Adam I. Rubin

Differential expression of pyloric atresia in junctional epidermolysis bullosa with ITGB4 mutations suggests that pyloric atresia is due to factors other than the mutations and not predictive of a poor outcome: three novel mutations and a review of the literature

Junctional epidermolysis bullosa with pyloric atresia (JEB-PA) is an autosomal recessive blistering disease including lethal and non-lethal variants due to mutations in ITGB4 and ITGA6. It is unclear whether PA is caused directly by the mutations in these genes or by other factors. Skin biopsies from patients with JEB were processed for immunofluorescence mapping. When staining for integrin beta4 or alpha6 was absent or reduced, ITGB4 was screened for mutations. A review of known mutations of ITGB4 and the phenotypes of patients with JEB-PA was undertaken. Three novel ITGB4 mutations were identified in 3 families with JEB-PA: 2 splice-site and one insertion mutation. Two families with lethal phenotypes (EB-050 and EB-049) were due to combinations of premature termination codons and missense mutations (658delC/R252C and 3903dupC/G273D, respectively). The third family EB-013 has 2 JEB affected siblings; a brother with PA and a sister without PA. Both were homo notzygous for ITGB4 264G>A/3111-1G>A. Two cases had no gastrointestinal symptoms or signs of PA. PA is an inconstant feature of the subtype of epidermolysis bullosa known as JEB-PA. It is most likely that multiple factors influence the development of PA and its presence is not predictive of a poor outcome. It is possible that institutions that do not routinely screen immunofluore notscence mapping for integrin alpha6beta4 staining in the absence of PA are missing this form of epidermolysis bullosa.

Six Novel Antimycotics

We have reviewed six new antimycotic agents which have potential applications for human cutaneous and mucosal diseases. Information on these six drugs was obtained via an English language search of PubMed through the US National Library of Medicine. The antimycotic agents reviewed include rilopirox, lanoconazole, NND-502, butenafine, eberconazole and voriconazole. Rilopirox is a synthetic pyridone derivative, related to ciclopirox, with a fungicidal action. Rilopirox is a hydrophobic, topical agent with potential application in mucosal candida infections, tinea versicolor and seborrheic dermatitis. Lanoconazole, an imidazole, is a topical agent with potential application in tinea infections and cutaneous candidiasis. The drug has been available for clinical use in Japan since 1994 and once-daily application to affected areas is recommended. In addition to its antifungal effect, animal data suggest that application of lanoconazole 0.5 or 1% cream is associated with accelerated wound healing. NND-502, a stereoselective analog of lanoconazole, is a topical agent with potential application in tinea pedis infection. NND-502 appears to be more effective in inhibiting ergosterol biosynthesis than lanoconazole or bifonazole and clinical trials comparing these agents are awaited. Butenafine is the first member of a new class of antifungals, the benzylamine derivatives, and has been approved for topical use in Japan (since 1992) and the US. Butenafine has a potent fungicidal action and the drug has been shown to be effective in multiple clinical trials in patients with tinea pedis, tinea corporis and tinea cruris. Butenafine has also been reported to exert an anti-inflammatory action after topical application and this may offer potential benefit over other topical antifungal agents. Eberconazole, an imidazole derivative, is a topical antifungal agent that has been shown to be effective in clinical trials in patients with tinea infections. Preliminary data indicate that the eberconazole is effective against some triazole-resistant yeasts such as Candida krusei and Candida glabrata. Voriconazole is an azole antifungal derivative of fluconazole. The drug is available in both oral and parenteral formulations. Oral voriconazole 200mg twice daily has been effective in treating oropharyngeal candidiasis and apergillosis in immunocompromised patients. After 12 weeks’ treatment, a similar dosage of the drug elicited a positive response in 69% of nonimmunocompromised patients with invasive aspergillosis.

Exophiala spinifera as a Cause of Cutaneous Phaeohyphomycosis: Case Study and Review of the Literature

Exophiala spinifera has been reported as an agent of cutaneous disease 18 times in the literature. Clinical presentations of cutaneous lesions vary widely, including erythematous papules, verrucous plaques, and deep subcutaneous abscesses. The clinical distribution and course of disease are also variable, depending on the age and immune competency of the patient. Histologic appearance occurs in one of two patterns--phaeohyphomycosis or chromoblastomycosis. While E. spinifera appears to be susceptible to multiple antimicrobial agents in vitro, clinical experience with treatment modalities has been variable. Prior to the availability of sequencing methods, species identification was based on the histopathologic presentation in tissue and morphologic features of the fungus in culture. It is likely that E. spinifera cutaneous infections have been underreported due to its incorrect identification based on earlier methods. We report an additional case of E. spinifera phaeohyphomycosis, the first to be definitively identified by sequencing. In addition, we summarize the variable clinical, histopathologic, and morphologic features, as well as treatment responses described in previously reported cutaneous infections caused by E. spinifera.

