HistoryThis section has been translated automatically.
Ferdinand v. Hebra 1866
DefinitionThis section has been translated automatically.
Relatively common, polyetiologic, mucocutaneous reaction pattern characterized by an acute to subacute, self-limited exanthema prone to recurrence with characteristic, slice-like structured (slice-in-slice structure) patches, plaques and blisters as well as possible mucosal involvement. Strictly speaking, it is not an entity but a group of polyetiologic diseases with the described leading clinical symptoms, which are pathogenetically characterized by a common cytotoxic immune reaction directed against keratinocytes with epidermal "saddle cell necrosis".
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Occurrence/EpidemiologyThis section has been translated automatically.
Mainly occurring in young adults, rarely in children. m>w; no ethnic prevalence known.
EtiopathogenesisThis section has been translated automatically.
Genetics: There is evidence of a genetic predisposition of EEM with the following HLA associations: HLA-DQw3, DRw53, AW33.
Infections: In the majority of adolescents and adults, herpes simplex type 1 (HSV-1) infections precede exanthema or become clinically apparent after the onset of exanthema. By molecular biology methods, HSV DNA has been detected in lesional skin. Associations with other infectious diseases such as HSV type II (HSV-2), varicella, parapoxviruses(Orf virus), parvovirus-B19, hepatitis C, SARS-CoV-2 (Thielmann CM et al. 2022), Histoplasma capsulatum, EBV infections, streptococci, or mycoplasma (mycoplasma infections occur frequently in children) have been reported. Less commonly, severe mycotic or Gardnerella vaginalis infections are causative.
Vaccinations: Not very rarely, vaccinations (masen-mumps-rubella vaccinations, hepatitis B vaccinations, vaccinations with the polyvalent HPV vaccine) precede erythema multiforme.
Medications: EM is frequently observed after medication (e.g. 5-fluorouracil and actinomycin D ) gfls. also in combination with viral or bacterial infections (Wang S et al. (2022) .
Multiforme "scatter reactions" may also occur in allergic contact dermatitis (e.g., paraphenylenediamine in tattoos).
ManifestationThis section has been translated automatically.
Occurs mainly in young adults, low androtrophy. Frequency peak: 20 - 40 LJ. Rarely in infants.
LocalizationThis section has been translated automatically.
Back of the hands, palms and soles, neck, face and neck, extensor sides of the upper extremity; grouped in the area of the elbow, rarely the knee. The trunk may also be affected (see Fig.). Mild (usually oral) mucosal involvement (lips, buccal mucosa and tongue) in about 50% of cases.
Clinical featuresThis section has been translated automatically.
Sudden onset without significant prodromes. Within 48-72 hours, formation of a disseminated, usually strictly symmetrical exanthema, which may occur in groups in the area of the elbow or knee and is asymptomatic or slightly burning to itchy.
Initial 0.1-0.3 cm reddish papules that expand within 24 hours to form (almost pathognomic) disc-shaped (cocard) plaques.
Their color is reddish-livid, also hemorrhagic. Blistering is possible in the center of the plaques. A linear arrangement of the lesions is often detectable ( Köbner phenomenon).
HistologyThis section has been translated automatically.
The histologic picture corresponds to that of classic acute cytotoxic interface dermatitis.
To be distinguished are:
- Early stage: Basket-weave orthokeratotic stratum corneum, edema of the papillary body with sparse lymphocytic infiltrate, scattered eosinophilic granulocytes, marked exocytosis with condensation of lymphocytes in the lower epithelial layers. Few dyskeratotic keratinocytes (amorphous eosinophilic cytoplasm with pyknotic condensed nuclei). Marked hydropic degeneration of the lower epithelial cell layers.
- Later stage: Basket-weave orthokeratotic stratum corneum, marked intra- and subepidermal edema to subepithelial blistering; vacuolar degeneration of epidermis. Vigorous lymphocytic infiltrate with variable admixture of eosinophilic granulocytes. Numerous dyskeratotic keratinocytes, which may also be aggregated into nests.
Differential diagnosisThis section has been translated automatically.
- Acute febrile neutrophilic dermatosis(Sweet syndrome): Clinically morphologically similar in the early phase of the disease. However, Sweet's syndrome lacks the erythema exsudativum multiforme cocardes. Always fever, severe malaise, and neutrophilic leukocytosis.
