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Erythema Multiforme

Erythema multiforme is a rare skin condition characterized by targetoid lesions.


The most common sign of EM is the presence of a target lesions, although they may not always be present and variable mucous membrane involvement [7]. EM minor presents as a mild to severe rash consisting of erythematous papules that are usually ranged symmetrically on the extremities and gradually enlarge. The typical lesions can develop a raised, edematous, pale ring and the outer edges will become a cyanotic or violaceous halo. After the inflammation resolves, hyperpigmentation or hypopigmentation can occur. Some affected individuals may experience pruritus and a burning sensation.

  • EM major often starts with a fever and joint aches. Besides the skin sores and mouth sores, there may be sores in the eyes, genitals, lung airways, or gut. Your health care provider will look at your skin to diagnose EM.[nlm.nih.gov]
  • Syphilis, erythema multiforme, fever and rash, fever of unknown origin Syphilis is a sexually transmitted disease known to present with highly variable manifestations, especially when left untreated.[ejcrim.com]
  • The patient was referred to Texas A&M Health Science Center's Baylor College of Dentistry for biopsy of recurrent mouth ulcers following an outbreak of a fever blister.[ncbi.nlm.nih.gov]
  • We report on the case of a 4 years old boy presenting high-grade fever associated with erythema multiforme and evidence of systemic inflammation who showed a good response to prompt treatment with intravenous immunoglobulins.[ncbi.nlm.nih.gov]
  • Blood test performed in 4 th day of fever confirmed the picture of systemic inflammation (Table 1 ). In 6 th day of fever the child showed mild bilateral bulbar conjunctival injection without exudate.[ijponline.biomedcentral.com]
  • Systemic side effects of PCV13 include chills, fever, headache, vomiting, fatigue, arthralgia, myalgias, decreased appetite, and diarrhea, whereas its cutaneous adverse reactions are local injection site reactions, Sweet's syndrome, and deep morphea.[ncbi.nlm.nih.gov]
  • Your child has a fever or chills. Watch closely for changes in your child's health, and be sure to contact your doctor or nurse call line if: Your child's rash is changing or getting worse. Your child does not get better as expected.[myhealth.alberta.ca]
  • Symptoms include fever, chills, fatigue, bloodshot eyes, eye pain, mouth sores, dry eyes, vision problems, general ill feeling, weakness and painful joints. Skin lesions will appear on the skin, a few to hundreds could erupt.[advanced-dermatology.com.au]
  • However, erythema multiforme major may be preceded by mild symptoms such as fever or chills, weakness or painful joints. Skin lesions Typically in erythema multiforme, few to hundreds of skin lesions erupt within a 24-hour period.[dermnetnz.org]
  • A week later, he was found to have oral candidiasis as well as multiple scaly erythematous plaques on the palms and soles, raising the suspicion of secondary syphilis and HIV infection, which were confirmed by positive syphilis serology (VDRL 1:256; TPHA[medicaljournals.se]
  • Recurrent EM is most commonly associated with the presence of recurrent outbreaks of oral/genital HSV, however, it has been reported in association with other recurrent infection with Mycoplasma pneumoniae, vulvovaginal candidiasis, chronic hepatitis[cancertherapyadvisor.com]
  • […] subtypes Most commonly reported causes Isolated Infections HSV Mycoplasma pneumoniae Drugs NSAIDs Sulfonamides Antiepileptics Antibiotics Recurrent ( 6 episodes of EM per year) Infections HSV infection M. pneumoniae infection Hepatitis C Vulvovaginal candidiasis[onlinelibrary.wiley.com]
