What Causes It?
In half of all cases of either erythema multiforme or erythema nodosum, the exact cause is not known. In other cases, a variety of causes may result in erythema.
- Infection, primarily from the herpes simplex virus (HSV)
- Medications, such as penicillin and sulfa drugs; antiseizure medications; nonsteroidal anti-inflammatory drugs (NSAIDs)
- Infections, including mononucleosis
- Connective tissue disorders, such as lupus
- Ulcerative colitis
- Bechet disease
- Crohn disease
- Medications, such as birth control pills; sulfa drugs
Signs and Symptoms
- Fatigue, fever, and itching (before lesions appear)
- Sudden outbreak of spots, bumps, and lesions (usually on knees, elbows, palms, hands, and feet)
- Target lesions (spots surrounded by rings of normal and red skin, looking like a target)
- Erythema infectiosum (caused by a virus and known as fifth disease), rash on face and arms lasting about 2 weeks
- Fatigue, flu-like symptoms (before lesions appear)
- Clusters of nodules (small round masses) and lesions on shins, forearms, thighs, and trunk
- Red, painful lesions become soft and bluish, and fade to yellow and brown
- Joint pain
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), the most severe forms of erythema multiforme, have a different set of symptoms. Target lesions on the trunk, hacking cough, fever, and blisters around the mouth, eyes, nostrils, and anal and vaginal areas are the key symptoms of SJS. A person with TEN will have symptoms of SJS that worsen to include peeling and detachment of the skin, pus-like infections, fluid loss, and even death.
What to Expect at Your Doctor's Office
Your doctor will perform a physical exam and may order a skin biopsy, throat culture, blood test, or x-ray to determine the type of erythema. These tests also may reveal any infections or medications that are contributing to symptoms.
Treat underlying diseases and avoid known triggers (certain medications, for example). It is also important to avoid the sun when taking certain medications.Treatment Plan
Your doctor will treat any underlying diseases, stop any drugs that may contribute to symptoms, and take steps to control your current symptoms. Mild cases may not require treatment. Bed rest and medication may be necessary for more severe cases.Drug Therapies
Complementary and Alternative Therapies
- Antihistamines for itching
- Antibiotics. If you have an infection, though research suggests many cases of erythema can be resolved without antibiotics
- Antiviral medications such as acyclovir and valacyclovir, if you have a virus
- Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs)
- Burrow's compresses, a solution used to soothe skin conditions, particularly blisters
- Corticosteroids, applied to the skin (topically); corticosteroids may also be taken orally to reduce symptoms of erythema nodosum
- Intravenous immunoglobulin, used experimentally for SJS and TEN
- Photomodulation therapy, use of a light-emitting diode to accelerate the resolution of erythema
To treat erythema, you must treat the underlying cause. It is important to get a proper diagnosis from your doctor before using complementary and alternative therapies (CAM). Not all CAM therapies are appropriate for all people, and some may interact with conventional medicines or therapies. You should use CAM therapies only under the guidance of a physician. Some CAM therapies may be used to:
- Reduce inflammation
- Boost the immune system
- Prevent infections
Antioxidants are molecules that scavenge free radicals (chemicals that can damage cells). Antioxidants also may protect skin against damage caused by ultraviolet (UV) sun rays. The following antioxidants have been shown to protect skin against damage in scientific studies:
- Beta-carotene and other carotenoids (up to 300 IU per day for beta-carotene): Beta-carotene is often used as a standard treatment for sun sensitivity, although studies have been mixed. In one trial, though, 20 healthy subjects received either carotenoids alone, mainly from beta-carotene, or carotenoids plus vitamin E. Both groups improved significantly, but vitamin E did not appear to add any benefits. Scientists think the protective effect of beta-carotene comes from its antioxidant effect, so it's possible other antioxidants may also help protect skin from damage.
- Vitamin B6 (100 mg per day for 3 months): Some case reports suggest that vitamin B6 can help reduce the reaction to sunlight. You should only take high doses of vitamin B6 under a doctor's supervision, because of the risk of side effects. Vitamin B6 can interfere with Amiodarone (Cordarone), Phenobarbital (Luminal), Phenytoin (Dilantin), and possibly Levodopa. Speak with your physician if you are taking any of these medications.
- Vitamin C (1 to 3 g per day, lower dose if diarrhea develops): Vitamin C is an antioxidant, so it may provide some protection against skin damage from sunlight. Vitamin C can negatively impact certain health conditions, and can interfere with some medications. Speak with your physician.
