Epidermolysis Bullosa, Lethal Acantholytic

Mutations in the desmoplakin (DSP) gene have been demonstrated to be associated with lethal acantholytic epidermolysis bullosa, cardiomyopathy, and palmoplantar keratoderma (PPK).

To better understand the relationship between PPK and the gene mutations in DSP.

A pedigree of PPK was subjected to heterozygous missense mutation analysis in the DSP gene. Dermoscopy, reflectance confocal microscopy, and histopathological examination were performed from each epidermis layer in this study. Samples were derived from the blood of patients and normal healthy controls. DSP gene sequence analysis and Q-PCR analysis was performed for evaluating DSP gene mutation and expression.

A novel heterozygous missense mutation c.3550 C>T in the coding region of the DSP gene, predicting substitution of arginine (Arg,R) by tryptophan (Trp,W) in the desmoplakin polypeptide, was discovered in a Chinese pedigree of PPK. In the meanwhile, this mutation was not found in 100 healthy individuals.

The novel missense mutation c.3550 C>T(p.Arg1184Trp) of DSP gene expanded the mutation spectrum in palmoplantar keratoderma.

The specific histopathologic diagnosis of a primary acantholytic disorder takes into account the distribution and extent of acantholysis, presence or absence of dyskeratosis, nature of the dermal inflammatory cell infiltrate, and immunofluorescence findings. Herpes virus infection is a common cause of secondary acantholysis where distinctive viral cytopathic changes aid in making it a clear-cut diagnosis in majority of cases. We present a case of coexistence of Hailey-Hailey disease and herpes simplex virus infection to compare and contrast their histopathologic features. This is imperative because acantholytic cells from primary acantholytic disorders may occasionally show cytological features traditionally associated with herpes virus infection (pseudoherpetic changes). The objective of this article is to create a greater awareness of pseudoherpetic changes and also to explore the clinical significance of coexistence of a primary acantholytic disorder and herpes virus infection, as in this case.

Grover disease is an acantholytic disorder that typically occurs on the trunk of older individuals, primarily white men, in association with heat and xerosis. Cases with extensive and/or atypical distributions have been reported.

To review the literature characterizing the population, morphology, associations, and disease course of extensive or atypical eruptions of Grover disease.

A systematic literature review identified 50 articles with 69 cases.

Patient age ranged from 14 to 83 years (mean age, 56 ± 15), with 71% of patients being male and 29% female. Areas of involvement included the trunk (90%), upper and lower extremities (63% and 61%, respectively), face/scalp (28%), neck (21%), groin (11%), buttocks (8%), and axillae (6%). The most common associations included a history of malignancy (61%), recent chemotherapy (38%), and recent transplant (20%).

Extensive cases with typical clinical morphology may not have been examined by biopsy or reported; thus, this review may have publication bias toward more severe or atypical presentations.

Greater variability exists among patients affected by extensive or atypical Grover disease than among those with typical disease. Malignancy is a common association, and there may be a role for immunosuppression in the pathogenesis of extensive or atypical Grover disease.