The severe itching and papular rash of a primary ordinary scabies infestation have skin lesions characterized by inflammatory cell infiltrates typical of a delayed sensitivity cell-mediated Regorafenib supplier immune reaction. Histopathological examination of skin biopsies from scabietic lesions reveals mite burrows surrounded by inflammatory
cell infiltrates comprising eosinophils, lymphocytes and macrophages. Predominantly, CD4+ T cells are observed to dominate the lymphocytic infiltrate of inflammatory skin lesions in ordinary scabies, with a reported CD4/CD8 ratio of 4 : 1 (68). However, biopsy specimens containing both mites and inflammatory papules were observed to also contain IgE deposits in vessel walls in the upper dermis, suggesting the occurrence of Type 1 hypersensitivity VX-809 nmr reactions in some cases (68). In contrast, immunohistology studies on patients with crusted scabies suggest the inflammatory skin response is comprised of predominantly CD8+ T cells (4). Microscopy showed the strong presence of T cells (anti-CD45+, anti CD43+), but interestingly no evidence of any B cells (CD20), and only the occasional macrophage
was evident. A predomination of infiltrating CD8 T lymphocytes in the dermis was observed. The proportions of T and B lymphocytes and T-cell subsets in the blood of these patients were within normal ranges, indicating a selective movement of CD8 T cells into the dermis. Activated CD8+ T cells in crusted scabies lesions may induce dysregulated keratinocyte apoptosis contributing to the elicitation and progress of epidermal hyperproliferation. This is comparative with psoriasis in which a pronounced CD8+ epidermotropism into the epidermis and dermis has been observed (69). These results suggest skin-homing cytotoxic T cells contribute to an imbalanced inflammatory
response in the dermis of crusted scabies lesional skin and may add to the failure of the skin immune system to mount an effective response resulting in uncontrolled growth of the parasite. Strong staining for the inflammatory cytokine IL-1β and anti-inflammatory cytokine TGF-β was also OSBPL9 observed in crusted scabies skin lesions. The observation of the anti-inflammatory cytokine TGFβ suggests some immune regulation occurring in CS lesional skin as TGFβ is a known immunosuppressive cytokine produced by monocytes and T cells that inhibits cell growth and induces IgA secretion (70). The clinical picture of psoriasis is somewhat similar to crusted scabies and is characterized with erythematous scaly papules and plaque formation as a result of abnormal keratinocyte hyperproliferation and infiltration of inflammatory cells into the epidermis and dermis. Data suggests psoriasis is induced and maintained by a complex pattern of overexpressed Th1 cytokines such as IL-2, IL-6, IL-8, or IFN-γ and TNF-α (71).