Arthritis, Connective Tissue Disease and Vasculitis Flashcards
Joints affected by Inflammatory arthritis (RA)
Small Joints, sparing the DIP
PIP, MCP, MTP, wrist
Pain pattern of an inflammatory arthritis (RA)
Improves with activity
Worse in the morning
>30 minutes of morning stiffness
Joints affected by Non-inflammatory arthritis (OA)
Large joints, and DIP
Knee, hip, shoulder, spine
Synovial fluid appearance in inflammatory arthritis
Cloudy, non-viscous (only non-infectious synovial is straw colored and clear)
Diseases that cause a cloudy, non-viscous synovial aspirate
RA, spondylitis, crystalline arthritis, viral/fungal infection
(inflammatory arthritis)
Joints most commonly affected by gout
Large toe
Knee
Ankle
Midfoot
Precipitating events for gout flares (9)
Alcohol Infection Surgery CKD Diuretics Aspirin Obesity High protein meals Cyclosporine
Main characteristics of an inflammatory arthritis
Stiffness >30 minutes
Morning Pain
Better with activity
Affects small joints most
Symptoms of an acute gout flare
Pain, swelling, and warmth in affected joint
Fever or sweating
Leukocytosis
Tophi
Deposits of urate crystals within the body
Locations that tophi can occur in gout patients
Fingers
Wrists
Knees
Olecranon
Pressure points (ulnar forearm, achilles tendon)
Visceral locations (heart, kidney, sclera)
Birefingence of gout crystals
Negative (gout = doubt)
Birefringence of CCPA crystals
Positive
Radiographic findings of gout joints
Erosive arthritis: punched out joints with overhanging bone lesions
Mechanism of damage in CCPA (calcium pyrophosphate arthritis)
Neutrophils swallow crystals and cause inflammation
Drugs of choice for managing an acute gout flare
Colchicine
NSAIDs
Steroids
Primary symptoms of CCPA
Mimics gout in pain and presentation
Does not have tophi typically, but DOES have dactylitis AKA boxer glove swelling
(also seen in RA and psoriatic arthritis)
Other diseases associated with CCPA
Hyperparathyroidism (high levels of Ca –> CPP deposition)
Hypothyroidism
Hemochromatosis
Hypomagnesemia (Calcium absorbed preferentially due to low levels)
hypophosphatemia (consumed in CPP crystals)
Factors that can precipitate CCPA/Pseudogout
Surgery
Infection
Trauma
But NOT alcohol like GOUT
Joints most commonly affected by CCPA
Knee
Wrist
Hand
Ankles
Treatment of choice for an acute CCPA flare
Same as gout
NSAIDs
Steroids
Cholicine
Prognosis of pseudogout
Typically resolves within 5-14 days
Chronic CPPA increases risk of osteoarthritis
MoA of Colchicine
Arrests microtubule assembly and inhibits inflammatory cells (via inhibition of cell division)
But only effective if given within 48 hours of a flare
Precautions for Colchicine Use
Affects Highly dividing cells: GI upset, bone marrow suppression.
Myopathy
CI in kidney disease due to electrolyte imbalances
NSAID of choice in treating gout
Indomethacin
Contraindications of indomethacin use in acute gout flares
Renal insufficiency (NSAIDs can precipitate renal hypoxia) Gastric ulcers
Treatment of choice for gout flares in patients with kidney disease or polyarticular manifestation
Steroids (colchicine and indomethacin are CI in kidney disease)
Drugs commonly used to treat chronic gout
Allopurinol (w/ colchicine)
Febuxostat
Uricase (uricosuric)
Probenecid
MoA of febuxostat
Xanthine oxidase inhibitor similar to allopurinol but with low risk of hypersensitivity reaction
Criteria for chronic gout arthritis
3+ flares in a year or 5+ lifetime flares
Urate level >13
Uric acid nephropathy
Tophi or erosions on radiograph
Prophylaxis to prevent tumor lysis syndrome when starting chemotherapy
Precautions in allopurinol use
Potential for hypersensitivity/SJS reaction (do not rechallenge)
Can worsen flares (give with colchicine)
Fever
Cytopenia (risk increased with azathioprine for RA or organ rejection)
Probenecid MoA
Increases uric acid excretion (requires >700mg/day clearance to be effective)
Uricase contraindications
Anaphylaxis to IV infusion
Cost
Situations in which uricase would be used for gout
Severe tophaceous or refractory gout due to its price
“Shared epitope” that increases RA risk in smokers
HLA-DRB1
HLA isotypes associated with RA
HLA-DR 1, 4, 10
Serum markers for RA
Rheumatoid factor
Anti-citrullinated protein antibody
Elevated ESR and CRP
Polyarthritis options if the patient does not have synovitis (non-inflammatory polyarthritis)
Osteoarthritis Viral arthralgia (hepatitis especially) Mechanical damage
Characteristic symptoms of rheumatoid arthritis
