Tacrolimus ointment: a novel and effective topical treatment of localized atopic dermatitis in a rhesus macaque (Macaca mulatta)

Abstract

An adult, male, rhesus macaque presented with pruritus and a focal, exudative, inflamed, erythematous skin lesion of approximately 2 cm in diameter on the ventral aspect of the mandible. The lesion resolved after 10 d of treatment with 1% chlorhexidine solution and triple-antibiotic ointment. However, the skin lesion subsequently recurred several times over a 2-mo period. A punch biopsy was performed, and histological changes were most consistent with a diagnosis of atopic dermatitis. Treatment with topical tacrolimus ointment, an immunosuppressive drug, proved successful in the resolution of all clinical signs after 4 mo. According to a literature review, this article is the first report of the use of tacrolimus ointment as a topical treatment of atopic dermatitis in a rhesus macaque.

Figure 1.

Adult male rhesus macaque with focal, exudative, erythematous, raised skin lesion of approximately 2 cm in diameter in the sparsely haired skin near the ventral mandibular symphysis under the chin. Alopecia, scaling, lichenification, and exfoliation are present at the papule site and its immediate surroundings.

Figure 2.

Biopsy of the skin lesion from the sparsely haired-skin of the ventral mandible from the rhesus macaque from Figure 1. (A) Diffuse acanthosis of the epidermis. Hematoxylin and eosin stain; bar, 200 μm. (B) Moderate superficial dermal fibrosis and moderate thickening of the walls of superficial dermal vessels. Hematoxylin and eosin stain; bar, 50 μm. (C) Moderate numbers of mast cells (arrows) are noted with a diffuse superficial dermal distribution. Toluidine blue stain; bar, 25 μm.

Figure 3.

Clinical course of the atopic dermatitis case.

Figure 4.

Mechanism of action of tacrolimus. In the cytoplasm, tacrolimus (T) binds to tacrolimus-binding protein (TBP), forming a tacrolimus–TBP complex, which binds to and blocks calcineurin (CaN). The T–TBP–CaN complex inhibits the activation of the nuclear factor of activated T cells (NF-ATc), thus preventing the entry of NF-ATc into the nucleus. Unable to bind to its nuclear component (NF-ATn), NF-ATc cannot bind to the promoter of the IL2 gene and initiate IL-2 production. T cells therefore will not produce IL2, which is necessary for full T-cell activation. (Modified from reference 28).