Central Nervous System Xanthoma Disseminatum: Response to 2CdA in an Adolescent.

Xanthoma disseminatum is a normolipemic non-Langerhans cell histiocytosis characterized by red-brown rubbery papules of the skin which coalesce into plaque-like lesions with symmetric involvement of face, flexor, and intertriginous areas. Less commonly, xanthoma disseminatum may affect mucosal linings, abdominal organs, and the central nervous system, leading to endocrinopathies. We report a 12-year-old adolescent with mucosal, central nervous system, and painful cutaneous lesions, further complicated by diabetes insipidus and amenorrhea. Treatment with 2-chlorodeoxyadenosine led to relief of pain and significant improvement of mucosal, central nervous system, and cutaneous lesions, with subsequent restoration of menstrual cycles.

Next-generation sequencing confirms T-cell clonality in a subset of pediatric pityriasis lichenoides.

BACKGROUND: Pityriasis lichenoides (PL) is a papulosquamous disease that affects both adults and children. Previous studies have shown a subset of this entity to have clonal T-cell populations via PCR-based assays. In this study, we sought to implement next-generation sequencing (NGS) as a more sensitive and specific test to examine for T-cell clonality within the pediatric population. METHODS: We identified 18 biopsy specimens from 12 pediatric patients with clinical and histopathologic findings compatible with PL. Patient demographics, clinical features, management, and histopathologic findings were reviewed. All specimens were analyzed for clonality with NGS of T-cell receptor beta (TRB) and gamma (TRG) genes. RESULTS: Of the 12 patients, 9 (75%) had complete resolution of lesions at the time of data collection (mean follow-up 31 months). The remaining three patients significantly improved with methotrexate (with or without acitretin). Interestingly, 7 of 12 patients (58%) and 9 of 17 biopsy specimens (53%) showed evidence of T-cell clonality. Two patients showed matching TRB clones from different anatomic sites. CONCLUSIONS: T-cell clonality is a common finding in PL, probably representing a "reactive clonality" rather than a true lymphoproliferative disorder. Clonality alone cannot be used as a means to distinguish PL from lymphomatoid papulosis or cutaneous lymphoma.

Well-Appearing Newborn With a Vesiculobullous Rash at Birth.

A term, appropriate-for-gestational-age, male infant born via normal spontaneous vaginal delivery presented at birth with a full-body erythematous, vesiculobullous rash. He was well-appearing with normal vital signs and hypoglycemia that quickly resolved. His father had a history of herpes labialis. His mother had an episode of herpes zoster during pregnancy and a prolonged rupture of membranes that was adequately treated. The patient underwent a sepsis workup, including 2 attempted but unsuccessful lumbar punctures, and was started on broad-spectrum antibiotics and acyclovir, given concerns about bacterial or viral infection. The rash evolved over the course of several days. Subsequent workup, with particular attention to his history and presentation, led to his diagnosis.

A Hyperpigmented Reticular Rash in a Patient on Peritoneal Dialysis.

Chronically ill patients often develop uncommon exam findings. A 16-year-old female with end-stage renal disease secondary to immune complex-mediated glomerulonephritis on peritoneal dialysis (PD) developed a pruritic, hyperpigmented reticular rash on her abdomen, sparing the PD catheter insertion site. The rash appeared approximately 6 weeks after initiating PD. She used a heating pad nightly during PD for dialysis drain pain. Testing for systemic and autoimmune disease was negative. She was referred to dermatology, where the diagnosis of erythema ab igne (EAI), a well-described but less well-known hyperpigmented reticular cutaneous eruption caused by chronic exposure to low levels of infrared heat, was confirmed. The eruption is typically painless but is often pruritic. Common sources of heat include fires, stoves, portable heaters, heating pads, and laptop computers. The association between EAI and PD is unknown. Our patient discontinued the heating pad and her rash resolved.

Plaque-like myofibroblastic tumor: report of three cases.