- Polymorphous light dermatosis: Occurring after UV exposure (sun pattern!); severe itching, never involvement of mucous membranes.
- Acute urticaria: Clinical determination of wheal (prove volatility by marking). No erythema exsudativum multiforme cocardes.
- Urticarial vasculitis: Pronounced episodic chronicity. Small-spotted, maculo-papular, pruritic or painful exanthema accompanied by episodes of fever. Neutrophilic leukocytosis is possible. Frequent arthralgias and arthritides; no erythema exsudativum multiforme cocardia. Lymph node swelling. Possibly positive ANA and signs of systemic lupus erythematosus. Histologically, signs of vasculitis are diagnostic.
- Subacute cutaneous lupus erythematosus: A picture similar to erythema exsudativum multiforme may develop, particularly in highly acute cases with disseminated plaques. Histology and immunohistology are diagnostic.
- Drug exanthema (maculo-papular): Not a real DD, as erythema exsudativum multiforme can be triggered by drugs. Maculo-papular drug ex anthema can be diagnosed if a link can be established with altered or intercurrent drug administration.
- Bullous pemphigoid: In some cases, especially in the initial phase of bullous pemphigoid, the pioneering blisters may be absent. This eliminates the leading clinical symptom of "bulging (firm) blister" and the clear clinical assignment to the blistering diseases. Histology and IF are demonstrative.
- Stevens-Johnson syndrome: Initial febrile, catarrhal prodromal symptoms, generalized lymphadenopathy, liver and spleen involvement. Always mucosal manifestations. Skin manifestations of variable extent: from a few atypical cocardes with a maximum of two zones to extensive scarlatiniform exanthema. Stevens-Johnson syndrome, in contrast to EEM, does not(!) show any slice-like efflorescences, but atypical cocardes with a maximum of two zones. In addition, unlike erythema multiforme, it can progress to toxic epidermal necrolysis(TEN).
:Notice. There are smooth transitions between erythema exsudativum multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Histologically, all diseases with (occasional) subepidermal blistering must be considered ( dermatitis solaris, graft-versus-host disease, ictus, lichen planus bullosus, lichen sclerosus et atrophícus, polymorphous light dermatosis, systemic amyloidosis, porphyria cutanea tarda).
- Toxic epidermal necrolysis (TEN): Subepidermal blister, broad necrosis of the entire epidermis, marked dermal edema. Only mild, diffuse lymphocyte infiltration; erythrocyte extravasation.
- Staphylococcal Scalded Skin Syndrome (SSSS): As previously seen with TEN; blistering, however, subcorneal.
- Drug reaction, fixed: Interface dermatitis with numerous apoptotic keratinocytes, lichenoid and perivascular inflammatory reaction of upper and middle (usually also deep) dermis; usually marked pigment incontinence.
- Graft-versus-host disease, acute: Apoptotic keratinocytes, possibly subepithelial blistering, lichenoid infiltrate, eosinophilic granulocytes.
- Urticaria: Only minor infiltrate; no apoptotic keratinocytes.
- Pityriasis lichenoides et varioliformis acuta: Interface dermatitis with irregular acanthosis, bilayered str. corneum with basket-weave orthokeratosis over continuous parakeratosis zone. In the dermis, more wedge-shaped, perivascular or even interstitial infiltrate of lymphocytes.
- Erythema elevatum diutinum: Rare disease! In the early stage always signs of leukocytoclastic vasculitis with leukocytoclasia and nuclear dust as well as fibrin in the vessel walls. Epidermis and skin appendages remain uninvolved.
TherapyThis section has been translated automatically.
It is an acute, self-liminating disease. In this respect, symptomatic therapy is generally sufficient.
External therapyThis section has been translated automatically.
Local treatment with Lotio alba is usually sufficient. For more severe itching and pronounced skin infestation, medium-strength glucocorticoid-containing externals such as 0.1% triamcinolone cream (e.g., Triamgalen, Delphicort,Triamcinolone acetonide cream hydrophilic 0.025/0.05/0.1% (NRF 11.38.), or 0.05-1% betamethasone emulsion (e.g., Betagalen®, Betnesol, betamethasone valerate emulsion hydrophilic 0.025/0.05 or 0.1% (NRF 11.47.) are indicated. If the oral mucosa is affected, mouth rinses with antiphlogistic preparations (e.g., chamomile extracts).