- Vitamin E: Vitamin E is also an antioxidant, and a few studies have shown that it can offer protection from sun damage to skin when taken with vitamin C (but not alone). However, other studies have not found the same results. Vitamin E may interact with certain medications, including but not limited to, blood-thinning medications, such as warfarin (Coumadin). It may also have negative effects on people with bleeding disorders, head and neck cancers, Retinitis Pigmentosa, and other conditions.
- Vitamin D: In animal studies, vitamin D helped protect against damage from UVB rays. It is not clear yet whether vitamin D supplements may protect humans in the same way. Vitamin D can interact with some medications, including but not limited to, Digoxin and Verapamil. It may also have a negative impact on some health conditions. Speak with your physician.
- Melatonin: Applying melatonin topically (either alone or in combination with vitamin E) seems to offer some protection against sunburn in healthy people, but it is not known whether melatonin also lessens effects in people prone to erythema.
- Zinc: Zinc is necessary for healthy skin and was used in a study along with other prescription medications as a treatment for a severe form of erythema multiforme similar to TEN. In the study, 5 out of 8 people treated with zinc showed a benefit. Because high doses of zinc can be dangerous, many doctors suggest doses below 50 mg per day. Talk to your doctor to determine which dose is right for you. Zinc can interact with certain antibiotics, Cisplatin, Amiloride, and Penicillamine (used for Wilson syndrome and Rheumatoid arthritis).
Flavonoids: Some of these plant-based antioxidants may protect skin from sun damage in healthy people. In one study, German researchers found that drinking high flavonol cocoa offered protection from the sun (the cocoa used was a special formulation that is not available commercially). In another study, pomegranate fruit extract helped protect skin cells in a test tube from UV light. It is not yet known whether taking the extract would provide any benefit. However, adding fruits and vegetables to your diet to eat more flavonoids may help. You can also take these flavonoids in dried extract form. Speak with your physician first, since certain flavonoids can interact with prescription medications:
- Catechin, quercetin, hesperidin, and rutin.
- Rose hips (Rosa canina) are also high in flavonoids and may be used as a tea. Drink 3 to 4 cups per day.
- Hesperidin methyl chalcone is a water-soluble form of quercetin that may act as an antihistamine.
Green tea (Camellia sinensis) may also protect against erythema caused by UV light because it contains antioxidants.
Herbs traditionally used topically to heal damaged skin, promote lymph circulation, and possibly treat the underlying cause of various skin conditions may be helpful. You should check with your doctor before using any of these remedies. Some examples include:
- Aloe vera: Used topically for skin inflammation. One study found that aloe vera displayed anti-inflammatory effects superior to 1% hydrocortisone gel.
- Burdock root (Arctium lappa): Used topically for skin inflammation and wound healing. Never apply to an open wound.
- Calendula (Calendula officinalis): Used topically for burns, wounds, and other skin conditions. Never apply to an open wound.
- Goldenseal (Hydrastis canadensis): Used for infections, including those causing skin lesions.
- Lemon balm (Melissa officinalis): Can be applied to HSV lesions as a cream or a wash.
- Sage extract: Applied topically to reduce inflammation. In one study, sage extract significantly reduced the ultraviolet induced erythema to a similar extent as hydrocortisone.
- Slippery elm (Ulmus fulva): Applied topically, in combination with goldenseal root. Never apply to an open wound.
- Yarrow (Achillea millefolium): Applied topically for skin inflammation and wound healing. Never apply to an open wound.
Although few studies have examined the effectiveness of specific homeopathic therapies, professional homeopaths may consider the following remedies for the treatment of erythema based on their knowledge and experience. Before prescribing a remedy, homeopaths take into account a person's constitutional type, includes your physical, emotional, and psychological makeup. An experienced homeopath assesses all of these factors when determining the most appropriate treatment for an individual.
- Apis mellifica: For skin rashes that feel hot and dry and are sensitive to touch; may be accompanied by sore throat. Symptoms are relieved by cool drinks and baths and worsened by heat and warm liquids. This remedy is most appropriate for individuals who often feel sad, disappointed, or even depressed. They tend to cry easily, but may also be irritable and envious by nature. They are also not thirsty but may crave milk.
- Calendula: For burns and skin lesions that are fairly superficial. This remedy is often used after the acute phase of the skin condition has subsided to aid in complete recovery.
