1. Rheumatology Review

2. SLE
Multisystem inflammatory autoimmune disorder: Antibody and immune complex deposition
Females >> Males, African-American, young to middle age
Symptoms/Signs
Constitutional: H/A, fatigue, fever, weight loss, arthralgias
MS: arthralgias, myalgia, arthritis
Derm/mucosal: patchy alopecia, malar rash, discoid lesions, livedo reticularis, vasculitic purpura, Raynaud phenomenon, photosensitivity, soft palate/oral ulcers
Renal: Glomerulonephritis, nephrotic/nephritic syndromes, ARF/CRF
Psychiatric/Neuro: H/A, depression, seizures, psychosis, TIA/CVA, peripheral and cranial neuropathy
Cardiac: pericarditis/pericardial effusion, Serositis, Libman-Sacks endocarditis  Mitral Regurgitation, CAD/infarction, coronary thrombosis
Pulmonary: pleural effusion, Serositis, pulmonary embolism, lupus pneumonitis, chronic lupus interstitial lung disease, infarction
GI: autoimmune hepatitis (jaundice), mesenteric vasculitis  bowel infarction, hepatosplenomegaly

3. SLE
Hematologic: anemia (Fe-deficient vs Anemia of chronic disease vs. Autoimmune hemolytic), pancytopenia (esp. lymphopenia), hypocomplementemia
Ocular: Keratoconjunctivitis Sicca, retinal hemorrhages, cotton wool spots, uveitis
Other: Antiphospholipid antibodies
Lupus Anticoagulant: prolongation of aPTT (clotting and recurrent miscarriage)
Anticardiolipin (ACL) antibodies
Antiphospholipid antibody syndrome
Recurrent vessel occlusion (Hypercoagulable state), fetal loss, thrombocytopenia, livedo recticularis + Antiphospholipid antibodies, but without features of SLE

4. Diagnostic Criteria: American Rheumatology Association
Any 4 of the Following:
Malar Rash
Discoid rash
Photosensitivity
Oral Ulcers
Arthritis involving more than 2 joints (Polyarthritis)
Serositis (Pleuritis, Pericarditis, Peritonitis)
Antinuclear Antibody titer positive
Renal disease (proteinuria)
Neurologic disorder (Seizures, Psychosis)
Anemia, Neutropenia or Thrombocytopenia
Anti-dsDNA, Anti-Sm positive, Syphilis False Positive

5. Diagnosis: SLE Antibodies
Antinuclear (ANA): highly sensitive only
Smith Antibody (Anti-Smith or Anti-Sm)
Low sensitivity, high specificity
Double Stranded DNA Antibody (Anti-dsDNA)
Correlates with disease activity and lupus nephritis
Histone Antibody (Anti-histone)
Associated with drug induced lupus (Procainamide, Isoniazid, Hydralazine)

6. SLE: Other + Antibodies, Other Diagnostics
Anti-ribosomal P (sPecific, Psychosis)
Anti-Ro (Anti-SSA)
Anti-La (Anti-SSB)
Anti-RNP
Coombs test–positive
Inflammatory markers: ESR, CRP

7. SLE: Treatment Supportive/emotional support Rest, NSAIDS: arthralgias
Corticosteroids: visceral complications
AntiMALARials: rash, arthralgias
Anticoagulation: Antiphospholipid antibody syndrome
Immunosuppressants: recalcitrant to steroids

8. RA
A chronic systemic inflammatory disease with synovial membrane affliction. Characterized by inflammation of ligaments and proliferation/thickening of synovium, leading to destruction of various tissues such as cartilage, bone, tendons, the joint capsule, ligaments, and blood vessels. The key component of immune complex formation occurs due to crosslinkage of rheumatoid factor (IgM) against IgG.
Joint changes: chronic synovitis with pannus formation  erosion of cartilage, ligaments, tendons, bone

9. RA Females > males, Middle aged Symptoms/Signs
MS: symmetric joint manifestations
Swelling, warmth, tenderness, pain, morning stiffness > 1 hour (↓ during day)
PIP, MCP joints, wrists; elbows, knees, ankles, MTP
Spares: DIPs, T-spine, LS-spine
Mononeuropathies: median nerve entrapment
Cervical spine: atlantoaxial subluxation

