Junctional Epidermolysis Bullosa Linked to Homozygous Mutation in LAMC2 Gene: A Case Report With Eosinophil-Rich Inflammatory Infiltrate.

ABSTRACT: Junctional epidermolysis bullosa (JEB) is a rare, incurable, devastating, and mostly fatal congenital genetic disorder characterized by painful blistering of the skin and mucous membranes in response to minor trauma or pressure. JEB is classified roughly into 2 subtypes: JEB-Herlitz is caused by mutations on genes encoding laminin-332. The authors present a patient consulted with a suspicion of primary immunodeficiency due to skin sores that started at the age of 1 month and a history of 3 siblings who died with similar sores, who was diagnosed with JEB-Herlitz after detecting a homozygous LAMC2 gene mutation in WES analysis. Microscopic evaluation of hematoxylin and eosin-stained sections showed vesicle formation with subepidermal separation, which is accompanied by striking neutrophil and eosinophil leukocyte infiltration both in the vesicle and papillary dermis (eosinophil-rich inflammatory infiltrate). Such a histopathological finding has been rarely reported in this condition.

Two siblings with PRKDC defect who presented with cutaneous granulomas and review of the literature.

V(D)J recombination, during which recognition and repair of broken DNA chains are accomplished by non-homologous end joining pathway, is a critical process in B and T cell development.Null mutations of each enzyme or protein of this pathway result in T- B- NK+ severe combined immunodeficiency whereas hypomorphic mutations result in atypical(leaky)severe combined immunodeficiency forms. We present two siblings with PRKDC (Protein Kinase, DNA-Activated, Catalytic Polypeptide) mutation who presented with granulomatous skin lesions and recurrent lung infections. Primary immune deficiencies may initially present with skin findings. Disruption in central and peripheral B-cell tolerance and impaired intrathymic T-cell maturation,a central player in T-cell tolerance, have been identified as the mechanism of autoimmunity and granuloma seen in patients. The variation in clinical phenotypes of patients with PRKDC mutation suggests that additional factors such as modifying genes, epigenetic and environmental factors may affect the severity and clinical phenotype of the disease. Functional studies during the follow-up and evaluation before and after hematopoeitic stem cell transplantation will hopefully increase our knowledge about the autoimmune and inflammatory process of the disease spectrum.