RHEUMATOLOGY SECTION

ABIM
BOARD REVIEW

Matt Husa, M.D.

UCSD Rheumatology Fellow
4/09/10
 Board Overview

• Know a few diseases—diagnosis more

important than treatment
• Diagnosis: history, physical exam, imaging,
labs
• Some pathophysiology
• Some common treatments/side
effects/contraindications
• Serologies
 Overview: Topics to Study
• RA
• RA vs. seronegative
• Mgmt of RA—TNFinhibitors
• OA
• Crystal disease
• SLE
• Pregnancy in SLE/autoimmune disease
• Management of monoarticular arthritis
• Vasculitis differential diagnosis—ANCA, pulm/renal
syndrome
• Serologies
• 2-3qu on less common rheumatic disease
 Rheum Clinical Pearls
• Arthritis vs. arthralgias
• Morning stiffness– resolves w/ movement, >30min is significant
• Malar erythema– spares nasolabial folds
• Objective muscular weakness: inflammatory myositis vs.
myopathy (PMR is achey pain, not objective weakness)
• Hip pain: groin area, internal/external rotation (lateral thigh pain =
trochanteric bursitis)
• DIP arthritis: CPPD/Gout vs. psoriatic arthritis vs. osteoarthritis
• Fever in rheumatic disease: SLE vs. vasculitis vs. adult onset
Still’s disease vs. periodic familial fever syndromes vs. crystal
arthropathy (less in others)
• Uveitis and arthritis: seronegatives, Wegeners, Behcets, IBD
• Arthritis and lung disease: scleroderma (ILD and PAH), SLE
(PAH), inflam myopathy (ILD), AS (upper lobes), vasculitis
 Labs in Rheumatology
• ESR/CRP: non-specific markers of inflammation,
valuable in RA, PMR, vasculitis, otherwise not
that helpful.
• CBC: lymphopenia, leukopenia, anemia chronic
disease, platelets increased or decreased
• RF and anti-cyclic citrulinated peptides (anti-
CCP)
• ANA
• Ro (SSA)/La (SSB)- SLE, Sjogren’s
• Anti-Smith: largely unused
 Labs in Rheumatology Cont’d
• Anti-ribonuclear protein (RNP)—MCTD
• Anti-DSDNA—SLE
• Scl70—systemic sclerosis, diffuse
• Anti-centromere—systemic sclerosis, limited
(CREST)
• ANCA—cANCA antiproteinase 3 vs. pANCA
myeloperoxidase vs. other
• C3/C4—low in autoimmune, high in infection
• U/A: proteinura, WBC, RBC, casts
 Imaging in Rheumatology
• Will likely see some radiology images
• Xrays:
– Bone (erosions, osteopenia)
– Characteristic images:
• Pencil-in-cup (psoriatic arthritis)
• Gouty tophi
• Osteoarthritis
• Ankylosing spondylitis
• Sacroilitis
• CPPD
• CXR with lung lesions (Wegeners, etc)
• MRI/US: better for early erosions, tendinitis,
rotator cuff, meniscus, myositis
 Rheumatological Drugs
• NSAIDS: COX1 vs. COX2 inhibitors
– Side effects: GI, renal, cardiovascular, platelet dysfunction,
asthma/nasal polyps/allergic rhinitis triad, asceptic meningitis
– Not used during 3rd trimester—fetal renal and cardiac
toxicities.
• Steroids:
– Side effects: insomnia, fluid/salt retention, weight gain, HTN,
diabetes, osteoperosis, AVN, myopathy
– Use of bisphosphonates rec for >5mg pred daily for >3months
– Also use with PPI, calcium/vit D
• Plaquenil: antimalarial
– Use: SLE, triple therapy for RA, Sjogrens
