Rheumatology summary

1. Rheumatology summary

2. Index SLE Scleroderma RA & JRA GOUT Behcet�s disease Spondyloarthropathy FMF

3. SLE

4. Autoimmune multisystem disease characterized by Widespread inflammation Production of autoantibodies Age: peak 15-40 years Sex: more women (10:1) Race :high prevalence in African Clinical: Fever Anorexia Weight loss Severe fatigue Lymphadenopathy

5. Drug induced Lupus Common with Procainamide Hydralazine Neurological, dermatological & renal involvement rare Arthralgia (most common) Malaise, low grade fever Pericarditis, pleural involvement may be seen ANA positive Histone anti bodies positive DsDNA and Smith anti bodies negative Treatment: Stop medication Short course of steroids

6. ACR Criteria

7. Dermatological features Malar rash: 30-60% an erythematous butterfly rash Over nasal bridge & malar bones Preserve nasolabial folds Photosensitivity: Rash over the sun exposed areas. Face Neck V shaped area of chest Less under the orbit protected areas Severity depending on exposure

8. Discoid lupus: Erythematous hyper pigmented margins Flat scarred hypo pigmented centers. Seen in SLE Pure cutaneous lupus

9. Arthritis: Non erosive arthritis 2 or more peripheral joints Characterized by Tenderness Swelling Effusion Serositis: Pleuritis: Pleuritic pain Pleural rub heard Pleural effusion Pericarditis: ECG Pericardial rub Pericardial effusion

10. Pulmonary: Pleuritis (30%) Peumonitis PE Pulmonary HTN Pulmonary hemorrhage the most dreadful with 50 % mortality with treatment CVS: Pericarditis (most common) Endocarditis Aortitis Valvulitis Aortic insufficiency (most common valvular lesion) Antibiotic prophylaxis indicated for Dental Surgical procedures Accelerated atherosclerosis with 10 times higher mortality from MI (age & sex matched)

11. Renal: Persistent proteinuria >0.5 g/day > 3+ Cellular casts Red cell Hemoglobin Granular Tubular Mixed Impaired kidney function Lupus nephritis predict out come (prognosis) Major cause of mortality Neyrological: Seizures Psychosis In the absence of Offending drugs Known metabolic derangements, e.g. Uremia Ketoacidosis Electrolyte imbalance

12. Hematological: Hemolytic anemia--with reticulocytosis Or Leukopenia : <4,000/mm total on 2 or more occasions Or Lymphopenia: <1,500/mm on 2 or more occasions Or Thrombocytopenia: <100,000/mm, in the absence of offending drugs Immunological: +ve DsDNA anti body or Anti smith antibody &/Or An abnormal serum level of IgG or IgM anticardiolipin antibodies. or A +ve test result for lupus anticoagulant using a standard method.

13. Antiphospholipid antibody syndrome primary or 20 associated with SLE Recurrent venous and arterial thrombosis Recurrent fetal loss Labs Thrombocytopenia Prolonged PTT Lupus anticoagulant by mixing studies Cardiolipin antibodies +ve

14. Labs in SLE ANA (99%) Sensitive, but not specific 5-10% positive general population Positive in other auto immune disease (thyroiditis) Anti DNA antibody (60%) Specific, but not sensitive Increase with active disease Anti smith antibody (30%) Specific for SLE Rheumatoid fact can be positive Depend on organ involved Leukopenia & lymphopenia (common) Thrombocytopenia Anemia of chronic disease Hemolytic anemia with high reticulocyte count, coombs +ve Proteinurea, casts Abnormal liver & kidney function

15. What possible on CXR Pleural effusion and pleural thickening Lung infiltrate from Infection Pulmonary embolism Peumonitis Interstitial lung disease Hemorrhage Pericardial effusion, cardiomegaly Lung congestion from heart failure

16. Treatment of SLE Depend on Organ involved & severity Multispecialty care Steroids: high dose when organ endangered. Immuno-suppressive Cyclophosphamide Azathioprine Anti-malarial hydroxychloroquine (skin & MS)

