Rheumatology Flashcards
Clinical findings in neonatal lupus
- Skin lesions
- Cardiac abnormalities: AV block, transposition of great arteries
- Valvular and septal defects
Pathophysiology of SLE
Autoimmune inflammatory condition involving autoantibody production, deposition of immune complexes, complement activation, and accompanying tissue destruction/vasculitis.
Discoid Lupus
Skin lesions without systemic disease
What is a serious cardiac complication of lupus?
Libman Sacks Endocarditis
Is ANA more sensitive or specific?
ANA is sensitive but not specific. That means that almost all patients with SLE have elevated serum ANA levels. But remember SNout, if it is not present, you almost rule out lupus.
ANA is positive in other diseases like RA, scleroderma, Sjogren’s syndrome, mixed connective tissue diseases, polymyositis and dermatomyositis, and drug induced lupus.
What two antibodies if positive are DIAGNOSTIC for SLE? Are these antibodies more sensitive or specific?
Anti-Sm and Anti-ds DNA. These are both very specific. SPin.
What antibodies are positive in drug induced lupus?
Anti-histone. These are present in 100% of cases of drug induced lupus. If negative, drug induced lupus can be ruled out.
Lab marker associated with Wegener’s Granulomatosis
C-ANCA
Lab marker associated with Polyarteritis Nodosa
P-ANCA
Which HLA marker is associated with SLE?
HLA-DR2 and HLA-DR3
Which HLA marker is associated with Sjogren’s Syndrome
HLA-DR3
Which HLA marker is associated with RA?
HLA-DR4
Which HLA marker is associated with ankylosing spondylitis, Reiter Syndrome and psoriatic arthritis?
HLA-B27
Are complement levels usually high or low in lupus?
complement levels are usually decreased.
What is the best long term treatment for SLE?
Antimalarial Hydroxychloroquine–> used for preventative measure even after resolution of symptoms. Good for constitutional, cutaneous, and articular manifestations.
What is the best tx for acute flare of SLE?
Corticosteroids (systemic)
What is the major toxicity of hydroxychloroquine and what should you do to screen for it?
Retinal toxicity, the patient should have annual eye exams.
What is the best treatment for glomerulonephritis associated with lupus?
Cyclophosphamide
What are the 2 most common causes of death in lupus?
Opportunistic infection and renal failure.
What is the pathophysiology of Systemic Scleroderma?
Cytokines stimulate fibroblasts, causing an abnormal amount of collagen deposition. it is the high quantity of collagen that causes the problems associated with the disease. Composition of collagen is normal.
Which type of scleroderma is more common?
Limited (80% of cases)
What is one major difference between drug induced lupus and SLE?
Drug induced lupus doesn’t affect the kidney or CNS
What are some common drugs implicated in drug induced lupus?
INH, hydralazine, procainamide, chlorpromazine, methyldopa, and quinidine
Treatment for antiphospholipid antibody syndrome
Long term anticoagulation
Typical findings in antiphospholipid antibody syndrome
- Recurrent venous thrombosis
- Recurrent arterial thrombosis
- Recurrent fetal loss
- Livedo reticularis
- Thrombocytopenia
What clinical finding is present in virtually all cases of systemic scleroderma?
Raynaud Phenomenon
What is the pathophysiology of Raynaud Phenomenon
Vasospasm and thickening of vessel walls in other digits
What are potential complications of Raynaud’s
ischemia, infarction, gangrene and ulceration
What other clinical findings are present in Systemic Scleroderma?
- Raynaud Phenomenon
- Cutaneous fibrosis
- GI involvement (both diffuse and limited)
Define sclerodactyly
claw like appearance of the hand due to cutaneous fibrosis resulting in tightening of the skin on the extremities.
What are the GI findings associated with systemic scleroderma?
- Dysphagia/reflux from esophageal immobility. When prolonged this can lead to esophageal strictures.
- Delayed gastric emptying
- Constipation/diarrhea
- abdominal distention
- Pseudo-obstruction
Which type of scleroderma is the only type to have pulmonary, cardiac, and renal involvement?
DIFFUSE
What is the most common cause of death from scleroderma?
Pulmonary involvement. This includes pulmonary fibrosis, and/or pulmonary hypertension.
Which antibody is specific for the diffuse form of systemic scleroderma?
