1. SJOGREN’S SYNDROME 10/21/20151Dr. Alka Stoelinga

2. SJOGREN’S SYNDROME Autoimmune disorder of unknown etiology Occurs as a result of chronic dysfunction of exocrine glands and is characterized by: – Dryness of mouth, eyes, and other areas covered by mucus membranes Onset:40-50 years F:M=9:1 10/21/20152Dr. Alka Stoelinga

3. Clinical features:  Salivary gland and lacrimal glands are mainly affected 1. Salavary gland enlargement Decrease salivary secretion—Dryness of mouth i.e Xerostomia leading to difficulty in speaking and swallowing, and to severe dental caries. There may be loss of taste and smell 2.Ocular: Decrease tear production Keratoconjunctivitis sicca– Results from inadequate tear production caused by lymphocyte and plasma cell infitration of lacrimal glands 3.Pancreatitis,Pleuritis,neuropsychiatric dysfunction and vasculitis may be present. 4.Renal tubular acidosis and chronic interestitial nephritis may also occur. 10/21/20153Dr. Alka Stoelinga

4. Revised Classification Criteria for Sjögren's Syndrome SS diagnosis requires the presence of signs, symptoms, and lab findings. Patient-reported symptoms must include 1.ocular symptoms, such as daily, persistent, troublesome dry eyes for more than 3 months, and 2.oral symptoms, such as needing to drink water to swallow food. Signs – Positive Schirmer's test Histopathology studies should show – Focal lymphocytic proliferation (Sialadenitis) – Ultrasound examinations  The parenchyma of the gland demonstrates multiple, small-2-6 mm hypoechoic lesions (lymphocytic infiltrates). Sialectasis with calculi are demonstrated if the disease is advanced – Parotid sialography, or salivary scintigraphy (Widespread puddling of the injected contrast scattered throughout the gland) – Autoantibodies against Ro (SSA) and/or La (SSB) antigens 10/21/20154Dr. Alka Stoelinga

5. Investigations: 1. Autoantibodies: ANA Rheumatoid Factor Anti-Ro, Anti-La 2. Schirmer’s test To determine/demonstrate decrease tear production 3. Raised ESR 4. Salivary gland biopsy 10/21/20155Dr. Alka Stoelinga

6. Management: 1.General Artificial tear drop Oral gel for soothing effect 2.Steroid Prednisolone 3. Immunosuppressive Methotrexate Azathioprine 10/21/20156Dr. Alka Stoelinga

7. INFLAMMATORY JOINT DISEASES Rheumatoid arthritis Seronegative spondarthritis Crystal-associated disease Joint infection Juvenile idiopathic arthritis 10/21/20157Dr. Alka Stoelinga

8. Look and Evaluate first for 1.Distribution of joint involvement – Four basic patterns Polyarticular symmetric – RA, SLE Monoarticular arthritis – OA, Gout, Septic arthritis Oligoarticular asymmetric- Spondyloarthropathis- AS Migratory arthropathy- RF, Gonococcal arthritis, Lyme disease 2.Acute or Chronic – Acute -Crystal induced arthritis (Gout, pseudogout), Septic arthritis – Chronic -OA 3.Evidence of systemic Manifestations – SLE – Skin, Lungs, Kidney, CNS, Hematologic manifestations – Systemic sclerosis- Skin+ Raynaud’s phenomenon – Sjögren's syndrome- Keratoconjunctivitis sicca+ Parotid enlargement – Wegener’s granulomatosis - Upper and lower RTI+ Renal involvement – OA- No systemic symptoms 4.Evidence of Inflammation – Joint inflammation- RA – No joint inflammation- OA, Osteoporosis 5.Findings – Morning stiffness >1 hr – Red, warm, erythematous joints – Elevated ESR 10/21/20158Dr. Alka Stoelinga

9. Rheumatoid arthritis 10/21/20159Dr. Alka Stoelinga

10. Case A 30 year old woman presents with 3 week h/o joint swelling and stiffness. She points to her PIPs and MCPs and wrists. She informs that the stiffness lasts for around 2 hrs every morning and symptoms improves as the day progresses. She denies back pain/ stiffness. She has fatigue and low grade fever, Swollen and reddened MCPs and PIPs, DIPs wnl. Fluid in wrist joints. Other examinations are wnl. 10/21/201510Dr. Alka Stoelinga

