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MCTD by Dr Zohaib.pptx
- 1. Mixed Connective Tissue Dis ease Dr Zohaib Abbasi
- 2. Mixed Connective Tissue Disease • Autoimmune Disease • Features of: • SLE • Scleroderma • Inflammatory Myositis (Polymyositis) • Rheumatoid Arthritis • Serology: positive anti U1-RNP Ab • Abreviated as MCTD
- 3. Terminology • Mixed Connective Tissue disease • Patient meets criteria for MCTD generally with antibody positivity (RNP Ab) • Overlap Syndrome • Some patient have features of more than one connectiv e tissue (RA and SLE, SLE and SS)in the absence of high t iter anti RNP.
- 4. UCTD vs Overlap vs MCTD Undifferentiated Connective Tissue Disease Polymyositis-Scleroderma O verlap Mixed Connective Tissue Di sease
- 5. Epidemiology of MCTD • Prevalence 3-4 per 100,000 population • Female to Male Ratio is 3:1 • Present in all races • Peak age of Onset: 15-25 • A key reason to identify this subset of patients is that pulmonary HTN and ILD are major caus e of mortality.
- 6. Sensitivity of ANA in Rheumatology RNP Antibody – Sensitivity is 100% in Mixed Connective Tissue Disease
- 7. Specific Antibodies in Rheumatology
- 8. Immunology of MCTD • Extractable Nuclear antigens: • Ribonucleoproteins extractable from nucleus • SSA, SSB, smith, RNP, Jo-1, Scl-70, others • U1-RNP Antibody – Antigen: complex of series of small ribonucleoprot eins containing (U1-snRNP) • 3 polypeptides (70 kd, A, C) • Linked to U1 RNA
- 9. Immunology of MCTD U1-snRNP usmle287.wordpress.com Gene Splicing www.biology.arizona.edu U1 RNA http://en.wikipedia.org/wiki/U1_spliceosomal_RNA genome.wellcome.ac.uk 70KD protein is dominant antigen U1RNA is another antigen
- 10. Anti-RNP Ab • Generally the IgG anti-U1 RNP Ab is checked • IgG form is generally more associated with MC TD, while IgM form may often occur in Lupus. • When found in isolation suggests MCTD
- 11. MCTD as separate entity
- 12. Clinical Features of MCTD • Early Features • Arthritis – can be erosive or non-erosive • Raynaud’s • Puffy Hands/sausage digits • Later features • Can develop skin thickening typical of Scleroderma • Can develop lupus manifestations • Can develop organ involvement: lungs, kidneys, muscle. Unlike SLE kidney and cns involvement is uncommon.
- 13. Exam Findings In MCTD • Scleroderma Features • SLE (Lupus) Features • Inflammatory Myositis Features • Rheumatoid Arthritis
- 14. Systemic Sclerosis (Scleroderma) • Limited Scleroderma • Skin thickening is distal to elbows and knees, not involving tr unk • Can involve perioral skin thickening (pursing of lips) • Less organ involvement • Seen in CREST syndrome • Isolated pulmonary hypertension can occur • Diffuse Scleroderma • Skin thickening proximal to elbows and knees, involving the t runk • More likely to have organ involvement • Pulmonary fibrosis and Renal Crisis are more common.
- 15. Scleroderma Features • Calcinosis • Raynaud’s • Esophageal Dysmotility • Sclerodactyly (skin thickening of digits) • Telangiectases
- 16. CREST Features ACR and Mayo Foundation
- 17. Calcinosis on x-ray Gupta E., et al. Malaysian Family P hysician. 2008;3(3):xx-xx ACR
- 18. Scleroderma Skin Manifestations Kahaleh B. Rheum Dis Clin N Amer 2008:57-71 Sclero.org International Scleroder ma Network ACR
- 20. SLE (Lupus) Features • Lupus: (MD SOAP N HAIR) • Malar Rash • Discoid Lesions • Serositis • Oral Ulcers • Arthritis • Photosensitivity • Neurologic (seizures, neuropsychiatric) • Hair Loss, Hematologic (cytopenias) • ANA Positivity • Immunologic (ds-DNA, Smith, RNP, anti-SSA, APLA) • Raynauds, Renal
- 21. Malar Rash • Often mildly scaly • Typically involves bridge of nose • Spares Nasolabial fold • Generally non-pruritic but can be American College of Rheumatology Slide Collection
- 22. Discoid Skin Lesions • Early: well demarkated, erythematous, indurated scaly plaques. • Late: atrophic, well demarkated scars. • Often occurs in people without Systemic Lupus Erythematosus American College of Rheumatology Slide Collection
- 23. Serositis • Chest Pain • Acute Abdomen Pleural effusions www.learningradiology.com Pericarditis www.bukisa.com reference.medscape.com Peritonitis reference.medscape.com
- 24. Other Features of Lupus Oral Ulcers Photosensitivity Arthritis/Arthralgias
- 25. Neurologic Manifestations of Lupus • Seizures (rare in MCTD) • Neuropsychiatric Lupus/Psychosis (rare in MCTD) • Strokes related to aniphospholipid syndrome. • Trigeminal Neuropathy (occurs in MCTD but less com monly in SLE).