– Side effects: retinopathy, rash, GI
 Rheumatological Drugs
• Methotrexate: dihydrofolate reductase inhibitor
– Taken w/ folic acid to reduce side effects
– Contraindicated in renal and liver disease
– Side effects: GI, mucosal ulcers, hepatotoxicity, b-marrow
suppression, pneumonitis/IPF, hair loss
– 8wk monitoring LFT’s, chem 10, cbc
• Sulfasalazine:
– use in seronegative spondylarthropathy and RA
– Contraindicated with sulfa allergy and G6PD deficiency
– Less toxicity—some liver, b-marrow, hemolytic anemia,
neutropenia
• Leflunamide: dihydrooratate dehydrogenase inhib
– Pyrimidine synthesis inh., alopecia, GI, hepatotox
 Rheumatological Drugs
• Imuran:
– Use in RA, SLE, vasculitis, inflam myopathy
– Side effects: infection, b-marrow, hepatitis, malignancy
– OK to use in pregnancy
• Cylcophosphamide: cytotoxic
– Use in organ-threatening SLE and vasculitis, SLE nephritis, lung disease in
systemic sclerosis,
– IV vs. oral (less side effects with IV)
– Side effects: alopecia, GI, infection, b-marrow suppression, infertility (worse
with age), hemorhagic cystitis, bladder cancer
– Cbc and u/a monthly
• Mycophenalate mofetil:
– Use in SLE nephritis, SLE moderate
– Side effects: b-marrow suppression, GI
 Rheumatological Drugs
• TNFinhibitors: etanercept, infliximab,
adilimumab, golimumab
– Use: AS, psoriatic, RA
– Best when combined w/ MTX for RA treatment
– Side effects: TB reactivation (extrapulmonary),
infections, heart failure contraindication,
leukemia/lymphoma, pancytopenia
 Rheumatological Drugs During
Pregnancy
• Steroids! (prednisone/solumedrol B) (cleft pallate)
• NSAIDS (B,C,D)- not during 3rd trimester (mom bleeding, fetal
cardiac and renal abnormalities)
• ASA (C,D) may prevent fetal loss in APS
• Plaquenil- not classified
• MTX (X) -contraindicated! Teratogenicity
• Sulfasalazine (B)- ok
• Leflunamide (X)- contraindicated, teratogenicity
• Azathioprine (D)- ok
• Cyclophosphamide (X)- contraindicated, teratogenicity
• TNFinh- unknown
• IVIG- probably safe
 Raynaud’s
• Cold or fright response-
hands/feet- white to blue to
red
• Primary vs. secondary
phenomenon (secondary =
worse, ulcerations)
• Assoc: SLE,
cryoglobulinemia,
scleroderma (Sjogren’s,
RA)
• vs. Buerger’s disease
(smoking and
ulceration/amputation of
digits)
 Bursitis
• Septic
• Crystal
• Trauma
• Dif: culture
and
microscopy
• Olecronanon,
trochanteric,
subdeltoid,
anserine
• Pitting edema
 Monoarticular arthritis
• Crystal vs. septic, (also-lyme, gonorrhea, reactive, sickle
cell)
• Small or large joint?
– Infected = large joint = 50% knee, hip, SI, wrist, elbow,
shoulder, ankle (rarely fingers/toes)
• Monoarticular or polyarticular?
– Polyarticular is rarely septic.
• Fever, serum WBC, uric acid, ESR/CRP = all USELESS
for differentiating between etiologies
• Recurrent: crystal, lyme, seronegatives
• Chronic: mycobacterium, fungi, borrelia,
hypogammaglobulinemia
 Arthrocentesis in Monoarticular
Arthritis

