Systemic Immune-Mediated Diseases

Chapter 24 Systemic Immune-Mediated Diseases

Immune-mediated diseases may affect multiple body systems; for example, polyarthritis may be associated with thrombocytopenia or proteinuria. A CBC, platelet count, chemical profile and urinalysis are considered the minimum database for any suspected immune-mediated disease. The diagnosis of “idiopathic immune-mediated disease” remains a diagnosis of exclusion. Infectious/parasitic, neoplastic, and toxic causes must always be excluded with appropriate testing and/or therapeutic trials.

Since many immune-mediated diseases are treated similarly, this chapter begins with a general discussion of treatment and commonly used drugs. This is followed by a discussion of immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, and systemic lupus erythematosus.

TREATMENT OF IMMUNE-MEDIATED DISEASES

Corticosteroids

Corticosteroids are effective immunosuppressive agents. Many animals tolerate their administration with only mild side effects, or the disease goes into remission and the corticosteroid treatment may be stopped. For many animals with immune-mediated disease, single agent therapy with corticosteroids is adequate.

• Prednisone is always included initially in immunosuppressive protocols. The dosage is approximately 2.2 mg/kg once daily in most cases; however 1 mg/kg/day may be used in less severe diseases. The dose may be divided into twice daily administration, but there is no obvious benefit from the division. Some dogs are intolerant to prednisone and will develop side effects (polyuria, polydipsia, polyphagia, panting, and/or lethargy) that are unacceptable to the owner.

Therapy with an equipotent dose of a different steroid (prednisolone, methylprednisolone, triamcinolone, or dexamethasone) often resolves unacceptable side effects of prednisone (Table 24-1).

Table 24-1 INITIAL IMMUNOSUPPRESSIVE DOSES OF CORTICOSTEROID AND THEIR AVAILABLE STRENGTHS IN THE UNITED STATES

Some cats do not effectively respond to prednisone. These cats may be “poor converters” that cannot metabolize inactive prednisone to the active form, prednisolone. Thus, when cats don’t respond well to prednisone, try using an alternate steroid (see Table 24-1).

• Corticosteroids are generally administered at full doses until the disease is in complete remission. Complete remission may be defined as resolution of signs of disease along with radiographic or laboratory changes that were initially present. After remission is attained the dose is cut, generally in half, for 4 weeks. Reevaluation is then performed, and if signs of disease are absent (on physical or laboratory data), the dose is again halved. This protocol is followed monthly until the animal either relapses or stops medication.

The minimum duration of therapy for any immune-mediated disease is 6 months.

• Many patients will experience a relapse as the dose is tapered. Relapse is treated with return to full dose administration, again with monthly tapering, but as the dose is approached that previously allowed relapse, the dosage may then either be held constant or tapered more slowly. If signs of relapse are mild, the dose may instead be increased to the most recently effective dose and held there for a few months before it is tapered again.

Combination Immunosuppression Therapy

Combination immunosuppression therapy is very useful, because the addition of another agent may allow a lower dose of corticosteroid to be used (prednisone-sparing effect). Additional medications may also increase the strength of immunosuppression because they work by different mechanisms. The drug most frequently used in combination with corticosteroids in dogs is azathioprine.

Combination immunosuppressive therapy is often more effective and has less side effects than prednisone therapy alone.

Azathioprine

• Azathioprine (Imuran) is administered orally. Adverse side effects are infrequent in dogs. The dose is approximately 2.2 mg/kg once daily until remission occurs, then the same dose is administered every other day.

• A potential side effect is bone marrow suppression, and a complete blood count (CBC) should be evaluated after 7 days, and then every 2 weeks while the patient is receiving daily treatment. Once the patient is receiving every other day therapy, a CBC should be evaluated every 3 months, but bone marrow suppression is unusual at this dose.

• Prednisone and azathioprine are frequently used in combination. The drugs are administered together once daily and then tapered after remission is attained. The method of tapering is somewhat arbitrary; if signs of prednisone intolerance are experienced then the prednisone is tapered first; if bone marrow disease is encountered the azathioprine should be tapered or discontinued first. If the disease was difficult to get into remission then only one drug should be tapered at a time; if the disease easily went into remission, then both drugs may be tapered concurrently. Tapering should be performed every 4 weeks, with the minimum duration of therapy being 6 months. It is important to have a therapeutic plan to follow. Notations in the medical record should include the intended date of recheck, with the tests to be performed and the expected decrease of dose if tests return results within normal limits. Relapse is treated with the administration of full dosage of both medications with gradual taper to the lowest effective dose. As the dose that allowed relapse is approached, the dosage may then either be held constant or tapered more slowly.

• Cats often develop life-threatening neutropenia with the use of azathioprine, and its use in this species is not recommended. Instead, the use of chlorambucil is recommended for cats that require immunosuppression in addition to prednisolone.

Chlorambucil

• Chlorambucil (Leukeran) is an oral drug, used in cats at 15 mg/m² (4 mg total dose for most cats) once daily for 4 days, repeated every 3 weeks.

• Potential side effects include anorexia and bone marrow suppression. A CBC should be evaluated 5 to 7 days after the last dose. If after two or more evaluations the CBC remains normal (no leukopenia), further monitoring may not be necessary. If leukopenia is detected (absolute neutrophil count < 3,000/μl), the dose of the next administration should be decreased by 25%. Signs of infection (loss of appetite along with fever) during the expected white blood cell count (WBC) nadir (3–10 days after administration) should be aggressively treated. Physical examination, CBC, and treatment with amoxicillin and enrofloxacin are indicated if severe neutropenia (<1,000/μl) and fever are present.

• In cats, the dosage of chlorambucil should be tapered before the dose of prednisolone is tapered.

Monitoring of Immunosuppressive Therapy

Side effects of immunosuppressive medications often lead to significant morbidity; treatment of any immune-mediated disease involves balancing the control of disease against the side effects of immunosuppressive therapeutics. Obesity related to prednisone is very common, and owners should be specifically counseled about its prevention. Body weight should be recorded and weight management discussed at each recheck. Long-term immunosuppressive therapy may also allow the development of asymptomatic infection, especially in the urinary system. Urine culture is recommended every 3 to 4 months regardless of the absence of clinical signs.

Many patients are euthanized due to side effects of prednisone. Strategies to decrease prednisone-induced side effects include: avoidance of obesity, exchanging equipotent doses of an alternate steroid, use of additional immunosuppressive agents, and routinely scheduled monitoring.

IMMUNE-MEDIATED HEMOLYTIC ANEMIA

The diagnosis of immune-mediated hemolytic anemia (IMHA) is suspected upon discovering severe anemia in the presence of normal serum protein levels (Figure 24-1). IMHA may be classified as regenerative or non-regenerative with red cell destruction in the bone marrow prior to the release of reticulocytes. Red cell destruction may be mild (low grade) or rapidly progressive.

Figure 24-1 Classification of anemia. PCV, packed cell volume; IMHA, immune-mediated hemolytic anemia.

Etiology

• Specific causes of IMHA are not known. However, genetic factors may play a role and certain breeds, such as cocker spaniels, poodles, and old English sheep dogs, show higher incidence of IMHA. Initiating events, such as vaccination, stress, or infectious agents can trigger IMHA in patients with the appropriate predisposing genes.

• In animals presenting with hemolytic anemia, IMHA must be differentiated from other causes of hemolytic anemia, both in dogs (Table 24-2) and in cats (Table 24-3). These are described in Chapter 22.

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Tags: Saunders Manual of Small Animal Practice

Aug 27, 2016 | Posted by admin in SMALL ANIMAL | Comments Off

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