Plaque-like myofibroblastic tumor of infancy (PMTI) was first reported in 2007. The first two cases described large, plaque-like tumors presenting in infancy with microscopic features consistent with dermatofibroma but with immunohistochemical features of myofibrocytic lineage. We present three additional cases of PMTI, the first cases reported since the initial two cases, and describe additional clinical features of this condition, including presentation in early childhood as opposed to infancy, development of ulceration, and aggressive growth. We propose shortening the name of this condition to plaque-like myofibroblastic tumor because presentation can occur in infancy or in early childhood.

Systemic treatments for severe pediatric psoriasis: a practical approach.

Severe psoriasis is uncommon in children, but when it occurs, can be physically, emotionally and socially disabling. Systemic treatments such as phototherapy, acitretin, methotrexate and cyclosporine have been used to manage severe pediatric psoriasis for decades. Newer biologic agents have demonstrated their effectiveness in adult psoriasis and are accumulating promising data in children. This article discusses the use of these treatments including their indications, efficacy, adverse effects, and monitoring requirements. The aim is to provide practical, clinically relevant information regarding the use of these medications alone and in various combinations based on available evidence and cumulative experience.

Propranolol and infantile hemangiomas four years later: a systematic review.

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.

Focal facial dermal dysplasia, type IV, is caused by mutations in CYP26C1.

Focal facial dermal dysplasia (FFDD) Type IV is a rare syndrome characterized by facial lesions resembling aplasia cutis in a preauricular distribution along the line of fusion of the maxillary and mandibular prominences. To identify the causative gene(s), exome sequencing was performed in a family with two affected siblings. Assuming autosomal recessive inheritance, two novel sequence variants were identified in both siblings in CYP26C1-a duplication of seven base pairs, which was maternally inherited, c.844_851dupCCATGCA, predicting p.Glu284fsX128 and a missense mutation, c.1433G>A, predicting p.Arg478His, that was paternally inherited. The duplication predicted a frameshift mutation that led to a premature stop codon and premature chain termination, whereas the missense mutation was not functional based on its in vitro expression in mammalian cells. The FFDD skin lesions arise along the sites of fusion of the maxillary and mandibular prominences early in facial development, and Cyp26c1 was expressed exactly along the fusion line for these facial prominences in the first branchial arch in mice. Sequencing of four additional, unrelated Type IV FFDD patients and eight Type II or III TWIST2-negative FFDD patients revealed that three of the Type IV patients were homozygous for the duplication, whereas none of the Type II or III patients had CYP26C1 mutations. The seven base pairs duplication was present in 0.3% of healthy controls and 0.3% of patients with other birth defects. These findings suggest that the phenotypic manifestations of FFDD Type IV can be non-penetrant or underascertained. Thus, FFDD Type IV results from the loss of function mutations in CYP26C1.

Depression and suicidal behavior in acne patients treated with isotretinoin: a systematic review.

Isotretinoin (13-cis retinoic acid) is an effective treatment for severe cystic or recalcitrant acne vulgaris; however, concerns have been raised regarding its potential association with depression and suicidal behavior. We sought to explore the proposed relationship between isotretinoin use and the risk of depression and attempted and completed suicide in patients with acne vulgaris by performing a systematic literature search for studies reporting primary data on depression and suicidal behavior in patients treated with isotretinoin for acne vulgaris. Nine studies met the qualifying criteria for our analysis. Rates of depression among isotretinoin users ranged from 1% to 11% across studies, with similar rates in oral antibiotic control groups. Overall, studies comparing depression before and after treatment did not show a statistically significant increase in depression diagnoses or depressive symptoms. Some, in fact, demonstrated a trend toward fewer or less severe depressive symptoms after isotretinoin therapy. This decrease was particularly evident in patients with pretreatment scores in the moderate or clinical depression range. No correlation between isotretinoin use and suicidal behavior was reported, although only one retrospective study presented data on this topic. Although the current literature does not support a causative association between isotretinoin use and depression, there are important limitations to many of the studies. The available data on suicidal behavior during isotretinoin treatment are insufficient to establish a meaningful causative association.

Keratosis pilaris rubra: a common but underrecognized condition.

