Title: Rheumatology
1- Rheumatology
- Summer Board Review
- Session 1
- Mashkur Husain
2Question 1
- A 47-year-old man is evaluated in the emergency
department for a 5-day history of acute swelling
and pain of the right knee. He has a 15-year
history of gout, with multiple attacks annually
he also has diabetes mellitus and chronic kidney
disease. Medications are enalapril, glipizide,
and allopurinol. - On physical examination, temperature is 38.2 C
(100.8 F), blood pressure is 146/88 mm Hg, pulse
rate is 96/min, and respiration rate is 15/min.
BMI is 27. Several nodules are noted on the
metacarpophalangeal and proximal interphalangeal
joints and within the olecranon bursa. The right
knee is swollen, erythematous, warm, tender, and
fluctuant.
3Question 1
- Laboratory studies
- Hemoglobin 10.1 g/dL (101 g/L)
- Leukocyte count 13,000/µL (13 109/L, 85
neutrophils) - Serum creatinine 2.8 mg/dL (247.5 µmol/L)
- Serum uric acid 9.2 mg/dL (0.54 mmol/L)
- Radiographs of the knee reveal soft-tissue
swelling. - Aspiration drainage of the right knee is
performed. Synovial fluid leukocyte count is
110,000/µL (110 109/L, 88 neutrophils).
Polarized light microscopy of the fluid
demonstrates extracellular and intracellular
negatively birefringent crystals. Gram stain is
negative for bacteria. Culture results are
pending.
4Answer Choice
- Which of the following is the most appropriate
initial treatment? - A Intra-articular methylprednisolone
- B prednisone
- C Surgical debridement and drainage
- D Vancomycin plus piperacillin-tazobactam
5Answer Choice
- Which of the following is the most appropriate
initial treatment? - A Intra-articular methylprednisolone
- B prednisone
- C Surgical debridement and drainage
- D Vancomycin plus piperacillin-tazobactam
6Explanation
- This patient requires empiric therapy with
vancomycin plus piperacillin-tazobactam, pending
the results of synovial fluid cultures. Based on
his history of gout as well as the presence of
tophi and intracellular and extracellular
negatively birefringent (urate) crystals, the
patient is currently having a gout attack.
However, an excessively high synovial fluid
leukocyte count of the joint (gt50,000/µL 50
109/L) requires that the acute joint process be
presumed infectious until proved otherwise. In
this setting, a negative Gram stain is of
insufficient sensitivity to rule out infection.
Patients with chronic joint damage such as that
seen in gout and other arthritides are at greater
risk for joint infection. This patient also has
diabetes mellitus and is presumed to be
immunocompromised and susceptible not only to
gram-positive, but also to gram-negative and
anaerobic, organisms. Therefore, empiric
combination therapy with vancomycin and
piperacillin-tazobactam is an appropriate
approach. - Although intra-articular methylprednisolone is an
appropriate approach to treat an acute gout
attack while minimizing systemic corticosteroid
effects, corticosteroids should never be injected
into potentially infected joints.
7Explanation
- Prednisone is also an effective treatment for
acute gout, particularly if polyarticular
however, use in this patient with diabetes and a
potential joint infection would not be
justifiable unless and until infection were ruled
out. - In this patient, infection is empirically assumed
but not proved, and the joint has been adequately
drained percutaneously for the time being.
Surgical debridement and drainage can be
considered for a definitively infected joint,
particularly if the percutaneous approach is
inadequate to fully drain the entire joint, but
is premature at this time.
8Key Points
- Manage infectious arthritis in a patient with
concurrent gout. - Bacterial infectious arthritis and gout can occur
concomitantly in the same joint and should be
suspected when there is a very high (gt50,000/µL
50 109/L) synovial fluid leukocyte count.
9Septic Arthritis
- Diagnosis
- Septic arthritis should be considered in any
patient who presents with - sudden onset of monoarthritis
- acute worsening of chronic joint disease
- previously painless joint prosthesis that is now
painful - radiographic loosening or migration of a cemented
prosthetic device - The risk for infection is increased in persons
with previously damaged joints (e.g., patients
with rheumatoid arthritis), in older adults, and
in immunosuppressed patients. In patients with
underlying rheumatologic disorders, a sudden
joint flare that is not accompanied by other
features of the preexisting disorder and is
unresponsive to usual therapy suggests a
diagnosis of infectious arthritis.
10Septic Arthritis
- The hallmark of a septic joint is pain on passive
range of motion in the absence of trauma, and an
infected joint typically appears swollen and warm
with overlying erythema. - Gonococcal arthritis is the most common form of
bacterial arthritis in young sexually active
persons in the United States. This condition
manifests as either a purulent arthritis or a
syndrome of disseminated gonococcemia. The
arthritis usually involves one or two joints
sequentially, most commonly the knees, wrists,
ankles, or elbows. Disseminated gonococcemia is
characterized by a prodrome of tenosynovitis,
polyarthralgia, and cutaneous lesions that
progress from papules or macules to pustules and
usually are sterile on culture. Fever and rigors
are common
11Septic Arthritis
- Most patients with purulent gonococcal arthritis
do not have systemic features or cutaneous
involvement therefore, gonococcal arthritis
should be considered in all sexually active
patients. Blood cultures for Neisseria
gonorrhoeae are positive in 50 of infected
patients. Obtaining culture specimens from the
pharynx, genitals, and rectum in addition to
synovial fluid cultures increases the diagnostic
yield. - Other less common causes of septic arthritis
- Gram-negative infections are more common in
older, immunosuppressed, and postoperative
patients and those with IV catheters. - Tuberculous arthritis typically is indolent, does
not cause systemic features, and is not
associated with positive TST synovial fluid is
usually inflammatory with a predominance of
polymorphonuclear cells and a negative Gram
stain. - Fungal arthritis typically manifests as subacute
monoarthritis in patients with a systemic fungal
infection.
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14Question 2
- A 36-year-old man is evaluated for a 5-month
history of left knee pain and swelling. He is a
gardener and frequently scrapes his knees while
working in the soil. He has mild but chronic
discomfort when walking and at rest. The patient
reports no diarrhea or urethral discharge and has
been sexually inactive for 2 years. He has a
10-year history of type 2 diabetes mellitus that
is managed with insulin. - On physical examination, temperature is 38.0 C
(100.4 F), blood pressure is 135/77 mm Hg, pulse
rate is 78/min, and respiration rate is 12/min.