11. Rheumatoid arthritis Chronic inflammatory multisystem disease with main target being synovium. Non suppurative, proliferative inflammation of synovium Progresses to destruction of the articular cartilage Cause bone erosions Deform joints Ankylosis ( stiffness ) of the joints. 10/21/201511Dr. Alka Stoelinga

12. HALLMARK OF RA Inflammatory synovitis Presenting in symmetrical distribution 10/21/201512Dr. Alka Stoelinga

13. Diagnostic criteria for rheumatoid arthritis Four of the following criteria must be met: – Morning stiffness for > 1 hour everyday for 6 weeks – Swelling of the wrists, MCPs, PIPs for 6 weeks – Swelling of 3 joints for 6 weeks – Symmetric joint swelling for 6 weeks – Joint erosions on X-Ray – RF positive – Rheumatoid nodules 10/21/201513Dr. Alka Stoelinga

14. NEWER CRITERIA 2010 ACR / EULAR Rheumatoid Arthritis Classification Criteria The American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) establish a point value between 0 and 10. Every patient with a point total of 6 or higher is unequivocally classified as an RA patient – Provided S/he has synovitis in at least one joint and – That there is no other diagnosis better explaining the synovitis. Four areas are covered in the diagnosis: 1.Joint involvement – depending on the type and number of joints: up to 5 points 2.Serological parameters – including the rheumatoid factors as well as ACPA (Anti- citrullinated protein antibody): up to 3 points depending on titre level 3.Duration of arthritis: 1 point for symptoms lasting six weeks or longer 4.Acute phase reactants: 1 point for elevated ESR, or elevated CRP value (c-reactive protein) 10/21/201514Dr. Alka Stoelinga

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16. Risk factors – Female – Genetic susceptibility – HLA DR4, DR1, DW15 – Monozygotic twins – I⁰ relatives – SE positive alleles (HLA DR β₁) – Cigarette smoking 10/21/201516Dr. Alka Stoelinga

17. Pathogenesis – RA is an autoimmune disease triggered by exposure of a genetically susceptible host Autoimmune reaction Activation of CD4 +T cells and lymphocytes and the release of inflammatory mediators and cytokines Produce stimulates Synovial cells Produce Various mediators of inflammation (PG ) and Matrix metalloproteinase (cartilage destruction) Produce by macrophages and synovial lining cells that are activated by the T – cells in the joints Osteoclasts Bone destruction Progressive joint damage Activates Promotes 10/21/201517Dr. Alka Stoelinga

18. Synovium ( hyperplastic ) Synovium rich in Inflammatory cells becomes adherent and grows over the articular surface, forming a Pannus - an inflammatory exdudate overlying the synovial cells on the inside of a joint stimulates Release of IL-1, platelet – derived growth factor Prostaglandin Cause cartilage destruction and bone erosion 10/21/201518Dr. Alka Stoelinga

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20. Clinical Features 1.Slow and Insidious onset – Joint pain, Stiffness, Symmetrical swelling of peripheral joints – Initially pain on movement of joint- later – rest pain – Florid morning stiffness – Polyarthritis- First affecting the small joints of fingers and toes; followed by wrists, elbows, shoulders, knees, ankles, subtalar and midtarsal joints – Swelling of PIP joints  Spindle shaped fingers – Swelling of MTP joints  Broadening of forefoot 2.Acute Onset – Acute Polyarthritis with severe systemic symptoms 3.Systemic Onset – Mild fever – Malaise – Fatigue – Weight loss 4.Palindromic onset – Recurrent acute episodes of joint pain and stiffness lasting for few hrs to days 10/21/201520Dr. Alka Stoelinga

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22. Clinical Features Damage to ligaments and tendons: – Radial deviation of wrists and Ulnar deviation of digits (due to rupture of the collateral ligaments at the MCP joints ) – Swan-neck deformity ( due to rupture of the volar plate of the PIP joints ) and – Boutonniere deformity (due to rupture of central extensors) of the fingers – Z- deformity of thumbs – Forefoot- Clawing of toes 10/21/201522Dr. Alka Stoelinga

23. Clinical Features 1.Systemic Fever Malaise Fatigue Weight loss 4.Lymphatic Splenomegaly Felty’s syndrome 7.Ocular Scleritis, Episcleritis Scleromalacia performs Keratoconjunctivitis sicca 2.Musculoskeletal Muscle wasting Tenosynovitis; Bursitis Osteoporosis 5.Pulmonary Pleurisy, Effusions Nodules in lungs and Pleura Fibrosing alveolitis 8.Vasculitis Digital Ischemia Leg Ulcers Pyoderma gangrenosum Mesenteric ischemia 3.Hematological Anemia Thrombocytosis Eosinophilia Felty’s syndrome (RA+ Neutropenia+ Splenomegaly) 6.Cardiac Pericarditis, Myocarditis, Endocarditis Nodules in Pericardium Pericardial Effusion 9.Neurological Peripheral neuropathy Spinal cord compression (Cervical) Mononeuritic Multiplex Carpal Tunnel Syndrome 10. Rheumatoid nodules11. Amyloidosis 10/21/201523Dr. Alka Stoelinga

