CONNECTIVE TISSUE DISEASES Dr. Müge Bıçakçıgil kalaycı Rheumatology department of Yeditepe University Medical Faculty
Indroduction • collagen vascular diseases,autoimmune diseases • difficult to diagnose – nonspecific symptoms – tend to overlap
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
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
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
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
common histiologic feature – inflammatory damage CT and blood vessels – fibrinoid material deposition
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)
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
Systemic Lupus Erythematosus (SLE) • - prototype autoimmune disease • - unknown etiology • - production of Ab to components of the cell nucleus
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
Clinical Features • Constitutional symptoms: • Fatique, fever, malaise, weigth loss • Low grade fever-active SLE • Rarely 39.5 C-(possible infection)
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
Discoid rash- erythematous patches with kerototic scaling • Maculopapular eruptions- face,V-of the neck,forearms
Butterfly facial rash Photosensitivity
Raynaud’s phenomenon(20-60%) Peripheral extremity changes induced by cold and may be complicated by digital ulcers • Livedoreticularis • Bullous and blistering lesions
Cutaneous vasculitis • Nailfold capillary changes • Alopecia • Ulcers in nose and mouth (20-50%)
Raynaud’s phenomenon Livedo reticularis
Alopecia diffuse or patchy
Mucosal ulcers Sicca symptoms- secondary Sjogren’s syndrome
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.
Renal involvement • The kidney is the most commonly involved visceral organ in SLE. • Glomerular disease usually develops within the first few years after onset.
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.
consider biopsy if: Proteinuria > 0.5 g/24 hours red or white cells in urine casts creatinine clearance reduced (<80ml/min)
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.
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.
Cardiac manifestations Pericarditis commonest
Pulmonary features pneumonitis/fibrosis or haemorrhage pleurisy commonest consider also PE and infection pulmonary hypertension
Hematologic abnormalities • leucopenia, • lymphopenia, • Anemia (hemolytic anemia) • thrombocytopenia
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
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
ANA • Antinuclear antibody is an autoantibody against a part of the nucleus • Frequent ANA patterns • Speckled • Homogeneous / Diffuse • Nucleolar • Rim / Peripheral • Centromere
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)
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
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
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)
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)
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.