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{{CMG}}; {{AE}}{{MIR}}
{{CMG}}; {{AE}}{{MIR}}
==Overview==
==Overview==
: Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as [differential dx1], [differential dx2], and [differential dx3].
: Systemic lupus erythematosus (SLE) must be differentiated from other diseases that cause arthritis, positive autoimmune serology, and constitutional symptoms, such as rheumatoid arthritis(RA), mixed connective tissue disease (MCTD), Systemic sclerosis (SSc), Dermatomyositis (DM), polymyositis(PM), and other autoimmune diseases.  
: OR
: [Disease name] must be differentiated from [[differential dx1], [differential dx2], and [differential dx3].
: OR
: [Disease name] must be differentiated from other causes of [symptom/sign], such as [Differential 1], [Differential 2], and [Differential 3].


==Differentiating systemic lupus erythematosus from other diseases==
==Differentiating systemic lupus erythematosus from other diseases==
Systemic lupus erythematosus (SLE) must be differentiated from other diseases that cause arthritis, positive autoimmune serology, and constitutional symptoms, such as rheumatoid arthritis(RA), mixed connective tissue disease (MCTD), Systemic sclerosis (SSc), Dermatomyositis (DM), polymyositis(PM), and other autoimmune diseases.
{| class="wikitable"
{| class="wikitable"
! colspan="2" |
! colspan="2" |
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|-
|-
| colspan="2" |Rheumatoid arthritis (RA)
| colspan="2" |Rheumatoid arthritis (RA)
|joint tenderness and swelling especially in early RA
|
swan neck deformities, ulnar deviation, and soft tissue laxity more common in RA but may seen in SLE as well
* Serositis
 
* Sicca symptoms
serositis, sicca symptoms, subcutaneous nodules, anemia, and fatigue
* Subcutaneous nodules
 
* Anemia
POsitive ANA: more common in SLE
* Fatigue
 
* Joint tenderness and swelling especially in early RA
positive RF: more common in RA
* Swan neck deformities, ulnar deviation, and soft tissue laxity more common in RA but may seen in SLE as well
|joint deformities in RA are often more extensive, and frequently erosive on plain radiographs
* Positive ANA: more common in SLE
presence of anti-cyclic citrullinated peptides (CCP)
* Positive RF: more common in RA
|
* Joint deformities in RA are often more extensive, and frequently erosive on plain radiographs
* Presence of anti-cyclic citrullinated peptides (CCP)
|
|
|-
|-
| colspan="2" |Rhupus
| colspan="2" |Rhupus
|patients with overlapping features of both SLE and RA
serologies consistent with both SLE and RA
erosive arthropathy that is atypical for SLE
|
|
* Patients with overlapping features of both SLE and RA
* Serologies consistent with both SLE and RA
|
* Erosive arthropathy that is atypical for SLE
|
|
|-
|-
| colspan="2" |Mixed connective tissue disease (MCTD)
| colspan="2" |Mixed connective tissue disease (MCTD)
|is characterized by overlapping features of SLE, systemic sclerosis (SSc), and polymyositis (PM), and by the presence of high titers of antibodies against U1 ribonucleoprotein (RNP)
|
|MCTD is a distinct clinical entity but it is evident that a subgroup of patients may evolve into another CTD during disease progression. Initial clinical features and autoantibodies can be useful to predict disease evolution
* A mix disease with overlapping features of SLE, systemic sclerosis (SSc), and polymyositis (PM)
* Antibodies against U1 ribonucleoprotein (RNP)
|
* MCTD patients may evolve into another connective tissue disorder during disease progression.
* Prediction of disease evolution may be possible by recognizing autoantibodies
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|-
|-
| colspan="2" |Undifferentiated connective tissue disease (UCTD)
| colspan="2" |Undifferentiated connective tissue disease (UCTD)
|arthritis and arthralgias, Raynaud phenomenon, and serological findings
|
signs and symptoms suggestive of a systemic autoimmune disease but do not satisfy the classification criteria for a defined connective tissue disease such as SLE or MCTD
* Arthritis and arthralgias
|maintain an undefined profile and have a mild disease course
* Raynaud phenomenon
* Serological findings
|
* Mild disease course
|
|
|-
|-
| colspan="2" |Systemic sclerosis (SSc)
| colspan="2" |Systemic sclerosis (SSc)
|
|
|sclerodactyly, telangiectasias, calcinosis, and malignant hypertension with acute renal failure are more consistent with SSc
* Positive ANA
positive ANA is present in most patients with SSc, while other serologies such as anti-double-stranded DNA (dsDNA) and anti-Smith (Sm) antibodies
* Positive anti-double-stranded DNA (dsDNA)
 
