Rheumatology Flashcards
Gout primarily affects the ________ joint or ________ joint but may involve the _______ joint as well.
first metatarsal
ankle
knee
The knee joint is the most common joint affected in which pathologies? (4)
bacterial infection, Lyme disease, pseudogout, and traumatic causes
Disseminated gonorrhea:
- initial syndrome?
- skin lesions?
- other MSK finding?
- gram stain/cultures?
- Tx?
initial syndrome: fever and migratory polyarthralgia.
Skin lesions: on the extremities; begin as small papules and quickly become pustular with a necrotic center.
Other: Tenosynovitis, usually in the tendons of the hands and fingers.
Gram stain: Gram stain and synovial cultures are often negative.
Treatment: ceftriaxone.
Fever and mono articular arthritis DDx (3)
bacterial infection
gout
rheumatologic disease
Gout crystal appearance
needle-shaped, negatively birefringent crystals
Pseudogout crystal appearance
rhomboid, weakly positive birefringence
Radiographs of the affected joint may show ____________ in pseudogout
chondrocalcinosis
Gout often occurs in the ________ or _______ joint.
__________ (6) increase risk for gout.
Treatment consists of ________ (4).
first metatarsal, ankle
diabetes mellitus, hypertension, obesity, hyperlipidemia, alcohol intake, and thiazide use
NSAIDs or colchicine (acute), allopurinol or probeniecid (recurrent gout)
Arthrocentesis leukocyte counts: in cells/mm3
- Normal fluid
- Noninflammatory (e.g., osteoarthritis)
- Mild to moderate inflammation (rheumatologic, crystalline)
- Severe inflammation (sepsis or gout)
- Sepsis until proven otherwise
Under 200 - Normal fluid
Under 2000 - Noninflammatory (e.g., osteoarthritis)
2000 to 50,000 - Mild to moderate inflammation (rheumatologic, crystalline)
50,000 to 100,000 - Severe inflammation (sepsis or gout)
Over 100,000 - Sepsis until proven otherwise
In patients with back pain, important “red flags” to obtain from the history are _________ (5)
past history of malignancy, fever, weight loss, bladder or bowel dysfunction, and “saddle anesthesia.”
Fever associated with back pain raises the suspicion of _______. (2)
osteomyelitis or epidural abscess
The evaluation of low back pain is focused on two key aspects: _________.
evidence of systemic disease and evidence of nerve compression
Low back pain DDx (13; 3 groups)
1 Musculoskeletal causes: Musculoligamentous injury Herniated intervertebral disk Spinal stenosis Vertebral compression fracture Spondylolysis or spondylolisthesis
2 Systemic causes: Malignancy (most commonly metastasis from breast, lung, prostate, kidney carcinoma, or multiple myeloma) Vertebral osteomyelitis Epidural abscess Spondyloarthropathy
3 Referred pain: Aortic dissection or aneurysm Pyelonephritis or nephrolithiasis Prostatitis Pancreatic carcinoma or pancreatitis
2 most common places where disk herniation occurs; findings to help tell them apart
L4 to L5 level = L5 nerve root; pain radiates to Anterolateral leg and great toe; deficient Dorsiflexion (ankle and great toe)
L5 to S1 = S1 nerve root; Pain radiates to Posterior leg and lateral toes; deficient Plantar flexion (ankle) and Decreased ankle reflex
Imaging for lower back pain: Patients at risk for compression fractures or malignancy should receive _________; _______ should be reserved for selected patients (eg suspected cauda equina syndrome)
a lumbar spine film
MRI
Rheumatoid arthritis (RA) is a symmetric inflammatory peripheral polyarthritis characterized by ___________ and __________.
lymphocytic infiltration of the synovial joints
granulomatous extra-articular nodules
Analysis of synovial tissue in RA reveals high levels of _______ (2) and blockade of their effects has an important role in RA treatment.
TNF-α and IL-1 (These factors upregulate the production of metalloproteinases, which are believed to be responsible for joint destruction.)
Treatment of RA consists of analgesia and early institution of DMARDS such as _________ (4).
_______ are useful adjuncts for refractory cases but increase risk for infection.
methotrexate, leflunomide, sulfasalazine, or hydroxychloroquine
Biologic agents (infliximab, adalimumab, etanercept, anakinra, Rituximab, Abatacept)
Extra-articular manifestations of RA include ___________ (4).