  • Other reported causes of recurrent EM include recurrent M pneumoniae infections, hepatitis C virus, vulvovaginal candidiasis, complex aphthosis, menses, polymorphic light eruption, and ingestion of benzoic acid, a preservative in food.[clinicaladvisor.com]
Hodgkin's Disease
  • The remaining chapters concentrate on major inflammatory skin diseases and lymphoproliferative disorders, including chronic lymphocytic leukemia, lupus, adult T cell leukemia, and primary cutaneous Hodgkin's disease.[books.google.de]
Chronic Diarrhea
  • The authors report a 67-year-old Asian male who presented with chronic diarrhea and developed erythema multiforme-like cutaneous lesions. A skin biopsy revealed extensive pagetoid spread of atypical lymphocytes in the epidermis.[ncbi.nlm.nih.gov]
Aphthous Stomatitis
  • Oral lesions must be distinguished from aphthous stomatitis, pemphigus, herpetic stomatitis, and hand-foot-and-mouth disease.[msdmanuals.com]
  • . • In the presence of oral lesions, – Aphthous stomatitis, – Contact dermatitis or stomatitis – Acute necrotizing gingivitis – Pemphigus, – Dermatitis herpetiformis, – Bullous lichen planus, – herpes zoster, – chickenpox – Toxic epidermal necrolysis[slideshare.net]
Sore Mouth
  • A very sore mouth may lead to dehydration and poor nutrition. Genitourinary lesions may result in urinary retention. If the eye is involved it is important to prevent infection or conjunctival scarring.[patient.info]
Red Eye
  • Other symptoms may include itchy or red eyes, eye pain, and abnormalities in vision. Kids affected by this condition may have itchy rashes that cause a burning sensation. The rash turns brown as it goes away.[news-medical.net]
  • eyes sensitivity to light and blurred vision aching joints These symptoms are more common in erythema multiforme major or a similar condition called Stevens-Johnson syndrome.[nidirect.gov.uk]
  • eyes sensitivity to light and blurred vision aching joints These symptoms are more common in erythema multiforme major or a similar condition called Stevens-Johnson syndrome .[nhs.uk]
  • Skin biopsy specimen showed compatible drug eruption. The discontinuation of crizotinib improved her eruption within one week.[ncbi.nlm.nih.gov]
  • […] usually occurring on the dorsal aspect of the hands and forearms Skin and mucous membrane disease characterized by an eruption of macules, papules, nodules, vesicles, and/or bullae with characteristic bull's-eye lesions usually occurring on the dorsal[icd9data.com]
  • We diagnosed the secondary widespread lesion as an EM-type drug eruption induced by acyclovir, or an EM associated with herpes zoster.[ncbi.nlm.nih.gov]
  • BACKGROUND: Mycoplasma pneumoniae infection is associated with extrapulmonary complications, including mucocutaneous eruptions.[ncbi.nlm.nih.gov]
  • Lesions characteristic for erythema multiforme may appear during the episode of acute contact dermatitis or may follow a nearly resolving vesicular eczematous eruption.[ncbi.nlm.nih.gov]
  • Three months after completing radiation therapy, he developed a pruritic red lesion within his radiation port on his right mid back with the formation of blisters a week later.[ncbi.nlm.nih.gov]
  • M pneumoniae patients were older at presentation (P .03) and more frequently had sore throat (P .01) and atypical targets with central blistering (P .01).[ncbi.nlm.nih.gov]
  • The patient was referred to Texas A&M Health Science Center's Baylor College of Dentistry for biopsy of recurrent mouth ulcers following an outbreak of a fever blister.[ncbi.nlm.nih.gov]
