Differentiating Mixed connective tissue disease from other diseases

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahshid Mir, M.D. [2]

Differentiating SLE from other diseases that may cause arthritis and rash

Abbreviations: ANA: Antinuclear antibody, RF: Rheumatoid factor, Anti-CCp: Anti-cyclic citrullinated protein antibody, Anti U1RNP: Anti-U1 ribonucleoprotein antibodies , Anti Sm : Anti-Sm antibodies, Anti Ro: Anti Ro antibody also called anti-Sjögren's-syndrome-related antigen A antibody, Anti-dsDNA: Anti-double stranded DNA.

Disease Arthritis Auto-antibodies Raynaud phenomenon Rash pattern Distinguishing/specific features
Polyarthritis Tenderness Edema Deformity /Erosion Pattern ANA RF Anti-CCp Anti U1RNP Anti Sm Anti Ro Anti-dsDNA
Systemic lupus erythematosus[1] + + + - Small joints ↑ - - - ↑ ↑ - + Malar rash and photosensitivity
Rheumatoid arthritis (RA)[2] + + + + Small and large joints - ↑↑ ↑↑ - - - - + Subcutaneous nodules Erosive arthropathy
Rhupus[3] + + + + Small and large joints ↑ ↑ ↑ ↑ ↑ - ↑ + Malar rash and photosensitivity Erosive arthropathy
Mixed connective tissue disease (MCTD)[4] - - - + Small and large joints - ↑↑ ↑ - - - - + Cutaneous eruptions, gottron’s papules, photodistributed erythema, poikiloderma, and calcinosis cutis Overlapping features of SLE, systemic sclerosis (SSc), and polymyositis (PM) that lead to more than one diagnosis
Undifferentiated connective tissue disease (UCTD)[5] + - - - Lower extremity ↑ ↑ - - ↑ - - + Erythematous macules, patches, or papules with delicate scale Multiple connective tissue diseases with no enough criteria for a single diagnosis
Systemic sclerosis (SSc)[6] +/- + + +/- Lower extremity ↑↑ - - - ↑ - ↑ + Hyperkeratosis, edema, and erythema Sclerodactyly, Telangiectasias, Calcinosis, Malignant hypertension, acute renal failure
Sjögren’s syndrome[7] +/- +/- - - Lower extremity, axiallary creases ↑ - - - ↑ ↑ - - Xerosis, scaly skin, annular erythema Keratoconjunctivitis sicca
Vasculitis Giant cell[8] - + + - Distal extremity - - - - - - - - Rare Involvement of cranial branches of arteries, visual loss
Takayasu[9] - +/- +/- - Transient extremity - - - - - - - Erythema nodosum, pyoderma gangrenosum Absent or weak peripheral pulse
Poly-arteritis nodosa[10] - +/- - - General and mild - - - - - - - Tender erythematous nodules, purpura, livedo reticularis, bullous or vesicular eruption Testicular pain or tenderness and neuropathies
Behçet’s syndrome[11] +/- +/- +/- - medium and large joints - - - - - - - - Recurrent and usually painful mucocutaneous ulcers, acneiform lesions, papulo-vesiculo-pustular eruptions, superficial thrombophlebitis Male dominancy
Kikuchi’s disease[12] - +/- - - medium and large joints ↑/↓ - - - - - - - Transient skin rashes, malar rash, erythematous macules, patches, papules, or plaques May be associated with SLE
Serum sickness[13] + + +/- - General - - - - - - - - Pruritic rash, urticaria and/or serpiginous macular rash Self-limited
Psoriatic arthritis[14] - - - - Small and large joints - - - - - - - - Psoriasis and onychodystrophy Dactylitis (sausage digits)
Human parvovirus B19 infection[15] + + - - Small joints - - - - - - - - Erythematous rashes Rare in adults, fifth's disease in children
  1. ↑ Ehmke TA, Cherian JJ, Wu ES, Jauregui JJ, Banerjee S, Mont MA (2014). "Treatment of osteonecrosis in systemic lupus erythematosus: a review". Curr Rheumatol Rep. 16 (9): 441. doi:10.1007/s11926-014-0441-8. PMID 25074031.
  2. ↑ Lee DM, Weinblatt ME (2001). "Rheumatoid arthritis". Lancet. 358 (9285): 903–11. doi:10.1016/S0140-6736(01)06075-5. PMID 11567728.