• New onset monoarticular arthritis should likely

be tapped
• Synovial fluid: cell cnt w/ dif, crystals, culture
and gram stain
• Synovial fluid cell cnt tells a lot about etiology
• PMNs > 50000 could be cyrstal or septic
 Rheumatoid Arthritis
• Epidemiology: F > M, 40-70yo
• Pathology:
– pannus formation in joint synovium, leads to erosions in bone.
– Matrix matolproteinases (MMP’s)
– Inflammatory cytokines: IL6, TNFalpha, IL1
– Synovial disease: angiogenesis, hyperplasia, cytokine release
• Clinical: symetric polyarticular inflamatory synovitis
including wrists and MCP’s usually
– Erosions in 2yrs, long-standing joint disfiguration
• RF and anti-CCP for prognosis/diagnosis
• Treatment: MTX and TNFinh = best treatment
– Alternatives: triple therapy (MTX, SSZ, Plaquenil), steroids,
other biologics, leflunomide,
Ulnar deviation

Physical exam
findings of hands in
RA

Swan neck

Boutonniere
synovitis
 Vascular formation

Syovial hyperplasia

Pannus formation in RA synovium

RA erosions in various stages
RA EXTRAARTICULAR -
VASCULTITIS
RA – EYE - SCLERITIS
RHEUMATOID
NODULE
SNSA’s
 SNSA UNIFYING FEATURES
• sacroiliac joint involvement (axial disease) with
inflammatory back pain
• peripheral joint involvement (non-axial disease)
• Can be asymetrical and lower extremity
• no RF or anti-CCP
• extra-articular features:
• HLA-B27 +
• enthesopathy (tendon insertion site inflam.)
• dactylitis (sausage digit)
• mucocutaneous disease
• conjunctivitis/uveitis
• cardiac disease (valvular / conduction)
• Colitis
• urethritis
SNSA’s--uveitis
SNSA’s--enthesitis
SNSA’s--dactylitis
SNSA’s—keratoderma blennorrhagica
Circinate balanitis
Less than 10% of people with HLA B27 will develop SNSA
But 95% of those with AS are B27 positive
ANKYLOSING SPONDYLITIS
• Male, young
• B27+
• Spine and SI joint involvement
• “bamboo spine”
• Inflammatory back pain, AM
stiffness
• Fusion of spine, increased
fracture
• Extrarticular: apical lung
fibrosis, aortitis

• Treatment: antiTNF inh

AS / PULMONARY DISEASE
SACROILIITIS--early
SACROILIITIS—late ankylosis
 SPONDYLITIS-
SYNDESMOPHYTES in AS
 REITER’S / REACTIVE
ARTHRITIS
Reiter’s Triad: urethritis, uveitis, arthritis
Reactive:
• 1-3wks after bacterial infection (GI/GU)
• May be monoarticular, asymetrical, oligoarthritis
• 80% B27 positive
• Male predominance
• May recur
• Bugs: chlamydia, salmonella, shigella, 25% unknown
• Tx: NSAIDS, SSZ, MTX, TNFinh
PSORIATIC ARTHRITIS
onycholysis DIP arthritis
PSORIATIC ARTHRITIS
 PSORIATIC ARTHRITIS

• Asymetric oligoarthritis
• axial disease (spondylitis)
• Small joint/RA-like distribution
• Can proceed skin lesions of psoriasis
• RF/CCP negative!
• Tx: SSZ, MTX, TNFinhibitor
 IBD-Related/Enteric Arthritis
• 20% of patients with Crohn’s/UC
• Peripheral (parallels IBD activity)
• Axial (does not parellel w/ IBD, more HLA B27+)
• Chronic or intermittent, likely asymetric
• Worse in patients w/ worse IBD (extraarticular)
• Other extraintestinal features
– Uveitis
– Sclerosing Cholangitis
– E. nodosum
– Pyoderma gangrenosum
• Tx: NOT NSAIDS, either SSZ or TNFinh
 OSTEOARTHRITIS
Epidemiology:
• Age-50%>65yrs old, 80% >80yo
• Weight/obesity
• Trauma
Clinical:
• Pain (doesn’t correlate with xrays)
• Heberdens/Bouchard’s nodes
• Possible joint effusions
• Crepitus on passive ROM
Imaging:
• Subchondral sclerosis/cysts
• Joint space narrowing, osteophytes
Treatment:
• Exercise, weight modification, quadriceps
strengthening, shoe inserts
• Caspacin cream, tylenol, NSAIDS, COX2inh.,
tramadol, glucosamine, intrarticular hylauronan
or steroids
NODAL OSTEOARTHRITIS
OSTEOARTHRITIS
HIP
EROSIVE OA—DIP, PIP joints
clinical inflammation
 OSTEOARTHRITIS
DISH—anterior longitudinal
ligament ossification
 OSTEOARTHRITIS
HEMOCHROMATOSIS
OSTEOARTHRITIS
AVN
SLE

