A case of mother and child with CANDLE syndrome: Diagnosis and subsequent treatment with baricitinib.

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) or proteasome-associated autoinflammatory syndrome is a rare autoinflammatory disorder that typically presents in infancy with characteristic symptoms, including recurrent fever, panniculitis, and progressive lipodystrophy, among other findings. We present a case of mother and child with CANDLE syndrome. The child was eventually started on baricitinib with normalization of rash and systemic findings.

Midline anterior neck inclusion cyst: A novel superficial congenital developmental anomaly of the neck.

BACKGROUND/OBJECTIVES: A variety of congenital developmental anomalies arise on the neck because of the many fusion planes and complex embryologic structures in this region. We describe a series of seven patients with a novel type of superficial midline congenital anomaly. METHODS: Retrospective case series. Clinical and histopathologic features were compared and used to describe this entity. RESULTS: Seven patients with nearly identical clinical findings were identified. In all cases, a small superficial cyst resembling a giant milium was observed at birth. There were no significant changes during infancy and no evidence of underlying abnormalities. The histopathologic findings were identical to those of an infundibular follicular cyst. CONCLUSION: We have termed this entity midline anterior neck inclusion cyst. We believe it is a superficial developmental anomaly, probably a forme fruste of a midline fusion developmental defect, which has not to our knowledge, previously been described.

Presumed ocular juvenile xanthogranuloma and biopsy-proven cutaneous mastocytosis occurring sequentially in a young boy.

Juvenile xanthogranuloma is a benign non-Langerhans cell histiocytosis characterized by skin lesions that tend to be self-limited. Ocular lesions can occur in juvenile xanthogranuloma, most commonly presenting as an iris granuloma. Skin lesions of juvenile xanthogranuloma may appear similar to lesions of mastocytosis. Mastocytosis includes a heterogeneous group of diseases characterized by the proliferation and abnormal infiltration of mast cells. Rubbing of cutaneous lesions leads to the release of histamine, causing the lesions to urticate. Juvenile xanthogranuloma and mastocytosis skin lesions occurring concurrently is extremely rare, with only four cases reported. Ocular juvenile xanthogranuloma and cutaneous lesions of mastocytosis have never been described in the same patient in the literature. The authors describe a patient with an ocular juvenile xanthogranuloma presenting at birth with cutaneous mastocytosis developing several years later.

Epidermolysis bullosa simplex with mottled pigmentation due to a rare keratin 5 mutation: cutaneous findings in infancy.

Epidermolysis bullosa simplex with mottled pigmentation (EBS-MP) is an autosomal dominant inherited blistering skin disease characterized by nonscarring blistering and reticulated hyperpigmentation. It is most commonly due to a heterozygous point mutation, P25L, in the nonhelical V1 domain of keratin 5 (KRT5). Here we present a case of EBS-MP with early onset of reticulated hyperpigmentation during infancy due to a rare 1649delG mutation in the V2 domain of KRT5.

Patient characteristics of neonatal eosinophilic pustulosis.

A 10-week old preterm infant boy presented with a pustular eruption of the face and blood eosinophilia. Histology demonstrated eosinophils without predominant follicular involvement. The lesions healed without intervention within 2 months. The presentation was consistent with neonatal eosinophilic pustulosis. We discuss the similarities between cases described in the literature and suggest that this entity affects a unique patient population of preterm infants.

Solitary mastocytoma of the eyelid.

Mastocytosis is a heterogeneous group of diseases characterized by the proliferation and abnormal infiltration of mast cells in tissue. These collections of mast cells are called mastocytomas. Solitary mastocytomas are cutaneous lesions, most commonly involving the extremities and trunk. Rubbing a cutaneous mastocytoma lesion leads to the release of histamine and other chemical mediators causing the lesion to become elevated and urticarial, similar to an allergic reaction. We describe a rare location of a presumed solitary mastocytoma of the lower eyelid in a young otherwise healthy child.

"Eczema coxsackium" and unusual cutaneous findings in an enterovirus outbreak.