17. Know side effects of medications Steroids in particular: some side effects Skin: thinning, bruises, acne like rash, stria Ophthalmic: cataract, precipitate glaucoma Bone: osteonecrosis, osteoporosis CVS: accelerate atherosclerosis Hyperglycemia, Hyperlipidemia suppress immunity, opportunistic infections Adrenal suppression Psychosis

18. Scleroderma

19. Also called Systemic sclerosis Multisystem disease Unknown etiology Rare Peak between age 35-65 More women affected Family hx of other auto immune diseases Ethnic background influence survival and disease manifestation. Pathogenesis: Immune system activation Endothelial activation Fibroblast activation Results in Small blood vessels damage Tissue fibrosis Clinical features Raynaud�s Typical skin changes Esophageal and small bowel dysfunction Interstitial lung disease Pulmonary HTN Renal crises

20. Raynaud�s Phenomenon Reversible skin color changes: White?blue?red Due to vasospasm Induced by cold of emotion Causes: Rheumatic diseases: Scleroderma, SLE, RA, CREST, MCTD, Myositis Occlusive arterial disease Repetitive vascular injury Hyperviscosity: Polycythemia, Cryoglobulinemia Thoracic outlet syndrome

21. Typical skin changes Tight thick skin Peaked nose Pursed mouth

22. Esophageal dysmotility: Heart burn & reflux symptoms Dilated esophagus on Esophagogram

23. Renal crises & HTN Major complication Early in disease first few years Acute onset HTN Renal impairment High Renin Microangiopathic hemolytic anemia, Thrombocytopenia RF can be reversible if BP treated DOC ACEIs

24. CREST Calcinosis Raynaud�s Esophageal dysmotility Sclerodactyly Telangiectasias

25. Diagnosis Clinical features ANA positive 90% Anti topoisomerase 1 antibody positive(scl-70) 30% in diffuse Anticentromere antibody positive in CREST & limited scleroderma Treatment CCBs: may help Raynaud�s Skin: No effective treatment 60% improve with time Treat ILD and pulmonary HTN Treat HTN early and aggressive to prevent renal damage and other HTN complications Avoid steroids (renal complications)

26. Rheumatoid Arthritis

27. Systemic disease Primarily Presents as Arthritis Etiology: Multifactor involved Diagnosis Typical clinical presentation RF not make or exclude diagnosis +ve RF More extrarticular manifestations More severe Exclude other diseases Symptoms & signs Low-grade fevers Excessive sweating Weight loss Fatigue Myalgia Morning stiffness Lymphadenopathy

29. Laboratory features Anemia Eosinophilia Thrombocytosis Inc. ALP, AST & GT Dec. albumin & prealbumin Elevated ESR & CRP

36. DDx Viral syndromes B19 mimic RA (months to years) Rubella HBV HCV (+ve RF) Bacterial infections Post Streptococcal Endocarditis Lyme disease Septic arthritis Psoriatic arthritis, reactive arthritis & other systemic rheumatological diseases Crystal arthropathy

37. Psoriatic arthritis Asymmetrical Affect DIP joints Skin changes of psoriasis Can affect SI joint and cause low back pain, while RA more likely to affect Cervical spine Dactylitis , enthesiopathy in psoriatic RF usually -ve More bone reaction and sclerosis on X-ray

38. Sc nodules in RA Look for Nodules Over Olecranon Achilles Occiput pressure areas RF +ve More extrarticular manifestations May worsen with treatment (methotrexate) Surgery for very large nodules Seen in other Rheumatic diseases SLE MCTD

40. Extrarticular manifestations

41. Major ocular manifestations Keratoconjunctivitis sicca Scleritis: painful & serious Episcleritis Uveitis

44. Signs of spinal cord damage Severe neck pain radiating to Occiput Tingling or numbness in fingers and feet Motor weakness Urinary bladder dysfunction Jumping legs

45. Treatment NSAIDS Steroids Hydroxychroloquine DMARD Methotrexate Leflunmide Sulfsalazine Azathioprine New agents Infliximab Etanercept

