What four characteristics of RA help distinguish it from OA?

What constitutional symptoms may be seen in RA?

What are three characteristic physical findings in RA?

What five diseases may mimic RA?

Which serologic tests may be useful in the diagnosis of RA?

Discussion

What four characteristics of RA help distinguish it from OA?

Unlike patients with OA (noninflammatory), those with RA (inflammatory) experience morning stiffness lasting more than 30 minutes plus gel phenomenon (worse stiffness after rest);symmetric joint disease;characteristic bilateral synovitis of the hands and feet (PIPs, MCPs, and MTPs);and an intermittent or waxing and waning course.

What constitutional symptoms may be seen in RA?

Most patients experience generalized malaise or fatigue. Occasionally weight
loss, low-grade fever, sleep disturbance, or mild lymphadenopathy may be
present. These symptoms may be the end result of circulating inflammatory cytokines produced in the inflamed synovial tissue of the affected joints.

What are three characteristic physical findings in RA?

Physical findings encountered in the setting of RA may include swelling and warmth of one or more joints typically in a symmetric distribution, tenderness on palpation of the swollen joints, and the presence of nontender subcutaneous nodules (rheumatoid nodules) over the extensor surface of the forearm, Achilles tendon, and digits of the hands.

What five diseases may mimic RA?

RA may be mimicked by SLE and other CTDs such as mixed connective tissue disease(MCTD), scleroderma, and PMR; polyarticular gout or pseudogout; the arthritis of subacute bacterial endocarditis; the arthritis secondary to malignancy; and the seronegative spondyloarthropathies. The diagnosis of RA is based on the history, physical examination, and laboratory findings.

Which serologic tests may be useful in the diagnosis of RA?

RFs are autoantibodies directed against the Fc portion of IgG. In RA, RF has a sensitivity of approximately 80% and specificity of 80%. Therefore, RF is detected in approximately 80% of patients with RA but it is nonspecific and can be detected in many other disorders such as other CTDs and chronic viral or bacterial infections. Anti-CCP antibodies are directed against citrullinemodified arginine residues in a protein. In RA, anti-CCP antibodies have a sensitivity of 60% to 75% and a high specificity of 90% to 96%. Therefore, anti-CCP antibodies are usually detected only in RA. Patients with RA who have a positive RF and/or anti-CCP antibodies are at a higher risk of developing erosive joint destruction and debility. An elevated ESR or C-reactive protein (CRP) level suggests the presence of an acute inflammatory disease. A complete blood count may show an anemia of chronic (inflammatory) disease. ANAs are found in 30% of patients with RA, usually in a low titer with a negative ANA profile, and are of little diagnostic value.

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A 45-year-old white man seeks medical care because of hemoptysis of 1-week duration. He has not felt well for approximately 4 months and has lost 10 lb (4.5 kg) during this time. He has been receiving various antibiotics for the treatment of chest radiographic abnormalities thought to represent pneumonia. Although these changes have varied in presentation, they have not disappeared. A few weeks earlier,he noted some bloody nasal discharge. He started coughing up blood 1 week ago but attributed it to his bloody nose. The patient also complains that his
left knee has been hurting and that red spots have appeared on his arms and legs. He denies fever, purulent sputum, allergies or asthma, known tuberculosis, or chest pain.

On physical examination,

there is a curious depression in his upper nose(saddle-nose deformity),
bloody discharge in his nasal cavity,
a painless ulcer on his soft palate,
and
a slightly warm and swollen left knee.

Chestfindings are normal.

There are many small, purpuric, raised lesions on the skin of his lower extremities that are painless.

What are four possible diagnoses in this patient?

What diagnostic studies or procedures might be of value in this patient?

Which disorders are associated with p-ANCA?

What constitutes appropriate therapy for this patient with Wegener's
granulomatosis?

Case Discussion

What are four possible diagnoses in this patient?

Four possible diagnoses in this patient are Wegener's granulomatosis, Churg-Strauss syndrome (allergic granulomatosis), intranasal drug abuse, or a lung tumor. Churg-Strauss syndrome occurs primarily in patients with a history of allergies or asthma and is often associated with peripheral eosinophilia. ANCA reacting with human neutrophil elastase can occur in cocaine-induced midline
destructive lesions. The saddle-nose deformity and palpable purpura would be uncommon manifestations of a primary lung carcinoma.

What diagnostic studies or procedures might be of value in this patient?

Nasopharyngeal examination with biopsy, CT scan of the sinuses and chest,creatinine and urinalysis, and bronchoscopy with biopsy or open lung biopsy would all be helpful in the evaluation of this patient's disorder. An ANCA should be ordered because most patients with systemic Wegener's granulomatosis are c-ANCA positive and have antiproteinase 3 antibodies. In approximately 60% of patients, c-ANCA titers correlate with Wegener's disease activity.

Which disorders are associated with p-ANCA?

A p-ANCA may be present due to a variety of different antibodies directedagainst myeloperoxidase, elastase, cathepsin, and lactoferrin, and can occur in many different diseases. Diseases associated with p-ANCA directed against myeloperoxidase include Wegener's granulomatosis (10%), Churg-Strauss syndrome (50%), MPA (50% to 80%), and idiopathic crescentic
glomerulonephritis (65%). Nonspecific p-ANCAs directed against other various proteins can occur in CTDs, Crohn's disease, ulcerative colitis, sclerosing cholangitis, cystic fibrosis, chronic infections, and rare drug-induced vasculitic syndromes associated with propylthiouracil, hydralazine, and minocycline.

What constitutes appropriate therapy for this patient with Wegener's granulomatosis?

