Dermal eosinophilic infiltrate in junctional epidermolysis bullosa

Abstract

Junctional epidermolysis bullosa (JEB) is a rare genodermatosis characterized by a split in the lamina lucida usually because of mutations in LAMA3, LAMB3 and LAMC2 resulting in absence or reduction of laminin-332. Rare subtypes of JEB have mutations in COL17A1, ITGB4, ITGA6 and ITGA3 leading to reduction or dysfunction of collagen XVII, integrin α6β4 and integrin α3. The classic finding under light microscopy is a paucicellular, subepidermal split. We describe the unusual presence of an eosinophilic infiltrate in the bullae and subjacent dermis in a neonate with JEB, generalized intermediate (formerly known as non-Herlitz-type JEB), discuss the histologic differential diagnosis for a subepidermal blister in a neonate, review the literature regarding cases of epidermolysis bullosa (EB) presenting with inflammatory infiltrates, and discuss mechanisms to explain these findings. This case highlights that eosinophils can rarely be seen in EB and should not mislead the dermatopathologist into diagnosing an autoimmune blistering disorder.

Prevalence, pathophysiology and management of itch in epidermolysis bullosa*

“…In particular, there are reports of eosinophilic infiltrates in skin biopsies across all EB types, observed both in the blister cavities and in the upper dermis (Figure 2). [28][29][30][31] Interestingly, this pattern of eosinophilic infiltration is similar to that which occurs in bullous pemphigoid (BP), where subepidermal blistering occurs secondary to autoantibodies principally against the hemidesmosomal antigen BP180 (collagen XVII). 32,33 Itch severity in BP was shown to correlate with the number of dermal eosinophils, the epidermal expression of neurokinin-1 receptor (NK1R), IL-31RA, oncostatin M receptor-b and the expression of T helper (Th) 2-associated mediators, including IL-4, IL-13 and periostin.…”

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

“…Under light microscopy, the characteristic finding of junctional EB is a subepidermal split containing a few inflammatory cells. It is highly unusual for eosinophils to be seen in JEB, as in our case 7 The current standard treatment for patients with JEB includes palliation of cutaneous disease manifestations with careful lancing of blisters, judicious wound care, infection management, and pain control as well as supportive care for systemic manifestations. 8 To avoid secondary complications, clinicians should pay attention to fluid and electrolyte balance in severely affected infants along with nutrition, supplementary vitamins, and other microelements such as zinc.…”

“…It is hypothesized that eosinophilic infiltrates in JEB may be due to excessive eosinophil chemotactic factors or nonspecific injury to the skin of neonates. 7,11,12 We rapidly performed WES analysis because there were 3 siblings in the family who had died with similar findings. Unfortunately, this patient also died in his home country when he was 3 months old.…”

A heterozygous mutation in ITGB4 causing a mild phenotype of junctional epidermolysis bullosa

“…Inherited epidermolysis bullosa (EB) is a heterogeneous group of mechanobullous disorders resulting from pathogenic variants in genes coding for proteins within the cutaneous basement membrane zone. EB is further classified into EB simplex, JEB, dystrophic EB, and Kindler syndrome based on the ultrastructural level of blistering in affected tissues 1 . Mutations of ITGB4 gene, encoding the hemidesmosomal integrin β4 protein, important in maintaining the integrity of skin and epithelial linings, usually lead to JEB with pyloric atresia (JEB‐PA; OMIM # 226730).…”

“…EB is further classified into EB simplex, JEB, dystrophic EB, and Kindler syndrome based on the ultrastructural level of blistering in affected tissues. 1 Mutations of ITGB4 gene, encoding the hemidesmosomal integrin β4 protein, important in maintaining the integrity of skin and epithelial linings, usually lead to JEB with pyloric atresia (JEB-PA; OMIM # 226730). JEB-PA is a rare autosomal recessive inherited disease characterized by blistering of the skin and mucous membranes usually associated with congenital gastrointestinal abnormalities, resulting in high mortality.…”