BMI is 20. The left knee is warm and swollen with
a palpable effusion. The knee has decreased
flexion, and increasing discomfort is noted at
the limits of range of motion. - Laboratory studies reveal a leukocyte count of
11,000/µL (11 109/L, 35 lymphocytes) and an
erythrocyte sedimentation rate of 48 mm/h.
15Question 2
- Radiographs of the left knee reveal soft-tissue
swelling and diffuse joint-space narrowing, with
periarticular osteopenia. Aspiration of the knee
is performed. Synovial fluid leukocyte count is
6500/µL (6.5 109/L, 65 lymphocytes).
Polarized light microscopy reveals no crystals.
Gram stain is negative. - Subsequent bacterial cultures, Lyme disease
titers, rheumatoid factor, and anticyclic
citrullinated peptide antibody titers are
negative. Tuberculin skin test results are
negative.
16Answer Choice
- Which of the following is the most appropriate
diagnostic test to perform next? - A Alizarin red staining of synovial fluid
- B Antistreptolysin O antibody titers
- C MRI of the knee
- D Synovial biopsy
17Answer Choice
- Which of the following is the most appropriate
diagnostic test to perform next? - A Alizarin red staining of synovial fluid
- B Antistreptolysin O antibody titers
- C MRI of the knee
- D Synovial biopsy
18Explanation
- Synovial biopsy is indicated for this patient
with probable fungal arthritis. Fungal arthritis
is rare, typically occurs in patients who are
immunocompromised, and manifests as subacute
monoarthritis. This patient has long-standing,
indolent, chronic monoarticular arthritis a
history of diabetes mellitus and recurrent skin
breaks with likely soil exposure. In this
setting, infection with a fungus, particularly
Sporothrix schenckii, is the likely cause. S.
schenckii is associated with plant litter and
other organic materials. S. schenckii arthritis
usually manifests as progressive joint pain,
swelling, and loss of range of motion. The
diagnosis of fungal arthritis requires a high
degree of suspicion and is most commonly made by
synovial biopsy and/or culture of joint fluid.
Because joint fluid culture may take weeks,
obtaining a synovial biopsy is appropriate at
this time. - Alizarin red staining of synovial fluid is not
done routinely but is theoretically helpful for
identifying basic calcium phosphate (BCP)
crystals, which are invisible under polarized
light microscopy. However, the chronic nature of
the patient's condition, along with his
relatively young age and an absence of
calcification seen on radiographs, makes a
diagnosis of BCP arthritis unlikely.
19Explanation
- Obtaining antistreptolysin O antibody titers
aids in the diagnosis of rheumatic fever
however, this patient lacks the systemic signs
(such as cardiac and/or neurologic involvement)
that warrant consideration of rheumatic fever. - MRI of the knee would help delineate the extent
of the joint damage but would not provide insight
into the nature of the infectious process. - Key Point
- Fungal arthritis is rare, typically occurs in
patients who are immunocompromised, and manifests
as subacute monoarthritis
20Question 3
- A 52-year-old man is evaluated for a 5-year
history of gradually progressive left knee pain.
He has 20 minutes of morning stiffness, which
returns after prolonged inactivity. He has
minimal to no pain at rest. He reports no
clicking or locking of the knee. Over the past
several months, the pain has limited his
ambulation to no more than a few blocks. - On physical examination, vital signs are normal.
BMI is 25. The left knee has a small effusion and
some fullness at the back of the knee the knee
is not erythematous or warm. Range of motion of
the knee elicits crepitus. There is medial joint
line tenderness to palpation, bony hypertrophy,
and a moderate varus deformity. There is no
evidence of joint instability on stress testing. - Radiographs of the knee reveal bone-on-bone
joint-space loss and numerous osteophytes
21Answer Choice
- Which of the following is the most appropriate
next diagnostic step for this patient? - A CT of the knee
- B Joint aspiration
- C MRI of the knee
- D No diagnostic testing
22Answer Choice
- Which of the following is the most appropriate
next diagnostic step for this patient? - A CT of the knee
- B Joint aspiration
- C MRI of the knee
- D No diagnostic testing
23Explanation
- No additional diagnostic testing is indicated for
this patient who has osteoarthritis, which is a
clinical diagnosis. According to the American
College of Rheumatology's clinical criteria, knee
osteoarthritis can be diagnosed if knee pain is
accompanied by at least three of the following
features age greater than 50 years, stiffness
lasting less than 30 minutes, crepitus, bony
tenderness, bony enlargement, and no palpable
warmth. These criteria are 95 sensitive and 69
specific but have not been validated for clinical
practice. Additional diagnostic testing is not
appropriate, because it has no impact on the
management of advanced disease. - CT of the knee is very sensitive for pathologic
findings in bone and can be used to look for
evidence of an occult fracture, osteomyelitis, or
bone erosions. However, none of these are
suspected in this patient. - Small- to moderate-sized effusions can occur in
patients with osteoarthritis, and the fluid is
typically noninflammatory. Joint aspiration in
this patient without evidence of joint
inflammation and evident osteoarthritis is not
useful diagnostically but is often done in the
context of intra-articular corticosteroid
injection or viscosupplementation.
24Explanation
- MRI is useful to evaluate soft-tissue structures
in the knee such as meniscal tears. Patients with
meniscal tears may report a clicking or locking
of the knee secondary to loose cartilage but
often have pain only on walking, particularly
going up or down stairs. Patients with
degenerative arthritis often have MRI findings
that indicate meniscus tears. These tears are
part of the degenerative process but do not
impact management arthroscopic knee surgery for
patients with osteoarthritis provides no clinical
benefit. The one exception may be in patients
with meniscal tears that result in a free flap or
loose body, producing painful locking of the
joint. These symptoms are not present in this
patient. - Key Point
- Osteoarthritis is diagnosed clinically and does
not require advanced imaging to establish the
diagnosis.
25Question 4
- A 76-year-old woman is evaluated for a 3-month
history of left knee pain of moderate intensity
that worsens with ambulation. She reports minimal
pain at rest and no nocturnal pain. There are no
clicking or locking symptoms. She has tried
naproxen and ibuprofen but developed dyspepsia
acetaminophen provides mild to moderate relief.
