Erythema multiforme L51.0

Ferdinand v. Hebra 1866

Relatively frequent, polyetiological, mucocutaneous clinical picture characterized by an acute to sub-acute, self-limiting exanthema with characteristic, ring-in-ring structured spots and plaques and a possible mucosal infection. Strictly speaking, it is not an entity but a group of polyaetiological diseases with the described clinical leading symptoms, which is pathogenetically characterized by a common cytotoxic immune reaction directed against keratinocytes.

Mainly occurring in young adults, rarely in children. m>w; no ethnic prevalence known.

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 biological methods HSV DNA could be detected in lesioned skin.

There is evidence for a genetic predisposition of the EEM with the following HLA associations: HLA-DQw3, DRw53, AW33.

Associations with other infectious diseases such as HSV type II (HSV-2), varicella, parapoxvirus(Orf virus), parvovirus-B19, hepatitis C, histoplasma capsulatum, EBV infections, streptococci or mycoplasma (mycoplasma infections are more common in children) have been reported.

More rarely, severe mycotic or Gardnerella vaginalis infections are the cause.

It is not uncommon for vaccinations (mass-mumps-rubella vaccinations, hepatitis B vaccinations, vaccinations with the polyvalent HPV vaccine) to precede an EEM.

EEM is often observed in combination with infections after taking medication.

Multiforme scattering reactions can also occur with allergic contact eczema (e.g. paraphenylenediamine in tattoos).

Occurs mainly in young adults, low androtrophy. Frequency peak: 20 - 40 LJ. Rarely in infants.

Sudden onset without significant prodromies. Within 48-72 hours development of a disseminated, symptomless or slightly burning to itchy exanthema which may also occur in groups in the area of the elbow or knee. Initially 0.1-0.3 cm large reddish papules, which expand within 24 hours to form (almost pathognomic) shooting disc-shaped (cockades) plaques. Their color is reddish-livid, also hemorrhagic. In the centre of the plaques blistering is possible. Often a linear arrangement of the lesions is detectable ( Koebner phenomenon).

The histological picture corresponds to that of classical acute cytotoxic interface dermatitis. A distinction must be made between:

• Early stage: plexus-like orthokeratotic stratum corneum, oedema of the papillary body with a thin lymphocytic infiltrate, isolated eosinophil granulocytes, distinct exocytosis with compression of the lymphocytes in the lower epithelial layers. Few dyskeratotic keratinocytes (amorphous eosinophilic cytoplasm in pynotically condensed nuclei). Significant hydropic degeneration of the lower epithelial cell layers.
• Later stage: plexus-like orthokeratotic stratum corneum, pronounced intra- and subepidermal edema up to subepithelial blistering; vacuum degeneration of the epidermis. Strong lymphocytic infiltrate with varying admixture of eosinophil granulocytes. Numerous dyskeratotic keratinocytes, which can also be aggregated to nests.

• Clinical:
  • Acute febrile neutrophilic dermatosis(Sweet's syndrome): Clinically and 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 exsudativum multiforme, it can progress to toxic epidermal necrolysis.
• Histologic

  :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 in 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.

It is an acute, self-liminating disease. In this respect, symptomatic therapy is generally sufficient.

Cheap. Self-limiting course with complete healing after 10 to 14 days.

Recurrent course is possible, with irregular occurrence of mostly 1-2 relapses/year, less frequently (up to 10 relapses/year).

More frequent episodes are observed in immunocompromised patients.

Some patients relapse 1 time per year in spring.

Depending on the expressivity, severity and localisation of the skin and mucous membrane changes, different terms were used in the past, the originality of which is doubted today:

• Erythema multiforme major
• Dermatostomatitis Baader
• Stevens-Johnson-Fuchs syndrome (syndrome muco-cutaneo-ocular fox)
• Fiessinger-Rendu syndrome (Ectodermosis érosive pluriorificielle).

Together with the Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN), they are now regarded as a disease spectrum with varying degrees of severity.

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