Connective Tissue Diseases with Dr. Müge Bıçakçıgil - Yeditepe University

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. SLE • Pathologic findings of SLE: • occur throughout the body and are manifested by • inflammation, blood vessel abnormalities • (vasculopathy and vasculitis), and immune • complex deposition.

13. 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

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

15. 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

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

17. Butterfly facial rash Photosensitivity

18. Systemic lupus erythematosus: butterfly rash

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

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

23. Raynaud’s phenomenon Livedo reticularis

24. Alopecia is a commonfeature of SLE. • Hairlossmay be diffuseorpatchy. • withbreakingoff of hairs in thefront of thescalpandalopeciaareata. • associatedwithexacerbations of thedisease-hairtendstoregrowwhenthedisease is undercontrol. • it mayresultfromtheextensivescarringof discoidlesions-may be permanent

25. Alopecia diffuse or patchy

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

29. Vasculitis

31. Systemic lupus erythematosus: hands, interarticular dermatitis

32. Nail fold microscopy • Normal capillaries. • Tortuous and enlarged capillaries

34. MusculoskeletalfeaturesArthritis • Involvement of thejointseither as arthralgias, arthritis, orboth is one of theearliestandmostcommonpresentingmanifestations • Thedeformingarthritisin systemiclupus can be categorizedintothreetypes: • a non-erosivearthropathy—Jaccoudarthritis, (2) an erosivesymmetricpolyarthritiswithrheumatoidarthritis–likedeformities—“rhupus,” and (3) milddeformingarthritis.

35. 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.

36. Synovitis and Jaccoud’s arthropathy

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

38. 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.

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

41. 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.

42. 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.

43. Cardiac manifestations Pericarditis commonest

45. Pleuralinvolvement • Pleuralmanifestations-30% to 60% • Pleuraleffusionsmayoccurandareusuallysmall but can occasionally be massive. Theyarealsofrequentlybilateral. • Thefluid is usually anexudate

46. Pneumonitis • Lupuspneumonitismaypresent as eitheracuteorchronic. • Acutelupuspneumonitisusuallyoccursduring a generalizedmultisystemlupusflare; • patientsmaypresentwithsymptoms of fever, dyspnea, cough, pleuriticchestpain, and, occasionally, hemoptysis. • Chestradiographyand CT scanshowunilateralorbilateralalveolarinfiltrateswithground-glassopacification. • Chroniclupuspneumonitispresents as interstitiallungdisease

47. Pulmonaryhemorrhage • Diffusealveolarhemorrhageis a veryseriouscondition • mortalityratesrangingfrom 50% to 90%. • abruptonset of dyspnea, cough, fever, infiltratesand a dramaticfall in hemoglobin. • dueto a vasculitis Pulmonaryhypertension • duetoeitherthediseaseprocessorcomplicationssuch as pulmonaryembolism, valvularheartdisease, andinterstitiallungdisease Shrinkinglungsyndrome • A subset of SLE patientspresentswithunexplaineddyspnea, smalllungvolumeswithrestrictivepulmonaryfunctionstudies, and an elevateddiaphragm.

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

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

50. 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