10. RA: Extra-Articular Signs
SQ Rheumatoid nodules
Of bony prominences, bursae, tendon sheaths
Constitutional: malaise, weight loss, low-grade fever, anorexia
Vasculitis: palmar erythema, digital hemorrhagic infarction, palpable purpura
Anemia of Chronic Disease (normochromic/cytic)
Cardiac: pericarditis/pericardial effusion, block
Pulmonary: effusion, pleuritis, interstitial fibrosis, nodules (Caplan syndrome), and bronchiolitis obliterans-organizing pneumonia (BOOP)
Ocular: Keratoconjunctivitis Sicca, Scleritis, Episcleritis, Keratitis, Scleromalacia

11. RA: Diagnosis Rheumatoid Factor + ANA Elevations in IgG and IgM
Sensitive, not specific
Present in 75% of those with disease
Correlates with disease severity and prognosis
+ ANA
Elevations in IgG and IgM
Normochromic/cytic anemia
Leukocytosis or leukopenia
ESR, CRP ↑
Radiological changes (X-Ray)
Early: soft tissue swelling, juxta-articular demineralization
Late: uniform joint space narrowing, bony erosions, subluxation

12. RA: Treatment Supportive Rest, emotional support Physical therapy
Joint rest
NSAIDS
DMARDS: methotrexate, antimalarials, steroids, sulfasalazine, leflunomide, azathioprine, cyclosporin A, minocycline, gold salts, penicillamine
TNF blockers: etanercept, infliximab, and adalimumab
Interleukin receptor blockers: anakinra

13. Juvenile RA (Still’s Disease)
Chronic synovial inflammation in children < 16 yrs old for at least 6 weeks; symmetric joint disease
3 Subtypes
Pauciarticular (Most common, females > males, age < 8)
Affects 4 or fewer joints, associated w/ Uveitis
Polyarticular: bimodal age distribution (1-6 or years), > 5 joints
Systemic: hepatomegaly and splenomegaly, lymphadenopathy, high daily relapsing/spiking fever, recurrent evanescent “salmon-pink” rash; pericarditis, heart failure

14. JRA: Diagnostics
ESR
ANA RF
Radiological
Echo

15. JRA: Treatment NSAIDS Methotrexate Ophthalmology consult
Physical therapy, splinting, orthotics

16. Rheumatic Fever
Develops in children and adolescents following pharyngitis with group A beta-hemolytic Streptococcus (Streptococcus pyogenes)
Diagnosis: Jones Criteria
Two Major Criteria or,
One Major and 2 Minor Criteria + Documented GABHS
Major
Carditis (ie, endocarditis  mitral stenosis, pericarditis)
Polyarthritis (transient, migratory)
Sydenham's Chorea
Erythema marginatum
Subcutaneous Nodules

17. Rheumatic Fever Minor Criteria Documented GABHS infection Arthralgias
Elevated Sedimentation Rate (ESR)
Elevated C-Reactive Protein
Prolonged PR interval on Electrocardiogram
Documented GABHS infection
Throat culture, Rapid Strep antigen test, antistreptolysin O (ASO)

18. Rheumatic Fever Treatment and Prevention: Complications
Appropriate antibiotics
Complications
Mitral insufficiency and stenosis
Endocarditis
Heart failure
Dysrrhythmia

19. Systemic Sclerosis
Chronic condition of skin and internal organ fibrosis; results from inflammation and progressive tissue fibrosis and occlusion of the microvasculature by excessive production and deposition of types I and III collagens
2 Subtypes
Limited (80%)
CREST syndrome, limited to face and hands
Calcinosis, Raynaud phenomenon, esophageal hypomotility (GERD  Barrett esophagitis), Sclerodactyly, Telangiectases
Diffuse
Sclerosis of trunk and proximal extremities

20. Systemic Sclerosis Musculoskeletal
arthralgia, myalgia, ↓range of motion, symptoms of carpal tunnel syndrome, muscle weakness
Respiratory
dyspnea, chest pain, pulmonary artery hypertension, dry persistent cough due to restrictive lung disease
Cardiovascular
pericardial effusion/pericarditis, CHF, myocardial fibrosis, RVF
Renal system
Hypertension, renal crisis, CRI
Vascular system
Raynaud phenomenon, fingertip ulcers, cutaneous & mucosal telangiectasis
Skin
Pruritus, tightness and induration, hyper/hypopigmentation

