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PubMed1983

Erythema multiforme: microvascular damage and infiltration of lymphocytes and basophils.

The sequence of alterations occurring in recurrent erythema multiforme was studied with clinical observations, 1-micrometer tissue sections, and immunofluorescence techniques. Lesions evolved through 3 stages: an initial red papule, a vesicle surmounting a red papule, and a target (iris) lesion. Focal endothelial cell swelling was present in clinically normal skin. In the red papule, endothelial cytoplasmic swelling, vacuolization, and nuclear hypertrophy with luminal obliteration of superficial venules developed. These venular alterations were more marked with endothelial cell necrosis, and involved deeper venules as well in vesicular and target lesions. Lymphocytes surrounded the venules and infiltrated the lower epidermis in the red papule and the vesicular lesions. Venular damage was correlated with the degree of infiltration by lymphocytes, apparently the primary effector cell, suggesting the venule as a primary target of injury. Hypogranulated basophils were noted around venules in vesicular and target lesions. Fibrin deposits were identified within and interstitially beneath the vesicles. The presence of lymphocytes, basophils, and interstitial fibrin deposition is similar to the changes of cutaneous delayed-type hypersensitivity and suggests a role for cell-mediated immunity in the pathogenesis of erythema multiforme.

Adolescent↗
PubMed1994

Erythema-multiforme-like, urticarial papular and plaque eruptions from bufexamac: report of 4 cases.

4 patients developed an erythema-multiforme-like reaction following acute contact dermatitis from 2 different bufexamac-containing topical preparations. Histologically, the lesions did not show changes that were typical of erythema multiforme. Patch testing gave positive reactions to bufexamac at 1, 2, 3 and 4 days. The histological picture of 2 positive test reactions was suggestive of a drug reaction in the 1st, and of an acute eczematous reaction in the 2nd, case. A systemic allergic reaction with spread of lesions could have been involved, following percutaneous absorption of the allergen.

Adult↗
PubMed1980

Erythema multiforme: direct immunofluorescence studies and detection of circulating immune complexes.

The immunologic parameters of 23 patients with erythema multiforme who were seen by us (17 patients) or who had biopsies sent for immunofluorescence testing (6 cases) are reviewed. Biopsy specimens were sectioned and tested with labeled antisera to human IgG, IgA, IgM, C3 and fibrin. Fourteen biopsies showed IgM deposits in the superficial blood vessels, 13 demonstrated C3, 15 showed fibrin deposition, and 1 biopsy showed IgA deposition. All biopsies were negative for IgG. Eight serum samples tested by indirect IF were negative for skin-reactive antibodies. In addition to IF testing, serum samples from 20 patients were tested for circulating immune complexes with a Clq binding radioassay and a monoclonal rheumatoid factor (mRF) inhibition assay. Immune complexes were not detected by the Clq binding assay, but 6 of 20 serum samples demonstrated low to moderate levels of immune complexes by the mRF inhibition assay. By sucrose density gradient ultracentrifugation in the mRF-reactive material in one serum sample sedimented in high molecular weight fractions and also demonstrated anticomplementary activity. These findings suggest that immune complex formation and subsequent deposition in the cutaneous microvasculature may play a role in the pathogenesis of erythema multiforme.

Antigen-Antibody Complex↗
PubMed1993

A case of herpes-associated erythema multiforme in a Japanese child.

A case of a five-year-old Japanese boy with herpes-associated erythema multiforme (HAEM) was reported. The patient had eleven recurrences of herpes labiaris within one year; four of these recurrences were accompanied by erythema multiforme. A study of the human leukocyte antigens revealed the presence of HLA-DQW3, which has been reported to be significantly frequent in Caucasian patients with HAEM. Oral administration of acyclovir at the onset of herpes labialis was effective in preventing HAEM. Early administration of oral steroids at the onset of HAEM also prevented its exacerbation.

Acyclovir↗
PubMed1981

Legionnaires' disease combined with erythema multiforme in a 3-year-old boy.

A case of Legionnaires' disease (LD) is described in a 3-year-old boy. He had fulminant disease with typical signs like bilateral pneumonia, gastrointestinal symptoms, and somnolence indicating involvement of the central nervous system. There was no premorbidity. An outstanding development was erythema multiforme, which has never previously been described in LD. The basic disease was caused by Legionella pneumophila. This is evidenced by specific serum IgM at admission and a subsequent significant rise in titers against L. pneumophila. At an early stage respiratory syncytial virus (RSV) was isolated from the patient's throat, although there was no antiviral serological response at the outset of erythema multiforme or 3 weeks after onset of disease; anti-RSV appeared later. The prolonged course of the disease can be explained by the successive occurrence of two infections. The possibility that the virus could have contributed to the development of erythema multiforme cannot be ruled out. The role of concomitant medication cannot be separated out, but on the basis of general knowledge of their immunogenicity and the fact that immunosuppressive cortisone was given at the time it is less likely that the antibiotics contributed significantly.