Associated conditions include __________ (2).
rheumatoid nodules (subQ, nontender, extensors), pleural effusions, vasculitis, and Felty syndrome (rheumatoid nodules, splenomegaly, and leukopenia)
atlantoaxial subluxation and Baker cysts
Conditions that may have a positive rheumatoid factor in the absence of rheumatoid arthritis (6)
Older age
Other autoimmune diseases (SLE, sarcoid, etc.)
Infective endocarditis
Liver disease (especially hepatitis C)
Chronic infections (syphilis, leprosy, parasites)
Hyperglobulinemic states
Criteria for Diagnosis of Rheumatoid Arthritis (7) and number of criteria required for Dx
Morning stiffness of joints >1 hr for at least 6 wk
Arthritis (soft tissue swelling) of three or more joints for at least 6 wk
Arthritis includes wrist, metacarpophalangeal, or proximal intraphalangeal joints
Arthritis is symmetric
Rheumatoid nodules
Elevated serum rheumatoid factor
Hand or wrist films showing erosions or periarticular osteopenia
(Four or more criteria are necessary for definite diagnosis.)
RF is positive in 70% to 80% of patients with RA. RF is not a specific test, and false positives occur ; Antibodies to ________ are more specific but this test is not included in the criteria for Dxing RA.
citrulline-containing proteins (anti-CCP)
The seronegative spondyloarthropathies are an interrelated group of inflammatory disorders affecting the ________ (3).
The spondyloarthropathies include: (4)
Which one is associated with IBD?
spine, joints, and periarticular structures
Ankylosing spondylitis (AS)
Psoriatic arthritis
Enteropathic arthritis (associated with inflammatory bowel disease [IBD])
Reactive arthritis
Patients with seronegative spondyloarthropathies have an increased incidence of HLA _______ and are seronegative for ______ (2).
B-27
rheumatoid factor and antinuclear antibodies
Complications in ankylosing spondylitis include: (4)
spinal fractures, atlantoaxial subluxation, aortic insufficiency, and cardiac conduction disease.
Reactive arthritis can occur after which infections? (2)
infectious diarrhea or urethritis (1-3 wks after)
Spondyloarthropathy should be suspected in ________ (young/old) patients complaining of _________ (2). Peripheral arthritis often appears as “___________.” Which organ is also usually affected?
younger individuals complaining of back pain with stiffness or asymmetric lower extremity arthritis.
sausage digits (reactive and psoriatic arthritis)
Eye involvement (conjunctivitis or uveitis) is also a key feature.
Radiograph features of ankylosing spondylitis include: (3)
Sacroiliitis (erosions of iliac bone lead to “pseudowidening” of the joint, followed by sclerosis and obliteration)
Squaring of vertebrae on lateral view of the spine
“Bamboo spine” - Ossification of ligaments between vertebral bodies
First-line therapy in the spondyloarthropathies is ________ (2).
_________ are generally not effective/recommended.
First line: NSAIDs, usually indomethacin.
In refractory cases, sulfasalazine (preferred in enteropathic arthritis since NSAIDs have been associated with IBD flares).
Glucocorticoids = not effective/recommended.
Spondyloarthropathies with M>F incidence (2)
Ankylosing spondylitis
Reactive arthritis
Spondyloarthropathy with infrequent spinal involvement (1)
Enteropathic arthritis
Skin involvement in each of the 4 spondyloarthropathies (names of assoc skin lesions in each)
Ankylosing Spondylitis: None
Reactive Arthritis: Circinate balanitis, keratoderma
Psoriatic Arthritis: Psoriatic plaques, nail pitting
Enteropathic Arthritis: Erythema nodosum, pyoderma gangrenosum
Natural history (chronic, etc) for each of the 4 spondyloarthropathies
Ankylosing Spondylitis: Chronic
Reactive Arthritis: Self-limiting (75%)
Psoriatic Arthritis: Chronic
Enteropathic Arthritis: Peripheral arthritis flares with bowel disease; spinal disease chronic
List of connective tissue diseases (6):
Systemic lupus erythematosus (SLE) Systemic sclerosis (SSc), also known as scleroderma Polymyositis/dermatomyositis (PM/DM) Sjögren syndrome Mixed connective-tissue disorder (MCTD) Rheumatoid arthritis
African Americans have a _____fold risk of SLE compared to whites. Deficiencies of complements _____ (3) increase the risk of SLE.
Fourfold
C1, C2, or C4
Many CTDs are associated with inheritance of _________ alleles. These gene products are important in the presentation of antigens to the immune system, so abnormalities may result in the production of __________; they _________ (are/are not) required for the development of disease.
particular MHC class II autoantibodies (most often against nuclear components) Are not
Pathogenesis in connective tissue disease (4 groups)
- Immune complex deposition: eg SLE, Circulating immune complexes deposit in the kidney (glomerulonephritis) or in skin.
