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PubMed2002

Neonatal erythema multiforme major.

A 25-day-old neonate developed an unusual eruption with bullae and marked systemic symptoms. Investigation for bacterial, viral, autoimmune and immunobullous causes did not reveal any identifiable trigger and histological examination was highly suggestive of bullous erythema multiforme. Pulmonary infiltrates were noted late in the course of the disease. Differential diagnoses included bullous impetigo, primary herpes simplex infection, immunobullous disease, neonatal lupus and erythema multiforme. This case illustrates the difficulties in diagnosing and managing an unwell child with bullae and emphasizes the need to exclude treatable underlying causes.

Biopsy↗
PubMed1997

The dermal type of erythema multiforme: a rare variant of Stevens-Johnson syndrome or cases of clinical misclassification?

Since 01.04.90 the Dokumentationszentrum schwerer Hautreaktionen (dZh) in Freiburg has registered cases of severe skin reactions like erythema exsudativum multiforme majus, Stevens-Johnson syndrome and toxic epidermal necrolysis in Germany. With the largest study so far of histological slides from patients included in this registry we were able to show that the epidermal type of erythema multiforme described by Orfanos et al. is the histopathological correlated of these severe skin reactions. Except two biopsies all of the specimens taken from the registered patients showed histological characteristics of this type of erythema multiforme. These two cases are now reported. Clinical data and photographic documentation did not prove authentic erythema multiforme. The lesions of both patients were described as atypical macules and papules; mucosal sites were only locally involved. Biopsies taken from the patients had the characteristics of the dermal type of erythema multiforme (Orfanos et al.). We conclude that histomorphological characteristics of the dermal type, in addition to an atypical clinical course, favour another diagnosis, such as multiforme-like eruption.

Aged↗
PubMed1980

Erythema multiforme -- an unusual reaction to BCG vaccination.

An eruptive form of erythema multiforme subsequent to BCG vaccination seen in a young Black nurse is reported. In a short review of the literature the author emphasizes that specific and nonspecific complications may occur after inoculation, but that the rare occurrence of these cutaneous manifestations cannot undermine the value of this preventive measure.

Adult↗
PubMed1996

Mycoplasma pneumoniae infection is associated with Stevens-Johnson syndrome, not erythema multiforme (von Hebra).

A review of the English-language medical literature revealed at least 70 cases of well-documented Mycoplasma pneumoniae infections associated with the Stevens-Johnson syndrome. There were no cases associated with erythema multiforme (von Hebra). Most of the patients were children and young adults, and male patients were more commonly affected. Most patients had prodromal symptoms of an upper respiratory tract infection before the onset of the eruption and an underlying pneumonia. Although the clinical course may be severe and prolonged, the prognosis is uniformly good with complete recovery in nearly all patients. Treatment is largely supportive and the use of antibiotics or steroids (or both) appears to have little effect on the course of the illness. We conclude that M. pneumoniae is the most common infectious agent associated with the Stevens-Johnson syndrome. It is not associated with erythema multiforme of von Hebra.

Adult↗
PubMed1994

Erythema multiforme during GM-CSF therapy.

A 52-year-old Caucasian man treated with granulocyte-macrophage colonystimulating factor (GM-CSF) developed a cutaneous eruption on legs and ankles with clinical and histologic features of erythema multiforme. Laboratory studies indicated that the eruption occurred at the time of peripheral blood lymphocyte recovery and that it was coincidental with serum peaks of interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6) and tumour necrosis factor-alpha. We postulate that GM-CSF provoked erythema multiforme in a predisposed individual as a consequence of either an inappropriate cytokine secretion or of an abnormal amplification mechanism following lymphocyte recovery.

Erythema Multiforme↗
PubMedDate not supplied

Erythema multiforme to amoxicillin with concurrent infection by Epstein-Barr virus.

BACKGROUND: The incidence of rashes following the intake of aminopenicillins during an acute episode of infectious mononucleosis is high, but severe cutaneous reactions as erythema multiforme or Stevens-Johnson syndrome are rare manifestations in childhood. MATERIAL AND METHODS: We report the case of a 7 year old girl that developed a generalized purpuric rash with target shaped areas, 9 days after starting treatment with amoxicillin-clavulanic acid. Laboratory investigation revealed a significant increase of Epstein Barr virus (EBV) specific IgM antibody. After skin biopse she was diagnosed as erythema multiforme syndrome. Prick, intradermal and patch tests were performed with penicilloylpolylysine, minor determinant mixture, benzylpenicillin, ampicillin, amoxicillin, cefazoline and cefotaxime, the 24 hours reading was positive for aminopenicillins. Patch tests were also positive only for aminopenicillins, other betalactams were negative. CONCLUSIONS: The interaction between an infectious agent (EBV) and amoxicillin could precipitate the severe skin reaction. Patch test and delayed intradermal reading with amoxicilllin were an useful tool for the diagnosis of the etiological agent in this reaction. The negative response to other beta-lactams, suggests that the aminobenzyl group of the side chain of amoxicillin plays a predominant role in this reaction.

