Micrograph showing vacuolar interface dermatitis, as may be seen in SLE. H&E stain. section of human skin prepared for direct immunofluorescence using an anti-IgG antibody. The skin is from a person with systemic<unk>  erythematosus and shows IgG deposits at two different places. The first is a bandlike deposit along the epidermal basement membrane <unk>  band test" is positive); the second is within the nuclei of the epidermal cells (antinuclear antibodies are present). Laboratory tests Antinuclear antibody (ANA) testing and anti-extractable nuclear antigen (anti-ENA) form the mainstay of serologic testing for SLE. If ANA is negative the disease can be ruled out. Several techniques are used to detect ANAs. The most widely used is indirect immunofluorescence (IF). The pattern of fluorescence suggests the type of antibody present in the people's serum. Direct immunofluorescence can detect deposits of immunoglobulins and complement proteins in people's skin. When skin not exposed to the sun is tested, a positive direct IF (the so-called<unk>  band test) is evidence of systemic<unk>  erythematosus. ANA screening yields positive results in many connective tissue disorders and other autoimmune diseases, and may occur in normal individuals. Subtypes of antinuclear antibodies include anti-Smith and anti-double stranded DNA (dsDNA) antibodies (which are linked to SLE) and anti-histone antibodies (which are linked to drug-induced<unk> . Anti-dsDNA antibodies are highly specific for SLE; they are present in 70% of cases, whereas they appear in only 0.5% of people without SLE. The anti-dsDNA antibody titers also tend to reflect disease activity, although not in all cases. Other ANA that may occur in people with SLE are anti-U1 RNP (which also appears in systemic sclerosis and mixed connective tissue disease), SS-A (or anti-Ro) and SS-B (or anti-La; both of which are more common in Sjögren's syndrome). SS-A and SS-B confer a specific risk for heart conduction block in neonatal<unk> . Other tests routinely performed in suspected SLE are complement system levels (low levels suggest consumption by the immune system), electrolytes and kidney function (disturbed if the kidney is involved), liver enzymes, and complete blood count. The<unk>  erythematosus (LE) cell test was commonly used for diagnosis, but it is no longer used because the LE cells are only found in 50–75% of SLE cases and they are also found in some people with rheumatoid arthritis, scleroderma, and drug sensitivities. Because of this, the LE cell test is now performed only rarely and is mostly of historical significance. Diagnostic criteria Some physicians make a diagnosis based on the American College of Rheumatology (ACR) classification criteria. The criteria, however, were established mainly for use in scientific research including use in randomized controlled trials which require higher confidence levels, so many people with SLE may not pass the full criteria. Criteria The American College of Rheumatology (ACR) established eleven criteria in 1982, which were revised in 1997 as a classificatory instrument to operationalise the definition of SLE in clinical trials. They were not intended to be used to diagnose individuals and do not do well in that capacity. For the purpose of identifying people for clinical studies, a person has SLE if any 4 out of 11 symptoms are present simultaneously or serially on two separate occasions. # Malar rash (rash on cheeks); sensitivity = 57%; specificity = 96%. # Discoid rash (red, scaly patches on skin that cause scarring); sensitivity = 18%; specificity = 99%. # Serositis: Pleurisy (inflammation of the membrane around the lungs) or pericarditis (inflammation of the membrane around the heart); sensitivity = 56%; specificity = 86% (pleural is more sensitive; cardiac is more specific). # Oral ulcers (includes oral or nasopharyngeal ulcers); sensitivity = 27%; specificity = 96%. # Arthritis: nonerosive arthritis of two or more peripheral joints, with tenderness, swelling, or effusion; sensitivity = 86%; specificity = 37%. # Photosensitivity (exposure to ultraviolet light causes rash, or other symptoms of SLE flareups); sensitivity = 43%; specificity = 96%. # Blood—hematologic disorder—hemolytic anemia (low red blood cell count), leukopenia (white blood cell count<4000/µl), lymphopenia (<1500/µl), or low platelet count (<100000/µl) in the absence of offending drug; sensitivity = 59%; specificity = 89%. Hypocomplementemia is also seen, due to either consumption of C3 and C4 by immune complex-induced inflammation or to congenitally complement deficiency, which may predispose to SLE. # Renal disorder: More than 0.5 g per day protein in urine or cellular casts seen in urine under a microscope; sensitivity = 51%; specificity = 94%. # Antinuclear antibody test positive; sensitivity = 99%; specificity = 49%. # Immunologic disorder: Positive anti-Smith, anti-ds DNA, antiphospholipid antibody, or false positive serological test for syphilis; sensitivity = 85%; specificity = 93%. Presence of anti-ss DNA in 70% of cases (though also positive with rheumatic disease and healthy persons). # Neurologic disorder: Seizures or psychosis; sensitivity = 20%; specificity = 98%. Other than the ACR criteria, people with<unk>  may also have: * fever (over 100 °F/ 37.7 °C) * extreme fatigue * hair loss * fingers turning white or blue when cold (Raynaud's phenomenon) Criteria for individual diagnosis Some people, especially those with antiphospholipid syndrome, may have SLE without four of the above criteria, and also SLE may present with features other than those listed in the criteria. Recursive partitioning has been used to identify more parsimonious criteria. This analysis presented two diagnostic classification trees: # Simplest classification tree: SLE is diagnosed if a person has an immunologic disorder (anti-DNA antibody, anti-Smith antibody, false positive syphilis test, or LE cells) or malar rash. It has sensitivity = 92% and specificity = 92%. # Full classification tree: Uses 6 criteria. It has sensitivity = 97% and specificity = 95%. Other alternative criteria have been suggested, e.g. the St. Thomas' Hospital "alternative" criteria in 1998.
Lupus
Scleroderma
Tumid lupus erythematosus
Serum sickness
Psoriasis
Huntington's disease
Vitiligo
Rheumatoid arthritis