1. CONNECTIVE TISSUE DISEASES Dr. Müge Bıçakçıgil kalaycı Rheumatology department of Yeditepe University Medical Faculty

2. Indroduction • collagen vascular diseases,autoimmune diseases • difficult to diagnose – nonspecific symptoms – tend to overlap

3. Common features: • Host and genetic predisposition – familial occurrence, female preponderance • Overlapping clinical features • Blood vessel as important target organ – vasculitis, vasculopathy • Immunologic correlates – circulating Ig, immune complexes

4. The Immune System: • designed to protect the host from invading pathogens • (non-self or foreign pathogens) and to eliminate • disease. • Lymphocytes: play a key role, has receptors to monitor these antigens • exquisitely responsive to invading pathogens while • retaining the capacity to recognize self antigens

5. Autoimmunity • arises when the body mounts an immune response against itself due to failure to distinguish self tissues and cells from foreign (non-self) antigens. • Primary mechanisms involved in pathogenesis is unclear

6. Autoimmune diseases • Characterized by production of: • a) autoantibodies that react with host tissue • b) Immune effector T cells that are autoreactive to endogenous self-peptides Tissue Injury

7. common histiologic feature – inflammatory damage CT and blood vessels – fibrinoid material deposition

8. Major groups of connective tissuedisease • Systemic lupus erythematosus (SLE) • Antiphospholipid syndrome (primary or secondary) • Systemic sclerosis (scleroderma) • Polymyositis and dermatomyositis • Sjögren's syndrome (primary and secondary) • Miscellaneous (Mixed CTD, undifferentiated CTD)

9. Systemic Lupus Erythematosus(SLE)

10. Systemic Lupus Erythematosus(SLE) • Chronic multisystemic disease of autoimmune origin • Characterized by flare-ups and remissions • Characteristically affects skin and joints, although any system can be involved

11. Systemic Lupus Erythematosus (SLE) • - prototype autoimmune disease • - unknown etiology • - production of Ab to components of the cell nucleus

12. Predominantly occurs in womens • F/M : 9/1 • Prevalence -1/1000 to 1/10.000 • Onset is usually after puberty (20s-30s) • More commonin African Americans than whites

13. Clinical Features • Constitutional symptoms: • Fatique, fever, malaise, weigth loss • Low grade fever-active SLE • Rarely 39.5 C-(possible infection)

14. Muco-cutaneous • Skin Rashes (55-90%) • Photosensitivity to sunlight • Malar rash-’butterfly rash’ fixed erythema, edema in sun-exposed areas(nose and cheeks)sparing the nasolabial fold

15. Discoid rash- erythematous patches with kerototic scaling • Maculopapular eruptions- face,V-of the neck,forearms

16. Butterfly facial rash Photosensitivity

17. Systemic lupus erythematosus: butterfly rash

20. Raynaud’s phenomenon(20-60%) Peripheral extremity changes induced by cold and may be complicated by digital ulcers • Livedoreticularis • Bullous and blistering lesions

21. Cutaneous vasculitis • Nailfold capillary changes • Alopecia • Ulcers in nose and mouth (20-50%)

22. Raynaud’s phenomenon Livedo reticularis

23. Alopecia diffuse or patchy

25. Mucosal ulcers Sicca symptoms- secondary Sjogren’s syndrome

27. Vasculitis

29. Systemic lupus erythematosus: hands, interarticular dermatitis

30. Musculoskelatal • Jaccoud arthropathy is the term for the nonerosive hand deformities This may mimic rheumatoid arthritis (RA) ulnar deviation and phalangeal subluxations. • Small-joint arthritis of the hands and wrists is most frequent • Myositis rarely occurs and is more commonly related to overlap syndromes or corticosteroid-induced myopathy.

31. Synovitis and Jaccoud’s arthropathy

32. Renal involvement • The kidney is the most commonly involved visceral organ in SLE. • Glomerular disease usually develops within the first few years after onset.

