Connective Tissue Diseases

1. Connective Tissue Diseases Betsy Evans PA-C Rheumatology Associates Portland, ME

2. Systemic Lupus Erythematosis(SLE) • Multi- system variable autoimmune disease of unknown etiology • Rare: 40-150 cases/100,000 • Hormones play a role! • Adult female:male 7-15:1 • Children female:male 3:1 • Age of onset: 65% between 16-55 yrs • Later onset (>50) usually has milder disease

3. Pathophysiology • Precise mechanism is still not known but abnormal cell apoptosis resulting in cellular breakdown and cellular antigens appear to play key role in the formation of polyclonal B-cell activation and autoantibody production. These lead to immune complex formation and deposition, resulting in complement-dependent inflammation of involved organs

4. Race Plays a Role • SLE occurs 3x more common in Afro-Americans than whites • Disease is more prevalent and tends to be more severe in Asians, Afro-Americans, Afro-Caribeans & Hispanics • More common in urban areas

5. Clinical Features • Must meet 4/11 Criteria defined by the American College of Rheumatology: • Malar rash • Discoid rash • Photosensitivity • Oral or nasal ulcerations • Arthritis of 2 or more joints • Serositis (pleuritis or pericarditis) • Renal disorder • Neurologic disorder • Hematologic disorder • Immunologic disorder • Antinuclear antibody

6. Other Nonspecific Sxs of SLE • Raynaud’s Phenomenon: fingers turn stark white, followed by blue and then painful red when they re-prefuse upon cold/stress exposure • Unexplained Fever • Alopecia • Fatigue • Myalgias/arthalgias

7. Malar Rash

8. Discoid Rash

9. Oral Ulcerations

10. Arthritis

11. Renal Involvement • Nephritis (5 different classes) • Nephrotic Syndrome • Tubulointerstitial disease • Clinically look for persistantproteinuria and cellular casts • Definitive diagnosis by biopsy

12. IgG Deposition, Glomerulus

13. Membranous Lupus Nephritis showing immune complex deposition

14. Neurologic Involvement • Seizures • Psychosis

16. Hematologic Involvement • Hemolytic Anemia • Leukopenia • Lymphopenia • Thrombocytopenia

17. Immunologic Disorder • Antiphospholipid Syndrome • A syndrome characterized by vascular thrombosis (can be arterial or venual), pregnancy mortality, + anticardiolipin Abs • +Lupus anticoagulant • Antibodies to double-stranded DNA • False positive serologic test for syphilis

18. ANA Patterns • Various patterns react to different parts of a cell • ‘Diffuse’ or ‘homogenous’ pattern is the least specific but can be associated with SLE if titers are high (usually >1:512) • dsDNA is the most specific; speckled and nucleolar are also important • Histone pattern -> think DRUG INDUCED! • Centromere pattern -> think CREST Syndrome

19. Drug Induced Lupus • Can act and look like SLE but entirely reversible once the offending drug is d’ced. • Known Offenders: Hydralazine, Procainimide, Minocycline, Chlorpromazine, Isoniazid, Penicillamine, Methyldopa, & Interferon-alpha

20. Discoid Lupus • Subset of lupus limited to the skin • Diagnosis confirmed by skin biopsy • ANA often negative • Prognosis usually good; <10% develop SLE

22. SLE Clinical Course • Highly variable. 5 year survival rate >90% • Poor prognostic indicators: • Renal disease • CNS disease • Early or late age • Males • Non whites • Overall disease activity

23. Clinical Course cont’d • Late in disease (>5 years) complications/death more likely due to thromboembolic disease • ? Due to steroid requirements vs chronic inflammatory states

24. SLE Diagnostic Studies • Good History and ROS! • Tissue biopsy if suspect renal involvement • Labs: CBC (look for cytopenias, anemia) • BUN/Cr (renal disease) • UA (proteinuria/cellular casts) • ANA (increased- watch the pattern) • C3/C4 (decreased) • CRP (normal or increased) • ESR (increased) • Ds DNA (present)

