surgical removal—usually performed by a plastic surgeon—is occasionally necessary for cosmetic reasons. This is particularly so when NS covers a portion of the face, or when the cosmetic implications of having a hairless plaque in the scalp are sufficiently distressing.
This patient and her parents were educated about the nature of the diagnosis and apprised of their options.
Editor's note: For a similar presentation with a very different diagnosis, see the March 2015 DermaDiagnosis case (http://bit.ly/1ye69Ym).
ANSWER
The correct answer is nevus sebaceous (choice “a”). This benign hamartomatous lesion is derived from local tissue and grows at the same rate.
It differs considerably from the other items in the differential, including aplasia cutis congenita (choice “b”). In this condition, a focal area of epidermis simply fails to develop, leaving a permanent hairless scar that contrasts sharply with the raised, mammillated plaque of nevus sebaceous.
Epidermal nevus (choice “c”) is usually a collection of tan to brown superficial nevoid papules that can be linear, agminated, or plaque-like. These lesions lack the color and mammillated surface of those seen in nevus sebaceous.
Neonatal lupus (choice “d”) can present at birth with hairless, cicatricial inflamed lesions. However, these tend to resolve quickly, often leaving focal scarring alopecia but no plaque formation.
DISCUSSION
Nevus sebaceous (NS), first described by Jadassohn in 1895, has long been recognized as an unusual but by no means rare congenital lesion. Occurring equally in both sexes and comprising sebaceous glands in a nevoid morphologic context, NS is considered a variant of sebaceous nevi and verrucous epidermal nevi in some circles. All three are derived from overgrowth of local, normal tissues that typically grow at the same rate as surrounding structures.
The vast majority of NS lesions are found in the scalp, although they can also develop on the ear or neck and, rarely, elsewhere on the body. This patient’s plaque—with its uniform surface; tiny, smooth, shiny papules; and (perhaps most important) total lack of hair—is typical. Other classic features are congenital onset and permanent nature, which distinguish them from the rest of the differential.
Focal malignant transformation of NS lesions has been reported—in fact, this author has seen two such cases in 30 years. Both were small basal cell carcinomas, although cases of melanoma and other malignancies have been reported.
Such changes are rare enough that most experts consider prophylactic removal to be unwarranted. Watching the lesions for change over the years is certainly reasonable, as is protecting them from sun exposure.
Surgical removal—usually performed by a plastic surgeon—is occasionally necessary for cosmetic reasons. This is particularly so when NS covers a portion of the face, or when the cosmetic implications of having a hairless plaque in the scalp are sufficiently distressing.
This patient and her parents were educated about the nature of the diagnosis and apprised of their options.
Editor's note: For a similar presentation with a very different diagnosis, see the March 2015 DermaDiagnosis case (http://bit.ly/1ye69Ym).
A “bald spot” is the chief complaint of a 12-year-old girl brought for evaluation by her mother. The lesion in her left parietal scalp has been there since birth, slowly growing but producing no symptoms. Although the child’s primary care provider has reassured the family that the “birthmark” is benign, they remain concerned. Furthermore, the patient has become increasingly distressed by the hairlessness. The child is otherwise healthy. There is no history of excessive sun exposure. The lesion is a roughly oval, uniformly pink, hairless 3.6-cm plaque with a faintly mammillated surface and well-defined margins. It is only visible when the surrounding hair is parted sufficiently to reveal it. Examination of the rest of the patient’s skin is unremarkable.
Nodule on the Second Toe in an Infant
The Diagnosis: Infantile Digital Fibromatosis
On examination, the patient appeared well developed, well nourished, and had a 1×0.5-cm, flesh-colored, firm, nontender nodule on the dorsolateral aspect of the left second toe. After excision by a pediatric surgeon, the specimen was submitted for histopathologic examination. Dense bands of collagen with spindled myofibroblasts containing characteristic eosinophilic cytoplasmic inclusion bodies staining with phosphotungstic acid hematoxylin confirmed the diagnosis of infantile digital fibromatosis (Figure). Postoperatively the patient did well with normal healing and no complications. After 4 months, a recurrence was noted and the parents were considering reexcision.
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Infantile digital fibromatosis is a rare, benign, often spontaneously regressing, fibrous tissue tumor of infancy and childhood.1 The prevalence of this tumor is unknown. It can be present at birth or more commonly appears in the first year of life. The lesions present as 1- to 2-cm, firm, flesh-colored nodules that initially grow slowly but have the potential for rapid growth in subsequent months. They occur preferentially on the extensor aspects of the digits, typically sparing the thumb and great toe.1 The clinical differential diagnosis includes keloids or hypertrophic scars, granuloma annulare, sarcoidosis, acral fibrokeratomas, periungual fibromas, supernumerary digits, pachydermodactyly, juvenile aponeurotic fibroma, and terminal osseous dysplasia and pigmentary defects.2
The histology of infantile digital fibromatosis is distinctive. Spindled myofibroblasts that contain round or ovoid, eosinophilic, cytoplasmic inclusion bodies composed of an accumulation of actin and vimentin filaments are characteristic.1 Inclusions are typically juxtanuclear and may indent the adjacent nucleus. The inclusion bodies stain red with Masson trichrome stain and purple with phosphotungstic acid hematoxylin stain.1 The histopathologic differential diagnosis includes scar, angiofibroma, dermatofibroma, neurofibroma, and angiofibromatous verruca vulgaris.
Although many treatments exist for infantile digital fibromatosis, optimal therapy is not standardized. Most lesions spontaneously regress, but func-tional disability with deforming contractures can occur if untreated. Topical therapy with imiquimod cream 5% and diflucortolone valerate cream have been reported to produce no effect on tumor size.3 Intralesional 5-fluorouracil was successful in treating a patient after 5 monthly injections.4 Intralesional triamcinolone 10 mg/cc injections were shown to be a well-tolerated and successful treatment in a case series of 7 patients.5 The most utilized intervention appears to be standard surgery, with a few patients treated with Mohs micrographic surgery.6,7
Treatment with surgical excision often results in recurrence, with studies showing a 50% to 75% recurrence rate.8,9 Our case is not atypical and illustrates this phenomenon. Other reported complications of surgical management include hypertrophic scarring and reduced distal interphalangeal joint mobility.5 Unless infantile digital fibromatosis causes mobility dysfunction or related disabilities, observation with regular follow-up should be considered, as lesions can spontaneously regress.
1. Heymann WR. Infantile digital fibromatosis. J Am Acad Dermatol. 2008;59:122-123.
2. Niamba P, Léauté-Labrèze C, Boralevi F, et al. Further documentation of spontaneous regression of infantile digital fibromatosis. Pediatr Dermatol. 2007;24:280-284.
3. Failla V, Wauters O, Nikkels-Tassoudji N, et al. Congenital infantile digital fibromatosis: a case report and review of the literature. Rare Tumors. 2009;1:e47.
4. Oh CK, Son HS, Kwon YW, et al. Intralesional fluorouracil injection in infantile digital fibromatosis. Arch Dermatol. 2005;141:549-550
5. Holmes WJ, Mishra A, McArthur P. Intra-lesional steroid for the management of symptomatic infantile digital fibromatosis. J Plast Reconstr Aesthet Surg. 2011;64:632-637.
6. Campbell LB, Petrick MG. Mohs micrographic surgery for a problematic infantile digital fibroma. Dermatol Surg. 2007;33:385-387.
7. Albertini JG, Welsch MJ, Conger LA, et al. Infantile digital fibroma treated with Mohs micrographic surgery. Dermatol Surg. 2002;28:959-961.
8. Kang SK, Chang SE, Choi JH, et al. A case of congenital infantile digital fibromatosis. Pediatr Dermatol. 2002;19:462-463.
9. Rimareix F, Bardot J, Andrac L, et al. Infantile digital fibroma—report on eleven cases. Eur J Pediatr Surg. 1997;7:345-348.
The Diagnosis: Infantile Digital Fibromatosis
On examination, the patient appeared well developed, well nourished, and had a 1×0.5-cm, flesh-colored, firm, nontender nodule on the dorsolateral aspect of the left second toe. After excision by a pediatric surgeon, the specimen was submitted for histopathologic examination. Dense bands of collagen with spindled myofibroblasts containing characteristic eosinophilic cytoplasmic inclusion bodies staining with phosphotungstic acid hematoxylin confirmed the diagnosis of infantile digital fibromatosis (Figure). Postoperatively the patient did well with normal healing and no complications. After 4 months, a recurrence was noted and the parents were considering reexcision.
|
Infantile digital fibromatosis is a rare, benign, often spontaneously regressing, fibrous tissue tumor of infancy and childhood.1 The prevalence of this tumor is unknown. It can be present at birth or more commonly appears in the first year of life. The lesions present as 1- to 2-cm, firm, flesh-colored nodules that initially grow slowly but have the potential for rapid growth in subsequent months. They occur preferentially on the extensor aspects of the digits, typically sparing the thumb and great toe.1 The clinical differential diagnosis includes keloids or hypertrophic scars, granuloma annulare, sarcoidosis, acral fibrokeratomas, periungual fibromas, supernumerary digits, pachydermodactyly, juvenile aponeurotic fibroma, and terminal osseous dysplasia and pigmentary defects.2
The histology of infantile digital fibromatosis is distinctive. Spindled myofibroblasts that contain round or ovoid, eosinophilic, cytoplasmic inclusion bodies composed of an accumulation of actin and vimentin filaments are characteristic.1 Inclusions are typically juxtanuclear and may indent the adjacent nucleus. The inclusion bodies stain red with Masson trichrome stain and purple with phosphotungstic acid hematoxylin stain.1 The histopathologic differential diagnosis includes scar, angiofibroma, dermatofibroma, neurofibroma, and angiofibromatous verruca vulgaris.
Although many treatments exist for infantile digital fibromatosis, optimal therapy is not standardized. Most lesions spontaneously regress, but func-tional disability with deforming contractures can occur if untreated. Topical therapy with imiquimod cream 5% and diflucortolone valerate cream have been reported to produce no effect on tumor size.3 Intralesional 5-fluorouracil was successful in treating a patient after 5 monthly injections.4 Intralesional triamcinolone 10 mg/cc injections were shown to be a well-tolerated and successful treatment in a case series of 7 patients.5 The most utilized intervention appears to be standard surgery, with a few patients treated with Mohs micrographic surgery.6,7
Treatment with surgical excision often results in recurrence, with studies showing a 50% to 75% recurrence rate.8,9 Our case is not atypical and illustrates this phenomenon. Other reported complications of surgical management include hypertrophic scarring and reduced distal interphalangeal joint mobility.5 Unless infantile digital fibromatosis causes mobility dysfunction or related disabilities, observation with regular follow-up should be considered, as lesions can spontaneously regress.
The Diagnosis: Infantile Digital Fibromatosis
On examination, the patient appeared well developed, well nourished, and had a 1×0.5-cm, flesh-colored, firm, nontender nodule on the dorsolateral aspect of the left second toe. After excision by a pediatric surgeon, the specimen was submitted for histopathologic examination. Dense bands of collagen with spindled myofibroblasts containing characteristic eosinophilic cytoplasmic inclusion bodies staining with phosphotungstic acid hematoxylin confirmed the diagnosis of infantile digital fibromatosis (Figure). Postoperatively the patient did well with normal healing and no complications. After 4 months, a recurrence was noted and the parents were considering reexcision.
|
Infantile digital fibromatosis is a rare, benign, often spontaneously regressing, fibrous tissue tumor of infancy and childhood.1 The prevalence of this tumor is unknown. It can be present at birth or more commonly appears in the first year of life. The lesions present as 1- to 2-cm, firm, flesh-colored nodules that initially grow slowly but have the potential for rapid growth in subsequent months. They occur preferentially on the extensor aspects of the digits, typically sparing the thumb and great toe.1 The clinical differential diagnosis includes keloids or hypertrophic scars, granuloma annulare, sarcoidosis, acral fibrokeratomas, periungual fibromas, supernumerary digits, pachydermodactyly, juvenile aponeurotic fibroma, and terminal osseous dysplasia and pigmentary defects.2
The histology of infantile digital fibromatosis is distinctive. Spindled myofibroblasts that contain round or ovoid, eosinophilic, cytoplasmic inclusion bodies composed of an accumulation of actin and vimentin filaments are characteristic.1 Inclusions are typically juxtanuclear and may indent the adjacent nucleus. The inclusion bodies stain red with Masson trichrome stain and purple with phosphotungstic acid hematoxylin stain.1 The histopathologic differential diagnosis includes scar, angiofibroma, dermatofibroma, neurofibroma, and angiofibromatous verruca vulgaris.
