Interferons systemic lupus erythematosus

Ronnblom, L.E., Aim, G.V., and Oberg, K.E., Possible induction of systemic lupus erythematosus by interferon-alpha treatment in a patient with a malignant carcinoid tumor, J Intern Med., 227, 207,1990. 

Crow, M.K. and Kirou, K.A., Interferon-alpha in systemic lupus erythematosus, Cum. Opin. Rheumatol., 16, 541, 2004. 

Autoimmune disorders Development or exacerbation of autoimmune disorders, including myositis, hepatitis, idiopathic thrombocytopenic purpura, psoriasis, rheumatoid arthritis, interstitial nephritis, thyroiditis, and systemic lupus erythematosus have been reported in patients receiving alpha interferon. 

Ozmen L, Roman D, Fountoualakis M, Schmid G, Ryffel B, Garotta G. Soluble interferon-gamma receptor a therapeutically useful drug for systemic lupus erythematosus. J Interferon Res 1994 14(5) 283-284. 

V3. Viallard, J. F., Pellegrin, J. L., Ranchin, V., Schaeverbeke, T., Dehais, J., Longy-Boursier, M., Ragnaud, J. M., Leng. B., and Moreau, J. F., Thl (IL-2, interferon-gamma (IFN-gamma)) and Th2 (IL-10, IL-4) cytokine production by peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE). Clin. Exp. Immunol. 115, 189-195... 

B11. Bengtsson, A. A., Sturfelt, G., Truedsson, L., Blomberg, J., Aim, G., etal., Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies. Lupus 9, 664-671 (2000). 

C6. Cederblad, B., Blomberg, S., Vallin, H., Perers, A., Aim, G. V., and Ronnblom, L., Patients with systemic lupus erythematosus have reduced numbers of circulating natural interferon-alpha-producing cells. J. Autoimmun. 11, 465-470 (1998). 

Y7. Ytterberg, S. R., and Schnitzer, T. J., Serum interferon levels in patients with systemic lupus erythematosus. Arthritis Rheum. 25, 401-406 (1982). 

Autoimmune diseases have been reported to be more frequent in human subjects treated with several recombinant cytokines [38], For instance, increased titers or the new occurrence of autoantibodies have been observed in hepatitis C patients treated with the recombinant interferons-alpha (IFNa). Quite a few clinical case reports describe the development of organ-specific as well as systemic autoimmune diseases including systemic lupus erythematosus, insulin-dependent type I diabetes mellitus, autoimmune thrombocytopenia, autoimmune hemolytic anemia, myasthenia gravis, and autoimmune thyroiditis in patients under IFNa therapy. Although the mechanism involved is not fully elucidated, the available data support the pathogenic potential of IFNa in autoimmunity [31]. In contrast, autoimmune effects associated with IFNp therapy are thought to be of lesser concern based on the current clinical evidence [38], Thyroid autoimmunity in contrast to other autoimmune diseases is frequent in patients treated with recombinant interleukin-2 (rIL-2). Thus, among 281 previously euthyroid cancer patients treated with rIL-2, up to 41%... 

Although the mechanism of this adverse effect was purely speculative, it was suggested that interferon alfa might have induced a reaction similar to the immunopathologi-cal mechanism involved in serositis associated with systemic lupus erythematosus. 

The possibility of autoimmune disorders during interferon alfa treatment has been addressed by many authors. The spectrum of interferon alfa-induced immune diseases includes organ-specific and systemic autoimmune diseases, such as thyroiditis, diabetes, hematological disorders, systemic lupus erythematosus, rheumatoid arthritis, dermatological disease, and myasthenia gravis (156). Several have been discussed in appropriate sections elsewhere in this monograph. The exact role of interferon alfa is usually difficult to ascertain, because the underlying disease, that is chronic hepatitis C, can also be associated with immune-mediated disease. 