21. Systemic Sclerosis GI ENT Constitutional - H/A, CVA
GER caused by lower esophageal sphincter (LES) incompetence and decreased or absent peristalsis in the lower 2/3 of the esophagus  hoarseness, aspiration pneumonia, and dysphagia. Also dyspepsia, bloating, early satiety, alternating constipation/diarrhea  malabsorption, impaired sphincter function
ENT
Sicca syndrome
Constitutional
Fever, malaise, weight loss
Neurological
- H/A, CVA

22. Systemic Sclerosis Raynaud phenomenon
pallor, cyanosis, and/or rubor on the hands bilaterally in response to cold or emotional stress
Treatment
Mainstay: Calcium channel blockers
Others: topical nitroglycerin

23. Systemic Sclerosis: Diagnostics
Antinuclear antibodies
Topoisomerase I antibodies (Scl-70)
Anticentromere antibodies
Radiological
CBC and BMP UA
PFT

24. Systemic Sclerosis: Treatment
GERD: H2 blockers, PPIs
GI hypomotility: prokinetic agents (cisapride)
Renal crisis prevention: ACE inhibitors
Pulmonary interstitial fibrosis: cyclophosphamide
GI malabsorption: tetracycline

25. Fibromyalgia
A common (3-5% prevalence), painful, female predominant rheumatic syndrome, without definite causation. Links to depression, viral infection, and abnormal sensory perception exist
Pain Pattern: bilateral, chronic, aching pain and tenderness, with stiffness, that is periarticluar, above and below the waist, > 3 months.
Concentration of pain and stiffness around the neck, shoulders, lower back, and hips

26. Fibromyalgia
Other Hx: sleep disruption, fatigue, depression, anxiety, mood changes, diminished concentration, digital numbness/tingling, altered temperature sensation, headaches, constipation/diarrhea, urinary frequency
Fever, weight loss, and weakness are not findings
Physical: Unremarkable except for multiple tender points in specific locations, > 11 tender points per patient

27. Fibromyalgia: Diagnostics
Negative work up
R/o serious illnesses: a diagnosis of exclusion
DDX
Chronic Fatigue Syndrome: Common in females/adolescents, characterized by persistent or relapsing fatigue/lassitude (not MS pain) over > 6 months. Must also have 4 of the following:
Constitutional: Sore Throat, low grade fever
Painful cervical or axillary lymph nodes
Forgetfulness or memory impairment
Myalgias or muscle discomfortMigratory, non-inflammatory arthralgia
New, Generalized Headaches
Sleep disturbance (not refreshing)
Generalized Fatigue after Exercise over 24 hours

28. Fibromyalgia: Treatment
Antidepressants
TCAs and SSRIs
Muscle relaxants
Flexeril
Exercise program
Physical therapy
Stress management, support groups
NSAIDS, opiates, and steroids are ineffective!
“It’s not in your head”

29. Vasculitis Syndromes
A group of disorders characterized by inflammation and necrosis of blood vessels. The purported cause is an autoimmune reponse to: infection, and reactions to drugs and vaccines
Are classified based on vessel size affliction and/or body system predilection
Symptoms arise from direct damage to the blood vessels or from indirect damage to tissues (such as nerves or organs) whose blood supply has been disrupted.

30. Buerger’s Disease
AKA Thromboangiitis Obliterans; small and
medium sized extremity vessels. Affects young male
smokers. Raynaud's Phenomenon, intermittent
claudication, digital ulcers, extremity numbness/tingling. All
labs normal
Behcet’s Disease
HLA-B51 relationship; a panvasculitis. Oral & genital ulcers,
anterior uveitis, seronegative polyarthritis, retinal vasculitis,
skin ulcers, erythema nodosum
Takayasu’s arteritis
large arteries, (aorta and branches), causing blockages and loss of pulse, chest pain; most common in children, young females
Polyarteritis Nodosa
Inflammatory necrotizing vasculitis of medium and small-sized arteries. Affects peripheral nerves (neuropathy), CNS, kidneys, liver, GI tract, skin (palpable purpura, infarctions, ulcerations, distal gangrene, subcutaneous nodules)
Temporal arteritis
Large vessel vasculitis; H/A, jaw claudication, visual loss, diplopia, temporal artery/scalp tenderness, constitutional. DX: Clinical/ESR/biopsy. TX: High dose prednisone

