LONDON SATURDAY 8 JANUARY 1972 MEDICAL Br Med J: first published as 10.1136/bmj.1.5792.63 on 8 January 1972. Downloaded from JOURNAL Erythema Multiforme The term erythema multiforme means different things to the names of Stevens and Johnson are correctly attached to different people. Unfortunately the word multiforme is often this syndrome4). Unlike the other types of erythema multi- taken as a licence to apply it to almost any form of erythema forme, in which constitutional upset is usually mild or none, of obscure origin. In some countries even such well-defined this can be a very severe illness, making the patient ex- diseases as pemphigoid have been included. However, there tremely miserable, with high fever and with an appreciable is much to be said for using the diagnosis to describe only mortality rate. Characteristically the mucous membrane of typical cases. It has recently been confirmed' that such the mouth is almost entirely denuded of epithelium and the cases do also have a typical histology distinguishable from eyes show a severe conjunctivitis or corneal damage. Lesions the other types of erythematous eruption. on the genitalia may give rise to retention of urine. Renal Clinically, typical erythema multiforme can occur in disease occurs rarely.5 Bronchitis or pneumonitis, often various forms which differ in the severity of the cell damage, more extensive on x-ray than suspected clinically, is com- so that individual lesions may be macules, papules, or have monly associated. superimposed blisters. The lesions also vary in number The differential diagnosis of the Stevens-Johnson syn- and distribution. Cases showing all types of lesion in any drome includes Behcet's disease, pemphigus, pemphigoid, http://www.bmj.com/ one attack, and cases showing the different clinical pictures and toxic epidermal necrolysis or Lyell's disease. Behqet's in subsequent attacks, leave little doubt that they are all disease should not cause confusion, as it essentially causes basically similar, though it can be argued that the most ulceration of the mouth rather than extensive erosions and severe forms, or Stevens-Johnson syndrome, should be kept is chronic. Pemphigus and pemphigoid are also chronic apart. diseases with characteristic blisters, and any doubts can be The mildest, papular or simplex, form of erythema multi- cleared up by histological examination. Toxic epidermal forme is the commonest. The patient presents with dull necrolysis, with its typical scalded-skin appearance, should on 1 October 2021 by guest. Protected copyright. red maculo-papules up to 2 cm in diameter, often showing not cause confusion, though it was perhaps often classified the characteristic target lesions due to central stagnation or with erythema multiforme before Lyell's description in extravasation of red cells. These tend to have a typical 1956.6 distribution on the backs and fronts of the hands and the The aetiology of all forms of erythema multiforme re- feet and on the extensor aspects of the elbows and knees, mains obscure in most cases. A variety of stimuli have been but may be more widespread. Occasionally they occur on known to trigger it off, with a latent interval of one to three mucous membranes. The differential diagnosis of this type weeks. They include especially virus infections like herpes must include drug eruptions; id eruptions from fungus, simplex and vaccinia, mycoplasma infections, drug sensi- bacterial, or virus infections; and eruptions which are diffi- tivities, pregnancy, and radiotherapy, but the list of re- cult to classify but which in appearance and natural history ported causes is large.78 The most important drugs are seem to be on the borderline between urticaria and erythema barbiturates, long-acting sulphonamides, and phenylbuta- multiforme. One particular type of chilblain with multiple zone.8-11 This all suggests that erythema multiforme is a small lesions on the fingers may closely resemble erythema pattern of reaction based on an immunological mechanism, multiforme.2 Typical erythema multiforme may be asso- though the exact type of this has yet to be demonstrated. ciated with erythema nodosum and then requires the Despite the occasional isolation of viruses or mycoplasmas usual investigations for the latter to exclude tuberculosis, from the blisters,12 it seems unlikely that there is a specific sarcoidosis, and streptococcal and other infections. infective organism. There is no reason to regard these If the inflammatory process is more severe, blisters will patients as being infectious, though they are often best form. Often the lesions are like the papular form, perhaps looked after in isolation for their own protection. only few in number, but with superimposed blisters. In the From the practical point of view erythema multiforme in most severe forms of the disease blistering may be very all its forms is a self-limiting disease over two to six weeks, severe, with extensive mucosal