- Vascular damage: may resemble primary vasculitides; due to abnormal immune responses.
- Overproduction and accumulation of extracellular matrix (ECM) components: eg systemic sclerosis
- Altered immune responses: predispose to viruses and encapsulated bacteria.
Key pathology in systemic sclerosis
Following vascular damage, deposition of collagen and other components of the ECM can occur. This is a key pathologic feature of systemic sclerosis and results in fibrosis of the skin and other organs.
Although Raynaud phenomenon can be seen in all CTDs, it is often the earliest symptom of _________.
Systemic sclerosis (scleroderma)
CREST syndrome
Calcinosis, Raynaud, esophageal dysmotility, sclerodactyly, and telangiectasia.
= limited form of scleroderma. Assoc with anti-centromere Abs, usually spares kidneys. Pulm hyperT if lungs are involved.
The antiphospholipid antibody syndrome (APS) occasionally seen in ________ may present with __________ (2).
SLE
thrombocytopenia and an elevated PTT - However, this is a hypercoagulable state, not a bleeding disorder.
Scleroderma renal crisis, presenting as _________, is seen in patients with _________, and it should be treated quickly with __________.
oliguric renal failure and malignant hypertension
diffuse scleroderma
ACE inhibitors
The mainstay of treatment for CTDs is ________ in SLE and PM/DM, with less effective treatment options for _________ (2). Tx for severe nephritis is _________ (2).
glucocorticoids
Scleroderma and Sjögren syndrome
cyclophosphamide or mycophenolate
Limited scleroderma, with skin thickening of hands and face, is associated with _________ (present in 60% of patients) and _______ syndrome.
anticentromere antibody
CREST
SLE is characterized by _______ (3).
_________ (2) can also be present.
_______ are present (usually in titers >1:80) in almost all (98%) of patients with SLE.
_________ (2) antibodies are specific for SLE.
Low _________ levels can indicate active disease.
small joint arthritis, rashes, and leukopenia Serositis and glomerulonephritis ANAs Anti-Sm and anti-dsDNA complement
Skin lesions assoc with dermatomyositis (2)
Heliotrope rash - purple-coloured, checks and nose, maybe eyelids and chest
Gottron papules - papular lesions on the dorsal interphalangeal joints that are seen in ~a third of patients with DM
These are NOT seen in polymyositis (which has no skin findings)
The characteristic skin finding in scleroderma is ________.
Limited vs diffuse scleroderma: skin finding is limited to which region of body in each?
Dangers assoc with each scleroderma subtype?
thickened, indurated skin with loss of folds.
Limited scleroderma: distal extremities and face
Diffuse scleroderma: spread to involve arms and trunk.
Limited: more likely to develop pulmonary hypertension, also more likely to have calcinosis (subcutaneous calcium deposits) and telangiectasias (–>CREST syndrome).
Diffuse: higher risk for visceral organ involvement.
MSK findings in polymyositis/dermatomyositis? (2)
Proximal limb muscle weakness, myalgias
Palpable purpura is a common finding in the vasculitides, especially ____________ (2). Purpura is also seen in the following life-threatening infections: (3).
hypersensitivity vasculitis (including Henoch-Schönlein purpura) and Churg-Strauss disease
gonococcemia, meningococcemia, and Rocky Mountain spotted fever
Vasculitis with pulmonary involvement occurs in _________ (2).
Wegener granulomatosis and Churg-Strauss disease
Churg-Strauss disease is characterized by: (3)
Pulmonary involvement, eosinophilia, and asthma.
Antibody to _________ is highly specific for Wegener granulomatosis, although it may be absent when disease is limited to the lungs.
proteinase 3 (which produces a C-ANCA pattern)
New-onset headache with an elevated ESR in an elderly patient is highly suggestive of _________.
__________ (2) are assoc Sx.
If highly suspected, what are the next steps? (2)
temporal arteritis
Scalp tenderness and jaw claudication
prednisone should be instituted and a prompt temporal artery biopsy obtained.
