Introduction:
Erythema marginatum is a blanchable, nonpruritic, not itchy, macular rash, and reactive inflammatory erythema commonly associated with acute rheumatic fever. It is of diagnostic value for acute rheumatic fever and other rare diseases. It is seen in the trunk and extremities of the body. In acute rheumatic fever, mortality can be prevented, but a quarter million people are dying because of this disease in poor and developing countries. With proper diagnosis and treatment, most deaths can be prevented. In developing nations, the ratio of disease occurrence is 100-200 per 100,000 people. The disease is related to poverty, overcrowding, and poor medical care. The condition is caused by Streptococcal infection. Every Streptococcus does not cause acute rheumatic fever. There is a particular type of Streptococcus that can produce acute rheumatic fever. They can cause disease only if involved in specific areas of the body. For example, the Streptococcus that consists of the throat only causes this fever. If it is present in other parts of the body, they do not cause the infection. The streptococcus present in the throat is followed by acute rheumatic fever. The streptococcal condition that causes sore throat, pharyngitis, and upper respiratory infections lead to acute rheumatic fever. Only three percent of the population develops this fever.
What Causes Acute Rheumatic Fever?
Acute rheumatic fever is caused by:
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Only beta-hemolytic streptococcus causes acute rheumatic fever. The fever is more common in children between 5 to 15 years of age.
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Acute rheumatic fever is caused by beta-hemolytic Streptococcus, a rheumatogenic strain of the Lancefield group. Once the infection has started, it takes two to four weeks to develop into a full-fledged immune response. The immune response triggered by Streptococcal infection will inappropriately cross-react with our tissues because some bacterial antigens are similar to human antigens. As a result, the immune system produces antibodies against the antigen. The immune system is supposed to attack bacterial antigens attack our tissues because the bacterial antigen structurally mimics our antigens. For example, the bacteria's cell wall containing the carbohydrate antigens is structurally very similar to heart valves.
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Post streptococcal infection, multisystem immune-mediated non-suppurative inflammation will occur, such as the cardiac tissues, skin, synovial joints, subcutaneous tissue, and the central nervous system.
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Since the rash is severe, lots of cytokines are produced. These cytokines go to the hypothalamus and precipitate fever. During rheumatic fever, multiple systems are inflamed.
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It produces symptoms such as sore throat, pharyngitis, or upper respiratory infection. Not all individuals are affected by the disease. Only three percent of the genetically vulnerable population is susceptible to the disease.
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The beta-hemolytic Streptococcus produces a toxin called hemolysin that clears the surrounding red blood cells in blood agar.
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Hemolysin attacks the mucosa and causes inflammation of the pharynx. Macrophages will produce antibodies. The fever subsides after the initial immune response in the average population. Still, in genetically susceptible people (three percent of the population), the fever does not subside, and the infection attacks other body parts.
What Is Erythema Marginatum in Acute Rheumatic Fever?
Erythema marginatum is a blanchable, non-suppurative, nonpruritic macular rash, reactive inflammatory erythema.
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Some of the skin antigens are very similar to bacterial antigens. So the immune system that attacks the bacteria may also react with the skin.
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In the skin, it will produce a particular type of lesions. The lesions form small macules that rapidly grow up, and when these macules quickly grow up, their centers heal, and their margins become very prominent. An inflamed, red area initially develops, and then they become more pronounced.
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Once the central location is healed, the inflammation starts moving to the margin of the lesion. Due to this reason, the lesions are called erythema marginatum. The lesions are red, especially in the margins that are advancing.
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The skin develops erythematous macules, rapidly developing and becoming large, while their central areas start healing. These are usually painless and are more commonly seen in the significant part of the body, less in the peripheral portion, and more on the trunk, the hands, and the feet while sparing the face.
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The condition will heal entirely, and no long-term complications will be seen. The common diseases associated with erythema marginatum include psittacosis and CI esterase inhibitor (hereditary angioedema).
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Erythema marginatum is reported in six percent of patients with acute rheumatic fever. The pathogenesis for lesions in hereditary angioedema is bradykinin because dense stromal and endothelial deposits of bradykinin are found in the biopsy specimen from the lesions of erythema marginatum from the hereditary angioedema patients.
What Are the Characteristics of Erythema Marginatum in Acute Rheumatic Fever?
The rash can be difficult to detect in dark people. It is not found on palms and soles. The rash appears as pink or red macules (flat spots) or papules (small lumps), which spread outwards in a circular shape. Later the edges become raised and red. The center gets cleared. They are not painful or itchy. It may go unnoticed by the patient. They can fade after some time and reappear within hours and in hot conditions. They persist for weeks or months, even after the successful treatment of acute rheumatic fever.
What Are the Diagnostic Test for Erythema Marginatum?
The laboratory investigations include:
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The complete blood count is done to look for rising antibodies against Streptococcus. The most commonly used tests are plasma antistreptolysin O and the anti-deoxyribonucleases B titers. Throat swabs and rapid antigen tests need to be more accurate.
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Erythrocyte sedimentation rate.
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Blood culture.
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EKG (electrocardiography) and echocardiography to identify heart involvement.
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Skin biopsy - The skin biopsy findings of erythema marginatum are nonspecific and consist of a perivascular mixed inflammatory infiltrate with neutrophilic predominance. Later stages are characterized by erythrocyte extravasation.
What Are the Treatments for Erythema Marginatum?
Following the initial attack, the patients are treated with penicillin. Continuous penicillin is given to patients with established heart disease. Constant antibiotics are given every four weeks for 15 years. Some patients may require lifelong treatment. In addition, aspirin is given for inflammation. There is no specific therapy for the skin condition as it is self-limited. In addition, treating underlying rheumatic fever does not alter the clinical course of the skin lesions. Traditional treatment methods include fresh frozen plasma infusion during acute attacks and short- and long-term prevention for patients with hereditary angioedema. Prophylaxis with plasma-derived or recombinant C1 esterase inhibitor infused at the time of appearance of the heralding erythema marginatum lesions is effective. Doxycycline at 100 mg every 12 hours for two weeks has been considered a treatment of choice for psittacosis. Macrolides, such as Azithromycin and Fluoroquinolones (third line), may be used for conditions where tetracyclines are contraindicated.
Conclusion:
Primary prevention is to avoid overcrowding and poor medical care, which has been identified as the most crucial reason for rheumatic fever. In addition, the patients initially have an unnoticed sore throat. So the patients are advised to seek medical opinions for sore throat, skin rash, fever, and joint pain.