Although many treatments exist for infantile digital fibromatosis, optimal therapy is not standardized. Most lesions spontaneously regress, but func-tional disability with deforming contractures can occur if untreated. Topical therapy with imiquimod cream 5% and diflucortolone valerate cream have been reported to produce no effect on tumor size.3 Intralesional 5-fluorouracil was successful in treating a patient after 5 monthly injections.4 Intralesional triamcinolone 10 mg/cc injections were shown to be a well-tolerated and successful treatment in a case series of 7 patients.5 The most utilized intervention appears to be standard surgery, with a few patients treated with Mohs micrographic surgery.6,7
Treatment with surgical excision often results in recurrence, with studies showing a 50% to 75% recurrence rate.8,9 Our case is not atypical and illustrates this phenomenon. Other reported complications of surgical management include hypertrophic scarring and reduced distal interphalangeal joint mobility.5 Unless infantile digital fibromatosis causes mobility dysfunction or related disabilities, observation with regular follow-up should be considered, as lesions can spontaneously regress.
1. Heymann WR. Infantile digital fibromatosis. J Am Acad Dermatol. 2008;59:122-123.
2. Niamba P, Léauté-Labrèze C, Boralevi F, et al. Further documentation of spontaneous regression of infantile digital fibromatosis. Pediatr Dermatol. 2007;24:280-284.
3. Failla V, Wauters O, Nikkels-Tassoudji N, et al. Congenital infantile digital fibromatosis: a case report and review of the literature. Rare Tumors. 2009;1:e47.
4. Oh CK, Son HS, Kwon YW, et al. Intralesional fluorouracil injection in infantile digital fibromatosis. Arch Dermatol. 2005;141:549-550
5. Holmes WJ, Mishra A, McArthur P. Intra-lesional steroid for the management of symptomatic infantile digital fibromatosis. J Plast Reconstr Aesthet Surg. 2011;64:632-637.
6. Campbell LB, Petrick MG. Mohs micrographic surgery for a problematic infantile digital fibroma. Dermatol Surg. 2007;33:385-387.
7. Albertini JG, Welsch MJ, Conger LA, et al. Infantile digital fibroma treated with Mohs micrographic surgery. Dermatol Surg. 2002;28:959-961.
8. Kang SK, Chang SE, Choi JH, et al. A case of congenital infantile digital fibromatosis. Pediatr Dermatol. 2002;19:462-463.
9. Rimareix F, Bardot J, Andrac L, et al. Infantile digital fibroma—report on eleven cases. Eur J Pediatr Surg. 1997;7:345-348.
1. Heymann WR. Infantile digital fibromatosis. J Am Acad Dermatol. 2008;59:122-123.
2. Niamba P, Léauté-Labrèze C, Boralevi F, et al. Further documentation of spontaneous regression of infantile digital fibromatosis. Pediatr Dermatol. 2007;24:280-284.
3. Failla V, Wauters O, Nikkels-Tassoudji N, et al. Congenital infantile digital fibromatosis: a case report and review of the literature. Rare Tumors. 2009;1:e47.
4. Oh CK, Son HS, Kwon YW, et al. Intralesional fluorouracil injection in infantile digital fibromatosis. Arch Dermatol. 2005;141:549-550
5. Holmes WJ, Mishra A, McArthur P. Intra-lesional steroid for the management of symptomatic infantile digital fibromatosis. J Plast Reconstr Aesthet Surg. 2011;64:632-637.
6. Campbell LB, Petrick MG. Mohs micrographic surgery for a problematic infantile digital fibroma. Dermatol Surg. 2007;33:385-387.
7. Albertini JG, Welsch MJ, Conger LA, et al. Infantile digital fibroma treated with Mohs micrographic surgery. Dermatol Surg. 2002;28:959-961.
8. Kang SK, Chang SE, Choi JH, et al. A case of congenital infantile digital fibromatosis. Pediatr Dermatol. 2002;19:462-463.
9. Rimareix F, Bardot J, Andrac L, et al. Infantile digital fibroma—report on eleven cases. Eur J Pediatr Surg. 1997;7:345-348.
A 6-month-old male infant presented with a 1×0.5-cm, flesh-colored nodule on the dorsolateral aspect of the left second toe. The persistent, slowly enlarging, painless lesion was first noticed at 3 months of age and did not cause functional impairment. There was no preceding trauma and the patient’s medical history was otherwise noncontributory.
Fibrous Forehead Plaque
The Diagnosis: Tuberous Sclerosis Complex
Tuberous sclerosis complex (TSC) is an autosomal-dominant neurocutaneous syndrome characterized by multiple hamartomas distributed in multiple organs of the body, most commonly the skin, brain, eyes, heart, kidneys, liver, and lungs. In 1908, Vogt1 elucidated the classic diagnostic triad of seizures, mental retardation, and facial angiofibromas (formerly termed adenoma sebaceum). However, the full triad is evident in only 29% of cases; 6% of TSC patients have none of these 3 findings.2 The disease is caused by alterations in 2 TSC genes, TSC1 and TSC2, on chromosomes 9 and 16, respectively. Both are tumor suppressor genes and mutations in either can be responsible for all the complications seen in the disease.3 The gene products of the 2 genes, hamartin and tuberin, appear to act together in the regulation of cell growth by inhibiting a substance known as the mechanistic target of rapamycin.4,5 Up to two-thirds of cases may occur from spontaneous mutations.2,6 The disease is extremely variable in its manifestations, particularly the skin manifestations. This discussion will review the many cutaneous manifestations of TSC, most of them documented in our patient, and their frequency of occurrence.
Early recognition of TSC is vital because prompt implementation of the recommended diagnostic evaluation (eg, neuroimaging studies, electroencephalogram, electrocardiography, renal ultrasonography, chest computed tomography) may prevent serious clinical consequences.7 Neurologic manifestations are the leading cause of morbidity and mortality in patients with TSC.2,8,9 Brain hamartomas in the form of cortical tubers, subependymal nodules, and subependymal giant cell astrocytomas often are responsible for intractable seizures, most commonly as infantile spasms. Approximately 90% to 96% of TSC patients have seizures.6 Renal manifestations are strongly associated with TSC. Angiomyolipoma is the most common renal lesion found in TSC patients.4,9,10 Up to 80% of patients have renal angiomyolipomas. Their incidence increases with age.4,11,12 Tuberous sclerosis complex is known as a cause of epilepsy and mental retardation, but renal disease is a major cause of morbidity.13 Cardiovascular manifestations often are the earliest diagnostic findings in patients with TSC. Rhabdomyoma is the most common primary cardiac tumor in infants and children.11,13,14 The most common ocular findings in TSC are retinal hamartomas, appearing in 40% to 50% of patients.15
Cutaneous features frequently occur and are the most clinically apparent findings of TSC; if overlooked, diagnosis could be delayed, which ultimately increases mortality. The diagnosis of TSC continues to be based primarily on clinical grounds because most patients older than 5 years demonstrate multiple skin lesions.6 In 1992, specific diagnostic clinical criteria were created for TSC, which stratified the clinical features of TSC into 3 tiers—primary, secondary, and tertiary—based on their specificity.16 In subsequent years, some of the classic clinical signs once regarded as pathognomonic for TSC, such as single ungual fibroma or multiple renal angiomyolipomas, were questioned. New modifications to the original diagnostic criteria were necessary given the advances in both TSC clinical information and molecular genetics. In the summer of 1998, a consensus conference held in Annapolis, Maryland, was assembled by the Tuberous Sclerosis Alliance for the purpose of reevaluating and updating the clinical diagnostic criteria.7 The revised criteria were simplified into 2 main categories—major and minor features—based on the diagnostic importance and degree of specificity for TSC of each clinical and radiographic feature (Table 1). There are a number of considerations that merit close attention when applying these clinical criteria. Despite the large number of clinical features delineated, the diagnosis of TSC may be challenging early in life, particularly in patients younger than 2 years. The value of the clinical criteria for early diagnosis and prompt management of TSC is limited by the fact that many stigmata become apparent only in late childhood or adulthood. The lack of pathognomonic signs of TSC can add to the challenge of diagnosing subtle or atypical cases.6
A careful skin examination of individuals at risk for TSC is the best and the easiest method of establishing the diagnosis in most cases. According to Gomez,17 96% of patients with TSC have one or more main skin lesions of the disease, including facial angiofibromas, ungual fibromas, shagreen patches, or hypomelanotic macules. However, the diagnosis is more difficult in small children because many skin lesions become obvious with age; in fact, the full dermatological spectrum may never develop.17
Facial angiofibromas, also known as sebaceous adenomas, are the most visible and unsightly cutaneous manifestations of TSC, often resulting in stigmatization for both the affected individuals and their family members. These facial lesions often do not appear until late childhood or adulthood. In this case, the initial diagnosis often is made by the dermatologist who appreciates the significance of the white macules in a neonate. However, these hypomelanotic macules cannot be detected by the unaided eye, thus a physician would be wise to examine an infant with infantile spasms or mental retardation with a Wood lamp, which accentuates the lesions.2
Hypomelanotic macules were the overwhelmingly most common early findings in TSC. Infants with seizures or other possible stigmata of TSC should be carefully evaluated for these hypomelanotic macules as well as for other associated findings. Hypomelanotic macules can appear anywhere on the body, except the hands, feet, and genitalia; they are most commonly found on the lower extremities. Wood lamp examination reveals an accentuation of the hypopigmentation, which is a decrease in but not an absence of pigmentation. Lance ovate hypomelanotic macules are pathognomonic for TSC, thus the presence of 3 or more macules in an infant seriously suggests the diagnosis of TSC and echocardiography should be performed. The combination of white macules and seizures also increases the likelihood of TSC.18
Angiofibromas typically are found in the butterfly region of the face. Nico et al19 reported 2 patients with the complete syndrome of TSC who had multiple papules on the genital area in addition to classic facial lesions. Thus, it is important to examine the genital region of TSC patients and not misdiagnose these lesions as genital warts.
Jóźwiak et al18 screened 106 children with TSC and listed the prevalence of the most common cutaneous lesions. The results are presented in Table 2.