Child, Preschool↗
PubMed1981

A case of contact dermatitis, erythema multiforme, and toxic epidermal necrolysis.

A young adult female patient, on prolonged corticosteroid therapy for nephrotic syndrome, developed erythema multiforme and toxic epidermal necrolysis following a double exposure to a locally applied perfume. We believe that this route of exposure should be re-emphasized. Toxic epidermal necrolysis, or the scalded skin syndrome, has become a well-recognized entity which may be divided into three distinct subgroups: the staphylococcal scalded skin syndrome, nonstaphylococcal or drug-induced scalded skin syndrome, and idiopathic. We present a patient who developed a dermatitis on her chest and abdomen after using a spray cologne, which resulted in the development of erythema multiforme with progression toxic epidermal necrolysis and, ultimately, her death.

Adrenal Cortex Hormones↗
PubMed1993

Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme.

BACKGROUND AND DESIGN: To conduct a prospective case-control study about causative factors of severe bullous erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, we needed to define criteria for classifying the cases and standardize the collection of data so that cases could be reliably diagnosed according to this classification. Based on review of case histories and photographs of patients, a group of experts proposed a classification based on the pattern of erythema multiforme-like lesions (categorized as typical targets, raised or flat atypical targets, and purpuric macules) and on the extent of epidermal detachment. An atlas illustrating this classification that included photographs and schematic drawings was developed. We compared the evaluations of 28 cases by four nonphysicians relying on the atlas with the evaluations of the same cases by five experts not using the atlas to determine the usefulness of this atlas for classifying cases according to our nosologic schema. RESULTS: The following consensus classification in five categories was proposed: bullous erythema multiforme, detachment below 10% of the body surface area plus localized "typical targets" or "raised atypical targets"; Stevens-Johnson syndrome, detachment below 10% of the body surface area plus widespread erythematous or purpuric macules or flat atypical targets; overlap Stevens-Johnson syndrome-toxic epidermal necrolysis, detachment between 10% and 30% of the body surface area plus widespread purpuric macules or flat atypical targets; toxic epidermal necrolysis with spots, detachment above 30% of the body surface area plus widespread purpuric macules or flat atypical targets; and toxic epidermal necrolysis without spots, detachment above 10% of the body surface area with large epidermal sheets and without any purpuric macule or target. Using the atlas, the nonexperts showed excellent agreement with the experts. CONCLUSION: This study suggests that an illustrated atlas is a useful tool for standardizing the diagnosis of acute severe bullous disorders that are attributed to drugs or infectious agents. Whether the five categories proposed represent distinct etiopathologic entities will require further epidemiologic and laboratory investigations.

Erythema Multiforme↗
PubMed1995

Erythema multiforme major and disseminated intravascular coagulation in a dog following application of a d-limonene-based insecticidal dip.

Erythema multiforme major and disseminated intravascular coagulation developed in a dog 24 hours after exposure to a d-limonene-based insecticidal dip. Clinical signs included severe lethargy and weakness, ulceration of the oral mucosa, and erythematous serpiginous, annular, and arciform lesions on the head, trunk, and limbs. Clinicopathologic abnormalities included leukocytosis with neutrophilia, normocytic normochromic anemia, thrombocytopenia, prolongation of prothrombin and partial thromboplastin times, increased fibrin degradation products, hypoproteinemia, hyponatremia, hypochloremia, azotemia, high serum alanine aminotransferase and alkaline phosphatase activities, and high serum bilirubin concentration. Despite intensive supportive care, the dog developed severe intrathoracic and abdominal hemorrhage and died. Necropsy revealed severe diffuse epidermal necrosis and widespread hemorrhage within organs. Insecticidal dips containing d-limonene have the potential to induce various toxic effects, including, possibly, erythema multiforme major, and should be used cautiously.

Animals↗
PubMed1985

Bullous erythema multiforme associated with Hemophilus influenzae pneumonia.

A 68-year-old woman with Hemophilus influenzae pneumonia experienced a bullous dermatosis. Further evaluation revealed bullous erythema multiforme of the minor type which resolved concurrently with treatment of the pneumonia. Clinicians should be aware that H. influenzae may be one of the bacterial agents known to cause erythema multiforme.

Aged↗
PubMed1984

Lupus erythematosus with erythema multiforme (Rowell's syndrome). A case report.

A patient who presented with erythema multiforme on clinical and histological examination but who subsequently developed fatal, fulminant systemic lupus erythematosus is reported. The prognostic significance of the development of erythema multiforme-type lesions in lupus erythematosus is discussed with reference to cases reported by Rowell et al. and Provost et al. The term 'Rowell's syndrome' is best avoided.

Adult↗
PubMed2000

Erythema multiforme: a case with unusual histopathological features.

