2. Arthritis Arthritis defined as articular swelling/effusion or the presence of two or more of the following signs: Limitation of range of movement Joint tenderness on palpation Pain on joint movement Increased heat over joint Arthritis lasting for > 6 weeks→ acute arthritis Arthritis lasts at least 6 weeks → chronic arthritis

3. Juvenile idiopathic arthritis Juvenile idiopathic arthritis (JIA) is a chronic, inflammatory disease of unknown etiology. The term “JIA” describes a clinically heterogeneous group of diseases characterized by arthritis that begins before the age of 16 years, involves one or more joints, and lasts at least 6 weeks. Distinct clinical features characterize each of the JIA categories during the first 6 months of the disease.

4. Classification There are seven subtypes of JIA: 1. Oligoarticular 2. Polyarticular (RhF negative) 3. Polyarticular (RhF positive) 4. Systemic 5. Enthesitis related 6. Psoriatic. Undifferentiated arthritis.

5. Oligoarticular JIA Affects four or less joints. This is the most common subtype The most commonly affected joints are the knees, elbows, and ankles

6. Oligoarticular JIA Antinuclear antibodies (ANAs) are frequently present and are associated with an increased risk of iridocyclitis/uveitis. Up to 20% of children with oligoarthritis may develop chronic anterior uveitis

7. Polyarticular (RF negative) when five or more joints are affected. Rheumatoid factor (RhF-). Polyarticular (RF positive) when five or more joints are affected and RhF is found on blood testing. This subtype may behave similarly to rheumatoid arthritis in adults Polyarticular JIA

8. Chronic arthritis associated with systemic features, including high spiking fever, transient episodic erythematous rash lymphadenopathy hepatosplenomegaly (systemic features often precede the arthritis ) Systemic JIA

10. Systemic-onset juvenile rheumatoid arthritis Treatment Steroid as soon as possible (Pulse steroids?) Immunosuppressives for maintain therapy Biological agent if needed (Anakinra)

11. Enthesitis Related Arthritis – (Previously known as juvenile spondyloarthropathy). This is a chronic arthritis associated with enthesitis (inflammation at insertion of tendons, ligaments or fascia to bone), or with lower axial skeletal involvement. HLA B27 is present or there is a family history of a first degree relative with a HLA B27 related disease.

12. Enthesitis Related Arthritis arthritis and enthesitis of at least 6 weeks’ duration in a child younger than 16 years, or arthritis or enthesitis plus two of the following: sacroiliac tenderness inflammatory spinal pain, HLA-B27 positivity, onset of arthritis in a male older than 6 years, and family history of HLA-B27-associated disease.

13. Common clinical manifestations of ERA include arthritis, enthesitis, and acute anterior uveitis. Enthesitis Related Arthritis

14. Psoriatic Chronic arthritis, usually with asymmetrical involvement of small and large joints, and either the development of psoriasis or other evidence of a psoriatic diathesis (two of the following) family history in a first degree relative, nail pits or onycholysis, dactylitis.

16. Diagnostic investigations in suspected JIA Base investigations usually include: ESR or C-reactive protein (CRP) Full blood count (FBC). Rheumatoid factor (RhF), Antinuclear antigen (ANA), Human leukocyte antigen (HLA) B27, Plain radiographs..

20. Definition Autoimmune multisystem disease characterized by widespread inflammation and production of autoantibodies This means wide spectrum of presentations

22. Main Pathology The plasma cells are producing antibodies that are specific for self proteins, namely ds-DNA Overactive B-cells Estrogen is a stimulator of B-cell activity Lupus is much more prevalent in females of ages 15-45 Suppressed regulatory function in T-cells Activation of the Complement system

24. Clinical Criteria  Acute cutaneous Lupus (Malar rash, bulllous lupus, toxic epidermal necrolysis variant of SLE, maculopapular lupus rash or subacute cutaneous lupus)  Chronic Cutaneous Lupus Classic discoid rash, lupus panniculiştis, mucosal lupus, lupus erythematous turnidus,chilblains lupus,discoid lupus/lichenplanus overlap  Oral or nasal ulcers  Nonscaring alopecia  Synovitis (≥ 1 joints)   Serositis  ( Pleurisy or pericardial pain≥ 1 day, pleural effusion or rub, pericardial effusion or rub, EKG evidence of perikarditis)

25.  Renal Presence of red blood cell casts or urine protein/creatinine ratio representing >500mg protein/24 hours  Neurologic Seizures, psychosis,mononeuritis multiplex, myelitis, peripheral or cranial neurapathy, or acute confusional state  Hemolytic anemia Leukopenia (<4,000/mm 3 ),or lymphopenia (<1,000/mm 3 )  Thrombocytopenia (<100,00/mm 3 )

26. 1-Pozitive antinuclear antibody 2-Positive double stranded DNA antibody 3-Pozitive anti-Smith antibody 4-Antiphospholipid antibody positivity Positive test for lupus anticoagulant False-positive test result for rapid plasma reagin,Medium or high-titer anticardiolipin antibody level (IgA, IgG, or IgM) Positive test result for anti–  2-glycoprotein I (IgA, IgG, or IgM) 5-Lower complement Low C3,C4 or CH50 6-Positive direct Coombs test (in the absence of hemolytic anemia ) Requirements :≥4 criteria (at least 1 clinical criteria and 1 laboratory criteria Or biopsy proven lupus nephrits with positive ANA or anti-DNA Requirements :≥4 criteria (at least 1 clinical criteria and 1 laboratory criteria Or biopsy proven lupus nephrits with positive ANA or anti-DNA