In a study by Webb et al,2 131 patients with TSC were examined and 126 (96%) exhibited skin signs. Although there was considerable variation in the age of expression of all the skin lesions, there was a trend toward the earlier expression of hypomelanotic macules and forehead fibrous plaques compared with facial angiofibromas and ungual fibromas. Shagreen patches usually were present by puberty. Ungual fibromas appeared for the first time as late as the fifth decade of life and were the only clinical feature in 3 patients. Ungual fibromas were present in 36% (47/131). Ten patients (8%) presented because of the skin manifestations and 21% (28/131) received treatment of symptomatic skin lesions. Two patients had large hamartomas at unusual sites, the occiput and forearm.2
Our 30-year-old patient presented to our clinic accompanied by her grandmother who served as legal guardian and historian for the patient. The patient experienced her first seizure at 15 months of age. She was evaluated by the neurology department at that time and was diagnosed with epilepsy. In the months following, she developed strabismus of the eyes and was examined by the ophthalmology department. Retinal hamartomas were discovered and she was diagnosed with TSC. Her seizure disorder was managed by a neurologist with the use of topiramate. In her 20s, she had renal and cardiac workups, which were negative, and she continued to be free of any genitourinary or cardiac concerns. One year prior to presentation she underwent a brain computed tomography scan after a bicycle accident and was informed that she had “scarlike” lesions within the cerebral cortex. There was no known history of TSC in other family members. On physical examination, she was noted to be delayed in mental development and intelligence. She stated her first notable skin lesions appeared at 10 years of age and were skin tags of the upper back and neck and over the face. Soon after, the cheeks and nose developed numerous shiny brownish pink papules (Figure 1). Over the course of the next 20 years she developed other skin findings noted on our present skin examination. The superior aspect of the mid forehead revealed a 4×2-cm, raised, flesh-colored, firm tumorous plaque. The neck and upper back had multiple 2- to 5-mm, soft, pedunculated, polypoid, brownish pink papules. Her mid back revealed ill-defined, slightly elevated, rosy plaques and macules with a roughened speckled appearance (Figure 2). Several of the toenails and fingernails showed firm, fleshy, spiculelike papules around and under the nail bed (Figure 3). The lower anterior tibia revealed several oval-shaped, flat, well-demarcated, hypopigmented macules (Figure 4). Lesions on the face and mid back were biopsied and histopathology confirmed angiofibroma and shagreen patch, or connective tissue nevus, respectively. Our patient did not undergo treatment of any of these skin lesions, particularly the facial angiofibromas. Cosmetic treatment options such as laser or surgical removal were presented to her, but she declined.
 |  |
A brief review of the literature for treatment options of facial angiofibromas and the fibrous forehead plaque indicated that current treatments include but are not limited to cryotherapy, electrocautery, electrosurgery, shave excision, chemical peels, argon laser, CO2 laser, and radiofrequency equipment.20 For the best outcome, these treatments have to be repeated throughout childhood and teenage years. Rapamycin, also known as sirolimus, and its analogs are new therapeutic options for TSC. Rapamycin is an inhibitor of the mechanistic target of rapamycin and can normalize this unregulated pathway in a TSC patient. Various preclinical models have shown that rapamycin treatment reduces TSC-related tumors, including brain, skin, and kidney tumors.21 A pilot study by Foster et al22 revealed improvement in the facial angiofibromas of 4 children treated with 2 topical preparations of rapamycin. The study revealed that younger patients with smaller angiofibromas had the best response with near-complete clearance. Rapamycin topical preparations were more cost effective than pulsed dye laser under general anesthesia.22
 |  |
Tuberous sclerosis complex is not the only syndrome that can present with facial angiofibromas or numerous skin tag–type lesions such as those in our patient. It is important to also consider Birt-Hogg-Dubé syndrome and multiple endocrine neoplasia type 1 in the differential diagnosis of multiple facial angiofibromas, particularly with adult onset.23
Our case was presented to review the cutaneous manifestations of TSC and their presentation frequency, with the intent to enable the dermatologist to make a more accurate and earlier diagnosis of TSC. In doing so, morbidity of TSC patients could be decreased and quality of life increased.
1. Vogt H. Zur Diagnostik der tuberosen sklerose. Z Erforsch Behandl Jugeudl Schwachsinns. 1908;2:1-6.
2. Webb DW, Clarke A, Fryer A, et al. The cutaneous features of tuberous sclerosis: a population study. Br J Dermatol. 1996;135:1-5.
3. van Slegtenhorst M, de Hoogt R, Hermans C, et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science. 1997;277:805-808.
4. O’Callaghan F. Tuberous sclerosis complex: from basic science to clinical phenotypes. Arch Dis Child. 2004;89:985.
5. Kwiatkowski DJ. Tuberous sclerosis: from tubers to mTOR. Ann Hum Genet. 2003;67:87-96.
6. Schwartz RA. Tuberous sclerosis complex: advances in diagnosis, genetics, and management. J Am Acad Dermatol. 2007;57:189-202.
7. Roach ES, Gomez MR, Northrup H. Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria. J Child Neurol. 1998;13:624-628.
8. Tworetzky W, McElhinney DB, Margossian R, et al. Association between cardiac tumors and tuberous sclerosis in the fetus and neonate. Am J Cardiol. 2003;92:487-489.
9. Casper KA, Donnelly LF, Chen B, et al. Tuberous sclerosis complex: renal imaging findings. Radiology. 2002;225:451-456.
10. El-Hashemite N, Zhang H, Henske EP, et al. Mutation in TSC2 and activation of mammalian target of rapamycin signaling pathway in renal angiomyolipoma. Lancet. 2003;361:1348-1349.
11. Jóźwiak S, Schwartz RA, Janniger CK, et al. Usefulness of diagnostic criteria of tuberous sclerosis complex in pediatric patients. J Child Neurol. 2000;15:652-659.
12. Ewalt DH, Sheffield E, Sparagana SP, et al. Renal lesion growth in children with tuberous sclerosis complex. J Urol. 1998;160:141-145.
13. Webb DW, Thomas RD, Osborne JP. Cardiac rhabdomyomas and their association with tuberous sclerosis. Arch Dis Child. 1993;68:367-370.
14. Holley DG, Martin GR, Brenner JI, et al. Diagnosis and management of fetal cardiac tumors: a multicenter experience and review of published reports. J Am Coll Cardiol. 1995;26:516-520.
15. Robertson DM. Ophthalmic manifestations of tuberous sclerosis. Ann N Y Acad Sci. 1991;615:17-25.
16. Roach ES, Smith M, Huttenlocher P, et al. Diagnostic criteria: tuberous sclerosis complex. J Child Neurol. 1992;7:221-224.
17. Gomez MR. Tuberous sclerosis. In: Gomez MR, ed. Neurocutaneous Diseases. A Practical Approach. Boston, MA: Butterworth; 1987:30-52.
18. Jóźwiak S, Schwartz RA, Janniger CK, et al. Skin lesions in children with tuberous sclerosis complex: their prevalence, natural course, and diagnostic significance. Int J Dermatol. 1998;37:911-917.
19. Nico MM, Ito LM, Valente NY. Genital angiofibromas in tuberous sclerosis: two cases. J Dermatol. 1999;26:111-114.
20. Gomes AA, Gomes YV, Lima FB, et al. Multiple facial angiofibromas treated with high frequency equipment. An Bras Dermatol. 2011;86:186-189.
21. Borkowska J, Schwartz RA, Kotulska K, et al. Tuberous sclerosis complex: tumors and tumorigenesis. Int J Dermatol. 2011;50:13-20.
22. Foster RS, Bint LJ, Halbert AR. Topical 0.1% rapamycin for angiofibromas in paediatric patients with tuberous sclerosis: a pilot study of four patients. Australas J Dermatol. 2012;53:52-56.
23. Schaffer JV, Gohara MA, McNiff JM, et al. Multiple facial angiofibromas: a cutaneous manifestation of Birt-Hogg-Dube syndrome. J Am Acad Dermatol. 2005;53:108-111.
The Diagnosis: Tuberous Sclerosis Complex
Tuberous sclerosis complex (TSC) is an autosomal-dominant neurocutaneous syndrome characterized by multiple hamartomas distributed in multiple organs of the body, most commonly the skin, brain, eyes, heart, kidneys, liver, and lungs. In 1908, Vogt1 elucidated the classic diagnostic triad of seizures, mental retardation, and facial angiofibromas (formerly termed adenoma sebaceum). However, the full triad is evident in only 29% of cases; 6% of TSC patients have none of these 3 findings.2 The disease is caused by alterations in 2 TSC genes, TSC1 and TSC2, on chromosomes 9 and 16, respectively. Both are tumor suppressor genes and mutations in either can be responsible for all the complications seen in the disease.3 The gene products of the 2 genes, hamartin and tuberin, appear to act together in the regulation of cell growth by inhibiting a substance known as the mechanistic target of rapamycin.4,5 Up to two-thirds of cases may occur from spontaneous mutations.2,6 The disease is extremely variable in its manifestations, particularly the skin manifestations. This discussion will review the many cutaneous manifestations of TSC, most of them documented in our patient, and their frequency of occurrence.
Early recognition of TSC is vital because prompt implementation of the recommended diagnostic evaluation (eg, neuroimaging studies, electroencephalogram, electrocardiography, renal ultrasonography, chest computed tomography) may prevent serious clinical consequences.7 Neurologic manifestations are the leading cause of morbidity and mortality in patients with TSC.2,8,9 Brain hamartomas in the form of cortical tubers, subependymal nodules, and subependymal giant cell astrocytomas often are responsible for intractable seizures, most commonly as infantile spasms. Approximately 90% to 96% of TSC patients have seizures.6 Renal manifestations are strongly associated with TSC. Angiomyolipoma is the most common renal lesion found in TSC patients.4,9,10 Up to 80% of patients have renal angiomyolipomas. Their incidence increases with age.4,11,12 Tuberous sclerosis complex is known as a cause of epilepsy and mental retardation, but renal disease is a major cause of morbidity.13 Cardiovascular manifestations often are the earliest diagnostic findings in patients with TSC. Rhabdomyoma is the most common primary cardiac tumor in infants and children.11,13,14 The most common ocular findings in TSC are retinal hamartomas, appearing in 40% to 50% of patients.15
Cutaneous features frequently occur and are the most clinically apparent findings of TSC; if overlooked, diagnosis could be delayed, which ultimately increases mortality. The diagnosis of TSC continues to be based primarily on clinical grounds because most patients older than 5 years demonstrate multiple skin lesions.6 In 1992, specific diagnostic clinical criteria were created for TSC, which stratified the clinical features of TSC into 3 tiers—primary, secondary, and tertiary—based on their specificity.16 In subsequent years, some of the classic clinical signs once regarded as pathognomonic for TSC, such as single ungual fibroma or multiple renal angiomyolipomas, were questioned. New modifications to the original diagnostic criteria were necessary given the advances in both TSC clinical information and molecular genetics. In the summer of 1998, a consensus conference held in Annapolis, Maryland, was assembled by the Tuberous Sclerosis Alliance for the purpose of reevaluating and updating the clinical diagnostic criteria.7 The revised criteria were simplified into 2 main categories—major and minor features—based on the diagnostic importance and degree of specificity for TSC of each clinical and radiographic feature (Table 1). There are a number of considerations that merit close attention when applying these clinical criteria. Despite the large number of clinical features delineated, the diagnosis of TSC may be challenging early in life, particularly in patients younger than 2 years. The value of the clinical criteria for early diagnosis and prompt management of TSC is limited by the fact that many stigmata become apparent only in late childhood or adulthood. The lack of pathognomonic signs of TSC can add to the challenge of diagnosing subtle or atypical cases.6
A careful skin examination of individuals at risk for TSC is the best and the easiest method of establishing the diagnosis in most cases. According to Gomez,17 96% of patients with TSC have one or more main skin lesions of the disease, including facial angiofibromas, ungual fibromas, shagreen patches, or hypomelanotic macules. However, the diagnosis is more difficult in small children because many skin lesions become obvious with age; in fact, the full dermatological spectrum may never develop.17
Facial angiofibromas, also known as sebaceous adenomas, are the most visible and unsightly cutaneous manifestations of TSC, often resulting in stigmatization for both the affected individuals and their family members. These facial lesions often do not appear until late childhood or adulthood. In this case, the initial diagnosis often is made by the dermatologist who appreciates the significance of the white macules in a neonate. However, these hypomelanotic macules cannot be detected by the unaided eye, thus a physician would be wise to examine an infant with infantile spasms or mental retardation with a Wood lamp, which accentuates the lesions.2
Hypomelanotic macules were the overwhelmingly most common early findings in TSC. Infants with seizures or other possible stigmata of TSC should be carefully evaluated for these hypomelanotic macules as well as for other associated findings. Hypomelanotic macules can appear anywhere on the body, except the hands, feet, and genitalia; they are most commonly found on the lower extremities. Wood lamp examination reveals an accentuation of the hypopigmentation, which is a decrease in but not an absence of pigmentation. Lance ovate hypomelanotic macules are pathognomonic for TSC, thus the presence of 3 or more macules in an infant seriously suggests the diagnosis of TSC and echocardiography should be performed. The combination of white macules and seizures also increases the likelihood of TSC.18
Angiofibromas typically are found in the butterfly region of the face. Nico et al19 reported 2 patients with the complete syndrome of TSC who had multiple papules on the genital area in addition to classic facial lesions. Thus, it is important to examine the genital region of TSC patients and not misdiagnose these lesions as genital warts.
Jóźwiak et al18 screened 106 children with TSC and listed the prevalence of the most common cutaneous lesions. The results are presented in Table 2.