Antitopoisomerase-I
Which antibody is specific for the limited form of systemic scleroderma?
Anticentromere antibody
Treatment for scleroderma?
SYMPTOMATIC:
- Bosentan for pulmonary hypertension
- ACE-inhibitors for renal hypertensive crisis
- Cyclophosphamide for pulmonary fibrosis
- Avoid the cold and smoking and use CCBs with Raynaud
- H2 blockers or PPIs for reflux
- NSAIDs for MSK pains
What is CREST syndrome?
A variant of limited systemic scleroderma:
C-calcinosis of the digits
R-raynaud phenomenon
E-esophageal motility dysfunction
S-sclerodactyly of the fingers
T-telangiectasis over the digits and under the nails
What two drugs can be used for lupus nephritis?
IV cyclophosphamide then move to oral mycophenolate mofetil
Which antibody is highly associated with lupus nephritis?
anti-ds-DNA
How do you make the diagnosis of lupus nephritis?
Biopsy (NOT just the antibody!)
What antibody is associated with autoimmune hepatitis?
Anti-smooth muscle antibody
What antibody is associated with Sjogren’s syndrome?
Anti-Ro, Anti-La
What antibody is associated with polymyositis or dermatomyositis?
Anti-Jo
What antibody is associated with primary biliary cirrhosis?
Anti-mitochondrial antibody
Describe the pathophysiology of Sjogren’s Syndrome
Lymphocyte infiltrate and destroy the lacrimal and salivary glands.
What is secondary Sjogren’s syndrome?
Patient’s have sjogren’s syndrome along with another connective tissue disease (SLE, RA, systemic sclerosis, polymyositis, etc.)
What is one feared complication of Sjogren’s Syndrome? It is also related to the most common cause of death.
With Sjogrens there is an increased risk of non-Hodgkin lymphoma. Malignancy is the most common cause of death.
What are some of the clinical features of Sjogren’s Syndromes
Dry eyes, dry mouth, cavities, arthralgia, fatigue, interstitial nephritis and vasculitis, keratoconjunctivitis sicca
What is the Schirmer Test?
You plate a filter paper in the eye to measure lacrimal gland output.
What is the most accurate way to diagnos Sjogren’s syndrome?
Salivary gland biopsy, but it is not always necessary for the diagnosis.
What is the treatment/therapy for Sjogren’s Syndrome?
- Pilocarpine or Cevimeline to enhance oral and ocular secretions
- Artificial tears
- Ensure good oral hygiene
- NSAIDs for athralgias
anti-U1-RNP antibody is associated with what disease?
Mixed Connective Tissue Disease
Pathophysiology of RA
Autoimmune conditions that causes inflammation and destruction of the synovium of the joints.
Which joints are typically NOT involved with RA?
The DIP joints are normally spared. It usually involves the MCP and PIP joints as well as the wrists.
What are the characteristic hand deformities associated with RA?
- Ulnar deviation of the MCP
- Boutonniére deformity of the PIP joints (PIP joint is flexed, DIP joint is hyperextended.
- Swan neck deformity (MCP joint is flexed, PIP joint is hyperextended, DIP is flexed)
How do you describe the morning stiffness associated with RA compared to OA?
In RA, there is morning stiffness that improves as the day progresses.
What is one bony involvement that can cause serious complications in patients with RA and what should you do about it?
C1-C2 subluxation which can cause neurologic injury. All RA patients should have C-spine radiographs before undergoing surgery as intubation can cause subluxation and complications.
Where do rheumatoid nodules occur?
They occur in the subcutaneous portion of the skin, over the extensor surfaces. They may also occur in the viscera.
The presence of these nodules portends a worse prognosis.
Are osteophytes present in RA?
No but they are in OA.
What lab findings are seen to make the diagnosis of RA?
- Rheumatoid factor may or may not be elevated
- Anti-citrullinated peptide antibodies: specificity is >90%
- Elevated ESR/CRP
- Anemia of chronic disease
What pattern of lung disease is associated with RA
Pulmonary fibrosis–> restrictive lung disease. Honeycomb pattern seen on CXR
What is a very common pulmonary complication of RA?
Pleural effusions. These characteristically have low levels of glucose in the fluid.
What is Felty Syndrome?
Triad of RA, Neutropenia and Splenomegaly . Also has anemia, thrombocytopenia and lymphadenopathy associated with an increased risk of infection.