A 14-year-old boy presented with widespread cutaneous and mucosal lesions clinically consistent with erythema multiforme. He gave a history of previous episodes of a similar eruption. Histological examination of a representative lesion showed changes consistent with erythema multiforme. It also, however, contained large numbers of eosinophils, forming a dermal interstitial infiltrate and epidermal microabscesses. The full blood examination showed a persistent eosinophilia. The appearances initially confused two experienced dermatopathologists.

Acyclovir↗
PubMed2004

Poison ivy: an underreported cause of erythema multiforme.

The relationship between herpes simplex virus (HSV) and erythema multiforme (EM) has been well described. Many authors contend that EM (excluding Stevens-Johnson syndrome and toxic epidermal necrolysis) occurs almost exclusively as a response to HSV infection. During the past year, however, we have observed several cases of EM complicating severe Rhus allergic contact dermatitis. Although this association has been previously documented, the paucity of cases in the literature, along with our experience, suggests that this is an underreported phenomenon. We describe 4 of our cases.

Adolescent↗
PubMed1988

Erythema multiforme is associated to HLA-Aw33 and DRw53.

Erythema multiforme is an acute eruption of the skin and mucous membranes of various aetiologies. Forty-one unrelated patients were HLA typed for 53 specificities of the HLA-A, B, C, DR and DQ series. Frequencies of Aw33 and DRw53 were significantly increased: Aw33, 17.0% in patients vs 2.8% in controls (corrected p = 0.01, relative risk = 7.2); DRw53, 70.7% in patients vs 30.5% in controls (corrected p = 0.0005, relative risk = 5.5).

Adult↗
PubMed2000

Diagnosis, classification, and management of erythema multiforme and Stevens-Johnson syndrome.

BACKGROUND: In adults, erythema multiforme (EM) is thought to be mainly related to herpes infection and Stevens-Johnson syndrome (SJS) to drug reactions. AIMS: To investigate this hypothesis in children, and to review our experience in the management of these patients. METHODS: A retrospective analysis of 77 paediatric cases of EM or SJS admitted to the Children's Hospital in Bordeaux between 1974 and 1998. RESULTS: Thirty five cases, inadequately documented or misdiagnosed mostly as urticarias or non-EM drug reactions were excluded. Among the remaining 42 patients (14 girls and 28 boys), 22 had EM (11 EM minor and 11 EM major), 17 had SJS, and three had isolated mucous membrane involvement and were classified separately. Childhood EM was mostly related to herpes infection and SJS to infectious agents, especially Mycoplasma pneumoniae. Only two cases were firmly attributed to drugs (antibiotics). No patient died. EM and SJS sequelae were minor and steroids were of no overall benefit. CONCLUSION: In paediatric practice EM is frequently misdiagnosed. The proposal that SJS is drug related in adults does not apply to children, and in our recruitment EM and SJS are mostly triggered by infectious agents. The course of both diseases, even though dramatic at onset, leads to low morbidity and mortality when appropriate symptomatic treatment is given.

Adolescent↗
PubMed2003

Herpes simplex virus (HSV)-associated erythema multiforme (HAEM): a viral disease with an autoimmune component.

Erythema multiforme (EM) is a clinical conundrum the name of which reflects the broad morphological spectrum of the lesions. Molecular and immunologic evidence that herpes simplex virus (HSV) causes a subset of EM lesions [herpes-associated EM (HAEM)] is reviewed, and new data are presented which suggest that autoreactive T-cells triggered by virus infection play an important role in HAEM pathogenesis. Disease development begins with viral DNA fragmentation and the transport of the DNA fragments to distant skin sites by peripheral blood mononuclear cells (PBMCs). HSV genes within DNA fragments deposited on the skin [notably DNA polymerase (Pol)] are expressed, leading to recruitment of HSV-specific CD4+ Th1 cells that respond to viral antigens with production of interferon-gamma (IFN-gamma). This step initiates an inflammatory cascade that includes expression of IFN-gamma induced genes, increased sequestration of circulating leukocytes, monocytes and natural killer (NK) cells, and the recruitment of autoreactive T-cells generated by molecular mimicry or the release of cellular antigens from lysed cells. The PBMCs that pick up the HSV DNA [viz. macrophages or CD34+ Langerhans cells (LC) precursors], their ability to process it, the viral proteins expressed in the skin and the presence of epitopes shared with cellular proteins may determine whether a specific HSV episode is followed by HAEM development. Drug-associated EM (DIEM) is a mechanistically distinct EM subset that involves expression of tumor necrosis factor alpha (TNF-alpha) in lesional skin. It is our thesis that the polymerase chain reaction (PCR) assay for HSV DNA detection in lesional skin and staining with antibodies to IFN-gamma and TNF-alpha, are important criteria for the diagnosis of skin eruptions and improved patient management.

Antigens, Surface↗