Internal therapyThis section has been translated automatically.
If symptoms are pronounced, systemic glucocorticoids such as prednisone (e.g. Decortin Tbl.) 50-75 mg/day. Additionally, in case of itching, antihistamines, e.g. desloratadine (Aerius), levocetirizine (Xyzall), cetirizine (Zyrtec) p.o. In case of frequent (postherpetic) recurrences, oral prophylaxis with aciclovir for 1 year is indicated (10 mg/kg bw/day) (evidence level: IB).
Progression/forecastThis section has been translated automatically.
Favorable. Self-limiting course with complete healing after 10 to 14 days.
Recurrent course is possible, with irregular occurrence of usually 1-2 recurrences/year, rarely more frequent (up to 10 recurrences/year).
More frequent episodes are observed in immunosuppressed individuals.
Some patients relapse 1 time/year in spring.
Note(s)This section has been translated automatically.
Depending on the expressivity, severity and localization of the skin and mucosal changes, different terms were used in the past, the independence of which is now doubted:
- Erythema multiforme major
- Baader's dermatostomatitis
- Stevens-Johnson-Fuchs syndrome (Syndroma muco-cutaneo-oculare Fuchs)
- Fiessinger-Rendu syndrome (ectodermosis érosive pluriorificielle).
LiteratureThis section has been translated automatically.
- Ayangco L et al (2003) Oral manifestations of erythema multiforme. Dermatol Clin 21: 195-205
- Das S et al (2000) Herpes simplex virus type 1 as a cause of widespread intracorneal blistering of the lower limbs. Clin Exp Dermatol 25: 119-121
- Hidajat C et al (2014) Drug-mediated rash: erythema multiforme versus Stevens-Johnson syndrome. BMJ Case Rep 22 PubMed PMID: 25246464.
- Johnston GA et al (2002) Neonatal erythema multiforme major. Clin Exp Dermatol 27: 661-664.
- Molnar I, Matulis M. (2002) Arthritis associated with recurrent erythema multiforme responding to oral acyclovir. Clin Rheumatol 21: 415-417.
- Samim F et al.(2013) Erythema multiforme: a review of epidemiology, pathogenesis, clinical features, and treatment. Dent Clin North Am 57:583-96.
- Seishima M, Oyama Z, Yamamura M (2001) Erythema multiforme associated with cytomegalovirus infection in nonimmunosuppressed patients. Dermatology 203: 299-302
- Sun J et al (2014) Stevens-Johnson syndrome and toxic epidermal necrolysis: a multi-aspect comparative 7-year study from the People's Republic of China. Drug Des Devel Ther 8:2539-1547.
- Tatnall FM et al (1995) A double-blind, placebo-controlled trial of continous acyclovir therapy in recurrent erythema multiforme. Br J Dermatol 132: 267-270
Thielmann CM et al (2022) COVID-19-triggered EEM-like skin lesions. Dtsch Arztebl Int 119:131.
- Trayes KP et al (2019) Erythema multiforme: recognition and management. Am Fam Physician. 100: 82-88.
- Von Hebra F, Kaposi M (1860) Textbook of skin diseases. Vol 1, Enke, Erlangen
Wang S et al. (2022) 5-Fluorouracil and actinomycin D lead to erythema multiforme drug eruption in chemotherapy of invasive mole: Case report and literature review. Medicine (Baltimore) 101:e31678
Incoming links (93)Abacavir; Acute hemorrhagic infantile edema; Acute Syndrome of Apoptotic Panepidermolysis; Amprenavir; Anonychie acquired; Antibiotic allergy; Aphthosis neumann; Azithromycin; Baader, dermatostomatitis; Balanitis symptomatica; ... Show all
Outgoing links (41)Aciclovir; Actinomycin d; Amyloidosis systemic (overview); Antihistamines; Betamethasone valerate emulsion hydrophilic 0,025/0,05 or 0,1 % (nrf 11.47.); Cetirizine; Contagious ecthyma; Desloratadine; Drug exanthema maculo-papular; Drug reaction fixe; ... Show all
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