* Positive anti-Smith (Sm) antibodies
antibodies to an antigen called Scl-70 (topoisomerase I) or antibodies to centromere proteins
|
* Sclerodactyly
* Telangiectasias
* Calcinosis
* Malignant hypertension with acute renal failure
* Positive antibodies to an antigen called Scl-70 (topoisomerase I)
* Positive antibodies to centromere proteins
|
|
|-
|-
| colspan="2" |Sjögren’s syndrome
| colspan="2" |Sjögren’s syndrome
|Extra-glandular manifestations
|
neurologic and pulmonary abnormalities
* Extra-glandular manifestations
* Neurologic abnormalities
* Pulmonary abnormalities
* Positive antibodies to Ro and La antigens


|keratoconjunctivitis sicca and xerostomia, and characteristic findings on salivary gland biopsy
|
commonly express antibodies to Ro and La antigens
* Keratoconjunctivitis sicca
* Xerostomia
* Salivary gland biopsy: Focal collection or collections of tightly aggregated lymphocytes, termed lymphocytic foci, which are typically periductal
|
|
|-
|-
| colspan="2" |Vasculitis
| colspan="2" |Vasculitis
|medium and small vessel vasculitides such as polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA) (Wegener’s), or microscopic polyangiitis (MPA)
|
constitutional symptoms, skin lesions, neuropathy and renal dysfunction
* Medium and small vessel vasculitides:
|ANA-negative
** Polyarteritis nodosa (PAN)
** Granulomatosis with polyangiitis (GPA) (Wegener’s)
** Microscopic polyangiitis (MPA)
* Constitutional symptoms
* Skin lesions
* Neuropathy
* Renal dysfunction
|
* ANA-negative
|
|
|-
|-
| colspan="2" |Behçet’s syndrome
| colspan="2" |Behçet’s syndrome
|Oral aphthae
|
inflammatory eye disease, neurologic disease, vascular disease, and arthritis
* Oral aphthae
|male dominancy and ANA-negative
* Inflammatory eye disease
 
* Neurologic disease
vascular involvement of any size (small, medium, large) is more common
* Vascular disease
* Arthritis
|
* Male dominancy
* ANA-negative
|
|
|-
|-
| colspan="2" |Dermatomyositis (DM) and polymyositis (PM)
| colspan="2" |Dermatomyositis (DM) and polymyositis (PM)
|positive ANA is observed in approximately 30 percent of patients
|
Gottron’s papules, a heliotrope eruption and photodistributed poikiloderma (including the shawl and V signs)
* Positive ANA: In approximately 30 percent of patients
|more overt proximal muscle weakness than SLE
* Gottron’s papules: A heliotrope eruption and photodistributed poikiloderma (including the shawl and V signs)
Absence of oral ulcers, arthritis, nephritis, and hematologic abnormalities
|
 