33. Acute nephritic disease may manifest as hypertension and hematuria. • Nephrotic syndrome may cause edema, weight gain, or hyperlipidemia. • Acute or chronic renal failure may cause symptoms related to uremia and fluid overload.

34. consider biopsy if: Proteinuria > 0.5 g/24 hours red or white cells in urine casts creatinine clearance reduced (<80ml/min)

36. Neuropsychiatric • Headache is the most common neurological symptom • Mood disorders-anxiety and depression • Cognitive disorders • Psychosis, Delirium • Seizures • Stroke and transient ischemic attack (TIA) may be related to vasculitis. • Aseptic meningitis may occur.

37. Cardiac • Pericarditis that manifests as chest pain is the most common cardiac manifestation of SLE and may occur with or without a detectable pericardial effusion. • Libman-Sacks endocarditis is noninfectious but may manifest with symptoms similar to those of infectious endocarditis. • Myocarditis may occur in SLE with heart failure symptomatology.

38. Cardiac manifestations Pericarditis commonest

40. Pulmonary features pneumonitis/fibrosis or haemorrhage pleurisy commonest consider also PE and infection pulmonary hypertension

41. Hematologic abnormalities • leucopenia, • lymphopenia, • Anemia (hemolytic anemia) • thrombocytopenia

42. Diagnosis • Diagnosis based on the clinical findings and laboratory evidence. • Screening laboratory studies to diagnose possible SLE should include: • CBC count with differential- help to screen for leucopenia, lymphopenia, anemia, and thrombocytopenia • serum creatinine

43. urinalysis with microscopy/ urine protein • proteinuria,hematuria, casts, or pyuria. • ANA • inflammatory markers. • Complement levels: C3 and C4 levels are often depressed in patients with active SLE

44. ANA • Antinuclear antibody is an autoantibody against a part of the nucleus • Frequent ANA patterns • Speckled • Homogeneous / Diffuse • Nucleolar • Rim / Peripheral • Centromere

45. In patients with high clinical suspicion or high ANA titers, additional testing is indicated. • Antinuclear antibodies (ANAs) - Higher titers generally more specific (>1:160) • This may include anti–double-stranded DNA (dsDNA)antibodies, complement, and ANA subtypes such as anti-Smith (Sm) antibodies , SSA, SSB, and ribonucleoprotein (RNP)

46. The following are autoantibody tests used in SLE diagnosis: • ANA - Screening test; sensitivity 95%; not diagnostic without clinical features • Anti-dsDNA - High specificity; sensitivity only 70%; level variable based on disease activity • Anti-Sm - Most specific antibody for SLE; only 30-40% sensitivity

47. Anti-SSA (Ro) or Anti-SSB (La) - Present in 15% of patients with SLE and Sekonder Sjögren syndrome; associated with neonatal lupus • Anti-RNP - may indicate mixed connective tissue disease with overlap SLE, scleroderma, and myositis

48. antiphospholipid antibodies (anticardiolipin immunoglobulin G [ACA IgG] or immunoglobulin M [ACA IgM] or lupus anticoagulant) • biologic false-positive serologic test results for syphilis • Anti-histone - Drug-induced lupus (DIL) ANA antibodies often this type (eg, with procainamide or hydralazine; minocycline)

49. Malar rash Discoid rash Photosensitivity Oral ulcers Arthritis Serositis Renal disorder proteinuria > 0.5g cells &/or casts Neurological disorder seizure or psychosis Haematologic disorder haemolytic anaemia leukopenia, lymphopenia thrombocytopenia Immunological disorder anti-DNA, anti-Sm anti-cardiolipin ANA positivity Classification criteria for diagnosis of SLE (>4 of 11)

50. Treatment • Guided by the individual patient's manifestations. • avoid sun exposure • Fever, rash, musculoskeletal, and serositis manifestations - hydroxychloroquine and NSAIDS. Low-to-moderate–dose steroids are necessary for acute flares.