OBJECTIVE: To characterize the atypical cutaneous presentations in the coxsackievirus A6 (CVA6)-associated North American enterovirus outbreak of 2011-2012. METHODS: We performed a retrospective case series of pediatric patients who presented with atypical cases of hand, foot, and mouth disease (HFMD) from July 2011 to June 2012 at 7 academic pediatric dermatology centers. Patients were included if they tested positive for CVA6 or if they met clinical criteria for atypical HFMD (an enanthem or exanthem characteristic of HFMD with unusual morphology or extent of cutaneous findings). We collected demographic, epidemiologic, and clinical data including history of skin conditions, morphology and extent of exanthem, systemic symptoms, and diagnostic test results. RESULTS: Eighty patients were included in this study (median age 1.5 years, range 4 months-16 years). Seventeen patients were CVA6-positive, and 63 met clinical inclusion criteria. Ninety-nine percent of patients exhibited a vesiculobullous and erosive eruption; 61% of patients had rash involving >10% body surface area. The exanthem had a perioral, extremity, and truncal distribution in addition to involving classic HFMD areas such as palms, soles, and buttocks. In 55% of patients, the eruption was accentuated in areas of eczematous dermatitis, termed "eczema coxsackium." Other morphologies included Gianotti-Crosti-like (37%), petechial/purpuric (17%) eruptions, and delayed onychomadesis and palm and sole desquamation. There were no patients with serious systemic complications. CONCLUSIONS: The CVA6-associated enterovirus outbreak was responsible for an exanthem potentially more widespread, severe, and varied than classic HFMD that could be confused with bullous impetigo, eczema herpeticum, vasculitis, and primary immunobullous disease.

Papular epidermal nevus with "skyline" basal cell layer (PENS).

BACKGROUND: Several types of epidermal keratinocytic nevus are recognized. OBJECTIVE: We sought to describe a previously unreported keratinocytic nevus with distinctive clinical and histopathologic features in 5 patients. METHODS: We performed a clinical and photographic review, and obtained skin biopsy samples for histopathologic examination from each patient. Genetic analysis to screen for fibroblast growth factor receptor 3 and phosphatidylinositol 3-kinase, catalytic, alpha hotspot mutations was performed on lesional skin from two patients. RESULTS: Five infants (2 male, 3 female) had from 1 to 11 lesions present since birth. These consisted of 1- to 7-mm hyperkeratotic papules with a rough, flat surface and a round, commalike, rectangular, or polygonal shape. Histopathologic examination showed acanthosis with broad and rectangular rete ridges, and strikingly arranged basal cells with palisaded nuclei. Genetic testing on paraffin-embedded specimens from two patients ruled out hotspot mutations in the fibroblast growth factor receptor 3 and phosphatidylinositol 3-kinase, catalytic, alpha genes. LIMITATIONS: A small number of patients are presented. CONCLUSION: We propose the name "papular epidermal nevus with 'skyline' basal cell layer" (PENS) for this newly recognized condition.

Autosomal recessive woolly hair with hypotrichosis caused by a novel homozygous mutation in the P2RY5 gene.

During the last decade, several causative genes for hereditary hair diseases have been identified, which have disclosed the molecular mechanisms involved in hair follicle morphogenesis and cycling. We and others recently reported that mutations in the P2RY5 gene, encoding an orphan G protein-coupled receptor, underlie autosomal recessive woolly hair (WH)/hypotrichosis. Although these findings clearly reveal the involvement of P2RY5 mutations in hereditary hair diseases, the clinical manifestations of P2RY5 mutations have not completely been elucidated because of limited information to date. In this study, we ascertained a consanguineous family of Iranian origin with an affected girl showing sparse and hypopigmented scalp hair. She exhibited the WH phenotype with normal hair density at birth, but progressed with age to develop hypotrichosis. Direct sequencing analysis resulted in the identification of a novel homozygous mutation in the P2RY5 gene of the patient, which results in a non-conservative amino acid change, G146R, at the protein level. Our findings extend the mutation spectrum of P2RY5 mutations, and further support a crucial role of P2Y5 in hair growth in humans.

Acquired zinc deficiency in full-term newborns from decreased zinc content in breast milk.