Two studies have provided insights into the incidence and risk factors of the immune-mediated comphcations of interferon alfa in patients with chronic myeloid leukemia. In the first study, 13 of 46 patients had autoimmune manifestations consisting of a combination of autoimmune thyroiditis in four, a direct antiglobulin test without hemolysis in eight, cryoagglutinins in one, Raynaud s phenomenon in two, and chronic autoimmune hepatitis in one (343). Overall, six patients had chnically symptomatic manifestations after a median of 15 months of treatment. In the second study, there were autoimmune diseases in seven of 76 patients after a median of 19 months of treatment, including hypothyroidism in one, immune-mediated hemolysis in two, systemic lupus erythematosus in two, Raynaud s phenomenon in one, and mixed connective tissue disease in one (344). In... 

Systemic lupus erythematosus and rheumatoid arthritis The possible role of interferon alfa in the development of rheumatoid arthritis or systemic lupus erythematosus has been described in isolated cases (363,364), and confirmed cases of systemic lupus erythematosus have very occasionally been reported (SED-13, 1096) (SEDA-20, 330). In most of these cases, the predominance of young patients and female sex, the presence of renal or skin involvement, the findings of positive antibodies to double-stranded DNA, and the rapid onset after the start of treatment, as well as persistence of symptoms after interferon alfa withdrawal, are more in keeping with unmasking by interferon alfa of idiopathic lupus rather than with a new drug-induced illness. The reactivation or appearance of inflammatory rheumatological disorders consistent with rheumatoid arthritis or lupus-like polyarthritis were... 

There was an unexpectedly high incidence of rheumatoid and lupus-like symptoms (27 of 137 patients), namely arthralgia, arthritis, myalgia, and Raynaud s phenomenon, in patients with myeloproliferative disorders taking interferon alfa alone or combined with interferon gamma (365). However, only a minority of affected patients fulfilled the diagnostic criteria for systemic lupus erythematosus. By contrast, systemic autoimmune diseases appeared to be genuine but very rare complications of interferon alfa in chronic hepatitis C, with only one case of lupus-like syndrome and two cases of polyarthritis in a survey of 677 patients (18). 

Systemic lupus erythematosus has been reported in two patients given interferon alfa for chronic hepatitis C (363,368). However, it is not known whether this complication was coincidental or treatment-related. 

Fukuyama S, Kajiwara E, Suzuki N, Miyazaki N, Sadoshima S, Onoyama K. Systemic lupus erythematosus after alpha-interferon therapy for chronic hepatitis C a case report and review of the hterature. Am J Gastroenterol 2000 95(1) 310-12. 

Gramnger WB, Hassfeld W, Pesau BB, Machold KP, Ziehnski CC, Smolen JS. Induction of systemic lupus erythematosus by interferon-gamma in a patient with rheumatoid arthritis. J Rheumatol 1991 18(10) 1621-2. 

Machold KP, Smolen JS. Interferon-gamma induced exacerbation of systemic lupus erythematosus. J Rheumatol 1990 17(6) 831-2. 

Hagiwara E, Gourley MF, Lee S, Klinman DK. Disease severity in patients with systemic lupus erythematosus correlates with an increased ratio of interleukin-10 interferon-gamma-secreting cells in the peripheral blood. Arthritis Rheum 1996 39 379-85. 

Systemic lupus erythematosus Malignant disease hormone Acne therapy Isotretinoin Other Interferon-beta-1 a... 

Sigurdsson S, Nordmark G, Goring HH et al 2005 Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus. Am J... 

Kawasaki M, Fujishiro M, Yamaguchi A, Nozawa K, Kaneko H, Takasaki Y, Takamori K, Ogawa H, Sekigawa I. Possible role of the JAK/STAT pathways in the regulation of T cell-interferon related genes in systemic lupus erythematosus. Lupus. 

Abbott IJ, Chang CC, Skinner MJ, Street A, Perry G, McLean C, Wright EJ, Cameron PU. Development and management of systemic lupus erythematosus in an HIV-infected man with hepatitis C and B co-infection following interferon therapy a case report. J Med Case Rep 2009 3 7289. 

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