In a study by Webb et al,2 131 patients with TSC were examined and 126 (96%) exhibited skin signs. Although there was considerable variation in the age of expression of all the skin lesions, there was a trend toward the earlier expression of hypomelanotic macules and forehead fibrous plaques compared with facial angiofibromas and ungual fibromas. Shagreen patches usually were present by puberty. Ungual fibromas appeared for the first time as late as the fifth decade of life and were the only clinical feature in 3 patients. Ungual fibromas were present in 36% (47/131). Ten patients (8%) presented because of the skin manifestations and 21% (28/131) received treatment of symptomatic skin lesions. Two patients had large hamartomas at unusual sites, the occiput and forearm.2
Our 30-year-old patient presented to our clinic accompanied by her grandmother who served as legal guardian and historian for the patient. The patient experienced her first seizure at 15 months of age. She was evaluated by the neurology department at that time and was diagnosed with epilepsy. In the months following, she developed strabismus of the eyes and was examined by the ophthalmology department. Retinal hamartomas were discovered and she was diagnosed with TSC. Her seizure disorder was managed by a neurologist with the use of topiramate. In her 20s, she had renal and cardiac workups, which were negative, and she continued to be free of any genitourinary or cardiac concerns. One year prior to presentation she underwent a brain computed tomography scan after a bicycle accident and was informed that she had “scarlike” lesions within the cerebral cortex. There was no known history of TSC in other family members. On physical examination, she was noted to be delayed in mental development and intelligence. She stated her first notable skin lesions appeared at 10 years of age and were skin tags of the upper back and neck and over the face. Soon after, the cheeks and nose developed numerous shiny brownish pink papules (Figure 1). Over the course of the next 20 years she developed other skin findings noted on our present skin examination. The superior aspect of the mid forehead revealed a 4×2-cm, raised, flesh-colored, firm tumorous plaque. The neck and upper back had multiple 2- to 5-mm, soft, pedunculated, polypoid, brownish pink papules. Her mid back revealed ill-defined, slightly elevated, rosy plaques and macules with a roughened speckled appearance (Figure 2). Several of the toenails and fingernails showed firm, fleshy, spiculelike papules around and under the nail bed (Figure 3). The lower anterior tibia revealed several oval-shaped, flat, well-demarcated, hypopigmented macules (Figure 4). Lesions on the face and mid back were biopsied and histopathology confirmed angiofibroma and shagreen patch, or connective tissue nevus, respectively. Our patient did not undergo treatment of any of these skin lesions, particularly the facial angiofibromas. Cosmetic treatment options such as laser or surgical removal were presented to her, but she declined.
| |
A brief review of the literature for treatment options of facial angiofibromas and the fibrous forehead plaque indicated that current treatments include but are not limited to cryotherapy, electrocautery, electrosurgery, shave excision, chemical peels, argon laser, CO2 laser, and radiofrequency equipment.20 For the best outcome, these treatments have to be repeated throughout childhood and teenage years. Rapamycin, also known as sirolimus, and its analogs are new therapeutic options for TSC. Rapamycin is an inhibitor of the mechanistic target of rapamycin and can normalize this unregulated pathway in a TSC patient. Various preclinical models have shown that rapamycin treatment reduces TSC-related tumors, including brain, skin, and kidney tumors.21 A pilot study by Foster et al22 revealed improvement in the facial angiofibromas of 4 children treated with 2 topical preparations of rapamycin. The study revealed that younger patients with smaller angiofibromas had the best response with near-complete clearance. Rapamycin topical preparations were more cost effective than pulsed dye laser under general anesthesia.22
| |
Tuberous sclerosis complex is not the only syndrome that can present with facial angiofibromas or numerous skin tag–type lesions such as those in our patient. It is important to also consider Birt-Hogg-Dubé syndrome and multiple endocrine neoplasia type 1 in the differential diagnosis of multiple facial angiofibromas, particularly with adult onset.23
Our case was presented to review the cutaneous manifestations of TSC and their presentation frequency, with the intent to enable the dermatologist to make a more accurate and earlier diagnosis of TSC. In doing so, morbidity of TSC patients could be decreased and quality of life increased.
The Diagnosis: Tuberous Sclerosis Complex
Tuberous sclerosis complex (TSC) is an autosomal-dominant neurocutaneous syndrome characterized by multiple hamartomas distributed in multiple organs of the body, most commonly the skin, brain, eyes, heart, kidneys, liver, and lungs. In 1908, Vogt1 elucidated the classic diagnostic triad of seizures, mental retardation, and facial angiofibromas (formerly termed adenoma sebaceum). However, the full triad is evident in only 29% of cases; 6% of TSC patients have none of these 3 findings.2 The disease is caused by alterations in 2 TSC genes, TSC1 and TSC2, on chromosomes 9 and 16, respectively. Both are tumor suppressor genes and mutations in either can be responsible for all the complications seen in the disease.3 The gene products of the 2 genes, hamartin and tuberin, appear to act together in the regulation of cell growth by inhibiting a substance known as the mechanistic target of rapamycin.4,5 Up to two-thirds of cases may occur from spontaneous mutations.2,6 The disease is extremely variable in its manifestations, particularly the skin manifestations. This discussion will review the many cutaneous manifestations of TSC, most of them documented in our patient, and their frequency of occurrence.
Early recognition of TSC is vital because prompt implementation of the recommended diagnostic evaluation (eg, neuroimaging studies, electroencephalogram, electrocardiography, renal ultrasonography, chest computed tomography) may prevent serious clinical consequences.7 Neurologic manifestations are the leading cause of morbidity and mortality in patients with TSC.2,8,9 Brain hamartomas in the form of cortical tubers, subependymal nodules, and subependymal giant cell astrocytomas often are responsible for intractable seizures, most commonly as infantile spasms. Approximately 90% to 96% of TSC patients have seizures.6 Renal manifestations are strongly associated with TSC. Angiomyolipoma is the most common renal lesion found in TSC patients.4,9,10 Up to 80% of patients have renal angiomyolipomas. Their incidence increases with age.4,11,12 Tuberous sclerosis complex is known as a cause of epilepsy and mental retardation, but renal disease is a major cause of morbidity.13 Cardiovascular manifestations often are the earliest diagnostic findings in patients with TSC. Rhabdomyoma is the most common primary cardiac tumor in infants and children.11,13,14 The most common ocular findings in TSC are retinal hamartomas, appearing in 40% to 50% of patients.15
Cutaneous features frequently occur and are the most clinically apparent findings of TSC; if overlooked, diagnosis could be delayed, which ultimately increases mortality. The diagnosis of TSC continues to be based primarily on clinical grounds because most patients older than 5 years demonstrate multiple skin lesions.6 In 1992, specific diagnostic clinical criteria were created for TSC, which stratified the clinical features of TSC into 3 tiers—primary, secondary, and tertiary—based on their specificity.16 In subsequent years, some of the classic clinical signs once regarded as pathognomonic for TSC, such as single ungual fibroma or multiple renal angiomyolipomas, were questioned. New modifications to the original diagnostic criteria were necessary given the advances in both TSC clinical information and molecular genetics. In the summer of 1998, a consensus conference held in Annapolis, Maryland, was assembled by the Tuberous Sclerosis Alliance for the purpose of reevaluating and updating the clinical diagnostic criteria.7 The revised criteria were simplified into 2 main categories—major and minor features—based on the diagnostic importance and degree of specificity for TSC of each clinical and radiographic feature (Table 1). There are a number of considerations that merit close attention when applying these clinical criteria. Despite the large number of clinical features delineated, the diagnosis of TSC may be challenging early in life, particularly in patients younger than 2 years. The value of the clinical criteria for early diagnosis and prompt management of TSC is limited by the fact that many stigmata become apparent only in late childhood or adulthood. The lack of pathognomonic signs of TSC can add to the challenge of diagnosing subtle or atypical cases.6
A careful skin examination of individuals at risk for TSC is the best and the easiest method of establishing the diagnosis in most cases. According to Gomez,17 96% of patients with TSC have one or more main skin lesions of the disease, including facial angiofibromas, ungual fibromas, shagreen patches, or hypomelanotic macules. However, the diagnosis is more difficult in small children because many skin lesions become obvious with age; in fact, the full dermatological spectrum may never develop.17
Facial angiofibromas, also known as sebaceous adenomas, are the most visible and unsightly cutaneous manifestations of TSC, often resulting in stigmatization for both the affected individuals and their family members. These facial lesions often do not appear until late childhood or adulthood. In this case, the initial diagnosis often is made by the dermatologist who appreciates the significance of the white macules in a neonate. However, these hypomelanotic macules cannot be detected by the unaided eye, thus a physician would be wise to examine an infant with infantile spasms or mental retardation with a Wood lamp, which accentuates the lesions.2
Hypomelanotic macules were the overwhelmingly most common early findings in TSC. Infants with seizures or other possible stigmata of TSC should be carefully evaluated for these hypomelanotic macules as well as for other associated findings. Hypomelanotic macules can appear anywhere on the body, except the hands, feet, and genitalia; they are most commonly found on the lower extremities. Wood lamp examination reveals an accentuation of the hypopigmentation, which is a decrease in but not an absence of pigmentation. Lance ovate hypomelanotic macules are pathognomonic for TSC, thus the presence of 3 or more macules in an infant seriously suggests the diagnosis of TSC and echocardiography should be performed. The combination of white macules and seizures also increases the likelihood of TSC.18
Angiofibromas typically are found in the butterfly region of the face. Nico et al19 reported 2 patients with the complete syndrome of TSC who had multiple papules on the genital area in addition to classic facial lesions. Thus, it is important to examine the genital region of TSC patients and not misdiagnose these lesions as genital warts.
Jóźwiak et al18 screened 106 children with TSC and listed the prevalence of the most common cutaneous lesions. The results are presented in Table 2.
In a study by Webb et al,2 131 patients with TSC were examined and 126 (96%) exhibited skin signs. Although there was considerable variation in the age of expression of all the skin lesions, there was a trend toward the earlier expression of hypomelanotic macules and forehead fibrous plaques compared with facial angiofibromas and ungual fibromas. Shagreen patches usually were present by puberty. Ungual fibromas appeared for the first time as late as the fifth decade of life and were the only clinical feature in 3 patients. Ungual fibromas were present in 36% (47/131). Ten patients (8%) presented because of the skin manifestations and 21% (28/131) received treatment of symptomatic skin lesions. Two patients had large hamartomas at unusual sites, the occiput and forearm.2
Our 30-year-old patient presented to our clinic accompanied by her grandmother who served as legal guardian and historian for the patient. The patient experienced her first seizure at 15 months of age. She was evaluated by the neurology department at that time and was diagnosed with epilepsy. In the months following, she developed strabismus of the eyes and was examined by the ophthalmology department. Retinal hamartomas were discovered and she was diagnosed with TSC. Her seizure disorder was managed by a neurologist with the use of topiramate. In her 20s, she had renal and cardiac workups, which were negative, and she continued to be free of any genitourinary or cardiac concerns. One year prior to presentation she underwent a brain computed tomography scan after a bicycle accident and was informed that she had “scarlike” lesions within the cerebral cortex. There was no known history of TSC in other family members. On physical examination, she was noted to be delayed in mental development and intelligence. She stated her first notable skin lesions appeared at 10 years of age and were skin tags of the upper back and neck and over the face. Soon after, the cheeks and nose developed numerous shiny brownish pink papules (Figure 1). Over the course of the next 20 years she developed other skin findings noted on our present skin examination. The superior aspect of the mid forehead revealed a 4×2-cm, raised, flesh-colored, firm tumorous plaque. The neck and upper back had multiple 2- to 5-mm, soft, pedunculated, polypoid, brownish pink papules. Her mid back revealed ill-defined, slightly elevated, rosy plaques and macules with a roughened speckled appearance (Figure 2). Several of the toenails and fingernails showed firm, fleshy, spiculelike papules around and under the nail bed (Figure 3). The lower anterior tibia revealed several oval-shaped, flat, well-demarcated, hypopigmented macules (Figure 4). Lesions on the face and mid back were biopsied and histopathology confirmed angiofibroma and shagreen patch, or connective tissue nevus, respectively. Our patient did not undergo treatment of any of these skin lesions, particularly the facial angiofibromas. Cosmetic treatment options such as laser or surgical removal were presented to her, but she declined.
| |
A brief review of the literature for treatment options of facial angiofibromas and the fibrous forehead plaque indicated that current treatments include but are not limited to cryotherapy, electrocautery, electrosurgery, shave excision, chemical peels, argon laser, CO2 laser, and radiofrequency equipment.20 For the best outcome, these treatments have to be repeated throughout childhood and teenage years. Rapamycin, also known as sirolimus, and its analogs are new therapeutic options for TSC. Rapamycin is an inhibitor of the mechanistic target of rapamycin and can normalize this unregulated pathway in a TSC patient. Various preclinical models have shown that rapamycin treatment reduces TSC-related tumors, including brain, skin, and kidney tumors.21 A pilot study by Foster et al22 revealed improvement in the facial angiofibromas of 4 children treated with 2 topical preparations of rapamycin. The study revealed that younger patients with smaller angiofibromas had the best response with near-complete clearance. Rapamycin topical preparations were more cost effective than pulsed dye laser under general anesthesia.22
| |
Tuberous sclerosis complex is not the only syndrome that can present with facial angiofibromas or numerous skin tag–type lesions such as those in our patient. It is important to also consider Birt-Hogg-Dubé syndrome and multiple endocrine neoplasia type 1 in the differential diagnosis of multiple facial angiofibromas, particularly with adult onset.23
Our case was presented to review the cutaneous manifestations of TSC and their presentation frequency, with the intent to enable the dermatologist to make a more accurate and earlier diagnosis of TSC. In doing so, morbidity of TSC patients could be decreased and quality of life increased.