Most vasculitides occur in middle-age individuals (mean, 40 to 45 years of age), with men affected slightly more often (ratio 1.3:1) except for: (4)
Temporal arteritis (elderly) Henoch-Schönlein purpura (mostly children and adolescents) Takayasu arteritis (adolescents and young women). Kawasaki disease (young children)
Vasculitides, diseases involving inflammation of blood vessels, are syndromes characterized by _______ (2).
the size of the blood vessel involved and the predominant organs affected
List of vasculitides: (8)
Polyarteritis nodosa (PAN)
Churg-Strauss disease (allergic angiitis and granulomatosis)
Wegener granulomatosis (WG)
Takayasu arteritis
Temporal arteritis
Hypersensitivity vasculitis (including Henoch-Schönlein purpura)
Microscopic polyangiitis (MPA)
Kawasaki disease (young children; predilection for coronary arteries)
Many cases of vasculitis, such as ________, may be associated with immune complex deposition.
hypersensitivity vasculitis
Vasculitides with more prominent granulomatous involvement (suggesting cell-mediated pathology) (2)
WG, Churg-Strauss
Hypersensitivity vasculitis may involve an offending drug (“serum sickness,” 7-10 d after exposure) or an associated disease such as: (3)
systemic lupus erythematosus (SLE), rheumatoid arthritis, and bacterial endocarditis
Chronic hepatitis B and C are associated with the following vasculitides. (2)
Microscopic polyangiitis (MPA) and polyarteritis nodosa (PAN)
Chronic hepatitis C may lead to _______, which can cause a hypersensitivity vasculitis.
essential mixed cryoglobulinemia
Nonspecific Sx in vasculitis (4)
fever, weight loss, malaise, and arthralgias
Polyarteritis nodosa affects the ________ arteries and may present with _______ (1).
- vessels (type and size) and organs (4) affected?
- Important sign/diagnostic feature?
Visceral; abdominal pain
medium and small-sized arteries (only), which become swollen and damaged from attack by rogue immune cells. Sx result from ischemic damage to affected organs, often the skin, heart, kidneys, and nervous system.
Rosary sign: small aneurysms are strung like the beads of a rosary
- The GI symptoms of Henoch-Schönlein purpura (________) (2) may precede the typical rash.
- Triad of H-S purpura?
- Pathogenesis?
- organs involved? (6)
abdominal pain and bleeding palpable purpura (small hemorrhages), arthritis, and abdominal pain.
Small-vessel vasculitis in which complexes of IgA and C3 are deposited on arterioles, capillaries, and venules.
Skin and connective tissues, scrotum, joints, gastrointestinal tract and kidneys
Churg-Strauss disease presents as __________.
recurrent asthma attacks
WG often involves the lungs and upper airways, presenting as: (4)
recurrent sinusitis, dyspnea, cough, and/or hemoptysis
Takayasu arteritis affects __________ vessels and may cause ________(2).
large vessels such as the carotid arteries
syncope and stroke
Palpable purpura characteristics (5)
- raised lesions
- red to purple
- do not blanch
- usually appear on the lower extremities.
- most common in Churg-Strauss disease but can be seen in the other vasculitides as well.
Hypertension is seen in those diseases involving the renal vasculature: (5)
PAN, Microscopic polyangiitis, WG, Takayasu arteritis, and Henoch-Schönlein purpura.
Involvement of the subclavian arteries in __________ arteritis leads to diminished peripheral pulses.
Takayasu arteritis (also known as “pulseless disease”)
Wegener’s is closely associated with ________, while Churg-Strauss and microscopic polyangiitis can be associated with elevations of _______.
Wegener’s: c-ANCA
Churg-Strauss: p-ANCA
Churg–Strauss syndrome (also known as eosinophilic granulomatosis with polyangiitis or allergic granulomatosis) is an autoimmune condition that causes inflammation of _______ vessels (size) in persons with a history of _______. Complications include: (2)
small and medium sized
Atopy
Signs of congestive heart failure are seen if there is cardiac involvement, and mononeuritis multiplex is seen if there is neuro involvement
causes of palpable purpura besides vasculitis (3)
disseminated meningococcal or gonococcal infection and Rocky Mountain spotted fever
Eosinophilia with pulmonary infiltrates is seen in: (DDx) (4)
Churg-Strauss disease (eosinophilia is the hallmark of this disease)
allergic bronchopulmonary aspergillosis
Loeffler syndrome (often parasitic)
chronic eosinophilic pneumonia.
In the patient with WG presenting with pulmonary and renal disease, the other Dx to consider is __________
Goodpasture syndrome (antiglomerular basement membrane [GBM] disease).
Bloods finding that is unusual in the vasculitides and which suggests an alternative Dx
Thrombocytopenia
High titers of rheumatoid factor (RF) may be seen in rheumatoid vasculitis, although RF is also positive in __________.
mixed cryoglobulinemia
Tx of Henoch-Schönlein purpura?
Henoch-Schönlein purpura often remits on its own.
