Subcorneal pustular dermatosis an immnohisto-pathological perspective

Abstract

Subcorneal pustular dermatosis (SPD) represents a chronic, relapsing sterile pustular eruption, involving the trunk and flexoral proximal extremities. A 54-year-old female presented with recurrent, flaccid pustules measuring several millimeters in diameter, on normal and mildly erythematous skin of the groin and submammary areas. Biopsies for hematoxylin and eosin (H&E) examination, direct immunofluorescence (DIF) and immunohistochemistry (IHC) analysis were performed. The H&E staining demonstrated typical features of SPD, including some damage within dermal pilosebaceous units subjacent to the subcorneal blistering process. DIF revealed strong deposits of immunoreactants IgG, IgM, fibrinogen and complement/C3, present in a shaggy pattern within the subcorneal disease areas; in focal, areas of the basement membrane junction and in focal pericytoplasmic areas of epidermal keratinocytes. IHC revealed strong positivity to HLA-DPDQDR, mast cell tryptase, CD68, and ZAP-70 in the subcorneal inflammatory infiltrate, and surrounding dermal blood vessels. Myeloperoxidase was also positive. Positive staining with the anti-ribosomal protein S6-pS240 at the edges of hair follicles and sebaceous glands subjacent to the subcorneal blisters was also noted.

Conclusions: We conclude that this disorder may have several components in its etiopathology, including a possible restricted immune response and a possible genetic component; these possibilities warrant further investigation.

Keywords: HLA-DPDQDR; Subcorneal pustular dermatosis; ZAP-70; anti-ribosomal protein S6-pS240; mast cell tryptase.

Figure 1

a. A group of clinical pustules near the axilla (black arrow). b. H & E stain, showing a subcorneal accumulation of neutrophils (blue arrow), within a subcorneal blister (black arrow). c. DIF showing localized deposits of FITC conjugated anti-human fibrinogen in multiple foci, including within a subcorneal blister (green staining; white arrow), within a dermal papillary tip (green staining; red arrow) and around upper dermal vessels (green staining; black arrow). Epidermal keratinocyte nuclei of are highlighted with 4',6-diamidino-2-phenylindole (Dapi) in blue d. Utilizing DIF and FITC conjugated fibrinogen in isolation, we were able to detect an identical reactivity pattern as observed in c (red arrows). e. IHC with anti-human fibrinogen antibody that corroborates our DIF findings of fibrinogen in a subcorneal blister (red arrow), within a dermal papillary tip (purple arrow) and around upper dermal blood vessels (black arrow). f. DIF showing staining between epidermal keratinocytes utilizing FITC conjugated anti-human IgG. The staining pattern resembles the intercellular staining pattern of pemphigus; however, the staining pattern observed in our patient appears more pericytoplasmic, and predominates in upper layers of the epidermis (white arrow). g. Similar to f, at higher magnification(white arrow) with epidermal keratinocyte nuclei counterstained with DAPI (light blue staining), h, i. Show similar DIF staining as f and g, but using FITC conjugated anti-human albumin. Please note enhanced staining in areas close to the epidermal corneal layer (red arrows). j and k, Show similar DIF staining as f and g, but using FITC conjugated anti-human-IgA. Please note enhanced staining in areas close to the epidermal corneal layer and the blister red arrows). l. Positive IHC staining with anti-human IgA within a subcorneal blister, and at multiple foci within the dermal extracellular matrix (brown staining, red arrows). m and n, IHCs demonstrating positive staining within a subcorneal blister and around upper dermal blood vessels with IgE in m, and with IgM in n (brown staining; red arrows). o. IHC, demonstrating strongly positive mast cell tryptase staining around the upper dermal blood vessels (brown staining). p, Strong IHC staining with anti-ribosomal protein S6-pS240.