Synovitis Pain lasting >6 weeks Pain is most often symmetric and proximal Joint erosion Extra-articular manifestations
Diseases in which rheumatoid factor may be positive
Rheumatoid arthritis Sjogren's syndrome sarcoid endocarditis hepatitis C infection (or hepatitis C arthritis) cryoglobulinemia
Diseaes in which anti-citrullinated protein antibodies may be positiveq
RA only, much more specific than RF and can predate symptoms by a few years
Characteristic radiographic findings for RA
Pannus formation within the joint space marginal erosions Symmetric joint space narrowing Ulnar deviation of joints Boutinniere joint (DIP extension) Swan neck (DIP flexion) Marginal erosions of bone near the synovium Rheumatic nodules
Extra-articular manifestations of RA
Skin: Nodules, scleritis, nail fold infarction, vasculitis ulcers
Lung: ILD, pleurisy, pulmonary nodules
Cardiac: accelerated CVD, myocardial nodules, aortitis (vasculitis)
Felty’s Disease: Anemia, thrombocytopenia, neutropenia, splenomegaly
Rheumatoid vasculitis
Drugs of choice for RA
Immunosuppression
Anti-inflammatories
DMARDs (hydroxychloroquine, methotrexate, lefunamide, sulfasalazine)
Anti-TNF agents
“Triple Therapy” of RA
Methotrexate + Sulfasalazine + Hydroxyquinone
= Anti TNFa effectivness
MoA for hydroxychloroquine in mild RA and Lupus
Reduces lysosomal fusion
Reduces DNA synthesis
Reduces platelet aggregation
Reduces cytokine release
Toxicity associated with hydroxychloroquine
Retinal or corneal deposits Vertigo Hypersensitivity reactions Neuropathy Cardiomyopathy
Toxicities associated with Methotrexate (non-obvious)
Acute or chronic pulmonary or liver toxicity
Major teratogen
CI in alcoholics
Mechanism of Leflunomide in RA treatment
Similar to methotrexate but affects dihydrooate and not foalte metabolism
Toxicities of Leflunomide in RA treatment
GI upset Alopecia HTN cytopenia liver toxicity (CI in alcoholics) teratogen (all similar to methotrexate except hypertension)
Can be easily reversed by cholestyramine in the case of an acute infection
Toxicities associated with sulfasalazine in RA treatment
GI upset, headache
Aplastic anemia, hepatitis, nephritis, pancreatitis are all rare.
Cannot be used with sulfa allergy
CAN be used in alcoholics
Review the biologic agents for RA
Review the biologic agents for RA
Primary concern in treating RA with rituxumab
Risk of hepatitis B reactivation or progressive multifocal leukoencephalopathy
Primary concern of anti-TNFa biologics
formation of anti-dsDNA and Lupus drug reaction
Unique features of Systemic Onset JIA
Least common JIA
Presents with fever, rash, and nodules (systemic part)
Affects any joint
Destructive arthritis, leukocytosis, anemia, and ESR are all marked
ANA is absent
Unique features of Pauciarticular JIA
Most common JIA but hard to diagnose due to relative lack of symptoms (Pauci)
Occurs early in childhood and is rare over age 10
Affects large joints but spares the hip (other JIAs will affect hip)
Uveitis
+ANA
Unique features of polyarticular JIA
Affects any joint, but the hip is never first (vs pauciarticular, which always spares hip)
Has less destructive arthritis, anemia, and ESR than systemic JIA
Only JIA that can possibly have a +RF
HLA isotype associated with ankylosing spondylitis and reactive arthritis
HLA-B27 (explains male gender preference in AS and reactive arthritis)
Shober manuver
Reduced back flexibility indicative of splondyloarthropathy
Common features of spolyloarthropathies
Very responsive to NSAIDs
Dactylitis (some)
Uveitis (ALL)
Strong association with HLA-B27
Features of Psoriatic Arthritis
Low Back Pain
Psoriasis
Asymmetric distribution of spondylitis
Dactylitis (sausage fingers)
Features of Aknylosing Spondylitis
Higher incidence in males High corellation with HLAB27 Symmetric sacroilitis Enthesitis (not seen only in IBD) Anterior uveitis Prostatitis (unique)
Features of Reactive Arthritis
Male predominancce Often occurs after an STI or GI infection Anterior uveitis, conjunctivitis Commonly affects large joints High HLA-B27 assocaiation SKIN LESIONS: Circinate balatitis, keratoderma Urethritis Oncholysis
Can’t see, can’t pee, can’t bend my knee
Symmetric spondylopathies (2)
AS and Reactive
Asymmetric spondylopathies (2)
Psoriatic and IBD associated
Only spondyloarthritis without enthesis
IBD
Therapeutic options for ankylosing spondyltitis
ROM excercises to avoid spinal fusion by syndesmophytes
NSAIDs
Sulfasalazine or methotrexate
TNF inhibitors
Presenting Symptoms of Lupus
SOAP BRAIN MD Serositis Oral and nasal ulcers (PAINLESS) Arthritis Photosensitivity
