Rheumatology Review

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RheumatologyReview
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SLE

• Multisystem inflammatory autoimmune disorder
  Antibody and immune complex deposition
• Females gtgt 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

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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

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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

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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)
• Low sensitivity, high specificity
• Correlates with disease activity and lupus
  nephritis
• Histone Antibody (Anti-histone)
• Associated with drug induced lupus (Procainamide,
  Isoniazid, Hydralazine)

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SLE Other Antibodies, Other Diagnostics

• Anti-ribosomal P (sPecific, Psychosis)
• Anti-Ro (Anti-SSA)
• Anti-La (Anti-SSB)
• Anti-RNP
• Coombs testpositive
• Inflammatory markers ESR, CRP

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SLE Treatment

• Supportive/emotional support
• Rest, NSAIDS arthralgias
• Corticosteroids visceral complications
• AntiMALARials rash, arthralgias
• Anticoagulation Antiphospholipid antibody
  syndrome
• Immunosuppressants recalcitrant to steroids

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RA

• A chronic systemic inflammatory disease with
  synovial membrane affliction. Characterized by
  inflammation of ligaments and proliferation/thicke
  ning 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

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RA

• Females gt males, Middle aged
• Symptoms/Signs
• MS symmetric joint manifestations
• Swelling, warmth, tenderness, pain, morning
  stiffness gt 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

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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

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RA Diagnosis

• Rheumatoid Factor
• 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

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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

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Juvenile RA (Stills Disease)

• Chronic synovial inflammation in children lt 16
  yrs old for at least 6 weeks symmetric joint
  disease
• 3 Subtypes
• Pauciarticular (Most common, females gt males, age
  lt 8)
• Affects 4 or fewer joints, associated w/ Uveitis
• Polyarticular bimodal age distribution (1-6 or
  11-16 years), gt 5 joints
• Systemic hepatomegaly and splenomegaly,
  lymphadenopathy, high daily relapsing/spiking
  fever, recurrent evanescent salmon-pink rash
  pericarditis, heart failure

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JRA Diagnostics

• ESR
• ANA
• RF
• Radiological
• Echo

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JRA Treatment

• NSAIDS
• Methotrexate
• Ophthalmology consult
• Physical therapy, splinting, orthotics

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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

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Rheumatic Fever

• Minor Criteria
• Arthralgias
• Fever
• 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)

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Rheumatic Fever

• Treatment and Prevention
• Appropriate antibiotics
• Complications
• Mitral insufficiency and stenosis
• Endocarditis
• Heart failure
• Dysrrhythmia

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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

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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

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Systemic Sclerosis

• GI
• 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

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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

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Systemic Sclerosis Diagnostics

• Antinuclear antibodies
• Topoisomerase I antibodies (Scl-70)
• Anticentromere antibodies
• Radiological
• CBC and BMP
• UA
• PFT

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Systemic Sclerosis Treatment

• GERD H2 blockers, PPIs
• GI hypomotility prokinetic agents (cisapride)
• Renal crisis prevention ACE inhibitors
• Pulmonary interstitial fibrosis cyclophosphamide
  
• GI malabsorption tetracycline

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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, gt 3
  months.
• Concentration of pain and stiffness around the
  neck, shoulders, lower back, and hips

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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, gt 11 tender points
  per patient

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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
  gt 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
  

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Fibromyalgia Treatment

• Antidepressants
• TCAs and SSRIs
• Muscle relaxants
• Flexeril
• Exercise program
• Physical therapy
• Stress management, support groups
• NSAIDS, opiates, and steroids are ineffective!
• Its not in your head

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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.

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Buergers 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
Behcets Disease HLA-B51 relationship a panvasculitis. Oral genital ulcers, anterior uveitis, seronegative polyarthritis, retinal vasculitis, skin ulcers, erythema nodosum
Takayasus 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
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Small Vessel Vasculitis

• Microscopic polyarteritis, microscopic
  polyangiitis (MPA)
• Manifestations
• Palpable purpura
• Hematuria (glomerulonephritis)
• Hemoptysis
• Arthralgias and Myalgias
• Neuropathy mononeuritis multiplex
• Constitutional

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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

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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 (Gottrons sign)
  dermatomyositis
• Labs ? creatine kinase, aldolase, ANA

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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)

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Gout Diagnosis

• ? uric acid, ESR, WBC
• X-Ray
• Joint fluid aspirate
• Needle-like sodium urate crystals, negatively
  birefringent

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Gout Treatment

• Acute Attack
• Indomethacin
• Colchicine
• COX-2 inhibitor
• Corticosteroids
• Maintenance
• Overproducer allopurinol
• Under-excreter probenecid

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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

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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 gt 50,000 cells/µL ( ? PMNs)
• Blood cultures

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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)

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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

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Reiters 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

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Reiters Syndrome

• Clinical tetrad urethritis, conjunctivitis (or
  uveitis), mucocutaneous lesions, and aseptic
  arthritis
• Labs
• normocytic normochromic anemia
• ? ESR, HLA-B27
• Tx
• NSAIDS
• Tetracyclines
• Sulfasalazine