The patient has hypertension, hypercholesterolemia
, and chronic stable angina. Medications are
lisinopril, metoprolol, simvastatin, low-dose
aspirin, and nitroglycerin as needed. - On physical examination, vital signs are normal.
BMI is 32. Range of motion of the left knee
elicits crepitus. There is a small effusion
without redness or warmth and tenderness to
palpation along the medial joint line. Testing
for meniscal or ligamentous injury is negative.
26Question 4
- Laboratory studies, including complete blood
count and erythrocyte sedimentation rate, are
normal. - Radiographs of the knee reveal medial
tibiofemoral compartment joint-space narrowing
and sclerosis small medial osteophytes are
present.
27Answer Choice
- Which of the following is the next best step in
management? - A Add celecoxib
- B Add glucosamine sulfate
- C MRI of the knee
- D Weight loss and exercise
28Answer Choice
- Which of the following is the next best step in
management? - A Add celecoxib
- B Add glucosamine sulfate
- C MRI of the knee
- D Weight loss and exercise
29Explanation
- Weight loss and exercise are indicated for this
patient with knee osteoarthritis. Her knee pain,
which is worse with weight bearing, is suggestive
of tibiofemoral knee osteoarthritis, a diagnosis
supported by the presence of medial joint line
tenderness and radiographic findings of medial
tibiofemoral compartment joint-space narrowing.
The strongest risk factors for osteoarthritis are
advancing age, obesity, female gender, joint
injury (caused by occupation, repetitive use, or
actual trauma), and genetic factors. Obesity, in
particular, is the most important modifiable risk
factor for knee osteoarthritis. Several trials
have demonstrated that weight loss and/or
exercise programs can offer relief of pain and
improved function comparable to the benefits of
NSAID use. In long-term studies, sustained weight
loss of approximately 6.8 kg (15 lb) has resulted
in symptomatic relief. - Celecoxib carries an increased myocardial risk
and is therefore not appropriate for this patient
who has coronary artery disease. Although
celecoxib has a lower risk of gastrointestinal
ulcers than other NSAIDs, it can still cause
dyspepsia, which occurred in this patient after
taking naproxen and ibuprofen.
30Explanation
- There have been several contradictory studies
regarding glucosamine sulfate in the management
of osteoarthritis. After several favorable
smaller studies, a trial sponsored by the
National Institutes of Health showed no
effectiveness in reducing pain. A recently
conducted meta-analysis also found negative
results for the use of glucosamine sulfate. - MRI of the knee would be indicated to evaluate
for meniscal or other ligamentous injuries, none
of which is suggested by this patient's history
(the knee locking or giving way) or examination
findings (negative examination for tendinous or
ligamentous injury). - Key Point
- Obesity is the most important modifiable risk
factor for knee osteoarthritis, and weight loss
and exercise are recommended to reduce pain and
improve function
31Osteoarthritis
- Diagnosis
- Age is the most important risk factor for
developing primary OA in women and men.
Additional risk factors include genetics,
obesity, and trauma-induced mechanical joint
instability. OA most often affects the lower
cervical and lumbar spine hips knees DIP, PIP,
and first carpometacarpal joints. - Characteristic findings include
- morning joint stiffness lasting lt30 minutes
- gelling (brief stiffness after inactivity)
- crepitus
- tenderness along the joint line
- reduced joint motion
- bony enlargement (including Heberden and Bouchard
nodes) - involvement of the first carpometacarpal joint
results in squaring at the base of the thumb
32Osteoarthritis
- Two important variants are erosive OA of the hand
and DISH. - Erosive inflammatory OA is characterized by pain
and palpable swelling of the soft tissue in the
PIP and DIP joints. This condition also may be
associated with disease flares during which these
joints become more swollen and painful. - DISH is an often asymptomatic form of OA that
causes significant radiographic changes similar
to those associated with degenerative spondylosis
or ankylosing spondylitis. X-rays of the spine in
patients with DISH reveal flowing ossification
that develops along the anterolateral aspect of
the vertebral bodies, particularly the anterior
longitudinal ligament. However, neither
disk-space narrowing nor syndesmophytes are
visible in this setting, as they are in lumbar
spondylosis or ankylosing spondylitis,
respectively.
33Osteoarthritis
- Secondary OA results from previous joint injury
or metabolic diseases such as hemochromatosis.
Consider metabolic causes when OA develops in
atypical joints (e.g., MCP joints, shoulder,
wrist). - Be alert for an acutely painful calf mimicking a
DVT, which represents a ruptured Baker cyst
(herniation of fluid-filled synovium of the
posterior knee) or ruptured gastrocnemius muscle. - No pathognomonic laboratory tests are available
for OA. An x-ray is not helpful in the diagnosis
of symptomatic hand OA (clinical examination is
more specific) but is the gold standard for hip
and knee OA. X-rays show joint-space narrowing,
subchondral sclerosis, and osteophytes. Synovial
fluid is usually noninflammatory, with a
leukocyte count lt2000/microliter. Ultrasonography
is useful in the diagnosis of Baker cyst.
34Bony enlargement of the DIP joints and squaring
of the first carpometacarpal joint characteristic
of osteoarthritis.
35Don't Be Tricked
- Typical OA radiographic changes do not exclude
other diagnoses. Be alert for - septic arthritis superimposed on OA
- trochanteric and anserine bursitis causing hip
and knee pain - de Quervain tenosynovitis mimicking
carpometacarpal OA - hemochromatosis, particularly if involving the
second and third metacarpophalangeal joints - gout or CPPD deposition disease
36Therapy
- Medical therapy includes
- acetaminophen as first-line therapy for hip and
knee OA - NSAIDs in patients who do not respond to
acetaminophen or as initial therapy for severe
pain - tramadol if NSAIDs are contraindicated or
ineffective - intra-articular corticosteroids for acute
exacerbations of knee OA - intra-articular hyaluronan injection, which has
comparable efficacy to NSAID therapy for knee OA - glucosamine sulfate, although data for its use
are conflicting - Patients with hip and knee OA benefit from weight
loss patients with knee OA benefit from
quadriceps-strengthening exercises. Joint
arthroplasty of the hip or knee is indicated for
pain that does not respond to nonsurgical
treatment, especially when lifestyle or
activities of daily living are affected.
