Faculty Bibliography

Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive, inborn error of bile acid metabolism characterized by diarrhea in infancy, juvenile cataracts in childhood, tendon xanthomas developing in the second to third decades of life, and progressive neurologic dysfunction in adulthood. The condition is caused by mutations in the CYP27A1 gene that result in decreased production of chenodeoxycholic acid (CDCA) and elevated levels of cholestanol and bile alcohols. We present a 36-year-old male of Han ethnicity who developed xanthomas of his Achilles tendons and suffered neurocognitive declines and gait deterioration in his second decade. The diagnosis of CTX was confirmed by marked elevation of the serum cholestanol level. Sequencing of CYP27A1 showed a paternally inherited splice mutation, c.446 + 1G>T, and a maternally inherited nonsense mutation, c.808C>T, predicting p.(Arg270*). Despite the advanced disease in this patient, treatment with CDCA reduced the xanthoma size and improved his cognition and strength, and the patient made significant gains in his ambulation and coordination. We report this case to illustrate the potential benefits of therapy in patients with CTX who have advanced disease at the time of diagnosis.

Background: Juvenile xanthogranuloma (JXG) is a benign, self-limited disease of infants and children occurring early in life with 20% present at birth. They are firm papules or nodules measuring 5 mm to 2 cm. Early JXGs can be more erythematous, but become increasingly yellow over time. JXGs usually run a benign course with regression by 3-6 years old with potential pigmentary alteration or atrophic scarring upon resolution. Extracutaneous involvement can occur, most commonly in the eye, with children having multiple lesions being at greatest risk. Giant JXGs are a rare variant greater than 2 cmin diameter. Unlike more common JXGs, the giant variant is typically present at birth, at an increased risk of ulceration, and may only partially involute over time. Observation: A 6-week-old male presented with a firm swelling of his right vertex scalp measuring 3 cm x 2 cm. His labor was difficult, given that he was 10 pounds, and after birth, his entire scalp was red and swollen. Over the subsequent 2 weeks, the redness subsided except for one spot that continued to become larger in size. Their pediatrician, an outside dermatologist, and a neurologist evaluated the lesion and ordered an ultrasound, which showed a soft tissue swelling with "fluid" per the mother, but no diagnosis was given. Exam revealed a non-tender nodule stable in size since 2 weeks old with overlying alopecia. Within the nodule, smaller papules were noted with a yellowish hue. A repeat ultrasound was performed which showed a hypodensity within the dermal layer and a hypoechoic collection deep to the dermis, but above the periosteum. Findings were most consistent with a scalp hematoma, specifically a caput secundum. Given that the history and exam findings were atypical for a hematoma, a biopsy was performed which showed a nodular infiltrate of histiocytes consistent with JXG. Evaluation by ophthalmology revealed no ocular involvement. Comment: Giant congenital JXGs are a rare variant of JXGs that can be mistaken for other infantile swellings and tumors including hematomas, infantile hemangiomas, Langerhans cell histiocytosis and other soft tissue neoplasms. Keep this diagnosis in mind when evaluating large congenital tumors in the neonatal period. A "watch and see" approach is still recommended as giant congenital JXGs do spontaneously regress and are not believed to be independently associated with systemic involvement

This report describes the clinical, radiologic, and autopsy findings of a newborn with PHACE syndrome (posterior fossa malformations, hemangioma, arterial anomalies, cardiac defects, and eye anomalies) and fetal alcohol spectrum disorder. To our knowledge, the concurrence of these conditions has not been reported in the literature.

Kaposiform hemangioendothelioma (KHE) is an infiltrative vascular tumor that classically presents in infancy. Management typically focuses on treating Kasabach-Merritt phenomenon (KMP), a disorder of severe and at times life-threatening platelet trapping. However, the morbidity of KHE extends beyond KMP. The infiltrative nature of the tumor can lead to long-term disability and often makes complete surgical resection impossible. We report the case of a 10-year-old boy with a KHE of his right distal thigh who was unable to walk without assistance due to fibrotic change and right knee contracture. He had no laboratory evidence of KMP at the time of representation. Rapamycin was started in hopes of reducing the tumor burden. Within 2 months of therapy, fibrotic areas softened, his contracture nearly resolved, and there was marked improvement in his mobility. Rapamycin has been previously reported to be effective in managing cases of KHE complicated by KMP. Our report emphasizes the role for rapamycin in the treatment of KHE in the absence of KMP through the inhibition of vasculogenesis and fibrotic pathways.

Hair re-pigmentation in adults is a rare phenomenon. We describe a 58-year-old woman who developed hair re-pigmentation on her vertex scalp as a marker of underlying melanoma. Histopathology revealed a nodular melanoma that was surrounding but not invading follicular epithelium. To our knowledge, there have only been 4 other previously published cases describing hair re-pigmentation in the setting of scalp melanoma. Focal hair re-pigmentation in adults should prompt a thorough evaluation for an underlying melanoma.

Autism spectrum disorder (ASD) is a neurodevelopmental condition that effects verbal and nonverbal communication and social cognition and often presents with altered sensory processing, stereotyped behavior, and restricted interests. The prevalence of this diagnosis has increased markedly over the past two decades. Dermatologists undoubtedly will be evaluating and managing more patients with this diagnosis, but there has been little written regarding the dermatologic care of patients with ASD. Difficulties with communication and sensory processing create significant challenges in clinical evaluation and management. Individuals with ASD are also at higher risk for certain dermatologic conditions. This review is intended to build an awareness of the complexity of caring for individuals with ASD and discuss strategies that can help improve the dermatologic care of these patients.

To systematically review the literature evaluating efficacy and adverse events of propranolol treatment for infantile hemangiomas, we searched the MEDLINE and Cochrane databases for all studies examining the response of infantile hemangiomas (IHs) to propranolol published between June 12, 2008, and June 15, 2012. Forty-one studies with 1,264 patients were included; 74% of patients were female and approximately 30% had received other treatments before propranolol. Propranolol was initiated at a mean age of 6.6 months at a mean dose of 2.1 mg/kg/day and for a mean treatment duration of 6.4 months. The response rate for patients with IHs treated with propranolol was 98% (range 82%-100%), with response rate defined as any improvement with propranolol. Treatment response rates were comparable for studies evaluating IHs at specific sites, such as periorbital IHs. Studies that followed patients after treatment completion reported IH rebound growth in 17% of patients. There were 371 adverse events reported in 1,189 patients. The most common adverse events were changes in sleep (n = 136) and acrocyanosis (n = 61). Serious adverse events were rare, with reports of symptomatic hypotension in five patients, hypoglycemia in four, and symptomatic bradycardia in one. This systematic review of 1,264 patients treated with propranolol for IHs showed a high rate of efficacy and a low rate of serious adverse events.