1. Vogt H. Zur Diagnostik der tuberosen sklerose. Z Erforsch Behandl Jugeudl Schwachsinns. 1908;2:1-6.
2. Webb DW, Clarke A, Fryer A, et al. The cutaneous features of tuberous sclerosis: a population study. Br J Dermatol. 1996;135:1-5.
3. van Slegtenhorst M, de Hoogt R, Hermans C, et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science. 1997;277:805-808.
4. O’Callaghan F. Tuberous sclerosis complex: from basic science to clinical phenotypes. Arch Dis Child. 2004;89:985.
5. Kwiatkowski DJ. Tuberous sclerosis: from tubers to mTOR. Ann Hum Genet. 2003;67:87-96.
6. Schwartz RA. Tuberous sclerosis complex: advances in diagnosis, genetics, and management. J Am Acad Dermatol. 2007;57:189-202.
7. Roach ES, Gomez MR, Northrup H. Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria. J Child Neurol. 1998;13:624-628.
8. Tworetzky W, McElhinney DB, Margossian R, et al. Association between cardiac tumors and tuberous sclerosis in the fetus and neonate. Am J Cardiol. 2003;92:487-489.
9. Casper KA, Donnelly LF, Chen B, et al. Tuberous sclerosis complex: renal imaging findings. Radiology. 2002;225:451-456.
10. El-Hashemite N, Zhang H, Henske EP, et al. Mutation in TSC2 and activation of mammalian target of rapamycin signaling pathway in renal angiomyolipoma. Lancet. 2003;361:1348-1349.
11. Jóźwiak S, Schwartz RA, Janniger CK, et al. Usefulness of diagnostic criteria of tuberous sclerosis complex in pediatric patients. J Child Neurol. 2000;15:652-659.
12. Ewalt DH, Sheffield E, Sparagana SP, et al. Renal lesion growth in children with tuberous sclerosis complex. J Urol. 1998;160:141-145.
13. Webb DW, Thomas RD, Osborne JP. Cardiac rhabdomyomas and their association with tuberous sclerosis. Arch Dis Child. 1993;68:367-370.
14. Holley DG, Martin GR, Brenner JI, et al. Diagnosis and management of fetal cardiac tumors: a multicenter experience and review of published reports. J Am Coll Cardiol. 1995;26:516-520.
15. Robertson DM. Ophthalmic manifestations of tuberous sclerosis. Ann N Y Acad Sci. 1991;615:17-25.
16. Roach ES, Smith M, Huttenlocher P, et al. Diagnostic criteria: tuberous sclerosis complex. J Child Neurol. 1992;7:221-224.
17. Gomez MR. Tuberous sclerosis. In: Gomez MR, ed. Neurocutaneous Diseases. A Practical Approach. Boston, MA: Butterworth; 1987:30-52.
18. Jóźwiak S, Schwartz RA, Janniger CK, et al. Skin lesions in children with tuberous sclerosis complex: their prevalence, natural course, and diagnostic significance. Int J Dermatol. 1998;37:911-917.
19. Nico MM, Ito LM, Valente NY. Genital angiofibromas in tuberous sclerosis: two cases. J Dermatol. 1999;26:111-114.
20. Gomes AA, Gomes YV, Lima FB, et al. Multiple facial angiofibromas treated with high frequency equipment. An Bras Dermatol. 2011;86:186-189.
21. Borkowska J, Schwartz RA, Kotulska K, et al. Tuberous sclerosis complex: tumors and tumorigenesis. Int J Dermatol. 2011;50:13-20.
22. Foster RS, Bint LJ, Halbert AR. Topical 0.1% rapamycin for angiofibromas in paediatric patients with tuberous sclerosis: a pilot study of four patients. Australas J Dermatol. 2012;53:52-56.
23. Schaffer JV, Gohara MA, McNiff JM, et al. Multiple facial angiofibromas: a cutaneous manifestation of Birt-Hogg-Dube syndrome. J Am Acad Dermatol. 2005;53:108-111.
1. Vogt H. Zur Diagnostik der tuberosen sklerose. Z Erforsch Behandl Jugeudl Schwachsinns. 1908;2:1-6.
2. Webb DW, Clarke A, Fryer A, et al. The cutaneous features of tuberous sclerosis: a population study. Br J Dermatol. 1996;135:1-5.
3. van Slegtenhorst M, de Hoogt R, Hermans C, et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science. 1997;277:805-808.
4. O’Callaghan F. Tuberous sclerosis complex: from basic science to clinical phenotypes. Arch Dis Child. 2004;89:985.
5. Kwiatkowski DJ. Tuberous sclerosis: from tubers to mTOR. Ann Hum Genet. 2003;67:87-96.
6. Schwartz RA. Tuberous sclerosis complex: advances in diagnosis, genetics, and management. J Am Acad Dermatol. 2007;57:189-202.
7. Roach ES, Gomez MR, Northrup H. Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria. J Child Neurol. 1998;13:624-628.
8. Tworetzky W, McElhinney DB, Margossian R, et al. Association between cardiac tumors and tuberous sclerosis in the fetus and neonate. Am J Cardiol. 2003;92:487-489.
9. Casper KA, Donnelly LF, Chen B, et al. Tuberous sclerosis complex: renal imaging findings. Radiology. 2002;225:451-456.
10. El-Hashemite N, Zhang H, Henske EP, et al. Mutation in TSC2 and activation of mammalian target of rapamycin signaling pathway in renal angiomyolipoma. Lancet. 2003;361:1348-1349.
11. Jóźwiak S, Schwartz RA, Janniger CK, et al. Usefulness of diagnostic criteria of tuberous sclerosis complex in pediatric patients. J Child Neurol. 2000;15:652-659.
12. Ewalt DH, Sheffield E, Sparagana SP, et al. Renal lesion growth in children with tuberous sclerosis complex. J Urol. 1998;160:141-145.
13. Webb DW, Thomas RD, Osborne JP. Cardiac rhabdomyomas and their association with tuberous sclerosis. Arch Dis Child. 1993;68:367-370.
14. Holley DG, Martin GR, Brenner JI, et al. Diagnosis and management of fetal cardiac tumors: a multicenter experience and review of published reports. J Am Coll Cardiol. 1995;26:516-520.
15. Robertson DM. Ophthalmic manifestations of tuberous sclerosis. Ann N Y Acad Sci. 1991;615:17-25.
16. Roach ES, Smith M, Huttenlocher P, et al. Diagnostic criteria: tuberous sclerosis complex. J Child Neurol. 1992;7:221-224.
17. Gomez MR. Tuberous sclerosis. In: Gomez MR, ed. Neurocutaneous Diseases. A Practical Approach. Boston, MA: Butterworth; 1987:30-52.
18. Jóźwiak S, Schwartz RA, Janniger CK, et al. Skin lesions in children with tuberous sclerosis complex: their prevalence, natural course, and diagnostic significance. Int J Dermatol. 1998;37:911-917.
19. Nico MM, Ito LM, Valente NY. Genital angiofibromas in tuberous sclerosis: two cases. J Dermatol. 1999;26:111-114.
20. Gomes AA, Gomes YV, Lima FB, et al. Multiple facial angiofibromas treated with high frequency equipment. An Bras Dermatol. 2011;86:186-189.
21. Borkowska J, Schwartz RA, Kotulska K, et al. Tuberous sclerosis complex: tumors and tumorigenesis. Int J Dermatol. 2011;50:13-20.
22. Foster RS, Bint LJ, Halbert AR. Topical 0.1% rapamycin for angiofibromas in paediatric patients with tuberous sclerosis: a pilot study of four patients. Australas J Dermatol. 2012;53:52-56.
23. Schaffer JV, Gohara MA, McNiff JM, et al. Multiple facial angiofibromas: a cutaneous manifestation of Birt-Hogg-Dube syndrome. J Am Acad Dermatol. 2005;53:108-111.
A 30-year-old woman presented to our dermatology clinic for evaluation and treatment options of a large 4×2-cm, firm, flesh-colored plaque on the superior aspect of the mid forehead. The plaque initially presented at 10 years of age and had grown since then. She reported no prior treatment of this nontender lesion and denied a family history of skin problems. She also had numerous skin tags all over the face, neck, and upper back that had increased in number for most of her adult life. In reviewing her medical history, she reported experiencing her first seizure at 15 months of age. She was evaluated by the neurology department at that time and was diagnosed with epilepsy.
Painful Purpura and Cutaneous Necrosis
The Diagnosis: Levamisole-Contaminated Cocaine
Physical examination revealed scattered palpable purpura including the nasal tip and large necrotizing skin lesions with bullae (Figure 1). Retiform purpura was noted on the patient’s trunk and legs. Purpuric plaques in various stages of necrosis were identified on the arms, trunk, breasts, and thighs, with an early lesion involving the left ear (Figure 2). Vitals revealed a blood pressure of 151/79 mm Hg and a temperature of 37.3°C. Although the patient initially denied illicit drug use, she later admitted to smoking crack cocaine prior to the skin eruption.
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Levamisole, an agent used in the veterinary setting to deworm cattle and pigs, is a common additive found in nearly 77% of the seized cocaine supplies in the United States.1 Because of its immunomodulator effects, the agent was once used in humans to treat conditions such as colon cancer, rheumatoid arthritis, and nephritic syndrome. Therapeutic levamisole use has been associated with purpura on the external ears, cheeks, and nasal tip. The predilection for purpura on the ears was first described in children using levam-isole as treatment of nephritic syndrome.2 Antinuclear cytoplasmic antibodies (ANCA) and antiphospholipid antibodies also were associated with therapeutic use.3 Reported effects of levamisole in cocaine users include fever, agranulocytosis, and infection. The mechanism is currently unknown but is thought to be an immunological process as evidenced by the presence of positive autoantibodies.4 Characteristic purpura in a cocaine abuser should alert the physician to consider levamisole as the culprit.
The diagnosis is largely a clinical one and other serious etiologies must be ruled out. The differential should include purpura fulminans, a rare hemorrhagic condition caused by severe infection, such as meningococcemia or deficiency of the vitamin K–dependent anticoagulants protein C and protein S. Given our patient’s history of hepatitis, purpura fulminans could have been likely. Purpura fulminans is rapidly progressive and is usually accompanied by disseminated intravascular coagulation. Coagulation studies and evidence of a consumptive coagulopathy such as thrombocytopenia, prolonged partial thromboplastin time, and activated partial thromboplastin time would favor this diagnosis. These studies as well as protein C and protein S were normal in our patient. Mixed cryoglobulinemia also should be suspected in a patient with hepatitis C virus who presents with vasculitis and arthralgia. An undetectable viral load in addition to a negative assay for cryoglobulins and normal complement (C3 and C4) levels make this diagnosis unlikely. Further, the purpura in cryoglobulinemia is typically confined to the lower extremities.5 Warfarin-induced skin necrosis also should be considered in patients who are taking warfarin.
