| Cause | Parvovirus B19 infection | Primarily associated with acute rheumatic fever (following streptococcal pharyngitis), but can also be seen in hereditary angioedema, and Lyme disease. | Lyme disease | Often triggered by infections (especially HSV), but can also be caused by medications, vaccinations and other infections. | Can be idiopathic (up to 55% of cases). Associated with infections (streptococcal infections, TB, etc.), sarcoidosis, IBD, pregnancy, medications (sulfa drugs, oral contraceptives). |
| Appearance | Classic “slapped-cheek” appearance (bright red rash on face), followed by a lacy, reticular rash on the trunk and extremities. | Evanescent (fades in and out), non-pruritic, blanchable, pink to red macules or papules that spread peripherally, forming rings or polycyclic shapes with central clearing. | Expanding, round or oval erythematous patch at the site of a tick bite. May have a “bull’s-eye” appearance (central clearing), but this is not always present. | ”Target” lesions (classic): concentric rings of color variation. May also have atypical raised papules. Distribution is symmetrical, often on extremities (especially hands and feet). | Tender, erythematous, subcutaneous nodules or plaques, typically on the shins (anterior lower legs), but can also appear on knees and arms. Lesions evolve, becoming bruise-like. |
| Location | Starts on the face (cheeks), then spreads to trunk and extremities. | Primarily on trunk and proximal extremities; spares the face. | Starts at the site of the tick bite (can be anywhere on the body). | Often favors extremities (especially hands, feet, elbows, knees), but can be widespread. Mucosal involvement (mouth, genitals, eyes) is possible, especially in Erythema Multiforme Major. | Primarily on the shins (anterior lower legs), but can involve other areas. |
| Other Symptoms | Mild fever, malaise, myalgias, headache, sometimes diarrhea and vomiting. In adults, may cause joint pain (arthralgia/arthritis). | Associated with other symptoms of rheumatic fever (fever, joint pain, carditis). Lesions themselves are typically asymptomatic (non-itchy, non-painful). | May be accompanied by flu-like symptoms (fatigue, headache, fever, muscle/joint pain). | May have prodromal symptoms (fatigue, fever, itching) before skin lesions. Lesions can be painful, itchy or swollen. | Often preceded or accompanied by fever, malaise, and joint pain (arthralgia, especially ankles). |
| Duration | Rash typically lasts 1-3 weeks. | Evanescent; may appear and disappear within hours, or last for days to weeks, often recurring. | Expands over days to weeks. Can persist for weeks to months if untreated. | Usually self-limiting, resolving within 2-4 weeks (minor) or longer (major). Can be recurrent, especially if associated with HSV. | Typically resolves within 3-6 weeks, but can last longer depending on the underlying cause. |
| Diagnosis | Usually a clinical diagnosis based on the characteristic rash. Parvovirus B19 serology (IgG, IgM) or PCR can confirm. | Clinical diagnosis, often in the context of rheumatic fever. | Clinical diagnosis based on history of tick bite and characteristic rash. Serological tests for Lyme disease are often unreliable in early stages. | Clinical diagnosis based on appearance and distribution of lesions. Biopsy can be helpful, but is not always necessary. Identify and treat underlying cause (e.g., HSV). | Clinical diagnosis. Investigations to identify underlying cause may include throat swab (for strep), chest X-ray (for sarcoidosis, TB), and blood tests. Skin biopsy can confirm. |
| Treatment | Symptomatic treatment (rest, fluids, pain relievers). | Treat underlying condition (rheumatic fever). The rash itself does not require specific treatment. | Antibiotics (doxycycline, amoxicillin, or cefuroxime). | Mild cases may not require treatment. Antiviral medication (acyclovir) for HSV-related EM. Topical corticosteroids for symptomatic relief. Severe cases may require systemic steroids. | Treatment of underlying cause. Rest, leg elevation, NSAIDs for pain and inflammation. Potassium iodide or systemic corticosteroids may be used in some cases. |