Standard therapy for Wegener's granulomatosis includes both high doses of corticosteroids and oral cyclophosphamide. Oral trimethoprim/sulfamethoxazole prophylaxis against Pneumocystis carinii should be considered while on the above therapy.

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Discussion On Following Headings

Vasculitis should be suspected in patients presenting with any combination of
what clinical manifestations?

Name the primary vasculitic disorders based on the dominant vessel size and
antineutrophil cytoplasmic antibodies (ANCA).

What serologic tests or diagnostic procedures should be performed in patients
with suspected vasculitis?


What more extensive procedures may be of value in helping to establish the
diagnosis of a specific form of vasculitis?


Vasculitis should be suspected in patients presenting with any combination of
what clinical manifestations?
Vasculitis comprises a heterogeneous group of diseases characterized by
inflammatory changes in the blood vessels with subsequent impairment of flow
and tissue/organ ischemia. Patients present with a multisystem inflammatory
disease often with fever of unknown origin and/or unexplained constitutional
symptoms; suspicious skin lesions such as ulcers, livedo reticularis, and
palpable purpura; ischemic neuropathies; and rapidly progressive organ
dysfunction such as strokes, pulmonary–renal syndromes, and other organ
ischemia.

Name the primary vasculitic disorders based on the dominant vessel size and
ANCA.

Vasculitides affecting large arteries:

Takayasu's arteritis: aortic arch and its branches, can involve any part of
the aorta; more claudication of upper than lower extremities, central
nervous system events; granulomatous panarteritis.

Giant cell (temporal) arteritis (GCA): temporal arteries, vessels
originating from the aortic arch, other arteries less common; temporal
headache, jaw claudication, scalp tenderness, visual loss; arteritis with
giant cells and disruption of the internal elastic lamina.
Vasculitides affecting predominantly medium-sized arteries:

Polyarteritis nodosa (PAN): small- and medium-sized arteries; may
affect any organ, but skin, joints, peripheral nerves, gut, and kidney are
most commonly involved; focal but panmural necrotizing arteritis with a
predilection for involvement at the vessel bifurcation.

Kawasaki disease: small- and medium-sized arteries; acute febrile
illness primarily affecting infants and young children; fever, prominent
mucocutaneous changes, cervical lymphadenopathy, polymorphous
rash, erythema and edema of hands and feet, desquamation,
myocarditis, coronary vasculitis; probable infectious vector resulting in
cytokine-mediated endothelial damage.
Vasculitides affecting predominantly small vessels (ANCA-positive):

Wegener's granulomatosis: small- and medium-sized arteries; upper
respiratory tract (sinuses), lungs, and kidneys, may affect other organs;
pauciimmune, necrotizing, granulomatous arteritis usually associated
with serum cytoplasmic–antineutrophil cytoplasmic antibodies (c-ANCA)
usually directed against proteinase 3 in the primary granules of neutrophils.

Microscopic polyangiitis (MPA): arterioles, capillaries, and venules;
pulmonary hemorrhage, glomerulonephritis, palpable purpura,
peripheral neuropathy, joint and abdominal pain; pauciimmune,
necrotizing vasculitis, serum perinuclear–antineutrophil cytoplasmic
antibodies usually directed against myeloperoxidase in the primary
granules of neutrophils.

Churg-Strauss syndrome: small arteries and venules; asthma,
eosinophilia, multiorgan involvement [lungs, skin, peripheral nerves,
gut, heart, and kidneys (rare)]; necrotizing extravascular granulomas
and vasculitis of small arteries and venules, eosinophils present in early
stage.
Vasculitides affecting predominantly small vessels (ANCA-negative):

Henoch-Schönlein purpura (HSP): arterioles and venules; palpable
purpuric skin lesions on lower extremities, arthritis, abdominal pain,
hematuria; leukocytoclastic (neutrophilic perivascular/transmural
infiltrate) or necrotizing vasculitis often with IgA deposition.

Cutaneous leukocytoclastic angiitis: arterioles and venules; palpable
purpuric skin lesions, arthralgias, systemic symptoms may be present,
usually secondary to immune complexes [drugs, bugs (infections), CTD
or malignancy]; leukocytoclastic vasculitis.

Cryoglobulinemic vasculitis: cryoglobulins are immunoglobulins that are
reversibly precipitated by reduced temperatures; cryoglobulins are
deposited in small vessels including glomerulocapillaries; purpura,
arthralgias, peripheral neuropathy, Raynaud's phenomenon, pulmonary
hemorrhage, glomerulonephritis are possible; often RF and hepatitis C
antibody positive

What serologic tests or diagnostic procedures should be performed in patients
with suspected vasculitis?

The diagnostic evaluation of a patient with suspected vasculitis should be
based on the clinical situation but often includes a chest radiographic study,
ESR, CRP, a complete blood count with differential, liver function tests, CPK,
creatinine and urinalysis, tests for the presence of ANAs, ANCAs and RF,
cryoglobulins, and biopsy of a skin lesion or an involved organ. In some types
of vasculitis, complement levels may be low secondary to consumption. An
ESR greater than 100 mm per hour and a CRP greater than 10 mg/dL in the
absence of a widespread malignancy or bacterial infection should suggest a
vasculitic process.

What more extensive procedures may be of value in helping to establish the
diagnosis of a specific form of vasculitis?

More extensive diagnostic procedures for establishing the diagnosis of a
specific form of vasculitis include arteriography of the mesenteric vessels if a
tissue biopsy is inaccessible, and an electromyography with evaluation of
nerve conduction velocities to evaluate a peripheral neuropathy or a
mononeuritis multiplex. A computed tomography (CT) scan of the sinuses and
chest is indicated if a diagnosis of Wegener's granulomatosis is being
considered.

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