* More overt proximal muscle weakness than SLE
myositis-specific antibodies such as anti-Jo-1
* Absence of oral ulcers, arthritis, nephritis, and hematologic abnormalities
* Myositis-specific antibodies such as anti-Jo-1


|
|
|-
|-
| colspan="2" |Adult Still’s disease (ASD)
| colspan="2" |Adult Still’s disease (ASD)
|fever, arthritis or arthralgias, and lymphadenopathy
|
|leukocytosis
* Fever
Negative ANA
* Arthritis or arthralgias
* Lymphadenopathy
|
* Leukocytosis
* Negative ANA
|
|
|-
|-
| colspan="2" |Kikuchi’s disease
| colspan="2" |Kikuchi’s disease
|lymphadenopathy as well as fever, myalgias, arthralgias, and, less commonly, hepatosplenomegaly
|
* Lymphadenopathy
* Fever
* Myalgias
* Arthralgias
* Hepatosplenomegaly
|
|
* May be associated with SLE
* May be associated with SLE
* Spontaneous remission often occurring within four months
* Spontaneous remission usually occurring within four months
* lymph node biopsy, which reveals a histiocytic cellular infiltrate.
* Lymph node biopsy: Histiocytic cellular infiltrate
|
|
|-
|-
| colspan="2" |Serum sickness
| colspan="2" |Serum sickness
|fever, lymphadenopathy, cutaneous eruptions, and arthralgias
|
during severe episodes, complement measurements including C3 and C4 can be depressed, as in SLE
* Fever
|ANAs are typically negative and the course tends to be self-limited
* Lymphadenopathy
* Cutaneous eruptions
* Arthralgias
* Depressed levels of C3 and C4  during severe episodes
|
* Negative ANA
* Self-limited
|
|
|-
|-
| colspan="2" |Fibromyalgia
| colspan="2" |Fibromyalgia
|generalized arthralgias, myalgias, and fatigue
|
|SLE patients may have concomitant fibromyalgia as the prevalence of fibromyalgia in patients with systemic rheumatoid diseases is more.
* Arthralgias
* Myalgias
* Fatigue
|
* SLE patients may have concomitant fibromyalgia as the prevalence of fibromyalgia in patients with systemic rheumatoid diseases is more.
|
|
|-
|-
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|
|
* Human parvovirus B19:
* Human parvovirus B19:
** flu-like symptoms
** Flu-like symptoms
** hematologic abnormalities such as leukopenia and thrombocytopenia
** Hematologic abnormalities such as leukopenia and thrombocytopenia
** arthralgias or arthritis.
** Arthralgias or arthritis
|Serologic assays can be diagnostic for many of these viruses
| rowspan="9" |
* Serologic assays can be diagnostic for many of these viruses
|
|
|-
|-
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** May lead to a positive ANA
** May lead to a positive ANA
** 3020161       
** 3020161       
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|-
|-
|Human immunodeficiency virus (HIV)
|Human immunodeficiency virus (HIV)
|
|
|
|-
|-
|Hepatitis B virus (HBV)
|Hepatitis B virus (HBV)
|
|
|
|-
|-
|Hepatitis C virus (HCV)
|Hepatitis C virus (HCV)
|
|
|
|-
|-
|Cytomegalovirus (CMV)
|Cytomegalovirus (CMV)
|
|
|
|-
|-
|Epstein-Barr virus (EBV)
|Epstein-Barr virus (EBV)
|
|
|
|-
|-
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|Salmonella
|Salmonella
|
|
|-
|Mycobacterium tuberculosis
|
|
|-
|-
|tuberculosis
| colspan="2" |Multiple sclerosis (MS)
|
|
* Cranial neuropathies
|
|
|-
* Unilateral optic neuritis
| colspan="2" |Multiple sclerosis (MS)
* Pyramidal syndrome
|cranial neuropathies
* Lesions detected by magnetic resonance imaging (MRI) suggesting dissemination in space and time
|Unilateral optic neuritis and pyramidal syndrome, with lesions detected by magnetic resonance imaging (MRI) suggesting dissemination in space and time are characteristic of MS
|
|
|-
|-
| colspan="2" |Malignancies
| colspan="2" |Malignancies
|
|
* Leukemia or myelodysplastic syndromes
* Leukemia, myelodysplastic syndromes, and lymphoma
* hematologic and constitutional symptoms similar to those observed in SLE
 