What are the 5 criteria needed for making the diagnosis of RA?
- Inflammatory arthritis of 3 or more joints (MCP, PIP, Wrists, Elbow, ankle, knee, MIP joints)
- Symptoms lasting at least 6 weeks
- Elevated CRP and ESR
- Positive serum RF or ACPA
- Radiographic changes consistent with RA (erosions and periarticular decalcification)
What are the radiographic findings associated with RA?
- Narrowing of the joint space
- Bone erosions
- Loss of bone mass near the finger joints
What are the two primary classes of medicines used to treat RA?
- DMARDs
- NSAIDs
What is the best initial DMARD for RA?
Methotrexate
What are the side effects of Methotrexate
- Bone marrow suppression (add folinic acid to prevent this)
- GI upset
- Alopecia
- Pulmonary fibrosis
- Heptotoxicity/elevated LFTs
What two thins should you monitor in someone on Methotrexate?
Renal and liver function
List the other DMARDs that can be used if Methotrexate is not effective
- Leflunomide
- Hydroxychloroquine
- Sulfasalazine
- Anti-TNF agents
What symptom is required to make the diagnosis of anklyosing spondylitis?
bilateral sacroiliitis
What is the pathophysiology of ankylosing spondylitis?
There is fusion of the spine in an ascending manner starting from the lumbar region.
How does the back pain associated with ankylosing spondylitis change during the day? What makes it worse or better?
Generally the back pain in the morning gets better as the day progresses. It improves with activity and a hot shower, and worsens with rest or inactivity.
Define enthesitis
Inflammation at tendinous insertions into the bone
What are some of the complications of ankylosing spondylitis?
- Chest pain and diminished chest expansion due to thoracic involvement.
- Enthesitis
- Shoulder and hip pain
- Constitutional symptoms
- Anterior uveitis
- AV heart block or aortic insufficiency
- loss of lumbar lordosis
- Cauda equina syndrome
- Restrictive lung disease
- Spinal fracture and spinal cord injury
- Osteoporosis
- Spondylodiscitis
How do you make the diagnosis of ankylosing spondylitis?
- Imaging of lumbar spine: Bamboo spine
- Elevated ESR
- HLA-B27 status not necessary for diagnosis
Treatment for ankylosing spondylitis
- NSAIDs
- Anti-TNF medications
- Physical therapy
- Surgery
- IMMEDIATE IMMOBILIZATION TO PREVENT SCI AFTER MINOR TRAUMA
What is the pathophysiology of reactive arthritis?
-Asymmetric inflammatory oligoarthritis of the lower extremities (UE is less common). The arthritis is preceded by an infectious process remote from the site of arthritis, usually after enteric or urogenital infections.
What is Reiter Syndrome
Arthritis, Uveitis, and Urethritis
What organisms are usually associated with reactive arthritis?
Salmonella, Campylobactor, Shigella, Chlamydia, Yersinia
Define undifferentiated spondyloarthropathy
When a patient has features of reactive arthritis but there is no evidence of previous infection and the classic findings of Reiter syndrome are absent.
Is the arthritis of reactive arthritis symmetric or asymmetric?
Asymmetric. New joints may become involved over days. They may have effusions and associated lack of mobility.
How do you diagnose reactive arthritis?
Synovial fluid analysis
Treatment of reactive arthritis
NSAIDs, possibly sulfasalazine and immunosuppressive agents like azathioprine if no response to NSAIDs.
How prevalent is psoriatic arthritis in people with psoriasis?
Not very. Only about 10% of patients with psoriasis get psoriatic arthritis.
What are two characteristic findings in psoriatic arthritis?
Sausage digits and nail pitting.
Describe the joint pain in psoriatic arthritis
Polyarticular and asymmetric.
Are UE or LE more commonly involved in psoriatic arthritis?
UE
What is the treatment for psoriatic arthritis?
NSAIDs, maybe methotrexate or anti-TNF agents.
List some causes of monoarticular joint pain
- Osteoarthritis
- Gout
- Pseudogout
- Trauma
- Septic arthritis
- Hemarthrosis
List some causes of polyarticular joint pain
- SLE
- RA
- Viral arthritis
- Reactive arthritis
- Psoriatic arthritis
- Rheumatic fever
- Reiter Syndrome
- Lyme Disease
- Gonococcal infection
- Drug-induced arthritis
Is RA Symmetric or Asymmetric?
