There are many protocols described in the literature for different immune-mediated diseases, but it is essential that the regimen should be individualized with consideration of the animal’s weight, body condition, previous exposure/response to glucocorticoids, severity of disease presentation and responsiveness once treatment has started. Three examples are provided here. It is vitally important that the diagnosis of immune-mediated disease is confirmed before undertaking any of these protocols.

PROTOCOL 1: Canine immune-mediated haemolytic anaemia (IMHA) and immune-mediated thrombocytopenia (ITP)

Induction:

Immunosuppression: Prednisolone 40 mg/m2(or 2 mg/kg if <15 kg) p.o. q24h, with or without:

• Azathioprine 2 mg/kg p.o. q24h or
• Ciclosporin 5 mg/kg p.o. q12h or
• Mycophenolate mofetil (MMF) 8–12 mg/kg p.o. q12h

See Appendix I for Safety and handling of chemotherapeutic agents.

There is no evidence to suggest that the addition of a second immunosuppressive agent from the onset of treatment will produce a better outcome, but it should be considered, particularly in:

• Dogs that experience or are expected to experience severe side effects with prednisolone treatment, so that the prednisolone dose may be decreased more rapidly
• Dogs with features of severe disease, such as marked hyperbilirubinaemia or continued transfusion dependence, because some dogs may not respond adequately to the first agent.

Dexamethasone (0.4 mg/kg i.v. q24h) may be substituted for prednisolone if the patient is unable to tolerate oral medications. Mycophenolate mofetil (7–10 mg/kg i.v. q12h) can be used intravenously if desired when oral medication is not tolerated, but preliminary data suggest this is unlikely to produce a faster onset of action. Once the patient can tolerate oral medications, substitute prednisolone for dexamethasone and switch to oral dosing of MMF if used (8–12 mg/kg p.o. q12h) or, if preferred, azathioprine at the above doses. 

A single dose of vincristine (0.02 mg/kg i.v.) may be used in cases of ITP because it may increase platelet numbers, but the extent of its benefits is unclear. Dyserythropoiesis may be observed (on blood smears) in such cases but is clinically insignificant.

Antithrombotics: Clopidogrel (1–2 mg/kg p.o. q24h) is indicated for dogs with IMHA that have a platelet count above 30 × 109/l, with or without low molecular weight heparins (e.g. dalteparin at 150–175 IU/kg s.c. q8h) if there is clinical evidence of thromboembolic disease. Discontinue on remission (or once the prednisolone is discontinued). 

Antibiotics: Not required unless there is a documented infection or known risk of infection (e.g. previous endocarditis). Empirical treatment with doxycycline (10 mg/kg p.o. q24h) may be indicated pending tests for tick-borne diseases in dogs with a history of travel or known tick exposure.

Gastrointestinal protection: In general, not required. In cases with known or suspected GI bleeding (melaena, haematemesis), omeprazole (1 mg/kg p.o., i.v. q12h) offers effective suppression of gastric acid secretion. The practice of administering ranitidine, for example, to every animal receiving high doses of steroids is not necessary and likely ineffective.

Relapse and rescue

If a mild relapse (e.g. a fall in packed cell volume (PCV) of <5% without any clinical signs of anaemia) occurs following documented remission, this may be treated by reinstigating the drug dosages used at the last visit when the animal was in remission. Severe relapses should be treated by reinstigation of induction doses of all drugs used initially. If this is ineffective, or if rescue is to be attempted during the initial induction phase of treatment (due to progressive deterioration), then additional immunosuppressants may be added. In cases of poor disease control, three immunosuppressive drugs may be used concurrently, but this carries a risk of opportunistic (fungal) infections. Note that azathioprine and MMF should not be administered concurrently in the same patient.

An infusion of human immunoglobulin (0.5–1.0 g/kg i.v. over 6–8 hours) may be administered in dogs not responding to other forms of treatment, but clinical benefit has not been proven.

In the non-acute setting, or if long-term control is necessary in a patient that has previously failed all other orally administered drugs, then leflunomide (2 mg/kg p.o. q24h) or splenectomy (if it can be tolerated by the patient) should be considered.

