Evaluation of inflammatory infiltrate and fibrogenic cytokines in pseudopelade of Brocq suggests the involvement of T-helper 2 and 3 cytokines

Abstract

Pseudopelade of Brocq (PB) is an acquired progressive cicatricial alopecia which is characterized by some distinctive clinical features. It may represent either a distinct entity, i.e. an idiopathic primary scarring alopecia, or the end stage of various forms of scarring alopecia such as discoid lupus erythematosus (DLE) or lichen planopilaris (LPP). The aim of the study was to evaluate a set of patients with a clinically defined PB, to ascertain whether their PB was idiopathic or secondary, and then to study the phenotype of the inflammatory infiltrate and the presence of any fibrogenic and antifibrogenic cytokines to identify idiopathic or secondary forms in more detail. Twelve female patients with PB were studied by means of histology, direct immunofluorescence (DIF) and immunohistochemistry, by using monoclonal antibodies to cell markers (lymphocyte subtypes, Langerhans cells, macrophages, fibroblasts, mastocytes and activation markers) and fibrogenic and antifibrogenic cytokines. Using histology and DIF, we diagnosed two cases as DLE and three cases as LPP. Seven cases had nonspecific histology or DIF appearances and were classified as noncharacterized pseudopelade (NCPB). Two major phenotypic patterns of dermal infiltrate were identified by immunohistochemistry. These were: (i) a conspicuous infiltrate of CD3+ cells with a high CD4+/CD8+ ratio, variable numbers of macrophages, mast cells and fibroblasts always fewer than lymphocytes; (ii) an infiltrate of CD3+ cells with variable CD4+/CD8+ ratio and conspicuous amounts of macrophages, mast cells and fibroblasts, more numerous than infiltrating lymphocytes. The first pattern was typical of DLE and LPP, the second one was typical of NCPB. Fibrogenic cytokines were observed in all cases, but basic fibroblastic growth factor (bFGF) and transforming growth factor (TGF)-beta were more strongly expressed in NCPB. Interferon (IFN)-gamma was found in LPP. In our PB patients we identified five of 12 secondary PB and seven of 12 idiopathic PB by means of histology and DIF. The phenotypic pattern of infiltration allowed us to further differentiate secondary (richer in lymphocytes) from idiopathic PB (richer in resident cells). The pattern of cytokine expression showed the presence of fibrogenic molecules (interleukins 4 and 6, bFGF and TGF-beta) in all cases, suggesting the involvement of mechanisms mediated by T-helper 2 and 3 cytokines in PB.