First-line therapy for WG, MPA, and PAN? (2)
Prednisone (1 mg/kg/day) and cyclophosphamide (2 mg/kg/day) are the first-line therapy for WG, MPA, and PAN.
Vessels involved and biopsy findings in each of the following: Hypersensitivity vasculitis Churg-Strauss disease Microscopic polyangiitis Wegener granulomatosis
Hypersensitivity vasculitis: Arterioles and venules; Leukocytoclastic vasculitis, IgA present in Henoch-Schönlein purpura
Churg-Strauss disease: Various sizes, including venules; Granulomas with eosinophils;
Microscopic polyangiitis: Small arteries and veins; Mononuclear or polymorphonuclear lymphocytes, necrotizing
Wegener granulomatosis: Small arteries and veins; Granulomas
Vessels involved and biopsy findings in each of the following:
Polyarteritis nodosa
Temporal arteritis
Takayasu arteritis
Polyarteritis nodosa: Small to medium arteries; Mononuclear or polymorphonuclear lymphocytes, necrotizing
Temporal arteritis: Medium arteries (temporal); Granulomas
Takayasu arteritis: Large arteries (aorta, subclavian); Usually not biopsied
Although amyloid fibrils can be made from many different proteins, all types of amyloid share the following common characteristics on pathologic examination: (3)
Amorphous, eosinophilic, extracellular deposition
Green birefringence under polarized light after staining with Congo red dye
Protein structure is a beta-pleated sheet
The two most common forms and causes of amyloidosis are _________ (2). In the United States, _____ is the most common cause. Amyloidosis sex preference?
AL amyloidosis caused by immunoglobulin light chain deposition and AA amyloidosis caused by deposition of the serum amyloid-A protein
AL is the most common cause
Occurs equally in men and women
Causes of AL Amyloidosis (2) and AA Amyloidosis (3). Two other noteworthy amyloid proteins involved in amyloidosis?
Causes of AL Amyloidosis:
Primary amyloidosis
Multiple myeloma
AA:
Rheumatoid arthritis
Chronic infection or inflammation
Familial Mediterranean fever
Others:
β2-Microglobulin (hemodialysis)
Transthyretin (familial amyloid polyneuropathy)
organs affected by AL or AA amyloid: (3)
kidney, heart, and liver.
Cardiac amyloidosis appears as a ____________ on physical examination. Findings? (3)
restrictive cardiomyopathy
Increased jugular venous pressure (JVP), Kussmaul sign (JVP increases instead of decreases with inspiration), rapid y descent of the JVP.
Amyloidosis skin involvement (2)
- signs of easy bruising, including periorbital ecchymoses.
- Amyloid deposition in the skin appears as raised waxy papules.
GI involvement in amyloidosis (2)
macroglossia or hepatomegaly
Amyloidosis common presentation (2)
generalized nonspecific symptoms, such as fatigue and weight loss. The weight loss is often marked and averages approximately 15 to 20 pounds
How to distinguish amyloidosis from light chain deposition disease? (2)
Light chain deposition disease is caused by tissue deposition of immunoglobulin light chains but without associated fibril formation. With light chain deposition disease, renal failure with nephritic syndrome is prominent, whereas cardiac or liver involvement is less common.
Px of amyloidosis? What does it depend on?
The prognosis in amyloidosis remains poor (average, 1 year) and depends on the extent of organ involvement.
Patients presenting with congestive heart failure (CHF) survive a median of 6 months, whereas patients presenting with peripheral neuropathy alone have median survivals of approximately 56 months.
Amyloidosis is a systemic disorder characterized by:
- where is protein deposited?
- how does it stain on H&E?
- what other stain is used to stain the protein?
Amyloidosis is a systemic disorder characterized by extracellular deposition of an amorphous eosinophilic protein that stains positive with Congo red stain.
Diagnosis of amyloidosis may be made by biopsy of any affected organ but is easiest and safest with an ________.
abdominal fat pad aspirate
Cardiac involvement in amyloidosis appears as _________ (2). Echocardiogram reveals a classic _________ pattern. Patients may be extremely sensitive to ______ (drug) toxicity.
a conduction disturbance and/or restrictive cardiomyopathy
“sparkling”
digoxin
Development of signs of amyloidosis (such as _________ (2)) in a patient on long-term hemodialysis should raise the suspicion of _____________.
carpal tunnel syndrome or polyneuropathy
β2-microglobulin-mediated amyloidosis
Treatment of amyloidosis is supportive, with the exception of _________ (3).
- colchicine for amyloidosis secondary to familial Mediterranean fever
- chemotherapy for multiple myeloma or for selected patients with primary amyloidosis.
