A systematic review of the safety of topical therapies for atopic dermatitis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75613/1/j.1365-2133.2006.07538.x.pd

Keratin 17 mutations cause either steatocystoma multiplex or pachyonychia congenita type 2

Pachyonychia congenita type 2 (PC-2; Jackson-Lawler syndrome) is an autosomal dominant disorder characterized by hypertrophic nail dystrophy, mild focal keratoderma, multiple pilosebaceous cysts and other features of ectodermal dysplasia, Keratin 17 (K17) is a differentiation-specific keratin expressed in the nail bed, hair follicle, sebaceous gland and other epidermal appendages, Previously, we have demonstrated that PC-2 is caused by mutations in K17 and that similar mutations in this gene can present as steatocystoma multiplex with little or no nail dystrophy Here, we describe three unrelated kindreds carrying K17 mutations. Two of these families have identical missense mutations (R94C) in the IA domain of K17, However, while affected members of one kindred have the classical features of PC-2, affected persons in the other family have the steatocystoma multiplex phenotype, In a third family with PC-2. mutation N92S was detected, bringing the total number of distinct mutations reported in K17 thus far to 11, These results demonstrate that K17 mutations commonly underlie both PC-2 and steatocystoma multiplex and that the alternate phenotypes which arise from these genetic lesions in K17 are independent of the specific mutation involved

Features of epidermolysis bullosa simplex due to mutations in the ectodomain of type XVII collagen

Background Mutations in COL17A1, coding for type XVII collagen, cause junctional epidermolysis bullosa with an ultrastructural plane of cleavage through the lamina lucida of the epidermal basement membrane. Objectives To identify the COL17A1 mutations in a child with reduced type XVII collagen expression and intraepidermal blister formation. Patients and methods Protein expression and level of tissue separation were studied by immunofluorescence and electron microscopy. The mutations were identified by analysing the patient's DNA and mRNA. Results Immunofluorescence microscopy performed on nonlesional skin demonstrated absence of the type XVII collagen endodomain and presence, although reduced, of the shed ectodomain. Electron microscopy showed that the plane of cleavage was through the basal cells, not through the lamina lucida. Two heterozygous mutations were identified in COL17A1: a new 3'-acceptor splice-site mutation in intron 21 (1877-2A-->C), and a deletion in exon 48 (3432delT). The splice-site mutation in intron 21 results in alternative transcripts of which two are in-frame, with deletions of the first nine codons of exon 22 and the entire exon 22, respectively. By Western blot analysis, a type XVII collagen molecule was detected that was slightly smaller than normal. Conclusions Occasionally mutations in the COL17A1 gene may result in split levels suggesting epidermolysis bullosa simplex rather than junctional epidermolysis bullosa

Restrictive dermopathy:Report of 12 cases

Background: This study describes 12 cases of restrictive dermopathy seen during a period of 8 years by the Dutch Task Force on Genodermatology. We present these unique consecutive cases to provide more insight into the clinical picture and pathogenesis of the disease. Observations: Clinical features in more than 85% of these 12 children were prematurity, fixed facial expression, micrognathia, mouth in o position, rigid and tense skin with erosions and denudations, and multiple joint contractures. Ten patients underwent histopathologic skin biopsy. The biopsy results showed flattening of rete ridges in all 10 patients, a thin dermis with collagen aligned parallel to the epidermis in 9 patients, and poorly developed dermal appendages in 9 patients. Additional findings in individual patients included blepharophimosis, inguinal skin tear, skin tear in the frontal neck area that developed during delivery, absent eyelashes, a nide ascendent aorta, and dextrocardia. Fibroblast cultures taken from 5 patients did not show abnormal alpha(2) beta(1) and alpha(1) beta(1) integrin expressions. Conclusions: The alleged rarity of restrictive dermopathy may be partially caused by medical unfamiliarity with this entity, despite its characteristic clinical and histopathologic picture. The pathogenesis of the disease still needs to be elucidated