37Don't Be Tricked
- Patients with signs of inflammation should not
undergo intra-articular corticosteroid therapy
until synovial fluid analysis excludes infection. - Do not select arthroscopic lavage, debridement,
or closed lavage for knee OA.
38Medial compartment joint space-narrowing and
subchondral sclerosis consistent with
osteoarthritis are shown.
39Question 5
- A 52-year-old man is evaluated for an 8-week
history of pain and 2 hours of morning stiffness
of the hands that improves with activity. The
patient has no pertinent personal or family
medical history. He takes no medications. - On physical examination, vital signs are normal.
Synovitis is noted at the metacarpophalangeal
joints of the second through fifth digits
bilaterally with swelling, tenderness, and pain
on range of motion. The remainder of the
examination is normal. - Laboratory studies, including complete blood
count, chemistries, liver chemistry tests,
thyroid-stimulating hormone, C-reactive protein,
and urinalysis, are normal erythrocyte
sedimentation rate is 13 mm/h, and rheumatoid
factor is negative. Parvovirus serology results
are negative. - Radiographs of the hands are normal
40Answer Choice
- Which of the following antibody assays is most
helpful in establishing this patient's diagnosis? - A Anticyclic citrullinated peptide antibodies
- B Antimitochondrial antibodies
- C Antineutrophil cytoplasmic antibodies
- D Antinuclear antibodies
41Answer Choice
- Which of the following antibody assays is most
helpful in establishing this patient's diagnosis? - A Anticyclic citrullinated peptide antibodies
- B Antimitochondrial antibodies
- C Antineutrophil cytoplasmic antibodies
- D Antinuclear antibodies
42Explanation
- An anticyclic citrullinated peptide (CCP)
antibody assay is warranted for this patient in
whom rheumatoid arthritis is suspected. Anti-CCP
antibodies are present in approximately 40 to
60 of patients with early rheumatoid arthritis,
including some patients with a negative
rheumatoid factor. These antibodies are 95
specific for rheumatoid arthritis. The presence
of higher titers of either rheumatoid factor or
anti-CCP antibodies or the presence of both
increases the likelihood of disease. Although
this patient's rheumatoid factor is negative and
his acute phase reactants are normal, rheumatoid
arthritis remains a significant concern because
he has synovitis of eight small joints and
morning stiffness lasting more than 1 hour,
common symptoms of rheumatoid arthritis. An
anti-CCP antibody assay is therefore appropriate
to determine whether this patient's symptoms are
caused by rheumatoid arthritis. - Antimitochondrial antibodies are present in
patients with autoimmune hepatitis. Patients with
this disease can develop arthralgia and arthritis
similar to this patient however, he does not
have liver chemistry test abnormalities that are
characteristic of autoimmune hepatitis.
43Explanation
- Antineutrophil cytoplasmic antibodies are
typically associated with vasculitis such as
granulomatosis with polyangiitis (also known as
Wegener granulomatosis), microscopic
polyangiitis, Churg-Strauss syndrome,
antiglomerular basement membrane antibody
disease, and drug-induced vasculitis. Arthritis
and arthralgia can be associated with these
syndromes however, the presence of these
vascular inflammatory disorders would be unusual
in the absence of other system involvement. - Antinuclear antibodies (ANA) can be clinically
useful when there is clinical suspicion for
autoimmune conditions associated with these
antibodies such as systemic lupus erythematosus
(SLE). SLE may present with arthritis but, in
this case, SLE is less likely than rheumatoid
arthritis. SLE typically occurs in women of
childbearing age, with additional clinical and/or
laboratory abnormalities rather than isolated
arthritis. ANA are present in some patients with
rheumatoid arthritis but are not specific for
this disorder. - Key Point
- Anticyclic citrullinated peptide antibodies are
a highly specific marker for rheumatoid
arthritis.
44Question 6
- A 36-year-old woman is evaluated for a 5-week
history of pain and swelling of the fingers
accompanied by morning stiffness lasting more
than 1 hour. Her only medication is ibuprofen,
which provides minimal relief. - On physical examination, vital signs are normal.
Musculoskeletal examination reveals tenderness
and swelling of the right second, third, and
fourth metacarpophalangeal joints and the left
third, fourth, and fifth metacarpophalangeal
joints. There is no bony enlargement, ulnar
deviation, or other abnormalities. - Radiographs of the hands and wrists are normal.
45Labs
Erythrocyte sedimentation rate 40 mm/h
Rheumatoid factor 43 units/mL (43 kU/L)
Antinuclear antibodies Negative
Anticyclic citrullinated peptide antibodies Positive
IgM antibodies against parvovirus B19 Negative
Hepatitis B surface antigen Negative
Hepatitis B surface antibodies Positive
Hepatitis C virus antibodies Negative
46Answer Choice
- Which of the following is the most appropriate
next step in management? - A Etanercept
- B Hydroxychloroquine
- C Methotrexate
- D Reevaluate in 6 weeks
47Answer Choice
- Which of the following is the most appropriate
next step in management? - A Etanercept
- B Hydroxychloroquine
- C Methotrexate
- D Reevaluate in 6 weeks
48Explanation
- Methotrexate is indicated for this patient with
early rheumatoid arthritis. Experts recommend
that patients begin disease-modifying
antirheumatic drug (DMARD) therapy within 3
months of onset. The sooner DMARDs are
instituted, the more likely that damage will be
limited. Methotrexate is the gold standard DMARD
therapy for rheumatoid arthritis and is central
to most treatments for the disease. This agent
can be effective as initial monotherapy for
patients with rheumatoid arthritis of any
duration or degree of activity. This patient has
synovitis of six metacarpophalangeal joints with
a symmetric distribution not involving the distal
interphalangeal joints, which is consistent with
rheumatoid arthritis. She has swelling, prolonged
morning stiffness, an elevated erythrocyte
sedimentation rate (ESR), and positive rheumatoid
factor, which further support the diagnosis of
rheumatoid arthritis, and initial treatment with
methotrexate is warranted at this time. - Etanercept is a tumor necrosis factor a inhibitor
used for initial therapy in some patients with
high disease activity and poor prognostic
features. This agent may be necessary for this
patient if her disease does not respond to
methotrexate. - Hydroxychloroquine as monotherapy may be
effective only in mild cases early in the disease
course for patients without poor prognostic
features. This patient has evidence of moderate
disease activity, given the extent of her
synovitis and elevated ESR therefore,
hydroxychloroquine as a single agent is unlikely
to control this degree of inflammation and is
more beneficial as an adjunctive agent.