Zinc deficiency occurs in children when the demand for zinc exceeds its supply. Malnutrition, prematurity, total parenteral nutrition dependence, and burns increase the demand for zinc, whereas congenital malabsorption syndromes represent clinical situations where less zinc is supplied to the growing child. Clinical recognition of acral eczematous lesions, alopecia, and gastrointestinal tract symptoms in settings of the aforementioned medical history often lead to the diagnosis. Zinc deficiency in healthy, full-term, breast-fed infants can occur. The cause of these deficiencies has been attributed to decreased zinc levels in maternal breast milk. We present a case of acquired zinc deficiency in a healthy breast-fed infant, with a review of the English language literature of reported cases.

The clonal nature of pityriasis lichenoides.

BACKGROUND: Pityriasis lichenoides et varioliformis acuta (PLEVA) and pityriasis lichenoides chronica (PLC) are benign lymphocytic infiltrates of the skin that classically present as either a recurrent papulonecrotic eruption (PLEVA) or a persistent, scaling, papular eruption (PLC). Observations of both types of lesions present on individual patients have led to speculation that both entities are related. Previous studies evaluating the DNA of biopsy specimens from patients with PLEVA and PLC revealed clonal T-cell receptor beta gene rearrangements. OBJECTIVE: To analyze and compare the T-cell populations between lesions of PLEVA and PLC. DESIGN: Retrospective and prospective analysis of patient tissue samples, classified by histologic analysis. Extracted DNA from 13 skin biopsy specimens with the diagnosis of PLC and 14 skin biopsy specimens with the diagnosis of PLEVA was analyzed by polymerase chain reaction/denaturing gradient gel electrophoresis (PCR/DGGE). SETTING: Molecular diagnostic laboratory at an academic medical center. PATIENTS: Twenty-seven tissue samples were obtained from patients with a histologic diagnosis of PLEVA or PLC. These samples were analyzed by PCR/DGGE. MAIN OUTCOME MEASURE: The presence or absence of T-cell receptor gene rearrangements on PCR/DGGE analysis corresponding to a clonal population of T cells. RESULTS: Of 14 PLEVA specimens, 8 (57%) demonstrated monoclonal T-cell receptor gene rearrangements; 1 (8%) of 13 PLC specimens showed a gene rearrangement (P =.008, Fisher exact test). CONCLUSIONS: Our results demonstrate the polyclonal nature of the lymphocytic infiltrate found in almost all of the PLC specimens, which contrasts with the monoclonal nature found in most of the PLEVA specimens. These differences may represent different stages of the clinical evolution of a single entity that results from varying host immune responses to pathogenic factors. Specifically, we propose that PLEVA is a benign clonal T-cell disorder in which the clone arises from a subset of T cells in lesions of PLC. The host immune response to this clone determines the clinical and histologic findings in PLEVA.

Compound heterozygosity for non-sense and mis-sense mutations in desmoplakin underlies skin fragility/woolly hair syndrome.

The constitutive desmosomal plaque protein desmoplakin plays a vital part in keratinocyte adhesion in linking the transmembranous desmosomal cadherins to the cytoplasmic keratin filament network. Recently, mutations in desmoplakin have been shown to underlie some cases of the autosomal dominant disorder, striate palmoplantar keratoderma, as well as an autosomal recessive condition characterized by dilated cardiomyopathy, woolly hair, and keratoderma. Here, we describe two unrelated individuals with a new autosomal recessive genodermatosis characterized by focal and diffuse palmoplantar keratoderma, hyperkeratotic plaques on the trunk and limbs, varying degrees of alopecia, but no apparent cardiac anomalies. Mutation screening of desmoplakin demonstrated compound heterozygosity for a non-sense/mis-sense combination of mutations in both cases, C809X/N287K and Q664X/R2366C, respectively. Heterozygous carriers of any of these mutations displayed no phenotypic abnormalities. Immunohistochemistry of skin biopsies from both affected individuals revealed that desmoplakin was not just located at the cell periphery but there was also cytoplasmic staining. In addition, electron microscopy demonstrated acantholysis throughout all layers of the skin, focal detachment of desmosomes into the intercellular spaces, and perinuclear condensation of the suprabasal keratin intermediate filament network. Clinicopathologic and mutational analyses therefore demonstrate that desmoplakin haploinsufficiency can be tolerated in some cases, but that in combination with a mis-sense mutation on the other allele, the consequences are a severe genodermatosis with specific clinical manifestations.