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25. NOTE Rheumatoid nodules – Initial event caused by vasculitis – Common Sites: Olecranon, Occiput, Achilles tendon Felty’s syndrome (RA+ Neutropenia+ Splenomegaly) Caplan syndrome (RA+ Pulmonary involvement) 10/21/201525Dr. Alka Stoelinga

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30. INVESTIGATIONS IMAGING 1.X-rays of Hands and Feet – Early Stage: No change – Juxta-articular osteopenia, soft tissue swelling and loss of joint space – Advanced Stage: Bony erosions and subluxation 2.High-frequency transducers - Can depict 20% more erosions than conventional radiography 3.Color Doppler and Power Doppler ultrasound- Show vascular signals of active synovitis depending on the degree of inflammation; are useful in assessing synovial inflammation BLOOD TESTS: 1.Immunological tests – Anti-citrullinated protein antibodies (ACPAs)- Anti-CCP/ Anti- MCV assays – Serological point-of-care test (POCT) – RF 2.OTHER TESTS: – ANA, ESR, CRP : usually raised but may be normal. – CBC- Normochromic, Normocytic anemia and reactive thrombocytosis. – Ferritin levels- Raised ferritin but low serum iron concentration and total iron binding capacity. – LFT- mild elevation of alkaline phosphatase – Uric acid/synovial fluid analysis: excludes polyarticular gout. – Urinalysis: microscopic hematuria/proteinuria may suggest connective tissue disease. 10/21/201530Dr. Alka Stoelinga

31. XRAY – Show soft tissue swelling, – periarticular osteopenia – loss of joint space – erosions – Deformity – Radial deviation of the wrist – Ulnar deviation of the fingers – Swan neck deformity ( flexon – hyperextension deformity ). 10/21/201531Dr. Alka Stoelinga

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33. DIAGNOSIS Based upon Clinical criteria 2010 ACR / EULAR Rheumatoid Arthritis Classification Criteria >/= 6 Anti-CCP (Positive in 67% of RA cases; but are rarely positive if RA is not present- Specificity- 95%) Anti MCV POCT (RF+ Anti MCV) for early diagnosis of RA (72% Sensitive; 99.7% Specificity) 10/21/201533Dr. Alka Stoelinga

34. TREATMENT The goal of treatment is: Alleviating the current symptoms Preventing the future destruction of the joints with the resulting handicap if the disease is left unchecked 10/21/2015Dr. Alka Stoelinga34

35. TREATMENT 1.Disease modifying anti-rheumatic drugs (DMARDs) – reduces the rate of damage to bone and cartilage – Methotrexate (MTX) – Cyclosporine – Sulfasalazine – Azathioprine – D-Penicillamine – Hydroxychloroquine 2.Combi-therapy of DMARDs – Methotrexate – Hydroxychloroquine – Methotrexate – sulfasalazine – Sulfasalazine – Hydroxychloroquine – Methotrexate – Hydroxychloroquine – sulfasalazine 3.Anti-inflammatory agents and analgesics – Glucocorticoids (Prednisolone, Methylprednisolone) – NSAIDS (Acetaminophen, Ibuprofen, Naproxen, meloxicam, etodolac, nabumetone, sulindac, tolementin, choline magnesium salicylate, diclofenac, diflusinal, indomethicin, Ketoprofen, Oxaprozin and piroxicam) 10/21/2015Dr. Alka Stoelinga35

36. TREATMENT 4.Surgery – Synovectomy – Osteotomy – Arthrodesis – Arthroplasties 10/21/2015Dr. Alka Stoelinga36

37. Prognosis Average life span is reduced by 8-15 years About 50%- 5 year survival rate with severe disease 50% disabled/ unable to work within 10 years Poorer prognosis is associated with: – Insidious onset – Extra-articular manifestations – Functional disability at 1 year after start of disease – High RF titres – HLA-DR4 present – X-Ray evidence of erosions within 3 years 10/21/201537Dr. Alka Stoelinga