Amoxicillin↗
PubMed1983

The ocular complications of erythema multiforme (Stevens Johnson syndrome) and their management.

Acute ocular complications of erythema multiforme such as infection causing conjunctivitis, suppurative keratitis or endophthalmitis are well recognized and usually easily managed. Late complications include disorders to tear production and drainage, position of lids, abberant or metaplastic lashes and metaplasia of the conjunctiva. Early detection and active management of these abnormalities greatly improves the long term prognosis. The techniques employed and the indications for their use in a recent series of 34 patients are presented.

Conjunctiva↗
PubMed1997

Acrosyringeal concentration of necrotic keratinocytes in erythema multiforme: a clue to drug etiology. Clinicopathologic review of 29 cases.

Erythema multiforme (EM) is caused by various insults, frequently an infectious agent or a drug. It is current practice that histologic identification of the precipitating factor is not possible. We have observed a pattern of acrosyringeal concentration of keratinocyte necrosis in certain cases of EM and retrospectively studied 29 consecutive cases of EM to establish clinicopathologic correlation for this finding. Acrosyringeal concentration was observed in 10 of 29 specimens, all 10 clinically drug related (Group 1). Nineteen specimens lacked this pattern (Group 2) of which 3 cases were clinically drug related (sensitivity = 0.8, specificity = 1.0). Eosinophils were present in the dermal infiltrate of 6 specimens from Group 1 and 2 specimens from Group 2 (p = 0.025). Acrosyringeal concentration of keratinocyte necrosis in EM occurs in drug-related cases and is more likely to be accompanied by a dermal inflammatory infiltrate containing eosinophils. Drug concentration in sweat may explain this pattern with subsequent toxic and immunologic mechanisms leading to the fully evolved lesion.

Adolescent↗
PubMed1995

A double-blind, placebo-controlled trial of continuous acyclovir therapy in recurrent erythema multiforme.

Twenty patients who suffered from more than four attacks of erythema multiforme (EM) per year were enrolled in a 6-month double-blind, placebo-controlled trial of acyclovir 400 mg twice daily. Fifteen patients had disease precipitated by recurrent herpes simplex. In the acyclovir-treated group the median number of EM attacks during the treatment period was zero, compared with three in the placebo-treated group (P < 0.0005, Wilcoxon rank sum test). Seven of the 11 patients treated with continuous acyclovir did not have any attacks of EM while taking the drug, and one showed almost complete disease suppression. Following treatment with acyclovir, two patients went into complete remission, whereas all individuals in the placebo group continued to have attacks. In the acyclovir-treated group nine of the 11 patients had herpes simplex-precipitated disease. One of the two patients with idiopathic disease showed complete disease suppression while on acyclovir, lending support to the view that idiopathic recurrent EM may be related to subclinical herpetic infection. In this study, we have shown that continuous acyclovir therapy can completely suppress attacks of recurrent EM and, in some cases, may induce disease remission.

Acyclovir↗
PubMed1998

Intraepidermal bile pigment in skin biopsy specimens for graft-versus-host disease versus erythema multiforme.

The differentiation of graft-verus-host disease (GVHD) from erythema multiforme (EM) presents a common diagnostic challenge in skin biopsy specimens from patients who have received patients allogeneic bone marrow transplants. The presence of gastrointestinal involvement might be the only way to make a diagnosis of GVHD in these cases. In the absence of liver function tests, gastrointestinal biopsy, or molecular techniques such as microsatellite DNA analysis, the presence of intraepidermal bile pigment might prove helpful in elucidating hyperbilirubinemia and allowing a pathologist to favor a diagnosis of GVHD over EM. Routinely processed archival tissue from 50 cases of GVHD (42 Caucasian and 8 of unknown race) and 50 cases of EM (31 Caucasian and 19 of unknown race) was examined for pigmentation. Intraepidermal pigmentation was stained for bile pigment and melanin. Among the intraepidermal EM lesions, 4 (8%) stained for intracorneal melanin, but none stained for bile pigment. Among the intraepidermal GVHD lesions, 8 (16%) stained for intracorneal melanin, but 3 (6%) stained for intracorneal bile pigment. In addition, 13 (26%) GVHD lesions and 9 (18%) EM lesions showed melanosis with melanin in all layers of the epidermis as well as within papillary dermal melanophages. Thus, when presented with a differential diagnosis of GVHD versus EM, the presence of intraepidermal bile pigment might suggest liver involvement and a diagnosis of GVHD.