involvement-the so-called and with the exception of drug sensitivities the initiating Stevens-Johnson syndrome3 (there is some doubt whether cause is often no longer active by the time the eruption © BRITISH MEDICAL JOURNAL 1972. AU reproduction rights reserved NO. 5792 PAGE 63 64 BRITISH MEDICAL JOURNAL 8 JANUARY 1972 has appeared. The disease runs much the same course patients believed to be taking prophylaxis conscientiously. whether a cause for it is found or not. The history and Florid rheumatic fever is now relatively rare and also less clinical examination must concentrate on drugs, infections, severe in the more economically advanced nations.4 Though and analysis of any other symptoms. The urine should always this decrease in prevalence and severity began before the Br Med J: first published as 10.1136/bmj.1.5792.63 on 8 January 1972. Downloaded from be examined for protein and red cells. Biopsy is seldom antibiotic era and has probably been associated with altered necessary to establish the diagnosis and does nothing to virulence of the streptococcus and improved social condi- help establish the underlying cause, though immuno- tions, prompt and effective antibiotic therapy in group A fluorescence studies may be helpful in the future. Skin test- streptococcal infections must have further lowered the in- ing has not been shown to be of any value, though occa- cidence. sional positive tests with herpes virus7 and other antigens The changing clinical pattern of rheumatic fever, with have been reported. When drugs are suspected to be caus- minimal or no fever, often a non-migratory monarthritis, ing it they are best avoided in the future irrespective of any arthralgia, abdominal pain, or even carditis as the presenting laboratory investigation. The danger that re-exposure will feature,5 must be appreciated or it may be unrecognized lead to one of the more severe forms of erythema multi- and therefore untreated. A. R. Feinstein6 and Feinstein and forme does not warrant even giving test doses. Serological M. Spagnuolo7 believed that recurrences of rheumatic fever evidence of a preceding infection-for example, myco- tend to repeat the features of the first attack. They claimed plasma-may be found in an appreciable number of cases, that if the first attack did not affect the heart recurrences but by the time the result is available it has usually become were also unlikely to do so, and they suggested that pro- somewhat academic. phylaxis might be reserved for those who develop heart Treatment is essentially symptomatic. The milder forms disease. Perry,3 however, was not so certain, and A. G. Kut- of the disease require little apart from reassurance, and local tner and F. E. Mayer8 noted that 25% of cases did not applications cannot be expected to be much more than follow a repetitive pattern. Nor does that take into account placebos. The ability of systemic steroids to reduce the minimal carditis, which could easily be missed and which mortality of the Stevens-Johnson syndrome has not been could be more severe in a second attack. Though the inci- proved, but there is no doubt that they can sometimes dence of streptococcal infections tends to decrease with age- provide dramatic symptomatic relief, with a starting dose ing the attack rate of rheumatic fever after an infection re- of prednisone 60 mg daily in a severe case. A systemic mains high in the susceptible. antibiotic is often combined to prevent secondary bacterial Spagnuolo, B. Pasternack, and A. Taranta9 recently infection of the denuded area. Probably the most important showed that symptoms of sore throat with fever were part of treatment is skilled nursing. Recovery can be ex- significantly associated with a high recurrence rate-up to pected to be complete, with the possible exception of the in children aged under 12 and 14% in adolescents- more severe ocular complications. 25% recurs, but there is little and particularly so when the interval since the preceding Erythema multiforme sometimes attack of rheumatic fever was short. Those with existing that can be done to prevent recurrences apart from avoid- had had a number ance of offending drugs. Possibly in those cases that follow rheumatic heart disease and those who herpes simplex infection some success may attend early of previous attacks were also particularly susceptible to re- treatment of the herpes with idoxuridine. currences, but there was no significant association between http://www.bmj.com/ recurrence and the rise in the antistreptolysin 0 titre. This Ackerman, A. B., Penneys, N. S., and Clark, W. H., British journal of means that prophylaxis is desirable in all children who have Dermatology, 1971, 84, 554. had rheumatic fever, while it is reasonable to instruct adults ' Haxthausen, H., Cold in Relation to Skin Diseases. Copenhagen, Levin and Munksgaard, 1930. in a first attack without carditis to seek treatment promptly 3 Ashby, D. W., and Lazar, T., Lancet, 1951, 1, 1091.