- Rhus toxicodendron: Used for blisters and vesicles accompanied by intense itching that worsens at night and improves with the application of heat. This remedy is most appropriate for individuals who are generally restless and unable to get comfortable at night.
- Sulphur: For skin disorders that are accompanied by fever and intense itching. This remedy is most appropriate for individuals who are thirsty, irritable while sick, lazy, and messy under ordinary circumstances, and who describe a sensation of internal heat and burning. Symptoms tend to improve with open, cold air and worsen with warmth.
When treated properly, signs and symptoms of erythema multiforme usually disappear within 4 to 6 weeks. Symptoms of erythema nodosum, however, may reappear for up to 2 years. Symptoms of SJS typically disappear in a month, but when the condition is not treated properly it may lead to blindness. Both SJS and TEN can cause death. If the drug causing either SJS or TEN is identified quickly, a person's chance of survival significantly improves.
Your doctor will monitor fluid and electrolyte levels, protein loss, and any organ damage. People with erythema multiforme may need treatment in a hospital burn unit if 20% or more of their body is affected.
If a pregnant woman develops erythema infectiosum (fifth disease), the virus can infect the fetus and cause fetal anemia, heart failure, hydrops (collection of watery fluid), and even death. Studies have also shown that pregnancy may trigger erythema nodosum.
Beers MH, Porter RS, et al. The Merck Manual of Diagnosis and Therapy. 18th ed. Whitehouse Station, NJ: Merck Research Laboratories; 2006:1642-1644.
Blumenthal M, Goldberg A, Brinckmann J, eds. Herbal Medicine: Expanded Commission E Monographs. Newton, Mass: Integrative Medicine Communications; 2000:230-239, 253-263, 419-423.
Bolognia: Dermatology. 3rd ed. St. Louis, MO: Elsevier Saunders; 2012.
Chen CW, Tsai TJ, Chen YF, Hung CM. Persistent erythema multiforme treated with thalidomide. Am J Clin Dermatol. 2008;9(2):123-7.
Dreher F, Denig N, Gabard B, Schwindt DA, Maibach HI. Effect of topical antioxidants on UV-induced erythema formation when administered after exposure. Dermatology. 1999;198(1):52-55.
Dreher F, Gabard B, Schwindt DA, Maibach HI. Topical melatonin in combination with vitamins E and C protects skin from ultraviolet-induced erythema: a human study in vivo. Br J Dermatol. 1998;139(2):332-339.
Eberlein-König B, Placzek M, Przybilla B. Protective effect against sunburn of combined systemic ascorbic acid (vitamin C) and d-alpha-tocopherol. J Am Acad Dermatol. 1998;38(1):45-48.
Fuchs J, Kern H. Modulation of UV-light-induced skin inflammation by D-alpha-tocopherol and L-ascorbic acid: a clinical study using solar simulated radiation. Free Radic Biol Med. 1998;25(9):1006-1012.
Garcia-Doval I, LeCleach L, Bocquet H, Otero XL, Roujeau JC. Toxic epidermal necrolysis and Stevens-Johnson syndrome: does early withdrawal of causative drugs decrease the risk of death? Arch Dermatol. 2000;136(3):323-327.
Garcia-Porrua C, Gonzalez-Gay MA, Vazquez-Caruncho M, et al. Erythema nodosum: etiologic and predictive factors in a defined population. Arthritis Rheum. 2000;43(3):584-592.
Geria AN, Holcomb KZ, Scheinfeld NS. Necrolytic acral erythema: a review of the literature. Cutis. 2009;83(6):309-14.
Grant WB, Holick MF. Benefits and requirements of vitamin D for optimal health: a review. Altern Med Rev. 2005 Jun;10(2):94-111. Review.
Halliday GM, Yuen KS, Bestak R, Barnetson RS. Sunscreens and vitamin E provide some protection to the skin immune system from solar-simulated UV radiation. Australas J Dermatol. 1998;39(2):71-75.
Hu JJ, Cui T, Rodriguez-Gil JL, et al. Complementary and alternative medicine in reducing radiation-induced skin toxicity. Radiat Environ Biophys. 2014;53(3):621-6.
Jonas WB, Jacobs J. Healing with Homeopathy: The Doctors' Guide. New York, NY: Warner Books; 1996:263-265.
Katiyar SK. Skin photoprotection by green tea: antioxidant and immunomodulatory effects. Curr Drug Targets Immune Endocr Metabol Disord. 2003 Sep;3(3):234-42. Review.
