Differentials
Large granular lymphocyte (LGL) syndrome
SIGNS / SYMPTOMS
A low-grade malignancy associated with neutropenia and splenomegaly.
Approximately 25% of patients with LGL syndrome have RA. LGL syndrome with RA and FS form an overlap condition with a similar immunogenetic background.[14]
Arthritis in LGL syndrome tends to be less aggressive than in FS with fewer extra-articular RA manifestations.[3]
LGL is more likely if onset of arthritis and neutropenia is simultaneous.
INVESTIGATIONS
Rheumatoid factor (RF) may be negative.
Peripheral blood smear and bone marrow exam show an expanded lymphocyte population with typical LGLs.
Immunophenotyping shows an expanded population of lymphocytes expressing CD2, 3, 8, 16, and 57.
T-cell receptor gene rearrangement studies show clonal cytogenetic abnormalities.
Lymphoproliferative disorders
SIGNS / SYMPTOMS
Typical features of RA may not be present on examination.
There may be widespread lymphadenopathy with hepatosplenomegaly.
History may reveal presence of B-cell symptoms (e.g., night sweats, fever, weight loss).
INVESTIGATIONS
RF may be negative.
Peripheral blood smear and bone marrow exam may show infiltration by lymphoma cells.
Lymph node excision biopsy may be necessary to characterize the type of lymphoma.
Myeloproliferative disorders
SIGNS / SYMPTOMS
Typical features of RA may be absent on examination.
INVESTIGATIONS
CBC may show anemia, neutropenia, lymphocytosis, thrombocytopenia, or thrombophilia.
Peripheral blood smear and bone marrow exam may show infiltration with abnormal cells, which can be characterized by cytogenetic analysis.
Systemic lupus erythematosus
SIGNS / SYMPTOMS
Absence of typical articular and extra-articular features of RA such as erosive arthritis or rheumatoid nodules.
Other features that may suggest systemic lupus erythematosus (SLE) include typical skin rashes such as a malar rash, photosensitivity, or discoid lupus, and presence of nephritis or central nervous system involvement.
INVESTIGATIONS
Lymphopenia is more common in SLE.
Hand X-rays are unlikely to show erosive changes.
High-titer antinuclear antibodies (ANA) and double-stranded (ds) DNA antibodies suggest SLE.
Urinalysis may show proteinuria and hematuria suggestive of SLE nephritis.
Anti-TNF-induced lupus
SIGNS / SYMPTOMS
Patients with RA treated with anti-TNF agents may develop anti-TNF-induced lupus (ATIL), characterized by increased ANA positivity, development of dsDNA antibodies, and clinical features of drug-induced lupus such as fever, malaise, myalgia, and rash.
Symptoms usually resolve on withdrawal of anti-TNF agent.[12]
Splenomegaly is not usually a feature of ATIL.[12]
INVESTIGATIONS
Increased titer of ANA, development of dsDNA antibodies, which are usually immunoglobulin M dsDNA.
HIV infection
SIGNS / SYMPTOMS
Typical features of RA may be absent.
Systemic symptoms, such as fevers or constitutional upset, may be common.
There may be risk factors for development of HIV infection.
INVESTIGATIONS
RF may be negative.
Virologic testing confirms HIV infection.
Cytomegalovirus infection
SIGNS / SYMPTOMS
Typical features of RA may be absent.
Systemic symptoms such as fevers or constitutional upset may be common.
INVESTIGATIONS
Inflammatory markers CRP and erythrocyte sedimentation rate may not be elevated in viral infection.
RF may be negative.
Virologic testing confirms cytomegalovirus infection.
Sarcoidosis
SIGNS / SYMPTOMS
Patients may have arthritis, typically involving ankles, knees, and hands, but it is rarely deforming or erosive.
Patients may also have uveitis, lymphadenopathy, parotid gland enlargement, enthesitis, skin involvement with erythema nodosum, or lupus pernio.
INVESTIGATIONS
CXR may reveal bilateral hilar lymphadenopathy.
Serum angiotensin-converting enzyme may be elevated.
Hand X-rays are unlikely to show RA changes and erosions.
Biopsy of lymph nodes, affected organs, or bone marrow may show noncaseating granulomas.
Amyloidosis
SIGNS / SYMPTOMS
Patients with long-standing RA are at risk of developing amyloidosis.
Nonspecific symptoms such as weight loss and fatigue, together with peripheral edema due to cardiac or renal involvement, may be present, as well as paresthesias suggesting peripheral neuropathy.
Examination may show cardiac failure.
INVESTIGATIONS
Urinalysis may show proteinuria.
Blood tests may show renal impairment.
CXR may show heart failure.
Abdominal ultrasound or CT scan may show hepatosplenomegaly.
Serum amyloid P component scintigraphy may confirm diagnosis.
Biopsy of rectum or affected organ stained with Congo red shows presence of amyloid.
Liver cirrhosis
SIGNS / SYMPTOMS
History of alcohol excess or chronic viral hepatitis infection that may suggest liver cirrhosis.
Typical features of RA may be absent on examination.
Typical features of chronic liver disease such as spider nevi, gynecomastia, ascites, or jaundice may be present.
INVESTIGATIONS
RF may be negative
LFTs may be abnormal.
Abdominal ultrasound may show features of cirrhosis and ascites.
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