Some acquired or transitory immunodeficiency conditions can be managed with antibiotic and supportive therapy during the period of disease susceptibility. In contrast, primary immunodeficiencies can markedly affect immune response irreversibly, and prognosis for life is guarded.

Within the humoral immunodeficiencies described, CVID is a condition that may require more prolonged patient care because of its progressive nature. Initially, prolonged parenteral antibiotic therapy seems to control infection and improve the clinical condition of non-hospitalized or hospitalized horse patients, but clinical signs tend to reoccur with time or when antibiotic therapy is discontinued. Horses with CVID should be monitored closely for signs of infection, so antibiotic therapy can be initiated immediately. Routine blood work to measure neutrophil and lymphocyte counts, and fibrinogen levels help to detect subtle infections or monitor response to treatment. Serum IgG and IgA concentrations monitored every 3 months indicate changes that reflect progression of the disease and, therefore, increased susceptibility to infections. In case of inadequate response to antibiotic therapy, infections with intracellular pathogens or fungal organisms should be investigated. Depression or neurologic signs may reflect bacteremia and meningitis; in these cases, blood culture and spinal fluid analysis can be used to confirm the diagnosis.

Periodic intravenous or subcutaneous plasma therapy to maintain serum IgG concentrations around 500 mg/dL is impractical and expensive for the adult horse, and there is no purified formula of equine IgG for continued clinical use. Euthanasia is often elected by the owner due to clinical complications of pneumonia and/or meningitis.

Minimizing stress to prevent secondary immunodeficiency is advised. More frequent deworming may be necessary to control gastro-intestinal parasites. The use of immunosuppressive drugs (e.g. corticosteroids) is contraindicated to preserve cellular immunity. Regular vaccination with inactivated vaccines is warranted; even though a humoral response may not be elicited, many vaccines promote a cellular immune response. Indeed, despite the fact that horses with CVID do not respond with immunoglobulin production to tetanus toxoid vaccination, tetanus has not been diagnosed in these patients. Vaccination of affected horses with modified-live vaccines is not advised, since some vaccines may pose risk of vaccine-organism replication and virulence recovery in immunocompromised individuals.