31. Small Vessel Vasculitis
Microscopic polyarteritis, microscopic polyangiitis (MPA)
Manifestations:
Palpable purpura
Hematuria (glomerulonephritis)
Hemoptysis
Arthralgias and Myalgias
Neuropathy: mononeuritis multiplex
Constitutional

32. Polymyalgia Rheumatica
Pain and stiffness in the shoulder and pelvic girdles + constitutional. Also: neck, arm, thigh pain; associated w/ temporal arteritis.
No weakness!
Labs:  ESR, normocytic/chromic anemia

33. Polymyositis/Dermatomyositis
Idiopathic inflammatory myopathy
Characterized by progressive proximal lower and upper extremity muscular weakness
Addition of: dusky red malar rash, heliotrope periorbital edematous rash, “shawl sign,” or dorsal PIP/MCP scaly patches (Gottron’s sign) = dermatomyositis
Labs:  creatine kinase, aldolase, ANA

34. Gouty Arthritis
Arthritis resulting from the deposition of sodium urate crystals in one or more joints. Due to: overproduction of uric acid and/or the underexcretion of uric acid
Presentation: sudden onset of intense monoarticular joint pain (m/c 1st MTP – podagra). Joints are tender, swollen, warm, with overlying erythema.
Fever, and tophi (w/ chronic dz)

35. Gout: Diagnosis  uric acid, ESR, WBC X-Ray Joint fluid aspirate
Needle-like sodium urate crystals, negatively birefringent

36. Gout: Treatment Acute Attack Maintenance Indomethacin Colchicine
COX-2 inhibitor
Corticosteroids
Maintenance
Overproducer: allopurinol
Under-excreter: probenecid

37. Pseudogout
Deposition of Calcium Pyrophosphate Dihydrate Crystals; associated with chondrocalcinosis of affected joints
Knee is the most commonly affected joint
Joint aspirate
CPPD crystals, rhomboid-shaped, positively birefringent Tx
Underlying chondrocalcinosis
NSAIDS, joint aspiration, steriods, COX-2 Inhibitors

38. Septic Arthritis Must always consider in DDX of gout/pseudogout
Nongonococcal (M/C: S. aureus) vs. N. gonorrhoeae
Sudden, acute pain, swelling, hot joint.
+ fever/chills
Usually knee; also hip, wrist, shoulder, ankle, elbow
Labs: Synovial fluid aspirate
Turbid: Non-GC Bacteria; clear to opaque: GC, TB
Gram stain & culture
Synovial fluid WBCs > 50,000 cells/µL (  PMNs)
Blood cultures

39. Seronegative Spondyloarthropathy
Absence of serum autoantibodies (i.e., RF)
HLA-B27 association
Psoriatic Arthritis
Ankylosing Spondylitis
Inflammatory Bowel Disease with Spondyloarthropathy
Reactive Arthritis (e.g. Reiter's Syndrome)

40. Ankylosing Spondylitis
Inflammatory axial joint disease; “Sacroiliitis”
Affects young males
Characterized by chronic lower back pain + radiation to thighs/gluteus, ascending, with stiffness and  ROM. Also: peripheral oligoarticular arthritis
Other:
Anterior Uveitis
Microscopic Colitis
Restricted lung disease (fibrosis), AV block, AI DX
X-ray: Bamboo spine, erosions, sclerosis
 ESR, + HLA-B27

41. Reiter’s Syndrome
“Reactive arthritis”: follows dysenteric infection (shigella, salmonella, yersinia, campylobacter), STD (chlamydia, ureaplasma), or HIV
Aseptic oligoarticular arthritis is asymmetric and affects knees & ankles. Also: sacroiliitis or ankylosing spondylitis
+ constitutional: fever, weight loss
Dermatological/mucosal
Oral ulcers and stomatitis, keratoderma blennorrhagica, circinate balanitis

42. Reiter’s Syndrome
Clinical tetrad: urethritis, conjunctivitis (or uveitis), mucocutaneous lesions, and aseptic arthritis
Labs:
normocytic normochromic anemia
↑ ESR, + HLA-B27
Tx:
NSAIDS
Tetracyclines
Sulfasalazine