Blood dyscrasias (anemia, thrombocytopenia, hemolysis is Coombs positive)
Renal disease
Autoimmune studies (+ANA)
Immunologic (anti-smith, anti-dsDNA, anti-PL)
Neurologic (seizures, psychosis)
Malar rash
Discoid rash
Also libman sacks endocarditis (vegetations on valves)
Number of SOAP BRAIN MD symptoms needed to Dx Lupus
4/11 of these symptoms are needed to diagnose Lupus
Risk factors for developing Lupus
Genetic factors on X chromosome (all females, males with Kleinfelter)
Estrogen therapy or early menarche
Childhood EBV infection
Exposures to smoking, silica, dust, UV light
OOPHORECTOMY can alleviate some risk in females
Primary mechanism of kidney disease in Lupus
Type III: immune complex deposition
Antibodies positive in Lupus
ANA (non-specific, highly sensitive)
Anti-dsDNA
Anti-phospholipid
Anti-smith
Anti-cardiolipin (causes cross reactions in VDRL and falsely prolongs PTT)
Anti-histone (in drug-induced lupus only)
Hypocomplementemia
Treatment for Lupus
NSAIDs steroids
Hydroxychloroquine
Cyclophosphalmide/mycophenolate only if severe disease
Rituxumab
Antibodies in Sjogren’s syndrome
> 90% have positive Rheumatoid factor
Anti-SSA
Anti-SSB
ANA
Non-glangular complications of Sjogren’s syndrome
Pancytopenia
Arthritis
lymphadenopathy (may be due to lymphatic blockage in swollen lacrimal/parotid glands)
Increased risk for lymphoma, MALT
Antibodies positive in diffuse scleroderma
Anti-scl70 (DNA polymerase)
Anti-nucleolar
ANA
Antibodies positive in local scleroderma
ANA
Anti-centromere
Symptoms of diffuse scleroderma
Raynaud’s
Esophageal dysmotility
Scleroderma (wide range)
Telangectasias
Widespread organ sclerosis with potential for pulmonary hypertension
Fingertip pitting
Mechanic hands (seen in both Limited and diffuse)
Renal crisis
Symptoms of limited scleroderma
Calcinosis Raynaud's Esophageal dysmotility Scleroderma restricted to hands, feet and face Telangectasias
Interstitial lung disease and pulm hypertension occur in much later stages than in diffuse
Common symptoms of Polymyositis and Dermatomyositis
Symmetric proximal limb weakness Difficulty swallowing with possible nasal regurg due to involvement of esophageal skeletal muscle Lung disease Myocarditis Raynaud Mechanics hands
Features unique to polymyositis (vs dermatomyositis)
CD8+ (poly = more!) endomysial inflammation
Features unique to dermatomyositis (vs polymyositis)
CD4+ perimysial inflammation SKIN INVOLVEMENT - Grotton's sign" rash on knuckles - Periorbial rash - Nail abnormalities
– Mechanic’s hands are seen in both
Prognosis of dermato/polymyositis
Increased mortality from malignancy, infection, or pulmonary compromise
Diagnostic criteria of dermato/polymyositis
CK levels should be elevated Electromyogram abnormalities Anti-Jo Anti-SRP Anti-MI2
Not to be confused with polymyalgia rheumatica which presents similarly but has normal CK
Treatment of dermato/polymyositis
Steroids for an acute flare
Long term immunosuppression
Large vessel vasculitides
Giant cell arteritis
Takayasu arteritis
Medium vessel vasculitides
Kawasaki
Polyarteritis nodosa
ANCA+ Small vessel vasculitides
Wegener’s (granuloma polyangiitis)
Churg-Strauss (Eos polyangiitis)
Microscopic polyangiitis
ANCA- Small vessel vasculitides (immune complex)
IgA vasculitis
Cryoglobulinemic vasculitis
Anti-GBM disease
Required before beginning immunosuppression in vasculitis
Get biopsy. Immunosuppression can worsen many mimic diseases.
Except with suspected GCA which gets empiric high dose steroids
Treatment options for small vessel vasculitis
Due to high mortality high-dose steroids are begun and tapered into a chronic immunosuppression with methotrexate or azathioprine.
If disease is life threatening, can give pulsed high dose (>1g/day) steroids with rituximab or cyclophosphamide.
Treatment for large vessel vasculitides
High dose steroids
Conditions associated with positive C-ANCA (PR3)
Wegner’s ONLY
Highly sensitive and specific
Conditions associated with P-ANCA (MPO)
Highly sensitive, but not specific
Non-Wegner's polyangiitis (Microscopic, Eosinophilic) IBD Liver disease HIV Lupus
Condition also associated with GCA
Polymyalgia rheumatica
Diagnostic features of takayasu’s arteritis
Female, asian
Narrowing of the aorta and proximal great vessels
upper extremity claudication
subclavian bruits
Diagnostic features of polyarteritis nodosum
Immune complex formation secondary to hepatitis B infection–> renal micro- anyrusms
Typically affects young adults
Renal involvement can cause hypertension
Vascular purura
