Immune-Mediated Complications during Interferon Therapy in Hematological Patients (2002)

Interferon (IFN), a leukocyte-derived cytokine, has been used to treat several hematological malignancies. The most common adverse effects of IFN are flu-like symptoms. Autoimmune side effects are infrequent but may be hazardous and irreversible. These may occur in several ways: autoantibodies may either appear during the treatment or existing titers may rise, subclinical autoimmune phenomena may become clinically manifest or autoimmune diseases may appear de novo. The main categories of IFN immune-mediated side effects are: thyroid, hematological, connective tissue, renal and miscellaneous disorders. The most common ones are thyroid disorders, which manifest either as hypo- or hyperthyroidism. Patients with pre-existing autoantibodies are more susceptible to the exacerbation of thyroid autoimmunity, probably since IFN enhances the levels of autoimmunity. Hematological disorders include autoimmune anemia and thrombocytopenia and thrombotic thrombocytopenic purpura. The immunological derangement of autoimmune hemolytic anemia manifests as enhanced destruction of antibody-coated red blood cells and induction of autoreactive B cells secreting these antibodies. Although autoimmune thrombocytopenia is rare, a sharp reduction in the platelet counts, beyond that expected from the antiproliferative effects of IFN, should raise this possibility. Thrombotic thrombocytopenic purpura has recently been included among the autoimmune disorders. Sporadic cases have been reported in association with IFN treatment. The clinical spectrum of IFN-induced connective tissue disorders ranges from typical systemic lupus erythematosus to seropositive or seronegative rheumatoid arthritis. Some authors also reported on the development of Behçet's disease in chronic myeloid leukemia patients treated with IFN. The underlying reason for the skin hyperreactivity in Behçet's disease and the effect of IFN treatment in these patients may be altered neutrophil activity in both disorders. Several series evaluated the incidence of Raynaud's phenomenon in patients treated with IFN for hematological disorders. Some of them reported on a rather high incidence of nailfold capillary microscopy abnormalities with or without Raynaud's phenomenon. Whether IFN-induced Raynaud's phenomenon is immune-mediated or directly caused vasospasm, is still unknown although the occurrence of several autoantibodies suggests an immune mechanism. Adverse effects of IFN therapy on the kidney include proteinuria and rarely nephrotic syndrome or acute and chronic renal failure. The mechanism of renal injury is unclear although an immune mechanism is suggested. Sporadic cases of other immune-mediated side effects have been published. These include dermatological adverse effects manifesting as psoriasis, pemphigus and vitiligo, and also rare cases of sarcoidosis, hepatitis, colitis or cryoglobulinemia. In conclusion, patients treated with IFN should be monitored for symptoms of autoimmunity. Patients with previous autoimmune phenomena should be treated, if possible, with alternative drugs since there is risk of exacerbation of these manifestations in these patients.