46. NSAIDS Symptomatic relieve Be aware of side effects: GI toxicity Fluid retention & hypertension Renal impairment Hepatic injury Use one your familiar with COX2, less GI toxicity but not 100% GI safe, other side effects may be more common, not cardio protective consider add ASA if patient has CVS risks

47. Steroids Very effective, fast action, used both as local as intra-articular injection or systematic. Induction therapy, and to treat flares Bridging therapy till other DMARDS start to act Treat RA vasculitis with DMARDS Local injection (into joints or soft tissue) Side effects Osteonecrosis Osteoporosis Hypertension, accelerated atherosclerosis Hyperglycemia Wt gain, Fluid retention, Cushenoid features Adrenal suppression Skin thinning, easy bruising, acne like rash Many other side effects

48. Hydroxychroloquine For mild disease and as part of multi drug therapy Usual dose 200mg bid po Very safe Delayed onset of action: within 3 months Retinopathy is rare and only if dosage of > 6mg/kg is used Eye exam 6 months to screen for retinopathy

49. Methotrexate Antimetabolite when treating cancer Inhibition of inflammation in RA by increasing intracellular adenosine and inhibit cells that participate in inflammation Main DMARD for RA Used alone or in combination Safe if used and monitored appropriately

50. Methotrexate continue� Usual starting dose 7.5-10mg given as single weekly dose, average dose 15-17.5mg, may need 20-25mg Po absorption is less when dose is higher than 15mg, better if given SQ Onset of action about 4 weeks Always give folate supplement to reduce adverse effects including: Stomatitis Hair loss BM suppression Hepatic toxicity monitor liver transaminases and albumin q 2 months Hypersensitivity peumonitis: stop MTX in case of unexplained cough or SOB Bone marrow suppression Teratogenic

51. Other DMARDs Leflunmide: effective as single or in combination 10-20mg qd, may cause Diarrhea Heaptotoxicity Sulfsalazine :slow acting, helps in combination therapy, cause Myelosuppression Rare heaptotoxicity Azathioprine :cause Myelosuppresion Hepatotoxicity

52. New agents Infliximab: chimeric antibody to TNF Etanercept: TNF soluble receptor Effective as single or combined Expensive Injection only Side effects: Local and systemic reaction to injection or infusion Opportunistic infection and sepsis, (test all for PPD) May trigger autoimmune antibodies Not to give with h/o recent malignancy(5y)

53. Juvenile Rheumatoid Arthritis

54. Juvenile Rheumatoid Arthritis Syndrome of several type of arthritis Most common chronic disease in children Etiology: unknown Treatment: NSAIDS Steroids: systemic & intra-articular DMARDS: Methotrexate Azathioprine TNF blocking ACR 1977 Criteria for JRA Onset <16 years of age Persistent arthritis > 6 weeks Types: Pauciarticular :< 5 joints Polyarticular :> 4 joints Systemic : Fever & rash

55. Systemic JRA Typical < 5 y old child Daily spiking fever Temp will go back to normal or bellow normal in between episodes. Transient macular salmon-pink rash (evening) Non- pruritic Over trunk and extremities Rash appear with fever & subside when fever subside Arthritis onset may be delayed Typically symmetrical polyarthritis Wrists & ankles most commonly affected Generalized lymphadenopathy Hepato-spleenomegaly Pericarditis Pleuritis Uveitis is uncommon Elevated: ESR, CRP, WBC, Plts RF & ANA typically �ve DDx: Infections and febrile illnesses Leukemia/lymphoma Other tumors of children Other CT diseases Reaction to drugs

56. Polyarticular Affect >4 joints, 2 main subtypes RF +ve usually > 8 years old More girls More erosive and aggressive disease Resemble adult RF+ RA Remission is rare Uveitis is uncommon but often develop pulmonary disease, keratitis, vasculitis and Sjogren syndrome RF -ve Less systemic features Less aggressive arthritis, ANA+ 50% Uveitis is common

57. Pauciarticular JRA Early onset type: age 1-5 More girls Often ANA+ Highest risk of eye involvement 30-50% 80% of whom has minimal or no symptoms Late onset: Affects more boys 50% HLA+ Affect large joints, spine, likely to have tendonitis, enthesitis Eye involvement less than early onset type