Symmetric
What is found in the biopsy of rheumatoid nodules?
Cholesterol
Why does gout develop?
- Increased production or uric acid
2. Decreased excretion of uric acid
What are some causes of increased production of uric acid?
- Lesch-Nyhan syndrome (HGPRT deficiency)
- Phosphoribosyl pyrophosphate synthetase overactivity
- Increased cell turnover due to a number of conditions.
What are some of the causes of decreased excretion of uric acid?
- Renal disease
- NSAIDs
- Diuretics
- Acidosis
Describe the pathophysiology of gout
IgGs coat monosodium urate crystals, which are phagocytized by PMNs leading to the release of inflammatory mediators and proteolytic enzymes from the PMNs which then results in inflammation.
What are some precipitants of an acute gout attack?
- Excess alcohol intake
- Starvation
- Stress (emotional or physical)
- Dehydration
- Decrease in temperature
What are the 4 stages of gout?
- Asymptomatic hyperuricemia
- Acute gouty arthritis
- Intercritical gout
- Chronic tophaceous gout
What are tophi?
Aggregates of urate crystals surrounded by giant cells in an inflammatory reaction. Tophi cause destruction of both hard and soft tissues.
How do you make the diagnosis of gout?
Joint aspiration will show needle-shaped and negatively birefringent urate crystals.
What x-ray finding is present in gout?
punched out erosions with overhanging rim of cortical bone.
Treatment of acute gout
-NSAIDs (Indomethacin)
-Colchicine
-Corticosteroids
in this order!
Prophylactic treatment of gout
- Allopurinol
- Uricosuric drug (probenecid, sulfinpyrazone)
What is the MOA of allopurinol?
Xanthine oxidase inhibitor, which decreases uric acid production
What is one side effect of allopurinol?
Rash/SJS
What level of uric acid excretion indicates overproduction?
> 800 mg/day
If the uric acid excretion level is <800 mg/day what does this indicate?
It indicates underexcretion of uric acid and you should use a uricosuric drug for treatment
What is the MOA of uricosuric drugs?
They increase renal excretion of uric acid, therefore they are contraindicated in patients with renal failure or a hx of nephrolithiasis.
What are risk factors for pseudogout?
- Elderly with degenerative joint disease
- Hyperparthyroidism
- Hemochromatosis
- hypothyroidism
- Bartter Syndrome
What joints are most commonly affected with pseudogout?
knees and wrists
How do you make the diagnosis of pseudogout?
It is diagnosed by joint aspiration showing weakly positive birefringent rod-shaped and rhomboidal crystals.
What do radiographs show in pseudogout?
Chrondrocalcinosis or cartilage calcification.
Treatment for pseudogout?
- Tx the underlying condition
- NSAIDs, Colchicine for prophylaxis, triamcinolone steroid injections intra-articularly.
- Joint replacement if symptoms are debilitating
mechanism of dermatomyositis?
Humoral immune mechanism
mechanism of polymyositis and IBM?
Cell mediated mechanism
Where is the muscle weakness of poly and dermatomyositis?
Proximal
list some features unique to dermatomyositis
- Heliotrope trash
- Gottron Papules
- V sign
- Shawl sign
- Periungual erythema with telangiectasias
- Increased incidence of malignancy!
How do you diagnose poly/dermatomyositis?
- CK: usually elevated
- EMG: abnormal
- Biopsy
- Elevated LDH, AST, ALT, aldolase
- Antibodies
- CT if malignancy is suspected
What antibodies are associated with dermatomyositis and polymyositis?
Anti-Jo1
Anti-Mi2
Anti-Signal Recognition Peptide
ANA
What does the muscle biopsy in dermatomyositis show?
Perivascular and perimysial inflammation
What does the muscle biopsy in polymyositis and IBM show?
Endomysial inflammation
What is the treatment for the inflammatory myopathies?
- Corticosteroids
- Immunosuppressive agents if they do not respond to corticosteroids
- Physical therapy
How does IBM differ from the other inflammatory myopathies?
- More common in men
- Not associated with autoantibodies
- Involves distal extremities/pain
- Relatively low CK
- Poor prognosis
- Loss of DTRs
- Asymmetrical weakness
What are the clinical features of polymyalgia rheumatica?