  3. ↑ Panush RS, Edwards NL, Longley S, Webster E (1988). "'Rhupus' syndrome". Arch. Intern. Med. 148 (7): 1633–6. PMID 3382309.
  4. ↑ Cappelli S, Bellando Randone S, Martinović D, Tamas MM, Pasalić K, Allanore Y, Mosca M, Talarico R, Opris D, Kiss CG, Tausche AK, Cardarelli S, Riccieri V, Koneva O, Cuomo G, Becker MO, Sulli A, Guiducci S, Radić M, Bombardieri S, Aringer M, Cozzi F, Valesini G, Ananyeva L, Valentini G, Riemekasten G, Cutolo M, Ionescu R, Czirják L, Damjanov N, Rednic S, Matucci Cerinic M (2012). ""To be or not to be," ten years after: evidence for mixed connective tissue disease as a distinct entity". Semin. Arthritis Rheum. 41 (4): 589–98. doi:10.1016/j.semarthrit.2011.07.010. PMID 21959290.
  5. ↑ Alarcón GS, Williams GV, Singer JZ, Steen VD, Clegg DO, Paulus HE, Billingsley LM, Luggen ME, Polisson RP, Willkens RF (1991). "Early undifferentiated connective tissue disease. I. Early clinical manifestation in a large cohort of patients with undifferentiated connective tissue diseases compared with cohorts of well established connective tissue disease". J. Rheumatol. 18 (9): 1332–9. PMID 1757934.
  6. ↑ LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA, Rowell N, Wollheim F (1988). "Scleroderma (systemic sclerosis): classification, subsets and pathogenesis". J. Rheumatol. 15 (2): 202–5. PMID 3361530.
  7. ↑ Roguedas AM, Misery L, Sassolas B, Le Masson G, Pennec YL, Youinou P (2004). "Cutaneous manifestations of primary Sjögren's syndrome are underestimated". Clin. Exp. Rheumatol. 22 (5): 632–6. PMID 15485020.
  8. ↑ Bablekos GD, Michaelides SA, Karachalios GN, Nicolaou IN, Batistatou AK, Charalabopoulos KA (2006). "Pericardial involvement as an atypical manifestation of giant cell arteritis: report of a clinical case and literature review". Am. J. Med. Sci. 332 (4): 198–204. PMID 17031245.
  9. ↑ Lupi-Herrera E, Sánchez-Torres G, Marcushamer J, Mispireta J, Horwitz S, Vela JE (1977). "Takayasu's arteritis. Clinical study of 107 cases". Am. Heart J. 93 (1): 94–103. PMID 12655.
  10. ↑ Pagnoux C, Seror R, Henegar C, Mahr A, Cohen P, Le Guern V, Bienvenu B, Mouthon L, Guillevin L (2010). "Clinical features and outcomes in 348 patients with polyarteritis nodosa: a systematic retrospective study of patients diagnosed between 1963 and 2005 and entered into the French Vasculitis Study Group Database". Arthritis Rheum. 62 (2): 616–26. doi:10.1002/art.27240. PMID 20112401.
  11. ↑ Tunç R, Uluhan A, Melikoğlu M, Ozyazgan Y, Ozdoğan H, Yazici H (2001). "A reassessment of the International Study Group criteria for the diagnosis (classification) of Behçet's syndrome". Clin. Exp. Rheumatol. 19 (5 Suppl 24): S45–7. PMID 11760398.
  12. ↑ Kucukardali Y, Solmazgul E, Kunter E, Oncul O, Yildirim S, Kaplan M (2007). "Kikuchi-Fujimoto Disease: analysis of 244 cases". Clin. Rheumatol. 26 (1): 50–4. doi:10.1007/s10067-006-0230-5. PMID 16538388.
  13. ↑ Kunnamo I, Kallio P, Pelkonen P, Viander M (1986). "Serum-sickness-like disease is a common cause of acute arthritis in children". Acta Paediatr Scand. 75 (6): 964–9. PMID 3564980.
  14. ↑ Oriente P, Biondi-Oriente C, Scarpa R (1994). "Psoriatic arthritis. Clinical manifestations". Baillieres Clin Rheumatol. 8 (2): 277–94. PMID 8076388.
  15. ↑ Kaufmann J, Buccola JM, Stead W, Rowley C, Wong M, Bates CK (2007). "Secondary symptomatic parvovirus B19 infection in a healthy adult". J Gen Intern Med. 22 (6): 877–8. doi:10.1007/s11606-007-0173-9. PMC 2219874. PMID 17384979.
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