- 26. Other Lupus Manifestations Specific Antibo dies Anti-RNP Anti-ds-DNA Anti-Smith Anti-SSA Antiphospholipid Hair loss / Alopeci a www.dermhairclinic.com ANA Positive en.wikipedia.org Immunologic Raynaud’s Syndrome
- 27. Inflammatory Myositis Features • Symptoms • Proximal Muscle weakness » Difficulty getting out of chairs or getting up from crouchin g » Difficulty lifting objects overhead • Generally is painless, though may have mild pain • Generally without significant muscle tenderness • Laboratory Tests: • Elevated muscle enzymes (CK, AST>ALT, Aldolase, Myog lobin) • Normal inflammatory markers: ESR and CRP
- 29. Inflammatory Myositis Manifestati ons & Workup • http://www.iomonitoring.pro/emg.htm
- 30. Inflammatory Myositis Manifestati ons & Workup Olsen NJ, et al. Rheum Dis Clin N. Amer 1996;22(4):783-796 http://www.rayur.com/muscle-biopsy.html
- 31. Inflammatory Myositis Manifestati ons & Workup • Biopsy helps to confirm disease Arq. Neuro-Psiquiatr. vol.62 no.4 São Paulo Dec. 2004
- 32. Classification Criteria for MCTD
- 33. MCTD Manifestations and frequency
- 35. Features of Diseases Feature MCTD SLE Scleroderma Polymyositis Renal Involvment Less Common Common Renal Crisis may occur Rare Pulmonary PAH/ILD Less common PAH/ILD ILD may occur Esophageal Dysmo tility Common Rare Common Uncommon, but dysphagia Antiphospholipid S yndrome Less common Common Less common Less common Cytopenias Can Occur Common Rare Rare Sclerodactyly Common Rare Common Rare Neurological Less Common, (t rigeminal) More Common Rare Rare
- 36. Treatment of MCTD • Arthritis • Prednisone • Hydroxychloroquine • Methotrexate • Biologics (Rituxan, Orencia, anti-TNF) – generally with e rosive disease and/or RF/CCP positive.
- 37. Treatment of MCTD • Raynaud’s • Nifedipine or amlodipine • Sildenafil • Nitroglycerine (not used as much – had been used as pa tch or ointment – cannot use with sildenafil) • Digital Ischemia – acute • Hospitalization with IV prostoglandins • Anticoagulation with heparin • Search for hypercoagulability (Antiphospholipid Ab) • Evaluation for vasculitis / arterial obstruction
- 38. Treatment of MCTD • Scleroderma Skin • Often no treatment for limited disease • Methotrexate • Mycophenolate
- 39. Treatment of MCTD • Inflammatory Myositis • Prednisone • Methotrexate • Azathioprine • Rituximab • mycophenolate • IVIG
- 40. Treatment of MCTD • Pulmonary Involvement – Interstitial Lung Disease • Prednisone • Mycophenolate • Cyclophosphamide • Rituximab • Azathioprine maintenence – Pulmonary Hypertension • Vasodilators (Ca chanel blockers, sildenafil, prostoglandi n)
- 41. Treatment of MCTD • Lupus Type Manifestations – Depends on manifestations • Prednisone • Hydroxychloroquine • Mycophenolate • Azathioprine • Methotrexate • Belimumab (Benlysta) • Rituximab • IVIG
- 42. Treatment of MCTD • Lupus Arthritis • Prednisone • Hydroxychloroquine • Methotrexate • Oral Ulcers • Hydroxychloroquine • Topical steroids • Raynaud’s • Vasodilators
- 43. Treatment of MCTD • Malar Rash • Prednisone • Hydroxychloroquine • Mycophenolate • Azathioprine • Thrombocytopenia • Prednisone • IVIG • Rituximab • Plaquenil
- 44. Treatment of MCTD • Leukocytopenia • Often no treatment required • Prednisone • Hydroxychloroquine • Mycophenolate • Antiphospholipid Syndrome • Anticoagulation • IVIG • Rituximab • Plaquenil • Avoid estrogen (avoid OCP’s with estrogen)
- 45. Treatment of MCTD • Lupus Nephritis • Prednisone • Mycophenolate • Cyclophosphamide • Azathioprine • Pericarditis/Pleuritis • NSAIDs • Prednisone
- 46. Prognosis in MCTD • Survival Rates • 5 yrs: 98% • 10 yrs: 96% • 15 yrs: 88% • Major causes of death • Pulmonary hypertension: 9/280 patients • Cardiovascular events: 7/280 • TTP: 3/280 • Infections 3/280 J Rheumatol. 2013 Jul;40(7):1134-42
- 47. MCTD Phenotypes Antiphospholipid Myositis/ILD RA/Scleroderma
- 49. Case 1 • A 47 year old female with Raynaud’s symptoms and puffy hands, hand pai n,who presents with difficulty lifting objects overhead and leg weakness. • Exam • Fluctuating pallor/cyanosis of few digts of hands • Lungs are clear • No sclerodactyly, oral ulcers, malar rash, alopecia • Strength significantly reduced in proximal upper and lower extremi ties; normal distally; neck strenght intact. • Labs • ANA positive, RNP Ab positive, ESR 10, CRP 0.5 • CK level 5000, Aldolase elevated • Antiphospholipid Ab’s negative, C3 & C4 normal, UA normal; anti-S mith/SSA/SSB/Jo-1/ds-DNA negative • What is the next step, diagnosis and treatment.