Katiyar SK, Matsui MS, Elmets CA, Mukhtar H. Polyphenolic antioxidant (-)-epigallocatechin-3-gallate from green tea reduces UVB-induced inflammatory responses and infiltration of leukocytes in human skin. Photochem Photobiol. 1999;69(2):148-153.
Khanna VJ, Shieh S, Benjamin J, et al. Necrolytic acral erythema associated with hepatitis C: effective treatment with interferon alfa and zinc. Arch Dermatol. 2000;136(6):755-757.
Khoury JG, Goldman MP. Use of light-emitting diode photomodulation therapy to accelerate resolution of post-intense pulsed light (IPL) erythema. J Cosmet Dermatol. 2008;7(1):30-4.
Lee J, Jiang S, Levine N, Watson RR. Carotenoid supplementation reduces erythema in human skin after simulated solar radiation exposure. Proc Soc Exp Biol Med. 2000;223(2):170-174.
Martinez AE, Atherton DJ. High-dose systemic corticosteroids can arrest recurrences of severe mucocutaneous erythema multiforme. Pediatr Dermatol. 2000;17(2):87-90.
Mert A, Kumbasar H, Ozaras R, Erten S, Tasli L, Tabak F, Ozturk R. Erythema nodosum: an evaluation of 100 cases. Clin Exp Rheumatol. 2007;25(4):563-70.
Murray M. Encyclopedia of Nutritional Supplements. Rocklin, CA: Prima Publishing; 1996:320-335.
Oresajo C, et al. Protective effects of a topical antioxidant mixture containing vitamin C, ferulic acid, and phloretin against ultraviolet-induced photodamage on human skin. J Cosmet Dermatol. 2008;7(4):290-7.
Ozcan H, Seyhan M, Yologlu S. Is metronidazole 0.75% gel effective in the treatment of seborrhoeic dermatitis? A double-blind, placebo controlled study. Eur J Dermatol. 2001;17(4):313-6.
Passarini B, Infusino SD. Erythema nodosum. G Ital Dematol Venereol. 2013;148(4):413-7.
Requena L, Sanchez Yus E. Erythema Nodosum. Dermatologic Clinics. 2008;26(4).
Reuter J, Jocher A, Hornstein S, Monting JS, Schempp CM. Sage extract rich in phenolic diterpenes inhibits ultraviolet-induced erythema in vivo. Planta Med. 2007;73(11):1190-1.
Reuter J, Jocher A, Stump J, Grossjohann B, Franke G, Schempp CM. Investigation of the anti-inflammatory potential of Aloe vera gel (97.5%) in the ultraviolet erythema test. Skin Pharmacol Physiol. 2008;21(2):106-10.
Schwartz R, Nervi S. Erythema Nodosum: A Sign of Systemic Disease. Am Fam Phys. 2007;75(5).
Sies H, Stahl W. Nutritional protection against skin damage from sunlight. Annu Rev Nutr. 2004;24:173-200. Review.
Sinclair SA, Reynolds NJ. Necrolytic migratory erythema and zinc deficiency. Br J Dermatol. 1997;136(5):783-785.
Stahl W, Heinrich U, Jungmann H, Sies H, Tronnier H. Carotenoids and carotenoids plus vitamin E protect against ultraviolet light-induced erythema in humans. Am J Clin Nutr. 2000;71(3):795-798.
Stern RS. Improving the outcome of patients with toxic epidermal necrolysis and Stevens-Johnson syndrome. Arch Dermatol. 2000;136(3):410-411.
Stupica D, Lusa L, Ruzic-Sabljic E, Cerar T, Strle F. Treatment of erythema migrans with doxycycline for 10 days versus 15 days. Clin Infect Dis. 2012;55(3):343-50.
Taylor SC, Averyhart AN, Heath CR. Postprocedural wound-healing efficacy following removal of dermatosis papulosa nigra lesions in an African American population: a comparison of a skin protectant ointment and a topical antibiotic. J Am Acad Dermatol. 2011;64(3 Suppl):S30-5.
Vickers AJ. Independent replication of pre-clinical research in homoeopathy: a systematic review. Forsch Komplementarmed. 1999;6(6):311-320.
Webb AR, Engelsen O. Ultraviolet exposure scenarios: risks of erythema from recommendations on cutaneous vitamin D synthesis. Adv Ex Med Biol. 2014;810:406-22.