* lymphoma
* Hematologic abnormalities
* Constitutional symptoms
|
|
* Monoclonal expansion of B and T cells (as assessed by immunophenotyping), monocytosis, or macrocytosis can distinguish these malignancies from SLE
* Monoclonal expansion of B and T cells (as assessed by immunophenotyping)
* Splenomegaly, lymphadenopathy, or increased lactate dehydrogenase (LDH) levels that are not observed in SLE but in lymphoma
* Monocytosis or macrocytosis
* Excisional tissue biopsy specially from lymph nodes in the case of lymphomas
* Lymphoma:
** Splenomegaly
** Lymphadenopathy
** Increased lactate dehydrogenase (LDH)
** Excisional tissue biopsy specially from lymph nodes for diagnosis
|
|
|-
|-
| colspan="2" |Thrombotic thrombocytopenic purpura (TTP)
| colspan="2" |Thrombotic thrombocytopenic purpura (TTP)
|fever and thrombocytopenia
|
* Fever
* Thrombocytopenia
|
|
* Microangiopathic hemolytic anemia
* Microangiopathic hemolytic anemia
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* Fluctuating neurological manifestations
* Fluctuating neurological manifestations
* Low levels of ADAMSTS13
* Low levels of ADAMSTS13
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Revision as of 23:05, 17 June 2017


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahshid Mir, M.D. [2]

Overview

Systemic lupus erythematosus (SLE) must be differentiated from other diseases that cause arthritis, positive autoimmune serology, and constitutional symptoms, such as rheumatoid arthritis(RA), mixed connective tissue disease (MCTD), Systemic sclerosis (SSc), Dermatomyositis (DM), polymyositis(PM), and other autoimmune diseases.

Differentiating systemic lupus erythematosus from other diseases

Systemic lupus erythematosus (SLE) must be differentiated from other diseases that cause arthritis, positive autoimmune serology, and constitutional symptoms, such as rheumatoid arthritis(RA), mixed connective tissue disease (MCTD), Systemic sclerosis (SSc), Dermatomyositis (DM), polymyositis(PM), and other autoimmune diseases.

Overlapping Features Distinguishing/specific features
Rheumatoid arthritis (RA)
  • Serositis
  • Sicca symptoms
  • Subcutaneous nodules
  • Anemia
  • Fatigue
  • Joint tenderness and swelling especially in early RA
  • Swan neck deformities, ulnar deviation, and soft tissue laxity more common in RA but may seen in SLE as well
  • Positive ANA: more common in SLE
  • Positive RF: more common in RA
  • Joint deformities in RA are often more extensive, and frequently erosive on plain radiographs
  • Presence of anti-cyclic citrullinated peptides (CCP)
Rhupus
  • Patients with overlapping features of both SLE and RA
  • Serologies consistent with both SLE and RA
  • Erosive arthropathy that is atypical for SLE
Mixed connective tissue disease (MCTD)
  • A mix disease with overlapping features of SLE, systemic sclerosis (SSc), and polymyositis (PM)
  • Antibodies against U1 ribonucleoprotein (RNP)
  • MCTD patients may evolve into another connective tissue disorder during disease progression.
  • Prediction of disease evolution may be possible by recognizing autoantibodies