Laboratory tests can be used to confirm the presence of infection, agranulocytosis, and coagulopathy. Although urine drug screen can confirm exposure to cocaine, levamisole is not detected in routine toxicology screening. Its half-life is between 5 and 6 hours; therefore, detection in blood or urine should be done within 48 hours of exposure.3,4 Unfortunately, our patient presented 2 weeks after cocaine use, making detection of levamisole unfeasible. Rheumatologic screening also is appropriate in cases of suspected vasculitis. Our patient had a negative antinuclear antibody but tested positive for lupus anticoagulant and perinuclear ANCA. IgA and IgG anticardiolipin were negative with an indeterminate IgM anticardiolipin level. The literature supports these findings, as ANCA antibodies occurred in more than 90% of reported cases.3 Further, IgM anticardiolipin antibodies and lupus anticoagulant were positive in 65% and 51% of cases, respectively.3 Leukocyte and neutrophil count were normal in our patient.
Management of these patients is mainly supportive. Complete avoidance of the offending agent is absolutely essential for resolution and avoidance of recurrence. Provided that the patient abstains from cocaine, the skin findings typically resolve in 2 to 3 weeks.3,6 The antibodies, however, may be present for up to 14 months.2,3,6 Treatment with steroids and other immunosuppressants has been reported, but evidence is lacking on their role in the resolution of the lesions.3 In patients who develop a temporary antiphospholipid syndrome, aspirin may be recommended as a preventative measure.6 Pain management, treatment of secondary infection especially in situations with agranulocytosis, and surgical debridement of wounds are all potential problems that can arise.
Our patient had complete resolution of the purpura involving the nose and ear over the course of 3 weeks. She did, however, have to undergo surgical debridement of the nonhealing full-thickness necrotic lesions on her legs and arms.
The 2013 National Survey on Drug Use and Health estimates 1.5 million individuals aged 12 years or older were current (within the last month) users of cocaine.7 With levamisole becoming more prevalent in cocaine supplies, clinicians should be aware of this emerging condition. Rapid recognition can spare the patient unnecessary testing and inappropriate treatment regimens. Because testing for levamisole is difficult and not routinely performed, this case highlights the importance of clinical clues and an accurate social history in clinching the diagnosis.
1. National drug threat assessment: 2011. National Drug Intelligence Center Web site. http://www.justice.gov/archive/ndic/pubs44/44849/44849p.pdf. Published August 2011. Accessed March 9, 2015.
2. Rongioletti F, Gio L, Ginevri F, et al. Purpura of the ears: a distinctive vasculopathy with circulating autoantibodies complicating long-term treatment with levamisole in children. Br J Dermatol. 1999;40:948-951.
3. Gulati S, Donato AA. Lupus anticoagulant and ANCA associated thrombotic vasculopathy due to cocaine contaminated with levamisole: a case report and review of the literature. J Thromb Thrombolysis. 2012;34:7-10.
4. de la Hera I, Sanz V, Cullen D, et al. Necrosis of ears after cocaine probably adulterated with levamisole. Dermatology. 2011;223:25-28.
5. Seo P. Immune complex-mediated vasculitis. In: Klippel JH. Primer on the Rheumatic Diseases. 13th ed. New York, NY: Springer Science+Business Media, LLC; 2008:427-443.
6. Ching JA, Smith DS. Levamisole-induced necrosis of skin, soft tissue, and bone: case report and review of literature. J Burn Care Res. 2012;33:e1-e5.
7. Substance Abuse and Mental Health Services Administration. Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings. NSDUH Series H-48, HHS Publication No. (SMA) 14-4863. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2014.
The Diagnosis: Levamisole-Contaminated Cocaine
Physical examination revealed scattered palpable purpura including the nasal tip and large necrotizing skin lesions with bullae (Figure 1). Retiform purpura was noted on the patient’s trunk and legs. Purpuric plaques in various stages of necrosis were identified on the arms, trunk, breasts, and thighs, with an early lesion involving the left ear (Figure 2). Vitals revealed a blood pressure of 151/79 mm Hg and a temperature of 37.3°C. Although the patient initially denied illicit drug use, she later admitted to smoking crack cocaine prior to the skin eruption.
|
Levamisole, an agent used in the veterinary setting to deworm cattle and pigs, is a common additive found in nearly 77% of the seized cocaine supplies in the United States.1 Because of its immunomodulator effects, the agent was once used in humans to treat conditions such as colon cancer, rheumatoid arthritis, and nephritic syndrome. Therapeutic levamisole use has been associated with purpura on the external ears, cheeks, and nasal tip. The predilection for purpura on the ears was first described in children using levam-isole as treatment of nephritic syndrome.2 Antinuclear cytoplasmic antibodies (ANCA) and antiphospholipid antibodies also were associated with therapeutic use.3 Reported effects of levamisole in cocaine users include fever, agranulocytosis, and infection. The mechanism is currently unknown but is thought to be an immunological process as evidenced by the presence of positive autoantibodies.4 Characteristic purpura in a cocaine abuser should alert the physician to consider levamisole as the culprit.
The diagnosis is largely a clinical one and other serious etiologies must be ruled out. The differential should include purpura fulminans, a rare hemorrhagic condition caused by severe infection, such as meningococcemia or deficiency of the vitamin K–dependent anticoagulants protein C and protein S. Given our patient’s history of hepatitis, purpura fulminans could have been likely. Purpura fulminans is rapidly progressive and is usually accompanied by disseminated intravascular coagulation. Coagulation studies and evidence of a consumptive coagulopathy such as thrombocytopenia, prolonged partial thromboplastin time, and activated partial thromboplastin time would favor this diagnosis. These studies as well as protein C and protein S were normal in our patient. Mixed cryoglobulinemia also should be suspected in a patient with hepatitis C virus who presents with vasculitis and arthralgia. An undetectable viral load in addition to a negative assay for cryoglobulins and normal complement (C3 and C4) levels make this diagnosis unlikely. Further, the purpura in cryoglobulinemia is typically confined to the lower extremities.5 Warfarin-induced skin necrosis also should be considered in patients who are taking warfarin.
Laboratory tests can be used to confirm the presence of infection, agranulocytosis, and coagulopathy. Although urine drug screen can confirm exposure to cocaine, levamisole is not detected in routine toxicology screening. Its half-life is between 5 and 6 hours; therefore, detection in blood or urine should be done within 48 hours of exposure.3,4 Unfortunately, our patient presented 2 weeks after cocaine use, making detection of levamisole unfeasible. Rheumatologic screening also is appropriate in cases of suspected vasculitis. Our patient had a negative antinuclear antibody but tested positive for lupus anticoagulant and perinuclear ANCA. IgA and IgG anticardiolipin were negative with an indeterminate IgM anticardiolipin level. The literature supports these findings, as ANCA antibodies occurred in more than 90% of reported cases.3 Further, IgM anticardiolipin antibodies and lupus anticoagulant were positive in 65% and 51% of cases, respectively.3 Leukocyte and neutrophil count were normal in our patient.
Management of these patients is mainly supportive. Complete avoidance of the offending agent is absolutely essential for resolution and avoidance of recurrence. Provided that the patient abstains from cocaine, the skin findings typically resolve in 2 to 3 weeks.3,6 The antibodies, however, may be present for up to 14 months.2,3,6 Treatment with steroids and other immunosuppressants has been reported, but evidence is lacking on their role in the resolution of the lesions.3 In patients who develop a temporary antiphospholipid syndrome, aspirin may be recommended as a preventative measure.6 Pain management, treatment of secondary infection especially in situations with agranulocytosis, and surgical debridement of wounds are all potential problems that can arise.
Our patient had complete resolution of the purpura involving the nose and ear over the course of 3 weeks. She did, however, have to undergo surgical debridement of the nonhealing full-thickness necrotic lesions on her legs and arms.
The 2013 National Survey on Drug Use and Health estimates 1.5 million individuals aged 12 years or older were current (within the last month) users of cocaine.7 With levamisole becoming more prevalent in cocaine supplies, clinicians should be aware of this emerging condition. Rapid recognition can spare the patient unnecessary testing and inappropriate treatment regimens. Because testing for levamisole is difficult and not routinely performed, this case highlights the importance of clinical clues and an accurate social history in clinching the diagnosis.
The Diagnosis: Levamisole-Contaminated Cocaine
Physical examination revealed scattered palpable purpura including the nasal tip and large necrotizing skin lesions with bullae (Figure 1). Retiform purpura was noted on the patient’s trunk and legs. Purpuric plaques in various stages of necrosis were identified on the arms, trunk, breasts, and thighs, with an early lesion involving the left ear (Figure 2). Vitals revealed a blood pressure of 151/79 mm Hg and a temperature of 37.3°C. Although the patient initially denied illicit drug use, she later admitted to smoking crack cocaine prior to the skin eruption.
|
Levamisole, an agent used in the veterinary setting to deworm cattle and pigs, is a common additive found in nearly 77% of the seized cocaine supplies in the United States.1 Because of its immunomodulator effects, the agent was once used in humans to treat conditions such as colon cancer, rheumatoid arthritis, and nephritic syndrome. Therapeutic levamisole use has been associated with purpura on the external ears, cheeks, and nasal tip. The predilection for purpura on the ears was first described in children using levam-isole as treatment of nephritic syndrome.2 Antinuclear cytoplasmic antibodies (ANCA) and antiphospholipid antibodies also were associated with therapeutic use.3 Reported effects of levamisole in cocaine users include fever, agranulocytosis, and infection. The mechanism is currently unknown but is thought to be an immunological process as evidenced by the presence of positive autoantibodies.4 Characteristic purpura in a cocaine abuser should alert the physician to consider levamisole as the culprit.
The diagnosis is largely a clinical one and other serious etiologies must be ruled out. The differential should include purpura fulminans, a rare hemorrhagic condition caused by severe infection, such as meningococcemia or deficiency of the vitamin K–dependent anticoagulants protein C and protein S. Given our patient’s history of hepatitis, purpura fulminans could have been likely. Purpura fulminans is rapidly progressive and is usually accompanied by disseminated intravascular coagulation. Coagulation studies and evidence of a consumptive coagulopathy such as thrombocytopenia, prolonged partial thromboplastin time, and activated partial thromboplastin time would favor this diagnosis. These studies as well as protein C and protein S were normal in our patient. Mixed cryoglobulinemia also should be suspected in a patient with hepatitis C virus who presents with vasculitis and arthralgia. An undetectable viral load in addition to a negative assay for cryoglobulins and normal complement (C3 and C4) levels make this diagnosis unlikely. Further, the purpura in cryoglobulinemia is typically confined to the lower extremities.5 Warfarin-induced skin necrosis also should be considered in patients who are taking warfarin.
Laboratory tests can be used to confirm the presence of infection, agranulocytosis, and coagulopathy. Although urine drug screen can confirm exposure to cocaine, levamisole is not detected in routine toxicology screening. Its half-life is between 5 and 6 hours; therefore, detection in blood or urine should be done within 48 hours of exposure.3,4 Unfortunately, our patient presented 2 weeks after cocaine use, making detection of levamisole unfeasible. Rheumatologic screening also is appropriate in cases of suspected vasculitis. Our patient had a negative antinuclear antibody but tested positive for lupus anticoagulant and perinuclear ANCA. IgA and IgG anticardiolipin were negative with an indeterminate IgM anticardiolipin level. The literature supports these findings, as ANCA antibodies occurred in more than 90% of reported cases.3 Further, IgM anticardiolipin antibodies and lupus anticoagulant were positive in 65% and 51% of cases, respectively.3 Leukocyte and neutrophil count were normal in our patient.
Management of these patients is mainly supportive. Complete avoidance of the offending agent is absolutely essential for resolution and avoidance of recurrence. Provided that the patient abstains from cocaine, the skin findings typically resolve in 2 to 3 weeks.3,6 The antibodies, however, may be present for up to 14 months.2,3,6 Treatment with steroids and other immunosuppressants has been reported, but evidence is lacking on their role in the resolution of the lesions.3 In patients who develop a temporary antiphospholipid syndrome, aspirin may be recommended as a preventative measure.6 Pain management, treatment of secondary infection especially in situations with agranulocytosis, and surgical debridement of wounds are all potential problems that can arise.
