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Connective tissue diseases (7)
The document provides an overview of connective tissue diseases, focusing on systemic lupus erythematosus (SLE) and rheumatoid arthritis, including their symptoms, diagnostic criteria, and treatment options. It highlights the autoimmune nature of these conditions, their prevalence, and various clinical manifestations affecting different organ systems. Additionally, the document discusses related syndromes like Sjögren's syndrome and the importance of differentiating these diseases based on specific autoimmune markers and clinical features.
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Connective tissue diseases (7)
- 1. Dr. Suhail S.KishawiDr. Suhail S. Kishawi Consultant in Endocrinology and DiabetesConsultant in Endocrinology and Diabetes Consultant in internal MedicineConsultant in internal Medicine
- 2. Connective Tissue Diseases Perivascularcollagen deposition=Collagen Vascular Diseases Autoimmune diseases-not the primary cause Exact cause remains obscure Different diseases associated with specific autoantibodies
- 3. Connective Tissue Diseases Histopathology:Connective tissue and blood vessel inflammation and abundant fibrinoid deposits Varying tissue distribution and pattern of organ involvement Symptoms nonspecific and overlapping Difficult to diagnose
- 4. Connective Tissue Diseases DiseaseAutoantibody Systemic Lupus Erythematosus Anti-dsDNA, Anti-SM Rheumatoid Arthritis RF, Anti-RA33 Sjögren's Syndrome Anti-Ro(SS-A),Anti-La(SS- B) Systemic Sclerosis Anti-Scl-70, Anti- centromere Polymyositis/ Dermatomyositis Anti-Jo-1 Mixed Connective Tissue Disease Anti-U1-RNP Wegener’s Granulomatosus c-ANCA
- 5. Systemic Lupus Erythematosus Inflammatory autoimmune disorder affecting multiple organ systems characterized by the production of autoantibodies directed against cell nuclei. The name by which this disease is known alludes to the wolf -lupus in Latin- because of the destructive injuries that can bring to mind the bites of this animal.
- 6. Systemic Lupus Erythematosus General Autoimmunemultisystem disease Prevalence 1 in 2,000 10 to 1: female to male (1 in 700) Peak age 15-25 Black > white (1:250 vs. 1:1000) HLA DR3 association, family history Immune complex deposition Photosensitive skin eruptions, serositis, pneumonitis, myocarditis, nephritis, CNS involvement Severity is equal in male and female
- 7. Systemic Lupus Erythematosus Specificnative(Double stranded) DNA, SM antigen Lupus like reaction by drugs (procainamide, hydralazine, ect) LE cells
- 8. LE Cell The LEcell is a neutrophil that has engulfed the antibody-coated nucleus of another neutrophil. LE cells may appear in rosettes where there are several neutrophils varying for an individual complement covered protein.
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- 10. CLINICAL FEATURES: Mucocutaneous Malar Rash(butterfly erythema) Discoid rash Photosensitive rash Subacute cutaneous LE Livedo reticularis Alopecia Raynaud’s Vasculitic ulceration Oral ulceration Nasal septal perforation Nailfold capillary changes
- 11. MALAR RASH Fixed erythema,flat or raised, over the malar eminences Tending to spare the nasolabial folds
- 12. DISCOID RASH Erythematous raised patcheswith adherent keratotic scaling and follicular plugging; Atrophic scarring may occur in older lesions
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- 16. ORAL ULCERS Oral ornasopharyngeal ulceration Usually painless, observed by a physician
- 17. SLE - VASCULOPATHY Small vessel vasculitis Raynaud's phenomenon is excessively reduced blood flow in response to cold or emotional stress, causing discoloration of the fingers, toes, and occasionally other areas. This condition may also cause nails to become brittle with longitudinal ridges, the phenomenon is believed to be the result of vasospasms that decrease blood supply to the respective regions. Antiphospholipid antibody syndrome
- 18. CLINICAL FEATURES: Musculoskeletal Arthritis isNONEROSIVE, transient, symmetrical, affecting small joints, seldom deforming, less severe than RA Most common presenting feature of SLE
- 19. CLINICAL FEATURES: Musculoskeletal Synovitis-90% patients,often the earliest sign Osteoporosis From SLE itself and therapy (usually steroids) Osteonecrosis (avascular necrosis) Can occur with & without history of steroid therapy
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- 21. CLINICAL FEATURES: Ocular Conjunctivitis Photophobia Monocularblindness-transient or permanent Blurred vision Cotton-Wool spots on retina-degeneration nerves fibers due to occlusion retinal blood vessels
- 22. CLINICAL FEATURES: PLEUROPULMONARY Pleuritis/Pleural effusion Infiltrates/Discoid Atelectasis Acute lupus pneumonitis Pulmonary hemorrhage “Shrinking lung” - diaphragm dysfunction Restrictive lung disease
- 23. CLINICAL FEATURES: Cardiac Pericarditis–in majority of patients Libman Sacks endocarditis Cardiac failure Cardiac Arrythmias-common Valvular heart disease Coronary Artery Disease
- 24. Lupus - Endocarditis Noninfectivethrombotic endocarditis involving mitral valve in SLE. Note nodular vegetations along line of closure and extending onto chordae tendineae.
