Organs and Systems Cardiovascular

Heart rate, ventricular or supraventricular extra beats, and asymptomatic cardiac events were not significantly different during treatment compared with baseline in 20 patients receiving interferon gamma (6). Interferon gamma rarely produced cardiovascular adverse effects. Hypotension, dysrhythmias, and possible coronary spasm were sometimes observed, mostly in patients receiving high doses or with previous cardiovascular disorders (SEDA-20, 333) (SEDA-22, 405) (7,8).

Exacerbation of Raynaud's syndrome occurred in five of 20 patients with systemic sclerosis treated with interferon gamma (SEDA-20, 333).

Respiratory

Of 10 patients treated with interferon gamma-lb 200 micrograms three times a week for advanced idio-pathic pulmonary fibrosis, four developed irreversible acute respiratory failure (9). All four patients had increasing dyspnea, fever, and rapidly progressive hypoxemia, and had new alveolar opacities on lung imaging. The symptoms occurred shortly after interferon gamma had been started in three patients, and after 35 injections in the fourth. Three patients died from refractory hypoxemia and the fourth underwent lung transplantation, but died a few weeks later. Pathological examination in two patients showed diffuse alveolar damage with pre-existing interstitial pneumoni-tis. Interferon gamma was suspected, as no other cause of abrupt pulmonary deterioration was found. Although the number of patients was small, the authors noted that before interferon beta pulmonary function tended to be worse in the four patients who developed acute respiratory failure than in the other six.

Psychological, psychiatric

Neuropsychiatric disturbances have not been consistently found in patients receiving interferon gamma, despite electroencephalographic monitoring and psychometric tests (10). However, careful examination led to the impression that interferon gamma can cause neurophysio-logical changes similar to those of interferon alfa (11), and data from the manufacturers also point to rare cases of nervous system adverse effects in patients treated with high-dose interferon gamma (1).

Endocrine

Interferon gamma can increase serum Cortisol concentrations (12).

Metabolism

Reversible dose-dependent hypertriglyceridemia has been attributed to interferon gamma (13).

Hyperglycemia, reversible on interferon gamma withdrawal and a short course of insulin, has been reported in one patient (SEDA-22, 406).

Hematologic

Interferon gamma was supposedly the cause of asymptomatic non-immune hemolytic anemia in one patient receiving both interleukin-2 and interferon gamma (14).

Only minimal effects of interferon gamma on white blood cell counts have been observed (15).

Auto-immune thrombocytopenia occurred in a patient receiving interferon gamma (SEDA-22, 406).

Gastrointestinal

A convincing case of severe aphthous stomatitis has been reported in a patient receiving interferon gamma (SEDA-20, 333).

Urinary tract

Dose-related asymptomatic proteinuria was sometimes observed, and severe proteinuria with nephrotic syndrome has been reported once after low-dose interferon gamma (SED-13, 1100). Acute renal insufficiency is extremely rare (SEDA-20, 333) (16).

Skin

Induction of psoriatic lesions at the injection site has been observed in 10 of 42 patients treated with interferon gamma for psoriatic arthritis, while the joint symptoms were improved (17).

Single or multiple lesions of erythema nodosum lepro-sum occurred in 60% of patients given intradermal interferon gamma for lepromatous leprosy, and severe systemic symptoms required thalidomide treatment in two patients (18).

Severe erythroderma was observed in five of 10 patients after interferon gamma was added to ciclosporin for autologous bone marrow transplantation (19).

Immunologic

An anaphylactoid reaction and severe bronchospasm have been reported once after the first injection of interferon gamma (10).

Although interferon gamma is mainly used for its immu-noregulatory properties, the possibility of clinical immune adverse consequences has been addressed in a limited number of prospective studies. In two studies involving patients with chronic hepatitis B treated for 4-6 months, most developed a new autoantibody (20,21), but none developed clinical evidence of autoimmune disease. However, other reports suggested that interferon gamma can either improve or aggravate immune or inflammatory conditions. Although no change in antinuclear antibodies was reported in a trial of 54 patients with rheumatoid arthritis (22), increased or new antinuclear antibodies were observed in three of six patients with rheumatoid arthritis who received interferon gamma for 2-8 months, and two patients had clinical exacerbations of the disease (23). Isolated cases of systemic lupus erythematosus have been reported in patients receiving interferon gamma for rheumatoid arthritis (24,25). Rheumatoid or lupus-like symptoms associated with raised antinuclear antibodies titers were also noted in 17% of patients receiving interferon alfa and interferon gamma for myeloproliferative disorders, and in only 8.3% of patients treated with interferon alfa alone (26). Interferon gamma was also involved in the induction or reactivation of seronegative arthritis in patients with cutaneous psoriasis (27) and the unexpected exacerbation of multiple sclerosis in 39% of patients (28). Finally, neutralizing antibodies have exceptionally been found (SEDA-20, 333).

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