Alopecia in Rhesus macaques correlates with immunophenotypic alterations in dermal inflammatory infiltrates consistent with hypersensitivity etiology

Abstract

Background: Although alopecia is a commonly recognized problem affecting many captive Rhesus macaque colonies, there is no consensus as to the underlying etiology or appropriate course of management.

Methods: We performed skin biopsies to assess underlying pathology in alopecic Rhesus macaques and performed immunohistochemical and metachromatic staining of these biopsies to assess the cellular infiltrates.

Results: Alopecia is associated with superficial dermal perivascular mononuclear cell infiltrates and skin pathology consistent with chronic hypersensitivity dermatitis. The inflammation is primarily composed of CD4+ cells admixed with histiocytes and mast cells. Inflammation is correlated with degree of alopecia. Further analysis in different groups of macaques revealed that animals born outdoors or infected with lung mites had reduced dermal inflammatory cell infiltrates and a lower incidence of alopecia.

Conclusions: These findings support a hypothesis that an altered housing status resulting in decreased pathogen burden in Rhesus macaque colonies may contribute to dermal immunophenotypic alterations and subsequent development of dermatitis with resultant alopecia.

Figure 1. Photomicrographs of normal, moderately affected, and severely affected lumbar skin from three Rhesus macaques

A) Normal skin with thin epidermis, scant perivascular mononuclear cell infiltrates and normal hair follicles. B) Skin from an animal with grade 3 alopecia showing acanthosis (*) with increased perivascular infiltrates (arrowhead) composed of predominantly lymphocytes, histiocytes, and mast cells. Numerous hair follicles are present. C) Skin from an animal with grade 5 alopecia showing acanthosis (*) with a marked perivascular infiltrate (arrowhead) composed of lymphocytes, mast cells, histiocytes and numerous eosinophils. Vessels are mildly distended and there is mild vascular stasis in the region. There is a reduction in the number of hair follicles in this section. H&E stained sections.

Figure 2. Phenotypic characterization of skin biopsies

Photomicrographs are from a macaque with normal skin (A and B) a macaque with moderate alopecia (C and D) and a Cynomolgus macaque (E and F) showing increased mast cells in the alopecic Rhesus macaque (C) compared with normal Rhesus and Cynomolgus skin (A and E) and increased CD3+ lymphocytes (D) compared with normal Rhesus and Cynomolgus skin (B and F). Top row, Toluidine blue staining mast cell granules purple and bottom row CD3 immunostain using avidin-biotin-peroxidase method with DAB counterstain.