Erythema multiforme (overview) L51.0

In 1860, Ferdinand von Hebra described erythema exsudativum multiforme for the first time in his textbook as a purely cutaneous, polymorphic erythema (exanthem) with a benign course. v. Hebra, 1867: “I have chosen the name‘erythema multiforme’ to designate this condition [!]. It is characterized [!] above all else [!] by its location [!]; namely, it always occurs on the back of the hands or feet, and only in more severe cases does it also appear on the forearms, lower legs, upper arms, thighs, and, in the most exceptional cases, on the trunk and face; however, in the latter cases, it is certainly never absent from: on the back of the hand, where the first eruptions [!] usually appear. These efflorescences [!] consist of flattened nodules or lumps ranging in size from a lentil to a bean, dark blue or brownish-red [!] in color, and occur in varying numbers.”

In 1876, clinically more severe, similar cases involving the skin and mucous membranes were described as erythema multiforme majus. 

In 1922, the clinical picture described by Stevens and Johnson (Stevens-Johnson syndrome) was published: a severe, febrile exanthem accompanied by stomatitis and purulent conjunctivitis.
In 1950, the British dermatologist Bernard Thomas proposed classifying erythema (exsudativum) multiforme into a less severe variant without fever and with primarily cutaneous involvement (erythema (exsudativum) multiforme minus)  and a severe, febrile variant with significant mucosal involvement as erythema (exsudativum) multiforme majus (Thomas, 1950).

In 1956, the term“toxic epidermal necrolysis”was additionally coined. 

Recently, there has been a tendency to group Stevens-Johnson syndrome andtoxic epidermal necrolysis under the umbrella term EN— epidermal necrolysis.  

Erythema multiforme (EM) is a polyetiologic inflammatory syndrome triggered by an infection-induced, hyperergic, systemic immune reaction that is projected either only onto the skin (erythema multiforme minus), onto skin and mucous membranes (erythema multiforme majus) or exclusively onto mucous membranes close to the surface (Fuchs syndrome).

Erythema multiforme is clinically characterized by an acute to subacute, self-limited exanthema prone to recurrence with characteristic, well-defined, targetoid (cocardia - disc-in-disc structure with heterogeneous ring formations, possibly also central blistering).

The classic erythema multiforme/EM-minus(first described by Ferdinand v. Hebra) is usually mild, skin-accentuated and is mainly caused by herpes simplex viruses but also other viruses and various bacteria (e.g. mycoplasma). Bacteria (e.g. mycoplasma). A few patients suffer a recurrent form (usually triggered by herpes simplex infections) with recurring episodes over months and years.

Erythema multiforme majus is much more severe than EM-minus with skin and varying degrees of mucosal involvement (conjunctiva, lip and oral mucosa, anal and genital mucosa).

A course of EM that is limited to mucous membranes can be referred to as Fuchs syndrome or mucosal EM.

Erythema (exsudativum) multiforme minus: mild (classic) form, which is mainly triggered by herpes simplex infections. Mucosal involvement is not observed in this variant. One part recurs. A recurrent course over many years is possible (recurrent erythema multiforme).

Erythema (exsudativum) multiforme majus: this severe, usually single, extremity variant with varying degrees of erosive mucosal involvement is also predominantly virus-induced. Typical and/or atypical cockades are detectable. In children and adolescents, Mycoplasma pneumoniae can be the trigger (EM strain - see also RIME)

Fuchs syndrome (mucosal EM): In this clinical variant of erythema multiforme major (first described in 1906), there is localized involvement of the conjunctiva (and oral mucosa). By definition, skin symptoms recede completely into the background. No cockades!

Ectodermosis erosiva pluriorificialis (Rendu-Fiessinger): Clinical variant of erythema multiforme major with polytopic involvement of the oral, genital and anal mucosa (a term that is not commonly used today - the changes are essentially assigned to Fuchs syndrome).

Reactive infectious mucocutaneous eruption (RIME): Clinical variant of erythema multiforme major which is mainly caused by Mycoplasmae pneumoniae.

Mycoplasma-induced rash and mucositis (MIRM ), an inflammatory mucocutaneous eruption in children and adolescents associated with infections caused by Mycoplasma pneumoniae. Other associated pathogens that cause this inflammatory symptomatology have since been identified. The name RIME is preferred.

See below for the respective disease binders.

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