49Explanation
- Reevaluation in 6 weeks is not indicated for this
patient whose laboratory studies reveal no
evidence of acute parvovirus or hepatitis B
infection. Such viral infections can cause an
acute polyarthritis syndrome that mimics
rheumatoid arthritis. The diagnosis of rheumatoid
arthritis previously was predicated on symptoms
lasting more than 6 weeks to exclude many
self-limiting viral syndromes. However,
classification criteria no longer require
symptoms to occur for 6 weeks to avoid delays in
treatment. The likelihood of rheumatoid arthritis
is now calculated on the distribution of joints
involved, rheumatoid factor, anticitrullinated
peptide antibodies, acute phase reactants, and
duration of symptoms. - Key Point
- Methotrexate is the gold standard
disease-modifying antirheumatic drug therapy for
rheumatoid arthritis and is central to most
treatments for the disease
50Rheumatoid Arthritis
- Diagnosis
- RA is a symmetric inflammatory polyarthritis that
primarily involves the small joints of the hands
and feet. Characteristic findings include - morning stiffness lasting gt1 hour
- seven classic sites of symmetric joint pain (PIP,
MCP, wrist, elbow, knee, ankle, and MTP joints) - synovitis characterized by soft-tissue swelling
or effusion - subcutaneous nodules over bony prominences or
extensor surfaces
51- Laboratory findings include
- positive rheumatoid factor (sensitivity 80
specificity 87) - elevated ESR or CRP level
- normocytic anemia
- positive anti-CCP antibody assay (sensitivity
76 specificity 96) - An x-ray can reveal periarticular osteopenia,
erosions, and symmetric joint-space narrowing.
MRI and ultrasonography are more sensitive for
detecting early RA.
52- Don't Be Tricked
- Negative rheumatoid factor does not exclude RA
anti-CCP antibody assay may be positive. - A positive rheumatoid factor alone is not
diagnostic of RA. - Not all symmetric arthritis is RA.
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54- RA extra-articular manifestations
- arm paresthesias and hyperreflexia ? C1-C2
subluxation (increased risk of cord compression
with tracheal intubation) - cough, fever, pulmonary infiltrates ? BOOP
- foot drop or wrist drop ? mononeuritis multiplex
(vasculitis) - hoarseness ? cricoarytenoid involvement
- multiple basilar pulmonary nodules ? Caplan
syndrome - dry eyes and/or mouth ? Sjögren syndrome
- pleural effusion with low plasma glucose (lt30
mg/dL) ? rheumatoid pleuritis - pulmonary fibrosis ? rheumatoid interstitial lung
disease - skin ulcers, peripheral neuropathy ? rheumatoid
vasculitis - splenomegaly and granulocytopenia ? Felty
syndrome - red, painful eye ? scleritis
- HF ? rheumatoid disease or anti-TNF therapy
- Other complications include increased risk of CAD
and osteoporosis.
55Carpal, metacarpal, and PIP joints show
periarticular osteopenia, joint-space narrowing,
and marginal erosions, all characteristic of
rheumatoid arthritis.
56Therapy
- Early treatment with one or more DMARDs is
essential. Choose NSAIDs and low-dose oral and
intra-articular corticosteroids for quick
symptomatic relief, but recognize these agents do
not alter the course of the disease. - Monotherapy with hydroxychloroquine or
sulfasalazine or combination therapy with these
agents is indicated to manage early, mild, and
nonerosive disease. - In the absence of contraindications, methotrexate
with or without the addition of another DMARD
should be instituted immediately in patients with
erosive disease. - In some patients, combination therapy with
hydroxychloroquine, sulfasalazine, and
methotrexate has been shown to be more effective
than monotherapy with methotrexate or
sulfasalazine plus hydroxychloroquine. - Initiate biologic therapy when adequate disease
control is not achieved with oral DMARDs. The
initial biologic therapy should be a TNF-a
inhibitor - add a TNF-a inhibitor to baseline methotrexate
therapy - screen for TB before starting therapy
- treat for latent TB if TST is positive before
beginning any biologic therapy
57Therapy
- perform periodic TST screening while the patient
continues to receive biologic therapy - Common toxicities of TNF-a inhibitor therapy
include pancytopenia, positive ANA formation
associated with lupus-like syndromes, and
demyelinating disorders. Combination therapy with
multiple biologic therapies is not recommended. - Indications for surgical intervention include
intractable pain or severe functional disability
from joint destruction. Patients may also require
surgical repair of ruptured tendons. - All patients taking corticosteroids require
osteoporosis screening and serum calcium and
vitamin D level measurement. If osteopenia or
osteoporosis is diagnosed, prescribe a
bisphosphonate. Annual influenza vaccination is
indicated for all patients using
immunosuppressants, and pneumococcal vaccination
is indicated before beginning treatment with
methotrexate, leflunomide, or a biologic agent.
58Therapy
- The most common cause of death in patients with
RA is CAD. Begin aggressive coronary risk factor
reduction in all patients. Also, begin adjuvant
physical and occupational therapy. - Don't Be Tricked
- Hydroxychloroquine and sulfasalazine can be used
during pregnancy. - Test Yourself
- A 46-year-old man has a 3-month history of
swelling of the PIP and MCP joints and 90 minutes
of morning stiffness. Rheumatoid factor is
negative. - ANSWER The probable diagnosis is RA. Select
anti-CCP antibody assay.
59Question 7
- A 56-year-old woman is evaluated during a
follow-up visit for a 6-year history of Sjögren
syndrome treated with low-dose hydroxychloroquine
and cyclosporine eyedrops. She has had two
episodes of cutaneous vasculitis, which resolved
with corticosteroids. - On physical examination, temperature is 36.4 C
(97.6 F), blood pressure is 116/64 mm Hg, pulse
rate is 72/min, and respiration rate is 18/min.