• Young women
• Path: autoantigens with
immune complex deposition
• Arthritis and rash most
common clinically
• DSDNA predicts nephritis
• Non-erosive arthritis
• Pulmonary artery hypertension
association
SLE
SLE
 SLE

malar discoid
SLE—Jacoud’s arthropathy
 SLE Treatment and Mortality

• Arthralgias/myalgias, rash, fatigue: NSAIDS, plaquenil

• Plaquenil: used in almost every SLE pt, steroid-sparing,
cholesterol lowering, anti-thrombotic properties, lowers flares
• Severe arthralgias: methotrexate
• Severe organ damage, eg. SLE nephritis: cyclophosphamide
vs. MMF, with high dose steroids
• Thrombocytopenia: steroids, IVIG

• Mortality: PAH, nephritis, accelerated atherosclerosis, other

end organ damage.
 SLE and Pregnancy

• Glomerulonephritis, HTN, APS = bad pregnancy outcomes

• HELLP/eclampsia/preeclampsia vs. SLE flair
• SSA/SSB screening during pregnancy: predicts neonatal
SLE/congenital heart block

• Treatment of SLE during pregnancy: steroids, plaquenil,

imuran. NO CYCLOPHOSPHAMIDE, MTX, or MMF!
 Drug-Induced SLE
• Clinically the same except no renal disease
• Anti-histone antibody
• No anti-Smith or anti-ds dna ab
• Complements normal
• Drugs: INH, procainamide, hydralazine
• Treatment. Short course of NSAIDs or
steroids and DC offending drug
 Antiphospholipid Syndrome
Clinical: Diagnositic:
• Elevated PT/PTT
• Anti-beta2 glycoprotein
• Anti-cardiolipin
• Increased DRVVT ratio
LIVEDO RETICULARIS
 MCTD

RA
Infectious Arthritis:
• Tuberculous arthritis
• Potts Disease: TB of the spinal column
• Parvovirus: symetric small joint arthritis,
parvovirus IgM +
• Lyme
• Rheumatic Fever
• Monoarticular arthritis
• Hepatitis C
• Cryptococcus
• HIV
PARVOVIRUS—self resolving
 Septic Arthritis
• How? Hematogenous seeding in a damaged (replaced or
diseased) joint
• Who? Immunocompromised, RA, elderly, IVDA
• Where? Almost always monoarticular, large joint
(knee 50%, rarely fingers or toes)
• Significant pain on passive ROM
• Bugs: S. aureus, strept, salmonella, pseudomonas (IVDA),
pasturella (animal bites)
• Arthrocentesis with culture for diagnosis
(culture/gram stain for gonorrhea are usually negative)
• Treatment: antibiotics (vanco to start unless concerned for
gram negative coverage; surgery pending abx course after
repeat arthrocentesis w/o improvement)
 DISSEMINATED GC