Our patient had complete resolution of the purpura involving the nose and ear over the course of 3 weeks. She did, however, have to undergo surgical debridement of the nonhealing full-thickness necrotic lesions on her legs and arms.
The 2013 National Survey on Drug Use and Health estimates 1.5 million individuals aged 12 years or older were current (within the last month) users of cocaine.7 With levamisole becoming more prevalent in cocaine supplies, clinicians should be aware of this emerging condition. Rapid recognition can spare the patient unnecessary testing and inappropriate treatment regimens. Because testing for levamisole is difficult and not routinely performed, this case highlights the importance of clinical clues and an accurate social history in clinching the diagnosis.
1. National drug threat assessment: 2011. National Drug Intelligence Center Web site. http://www.justice.gov/archive/ndic/pubs44/44849/44849p.pdf. Published August 2011. Accessed March 9, 2015.
2. Rongioletti F, Gio L, Ginevri F, et al. Purpura of the ears: a distinctive vasculopathy with circulating autoantibodies complicating long-term treatment with levamisole in children. Br J Dermatol. 1999;40:948-951.
3. Gulati S, Donato AA. Lupus anticoagulant and ANCA associated thrombotic vasculopathy due to cocaine contaminated with levamisole: a case report and review of the literature. J Thromb Thrombolysis. 2012;34:7-10.
4. de la Hera I, Sanz V, Cullen D, et al. Necrosis of ears after cocaine probably adulterated with levamisole. Dermatology. 2011;223:25-28.
5. Seo P. Immune complex-mediated vasculitis. In: Klippel JH. Primer on the Rheumatic Diseases. 13th ed. New York, NY: Springer Science+Business Media, LLC; 2008:427-443.
6. Ching JA, Smith DS. Levamisole-induced necrosis of skin, soft tissue, and bone: case report and review of literature. J Burn Care Res. 2012;33:e1-e5.
7. Substance Abuse and Mental Health Services Administration. Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings. NSDUH Series H-48, HHS Publication No. (SMA) 14-4863. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2014.
1. National drug threat assessment: 2011. National Drug Intelligence Center Web site. http://www.justice.gov/archive/ndic/pubs44/44849/44849p.pdf. Published August 2011. Accessed March 9, 2015.
2. Rongioletti F, Gio L, Ginevri F, et al. Purpura of the ears: a distinctive vasculopathy with circulating autoantibodies complicating long-term treatment with levamisole in children. Br J Dermatol. 1999;40:948-951.
3. Gulati S, Donato AA. Lupus anticoagulant and ANCA associated thrombotic vasculopathy due to cocaine contaminated with levamisole: a case report and review of the literature. J Thromb Thrombolysis. 2012;34:7-10.
4. de la Hera I, Sanz V, Cullen D, et al. Necrosis of ears after cocaine probably adulterated with levamisole. Dermatology. 2011;223:25-28.
5. Seo P. Immune complex-mediated vasculitis. In: Klippel JH. Primer on the Rheumatic Diseases. 13th ed. New York, NY: Springer Science+Business Media, LLC; 2008:427-443.
6. Ching JA, Smith DS. Levamisole-induced necrosis of skin, soft tissue, and bone: case report and review of literature. J Burn Care Res. 2012;33:e1-e5.
7. Substance Abuse and Mental Health Services Administration. Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings. NSDUH Series H-48, HHS Publication No. (SMA) 14-4863. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2014.
A 44-year-old woman with a history of hepatitis C virus and cocaine abuse presented with painful bruising and skin breakdown. Three weeks prior she was treated at an urgent care clinic with oral clindamycin for a recurrent Staphylococcus infection of her finger. One week later she started developing purpura and painful skin necrosis and ulceration. Most notable was the purpura on the tip of the nose. She also reported arthralgia and low-grade fever.
A Not-So-Old Football Injury
ANSWER
Imaging shows a ventral dislocation of the lunate. There is also a tiny avulsion fracture on the ulnar aspect of the adjacent triquetrum.
The patient was referred to orthopedics for a perilunate dislocation of the left wrist. He underwent successful closed reduction and was placed in a short arm cast for four weeks.
ANSWER
Imaging shows a ventral dislocation of the lunate. There is also a tiny avulsion fracture on the ulnar aspect of the adjacent triquetrum.
The patient was referred to orthopedics for a perilunate dislocation of the left wrist. He underwent successful closed reduction and was placed in a short arm cast for four weeks.
ANSWER
Imaging shows a ventral dislocation of the lunate. There is also a tiny avulsion fracture on the ulnar aspect of the adjacent triquetrum.
The patient was referred to orthopedics for a perilunate dislocation of the left wrist. He underwent successful closed reduction and was placed in a short arm cast for four weeks.
A 15-year-old boy presents for evaluation of left wrist pain. He says that two days ago, while playing football, he fell onto his outstretched left hand, which twisted upon impact with the ground. Immediately after the fall, he experienced severe pain. Since then, the pain has been constant, although it lessens to a moderate dull ache at rest and sharpens with activity. He denies any numbness or tingling in the affected hand and wrist. There are no other areas of injury from the fall, nor is there significant medical history. Physical exam identifies moderate left wrist swelling with focal tenderness over the volar aspect of the distal radius, extending to the wrist. The patient has limited active and passive flexion and extension of the left hand and wrist, along with reduced grip strength due to pain. There is mild navicular tenderness. Radial pulse is 2+, the hand is warm to the touch, and the skin is intact. Sensation is intact in all of the digits, which also demonstrate brisk capillary refill. Radiographs of the left wrist are obtained. What is your impression?
Postoperative Patient Suddenly Worsens
ANSWER
The radiograph demonstrates bilateral elevated diaphragm with a moderate amount of visible free air. With no history of recent abdominal procedures, the primary concern is a perforated viscus.
Urgent surgical consultation, as well as CT of the abdomen and pelvis, was obtained. The imaging confirmed the free air but provided no clear etiology. The patient underwent emergent laparotomy later that day and was found to have a perforated colon.
ANSWER
The radiograph demonstrates bilateral elevated diaphragm with a moderate amount of visible free air. With no history of recent abdominal procedures, the primary concern is a perforated viscus.
Urgent surgical consultation, as well as CT of the abdomen and pelvis, was obtained. The imaging confirmed the free air but provided no clear etiology. The patient underwent emergent laparotomy later that day and was found to have a perforated colon.
ANSWER
The radiograph demonstrates bilateral elevated diaphragm with a moderate amount of visible free air. With no history of recent abdominal procedures, the primary concern is a perforated viscus.
Urgent surgical consultation, as well as CT of the abdomen and pelvis, was obtained. The imaging confirmed the free air but provided no clear etiology. The patient underwent emergent laparotomy later that day and was found to have a perforated colon.
A 55-year-old man undergoes an elective craniotomy for tumor resection, with uneventful preoperative and intraoperative stages. Immediately postoperative, however, he experiences seizures. Noncontrast CT of the head is negative except for postoperative changes. The patient is placed in the ICU for close monitoring. He is slowly improving when, on the fifth postoperative day, tachypnea and dyspnea are observed. The patient is afebrile. His blood pressure is 116/70 mm Hg; pulse, 90 beats/min; respiratory rate, 30 breaths/min; and O2 saturation, 98%. A stat portable chest radiograph is obtained. What is your impression?
Leg Swelling Accompanied by Weight Gain
In the past two weeks, a 59-year-old postmenopausal woman has noticed swelling in her legs and a 10-lb weight gain. For the past three days, she has also had a vague, aching pain in the right upper abdominal quadrant, which surprises her, since her gall bladder was removed long ago. There is no prior history of chest pain, dyspnea, or systemic hypertension.
The patient does have a history of paroxysmal atrial fibrillation, palpitations, and pulmonary hypertension. She is chronically obese and has hypothyroidism. Surgical history is significant for cholecystectomy, hysterectomy, and left breast lumpectomy with axillary node dissection.
Her job at a local factory, assembling components for pressure washer pumps, requires her to sit for extended periods. She smokes 1.5 packs of cigarettes per day, a habit that began when she was 16. She drinks one or two beers daily and admits she has “many more” on the weekends. She has used marijuana in the recent past but not in the past month. She denies use of any other illicit drugs or homeopathic medications.
Her medication list includes levothyroxine sodium and ibuprofen. She says she’s “supposed to be taking some kind of heart medication” but hasn’t taken it for several months (and cannot remember the name). It was prescribed for her when she was on vacation in the Florida Keys and experienced similar symptoms. She sheepishly admits to trying her husband’s sildenafil, as she’s been told it works for pulmonary hypertension. She is allergic to sulfa and tetracycline.
Review of systems is remarkable for bilateral hip and ankle pain, which she attributes to her weight. She has had no change in bowel or bladder function. The remainder of the review is unremarkable.
Physical exam reveals a weight of 297 lb and height of 5’6”. Vital signs include a blood pressure of 128/88 mm Hg; pulse, 90 beats/min; respiratory rate, 14 breaths/min-1; temperature, 98.2°F; and O2 saturation, 98.2%.
She is morbidly obese and in no distress. Pertinent physical findings include elevated jugular venous return, bilateral rales in both lung bases, a soft, early diastolic murmur best heard at the left lower sternal border, and a regular rate and rhythm. She also has mild tenderness to deep palpation in the right upper abdominal quadrant. Her lower extremities demonstrate 3+ pitting edema to the level of the knees bilaterally. There are no skin lesions, and the neurologic exam is grossly intact.
As part of her workup, you order an ECG, which reveals a ventricular rate of 94 beats/min; PR interval, 130 ms; QRS duration, 76 ms; QT/QTc interval, 394/492 ms; P axis, 50°; R axis, 80°; and T axis, 47°. What is your interpretation?
ANSWER
Pertinent findings on this ECG include normal sinus rhythm, right atrial enlargement, and a prolonged QT interval. Criteria for right atrial enlargement include P waves > 2.5 mm in leads II, III, and aVF and > 1.5 mm in leads V1 and V2. A prolonged QT interval is evidenced by a QTc > 470 ms using Bazett’s formula (QTc = QT divided by the square root of the RR interval).
The patient’s symptoms and ECG finding of right atrial enlargement coincide with pulmonary hypertension and right-sided heart failure. The prolonged QT interval may be due to her history of hypothyroidism; however, this has not been confirmed.
In the past two weeks, a 59-year-old postmenopausal woman has noticed swelling in her legs and a 10-lb weight gain. For the past three days, she has also had a vague, aching pain in the right upper abdominal quadrant, which surprises her, since her gall bladder was removed long ago. There is no prior history of chest pain, dyspnea, or systemic hypertension.
The patient does have a history of paroxysmal atrial fibrillation, palpitations, and pulmonary hypertension. She is chronically obese and has hypothyroidism. Surgical history is significant for cholecystectomy, hysterectomy, and left breast lumpectomy with axillary node dissection.
Her job at a local factory, assembling components for pressure washer pumps, requires her to sit for extended periods. She smokes 1.5 packs of cigarettes per day, a habit that began when she was 16. She drinks one or two beers daily and admits she has “many more” on the weekends. She has used marijuana in the recent past but not in the past month. She denies use of any other illicit drugs or homeopathic medications.
Her medication list includes levothyroxine sodium and ibuprofen. She says she’s “supposed to be taking some kind of heart medication” but hasn’t taken it for several months (and cannot remember the name). It was prescribed for her when she was on vacation in the Florida Keys and experienced similar symptoms. She sheepishly admits to trying her husband’s sildenafil, as she’s been told it works for pulmonary hypertension. She is allergic to sulfa and tetracycline.
Review of systems is remarkable for bilateral hip and ankle pain, which she attributes to her weight. She has had no change in bowel or bladder function. The remainder of the review is unremarkable.
Physical exam reveals a weight of 297 lb and height of 5’6”. Vital signs include a blood pressure of 128/88 mm Hg; pulse, 90 beats/min; respiratory rate, 14 breaths/min-1; temperature, 98.2°F; and O2 saturation, 98.2%.