Oral mucous membranes are dry. There is a new
firm, left parotid gland enlargement without
tenderness or warmth, reported by the patient to
be progressive over several months, with
asymmetry of the parotid glands. - Laboratory studies at the time of diagnosis
revealed elevated serum immunoglobulin levels
positive mixed monoclonal cryoglobulin levels
and positive rheumatoid factor, antinuclear
antibodies, and anti-Ro/SSA antibodies.
60Labs
Complete blood count Normal
Alkaline phosphatase Normal
Calcium Normal
Rheumatoid factor Negative
C3 Normal
C4 Decreased
Antinuclear antibodies Positive
Anti-Ro/SSA antibodies Positive
61Answer Choice
- Which of the following is the most appropriate
management? - A Add pilocarpine
- B Add prednisone
- C Bone marrow biopsy
- D Increase hydroxychloroquine
- E Parotid gland biopsy
62Answer Choice
- Which of the following is the most appropriate
management? - A Add pilocarpine
- B Add prednisone
- C Bone marrow biopsy
- D Increase hydroxychloroquine
- E Parotid gland biopsy
63Explanation
- Parotid gland biopsy is indicated for this
patient who has Sjögren syndrome and progressive
parotid swelling suggesting possible non-Hodgkin
lymphoma. Patients with Sjögren syndrome have up
to a 44-fold increased incidence of lymphoma,
which may be confined to glandular tissue. Risk
factors for the development of lymphoma include
disappearance of rheumatoid factor, the presence
of mixed monoclonal cryoglobulinemia, cutaneous
vasculitis, and low C4 levels, all of which are
seen in this patient. Although benign parotid
gland swelling can occur and be unilateral or
bilateral in patients with Sjögren syndrome, this
patient's high-risk profile and new asymmetric
parotid enlargement should prompt a biopsy to
evaluate for extranodal lymphoma in the parotid
gland. Extranodal marginal zone B-cell lymphomas
of the mucosa-associated lymphoid tissue (MALT)
are the most common lymphomas in patients with
Sjögren syndrome, and salivary glands are the
most common location other extranodal sites
include the stomach, nasopharynx, skin, liver,
and lungs. The risk of nodal lymphoma is also
increased in Sjögren syndrome. Although benign
lymphadenopathy is a common disease
manifestation, the presence of new or rapidly
enlarging lymph nodes may indicate development of
nodal lymphoma and should prompt biopsy. - Pilocarpine is effective for reducing dry mouth
symptoms but is not used to treat parotid
enlargement.
64Explanation
- Prednisone is generally used to treat
inflammatory symptoms of Sjögren syndrome,
including arthritis, vasculitis, and cytopenias,
but does not reduce parotid swelling or treat
symptoms of keratoconjunctivitis sicca and
xerostomia (dry eyes and dry mouth). - Patients with Sjögren syndrome often have
elevated immunoglobulin levels with monoclonal
gammopathy stability of this during the
patient's disease course, as well as normal
hemoglobin, calcium, and alkaline phosphatase
levels, suggests that bone marrow biopsy to
evaluate for myeloma is not warranted. Extranodal
lymphoma in Sjögren syndrome involves the bone
marrow in less than 10 of patients. - Hydroxychloroquine is used to treat arthritis
associated with Sjögren syndrome however, it is
unclear if this agent has efficacy in reducing
sicca symptoms or parotid swelling. - Key Point
- Patients with Sjögren syndrome have up to a
44-fold increased incidence of lymphoma, which
may be confined to glandular tissue
65Sjögren Syndrome
- Diagnosis
- Sjögren syndrome is an autoimmune disease
characterized by keratoconjunctivitis sicca and
xerostomia. Salivary gland enlargement occurs in
nearly half of patients during the course of the
disease and is most obvious in the parotid
glands. This condition may occur as a primary
disease process or may be associated with another
autoimmune disease, most commonly rheumatoid
arthritis. A cardinal feature of Sjögren syndrome
is the presence of antibodies to Ro/SSA and
La/SSB. A positive ANA, RF, and
hypergammaglobulinemia are also frequently found.
Diagnosis is established by biopsy of a labial
minor salivary gland. Patients with Sjögren
syndrome are up to 44 times more likely than the
general population to have a B-cell lymphoma.
Careful follow-up is therefore required.
66Bilateral parotid gland enlargement in a patient
with Sjögren syndrome.
67Therapy
- Treatment is symptomatic. Choose artificial tear
replacement and artificial saliva and mouth
lubricants. Systemic immunosuppressive therapy is
indicated only in patients with severe systemic
manifestations.
68Spondyloarthritis
- Key Considerations
- Spondyloarthritis comprises several systemic
inflammatory joint disorders that share distinct
clinical, radiographic, and genetic features.
These disorders are - psoriatic arthritis
- reactive arthritis (formerly Reiter syndrome)
- ankylosing spondylitis
- IBD-associated arthritis
- Characteristics include
- inflammatory spine and sacroiliac disease
- asymmetric inflammation in four or fewer
peripheral joints (typically large joints) - inflammation at the sites of ligament and tendon
insertion (enthesitis) - the presence of HLA-B27
- extra-articular conditions, such as uveitis,
colitis, urethritis, aortitis, and psoriasis
69Question 8
- A 42-year-old man is evaluated for a 1-month
history of a painful, swollen right finger and a
swollen left toe. - On physical examination, vital signs are normal.
The right third distal interphalangeal joint is
swollen, with localized tenderness to palpation
and pain with active and passive range of motion.
The appearance of the nails - is shown
- The left second toe is remarkable for fusiform
swelling and mild diffuse tenderness, with
decreased active and passive range of motion.
There is onycholysis of several toenails,
including the left second toenail. The remainder
of the physical examination is normal.
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71Answer Choice
- Which of the following is the most likely
diagnosis? - A Lyme arthritis
- B Osteoarthritis
- C Psoriatic arthritis
- D Rheumatoid arthritis
72Answer Choice
- Which of the following is the most likely
diagnosis? - A Lyme arthritis
- B Osteoarthritis
- C Psoriatic arthritis
- D Rheumatoid arthritis
73Explanation
- This patient has psoriatic arthritis, a systemic
chronic inflammatory arthritis associated with
numerous clinical manifestations. Typically,
psoriasis predates the arthritis by years,
whereas arthritis develops before skin disease in
15 of patients. Although there is a poor
correlation between the severity of skin and
joint disease, there is a good correlation
between the severity of nail disease and the
severity of both skin and joint disease.