  • An active duty male Soldier presents to your clinic with concerns of blister-like lesions on both hands and feet several weeks after receiving immunizations.[ncbi.nlm.nih.gov]
  • Painful blisters or sores often form on the lips and lining of the mouth and rarely in the eyes. Doctors diagnose erythema multiforme by its characteristic appearance.[merckmanuals.com]
  • Dermatographic urticaria · Cold urticaria · Cholinergic urticaria Erythema Erythema multiforme / drug eruptions : Stevens-Johnson syndrome · Toxic epidermal necrolysis · Erythema nodosum Other erythema : Erythema annulare centrifugum · Erythema marginatum[wikidoc.org]
  • Most misdiagnosed cases were non-specific eruptions and urticaria multiforme. Mean age was 11.3 years. Fifty percent had mucosal involvement. An aetiology was observed in half of the patients.[ncbi.nlm.nih.gov]
  • L50.6 Contact urticaria L50.8 Other urticaria L50.9 Urticaria, unspecified L51 Erythema multiforme L51.0 Nonbullous erythema multiforme L51.1 Stevens-Johnson syndrome L51.2 Toxic epidermal necrolysis [Lyell] L51.3 Stevens-Johnson syndrome-toxic epidermal[icd10data.com]
  • EM is very commonly confused with annular urticaria (hives). Urticaria is far more common than EM.[cancertherapyadvisor.com]
Nikolsky's Sign
  • […] can aid diagnosis Differential Diagnosis SJS/TEN (flat lesions, tender, always with mucous involvement, Nikolsky sign) Urticaria (annular lesions) Erythema nodosum Viral exanthems Treatment Supportive care Corticosteroids if severe Treat underlying cause[medbullets.com]
  • sign) Urticaria (annular lesions) Erythema nodosum Viral exanthems Treatment EM major corticosteroids opthalmology consult if ocular involvement EM minor – usually self-limited supportive care Treat underlying cause if identified oral acyclovir for HSV[medbullets.com]
  • Nikolsky sign is negative. Acute and convalescent mycoplasma titers may be employed to help to establish this diagnosis in the correct clinical scenario.[visualdx.com]
  • sign (as opposed to SJS/TEN) Generally mild burning or itchiness; nontender Most commonly involves palms/soles backs of hands and feet extensor aspects of forearms and legs Must also examine mucosal surfaces and eyes oral genital/anal iris Symptomatic[smartypance.com]
  • Nikolsky sign was negative. Generalized erythema is visualized throughout the oral cavity. The buccal mucosa was markedly erythematous with hyperkeratotic & white plaque-like lesions present bilaterally.[austinpublishinggroup.com]
  • 709 ) Infections Bacterial skin disease Staphylococcus ( Staphylococcal scalded skin syndrome, Impetigo, Boil, Carbuncle ) · Strep ( Impetigo ) · Corynebacterium ( Erythrasma ) Viral skin disease Wart · Molluscum contagiosum · Erythema infectiosum · Exanthema[wikidoc.org]
  • Frequent skin side effects include morbilliform exanthemas (69%), urticarial eruptions (19%), dermatitis (6%) and acneiform eruptions (3%) as documented in a retrospective study in 98 patients [ 9 ].[omicsonline.org]
  • In 1922 Stevens and Johnson described two children who had fever, conjunctivitis, stomatitis, and a generalised exanthema with skin lesions distinct from EM 14 ; but in the past 30 years it has become widely accepted that EM and SJS, as well as toxic[adc.bmj.com]
Involuntary Movements
  • Adverse effects, observed in 4 patients, included fatigue, macrocytic anemia, anxiety, insomnia and involuntary movements, and drug-induced lupus erythematosus.[ncbi.nlm.nih.gov]
  • This was accompanied by marked bilateral submandibular and cervical lymphadenopathy, tremor and sweating. Clinical and laboratory investigations led to a diagnosis of erythema multiforme.[ncbi.nlm.nih.gov]


