Autoimmune lymphoproliferative syndrome in Boerboel dogs: treatment, clinical outcomes and prevention.

Abstract

BACKGROUND: Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder caused by defective Fas cell surface death receptor-mediated lymphocyte apoptosis, resulting in chronic lymphadenomegaly, splenomegaly, and autoimmune cytopenias. Management of ALPS in dogs has not been reported previously. HYPOTHESIS/OBJECTIVES: Describe treatment, therapeutic drug monitoring (TDM), and clinical and laboratory outcomes in Boerboel dogs with genetically confirmed ALPS. ANIMALS: Four affected Boerboel pups from a litter studied prospectively and 2 retrospectively identified littermates from a different litter. METHODS: Prospective case series. All 4 index puppies received prednisolone and proprietary sirolimus; 3 subsequently received generic sirolimus. Clinical response was assessed through physical examinations, CBCs, serum biochemistry profiles, and TDM. Two additional affected dogs were reviewed retrospectively. RESULTS: Initiation of proprietary sirolimus in the index litter was associated with resolution or near resolution of lymphadenomegaly and abdominal distension, improvement in hematologic variables, and decreased corticosteroid requirements. Gastrointestinal signs improved but recurred intermittently in pups 1 and 4. By 10 months of age, pups 2 and 3 achieved sustained, marked clinical improvement. Notably, pup 2 had all drugs discontinued and remained clinically well. A fourteen-month follow-up showed sustained overall clinical improvement in the index litter. CONCLUSIONS AND CLINICAL IMPORTANCE: Autoimmune lymphoproliferative syndrome can cause clinically relevant morbidity in dogs. Sirolimus, alone or with prednisolone, appeared effective and well tolerated, decreasing corticosteroid requirements and adverse effects. Genetic screening and management with sirolimus focused on patient comfort were beneficial. Clinical signs appeared to improve with age in some individuals, suggesting that de-escalation or discontinuation of treatment may be possible in selected cases.