Epidermolysis bullosa simplex with Mottled Pigmentation

Abstract

Epidermolysis bullosa simplex with mottled pigmentation (EBS-MP) is a rare genodermatosis of which only 4 pedigrees have so far been reported. We present herein a new family with EBS-MP comprising a peculiar punctate digital keratoderma. The propositus was an 18-year-old patient who had suffered since birth from posttraumatic bullae, followed by mottled pigmentation, plantar keratosis, nail dystrophy and peculiar punctate keratoses of the fingers. Histology, immunofluorescence and electron microscopy of a bullous lesion showed an intraepidermal cleavage and an increased number of melanosomes within basal keratinocytes, dermal macrophages and Schwann cells. The precise genetic defect responsible for EBS-MP is not known but could be due to two distinct, closely linked mutations. The nosologic relationship between EBS-MP and other forms of EBS as well as cases of hereditary bullous poikilodermic acrokeratosis is discussed.

Epidermolysis bullosa simplex with mottled pigmentation: Clinical aspects and confirmation of the P24L mutation in theKRT5 gene in further patients

“…They also show that there can be moderate variation among affected family members with regard to the course of the disease and to the severity of expression. All this is in keeping with previous reports [Fischer and Gedde-Dahl, 1979;Bruckner-Tuderman et al, 1989;Combemale and Kanitakis, 1994].…”

“…Furthermore, there is severe hypoor anhydrosis, in line with an ectodermal dysplasia. Therefore, we hesitate to agree with Combemale and Kanitakis [1994] that the family described by Sparrow et al [1976] in reality might have been a case of EBS-MP.…”

“…In EBS-MP, the blisters arise spontaneously or after minor trauma from birth or in early infancy. Acral sites and distal extremities are predilected for blister formation; mucous membranes are generally spared [Fischer and Gedde-Dahl, 1979;Bruckner-Tuderman et al, 1989;Combemale and Kanitakis, 1994]. Next to blistering, the most striking lesions are hyperpigmented macules of 2 to 5 mm in diameter arranged in a reticular pattern which gives the skin a "dirty" or mottled appearance.…”

The genetic basis of epidermolysis bullosa simplex with mottled pigmentation.

“…5). This exact same nucleotide substitution, predicting a P24L mutation in one of the two KS alleles, was found in affected family members 22,32,33,34,36,41,42,44,46, 51, and 55, and not in unaffected members 35,37,43,47,49,52, and 54 (representative examples of these data are shown in Fig. 5).…”

“…EBS-MP is unusual in that patients have skin blistering similar to that of EBS, but in addition, they have striking MP (4,(30)(31)(32)(33) (35,37), and polymerase chain reaction (PCR) amplification was performed to amplify KS sequences from patients EBS 44-3 and SEB1-22. DNAs were then resolved by gel electrophoresis, and fragments were subcloned into the pCRII plasmid vector (TA Cloning System, Invitrogen).…”