Differentials

Rheumatoid arthritis

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

May be difficult to differentiate clinically.

Patients with SLE frequently present with an inflammatory arthritis with a similar pattern to rheumatoid arthritis, although it tends to be less symmetrical.

INVESTIGATIONS

Joint x-rays demonstrate symmetrical, erosive arthritis.

Antiphospholipid syndrome

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Characterized by the occurrence of venous or arterial thrombosis or recurrent fetal loss in the presence of antiphospholipid antibodies.

INVESTIGATIONS

Antiphospholipid antibodies: anticardiolipin antibodies IgG or IgM present in moderate or high levels on ≥2 occasions at least 6 weeks apart and lupus anticoagulant detected on ≥2 occasions at least 6 weeks apart. These antibodies may also be positive in SLE.

About 10% of patients with antiphospholipid syndrome are b2-glycoprotein positive.[80]

Venereal Disease Research Laboratory (VDRL) test: false-positive result.

Systemic sclerosis

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Raynaud phenomenon is present in almost all patients with systemic sclerosis, being the initial symptom in about 70% of patients.

Patients with SLE often have Raynaud phenomenon as well, but these tend not to ulcerate compared with patients with systemic sclerosis.

Patients with systemic sclerosis have characteristic sclerodactyly and calcinosis, not present in SLE.

INVESTIGATIONS

Autoantibodies: positive anti-centromere antibodies (limited cutaneous systemic sclerosis) or anti-topoisomerase 1 (Scl-70) antibodies (diffuse cutaneous systemic sclerosis).

Mixed connective tissue disease

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SIGNS / SYMPTOMS

Mixed connective tissue disease (MCTD) is characterized by a combination of manifestations similar to those in SLE, systemic sclerosis, and myositis. Difficult to differentiate clinically.

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Autoantibodies: positive anti-RNP antibodies are specific to MCTD.

Patients with MCTD tend to lack other antibodies such as anti-Sm, anti-Ro, anti-La, and anti-dsDNA.

Adult Still disease

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

A variant of juvenile rheumatoid arthritis characterized by seronegative chronic polyarthritis in association with a systemic inflammatory illness, which manifests as symptoms similar to those of SLE.

The fever in adult Still disease usually occurs once or twice daily with marked temperature elevation and normal temperature in between.

The rash is often only seen during febrile periods and is a salmon-colored macular or maculopapular nonpruritic lesion.

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Elevated ferritin has been reported in most patients. Ferritin should therefore be checked in patients presenting with such symptoms and, if elevated, lead to a suspicion of adult Still disease.

Joint symptoms are similar to rheumatoid arthritis and joint erosions and fusion on x-ray may occur, unlike in SLE.

Lyme disease

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SIGNS / SYMPTOMS

May be difficult to distinguish clinically.

History of possible erythema migrans or exposure to ticks.

INVESTIGATIONS

Lyme-specific IgM and IgG are positive.

Although the presence of antinuclear antibody is common, the presence of dsDNA and Smith antibodies are not.

HIV

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

May be difficult to distinguish clinically.

History of exposure to risk factors for HIV.

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Serum HIV enzyme-linked immunosorbent assay test is positive.

Although the presence of antinuclear antibody is common, the presence of dsDNA and Smith antibodies are not.

Cytomegalovirus

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

May be difficult to distinguish clinically.

May be asymptomatic.

INVESTIGATIONS

Cytomegalovirus serology is positive for infection.

Although the presence of antinuclear antibody is common, the presence of dsDNA and Smith antibodies is not.

Infectious mononucleosis

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

May be difficult to distinguish clinically.

INVESTIGATIONS

Positive agglutination test (e.g., monospot).

Although the presence of antinuclear antibody is common, the presence of dsDNA and Smith antibodies is not.

Hematologic malignancy

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SIGNS / SYMPTOMS

SLE may be difficult to distinguish clinically from hematologic malignancy.

INVESTIGATIONS

Bone marrow, other histology or imaging tests may distinguish the diagnosis.

Autoantibodies will be negative.

Glomerulonephritis

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Difficult to differentiate clinically if no other symptoms or signs associated with SLE are present (e.g., Raynaud phenomenon, rash).

INVESTIGATIONS

Antibodies for dsDNA may be positive if SLE is the cause.

Renal biopsy may aid in diagnosis.

Chronic fatigue syndrome

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

No other signs that are typically associated with SLE (e.g., Raynaud phenomenon, rash) will be present

INVESTIGATIONS

Autoantibodies will be negative.

Generalized tonic-clonic seizures

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

May be difficult to differentiate clinically as seizures can be a feature of SLE. However, no other signs that are typically associated with SLE (e.g., Raynaud phenomenon, rash) will be present.

INVESTIGATIONS

EEG will demonstrate epileptiform activity.

Brain MRI may demonstrate a lesion.

Autoantibodies will be negative in epilepsy.

Fibromyalgia

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Poorly localized symmetrical musculoskeletal pain with no diurnal variation.

Poorly responsive to analgesics/nonsteroidal anti-inflammatory drugs.

May coexist with SLE.

Positive typical tender points.

INVESTIGATIONS

Diagnosis is typically clinical.

Autoantibodies will be negative.

Depression

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Typically no systemic manifestations (e.g., rash) unless coexists with SLE.

INVESTIGATIONS

Diagnosis is typically clinical.

Autoantibodies will be negative.

Septic arthritis

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

May be difficult to differentiate clinically if patient presents with monoarthritis and no other features of SLE.

INVESTIGATIONS

Joint aspiration or synovial biopsy yields positive culture.

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