• Young, sexually active,

usually knee
• Can be migratory arthritis
CRYSTALLINE ARTHRITIS: Gout
• Men
• Monoarticular flairs vs. chronic
polyarticular
• Monosodium urate crystal deposition
in synovium, tendon sheaths, bursae
• Inflam: innate immunity, NALP3
inflammasome, IL1
• Negative birefringence
• Precipiates > 6.7mg/dL
• Diet: shellfish, red meat, EtOH
• Tophi: soft tissue deposits
• CKD = largest risk factor (decreased
excretion of urate)
• Drugs: cyclosporin, HCTZ,
furosemide
• Diagnosis: crystals
GOUT
GOUT
 Gout Treatment
• Acute gouty flair:
NSAIDS, colchicine, steroids
• Prevention:
1. Daily colchicine: monitor for axonal neuropathy, myopathy,
renal/liver insufficieny, pancytopenia. Interacts with
macrolides, statins, and cyclosporin
2. Uric acid lowering therapy:
• Allopurinol (xanthine oxidase inhibition)
• Side effects: Stevens Johnson/rash, toxicity in
renal/liver insufficiency
• Febuxostat (used in renal and liver insufficiency)
• Probenecid: increased uric acid renal excretion, measure
urine uric acid first to prevent kidney stones
 CPPD
Indolent (pseudoOA, pseudoRA) vs. gouty-like
Age-associated
Positive birefringence
Assoc: acute illness, hyperparathyroid, Wilsons, hemachromatosis
Treatment: like gout, but not uric acid lowering
 Systemic Sclerosis (Scleroderma)
Connective tissue disease, fibroblast activation, microvascular injury
Diagnosis: skin thickening and sclerodactyly are the hallmarks
Classification:
1. Limited Systemic Sclerosis (CREST)
• Calcinosis, Raynaud’s, esophageal dysmotility, sclerodactyly,
telangiectasias
• Skin thickening only distal to elbow/knee, +/- face
2. Diffuse Systemic Sclerosis
• Skin thickening proximal to elbow/knee, +/- face
Skin: thickening, flexion contractures, calcinosis, ulcers, telangiectasias
Raynaud’s (95%)
MSKL: palpable tendon friction rubs, inflammatory arthritis, inflam
myopathy overlaps
GI: all scleroderma has some GI invovlement—esophageal most
common (GERD, Barrets, strictures), illeus, pseudoobstruction
 Systemic Sclerosis (Scleroderma)
Pulmonary: high mortality!
1. ILD (diffuse scleroderma—bibasilar ground glass, reticulolinear
scarring)
2. PAH (limited scleroderma)
Renal: scleroderma renal crisis (diffuse scleroderma)
• Characterized by severe HTN, hemalytic anemia, low plts,
proteinuria and renal failure
• Treatment: rapid uptitration of ACEinhibitors
• Risk: prednisone treatment of scleroderma
Systemic Sclerosis sine scleroderma: characteristic organ involvement
without associated skin thickening
 MORPHEA & LINEAR
SCLERODERMA (isolated skin
thickening)
CREST
PSS SKIN
SCLERODERMA GI
SCLERODERMA
ANTIBODIES
SCLERODERMA LUNG
POLYMYOSITIS / DERMATOMYOSITIS
Clinically: symetric proximal muscle weakness, +/- esophageal, neck
and/or respt muscle weakness
ILD association with either
Labs: elevated CK most sensitive (also aldolase, CKMB, AST/ALT)
Usually +ANA
Anti-Jo1: 20% pts, anti-histidyl tRNA synthetase (assoc. with ILD,
polyarthritis and Raynauds)
Diagnosis: clinical suspicion with elevated CK, EMG and MRI findings
of weak proximal muscles, biopsy = gold standard
Treatment: high dose steroids until CK decreases, then MTX or steroid-
spairring agent. Cylcophsphamide for ILD, IVIG may work
Dermatomyositis: association with age-appropriate cancer, ovarian
cancer
 DM

Shawl sign heliotrope

GOTTRON’S (DM)
IBM
 Vasculitis
Large Vessel Vasculitis:
• Giant Cell Arteritis’/PMR
• Takayasu’s arteritis

Medium Vessel Vasculitis:

• Kawasaki’s
• PAN

Small Vessel Vasculitis:

• Wegener’s
• Churg-Strauss
• MPA
• HSP
• Cyroglobulinemic
• Cutaneous
leukocytoclastic
 Giant Cell Arteritis
• Granulomatous vasculitis
• Extracranial branches of the internal carotid
• Women >50yo
• Clinical: headache, jaw claudication,
systemic symptoms, fever, visual
disturbance, tenderness of temporal artery
• Diagnosis: clinical features + ESR = biopsy
• High dose steroids/ASA if suspect, b/f
biopsy to prevent blindness/stroke
• Long steroid course (2yrs plus), relapsing
 PMR
• Acheing and morning stiffness in pelvic and
shoulder girdles, in conjunction with high ESR
• Old white people
• 40-50% of pts with GCA have PMR, only 10% of
PMR pts have GCA
• Clinical/lab diagnosis
• Diagnostic and therapeutic: rapid response to 10-
20mg of prednisone
 Takayasu’s Arteritis
• Granulomatous branches of aorta and its
branches and the pulmonary arteries
• Young women
• Systemic constitutional symptoms, HTN,
asmetrical limb blood pressure, symptoms
of occlusion (stroke, vision changes, etc)
• Dx: arteriography
• Tx: MTX and prednisone
• Chronic illness, relapse, some w/o
remission
TAKAYASU’S
 Polyarteritis nodosa
• Necrotizing inflammation of medium-small
arteries without glomerulonephritis
• Clinical: hypertension, fever, mskl symptoms,
vasculitis of GI, heart and renal arteries
• Dx: arteriography of visceral/abdominal
arteries: microaneurysms, stenosis, “string of
beads”
• Tx: cylcophosphamide and steroids for
involvement of GI, heart, or CNS
• No relapse
POLYARTERITIS NODOSA
 Wegener’s Granulomatosis
• Necrotizing granulomatous vasculitis
• Lung nodules, sinus/cartilage damage,
glomerulonephritis
• Dx: biopsy, usually VATS, of lung tissue
• focal/ semgental necrotising
glomerulonephritris, pauci-immune.
• C-ANCA anti-PR3 positive
• Tx: cyclophosphamide/high dose steroids
WEGENER’S
 Microscopic Polyangiitis
• Small vessel necrotising, non-granulomatous
vasculitis
• Clinical: glomerulonephritis, pulmonary
hemorrhage, mononeuritis multiplex, cutaneous
small vessel vasculitis with palpable purpura,
fever
• Dx: biopsy, pauci-immune
• P-ANCA, MPO positive
• Tx: cyclophosphamide, high dose prednisone
 ANCA
C-ANCA (PR3)-Wegener’s
P-ANCA (MPO)-CSS/MPA
 Churg-Strauss Syndrome
• Clinical: asthma, fever, hyper-eosinophilia, and
vasculitis
• Vasculitis of many different organs possible
• Some have c or p-anca
• Tx: prednisone (unless life threatening =
cyclophosphamide)
 Other small vessel vasculitides
• HSP
• Cyroglobulinemic
• Cutaneous leukocytoclastic
• Drug-induced
HYPERSENSITIVITY
VASCULITIS / HSP
CRYOGLOBULINEMIA
 FIBROMYALGIA
MSKL pain with palpation, without evidence of arthritis
Treatment: antidepressants, exercise, OSA treatment
 HIV
• Incomplete Reiter’s
• PsA
• RA goes away..
• Myopathies
SARCOIDOSIS
REFLEX SYMPATHETIC
DYSTROPHY
REFLEX SYMPATHETIC
DYSTROPHY
 Sjogren’s Syndrome
• Sicca complex
– Keratoconjunctivitis (lacrimal gland)
– Oral sicca (parotid)
– Lymphocytic infiltrate (CD4)
– SSA (Ro), SSB (La), RF, ANA, polyclonal
gammopathy
– Woman age 30-50
– Extraglandular
• ILD, PBC, vasculitis, neuropathy, arthritis, Raynaud’s, fever,
fatigue, adenopathy/lymphoma, Hashimoto’s, myositis
– Primary vs secondary (RA)
BEHCET’S
BEHCET’S
 Relapsing Polychondritis
• Inflammation and destruction of cartilage
structures (ears, nose,throat)
• Auricular/ear pain and swelling, califlower
ear, saddle nose deformity, upper
respiratory cartilage destruction
• NSAIDs, dapson, or steroids
 Adult Still’s Disease
Major Criteria:
• Fever >39
• Arthralgias/arthritis (synovitis)
• Salmon-pink macular rash on trunk/extrem
• Lekuocytosis, prominent left shift
Minor Criteria:
• Sore throat, LAD, elev LDH, AST/ALT, negative
ANA and RF
Treatment: depends—usually NSAIDs and ASA for
minor symptoms,