Bile Pigments↗
PubMed2003

Erythema multiforme due to contact with weeds: a recurrence after patch testing.

Erythema multiforme (EM) as a complication of patch testing (PT) is rare. A 52-year-old woman with a 13-year history of episodes of EM, after contact with weeds during home gardening, had had no recent history of herpes simplex, other infection, drug ingestion or vaccination. On examination, EM lesions were distributed on the exposed skin. 5 weeks after complete resolution, PT and photopatch testing (PPT) were done with fresh plants she brought in. She was PT with a standard series and the Hermal-Trolab plants, woods, tars, balsams and flavors series. Intradermal testing, with a 3 + reaction to mixed weed pollens, was done 3 weeks later. Specific IgE to weed pollens class 1 (CAP-Pharmacia) was detected. Eczematous PT reactions were obtained with fresh leaves: common chickweed (Stellaria media Caryophyllaceae), dandelion (Taraxacum officinale Compositae), field-milk thistle (Sonchus arvensis Compositae) and white clover (Trifolium repens Leguminosae). Photoaggravation was seen to common chickweed and dandelion. Positive PT was also seen with alantolactone. By the 4-day reading, a typical EM had commenced, coming up to quite the same extent as seen on admission. There was no photosensitivity (UV skin tester, K. Waldmann). In the essential oil obtained from common chickweed, thin layer chromatography (TLC) revealed the well-known contact allergens borneol, menthol, linalool, 1,8-cineole, and other terpenes such as epoxy-dehydro-caryophyllene, monoterpene alcohol-ester and caryophyllene. Up to now, no data on essential oil in Stellaria media (common chickweed) have been reported. It can be concluded that EM developed due to contact with weeds, and recurred after patch testing. Neither blistering nor eczematous lesions have been seen on her skin, making this case very unusual. As far as the world literature is concerned, this is only the 4th report of EM developing in association with patch testing.

Dermatitis, Occupational↗
PubMed1979

Kawasaki's disease appearing as erythema multiforme.

In 1967, Kawasaki reported an acute, febrile, mucocutaneous condition accompanied by swelling of cervical lymph nodes that affected infants and young children in Japan. He called it mucocutaneous lymph node syndrome. We report here a case of Kawasaki's disease with characteristic findings that demonstrated a typical erythema multiforme rash. With the increased number of reported cases of Kawasaki's disease in the United States, it becomes increasingly important to differentiate the exanthem of Kawasaki's disease from early erythema multiforme.

Diagnosis, Differential↗
PubMed1982

Herpetiform eruption with leukocytoclasis: a distinctive clinico-pathological variety of erythema multiforme.

Six patients are described who experienced a prodromal period suggesting an infective process, followed by a distinctive polymorphous cutaneous eruption. The most striking lesion, present in all of them and giving the eruption a distinctive herpetiform appearance, included closely grouped vesicles resting on an erythematous base. Histopathological examination of these lesions showed features of dermal and epidermal types of erythema multiforme but with prominent leukocytoclasis. We suggest that the clinico-pathological picture of our patients may be considered a distinctive clinico-pathological variety of erythema multiforme.

Adult↗
PubMed2001

Interaction of HSV-1 infected peripheral blood mononuclear cells with cultured dermal microvascular endothelial cells: a potential model for the pathogenesis of HSV-1 induced erythema multiforme.

The effect of herpes virus infection on human dermal microvascular endothelial cells and herpes-virus-1-infected peripheral blood mononuclear cells on human dermal microvascular endothelial cells was studied as a model of herpes-associated erythema multiforme. After infection of human dermal microvascular endothelial cells with native herpes virus and overnight culture, 60%--90% of human dermal microvascular endothelial cells showed cytopathic effects. HLA class I molecules and CD31 (PECAM-1) surface expression in herpes-virus-infected endothelial cells were substantially downregulated, whereas CD54 (ICAM-1) remained unchanged. Cocultivation with herpes-virus-1-infected peripheral blood mononuclear cells left characteristic plaques on the human dermal microvascular endothelial cell monolayer; however, very few human dermal microvascular endothelial cells (1%--3%) were infected. Adhesion molecule expression of human dermal microvascular endothelial cells cocultivated with herpes-virus-infected peripheral blood mononuclear cells demonstrated a 5-fold increase in CD54 expression, a 2-fold increase in HLA class I expression, but no change of CD31 by fluorescence-activated cell sorter analysis. Incubation of human dermal microvascular endothelial cells with ultraviolet-C irradiated herpes-virus-infected peripheral blood mononuclear cells had no effect on morphology or adhesion molecule expression levels. Changes of adhesion molecule expression by direct infection or cocultivation with peripheral blood mononuclear cells (with native and ultraviolet-C inactivated herpes virus infection) were also documented at the mRNA level. Adhesion assays demonstrated an increased binding of herpes-virus-infected peripheral blood mononuclear cells versus noninfected peripheral blood mononuclear cells to noninfected human dermal microvascular endothelial cells. Our results suggest that incubation of herpes-virus-infected peripheral blood mononuclear cells with human dermal microvascular endothelial cells induces significant upregulation of CD54 and major histocompatibility complex class I molecules in the surrounding noninfected human dermal microvascular endothelial cells, which is associated with an increased binding of peripheral blood mononuclear cells. Our in vitro findings may serve as a model for herpes-associated erythema multiforme possibly explaining the dermal inflammatory reaction seen in that condition.

