Rheumatology Advance Access originally published online on May 11, 2006
Rheumatology 2006 45(7):915-916; doi:10.1093/rheumatology/kel162
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LETTER TO THE EDITOR |
Therapy-resistent lupus skin disease successfully treated with rituximab
Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands
Correspondence to: Prof. Dr C. G. M. Kallenberg, MD, PhD, Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. E-mail: c.g.m.kallenberg{at}int.umcg.nl
SIR, Cutaneous lesions are common in systemic lupus erythematosus (SLE), and occur in 
70% of patients [1]. Topical therapy consisting of sunscreens and corticosteroids is effective in controlling skin lesions in most cases. More serious skin lesions can cause significant morbidity and require systemic therapy. Anti-malarials are the treatment of choice. When this standard therapy fails, other (immunosuppressive) medication might be effective [2]. However, some patients suffer from severe skin disease refractory to current treatment options.
Recently, rituximab (anti-CD20 monoclonal antibody) has successfully been used in the treatment of patients with severe therapy-resistent SLE and other autoimmune diseases.
Here, we report two consecutive patients with predominant lupus skin disease for whom current treatment was unsuccessful or contra-indicated because of serious adverse events. Rituximab treatment (2 x 1000 mg/m2 with methylprednisolone 100 mg i.v. at 2 weeks interval) resulted in dramatic and persistent improvement of skin manifestations in both patients.
Patient 1
A 52-yr old woman was diagnosed with SLE in 1997 based on erythematous photosensitive rash, arthritis, leucopenia and thrombopenia, and positive ANA. Additionally, she suffered from Raynaud's phenomenon and sicca complaints, with positive anti-SSA and anti-SSB antibodies. Her symptoms were mainly cutaneous, and her disease was treated with prednisolone (15–35 mg daily) from 1999 onwards. Addition of hydroxychloroquine, azathioprine, pulse cyclophosphamide, methotrexate and high-dose i.v. immunoglobulins proved ineffective or resulted in serious adverse events. And she was reluctant to use thalidomide. In June 2005, she experienced a relapse, consisting of leucocytoclastic vasculitis with diffuse urticarial rash. Combined treatment with prednisolone 60 mg daily, hydroxychloroquine and mycophenolate mofetil initially slightly improved her skin symptoms. However, upon tapering of prednisolone, symptoms re-emerged severely in August 2005 (Fig. 1, left). In September 2005, she received rituximab, while continuing other medication. Her skin manifestations improved quickly and markedly (Fig. 1, right), and prednisolone dosage could be tapered. At present, January 2006, she is without skin lesions and still tapering prednisolone to <15 mg daily, a dose she never reached in the last 5 yrs.
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Patient 2
A 44-yr old woman was diagnosed with mixed connective tissue disease in 1987. Her symptoms consisted of polymyositis, Raynaud's phenomenon and restrictive lung function disturbances with decreased diffusion capacity. In 1989, she developed a photosensitive rash, arthralgia and synovitis with high levels of anti-dsDNA antibodies, consistent with a diagnosis of SLE. Addition of hydroxychloroquine, azathioprine or thalidomide to daily treatment with prednisolone proved to be either ineffective in the long run or to cause serious adverse events. Increased dosages of prednisolone were repetitively necessary to treat exacerbations, consisting of arthritis, muscle weakness and skin manifestations. In July 2005, a diffuse generalized skin rash had emerged with diffuse painful erythema and scaly skin, particularly on her feet and hands. In August 2005, these skin manifestations had worsened, while the preceding muscle weakness had improved. In September 2005, she received rituximab, which induced marked improvements of her skin manifestations. At present, January 2006, skin lesions are still absent, and prednisolone has been tapered from 60 mg to 12
mg daily.
Discussion
The above described two patients suffered from lupus skin disease, and the severity of their symptoms made systemic therapy necessary. Anti-malarials are the systemic therapy of first choice for lupus skin disease, either as monotherapy or in combination. When this treatment fails, dapsone and retinoids might be effective. Immunosuppressive agents and corticosteroids may be required to manage severe (systemic) disease activity. Prednisolone or pulse methylprednisolone are useful in treating relapses. Often, continued treatment with oral prednisolone is necessary to control cutaneous symptoms. Azathioprine, methotrexate, cyclophosphamide, mycophenolate mofetil and thalidomide can be effective in treating chronic cutaneous lupus erythematosus [2–4]. However, randomized controlled trials are hardly available to prove or compare the effectiveness of different treatment modalities for lupus skin disease.
Various combinations of current therapeutic options had been used in the two patients described. They were either unsuccessful in ameliorating disease, or induced adverse events. Therefore, rituximab was administered.
Rituximab is a chimeric monoclonal anti-CD20 antibody that depletes mature B-cells for a median 6 months, sparing progenitor B-cells and plasma cells. Initially used in treating lymphoma, rituximab has been successfully applied in several autoimmune diseases [5], among which pemphigus vulgaris resistent to conventional immunosuppressives [6, 7]. It induced long-term B-cell depletion (6–12 months) with an even longer period of remission in the few patients studied. It has also shown to be effective and safe in treating severe therapy-resistent SLE [8, 9], with the possibility of maintenance therapy [10]. Treated SLE patients mostly suffered from severe renal, haematological or central nervous system disease. Here, we described successful treatment of two patients with predominant lupus skin disease, refractory to other therapy, suggesting that rituximab might be an alternative for the treatment of therapy-resistant lupus skin disease.
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The authors have declared no conflicts of interest.
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[Abstract/Free Full Text] - Weide R, Heymanns J, Pandorf A, Köppler H. Successful long-term treatment of systemic lupus erythematosus with rituximab maintenance therapy. Lupus 2003;12:779–82.
[Abstract/Free Full Text]
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