- 25. CLINICAL FEATURES: HEMATOLOGICDISORDER A) Hemolyticanemia - with reticulocytosis OR B) Leukopenia - less than 4,000/mm3 total on 2 or more occasions OR C) Lymphopenia - less than 1,500/mm3 on 2 or more occasions OR D) Thrombocytopenia - less than 100,000/mm3 in the absence of offending drugs
- 26. CLINICAL FEATURES: Neurologic Behavior/Personalitychanges, depression Cognitive dysfunction Psychosis May be difficult to distinguish from steroid psychosis or primary psychiatric disease Seizures Stroke Chorea Pseudotumor cerebri Transverse myelitis Peripheral neuropathy
- 27. CLINICAL FEATURES: Renal(Lupus Nephritis) Develops in up to 50% of patients 10% SLE patients go to dialysis or transplant Hallmark clinical finding is proteinuria Advancing renal failure complicates assessment of SLE disease activity Nephritis remains the most frequent cause of disease-related death.
- 28. CLINICAL FEATURES: Renal(Lupus Nephritis) Usually asymptomatic Gross hematuria Nephrotic syndrome Acute renal failure Hypertension End stage renal failure (ESRD)
- 29. CLINICAL FEATURES: Gastrointestinal& Hepatic Uncommon SLE manifestation Severe abdominal pain syndromes in SLE often indicate mesenteric vasculitis, resembling medium vessel vasculitis (PAN) Diverticulitis may be masked by steroids Hepatic abnormalities more often due to therapy than to SLE itself
- 30. Laboratory Findings Complete bloodcount Anemia Leukopenia Lymphopenia Thrombocytopenia Urine Analysis Hematuria Proteinuria Granular casts
- 31. Monitoring Test: ErythrocyteSedimentation Rate
- 32. Immunological findings ANA- 95-100%-sensitive but not specific for SLE Anti -ds DNA-specific(60%)-specific for SLE, but positive to other non lupus conditions 4 RNA associated antibodies Anti-Sm (Smith) Anti Ro/SSA-antibody Anti La/SSB-antibody Anti-RNP Antiphospholipid antibody Biologic false + RPR Lupus anticoagulant-antibodies coagulation factors, risk factor for venous and arterial thrombosis and miscarriage. Anti-cardiolipin Depressed serum complement
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- 35. DIFFERENTIAL DIAGNOSIS Almosttoo broad to consider given number of clinical manifestations Rheumatic: RA, Sjogren’s syndrome, systemic sclerosis, dermatomyositis Nonrheumatic: HIV, endocarditis, viral infections, hematologic malignancies, vasculitis, ITP, other causes of nephritis “Overlap Syndrome” (MCTD)* *MCTD ( Mixed Connective Tissue Disease)
- 36. CLASSIFICATION 1. Malar rash 2.Discoid rash 3. Photosensitivity 4. Oral ulcers 5. Arthritis 6. Serositis 7. Renal disease. > 0.5 g/d proteinuria ≥ 3+ dipstick proteinuria Cellular casts 8. Neurologic disease. Seizures Psychosis (without other cause) 9. Hematologic disorders. Hemolytic anemia Leukopenia (< 4000/uL) Lymphopenia (< 1500/uL) Thrombocytopenia (< 100,000/uL) 10. Immunologic abnormalities. Positive LE cell Anti-ds- DNA Anti- Sm Any antiphospholipid 11. Positive ANA ( 95-100% ) THE 1982 REVISED CRITERIA FOR CLASSIFICATION OF SLE
- 37. Systemic Lupus Erythematosus:Diagnostic Criteria
