Two missense mutations in Dystonin lead to epidermolysis bullosa simplex complicated with lepromatous leprosy: a case report.

BACKGROUND: Epidermolysis bullosa (EB) is a severe, single-gene hereditary skin condition characterized by blisters, bullae, and erosion following minor trauma. Epidermolysis bullosa simplex (EBS), one of the four major types of EB, is typically caused by mutations in the KRT5 or KRT14 genes. However, mutations in the Dystonin (DST) gene, which is also involved in maintaining skin integrity, can lead to EBS. This study aims to report a unique case of EBS caused by two novel heterozygous mutations in the DST gene, complicated by lepromatous leprosy (LL), a chronic infectious disease caused by Mycobacterium leprae (M. leprae). These mutations, not previously reported in the literature, expand the known spectrum of DST-related EBS and highlight the importance of comprehensive diagnostic approaches in patients with complex skin conditions.

CASE DESCRIPTION: This report describes a 32-year-old man presented with erythema, blisters and yellow nodules on his limbs, initially diagnosed as bullous pemphigoid (BP). Over time, his symptoms evolved to include features of LL and erythema nodosum leprosum (ENL), a severe inflammatory reaction often associated with leprosy. Further genetic testing revealed two missense mutations in the DST gene: c.5972A>G(p.Asn1991Ser) and c.5137A>G(p.Asn1713Asp). Both variants were predicted to be damaging by in silico analyses and are rare in population databases. The patient was diagnosed with EBS that causes the skin to be very fragile and blister easily. The combination of EBS, LL and ENL is rare.

CONCLUSIONS: This case highlights EBS caused by DST mutations, emphasizing the importance of comprehensive diagnostic workup in patients with bullous diseases. Additionally, it underscores the importance of rational glucocorticoid use and careful skin wound care in treating bullous skin diseases.