25. SLE Interventions/Therapeutics • Depends on the severity of disease • Hydroxychloroquine helpful for fatigue and skin rashes • Renal disease often requires high dose corticosteroids and/or powerful immunosuppressants like Cyclophosphamide • Other immunosuppressants often used and considered ‘steroid-sparing’: Azathioprine, Mycophenalate, Methotrexate

26. SLE Interventions • Other considerations: • Treat side effects of medications eg atherosclerosis and osteoporosis • Pregnancy can be very risky for a female with SLE. Effective birth control and family planning are important. All efforts to have her disease under excellent control prior to conception and then close monitoring during pregnancy for any flares are imperative

27. SLE Final Thoughts Don’t rely on the ANA to make or break the diagnosis; instead listen to your patient and look for other criteria. If they aren’t present, it probably isn’t SLE. If in doubt, refer to a Rheumatologist for eval Don’t be fooled by a low titer + ANA- remember it is NONSPECIFIC!

28. SCLERODERMA Systemic Sclerosis (SS) CREST Syndrome

29. Scleroderma • From the Greek “scleros”, describing thickened, hardened skin • 2 forms: Systemic Sclerosis (SS) and Crest Syndrome (limited) • Very rare: 240 cases/million • Cause unknown • Females>>males, peak onset 30-50 y.o.

30. Scleroderma Pathophysiology • Poorly understood. Unknown trigger in a genetically susceptible person leads to immune system activation and vascular reactivity followed by the deposition of collagen and other matrix proteins in affected tissues.

31. Clinical Presentation of SS • Skin: Raynaud’s phenomenon with diffuse thickening including chest, abdomen, face, upper arms, shoulders as well as hands and feet • Pulmonary: interstitial lung disease and fibrosis, less often pulm HTN • GI: dysmotility, “watermelon stomach” • Renal: Scleroderma Renal Crisis: acute renal failure with abrupt onset of HTN. UA reveals only mild proteinuria. • Cardiac • Musculoskeletal: arthralgias, puffy hands early on, carpal tunnel • + ANA: often speckled pattern

32. Raynauds

33. Puffy hand stage

36. SS Clinical Intervention • No single disease modifier. Instead treatment is aimed at the organs involved: • ACE inhibitors for renal protection • Calcium channel blockers for Raynaud’s • Promotility agents for GI • Cyclophosphamide debatable for lung disease, Viagra/Levitra and Bosantan for pHTN • AVOID high dose steroids; can lead to renal crisis

37. SS Clinical Course • Variable. Early stages: Raynaud’s, puffy hands, fatigue malaise, arthalgias/myalgias. Patients can also present with dyspnea +/- GI symptoms • Poor prognosis with pulmonary involvement and rapid progression. Use of ACE inhibitors has improved renal outcomes.

38. CREST Syndrome • AKA Limited Scleroderma • Calcinosis • Raynaud’s • Esophageal Dysmotility • Sclerodactyly of the fingers to the MCPs • Telangiectasia

39. Calcinosis

41. CREST Clinical Course • Tends to be more benign than Systemic Sclerosis • Complication: pulmonary HTN- get annual PFTs/DLCO • Treat symptomatically

42. POLYMYOSITIS/DERMATOMYOSITS • Autoimmune inflammatory myopathy resulting in painless muscle weakness +/- rash • DM is often associated with an underlying malignancy in adults but not in children • Rare: 2-10/100,000, more common in females • Peak ages 40-60 yo

43. Clinical Manifestations • Painless muscle weakness of the proximal muscle groups with gradual onset. Patients will complain that they have difficulty getting out of a chair, climbing stairs, styling their hair due to lack of power • Early on no signs of fasiculations or muscle atrophy

44. Skin Manifestations of DM • Heliotrope rash of eyelids • Gottren’s papules on hands • Shawl sign • Mechanic hands • Periungalerythema • Calcinosis cutis

45. Heliotrope Rash

46. Gottron’s Papules

47. Shawl Sign

48. Mechanic’s hands

49. Periungual Involvement

50. Other Manifestations • Pulmonary: Interstitial Lung Disease, BOOP, diffuse alveolar damage • Esophagus: dysphagia and gagging • Misc: fever, polyarthritis, Raynaud’s • + ANA plus other autoantibodies • Elevated CPK. Aldolase, AST and ALT may also be elevated