Laboratory Tests for Unidentified Circular Red Rash in Adults
For an unidentified circular red rash in adults, a skin biopsy is the most essential laboratory test to establish the diagnosis, accompanied by a complete blood count, erythrocyte sedimentation rate, and C-reactive protein to assess for systemic inflammation. 1
Initial Laboratory Evaluation
The diagnostic approach to an unidentified circular red rash should be guided by the clinical presentation and history. The following tests are recommended:
Complete blood count (CBC) with differential - To detect potential eosinophilia (suggesting allergic or parasitic conditions), leukopenia (may indicate systemic lupus erythematosus), or thrombocytopenia (seen in various inflammatory conditions) 1, 2
Erythrocyte sedimentation rate (ESR) - Useful for monitoring chronic inflammatory conditions and provides information about the acute phase response 3, 2
C-reactive protein (CRP) - More sensitive for acute inflammatory conditions and infections; rises and falls more rapidly than ESR 3, 4
Comprehensive metabolic panel - To assess liver function, as hepatic abnormalities may be present in up to 50-75% of patients with certain inflammatory conditions 1
Skin biopsy - Essential for histopathological examination to distinguish between various dermatological conditions; should be taken from lesional skin, just adjacent to any blister if present 1
Additional Tests Based on Clinical Suspicion
If Urticaria is Suspected:
Thyroid function tests and thyroid autoantibodies - Particularly important if chronic urticaria is suspected, as thyroid autoimmunity is more prevalent (14%) in chronic ordinary urticaria than in the general population (6%) 1
Autologous serum skin test (ASST) - For screening of autoimmune urticaria in centers with experience performing this test 1
If Vasculitis is Suspected:
Serum complement assays (C3 and C4) - To distinguish normocomplementaemic from hypocomplementaemic urticarial vasculitis 1
Lesional skin biopsy - Essential to confirm small-vessel vasculitis histologically 1
If Tickborne Illness is Suspected:
Serology for tickborne diseases - Including tests for Rocky Mountain spotted fever, ehrlichiosis, and anaplasmosis, especially if the patient has been in endemic areas 1
PCR testing - For specific pathogens such as Ehrlichia chaffeensis or Anaplasma phagocytophilum 1
If Angioedema is Present:
Serum C4 - Initial screening test for hereditary and acquired C1 inhibitor deficiency 1
C1 inhibitor quantitative and functional assays - If C4 is low, to confirm C1 inhibitor deficiency 1
Special Considerations
Discordance between ESR and CRP occurs in approximately 12% of patients and may provide diagnostic clues. High CRP with normal ESR is often seen in infections, while high ESR with normal CRP may indicate connective tissue diseases or stroke 4, 5
Ferritin levels should be considered, particularly if Adult-Onset Still's Disease is suspected, as very high levels (4,000-30,000 ng/ml) are common in this condition 1
Mycoplasma serology should be included if the rash is accompanied by respiratory symptoms 1
Bacterial cultures from lesional skin should be obtained if infection is suspected 1
Pitfalls and Caveats
Laboratory tests should be guided by the clinical presentation and not performed indiscriminately in all patients 1
The diagnosis of many rash conditions is primarily clinical, with laboratory tests serving as confirmatory tools 1
For urticaria, no investigations are required for the majority of patients with mild disease responding to antihistamines 1
False-positive and false-negative results can occur with many tests, so results should always be interpreted in the clinical context 1
Documentation of the rash's appearance, distribution, and progression is crucial for diagnosis and should accompany laboratory testing 1