59. GOUT

60. Disease of adult men with peak in 5th decade. Very rare before puberty & in premenopausal women. <25% of hyperuricemic develop GOUT 20% family history Duration & serum uric acid directly correlate with Gout development Caused by tissue deposition of Monosodium urate crystals Hyperuricemia Serum uric acid >7mg for adult men > 6mg for adult women Only 15-20% develop gout. Mechanism: Overproduction of urate Endogenous Exogenous Underexcretion of urate (90%) Combination

61. Primary Under excretion: Idiopathic (90%) Normal excretion only when serum uric acid high Over production: rare Idiopathic Hypoxanthine-guanine phosphoribosyltransferase deficiency Phosphoribosyl-1-pyrophosphate synthetase super activity.

62. ACQUIRED CAUSES OF HYEPERURICEMIA URATE OVERPRODUCTION Excess dietary purine consumption Accelerated ATP degradation: Alcohol abuse Glycogen storage disease, Myeloproliferative and Lymphoproliferative disorders Urate under excretion Renal disease Poly cystic kidney disease HTN Hyperparathyroidism Hypothyroidism DRUGS, decreased renal excretion Cyclosporine Alcohol Increases lactic acid Increased ATP degradation Contain purine guanosine Nicotinic acid Thiazide Lasix (furosemide) Aspirin (low dose) Ethambutol (anti-TB) Pyrazinamide (anti-TB)

63. Stages: Prolonged a symptomatic hyperuricemia (years) Acute intermittent Gout Chronic tophaceous Gout Clinical: Recurrent Gouty Arthritis (articular & periarticular) Tophi Uric acid urinary calculi Interstitial nephropathy with renal function impairment

64. PodagraGout of ankle joint Acute onset Affect 75% 1st MTP Severe pain Very tender Erythema May be febrile Resolve 3-10 days

67. DDx: Pseudo Gout (CPPD) Septic arthritis Reactive arthritis Other inflammatory arthritis Treatment: NSAIDs (indomethacin) Colchicine Steroids Uricosuric agents Probencid Sulfinprazone Xanthine oxidase inhibitor Allopurinol Prophylaxix Colchicine Steroids

68. MANAGEMENT OF ACUTE GOUT NSAID: Indomethacin used more than other NSAIDs May use any other NSAIDs at full dose like ibuprofen 800mg TID or Naprosyn 500mg bid expect to as effective as indomethacin and my be less toxic Know NSAID toxicities Know NSAIDs contraindications,

69. CONTINUE ACUTE GOUT MANAGMENT Colchicine: 0.6-1mg bid oral Limited because of toxicity Main side effects GI: Abdominal pain Diarrhea Nausea Need adjustment in renal impairment May cause myelosuppression May be linked to azospermia and infertility IV Colchicine very toxic to BM

70. CONTINUE ACUTE GOUT MANAGEMENT Steroids safe for acute management with fast results, and when NSAID and Colchicine use not warranted Intra-articular injection of triamcinolone is fastest way to get relief ,at the same time can get synovial fluid for analysis Oral or parentral steroids e.g.: prednisolone oral 20-40 mg daily for 5-7 days, equivalent doses of IV steroids may be used if unable to take oral Always make sure no infection coexist.

71. Prevention & control of hyperuricemia indications Recurrent attacks of Gout Tophaceous Gout Chronic gout with joint damage and erosions Hyperuricemia uric acid > 12mg/dl Renal stones 24 hr urine excretion of >1100 mg uric acid

72. Uricosuric agentsProbencid, sulfinprazone Who is good candidate Age <60 Creatinine clearance >50ml/min 24 hr urine of uric acid <700mg (under excretion) No history of renal stone Xanthine oxidase inhibitorAllopurinol Hyperuricemia with : Urinary uric acid >1000mg Uric acid nephropathy Nephrolithiasis Renal insufficiency GFR<50 Before chemotherapy Allergy to Uricosuric agents

73. Allopurinol Average dose 300mg Renal impairment use lower dose May precipitate acute gout when first used Side effects can be very serious range from Dyspepsia Diarrhea Headache Rash to more severe including Fever Hepatitis Interstitial nephritis, acute renal failure Vasculitis Toxic epidermal necrolysis Esosinophilia Hypersensitivity syndrome.