Decreasing doses:

Principles for dose reduction: Reduction of the prednisolone dose should be considered as soon as a clinical response is apparent (resolution of agglutination, spherocytosis, hyperbilirubinaemia/haemolysed plasma, and the PCV is stable or increasing); it is not necessary to wait until the PCV returns to a normal value. The prednisolone dose should be decreased by 25–33% every 2–3 weeks, depending on the severity of the side effects and whether the features of disease are well controlled. Expected overall duration of treatment is approximately 3–5 months provided there is no relapse.

UC = dose unchanged.

Notes: Complete blood count to be rechecked at each visit (including 4 and 8 weeks after cessation of therapy) and remission confirmed prior to each dose reduction. Liver parameters should be rechecked at remission and monthly if using azathioprine.

PROTOCOL 2: Feline immune-mediated haemolytic anaemia

Induction:

Immunosuppression: Prednisolone: 3–4 mg/kg p.o. q24h, with or without:

• Chlorambucil: >4 kg bodyweight, 2 mg p.o. q48h; <4 kg bodyweight, 2 mg p.o. q72h or
• Ciclosporin: 5 mg/kg p.o. q12h or
• Mycophenolic acid (MPA): 10 mg/kg p.o. q12h.

See Appendix I for Safety and handling of chemotherapeutic agents

If the patient is unable to tolerate oral medications, then dexamethasone (0.6–1.0 mg/kg i.v. q24h) may be substituted for prednisolone, and MMF (7–10 mg/kg i.v. q12h) may be substituted for MPA. Note that azathioprine should not be used in cats.

Antithrombotics: Avoid in cats as there is no evidence of a risk of thrombosis in cats with IMHA, but there is a risk of side effects.

Antibiotics: Not required unless there is a documented infection or known risk of infection (e.g. previous endocarditis) or known exposure to ticks. Empirical treatment with doxycycline (10 mg/kg p.o. q24h) may be indicated pending tests for Mycoplasma spp.

Gastrointestinal protection: Not required unless GI bleeding has been diagnosed, in which case effective suppression of gastric acid production is required. Current evidence suggests that only famotidine (1 mg/kg p.o. q12h) or omeprazole (1 mg/kg p.o., i.v. q12h) will provide this. The practice of administering ranitidine, for example, to every animal receiving high doses of steroids is not necessary and likely ineffective.

Relapse and rescue

See Protocol 1, above, for details.

Decreasing doses

See Protocol 1, above, for details.

(NB: reports of feline ITP are too rare to provide a protocol for treatment, but it is likely that a similar approach should be adopted.)

PROTOCOL 3: Steroid-responsive meningitis–arteritis (SRMA)

Induction:

Immunosuppression: Prednisolone: 2 mg/kg p.o. q24h (as a single dose or divided) for 7–14 days. Dexamethasone (0.4 mg/kg i.v. q24h) may be substituted for prednisolone for the first 2 days if the patient is unable to tolerate oral medications.

Antibiotics: Not required unless there is a documented infection, known risk of infection (e.g. previous endocarditis) or known exposure to ticks.

Gastrointestinal protection: In general, not required.

Remission: If remission is achieved, 1 mg/kg p.o. q24h for 6 weeks, followed by 0.5 mg/kg p.o. q24h for 6 weeks, followed by 0.5 mg/kg p.o. q48h for 6 weeks, followed by 0.5 mg/kg p.o. q72h for 6 weeks, then stop.

Relapse: In the event of a relapse during or after completion of the protocol (or if remission is not achieved), 2 mg/kg p.o. q24h can be reinstigated (or continued if remission not achieved) for a further 2 weeks and then continued as the 24-week remission protocol.

Adapted from Lowrie M, Penderis J, McLaughlin M, Eckersall PD and Anderson TJ (2009) Steroid-responsive meningitis–arteritis: a prospective study of potential disease markers, prednisolone treatment, and long-term outcome in 20 dogs (2006–2008).Journal of Veterinary Internal Medicine 23, 862–870