Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 1980;23:581â90. under IVIg treatment in some cases [7]. All patients.
Letters to the Editor
U. S, T. L, R. G, B. D. W Department of Rheumatology, University Hospital of Wales, Cardiff, UK Accepted 2 May 2000 1. Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 1980;23:581–90. 2. Barnett AJ, Miller MH, Littlejohn GO. A survival study of patients with scleroderma diagnosed over 30 years. J Rheumatol 1988;15:276–7. 3. Silman AJ. Scleroderma—Demographics and survival. J Rheumatol 1997;(Suppl. 48)24:58–61. 4. Rosenthal AK, McLaughlin JK, Linet MS, Persson I. Scleroderma and malignancy: An epidemiologic study. Ann Rheum Dis 1993;52:531–3. 5. Abu-Shakra M, Guillemin F, Lee P. Cancer in systemic sclerosis. Arthritis Rheum 1993;36:460–4. 6. Roumm AD, Medsger T. Cancer and systemic sclerosis. Arthritis Rheum 1985;28:1336–40. 7. Jacobsen S, Halberg P, Ullman S. Mortality and causes of death of 344 Danish patients with systemic sclerosis (scleroderma). Br J Rheumatol 1998;37:750–5. 8. Le CH, Morales A, Trentham DE. Minocycline in early diffuse scleroderma. Lancet 1998;352:1755–6. 9. Abu-Shakra M, Lee P. Exaggerated fibrosis in patients with systemic sclerosis (scleroderma) following radiation therapy. J Rheumatol 1993;20:1601–3. 10. Davis DA, Cohen PR, McNeese MD, Duvic M. Localized scleroderma in breast cancer patients treated with supervoltage external beam radiation: radiation port scleroderma. J Am Acad Dermatol 1996;35:923–7. 11. Forbes AM, Woodrow JC, Verbov JL, Graham RM. Carcinoma of breast and scleroderma. Br J Rheumatol 1989;28:65–9.
Rheumatology 2000;39:1301–1302
Treatment of acute exacerbation of systemic lupus erythematosus with high-dose intravenous immunoglobulin S, Intravenous immunoglobulin (IVIg) treatment has been approved by the Food and Drug Administration for immune-mediated thrombocytopenia, and Kawasaki’s syndrome, and has been shown to be effective in other autoimmune diseases. For patients with systemic lupus erythematosus (SLE ) there are no general valid guidelines of therapy applicable. IVIg has been demonstrated to enhance the catabolism of IgG, to block Fcc receptor-mediated mechanisms, and to inhibit Fas receptor-induced apoptosis [1, 2]. Furthermore, IVIg preparations contain anti-DNA idiotypic antibodies, which might influence the idiopathic network [3]. These mechanisms have been shown to be able to control the pathogenesis of SLE. Moreover, the efficacy of IVIg treatment has been demonstrated in case reports of patients with various manifestations of SLE, especially in those with thrombocytopenia and antiphospholipid antibody syndrome [4, 5]. However, prospective studies of the treatment of acute exacerbation of SLE with IVIg are rare. Therefore, we performed an uncontrolled multicentre trial.
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Thirteen female patients fulfilling at least five American College of Rheumatology (ACR) criteria with an acute exacerbation of SLE were enrolled. The flare was defined as an increase in modified European Consensus Lupus Activity Measurement (mECLAM ) by 4 points in comparison with a retrospective score covering the 3 months before the patient entered the study [6 ]. Patients with acute lupus nephritis were excluded because of reported worsening of renal function under IVIg treatment in some cases [7]. All patients received 0.4 g/kg body weight pasteurized IVIg once a day for 5 consecutive days. The mECLAM was determined retrospectively (not more than 3 months before acute exacerbation, score 0), at screening, at the end of treatment, and at weeks 1, 4 and 12 of the follow-up. Concomitant SLE therapy should not be changed during the study period. A decline of 3 points in mECLAM at week 4 after the end of the study treatment compared with the time of screening was defined as a full response. The median retrospective mECLAM (score 0) before flare was 6 points (range 1–13) (Fig. 1). The median mECLAM at study entry (screening) was 12 points (range 6–20). The median increase in mECLAM was 7 points (range 4–11). After IVIg treatment, mECLAM had declined in 12 of 13 patients by 3 points at week 4 of follow-up (the primary endpoint of the study). The median reduction in disease activity was 7 points [range 1–12, P = 0.0002, 95% confidence interval (CI ) 4.6–8.1; Wilcoxon signed rank test]. Although we aimed to keep concomitant therapy constant, the treatment was changed in six patients before week 4 of follow-up by a decision of the treating physician. The groups of patients with and without change in concomitant therapy did not differ significantly in severity of flare or in their course of disease activity (P > 0.3 at all time points, Mann–Whitney test). The effects of IVIg treatment in the remaining seven patients for whom there was no alteration of concomitant SLE therapy were analysed further. The median
F. 1. Effect of IVIg treatment in SLE exacerbation. Time course of mECLAM in patients whose concomitant therapy was unchanged (closed circles, solid line) and changed (open circles, dashed line) before week 4 of follow-up. EOT, end of treatment.