Psoriatic findings may also be limited to nail
pitting and onycholysis. There are five patterns
of joint involvement in psoriatic arthritis
involvement of the distal interphalangeal joints
asymmetric oligoarthritis symmetric
polyarthritis (similar to that of rheumatoid
arthritis) arthritis mutilans (extensive
osteolysis of the digits with striking
deformity) and spondylitis. Characteristic
features of psoriatic arthritis include
enthesitis, dactylitis, and tenosynovitis. This
patient has findings characteristic of psoriatic
arthritis, including inflammation of a distal
interphalangeal joint and dactylitis of a toe. He
also has nail changes, including pitting and
onycholysis. - Lyme arthritis typically involves medium- or
large-sized joints rather than distal
interphalangeal joints and does not typically
cause tenosynovitis. Furthermore, this disorder
does not cause nail changes, as seen in this
patient. - Osteoarthritis can involve the distal
interphalangeal joints but does not cause
dactylitis or nail changes.
74Explanation
- Rheumatoid arthritis can initially present with
an asymmetric pattern, although it classically
takes on a symmetric distribution with time. In
contrast to this case, rheumatoid arthritis
typically spares the distal interphalangeal
joints, involving the proximal interphalangeal
joints and metacarpophalangeal joints
preferentially. Finally, this condition does not
cause nail changes - Key Point
- Psoriatic arthritis is associated with various
patterns of joint involvement, most notably
distal interphalangeal joint involvement, and is
characterized by enthesitis, dactylitis,
tenosynovitis, and cutaneous involvement such as
nail pitting
75Psoriatic Arthritis
- Characteristic findings are classic psoriasis
(thick silvery scale on a well-demarcated red
patch) and nail pitting in a patient with joint
pain and stiffness. Skin involvement commonly
precedes joint inflammation, although 15 of
patients first develop joint inflammation. - Patterns of joint involvement are various.
Approximately 40 of patients present with
symmetric oligoarthritis of the large joints of
the lower extremities, and 25 of these patients
develop small-joint polyarthritis, similar to RA.
Spinal involvement occurs in almost 50 of
patients with psoriatic arthritis. A
sausage-shaped finger or toe (dactylitis) may be
found and the DIP joints are often involved,
which helps distinguishes psoriatic arthritis
from RA. - Patients with psoriatic arthritis tend to be
seronegative for rheumatoid factor, but at least
15 are seropositive, as are a similar percentage
of patients with uncomplicated psoriasis. Serum
uric acid levels may be elevated in patients with
psoriatic arthritis because of rapid turnover of
skin cells. X-rays may show a pencil-in-the-cup
appearance of one or more involved joints. Other
radiographic findings include syndesmophytes and
sacroiliitis of the axial skeleton.
76- Don't Be Tricked
- No relationship exists between the extent of skin
and joint disease in patients with psoriatic
arthritis. - Do not make a diagnosis of gout based solely on
joint pain and elevated serum uric acid levels. - Use NSAIDs for mild joint inflammation and
minimal skin involvement prescribe methotrexate
for severe skin and erosive peripheral joint
disease. A TNF-a inhibitor is indicated for
methotrexate-resistant peripheral disease and may
be indicated as first-line treatment for patients
with axial involvement and for those with
dactylitis or enthesitis that does not respond to
NSAIDs and locally injected corticosteroids.
NSAIDs, antimalarial drugs, and (withdrawal from)
oral corticosteroids may exacerbate psorias
77Diffuse swelling of the left third and fourth
toes and right fourth toe characteristic of
dactylitis.
78Tiny pits scattered over the nail plate resulting
from psoriatic involvement of the nail matrix.
79Question 9
- A 24-year-old woman is evaluated for a 3-week
history of pain and swelling of the right knee
and left ankle. She also has urinary frequency
and urgency. The patient has no history of tick
exposure, skin rash, diarrhea, or abdominal pain.
She has not been sexually active in the past
month. She takes no medications. - On physical examination, vital signs are normal.
Musculoskeletal examination reveals swelling,
tenderness, warmth, pain on active and passive
range of motion, and a palpable effusion of the
right knee the left ankle is swollen and tender,
with pain at the extremes of active range of
motion and no significant pain with passive range
of motion. - Serologic test results for Borrelia burgdorferi
are negative. Urinalysis reveals 2 leukocyte
esterase, 18 leukocytes/hpf, and no protein,
bacteria, squamous epithelial cells, or
erythrocytes. - Aspiration of the right knee is performed
synovial fluid analysis reveals an erythrocyte
count of 150/µL and a leukocyte count of 7500/µL
(7.5 109/L). Gram stain is negative. Synovial
fluid culture results are pending.
80Answer Choice
- Which of the following is the most appropriate
next step in management? - A Antinuclear antibody testing
- B Rheumatoid factor testing
- C Synovial fluid polymerase chain reaction
testing for Borrelia burgdorferi - D Urine nucleic acid amplification testing for
Chlamydia trachomatis and Neisseria gonorrhoeae
81Answer Choice
- Which of the following is the most appropriate
next step in management? - A Antinuclear antibody testing
- B Rheumatoid factor testing
- C Synovial fluid polymerase chain reaction
testing for Borrelia burgdorferi - D Urine nucleic acid amplification testing for
Chlamydia trachomatis and Neisseria gonorrhoeae
82Explanation
- This patient requires urine nucleic acid
amplification testing for Chlamydia trachomatis
and Neisseria gonorrhoeae. She has acute
arthritis of the right knee, enthesitis of the
left ankle, and urethritis, all of which can be
seen with disseminated gonorrheal infection
however, in the absence of any recent history of
sexual activity, these findings are more
suggestive of reactive arthritis as can be seen
after C. trachomatis infection. Reactive
arthritis occurs in both men and women, and
enthesitis and oligoarthritis are common. The
classic triad of arthritis, urethritis, and
conjunctivitis occurs in only one third of
patients. Symptoms typically develop 2 to 4 weeks
after an infection. - Classic pathogens associated with reactive
arthritis include C. trachomatis as well as
several enteric pathogens. C. trachomatis
infection may be asymptomatic. Urine sample
evaluation with ligase reaction can establish a
diagnosis of C. trachomatis infection at that
time, antibiotic treatment (azithromycin or
levofloxacin) is warranted to prevent potential
sequelae of untreated disease. Sexual partners
should also be counseled and treated. - Antinuclear antibody testing can be helpful in
the diagnosis of systemic lupus erythematosus
(SLE). Although arthritis and pyuria can be seen
in SLE, the pyuria typically results from
glomerulonephritis and is therefore not
associated with the lower urinary tract symptoms
of frequency and urgency. The patient does not
have any other symptoms or signs of SLE.
