Treatment of exfoliative cutaneous lupus erythematosus in a German shorthaired pointer dog with mycophenolate mofetil

Abstract

Background Immune‐modulating drugs show limited therapeutic efficacy in canine exfoliative cutaneous lupus erythematosus (ECLE); over half of ECLE dogs are eventually euthanized for their lack of response to therapy. Objective To describe a case of generalized ECLE in a dog in which mycophenolate mofetil (MMF) treatment achieved complete remission. Animal A 3‐year‐old, male castrated German shorthaired pointer was presented with a three months history of generalized scaling, erythematous macules and plaques, follicular casts and hypotrichosis affecting the head, trunk, ventrum and medial aspects of all limbs. The dog exhibited lameness and stiff gait. Methods and materials Complete blood count, serum chemistry profile, urinalysis, serum antinuclear antibody test, histopathological examination and RT‐qPCR of skin biopsies. Results Histologically, skin biopsy specimens revealed lymphocyte‐rich interface dermatitis, infundibular interface mural folliculitis and periglandular lymphocytic infiltrate. The absence of systemic signs and unremarkable laboratory tests excluded concurrent systemic lupus erythematosus. Treatment of ECLE was initiated with oral MMF (22 mg/kg, twice daily). Within three weeks of starting MMF therapy, a marked improvement in lameness and a moderate decrease in erythema and scaling was observed. After four months, erythema, scaling and follicular casts had completely resolved, and at the time of writing the dog's ECLE remains in complete remission with twice daily MMF (10 mg/kg). The lesional skin transcriptome revealed predominant T helper 1 (Th1) lymphocytic inflammatory response with strong upregulation of interferon pathway. Conclusions and clinical importance To the best of the authors’ knowledge, this is the first reported case of successful treatment of ECLE with MMF as a single‐agent therapy.

Pharmacokinetics of mycophenolate mofetil following single-dose intravenous and single- and multiple-dose oral administration and clinicopathologic effects of mycophenolate mofetil following long-term oral administration in healthy horses

“…Long-term administration of MMF to humans and dogs is commonplace 12,13,25,27,28 ; therefore, the pharmacokinetics of MMF following multiple-dose PO administration in horses was investigated to assess the potential for bioaccumulation and nonlinear elimination. The multiple-dose PO protocol of 5 mg/kg once daily for 30 days followed by once every 48 hours for 30 days was based on the protocol used in a previous study 22 of the pharmacokinetics of azathioprine in horses.…”

“…Although MMF was originally developed to suppress organ rejection in hu- man transplant recipients, more recently it has been used as a treatment for immune-mediated diseases in people and (as the oral form) small animals. [11][12][13][14][15][16] Safety studies of cats [17][18][19] and pharmacokinetic and pharmacodynamic studies 20,21 of dogs have provided evidence of the safety (although not necessarily the efficacy) of MMF administered at a dose of 10 mg/kg twice daily in cats and a dose of 8 to 15 mg/kg twice daily in dogs. Adverse effects of MMF treatment generally involve the gastrointestinal tract (eg, vomiting and diarrhea).…”

“…Adverse effects of MMF treatment generally involve the gastrointestinal tract (eg, vomiting and diarrhea). 12,13,19 The objective of the study reported here was to characterize the pharmacokinetics of MMF following single-dose IV or PO administration, characterize the pharmacokinetics of MMF following multiple-dose PO administration, and describe the clinicopathologic effects of long-term PO MMF administration in horses.…”

Successful Treatment of Mucocutaneous Lupus Erythematosus in a Dog with Prednisolone, Mycophenolate Mofetil and Tacrolimus

“…For long-term treatment, tetracycline/niacinamide may be beneficial; however, it is necessary to evaluate the efficacy of topical or other systemic immunosuppressive drugs. Mycophenolate mofetil (MMF) has been used for several years in veterinary medicine to treat immune-mediated inflammatory diseases, especially immune-mediated haemolytic anaemia, and its effects have also been reported in various skin diseases, including pemphigus foliaceus, vasculitis, subepidermal bullous disease, exfoliative cutaneous lupus erythematosus (ECLE) and vesicular cutaneous lupus erythematosus (VCLE) [ 5 , 6 , 7 , 8 ]. When compared with other adjunct immunosuppressive agents, MMF exhibits a rapid onset of action and tolerable side effects, based on which it can be suggested as a steroid-sparing agent for treating dogs with autoimmune or immune-mediated skin diseases [ 5 , 7 ].…”

A Missense Variant Affecting the C-Terminal Tail of UNC93B1 in Dogs with Exfoliative Cutaneous Lupus Erythematosus (ECLE)

“…In later stages, ECLE often additionally affects the joints with severe pain, but a progression to classic antinuclear antibody-positive SLE is usually not seen [4,[16][17][18]. The treatment of ECLE-affected dogs with immunomodulatory drugs often is insufficient to achieve long-lasting control of the disease, leading to a guarded prognosis [18,19]. Dogs affected with ECLE often are euthanized due to the severity of their disease.…”