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]

Differentiating systemic lupus erythematosus from other diseases

		Overlapping Features	Distinguishing/specific features
Rheumatoid arthritis (RA)
Rhupus
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 21959290
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	maintain an undefined profile and have a mild disease course
Systemic sclerosis (SSc)			sclerodactyly, telangiectasias, calcinosis, and malignant hypertension with acute renal failure are more consistent with SSc positive ANA is present in most patients with SSc, while other serologies such as anti-double-stranded DNA (dsDNA) and anti-Smith (Sm) antibodies antibodies to an antigen called Scl-70 (topoisomerase I) or antibodies to centromere proteins
Sjögren’s syndrome		Extra-glandular manifestations neurologic and pulmonary abnormalities	keratoconjunctivitis sicca and xerostomia, and characteristic findings on salivary gland biopsy commonly express antibodies to Ro and La antigens
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	ANA-negative
Behçet’s syndrome		Oral aphthae inflammatory eye disease, neurologic disease, vascular disease, and arthritis	male dominancy and ANA-negative vascular involvement of any size (small, medium, large) is more common
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)	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, and lymphadenopathy	leukocytosis Negative ANA
Kikuchi’s disease		lymphadenopathy as well as fever, myalgias, arthralgias, and, less commonly, hepatosplenomegaly	May be associated with SLE Spontaneous remission often occurring within four months lymph node biopsy, which reveals a histiocytic cellular infiltrate.
Serum sickness		fever, lymphadenopathy, cutaneous eruptions, and arthralgias during severe episodes, complement measurements including C3 and C4 can be depressed, as in SLE	ANAs are typically negative and the course tends to be self-limited
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.
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
		tuberculosis
Multiple sclerosis (MS)		cranial neuropathies	Unilateral optic neuritis and pyramidal syndrome, with lesions detected by magnetic resonance imaging (MRI) suggesting dissemination in space and time are characteristic of MS
Malignancies		Leukemia or myelodysplastic syndromes hematologic and constitutional symptoms similar to those observed in SLE lymphoma	Monoclonal expansion of B and T cells (as assessed by immunophenotyping), monocytosis, or macrocytosis can distinguish these malignancies from SLE Splenomegaly, lymphadenopathy, or increased lactate dehydrogenase (LDH) levels that are not observed in SLE but in lymphoma Excisional tissue biopsy specially from lymph nodes in the case of lymphomas
Thrombotic thrombocytopenic purpura (TTP)		fever and thrombocytopenia	Microangiopathic hemolytic anemia Acute renal insufficiency Fluctuating neurological manifestations Low levels of ADAMSTS13