New insights into disease pathogenesis in crusted (Norwegian) scabies: the skin immune response in crusted scabies

• Published in: British journal of dermatology (1951) Vol. 158; no. 6; pp. 1247 - 1255
• Main Authors: Walton, S.F., Beroukas, D., Roberts-Thomson, P., Currie, B.J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2008; Blackwell
• Subjects: Adult; Animals; B-Lymphocytes - immunology; Biological and medical sciences; CD4-CD8 Ratio; Dermatology; Disease Progression; Female; General aspects; Human parasitic diseases due to arthropods; Humans; immune markers; Immunity, Cellular; Immunoglobulin E - immunology; Immunohistochemistry - methods; Infectious diseases; inflammatory skin disease; Male; Medical sciences; Parasitic diseases; parasitic skin diseases; Sarcoptes scabiei; scabies; Scabies - immunology; Scabies - pathology; Skin - immunology; Skin - parasitology; Skin - pathology; T-Lymphocytes - immunology; T-Lymphocytes, Helper-Inducer - immunology; Transforming Growth Factor beta - immunology; Skin disease; Immune response; parasitic skin diseases; Dermatology; Pathogenesis; inflammatory skin disease; scabies; Parasitosis; Marker; Inflammatory disease; Infection; immune markers; Skin; Norwegian scabies
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/j.1365-2133.2008.08541.x

Summary Background  Crusted scabies is a rare and severely debilitating disease characterized by infestation of the skin with up to millions of Sarcoptes scabiei mites, high total IgG levels, extremely high total IgE levels, and the development of hyperkeratotic skin crusts that may be loose, scaly and flaky or thick and adherent. Objectives  To describe crusted scabies skin pathogenesis and identify markers associated with an inappropriate immune response leading to disease progression. Patients/methods  Serial sections from skin biopsies obtained from two patients with severe crusted scabies were examined by immunohistochemistry for cell surface markers and inflammatory and regulatory cytokines. Concurrent levels of total B‐ and T‐cell subsets and IgE, IgA, IgM, IgG and IgG subclasses were analysed in the blood. In addition antibody levels were recorded in a further 33 patients with crusted scabies and 14 patients with ordinary scabies. Results  A predomination of infiltrating CD8+ T lymphocytes in the dermis was observed compared with minimal helper T lymphocytes (CD4+) and the absence of any B cells. The proportion 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. Furthermore, strong staining for the inflammatory cytokine interleukin‐1β and anti‐inflammatory cytokine transforming growth factor‐β1 was observed. Elevated levels of IgE, IgG, IgG1, IgG3 and IgG4 were recorded. Conclusions  Skin‐homing cytotoxic T cells contribute to an imbalanced inflammatory response in the dermis of crusted scabies lesional skin. This, in combination with the lack of B cells, is contributing to the failure of the skin immune system to mount an effective response resulting in uncontrolled growth of the parasite.