Laboratory tests are usually not required to confirm the presence of EM as a diagnosis is made clinically [8]. Imaging studies are not needed in most cases either, although chest radiography can be useful if a patient has respiratory symptoms or an underlying pulmonary infection.

If the condition is considered to be severe, there may be specific tests conducted. Elevation of the erythrocyte sedimentation rate and leukocytosis may be present. Cultures including blood cultures, mucosal lesions cultures, and sputum cultures are also taken in these cases.

Macrocytic Anemia
  • Adverse effects, observed in 4 patients, included fatigue, macrocytic anemia, anxiety, insomnia and involuntary movements, and drug-induced lupus erythematosus.[ncbi.nlm.nih.gov]
Francisella Tularensis
  • Tularemia is a rare and potentially life-threatening infection caused by the highly infectious gram-negative coccobacillus Francisella tularensis.[ncbi.nlm.nih.gov]
Coccidioides Immitis
  • Fungal ( Coccidioides immitis ) Parasitic ( Trichomonas species, Toxoplasma gondii ), Viral (especially Herpes simplex ) Drug reactions, most commonly to: antibiotics (including, sulphonamides, penicillin ), anticonvulsants ( phenytoin, barbiturates )[en.wikipedia.org]


Before any treatment for EM can be done, the underlying cause of the disorder will need to be identified. If erythema multiforme is drug-induced, the offending medication must be withdrawn. If the cause is an infection, that condition should be treated first.

Symptomatic treatment includes oral antihistamines, analgesics, and mouthwashes [9]. Various topical steroids can be used. If the eyes are affected, topical lubricants and supportive care can be used in treatment. Recurrent and severe forms require further treatment, frequently with continuous oral acyclovir.


In most cases EM is considered to be self-limited. The lesions that are associated with the minor form of EM usually resolve over two to three weeks without scarring [6]. It is common for EM minor to recur especially in patients with a condition caused by the herpes simplex virus.

The more severe form, EM major, is associated with a mortality rate of under five percent. Mortality in relation to EM major is usually due to sepsis or penumonia. The associated lesions usually heal without scarring but they can cause postinflammatory hypopigmentation or hyperpigmentation and rarely scarring due to a secondary infection. Ocular involvement may lead to keratitis, conjunctival scarring, and visual impairment in rare cases.


The disorder is believed to be caused by a number of different factors that can vary from case to case [3]. In about half of the reported cases of the disorder there is no one identifiable factor behind the occurrence of the EM and it is considered to be idiopathic. Certain medications such as antibiotics, anticonvulsants or antituberculoids can trigger the the disorder and bacterial, viral, parasitic and fungal infections are also a common cause of the condition. There are records of EM related to post-vaccinations including the Bacille Calmette-Guerin vaccination, the oral polio vaccine, and the tetanus/diphtheria vaccine. Erythema multiforme may also be associated with radiation, autoimmune diseases, and malignancies. 


On an international scale EM is uncommon and the incidence is reported to be 00.1% to 1% of the population. Erythema multiforme occurs predominantly in adults between 20 and 40 years of age, although it can affect individuals of all ages. Men and women are equally affected.

Sex distribution
Age distribution


It is believed that EM is an immunological disorder that results from a hypersensitive reaction triggered by various etiologic agents. However, the complete pathogenesis of erythema multiforme is not yet fully understood [5].

The pathogenesis of erythema multiforme due to herpes simplex virus has been investigated and is consistent with a delayed-type hypersensitivity reaction. It is however unclear, whether a similar mechanism is responsible for the development of the disorder related to other etiologic factors. 

There may be a genetic predisposition in the development of EM. Especially HLA-DQB1*0301 was detected more frequently in patients with erythema multiforme. Other HLA types may play a role as well.


There is no way to prevent EM from occurring [10]. When a person develops EM, it is important to figure out what triggered the disorder. This will allow them to better prevent recurrences.


Erythema multiforme (EM) is a self-limited, acute skin condition possibly mediated by of a type IV hypersensitivity that is associated with various infections or drug exposure [1]. This disorder can vary in severity based on the affected person and can be triggered by different catalysts. EM is divided in two forms: Erythema multiforme minor and erythema multiforme major [2].

Patient Information

Erythema multiforme (EM) is a skin condition that is caused by various factors, but is mainly caused by a reaction to a medication, vaccine or infection. There are two forms of the disorder, a minor and a major form. Each form varies in intensity and can take anywhere from one week to six weeks to clear up. The minor form of EM is a slight skin disorder that clears up quickly while the major form of EM can be severe and, in some cases, life threatening. EM is characterized by lesions that look like targets. They appear on the extremities and inside of the mouth. The severity of the individual case will usually determine the type of medical treatment needed.

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Last updated: 2019-07-11 21:20