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CMDT 2008
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OVERLAP (OR MIXED) CONNECTIVE TISSUE DISEASE
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Many patients with symptoms and signs compatible with a connective tissue disease have features consistent with more than one type of rheumatic disease Special attention has been drawn to patients who have overlapping features of SLE, systemic sclerosis, and inflammatory myopathy Initially, these patients were thought to have a distinct entity ( mixed connective tissue disease ) defined by a specific autoantibody to ribonuclear protein (RNP) In many patients, the manifestations evolve to one predominant disease in time, such as scleroderma, and many patients with antibodies to RNP develop unequivocal SLE Therefore, overlap connective tissue disease is the preferred designation for patients having features of different rheumatic diseases Treatments are guided more by the distribution and severity of patients organ system involvement than by therapies specific to these diverse syndromes
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Wigley FM et al The prevalence of undiagnosed pulmonary arterial hypertension in subjects with connective tissue disease at the secondary health care level of community-based rheumatologists (the UNCOVER study) Arthritis Rheum 2005 Jul;52(7):2125 32 [PMID: 15986394]
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Treatment
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Most patients respond to corticosteroids Often a daily dose of 40 60 mg or more of oral prednisone is required initially The dose is then adjusted downward according to the response of sequentially observed serum levels of muscle enzymes Longterm use of corticosteroids is often needed, and the disease may recur or reemerge when they are withdrawn Patients with an associated neoplasm have a poor prognosis, although remission may follow treatment of the tumor; corticosteroids may or may not be effective in these patients In patients resistant or intolerant to corticosteroids, therapy with methotrexate or azathioprine may be helpful Intravenous immune globulin has also been shown to be effective for dermatomyositis resistant to prednisone TNFs do not appear to be effective in the inflammatory myopathies Mycophenolate mofetil (10 15 g twice daily) may be useful as a steroid-sparing agent B cell depletion therapies eg, rituximab (either 375 mg/m2 administered intravenously once weekly for 4 weeks, or 1 g/wk intravenously for 2 weeks) are a promising avenue of current investigation Since the rash of dermatomyositis is often photosensitive, patients should limit sun exposure Hydroxychloroquine (200 400 mg daily not to exceed 65 mg/kg) can also help ameliorate the skin disease
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Callen JP et al Dermatomyositis Clin Dermatol 2006 Sep Oct;24(5):363 73 [PMID: 16966018] Troyanov Y et al Novel classification of idiopathic inflammatory myopathies based on overlap syndrome features and autoantibodies: analysis of 100 French Canadian patients Medicine (Baltimore) 2005 Jul;84(4):231 49 [PMID: 16010208] Ytterberg SR Treatment of refractory polymyositis and dermatomyositis Curr Rheumatol Rep 2006 Jun;8(3):167 73 [PMID: 16901073]
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SJ GREN S SYNDROME
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Women are 90% of patients; the average age is 50 years Dryness of eyes and dry mouth (sicca components) are the most common features; they occur alone or in association with rheumatoid arthritis or other connective tissue disease Rheumatoid factor and other autoantibodies common Increased incidence of lymphoma
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General Considerations
Sj gren s syndrome, an autoimmune disorder, is the result of chronic dysfunction of exocrine glands in many areas of the body It is characterized by dryness of the eyes, mouth, and other areas covered by mucous membranes and is frequently associated with a rheumatic disease, most often rheumatoid arthritis The disorder is predominantly a disease of women, in a ratio of 9:1, with greatest incidence between age 40 and 60 years Disorders with which Sj gren s syndrome is frequently associated include rheumatoid arthritis, SLE, primary biliary cirrhosis, scleroderma, polymyositis, Hashimoto s thyroiditis, polyarteritis, and interstitial pulmonary fibrosis When Sj gren s syndrome occurs without rheumatoid arthritis, HLA-DR2 and -DR3 antigens are present with increased frequency
CMDT 2008
cated Sipping water frequently or using sugar-free gums and hard candies usually relieves dry mouth symptoms Pilocarpine (5 mg orally four times daily) and the acetylcholine derivative cevimeline (30 mg orally three times daily) may improve xerostomia symptoms Atropinic drugs and decongestants decrease salivary secretions and should be avoided A program of oral hygiene, including fluoride treatment, is essential in order to preserve dentition If there is an associated rheumatic disease, its systemic treatment is not altered by the presence of Sj gren s syndrome Although Sj gren s syndrome may compromise patients quality of life significantly, the disease is usually consistent with a normal life span Poor prognoses are influenced mainly by the presence of systemic features associated with underlying disorders, the development in some patients of lymphocytic vasculitis, the occurrence of a painful peripheral neuropathy, and the complication (in a minority of patients) of lymphoma The patients (3 10% of the total Sj gren s population) at greatest risk for developing lymphoma are those with severe exocrine dysfunction, marked parotid gland enlargement, splenomegaly, vasculitis, peripheral neuropathy, anemia, and mixed monoclonal cryoglobulinemia
Brito-Zeron P et al Circulating monoclonal immunoglobulins in Sj gren syndrome: prevalence and clinical significance in 237 patients Medicine (Baltimore) 2005 Mar;84(2):90 7 [PMID: 15758838] Goransson LG et al Peripheral neuropathy in primary Sj gren syndrome: a population-based study Arch Neurol 2006 Nov;63(11):1612 5 [PMID: 17101831] Ono M et al Therapeutic effect of cevimeline on dry eye in patients with Sj gren s syndrome: a randomized, doubleblind clinical study Am J Ophthalmol 2004 Jul;138(1):6 17 [PMID: 15234277] Ramos-Casals M et al Cutaneous vasculitis in primary Sj gren syndrome: classification and clinical significance of 52 patients Medicine (Baltimore) 2004 Mar;83(2):96 106 [PMID: 15028963]
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