77. Behcet�s disease

78. Chronic relapsing systemic inflammatory disease More common & severe along the silk road from eastern Asia to the Mediterranean Slightly more men, ages 20-40 Etiology & Pathogenesis Auto immune disease Unknown cause Genetically predisposed Aberrant immune response triggered by infections Increased Immune complexes Cytokines CD8/CD4 ratio Decrease CD4 suppressor

79. Also evidence Endothelial activation with low activated protein C levels , VEGF high Vasculitis with lymphocytic infiltration of mucocutaneous lesion and neutrophilic infiltrate in pathergy test.

81. Clinical manifestations Recurrent oral ulcers Genital ulcers Ocular lesions Skin lesions Pathergy test Neurological Vasculitis Arthritis Renal GI Coetaneous lesion Acne like rash Pseudofolliculitis superficial thrombophlebitis Erythema nodosum (EN) Pyoderma gangrenosum-type lesions Nodules Palpable purpura

82. Oral ulcers Painful Similar to common aphthus ulcers but More extensive Multiple Size (mm - cm) Spontaneously heal within 1-3 weeks Can be continuous Criteria: Recurrence of ulcers >3X/year Usually first & last manifestation of the disease leave Pathergy test skin prick by a needle After 24-48 hrs Erythematous papular/pustular response 2mm or more considered +ve test 50-75% of eastern patients 10-20% of north European patients only

84. Ocular lesions (25-75%) Pan uveitis ,episodic, bilateral ,may lead to blindness Retinal vasculitis Optic neuritis Vascular occlusion Treatment: Immunosuppressant Neurological (20%) Meningitis Encephalitis Focal deficits cerebral more than cerebellar CN palsies Psychiatric conditions Dementia Peripheral neuropathy uncommon

85. CSF Elevated protein & pleocytosis Elevated pressure MRI Brainstem Basal ganglion lesions White matter Periventricular lesions Dural sinus thrombosis (venous & arterial) Angiogram (vasculitis) Subarachnoid hemorrhage Prognosis Bad prognosis CSF with high protein and pleocytosis Parenchymal lesion Death (90%) Good prognosis Normal CSF

86. Vascular Affects 1/3 Manifestations Small to large vessel vasculitis Aneurysm formation Arterial or venous thrombosis Varices Arterial vasculitis with aneurysm formation may affect (life-threatening) Aorta Large vessels (pulmonary artery) Pulmonary vascular Hemoptysis (pulmonary artery-bronchus fistulae) Misdiagnosis of PE Pulmonary arteriography is diagnostic. Pulmonary infarction is uncommon. Other vascular Superficial thrombophlibitis DVT Budd-Chiari syndrome IVC thrombosis MI & arterial thrombosis Pulse less disease like pictures

87. Arthritis Affects � More women Affects medium-large joints Most common knee followed by ankle and wrist joint Typically asymmetrical. Inflammatory type Sacroiliitis may develop particularly with HLA-27 +ve.

88. Renal Common Usually mild Amyloidosis may be seen Proteinurea, hematuria Mild renal impairment Rarely progress to ESRD Pathology: Crescentic GN Proliferative GN IgA nephritis GI Oral ulcers Ulceration in esophagus, terminal ileum, cecum & ascending colon DD: IBD Pancreatitis reported

89. DDx: Common oral ulcers IBD Rheumatic diseases (SLE) Vasculitis Drug reaction (Methotrexate) Pemphigus and pemphigoid Treatment: Steroids Colchicine Immunesuppressant Aspirin Anticoagulation

90. Treatment Mucocutaneous: topical steroid, colchicine, thalidomide, Dapsone Resistant lesions may use azathioprine, methotrexate Ocular disease :use local and systemic steroids & immunosuppressant with azathioprine, cyclosporine, methotrexate Major organ involved CNS, Lungs and vasculitis high dose steroid and immunosuppressant drugs are used Immunosuppressant includes cyclophosphamide ,chlorambucil, interferon alfa ,TNF inhibitors, mycophenolate mofetil Superficial thrombophlibitis :low dose aspirin DVT and PE use systemic anticoagulation and consider immunosuppressant Concern with anticoagulation presence of pseudo aneurysms and risk of bleeding which can be fatal.