She is morbidly obese and in no distress. Pertinent physical findings include elevated jugular venous return, bilateral rales in both lung bases, a soft, early diastolic murmur best heard at the left lower sternal border, and a regular rate and rhythm. She also has mild tenderness to deep palpation in the right upper abdominal quadrant. Her lower extremities demonstrate 3+ pitting edema to the level of the knees bilaterally. There are no skin lesions, and the neurologic exam is grossly intact.
As part of her workup, you order an ECG, which reveals a ventricular rate of 94 beats/min; PR interval, 130 ms; QRS duration, 76 ms; QT/QTc interval, 394/492 ms; P axis, 50°; R axis, 80°; and T axis, 47°. What is your interpretation?
ANSWER
Pertinent findings on this ECG include normal sinus rhythm, right atrial enlargement, and a prolonged QT interval. Criteria for right atrial enlargement include P waves > 2.5 mm in leads II, III, and aVF and > 1.5 mm in leads V1 and V2. A prolonged QT interval is evidenced by a QTc > 470 ms using Bazett’s formula (QTc = QT divided by the square root of the RR interval).
The patient’s symptoms and ECG finding of right atrial enlargement coincide with pulmonary hypertension and right-sided heart failure. The prolonged QT interval may be due to her history of hypothyroidism; however, this has not been confirmed.
In the past two weeks, a 59-year-old postmenopausal woman has noticed swelling in her legs and a 10-lb weight gain. For the past three days, she has also had a vague, aching pain in the right upper abdominal quadrant, which surprises her, since her gall bladder was removed long ago. There is no prior history of chest pain, dyspnea, or systemic hypertension.
The patient does have a history of paroxysmal atrial fibrillation, palpitations, and pulmonary hypertension. She is chronically obese and has hypothyroidism. Surgical history is significant for cholecystectomy, hysterectomy, and left breast lumpectomy with axillary node dissection.
Her job at a local factory, assembling components for pressure washer pumps, requires her to sit for extended periods. She smokes 1.5 packs of cigarettes per day, a habit that began when she was 16. She drinks one or two beers daily and admits she has “many more” on the weekends. She has used marijuana in the recent past but not in the past month. She denies use of any other illicit drugs or homeopathic medications.
Her medication list includes levothyroxine sodium and ibuprofen. She says she’s “supposed to be taking some kind of heart medication” but hasn’t taken it for several months (and cannot remember the name). It was prescribed for her when she was on vacation in the Florida Keys and experienced similar symptoms. She sheepishly admits to trying her husband’s sildenafil, as she’s been told it works for pulmonary hypertension. She is allergic to sulfa and tetracycline.
Review of systems is remarkable for bilateral hip and ankle pain, which she attributes to her weight. She has had no change in bowel or bladder function. The remainder of the review is unremarkable.
Physical exam reveals a weight of 297 lb and height of 5’6”. Vital signs include a blood pressure of 128/88 mm Hg; pulse, 90 beats/min; respiratory rate, 14 breaths/min-1; temperature, 98.2°F; and O2 saturation, 98.2%.
She is morbidly obese and in no distress. Pertinent physical findings include elevated jugular venous return, bilateral rales in both lung bases, a soft, early diastolic murmur best heard at the left lower sternal border, and a regular rate and rhythm. She also has mild tenderness to deep palpation in the right upper abdominal quadrant. Her lower extremities demonstrate 3+ pitting edema to the level of the knees bilaterally. There are no skin lesions, and the neurologic exam is grossly intact.
As part of her workup, you order an ECG, which reveals a ventricular rate of 94 beats/min; PR interval, 130 ms; QRS duration, 76 ms; QT/QTc interval, 394/492 ms; P axis, 50°; R axis, 80°; and T axis, 47°. What is your interpretation?
ANSWER
Pertinent findings on this ECG include normal sinus rhythm, right atrial enlargement, and a prolonged QT interval. Criteria for right atrial enlargement include P waves > 2.5 mm in leads II, III, and aVF and > 1.5 mm in leads V1 and V2. A prolonged QT interval is evidenced by a QTc > 470 ms using Bazett’s formula (QTc = QT divided by the square root of the RR interval).
The patient’s symptoms and ECG finding of right atrial enlargement coincide with pulmonary hypertension and right-sided heart failure. The prolonged QT interval may be due to her history of hypothyroidism; however, this has not been confirmed.
Those symptoms first appeared two weeks ago. Now, this woman also has abdominal pain. What does an ECG add to the clinical picture?
As Problem Spreads, Man Seeks Help
ANSWER
The correct answer is Schamberg disease (choice “b”), a benign form of capillaritis; see Discussion for more information.
Scurvy patients can present with ecchymosis (among other findings that were missing in this case). But scurvy (choice “a”) is rare, and by the time the disease is evident, the patient is typically quite ill.
Cutaneous T-cell lymphoma (choice “c”) can manifest as purpuric annular lesions. However, these would be unlikely to take the distributive pattern seen in this case, and they usually have an atrophic surface.
Thrombocytopenia (choice “d”) and other coagulopathies, although rightly considered, would probably manifest in other ways as well (ie, not just cutaneously).
Continue for the discussion >>
DISCUSSION
Schamberg disease is typical of a whole class of conditions in which red blood cells (RBCs) are extravasated from slightly damaged capillaries. This results in nonblanchable purpura and subsequent hemosiderin staining caused by phagocytosis of the RBCs by macrophages. Clinically, this family of diseases present as cayenne pepper–colored macules, most of which are annular in configuration.
Schamberg is, by far, the most common of these conditions. This presentation was typical: manifestation on the knees and ankles followed by upward spread (hence the condition’s other name, progressive pigmentary purpura). Usually resolving on their own within months, these lesions are almost always asymptomatic—but nonetheless alarming to the patient.
Other equally benign, self-limited forms of capillaritis include those in which lesions are pruritic (eg, purpura of Doucas and Kapetanakis) or lichenoid (purpura of Gougerot-Blum). Another example is lichen aureus, in which only one or two lesions, more gold than brown, appear on the legs of younger patients.
There are many theories as to these conditions’ cause, the most common of which is increased intravascular pressure secondary to dependence. However, if this were so, we’d likely see a great deal more cases, since many patients have problems related to venous insufficiency.
In some cases, skin biopsy (usually 4-mm punch) is necessary to rule out more serious diseases, such as an early form of cutaneous T-cell lymphoma. When a coagulopathy is suspected, blood work is necessary to confirm or rule out the diagnosis. In this case, there was no reason to suspect coagulopathy (or scurvy), since no other signs were seen.
This patient was educated about his diagnosis and provided Web-based resources he could consult. Various treatments—topical steroids, increased vitamin C intake, and increased exposure to UV light—have been tried but with disappointing results.
ANSWER
The correct answer is Schamberg disease (choice “b”), a benign form of capillaritis; see Discussion for more information.
Scurvy patients can present with ecchymosis (among other findings that were missing in this case). But scurvy (choice “a”) is rare, and by the time the disease is evident, the patient is typically quite ill.
Cutaneous T-cell lymphoma (choice “c”) can manifest as purpuric annular lesions. However, these would be unlikely to take the distributive pattern seen in this case, and they usually have an atrophic surface.
Thrombocytopenia (choice “d”) and other coagulopathies, although rightly considered, would probably manifest in other ways as well (ie, not just cutaneously).
Continue for the discussion >>
DISCUSSION
Schamberg disease is typical of a whole class of conditions in which red blood cells (RBCs) are extravasated from slightly damaged capillaries. This results in nonblanchable purpura and subsequent hemosiderin staining caused by phagocytosis of the RBCs by macrophages. Clinically, this family of diseases present as cayenne pepper–colored macules, most of which are annular in configuration.
Schamberg is, by far, the most common of these conditions. This presentation was typical: manifestation on the knees and ankles followed by upward spread (hence the condition’s other name, progressive pigmentary purpura). Usually resolving on their own within months, these lesions are almost always asymptomatic—but nonetheless alarming to the patient.
Other equally benign, self-limited forms of capillaritis include those in which lesions are pruritic (eg, purpura of Doucas and Kapetanakis) or lichenoid (purpura of Gougerot-Blum). Another example is lichen aureus, in which only one or two lesions, more gold than brown, appear on the legs of younger patients.
There are many theories as to these conditions’ cause, the most common of which is increased intravascular pressure secondary to dependence. However, if this were so, we’d likely see a great deal more cases, since many patients have problems related to venous insufficiency.
In some cases, skin biopsy (usually 4-mm punch) is necessary to rule out more serious diseases, such as an early form of cutaneous T-cell lymphoma. When a coagulopathy is suspected, blood work is necessary to confirm or rule out the diagnosis. In this case, there was no reason to suspect coagulopathy (or scurvy), since no other signs were seen.
This patient was educated about his diagnosis and provided Web-based resources he could consult. Various treatments—topical steroids, increased vitamin C intake, and increased exposure to UV light—have been tried but with disappointing results.
ANSWER
The correct answer is Schamberg disease (choice “b”), a benign form of capillaritis; see Discussion for more information.
Scurvy patients can present with ecchymosis (among other findings that were missing in this case). But scurvy (choice “a”) is rare, and by the time the disease is evident, the patient is typically quite ill.
Cutaneous T-cell lymphoma (choice “c”) can manifest as purpuric annular lesions. However, these would be unlikely to take the distributive pattern seen in this case, and they usually have an atrophic surface.
Thrombocytopenia (choice “d”) and other coagulopathies, although rightly considered, would probably manifest in other ways as well (ie, not just cutaneously).
Continue for the discussion >>
DISCUSSION
Schamberg disease is typical of a whole class of conditions in which red blood cells (RBCs) are extravasated from slightly damaged capillaries. This results in nonblanchable purpura and subsequent hemosiderin staining caused by phagocytosis of the RBCs by macrophages. Clinically, this family of diseases present as cayenne pepper–colored macules, most of which are annular in configuration.
Schamberg is, by far, the most common of these conditions. This presentation was typical: manifestation on the knees and ankles followed by upward spread (hence the condition’s other name, progressive pigmentary purpura). Usually resolving on their own within months, these lesions are almost always asymptomatic—but nonetheless alarming to the patient.
Other equally benign, self-limited forms of capillaritis include those in which lesions are pruritic (eg, purpura of Doucas and Kapetanakis) or lichenoid (purpura of Gougerot-Blum). Another example is lichen aureus, in which only one or two lesions, more gold than brown, appear on the legs of younger patients.
There are many theories as to these conditions’ cause, the most common of which is increased intravascular pressure secondary to dependence. However, if this were so, we’d likely see a great deal more cases, since many patients have problems related to venous insufficiency.
In some cases, skin biopsy (usually 4-mm punch) is necessary to rule out more serious diseases, such as an early form of cutaneous T-cell lymphoma. When a coagulopathy is suspected, blood work is necessary to confirm or rule out the diagnosis. In this case, there was no reason to suspect coagulopathy (or scurvy), since no other signs were seen.
This patient was educated about his diagnosis and provided Web-based resources he could consult. Various treatments—topical steroids, increased vitamin C intake, and increased exposure to UV light—have been tried but with disappointing results.
For several months, a 30-year-old man has had an asymptomatic rash on his legs. The lesions first appeared on his lower legs and ankles; over the subsequent months, they have spread upward. Now, the rash reaches to just below his knees. During this time, he has had two bouts of strep throat, both adequately treated. He denies any other skin problems and has no relevant family history. The patient denies alcohol or drug abuse and is not taking any prescription medications. Prior to referral to dermatology, he was seen in two urgent care clinics; at one, he received a diagnosis of fungal infection and at the other, of “vitamin deficiency.” He was given a month-long course of terbinafine (250 mg/d) that produced no change in his rash. He achieved the same (non)result from an increased intake of vitamins. Examination reveals annular reddish brown macules, measuring 1 to 3 cm, sparsely distributed from the knees to just above the ankles on both legs. The lesions are a bit more densely arrayed on the anterior legs. There is no palpable component to any of them and no discernable surface scale. Digital pressure fails to blanch the lesions. The hairs and follicles on the patient’s legs appear normal. There are no notable skin changes elsewhere, and the patient is alert, oriented, and in no distress.
