Erythema Marginatum · What Is It, Causes, Signs and Symptoms, Diagnosis, and More

Several medical conditions can cause erythema marginatum. The most common is rheumatic fever, an inflammatory disease that can damage the heart tissue and lead to rheumatic heart disease. Rheumatic fever develops after streptococcal pharyngitis, or strep throat, a bacterial infection of the throat caused by Streptococcus pyogenes (i.e., Group A streptococcus), characterized by fever and sore throat. 

Erythema marginatum may also be a sign of hereditary angioedema, a condition usually caused by a deficiency of the C1 esterase inhibitor. This protein regulates the complement system (i.e., part of the immune system that helps antibodies and phagocytic cells fight infections). Angioedema typically refers to localized skin swelling; however, some angioedema attacks may be characterized as anaphylactic reactions, which are systemic, severe, and often life-threatening.   

Another cause of erythema marginatum is Lyme disease, an infectious disease caused by the bacterium Borrelia burgdorferi. It is a vector-borne infection transmitted by the bite of an infected deer tick, which is usually found in wooded areas, thick brush, and tall grass. It’s important to note that in Lyme disease, most individuals present with the characteristic bull’s-eye rash, an expanding rash with target-like appearance also known as erythema migrans, but may also experience erythema marginatum.   

Finally, allergic reactions to certain medications, such as the combination antibiotic amoxicillin-clavulanate (i.e., Augmentin), can cause erythema marginatum.  

Diagnosis of erythema marginatum and identification of the underlying medical condition is based on the patient's medical history, physical examination, and various diagnostic tests. Other types of skin rashes that should also be considered and excluded include erythema migrans, which tends to stay localized in one location; erythema multiforme, appearing as raised, crusted patches that can spread over the body; and erythema annulare centrifugum, which appears as itchy scales usually on the thighs and legs.  

Rheumatic fever is typically suspected if there is a history of Group A streptococcal infection. The major criteria for rheumatic fever diagnosis, collectively known as the Jones criteria, include five signs: non-pruritic erythema marginatum, arthritis, carditis, subcutaneous nodules, and Sydenham chorea. Some minor criteria may help make the diagnosis, such as fever; joint pain; changes in an individual’s electrocardiogram (ECG); elevated inflammatory markers, like C-reactive protein; and a blood test that shows evidence of previous streptococcal infection, known as anti-streptolysin-O, or ASO.  

Blood tests to assess levels of complement C1 inhibitor may also be ordered if hereditary angioedema is suspected. Diagnosis of Lyme disease can be confirmed using tests that detect antibodies against Borrelia burgdorferi, such as enzyme-linked immunosorbent assay (ELISA), or immunofluorescence assay (IFA). These can be followed by Western blot, the gold standard for detecting IgG antibodies against Borrelia burgdorferi. Finally, the diagnosis of an allergic reaction is typically based on the patient's history and physical exam.  

Treatment of erythema marginatum depends on the underlying cause. In rheumatic fever, antibiotics such as penicillin are used to treat the underlying streptococcal infection, and anti-inflammatory medications, like aspirin, to reduce pain and inflammation.  

Although hereditary angioedema cannot be cured, medication such as icatibant, which can reduce swelling, and C1 esterase inhibitor replacement, can increase the levels of C1 esterase inhibitor in the body. Fresh frozen plasma is sometimes used to improve symptoms during acute episodes. Finally, plasma kallikrein inhibitors (e.g., berotralstat) and androgenic hormones (e.g., danazol) can be used to prevent future attacks.  

Lyme disease management includes oral antibiotics, such as doxycycline, cefuroxime, and amoxicillin and intravenous antibiotics (e.g., ceftriaxone) for individuals with systemic complications such as carditis or meningitis.  

Lastly, treatment of allergic reactions can include withdrawing the offending agent (when applicable), as well as a variety of medications, such as antihistamines (e.g., loratadine) and corticosteroids (e.g., prednisone). Severe allergic reactions can be treated with epinephrine.