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Letters to the Editor
reduction in mECLAM was 8 points (range 1–8, P = 0.0156, 95% CI 3.7–8.8; Wilcoxon signed rank test). Fatigue, myalgia and fever improved in all affected patients. Arthralgia or arthritis diminished in four of six patients. Clinical deterioration was rare (fatigue in one patient). The improvement in laboratory test results after IVIg treatment was less impressive. Erythrocytes and platelets increased in one patient with anaemia and thrombocytopenia. The erythrocyte sedimentation rate ( ESR) decreased in two of three patients with an abnormal ESR. The DNA antibody titre improved in four of six patients. IVIg-related adverse effects during infusion phases were rare and mild. In addition, no worsening of renal function was observed during follow-up. We have described the efficacy of high-dose IVIg treatment in 13 patients with acute exacerbation of SLE. Twelve of 13 patients (92%) were full responders (decrease in mECLAM by 3 points at week 4 of follow-up). In addition to the study treatment with IVIg, intensification of concomitant SLE therapy was given to six of 13 patients before week 4 of follow-up. Five (83%) of these six patients responded to IVIg treatment, measured by a decrease in mECLAM by 3 points: three showed a response at the end of the study treatment and two patients at week 1 of follow-up. Of the seven patients who were treated only by the addition of IVIg, six (86%) were full responders. If the six patients who received intensified concomitant SLE therapy before week 4 of follow-up are classified as non-responders, only six of 13 patients (46%) were full responders. These results agree with previous studies demonstrating positive effects of high-dose IVIg treatment in SLE [8, 9]. In our study, IVIg was very efficient in improving myalgia. In refractory dermatomyositis, a double-blind placebocontrolled study has demonstrated the effectiveness of IVIg treatment [10]. These results suggest that SLE patients with myalgia may represent a new subgroup who might benefit from IVIg treatment. Because we used only a single course of IVIg treatment, no statement about the efficacy of long-term therapy can be made. However, progressive clinical improvement has been demonstrated after monthly administration of IVIg [11]. Considering the risks and benefits of a 5-day, high-dose IVIg treatment in SLE exacerbations, we conclude that this regimen is safe and effective and may be used as an addition to conventional therapy. M. H, K. M1, T. D2, B. G3, P. K3, A. R1, D. W4, G. R. B2, H. H. P3, J. R. K1, R. E. S Department of Clinical Immunology, Hanover Medical School, 1Department of Medicine III, University of Erlangen-Nu¨rnberg, 2Department of Rheumatology and Clinical Immunology, Charite´ University Hospital, Berlin, 3Department of Rheumatology and Clinical Immunology, University of Freiburg and 4Grifols Deutschland GmbH, Langen, Germany Accepted 2 May 2000
Correspondence to: M. Hundt, Abteilung Klinische Immunologie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany. 1. Yu Z, Lennon VA. Mechanism of intravenous immune globulin therapy in antibody-mediated autoimmune diseases. N Engl J Med 1999;340:227–8. 2. Gessner JE, Heiken H, Tamm A, Schmidt RE. The IgG Fc receptor family. Ann Hematol 1998;76:231–48. 3. Burny W, Lebrun P, Cosyns JP, Saint-Remy JM. Treatment with dsDNA-anti-dsDNA antibody complexes extends survival, decreases anti-dsDNA antibody production and reduces severity of nephritis in MRLlpr mice. Lupus 1997;6:4–17. 4. Corvetta A, Della BR, Gabrielli A, Spaeth PJ, Danieli G. Use of high-dose intravenous immunoglobulin in systemic lupus erythematosus: report of three cases. Clin Exp Rheumatol 1989;7:295–9. 5. Maier WP, Gordon DS, Howard RF et al. Intravenous immunoglobulin therapy in systemic lupus erythematosus-associated thrombocytopenia. Arthritis Rheum 1990;33:1233–9. 6. Vitali C, Bencivelli W, Isenberg DA et al. Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. II. Identification of the variables indicative of disease activity and their use in the development of an activity score. The European Consensus Study Group for Disease Activity in SLE. Clin Exp Rheumatol 1992;10:541–7. 7. Schifferli J, Leski M, Favre H, Imbach P, Nydegger U, Davies K. High-dose intravenous IgG treatment and renal function. Lancet 1991;337:457–8. 8. Schroeder JO, Zeuner RA, Euler HH, Loffler H. High dose intravenous immunoglobulins in systemic lupus erythematosus: clinical and serological results of a pilot study. J Rheumatol 1996;23:71–5. 9. Boletis JN, Ioannidis JPA, Boki KA, Moutsopoulos HM. Intravenous immunoglobulin compared with cyclophosphamide for proliferative lupus nephritis. Lancet 1999;354:569–70. 10. Dalakas MC, Illa I, Dambrosia JM et al. A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis. N Engl J Med 1993;329:1993–2000. 11. Francioni C, Galeazzi M, Fioravanti A, Gelli R, Megale F, Marcolongo R. Long-term i.v. Ig treatment in systemic lupus erythematosus. Clin Exp Rheumatol 1994;12:163–8.
Rheumatology 2000;39:1302–1304
Kikuchi–Fujimoto disease associated with polymyositis S, I present the case of a 41-yr-old lady diagnosed with Kikuchi–Fujimoto disease ( KFD) by clinical features and lymph node histology, who subsequently developed polymyositis with pulmonary involvement. There are no reports of this association in the literature. A 41-yr-old female of Indian origin was admitted with a day’s history of periumbilical pain and 3 weeks of fever, general malaise, weight loss and painful lymphadenopathy. Her past history includes pulmonary tuberculosis. Physical examination revealed a fever of 38°C and tenderness in the right iliac fossa. Matted, tender, erythematous lymph nodes were present in the left axilla, and smaller lymph nodes in the right posterior triangle of the neck and right axilla. Laboratory findings revealed a lymphopenia of 0.9 × 10/l. Further investigations showed normal plasma viscosity, chest X-ray and abdominal ultrasound. Blood cultures, sputum for TB culture and autoantibody screens were negative. Serology excluded active infection with