- 38. CLASSIFICATION CRITERIA Must have4 of 11 for Classification Like RA, diagnosis is ultimately clinical Not all “Lupus” is SLE Discoid Lupus Overlap syndrome Drug induced lupus Subacute Cutaneous Lupus
- 39. LUPUS RELATED SYNDROMES DrugInduced Lupus Classically associated with hydralazine, isoniazid, procainamide Male: Female ratio is equal Nephritis and CNS abnormalities rare Normal complement and no anti-DNA antibodies Symptoms usually resolve with stopping drug
- 40. LUPUS RELATED SYNDROMES Antiphospholipid Syndrome (APS) Hypercoagulability with recurrent thrombosis of either venous or arterial circulation Thrombocytopenia-common Pregnancy complication-miscarriage in first trimester Lifelong anticoagulation warfarin is currently recommended for patients with serious complications due to common recurrence of thrombosis Antiphospholipid Antibodies Primary when present without other SLE feature. Secondary when usual SLE features present
- 41. LUPUS RELATED SYNDROMES Raynaud’sSyndrome: Not part of the diagnostic criteria for SLE Does NOT warrant ANA if no other clinical evidence to suggest autoimmune disease
- 42. SLE – treatment Mild cases (mild skin or joint involvement): NSAID, local treatment, hydroxy-chloroquin Cases of intermediate severity (serositis, cytopenia, marked skin or joint involvement): corticosteroid (12-64 mg methylprednisolon), azathioprin, methotrexat Severe, life-threatening organ involvements (carditis, nephritis, systemic vasculitis, cerebral manifestations): high-dose intravenous corticosteroid + iv. cyclophosphamide + in some cases: plasmapheresis or iv. immunoglobulin, or, instead of cyclophosphamide: mycophenolate mofetil Some cases of nephritis (especially membranous), myositis, thrombocytopenia: cyclosporine
- 43. PROGNOSIS Unpredictable course 10 yearsurvival rates exceed 85% Most SLE patients die from infection, probably related to therapy which suppresses immune system and renal failure Recommend smoking cessation, yearly flu shots, pneumovax q5years, and preventive cancer screening recommendations
- 45. Rheumatoid Arthritis 1% ofthe population Women affected 2-3 X more than men Age of onset is 40-50 Juvenile form
- 46. Rheumatoid Arthritis Inflammation ofthe synovial tissue (lymphocytic) with synovial proliferation Symmetric involvement of peripheral joints, hands, feet and wrists Occasional systemic effects: vasculitis, visceral nodules, Sjogren syndrome, pulmonary fibrosis Anti-RA-33 autoantibodies RA associated nuclear antigen (RANA)
- 47. Rheumatoid Arthritis: DiagnosticCriteria 1. Morning stiffness (>1h) 2. Swelling of three or more joints 3. Swelling of hand joints (proximal interphalangeal, metacarpophalyngeal, or wrist) 4. Symmetric joint swelling 5. Subcutaneous nodules 6. Serum Rheumatoid Factor 7. Radiographic evidence of erosions or periarticular osteopenia in hand or wrists Criteria 1-4 must have been present continuously for 6 weeks or longer and must be observed by a physician. A diagnosis of rheumatoid arthritis requires that 4 of the 7 criteria are fulfilled.