91. Prognosis and course Disease characterized by exacerbations and remissions Worse in young adult males Neurological, ocular, and large vessel arterial or venous disease carries highest morbidity & mortality. 5 year survival 80% Prognosis seems better with treatment

92. Spondyloarthropathies

93. Group of disorders Inflammatory axial spine involvement Asymmetrical peripheral arthritis Enthesopathy Inflammatory eye disease Mucocutaneous features RF -ve High frequency of HLA B27 AG Familial aggregation

94. Ankylosing Spondylitis Reactive Arthritis Reiter�s syndrome Psoriatic Arthritis Enteropathic Arthritis: Ulcerative & Crohn�s Juvenile Ankylosing Spondylitis

95. Clinical 7-D-47-D-4

96. 7-D-37-D-3

97. 7-C-17-C-1

98. 7-C-47-C-4

99. 7-R- 47-R- 4

100. 7-R-127-R-12

101. 7-D-87-D-8

102. 7-C-217-C-21

103. 7-C-187-C-18

104. 7-C-137-C-13

105. 7-R-187-R-18

107. 7-D-67-D-6

108. 7-D-77-D-7

109. 7-C-57-C-5

110. 7-C-97-C-9

111. 7-R-157-R-15

112. Treatment NSAIDs (symptoms) Physical therapy Maintain good posture Sulfasalazine & methotrexate Anti TNF drugs Prevent eye complications Be aware of association IBD Inflammatory eye disease Pulmonary fibrosis (1% AS) Aortitis, aortic regurgitation (1% AS) Severe reactive arthritis & HIV

113. FMF

114. Familial Mediterranean Fever AR disease Located in short arm of ch. 16 MEFV gene encodes protein (pyrin, marenostrin) Pyrin in cytoplasm of neutrophils 28 mutation most common M694V More severe disease Higher risk of amyloidosis V726A Acute & sudden last from 6-96 hrs 1st attack <20y (90%) Characterized by Fever Serositis

115. Clinical Fever alone/with Abdominal pain (95%) Mono arthritis with effusion (75%), mostly Knees Ankles Wrists Chest pain/ pleuritis (unilateral) 30% Pericarditis rare 1% Treatment Colchicine Abort 60% of attacks Modifies 20-30 % Also prevents amyloidosis Dose 1-2 mg QD NSAID may help abort attack

116. Idiopathic Inflammatory Myopathies

117. Rare disease incidence of 2-10/million Bimodal Peak 10-15, 45-55y F:M 2:1 Malignancy associated more after age 50 Group of autoimmune diseases characterized by: Proximal muscle weakness Non suppurative inflammation Extramuscular features Pulmonary: interstitial Peumonitis & fibrosis Cardiac: SVT, Cardiomyopathy, HF

118. Classification Adult Polymyositis Adult Dermatomyositis Childhood DM/PM PM/DM associated with malignancy PM/DM associated with CT diseases Clinical features Proximal muscle weakness Difficulty swallowing Arthralgia (common) Myalgia (severe pain & tenderness) Skin Rash

120. DDx: Endocrine: Hypo/hyperthyroidism Hypo/hyperparathyroidism Cushing�s Hypoadrenalism Infections: Viral Toxoplasma Trichinosis CT diseases SLE, Scleroderma RA, Vasculitis Drugs Alcohol Cholesterol lowering medications Labs Elevated enzymes: Creatinine kinase Aldolase LDH AST, ALT ESR only elevated in 50%

121. Criteria of the Diagnosis Proximal muscle weakness Elevated muscle enzymes Myopathic changes by EMG Muscle inflammation on biopsy Skin rash with Dermatomyositis Treatment Steroids Immunosuppressive (steroid conserving) like Methotrexate, Azathioprine. IVIg Physical therapy and rehabilitation