The HoVert technique: a novel method for the sectioning of alopecia biopsies.

Background: Cicatricial forms of alopecia, including lichen planopilaris (LPP) and discoid lupus erythematosus (DLE), may present with overlapping clinical features. In such cases, histopathological examination may provide key information for resolving the differential diagnosis. Optimally, microscopical analysis for alopecia requires both vertical and horizontal sections, and this may necessitate multiple samples. Here, we present what we term the “HoVert” technique, which produces horizontal and vertical sections from a single biopsy. We hypothesize that the HoVert technique should be useful for differentiating DLE from LPP.

Cuterebra cutaneous myiasis: case report and world literature review

Background  Most cases of myiasis in North America are caused by fly larvae from South America or Africa, as these cases represent travelers returning from endemic regions. The etiology of creeping eruptions and furuncular lesions in North American patients who have no history of recent travel can therefore be a diagnostic problem. Among cases acquired in North America, Cuterebra species are the usual cause. Dermatologists and dermatopathologists should be aware that this unusual infestation may occur without a travel history.

Pigmented Onychomatricoma: A Rare Pigmented Nail Unit Tumor Presenting as Longitudinal Melanonychia That Has Potential for Misdiagnosis as Melanoma

Pigmented onychomatricoma is a rare nail unit tumor that can clinically mimic nail unit melanoma. We report the case of a 63-year-old male with new-onset longitudinal melanonychia involving his right second toe. An excisional biopsy was performed and demonstrated pigmented onychomatricoma. We present this case to alert clinicians of this rare nail unit tumor and the importance of clinicopathologic correlation to avoid misdiagnosis.

WNT10A mutation causes ectodermal dysplasia by impairing progenitor cell proliferation and KLF4-mediated differentiation

Human WNT10A mutations are associated with developmental tooth abnormalities and adolescent onset of a broad range of ectodermal defects. Here we show that β-catenin pathway activity and adult epithelial progenitor proliferation are reduced in the absence of WNT10A, and identify Wnt-active self-renewing stem cells in affected tissues including hair follicles, sebaceous glands, taste buds, nails and sweat ducts. Human and mouse WNT10A mutant palmoplantar and tongue epithelia also display specific differentiation defects that are mimicked by loss of the transcription factor KLF4. We find that β-catenin interacts directly with region-specific LEF/TCF factors, and with KLF4 in differentiating, but not proliferating, cells to promote expression of specialized keratins required for normal tissue structure and integrity. Our data identify WNT10A as a critical ligand controlling adult epithelial proliferation and region-specific differentiation, and suggest downstream β-catenin pathway activation as a potential approach to ameliorate regenerative defects in WNT10A patients.

Nodular Scleroderma : A Report of 2 Cases

Nodular scleroderma, also known as keloidal scleroderma, is a rare form of scleroderma that may occur with either systemic sclerosis or localized scleroderma. Clinically, this disorder is characterized by keloidal nodules that form in sclerodermatous areas. These nodules may histologically show the presence of keloidal collagen. Because of the rarity of this condition, clinicians may not be familiar with the clinical and histologic features relevant to this scleroderma variant. In this report, we describe 2 cases of nodular scleroderma.

Diagnosis and Management of Nail Disorders in Children

The authors herein describe several nail conditions, which the general pediatrician is likely to encounter in the course of routine practice. Because pediatric nail disorders represent a limited component of a general pediatric practice, it can be challenging for practitioners to establish expertise in the diagnosis and treatment of these conditions and to recognize when reassurance is appropriate or when referral to a specialist is necessary. This article summarizes the anatomy of the normal nail unit, as well as the evaluation and management of onychomycosis, melanonychia, trachyonychia, onychomadesis, and nail pitting.

Hypopigmented onychocytic matricoma as a clinical mimic of onychomatricoma: clinical, intraoperative and histopathologic correlations.

Onychocytic matricoma is a newly described matrical tumor of the nail unit that clinically presents with localized thickening of the nail plate and melanonychia and represents a benign acanthoma of onychocytes. Onychocytic matricoma can be classified according to its histopathologic type (acanthotic, papillomatous or keratogenous with retarded maturation) and pigmentation (pigmented, melanocytic or non‐pigmented). However, there are no published reports of non‐pigmented onychocytic matricoma. We report a case of hypopigmented onychocytic matricoma that presented with a thickened nail plate, xanthonychia and histopathologic features of acanthosis, prekeratogenous zone and keratogenous zone cells forming pseudosquamous eddies, and minimal pigmentation with Fontana staining. We also provide detailed clinical, intraoperative and histopathologic correlations of this rare tumor. Both clinicians and dermatopathologists should be aware that onychocytic matricoma can present with xanthonychia, thickening of the nail plate and mimic an onychomatricoma.