Antigens, Surface↗
PubMed2004

Erythema multiforme associated with phenytoin and cranial radiation therapy: a report of three patients and review of the literature.

BACKGROUND: Intracranial malignancies (primary and metastatic) are often complicated by seizure activity. Phenytoin (Dilantin) is typically employed as prophylactic anticonvulsant in this setting. Uncommonly, erythema multiforme (EM) can develop in such patients at the port site during or soon after cranial radiation and can rapidly progress to EM major. Herein, in addition to a comprehensive literature review of this entity, three additional patients are presented. The acronym 'EMPACT' is suggested (E: erythema; M: multiforme; associated with P: phenytoin; A: and; C: cranial, radiation; T: therapy) to best describe this disorder. METHODS: An extensive review of the English medical literature through the National Library of Medicine (PUBMED) was performed to identify patients who had received or continued to receive radiation therapy while on phenytoin. A total of 24 patients were identified and clinical information of varying detail was available in all cases. Clinical and histological information on three additional patients seen at two institutions (Rochester Methodist Hospital, Rochester, MN, and Fairview-University Medical Center, Minneapolis, MN) by the authors were also compiled. RESULTS: The mean age was 44 years (range: 23-67) and no sexual predisposition was noted. All patients had taken phenytoin for variable time periods (range 16-80 days; mean: 40) and were on the medication when the skin lesions first appeared. These lesions developed within the port site during the radiation treatments (11 cases) or soon after (nine cases) its completion (mean: 16 days; range: 2-35). Subsequent disease evolution to EM major occurred in all cases (Stevens-Johnsons syndrome developed in 73% of patients). No relationship was identified between the extent and the severity of the skin lesions with the phenytoin and radiation dosages and with the histologic type and origin of the intracranial malignancy. None of the patients demonstrated the requisite features of the 'Dilantin hypersensitivity syndrome'. Although, a systemic steroid taper was employed in 10 out of the 14 patients before the development of the skin lesions, the subsequent progression of the skin lesions was not influenced by the use of systemic steroid therapy. Complete recovery occurred in all but two patients typically within 1-8 weeks of discontinuation of phenytoin. CONCLUSIONS: The need for prophylactic anticonvulsant therapy especially utilizing phenytoin in patients undergoing cranial radiation therapy should be assessed on a case by case basis. If anticonvulsants are employed, then they must be administered with caution, and all cutaneous reactions developing subsequently within the radiation site must be promptly evaluated with a high index of suspicion for erythema multiforme.

Anticonvulsants↗
PubMed1999

Increased risk of erythema multiforme major with combination anticonvulsant and radiation therapies.

Erythema multiforme major (EMM; Stevens-Johnson syndrome) is a cutaneous disorder associated with a wide variety of factors including ingestion of drugs such as phenytoin and exposure to intracranial radiation therapy. Based on observations of a 47-year-old black man with brain metastases who developed EMM after combined phenytoin and radiation therapy, we conducted a MEDLINE literature search for articles on similar cases from 1966 to the present. Twenty cases were identified that support the hypothesis that EMM is associated with combined phenytoin and radiation therapy. The reaction, or its severity, has no relationship to the phenytoin or radiation therapy dosage, or to the histologic type of brain tumor. Also, EMM has no apparent age or gender predisposition in association with phenytoin-radiation therapy. Thus this is a clinical phenomenon that occurs with unusual frequency in patients with brain tumor who undergo radiation therapy while taking phenytoin. Phenytoin and other anticonvulsants such as phenobarbital and carbamazepine induce cytochrome P450 3A and produce oxidative reactive intermediates that may be implicated in hypersensitivity reactions such as EMM. Both carbamazepine and barbiturates have shown cross-sensitivity with phenytoin; furthermore, a case of EMM in a patient receiving carbamazepine and whole brain radiation therapy has been reported. As carbamazepine, valproate, and barbiturates have been associated with EMM, gabapentin may be considered as alternative anticonvulsant therapy when appropriate.

Adult↗