Rheumatology
Review
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
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
Diagnostic Criteria: American
Rheumatology Association
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Any 4 of the Following:
1. Malar Rash
2. Discoid rash
3. Photosensitivity
4. Oral Ulcers
5. Arthritis involving more than 2 joints (Polyarthritis)
6. Serositis (Pleuritis, Pericarditis, Peritonitis)
7. Antinuclear Antibody titer positive
8. Renal disease (proteinuria)
9. Neurologic disorder (Seizures, Psychosis)
10. Anemia, Neutropenia or Thrombocytopenia
11. Anti-dsDNA, Anti-Sm positive, Syphilis False Positive
Diagnosis: SLE Antibodies
• Antinuclear (ANA): highly sensitive only
• Smith Antibody (Anti-Smith or Anti-Sm)
– Low sensitivity, high specificity
• Double Stranded DNA Antibody (AntidsDNA)
– 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 test–positive
Inflammatory markers: ESR, CRP
SLE: Treatment
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Supportive/emotional support
Rest, NSAIDS: arthralgias
Corticosteroids: visceral complications
AntiMALARials: rash, arthralgias
Anticoagulation: Antiphospholipid
antibody syndrome
• Immunosuppressants: recalcitrant to
steroids
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
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
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
RA: Diagnosis
• Rheumatoid Factor
– Sensitive, not specific
– Present in 75% of those with disease
– Correlates with disease severity and prognosis
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+ 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
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 11-16 years),
> 5 joints
– Systemic: hepatomegaly and splenomegaly,
lymphadenopathy, high daily relapsing/spiking fever,
recurrent evanescent “salmon-pink” rash;
pericarditis, heart failure
JRA: Diagnostics
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ESR
ANA
RF
Radiological
Echo
JRA: Treatment
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NSAIDS
Methotrexate
Ophthalmology consult
Physical therapy, splinting, orthotics
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
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)
Rheumatic Fever
Treatment and Prevention:
• Appropriate antibiotics
Complications
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Mitral insufficiency and stenosis
Endocarditis
Heart failure
Dysrrhythmia
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
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
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
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
Systemic Sclerosis: Diagnostics
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Antinuclear antibodies
Topoisomerase I antibodies (Scl-70)
Anticentromere antibodies
Radiological
CBC and BMP
UA
PFT
Systemic Sclerosis: Treatment
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GERD: H2 blockers, PPIs
GI hypomotility: prokinetic agents (cisapride)
Renal crisis prevention: ACE inhibitors
Pulmonary interstitial fibrosis:
cyclophosphamide
• GI malabsorption: tetracycline
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
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
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:
A.
B.
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Constitutional: Sore Throat, low grade fever
Painful cervical or axillary lymph nodes
Forgetfulness or memory impairment
Myalgias or muscle discomfortMigratory, non-inflammatory
arthralgia
E. New, Generalized Headaches
F. Sleep disturbance (not refreshing)
G. Generalized Fatigue after Exercise over 24 hours
Fibromyalgia: Treatment
• Antidepressants
– TCAs and SSRIs
• Muscle relaxants
– Flexeril
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Exercise program
Physical therapy
Stress management, support groups
NSAIDS, opiates, and steroids are
ineffective!
• “It’s not in your head”
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.
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
Small Vessel Vasculitis
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Microscopic polyarteritis, microscopic
polyangiitis (MPA)
• Manifestations:
– Palpable purpura
– Hematuria (glomerulonephritis)
– Hemoptysis
– Arthralgias and Myalgias
– Neuropathy: mononeuritis multiplex
– Constitutional
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
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
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)
Gout: Diagnosis
•  uric acid, ESR, WBC
• X-Ray
• Joint fluid aspirate
– Needle-like sodium urate crystals,
negatively birefringent
Gout: Treatment
• Acute Attack
– Indomethacin
– Colchicine
– COX-2 inhibitor
– Corticosteroids
• Maintenance
– Overproducer: allopurinol
– Under-excreter: probenecid
Pseudogout
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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
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Tx
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Underlying chondrocalcinosis
NSAIDS, joint aspiration, steriods, COX-2
Inhibitors
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
Seronegative Spondyloarthropathy
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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)
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
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
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