- 50. Case 1 • Next steps: • Obtain MRI of weakest thigh or proximal arm • Obtain muscle biopsy • CXR baseline is normal • Diagnosis • Mixed Connective Tissue Disease with primary features of Polymyo sitis • Treatment • Start Prednisone • Start methotrexate or azathioprine • Course: • Over a period of months strength gradually improves and CK level declines; there is decrease in puffy hands and hand pain with treat ment.
- 51. Case 2 • A 60 year old female with history of Mixed Connective tissue disease with positive RNP antibody, sclerodactyly, Raynaud’s, past inflammatory myositi s presents with left lower extremity DVT; lab tests are performed at the ti me. • Exam • Sclerodactyly to MCP joints in both hands • Lungs are clear • No oral ulcers, malar rash, alopecia • Strength intact. • Labs • ANA positive, RNP Ab positive, ESR 30, CRP 1.0, CK normal • C3 & C4 normal, UA normal; anti-Smith/SSA/SSB/Jo-1 negative • Anticardiolipin Ab 80, Lupus anticoagulant positive, B2 GP Ab nega tive. • What is the treatment, diagnosis, possible complication.
- 52. Case 2 • Treatment/Next Step • Anticoagulation with Lovenox bridge to coumadin • Repeat antiphospholipid antibodies in 12 weeks; if still present, patient will require indefinite anticoagulation. • Diagnosis • Mixed Connective Tissue disease with scleroderma and myositis components with secondary antiphospholipid syndrome. • Potential Complication • Pulmonary hypertension with antiphospholipid antibod ies
- 53. Case 3 • A 22 year old female previously healthy develops Raynauds, malar rash, an d oral ulcers in the past 3 months. She has had fatigue and joint pain witho ut swelling involving the hands. She denies dry eyes or dry mouth. LMP 1 week ago. • Exam • Malar rash sparing nasolabial fold and oral ulcers noted, mild fluct uating cyanosis of several digits noted during visit, puffy hands. • Lungs are clear, oral mucosa moist. • No sclerodactyly or alopecia noted. • Strength intact. • Labs • ANA positive, RNP Ab positive, anti-SSA positive ESR 90, CRP 1.2, C K normal, low C3 and C4. • UA normal; anti-Smith/SSB/Jo-1/ds-DNA negative • Antiphospholipid antibodies negative, urine pregnancy test neg. • What is the diagnosis, treatment, important counseling information.
- 54. Case 3 • Diagnosis: • Mixed Connective Tissue Disease with primary features of Lupus (S LE) • Treatment • Start Prednisone • Start hydroxychloroquine (Plaquenil) • May need to consider Azathioprine or mycophenolate if steroid sp aring agent is needed to decrease steroids. • Counseling information: • Due to lupus and positive she would need high risk OB when she w ould like to become pregnant. • With positive anti-SSA Ab there is 1-3% risk of neonatal lupus with heart block but this can be monitored and potentially treated. • Would be best to wait until disease is better to control to plan for pregnancy
- 55. References • Up to Date • Medscape • Ortega-Hernandez OD, et al; Best Practice & Research Clinical Rheumatology 26 (2012) 61–72 • Hoffman RW; Clinical Immunology 2008 (128); 8-17 • Cappelli S, et al; j.semarthrit.2011.07.010 • Szodoray P, et al; Lupus 2012 (21); 1412-1422 • Keith MP; et al; Autoimmunity Reviews 6 (2007) 232–236 • Faye N; et al; Clin Chest Med 31 (2010) 433–449 • Schur PH; The Rheumatologist, February 2009 • Hajas A; J Rheum 2013 (40; 7) 1134-1142 • Prete M, et al; Autoimmunity Reviews xxx (2014) xxx–xxx