29.  Mild cases (mild skin or joint involvement): NSAID, local treatment, hydroxy-chloroquine  Cases of intermediate severity (serositis, cytopenia, marked skin or joint involvement): corticosteroid, azathioprine, methotrexate

30.  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

32.  JDMS is a multisystem occlusive vasculopathy predominantly affecting vessels in skin(typical rash), muscle(muscle weakness), and gastrointestinal tract

33.  4/5 criteria  Symmetric weakness of the proximal musculature  Cutaneous findings  heliotrope discoloration of the eyelids with periorbital edema  erythematous, scaly rash over the dorsal aspect of the metacarpophalangeal and proximal interphalangeal joints (Gottron’s papules)

34. Elevation of skeletal muscle enzymes: ○ CPK, AST, ALT, lactic dehydrogenase, and aldolase. Electromyographic evidence of myopathy and denervation characterized ○ brief polyphasic motor units of decreased amplitude and high frequency discharges. Muscle biopsy findings ○ evidence of necrosis of fibers with small blood vessel vasculitis.

36. Scleroderma

37.  Localized scleroderma – most common in children.  This form of scleroderma does not change into the generalized forms of scleroderma.  Systemic scleroderma (sclerosis) – rare in children

38.  Systemic sclerosis (SSc) is a rare multisystemic disease characterized by inflammation, vascular abnormalities, and fibrosis that affects the skin and various internal organs

39. Clinical Findings in Systemic Sclerosis

40. Raynaud’s Phenomenon

41. Systemic sclerosis is a rare, heterogeneous, slow-motion disease, with (allegedly) a small window of opportunity to fundamentally change the course of the disease.

45.  Mixed connective tissue disease has signs and symptoms of a combination of disorders — primarily lupus, scleroderma and polymyositis.

46.  Early Features  Arthritis – can be erosive or non-erosive  Raynaud’s  Puffy Hands/sausage digits  Later features  Can develop skin thickening typical of Scleroderma  Can develop lupus manifestations  Can develop organ involvement: lungs, kidneys, muscle.

47.  Scleroderma Features  SLE (Lupus) Features  Inflammatory Myositis Features  Rheumatoid Arthritis

48.  Extractable Nuclear antigens:  Ribonucleoproteins extractable from nucleus  SSA, SSB, smith, RNP, Jo-1, Scl-70, others  U1-RNP Antibody  Antigen: complex of series of small ribonucleoproteins containing (U1-snRNP)  3 polypeptides (70 kd, A, C)  Linked to U1 RNA

49.  Diagnostic criteria  elevated anti U1-RNP plus  three of either  hand edema  synovitis  myositis  Raynaud’s phenomenon  acrosclerosis

50.  Familial Mediterranean Fever is a rare autosomal recessive an systemic autoinflammatory disorder characterized by recurrent bouts of fever, serositis, synovitis, and/orcutaneous inflammation

51. Autosomal recessive condition Genetic Locus: 16p13.3 Gene: MEditerranean FeVer (MEFV) Protein: Pyrin / Marenostrin The most common mutations in Turkey M694V, M680I, Val 726, E148Q Familial Mediterranean Fever

54. Clinic; Fever Arthritis Polyserositis ( inflammation of the pleura and/or peritonea) Chest and abdominal pain Familial Mediterranean Fever

55. Major criteria 1.Painful inflammatory manifestations in the abdomen, chest, joints, or skin, associated with the fever. 2.Amyloidosis. 3.Dramatic response to continuous colchicine treatment in abolishing or reducing febrile attacks Minor criteria 4.Short attacks of fever recurring at irregular intervals. 5. Family history 6. Erysipelas like rash Diagnosis- 2 major or 1 major 2 minor criteria

57. Erysipelas like erythema

58.  Non-specific.  ESR is increased  CRP, fibrinogen, serum amyloid A is raised, especially during attacks

59.  Daily prophylactic treatment with colchicine  It inhibits the microtubule system during metaphase, decreases of chemotaxis  It increases the cAMP levels ın leucocytes and inhibits lisosomal degranulation  Treatment is started with 0.5 -1 mg colchicine/day, regardless of age or severity of attacks.  This dose is increased if necessary to 1.5 to 2 mg, until remission from attacks is achieved.  Continuous prophylactic treatment with colchicine in patients inhibits the development of amyloidosis.

60.  The most serious complication of FMF  Serum Amiloid A first accumulates in kidneys and additionally adrenals, gut, spleen, lung, liver, testis  Results: irreversible organ damage Amiloidosis

62. Behçet’s Disease Behçet’s Disease (also called Behçet’s Syndrome) is a disease causing inflammation in the body, including the blood vessels (vasculitis).

64. Oral ülserler

65. Papülopüstüler lezyonlar

67.  The treatment approach depends on the individual patient, severity of disease,  Mouth and genital ulcers are treated where possible with topical agents including steroid pastes, creams and/or sprays.  Mild disease affecting other organs (such as arthritis) can be treated with anti-inflammatory medicines (including colchicine, or medicines like ibuprofen).  More severe disease requires immunosuppressant medicines such as azathioprine, mycophenolate mofetil, ciclosporin, tacrolimus or cyclophosphamide, often used in combination with corticosteroids depending on the severity of the disease.major organ involvement.