Identification of two rare and novel large deletions in ITGB4 gene causing epidermolysis bullosa with pyloric atresia.

Epidermolysis bullosa with pyloric atresia (EB-PA) is a rare autosomal recessive hereditary disease with a variable prognosis from lethal to very mild. EB-PA is classified into Simplex form (EBS-PA: OMIM #612138) and Junctional form (JEB-PA: OMIM #226730), and it is caused by mutations in ITGA6, ITGB4 and PLEC genes. We report the analysis of six patients with EB-PA, including two dizygotic twins. Skin immunofluorescence epitope mapping was performed followed by PCR and direct sequencing of the ITGB4 gene. Two of the patients presented with non-lethal EB-PA associated with missense ITGB4 gene mutations. For the other four, early postnatal demise was associated with complete lack of ß4 integrin due to a variety of ITGB4 novel mutations (2 large deletions, 1 splice-site mutation and 3 missense mutations). One of the deletions spanned 278 bp, being one of the largest reported to date for this gene. Remarkably, we also found for the first time a founder effect for one novel mutation in the ITGB4 gene. We have identified 6 novel mutations in the ITGB4 gene to be added to the mutation database. Our results reveal genotype-phenotype correlations that contribute to the molecular understanding of this heterogeneous disease, a pivotal issue for prognosis and for the development of novel evidence-based therapeutic options for EB management.

Facial lesions in frontal fibrosing alopecia (FFA): Clinicopathological features in a series of 12 cases.

BACKGROUND: Facial lesions in frontal fibrosing alopecia (FFA) have been poorly described in published series. OBJECTIVE: We sought to describe facial lesions in FFA. METHODS: We reviewed our series of 55 cases of FFA, selecting 12 cases with clinically significant facial lesions. We performed a histologic study of these lesions. RESULTS: In addition to the observations already described in the literature such as facial papules or follicular red dots, we observed perifollicular and diffuse erythema, sometimes with a reticular pattern, and the gradual appearance of pigmented macules on facial skin. Biopsy specimens from the areas with facial erythema showed perifollicular and interfollicular lymphocytic infiltrate and fibrosis around vellus hair follicles. Histologic evaluation of pigmented macules sometimes exhibited an increased epidermal pigmentation and on occasions, pigmentary incontinence. LIMITATIONS: More patients are needed to determine the prevalence of these lesions in FFA. CONCLUSION: On facial skin of patients with FFA, we can observe papules or perifollicular erythema secondary to vellus hair follicle involvement. We describe diffuse erythema, owing to follicular and interfollicular lichenoid infiltrate, and the gradual appearance of pigmented macules, which could be secondary to an increased epidermal pigmentation or to pigmentary incontinence.

Letter: Photodistributed reticulated hyperpigmentation related to diltiazem.

Diltiazem is a calcium channel blocking agent used for the treatment of hypertension. Cutaneous adverse effects are uncommon. The most frequently reported are itching, urticaria, and maculopapular eruption. A peculiar, cutaneous photodistributed reticulated hyperpigmentation secondary to diltiazem has been recently reported. A 66-year-old white woman with a 2 year history of pruritic hyperpigmented lesions on her face was seen in the clinic. Past medical history was remarkable for hypertension, which had been treated with diltiazem. Physical examination showed slate-gray to brown reticulated hyperpigmentation in the photo-exposed areas of the face and neck. Histological examination revealed interface dermatitis with liquefactive degeneration of the basal layer, necrotic keratinocytes, lymphocytic inflammatory infiltrate, and melanophages in the superficial dermis. A diagnosis of diltiazem-induced hyperpigmentation was established and diltiazem was stopped. Gradual resolution of the hyperpigmentation was observed over the following months. Although diltiazem has been marketed for over 20 years, the first cases of this particular type of reticulated hyperpigmentation were described in 2001. Since then, to our knowledge, only 17 cases have been reported in the literature. In all cases, cutaneous lesions appeared at least 6 months after this treatment had been started. Hyperpigmentation was controlled by means of photoprotection and discontinuation of diltiazem. Diltiazem can produce a characteristic lichenoid dermatitis with reticulated hyperpigmentation on sun-exposed areas.