83Explanation
- Rheumatoid factor is present in approximately 70
of patients with rheumatoid arthritis. This
disorder typically presents with a symmetric,
small joint polyarthritis and does not explain
this patient's urinary symptoms and pyuria. - This patient's negative Lyme disease serology
results indicate that she does not have Lyme
arthritis, and testing the synovial fluid for
Borrelia burgdorferi infection is not needed. In
patients with Lyme arthritis, testing by
polymerase chain reaction (PCR) can detect B.
burgdorferi DNA in synovial fluid. Unlike B.
burgdorferi serology, synovial fluid PCR testing
becomes negative after successful antibiotic
treatment. However, synovial fluid PCR testing
has not been validated for wide use. - Key Point
- Detection of pathogens such as Chlamydia
trachomatis in patients with arthritis,
urethritis, conjunctivitis, and/or enthesitis
supports a diagnosis of reactive arthritis.
84Reactive Arthritis
- Reactive arthritis is an acute aseptic
inflammatory arthritis that occurs 1 to 3 weeks
after an infectious event originating in the GU
or GI tract. A high prevalence of HIV infection
is found in patients with symptoms of reactive
arthritis. - Characteristic findings include
- acute asymmetric oligoarthritis (usually in
weight-bearing joints) - dactylitis
- mouth ulcers
- inflammatory eye conditions
- Patients may also have keratoderma
blennorrhagicum (a psoriasis-like skin lesion on
the palms and soles) or circinate balanitis
(shallow, moist, serpiginous ulcers with raised
borders on the glans penis).
85- Diagnostic studies include throat culture for
Streptococcus, urogenital culture for Chlamydia,
and serologic studies for Salmonella, Yersinia,
Campylobacter, Neisseria, and HIV. Obtain
urinalysis for protein, blood, and leukocytes. - If the causative organism can be isolated
(ß-hemolytic streptococci, N. gonorrhoeae,
Chlamydia), begin specific antibiotics. If
infection is ruled out, treat with an
intra-articular corticosteroid injection in the
acutely inflamed joint. If arthritis persists for
longer than 3 to 5 months, begin DMARDs.
Sulfasalazine is a common first-line choice. - Don't Be Tricked
- The classic triad of arthritis, conjunctivitis,
and urethritis (or cervicitis) is found in only
one third of patients with reactive arthritis. - Do not prescribe chronic antibiotic therapy for
patients with reactive arthritis.
86A papular and pustular rash of the palms and
soles is associated with reactive arthritis.
87Ankylosing Spondylitis
- Ankylosing spondylitis primarily affects the
spine and sacroiliac joints. It also may involve
the shoulders and hips, although the small
peripheral joints are not affected. Ankylosing
spondylitis occurs most often in patients lt40
years of age and presents as chronic low back
pain. Characteristic findings are pain and
stiffness that worsen at night and are relieved
with physical activity or heat. - Physical examination findings include
- decreased hyperextension, forward flexion,
lateral flexion, and axial rotation - diminished chest expansion
- asymmetric peripheral arthritis involving the
large joints - painful heels (enthesitis)
- X-rays show subchondral bony sclerosis, vertebral
body squaring, and bony ankylosis (bamboo
spine). When radiographic findings are equivocal
or absent, MRI can detect the early changes of
sacroiliitis. HLA-B27 testing is neither
sensitive nor specific for ankylosing spondylitis
and does not distinguish ankylosing spondylitis
from other spondyloarthropathies.
88- Extra-articular manifestations include acute
anterior uveitis (most common), aortic valvular
regurgitation and cardiac conduction defects,
apical pulmonary fibrosis and cavitation, and
cauda equina syndrome. - A patient with ankylosing spondylitis with
increased pain and mobility of the neck following
a minor accident may have a fracture and requires
an urgent CT of the cervical spine. - Don't Be Tricked
- Ankylosing spondylitis occurs in both men and
women. - NSAIDs, not aspirin, are the mainstay of
management. Use corticosteroid injections for
recalcitrant enthesitis and persistent synovitis.
Prescribe sulfasalazine for patients with
primarily peripheral arthritis and a TNF-a
inhibitor for primarily axial disease. Calcium
and vitamin D supplements and exercise to retain
good posture, spinal mobility, and chest
expansion are beneficial. Begin a bisphosphonate
if osteopenia or osteoporosis is present. - Don't Be Tricked
- Do not prescribe traditional DMARDs for patients
with axial disease because they are ineffective.
Select a TNF-a inhibitor.
89Sclerosis and erosions of sacroiliac joints and
bridging of the intervertebral disks by
syndesmophytes are characteristic of ankylosing
spondylitis.
90IBD-Associated Arthritis
- Inflammatory arthritis can complicate Crohn
disease and ulcerative colitis. Up to 20 of
patients with IBD develop a peripheral arthritis,
which manifests as either a polyarticular
arthritis resembling RA or an asymmetric
oligoarthritis predominantly of the lower
extremities resembling reactive arthritis. The
course of arthritis often fluctuates with the
activity of the underlying bowel involvement.
Another 20 of patients have spinal involvement
ranging from asymptomatic sacroiliac disease to a
clinical presentation identical to that of
ankylosing spondylitis. Unlike peripheral
arthritis, the progression of spinal involvement
is independent of the course of the bowel
disease. - The therapies that benefit intestinal disease
also have efficacy in the treatment of the
associated peripheral joint and extra-articular
manifestations. These therapies include
corticosteroids, sulfasalazine, azathioprine,
methotrexate, infliximab, and adalimumab. - Don't Be Tricked
- Etanercept has not shown efficacy in treating IBD.
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