21959290

Undifferentiated connective tissue disease (UCTD)
  • Arthritis and arthralgias
  • Raynaud phenomenon
  • Serological findings
  • Mild disease course
Systemic sclerosis (SSc)
  • Positive ANA
  • Positive anti-double-stranded DNA (dsDNA)
  • Positive anti-Smith (Sm) antibodies
  • Sclerodactyly
  • Telangiectasias
  • Calcinosis
  • Malignant hypertension with acute renal failure
  • Positive antibodies to an antigen called Scl-70 (topoisomerase I)
  • Positive antibodies to centromere proteins
Sjögren’s syndrome
  • Extra-glandular manifestations
  • Neurologic abnormalities
  • Pulmonary abnormalities
  • Positive antibodies to Ro and La antigens
  • Keratoconjunctivitis sicca
  • Xerostomia
  • Salivary gland biopsy: Focal collection or collections of tightly aggregated lymphocytes, termed lymphocytic foci, which are typically periductal
Vasculitis
  • Medium and small vessel vasculitides:
    • Polyarteritis nodosa (PAN)
    • Granulomatosis with polyangiitis (GPA) (Wegener’s)
    • Microscopic polyangiitis (MPA)
  • Constitutional symptoms
  • Skin lesions
  • Neuropathy
  • Renal dysfunction
  • ANA-negative
Behçet’s syndrome
  • Oral aphthae
  • Inflammatory eye disease
  • Neurologic disease
  • Vascular disease
  • Arthritis
  • Male dominancy
  • ANA-negative
Dermatomyositis (DM) and polymyositis (PM)
  • Positive ANA: In approximately 30 percent of patients
  • Gottron’s papules: A heliotrope eruption and photodistributed poikiloderma (including the shawl and V signs)
  • More overt proximal muscle weakness than SLE
  • Absence of oral ulcers, arthritis, nephritis, and hematologic abnormalities
  • Myositis-specific antibodies such as anti-Jo-1
Adult Still’s disease (ASD)
  • Fever
  • Arthritis or arthralgias
  • Lymphadenopathy
  • Leukocytosis
  • Negative ANA
Kikuchi’s disease
  • Lymphadenopathy
  • Fever
  • Myalgias
  • Arthralgias
  • Hepatosplenomegaly
  • May be associated with SLE
  • Spontaneous remission usually occurring within four months
  • Lymph node biopsy: Histiocytic cellular infiltrate
Serum sickness
  • Fever
  • Lymphadenopathy
  • Cutaneous eruptions
  • Arthralgias
  • Depressed levels of C3 and C4 during severe episodes
  • Negative ANA
  • Self-limited
Fibromyalgia
  • Arthralgias
  • Myalgias
  • Fatigue
  • SLE patients may have concomitant fibromyalgia as the prevalence of fibromyalgia in patients with systemic rheumatoid diseases is more.
Infections Viruses
  • Human parvovirus B19:
    • Flu-like symptoms
    • Hematologic abnormalities such as leukopenia and thrombocytopenia
    • Arthralgias or arthritis
  • Serologic assays can be diagnostic for many of these viruses
  • EBV
    • May lead to a positive ANA
    • 3020161
Human immunodeficiency virus (HIV)
Hepatitis B virus (HBV)
Hepatitis C virus (HCV)
Cytomegalovirus (CMV)
Epstein-Barr virus (EBV)
Bacterias Salmonella
Mycobacterium tuberculosis
Multiple sclerosis (MS)
  • Cranial neuropathies
  • Unilateral optic neuritis
  • Pyramidal syndrome
  • Lesions detected by magnetic resonance imaging (MRI) suggesting dissemination in space and time
Malignancies
  • Leukemia, myelodysplastic syndromes, and lymphoma
  • Hematologic abnormalities
  • Constitutional symptoms
  • Monoclonal expansion of B and T cells (as assessed by immunophenotyping)
  • Monocytosis or macrocytosis
  • Lymphoma:
    • Splenomegaly
    • Lymphadenopathy
    • Increased lactate dehydrogenase (LDH)
    • Excisional tissue biopsy specially from lymph nodes for diagnosis
Thrombotic thrombocytopenic purpura (TTP)
  • Fever
  • Thrombocytopenia
  • Microangiopathic hemolytic anemia
  • Acute renal insufficiency
  • Fluctuating neurological manifestations
  • Low levels of ADAMSTS13

References

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