- 48. Rheumatoid Arthritis General Nonarticular muscularstructures Tendon, ligament, fascia Systemic disease occas. Vasculitis, pulmonary fibrosis Pathogenosis Inflammatory cell infiltrates Synovial proliferation HLA Dw4
- 49. Rheumatoid Arthritis General Prevalence 1%of population 2-3 times F>M 4th and 5th decade Signs and symptoms Morning stiffness lasting greater than 30 min Subcutaneous rheumatoid nodules Synovial fluid inflammation
- 50. Rheumatoid Arthritis General Synovial tissue involvement Symmetricperipheral joints (hands, feet, wrists)
- 51. Rheumatoid Arthritis General Diagnosis basedon clinical grounds Labs RF pos. in 12 months 90% RA associated nuclear antigen anti-RA-33
- 52. Rheumatoid Arthritis Head andNeck Manifestations TM joint 55% symptomatic 70% incidence on X-ray Juvenile RA – micrognathia : is a condition where the jaw is undersized. It is also sometimes called "Mandibular hypoplasia"
- 53. Rheumatoid Arthritis Head andNeck Manifestations Cricoarytenoid joint Most common cause of arthritis 30% patients hoarse 86% pathologic involvement Exertional dyspnea, ear pain, globus Hoarseness Rheumatoid nodules, recurrent nerve involvement Stridor Local/systemic steroids Possible Tracheotomy
- 54. Rheumatoid Arthritis Treatment Physicaltherapy, daily exercise, splinting, joint protection Salicylates, NSAID’s, gold salts, penicillamine, hydroxychloroquine, immunosuppressive agents Systemic steroids should be avoided Prognosis 10-15 yrs of disease 50% fully employed 10% incapacitated 10-20% remission
- 55. Sjögren's Syndrome Chronicdisorder characterized by immune-mediated destruction of exocrine glands Primary vs Secondary: Primary” Sjögren's syndrome occurs in people with no other rheumatologic disease. “Secondary” Sjögren's occurs in people who have another rheumatologic disease, most often systemic lupus erythematosus and rheumatoid arthritis. Primary is diagnosis of exclusion Secondary refers to the sicca complex accompanying any of the connective tissue diseases (xerophthalmia, keratoconjuntivitis, xerostomia with/without salivary gland enlargement)
- 56. Sjögren's Syndrome 1% ofthe population and in 10-15% of RA patients 9:1 female:male preponderance Age of onset 40-60 years Associated with a 30-40 times increased risk of lymphoma.
- 57. Sjögren's Syndrome May affectthe skin, external genitalia, GI tract, kidneys, and lungs Minor salivary gland biopsy demonstrates lymphocytic infiltration. Parotid biopsy more sensitive and specific
- 58. Sjögren's Syndrome :Diagnostic Criteria 1. Dry eyes (>3mos), sensation of sand or gravel in eyes, or use of tear substitutes>3x per day 2. Dry mouth (>3mos), recurrent or persistent swollen salivary glands, or frequent drinking of liquids to aid in swallowing dry foods. 3. Schirmer-I test (<5mm in 5 min) or Rose Bengal score >4. 4. >50 mononuclear cells/4mm2 glandular tissue 5. Abnormal salivary scintigraphy or parotid sialography or unstimulated salivary flow <1.5ml in 15 min 6. Presence of anti-Ro/SS-A, anti-La/SS-b, antinuclear antibodies, or rheumatoid factor.
- 59. Sjögren's Syndrome 80% experiencexerostomia Difficulty chewing, dysphagia, taste changes, fissures of tongue and lips, increased dental caries and oral candidiasis Salivary gland enlargement Sicca syndrome
- 60. Sjogren’s Syndrome General Clinical manifestations Xerophthalmia, keratoconjunctivitis Xerostomia Other areas Skin, vagina, genitalia, chronic bronchitis, GI tract, renal tubules Diagnosis Minor salivary gland biopsy Labs RF and ANA SS-A/ro 60% SS-B/La 30%
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- 62. Sjögren's Syndrome Head andneck manifestations 80% c/o xerostomia, most prominent symptom Difficulty chewing, dysphagia, taste changes, fissures of tongue and lips, increased dental caries, oral candidiasis
- 63. Sjögren's Syndrome Head andNeck Manifestations Salivary quantification- salivary scintigraphy Salivary gland enlargement
- 64. Sjögren's Syndrome Eye complaints Dryness, burning, itching, foreign body sensation Keratoconjunctivitis sicca Corneal abrasions - rose bengal staining
- 65. Sjögren's Syndrome: Treatment Symptomatic: saliva substitutes, artificial tears, increased oral fluid intake Avoid decongestants, antihistamines, anticholinergics, diuretics Pilocarpine, antifungals, close dental follow-up, surveillance for malignancy
- 66. Sjögren's Syndrome Treatment Symptomatic Oralfluid intake Saliva substitutes Artificial tears Avoid Decongestants Antihistamines Diuretics Anticholinergic
- 67. POINTS TO REMEMBER •To reducerisk for cavities and other dental problems, patients must pay close attention to proper oral hygiene and regular dental care.