- Bilateral hip and shoulder pain, stiffness after inactivity, profound morning stiffness, normal strength.
- Constitutional symptoms
- Joint swelling
- Possible signs of temporal arteritis
How do you diagnose polymyalgia rheumatica?
- Essentially a clinical diagnosis
- ESR is elevated and correlates with disease activity
How do you treat polymyalgia rheuamtica/what is the regimen?
Corticosteroids! May taper after 4-6 weeks, and they generally can stop within 2 years.
What are the large vessel vasculitides?
- Takayasu arteritis
- Temporal arteritis
What are the medium vessel vasculitides?
- PAN
- Kawasaki’s Disease
- Wegener’s Granulomatosis
- Churg-Strauss Syndrome
- Microscopic Polyangiitis
What are the small vessel vasculitides?
- HSP
- HSN vasculitis
- Behcet Syndrome
List the clinical features of temporal arteritis
- Headaches
- Jaw claudication
- Visual impairment
- Tenderness over temporal artery
- Possible polymyalgia rheumatica
What causes the visual impairment of temporal arteritis?
Disease involving the ophthalmic artery
How do you diagnose temporal arteritis?
Biopsy. But go ahead and start high dose steroids if it is even suspected in order to prevent visual loss.
“Keys to Diagnosing Temporal Arteritis”
- Age >50 yo
- New headache
- Tender/Palpable Temporal Artery
- High ESR
- Jaw Claudication
Describe the pathophysiology of Takayasu Arteritis
Granulomatous vasculitis of the aortic arch and its major branches leading to fibrosis and potentially causing stenosis or narrowing of vessels.
How do you diagnose takayasu arteritis?
Get an arteriogram
Clinical features of Takayasu arteritis
- Absent or diminished pulses
- Signs and sx of ischemia
- Constitutional symptoms
What are some complications of Takayasu arteritis?
- Aortic regurg
- Stroke
- Aortic aneurysm
- Secondary HTN due to renal artery stenosis
- Limb ischemia
Treatment for Takayasu
- Steroids
- treat the HTN
- Possible vessel recanalization
Clinical Features of Churg-Strauss
- Constitutional symptoms
- Asthma
- Skin lesions (purpura)
- Eosinophilia
How do you diagnose Churg-Strauss?
biopsy of lung or skin tissue
What marker is Churg-Strauss associated with?
p-ANCA
Clinical Features of Wegener Granulomatosis
- Sinusitis
- Pulmonary symptoms (hemoptysis, cough)
- Oral ulcers
- Glomerulonephritis
- Eye disease
- Arthralgias/myalgias
- Tracheal stenosis
- Constitutional symptoms
How do you diagnose Wegeners?
Open lung biopsy
What abnormal lab findings are associated with Wegeners?
- c-ANCA
- Elevated ESR
- Anemia
- Thrombocytopenia
Treatment of Wegener’s
- Cyclophosphomide and corticosteroids
- Possible renal transplant
What other conditions is polyarteritis nodosa associated with?
- Hep B
- HIV
- Drug reactions
What is one characteristic that distinguishes PAN from Wegeners?
PAN has no pulmonary involvement
Describe the pathophysiology of PAN
PMN invasion of all layers and fibrinoid necrosis plus resulting intimal proliferation leading to reduced luminal area, which results in ischemia, infarction, and aneurysms. Necrosis is SEGMENTED, leading to the “rosary sign”
What are some of the clinical findings associated with PAN?
- Bowel angina
- Mononeuritis multiplex
- Livedo reticularis
- HTN
- constitutional, myalgias, arthralgias
Treatment for PAN
Cyclophosphamide and corticosteroids
Clinical features of Behcet’s Disease
- Painful oral and genital ulcers (pathergy)
- Eye involvement (uveitis, iritis, optic neuritis, conjunctivitis)
- CNS involvement (meningoencephalitis, intracranial HTN)
- fever, weight loss, arthritis
Pathophysiology of Buerger Disease
-Acute, segmental inflamation of small and medium sized arteries and veins, affecting the arms and legs.
Clinical features of Buerger’s
superficial nodular phlebitis
- Raynaud phenomenon
- Ischemic claudication
- cold cyanotic painful extremities
- Paresthesias
- ulceration
- possible gangrene and autoamputation