BACKGROUND: Keratosis pilaris is a common skin disorder of childhood that often improves with age. Less common variants of keratosis pilaris include keratosis pilaris atrophicans and atrophodermia vermiculata. OBSERVATIONS: In this case series from dermatology practices in the United States, Canada, Israel, and Australia, the clinical characteristics of 27 patients with keratosis pilaris rubra are described. Marked erythema with follicular prominence was noted in all patients, most commonly affecting the lateral aspects of the cheeks and the proximal arms and legs, with both more marked erythema and widespread extent of disease than in keratosis pilaris. The mean age at onset was 5 years (range, birth to 12 years). Sixty-three percent of patients were male. No patients had atrophy or scarring from their lesions. Various treatments were used, with minimal or no improvement in most cases. CONCLUSIONS: Keratosis pilaris rubra is a variant of keratosis pilaris, with more prominent erythema and with more widespread areas of skin involvement in some cases, but without the atrophy or hyperpigmentation noted in certain keratosis pilaris variants. It seems to be a relatively common but uncommonly reported condition.

A population-based analysis of laboratory abnormalities during isotretinoin therapy for acne vulgaris.

OBJECTIVE: To determine the incidence of abnormal laboratory test results among isotretinoin users. DESIGN: Retrospective cohort. SETTING: Comprehensive managed care health plan in Northern California. PARTICIPANTS: The study population comprised 13 772 patients aged 13 to 50 years with acne, undergoing oral isotretinoin therapy between March 1995 and September 2002. MAIN OUTCOME MEASURES: Laboratory values for serum triglyceride, total cholesterol, and liver transaminase levels; white blood cell count, hemoglobin level, and platelet count; and frequency of abnormal laboratory results by severity grade as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. RESULTS: Substantial increases in the cumulative incidence of abnormalities were seen in serum lipid and transaminase levels, but not in hematologic parameters, during isotretinoin treatment compared with the baseline period. The cumulative incidence of new abnormalities in patients with normal values at baseline was 44% for triglyceride level, 31% for total cholesterol level, and 11% for transaminase level. Moderate to severe abnormalities in lipid and transaminase levels were generally transient and reversible. New abnormalities in hematological test results were uncommon. CONCLUSIONS: The incidence of abnormally high serum lipid levels during isotretinoin treatment may be greater than previously estimated. Elevations in transaminase level are generally mild. Normal baseline values of serum lipid and transaminase levels do not preclude the development of new abnormalities during isotretinoin treatment. Routine monitoring of white blood cell count, hemoglobin level, and platelet count during isotretinoin therapy may be of little utility without clinical suspicion of an abnormality. The clinical significance of laboratory abnormalities during isotretinoin therapy remains to be determined.

Depression and suicidal behavior in acne patients treated with isotretinoin: a systematic review.

Isotretinoin (13-cis retinoic acid) is an effective treatment for severe cystic or recalcitrant acne vulgaris; however, concerns have been raised regarding its potential association with depression and suicidal behavior. We sought to explore the proposed relationship between isotretinoin use and the risk of depression and attempted and completed suicide in patients with acne vulgaris by performing a systematic literature search for studies reporting primary data on depression and suicidal behavior in patients treated with isotretinoin for acne vulgaris. Nine studies met the qualifying criteria for our analysis. Rates of depression among isotretinoin users ranged from 1% to 11% across studies, with similar rates in oral antibiotic control groups. Overall, studies comparing depression before and after treatment did not show a statistically significant increase in depression diagnoses or depressive symptoms. Some, in fact, demonstrated a trend toward fewer or less severe depressive symptoms after isotretinoin therapy. This decrease was particularly evident in patients with pretreatment scores in the moderate or clinical depression range. No correlation between isotretinoin use and suicidal behavior was reported, although only one retrospective study presented data on this topic. Although the current literature does not support a causative association between isotretinoin use and depression, there are important limitations to many of the studies. The available data on suicidal behavior during isotretinoin treatment are insufficient to establish a meaningful causative association.