- 68. POINTS TO REMEMBER Sjögren's syndrome is an autoimmune condition that can occur at any age, but is most common in older women. Many patients develop Sjögren's syndrome as a complication of another autoimmune disease, such as rheumatoid arthritis or lupus. Most of the treatment for Sjögren's syndrome is aimed at relieving symptoms of dry eyes and mouth and preventing and treating long- term complications such as infection and dental disease. Treatments often do not completely eliminate the symptoms of dryness. Most patients with Sjögren's syndrome remain healthy, but some rare complications have been described, including an increased risk for cancer of the lymph glands (lymphoma). Thus, regular medical care and follow up is important for all patients.
- 69. Scleroderma(Progressive Sclerosis) General Increased depostioncollagen in interstitium of small arteries and connective tissue Sclerotic skin changes, often multisystem disease Prevalence 4-12/million/year 3-4 to 1 F>M 30-50 yrs Prognosis Black worse than white Men worse than women
- 70. Scleroderma General Presentation Raynaud’s phenomenon Edema fingers and hands Skin thickening Visceral manifestations GI tract, lung, hear, kidneys, thyroid Arthralgias and muscle weakness often
- 71. Scleroderma General Four categories 1. Diffusecutaneous Worse prognosis 1. Limited cutaneous (CREST) More benign, less renal 1. Systemic sclerosis sine scleroderma Visceral manifestations without skin changes 1. Systemic sclerosis in overlap Concomitant with SLE, polymyositis, RA
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- 74. Scleroderma Head and neckmanifestations 80 % have, 30% present with Tight skin, thin lips, vertical perioral furrows Dermal and subcutaneous inflammatory process Edema precedes epidermal atrophy, loss of appendages
- 75. Scleroderma Head and neckmanifestations Dysphagia Most common initial complaint 80% distal 2/3 pathology on BS Decrease/absent paristalsis, dilation, hiatal hernia
- 76. Scleroderma Head and neckmanifestations Decreased mouth opening Initial complaint 19%
- 77. Scleroderma Treatment Symptomatic Calcium channelblockers in raynaud’s H2 blockers for reflux NSAID’s and steroids for arthralgias and myalgias Hand rehab Intra-arterial reserpine- decreases vasoconstriction>healing
- 78. Mixed Connective TissueDisease Head and neck manifestations Combination of features of other CTD Mucocutaneous rash, malar rash, discoid lupus, sclerodermatous changes, nasal septal perforation, esophageal dysfunction Treatment Steroid therapy for symptomatic relief Immunosuppressives for complications of vital organs
- 79. Vasculitides Inflammation and necrosisof blood vessels Immunologic mechanism Any blood vessel involved Diverse symptoms and overlap Difficult classification
- 80. Vasculitides Pathogenesis Unclear Deposition of antibody-antigen-complementin vessel walls Antigen deposition triggering lymphcytic reaction
- 81. Classification of SystemicVasculitides
- 82. Behcet’s Disease Vasculitis with triad Oral, genital ulcers, uveitis or iritis Oral Aphthous-like Painful, clusters on lips, gingiva, buccal, tongue Less often palate, oropharynx
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- 84. Behcet’s Disease Occular Uveitis,iritis Hypopyon Healing in days to weeks some scarring Symptoms simultaneousl y, months apart
- 85. Behcet’s Disease Other findings Progressive SNHL ( sensorineural hearing loss), tinnitus, vertigo Nasal, laryngeal, tracheal mucosal ulceration CNS involvement, bowel dysfunction, large vessel arteritis Treatment Azothioprine, methotrexate possibly, not documented
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