Differentiating systemic lupus erythematosus from other diseases

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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 skin rash, arthritis, positive autoimmune serology, weight loss, fevers and chronic pain, 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 skin rash, arthritis, positive autoimmune serology, weight loss, fevers and chronic pain, such as rheumatoid arthritis(RA), mixed connective tissue disease (MCTD), systemic sclerosis (SSc), dermatomyositis (DM), polymyositis(PM), and other autoimmune diseases.

Differetiating SLE from other diseases that cause arthritis and rash

n		Arthritis				Auto-antibodies								Rash pattern	Distinguishing/specific features
		Polyarthritis	Tenderness	Edema	Deformity /Erosion	ANA	RF	Anti-CCp	anti U1RNP	AntiSm	AntiRo	Anti-dsDNA	Raynaud phenamon
Rheumatoid arthritis (RA)		+	+	+	+		↑↑	↑↑					+	Serositis Sicca symptoms (photosensitivity, dry eyes, dry mouth) 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 Rheumatoid factor (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)
Undifferentiated connective tissue disease (UCTD)		+				↑	↑			↑			+	erythematous macules, patches, or papules with delicate scale mostly in lower extremities	sclerodactyly telangiectasias calcinosis malignant hypertension acute renal failure
Systemic sclerosis (SSc)		+/-	+	+	+/-	↑↑				↑		↑	+	skin thickening and hardening Edematous swelling and erythema	Sclerodactyly Telangiectasias Calcinosis Malignant hypertension acute renal failure
Sjögren’s syndrome 15485020		+/-	+/-			↑					↑			Xerosis ry, scaly skin, most often affecting the lower extremities and axillary creases annular erythema	Keratoconjunctivitis sicca Xerostomia
Vasculitis	Giant cell		+	+										Rare	cranial branches of arteries visual loss
	Takayasu		+/-	+/-										erythema nodosum or pyoderma gangrenosum
	Poly-arteritis nodosa		+/-											tender erythematous nodules, purpura, livedo reticularis, ulcers, and bullous or vesicular eruption
Behçet’s syndrome		+/-	+/-	+/-										acneiform lesions, papulo-vesiculo-pustular eruptions, pseudofolliculitis, nodules, erythema nodosum (septal panniculitis), superficial thrombophlebitis, pyoderma gangrenosum-type lesions, erythema multiforme-like lesions, and palpable purpura.	Male dominancy ANA-negative
Kikuchi’s disease			+/-			↑/↓								Transient skin rashes similar to rubella or drug-induced eruptions malar rash erythematous macules, patches, papules, or plaques	May be associated with SLE
Serum sickness		+/-	+	+/-										pruritic rash urticarial and/or serpiginous macular rash	Negative ANA Self-limited
Infections	Viruses													Human parvovirus B19: Flu-like symptoms (fever,malaise, dry cough, loss of appetite, body aches) 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
														Human immunodeficiency virus (HIV)
														Hepatitis B virus (HBV)
														Hepatitis C virus (HCV)
														Cytomegalovirus (CMV)
														Epstein-Barr virus (EBV)
	Bacterias													Salmonella
														Mycobacterium tuberculosis