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©2013 UpToDate ® Print Email Algorithm for diagnosis of undifferentiated connective tissue diseases (UCTDs) • First, rule out osteoarthritis, bursitis/tendinitis and myofascial pain syndromes. • Does the patient have clinical evidence for any of the following problems? Persistent arthritis Episodic arthritis Muscle pain/weakness Raynaud's phenomenon • If "NO" consider a diagnosis of possible fibromyalgia and follow. • If "YES" look for clinical, serological and other evidence for: Persistent arthritis Episodic arthritis Muscle pain/weakness Raynaud's phenomenon Rheumatoid arthritis Gout Inflammatory myositis Primary Raynaud's (benign) Psoriatic arthritis Pseudogout Vasculitis Scleroderma / MCTD/ SLE Reactive arthritis Viral arthritis Metabolic myopathy CREST Rheumatic fever Palindromic rheumatism Drug reaction (eg, statins) Myositis overlap SLE / MCTD Serum sickness Hypothyroidism Takayasu's arteritis Drug induced lupus Reactive arthritis Acromegaly Vasculitis Enteropathic arthritis Bacterial endocarditis Viral infection Thoracic outlet syndrome Ankylosing spondylitis Lyme disease Overuse syndrome Antiphospholipid syndrome Tophaceous gout Bechet's disease Osteomalacia Thromboangiitis obliterans Lyme disease Relapsing polychondritis Sarcoidosis Atheroembolic disease Acromegaly Sarcoidosis Polymyalgia rheumatica Cryoglobulinemia Hemochromatosis Sjogren's syndrome Sjogren's syndrome Bacterial endocarditis Sarcoidosis Malignancy Peripheral neuropathies Polycythemia vera Whipple's disease Hyperparathyroidism Medication induced* Polymyalgia rheumatica Malignancy • If a specific diagnosis can be made, manage as per contemporary treatment guidelines. • If no specific diagnosis can be made, consider a diagnosis of a UCTD or overlap syndrome. • Are any of the following features present? Clinical features Autoantibodies Raynaud's phenomenon UI RNP Proximal sclerodactyly U2 RNP Interstitial lung disease Fibrillarin Esophageal hypomotility Synthetases Trigeminal neuropathy PM/Scl Puffy hands RNA polymerases SRP Ku Th • If "YES" follow up as a potential overlap syndrome. If patient has Raynaud's phenomenon and systemic involvement in conjunction with persistent U1-RNP antibodies, the most likely diagnosis will turn out to be mixed connective tissue disease (MCTD). * Drugs associated with Raynaud's phenomenon: Beta blockers, amphetamines, nicotine, bleomycin, vinblastine, clonidine, cisplatin, cocaine, cyclosporine, ergot, methysergide and vinyl chloride.

• If "YES" follow up as a potential overlap syndrome. If patient has Raynaud's phenomenon and systemic involvement in conjunction with persistent U1-RNP antibodies, the most likely diagnosis will turn out to be mixed connective tissue disease (MCTD). * Drugs associated with Raynaud's phenomenon: Beta blockers, amphetamines, nicotine, bleomycin, vinblastine, clonidine, cisplatin, cocaine, cyclosporine, ergot, methysergide and vinyl chloride. Original figure modified for this publication. Bennett, RM. Overlap Syndromes. Textbook of Rheumatology, 8th Edition, W.B. Saunders Co., Philadelphia 2009. Illustration used with the permission of Elsevier, Inc. All rights reserved.