Erythema Multiforme Major Research Articles

Ocular Manifestations in Paediatric Erythema Multiforme: A Case Report

Erythema multiforme (EM) is a type IV cytotoxic hypersensitivity reaction characterized by classic target lesions on the skin and mucosa, typically affecting the oral, genital, and rarely, ocular mucosa. We describe a 9-year-old girl with widespread rashes, blisters and target lesions on her trunkfor three days. She had eye redness, discomfort, a week-long fever, and a dry cough, without any medication. Ophthalmological examination revealed localized conjunctival injection in her right eye, with no visual impairment or corneal lesions. The diagnosis of EM major (EMM) was based on prior infection, characteristic skin lesions, and mucosal involvement, including ocular manifestation of conjunctival injection. Treatment requires addressing the underlying cause and ophthalmologic consultation for systemic or topical corticosteroids, antibiotics, lubricants, and antihistamines. This case highlights the diagnostic challenges of atypical EM presentations, emphasizing the need for comprehensive evaluation, early recognition, and interdisciplinary collaboration to prevent severe ocular complications and preserve vision.

A case of Mycoplasma pneumoniae‐induced rash and mucositis with recent influenza vaccination

AbstractA 33‐year‐old female presented with coryzal symptoms, facial swelling, severe haemorrhagic stomatitis, blistering oral mucositis, conjunctival injection and a sparse targetoid rash on the back and face, requiring admission to hospital. She had received the seasonal influenza vaccination 3 days prior to feeling unwell. Differential diagnosis included erythema multiforme major (EMM) secondary to the influenza vaccine or Mycoplasma pneumoniae‐induced rash and mucositis (MIRM). Oropharyngeal swabs were negative on PCR for cutaneous viruses and Mycoplasma pneumoniae (MP). A skin biopsy from a targetoid lesion on the body showed full thickness epidermal necrosis with epidermal–dermal clefting, numerous civatte bodies and a moderate perivascular infiltrate of lymphocytes and plasma cells in the papillary dermis. She was successfully treated with oral prednisolone and azithromycin. Following discharge from hospital, the paired serological testing for MP returned positive, confirming a diagnosis of MIRM. Our case highlights the difficulties in detecting MP as two diagnostic methods yielded different results, and so we advocate performing both MP PCR and serology to maximise the yield and speed of diagnosis. Secondly, our case highlights the clinical challenge in differentiating MIRM from EMM or Stevens–Johnson syndrome, particularly if there is a potential drug trigger (in our case the influenza vaccine), as all these conditions can feature a severe mucositis with often indistinguishable histological findings. Correct diagnosis of MIRM is important for appropriate and timely administration of anti‐MP antibiotic therapy to facilitate recovery and minimise complications.

Nimesulide-induced Erythema Multiforme Major: A Case Report

Erythema Multiforme Major (EMM) is a rare hypersensitivity reaction that primarily affects the skin and mucosa, typically self-limiting. This case discusses a patient who developed severe EMM lesions after consuming nimesulide, a non-steroidal anti-inflammatory drug (NSAID), for abdominal discomfort. Patient was admitted to the hospital, the drug was discontinued, and supportive measures such as pain management and fluid replacement were initiated. This case, being the first to identify nimesulide as a possible trigger for EMM, aims to contribute to the growing body of knowledge on this topic. It emphasizes the need for vigilance and swift intervention for unusual drug reactions.

Childhood epidermal necrolysis and erythema multiforme major: a multicentre French cohort study of 62 patients.

The distinction between epidermal necrolysis [EN; including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and overlap syndrome] and erythema multiforme major (EMM) in children is confusing. We aimed to better describe and compare these entities. This French retrospective multicentre study included children ≤18years old referred for EN or EMM between 1 January 2008 and 1 March 2019. According to pictures, children were reclassified into TEN/overlap, SJS or EMM/unclassified (SJS/EMM) groups and compared for epidemiological and clinical data, triggers, histology and follow-up. We included 62 children [43 boys, median age 10years (range 3-18)]: 16 with TEN/overlap, 11 SJS and 35 EMM. The main aetiologies were drugs in EN and infections (especially Mycoplasma pneumoniae) in EMM (P<0.001), but 35% of cases remained idiopathic (TEN/overlap, 47%; SJS, 24%; EMM, 34%). The typical target lesions predominated in EMM (P<0.001), the trunk was more often affected in EN (P<0.001), and the body surface area involved was more extensive in EN (P<0.001). Mucosal involvement did not differ between the groups. Two patients with idiopathic TEN died. Histology of EMM and EN showed similar features. The recurrence rate was 42% with EMM, 7% with TEN/overlap and 0 with SJS (P<0.001). Sequelae occurred in 75% of EN but involved 55% of EMM. Clinical features of EN and EMM appeared well demarcated, with few overlapping cases. Idiopathic forms were frequent, especially for EN, meaning that a wide and thorough infectious screening, repeated if needed, is indicated for all paediatric cases of EN/EMM without any trigger drug. We propose a comprehensive panel of investigations which could be a standard work-up in such situation. Sequelae affected both EN and EMM.

Clonal expansion of CD4+CD8+ T cells in an adult patient with Mycoplasma pneumoniae-associated Erythema multiforme majus

BackgroundErythema multiforme (EM) is an acute, immune-mediated mucocutaneous disease, most often preceded by herpes simplex virus (HSV) infection or reactivation. Mycoplasma pneumoniae (Mp) is considered the second major trigger of EM and is often associated with an atypical and more severe presentation of disease, characterized by prominent mucosal involvement. However, contrary to HSV-associated Erythema multiforme (HAEM), immunological mechanisms of Mp-associated EM remain unclear.Case presentationWe present the case of a 50-year-old male patient presenting with community-acquired pneumonia (CAP) and erythema multiforme majus (EMM). Acute Mp infection was diagnosed by seroconversion, with no evidence of HSV infection as a cause of EMM. We performed immune phenotyping of blister fluid (BF) and peripheral blood (PB) T cells and detected a clonally expanded TCRVβ2+ T cell population that was double positive for CD4 and CD8, and expressed the cytotoxic markers granulysin and perforin. This CD4+CD8+ population comprised up to 50.7% of BF T cells and 24.9% of PB T cells. Two years prior to the onset of disease, the frequency of PB CD4+CD8+T cells had been within normal range and it gradually returned to baseline levels with the resolution of symptoms, suggesting an involvement of this population in EMM disease pathophysiology.ConclusionsThis report is the first to provide a phenotypic description of lesional T cells in Mp-associated EMM. Characterizing the local immune response might help to address pathophysiological questions and warrants further systematic research.

A case of erythema multiforme major presenting with varicella‐like manifestations

A case of erythema multiforme major presenting with varicella‐like manifestations

Erythema Multiforme Major Induced by Lysergic Acid Diethylamide

Erythema multiforme major (EMM) is a severe hypersensitivity skin reaction that is potentially life threatening. We present a case report of a gentleman who presented with EMM induced by Lysergic acid diethylamide. The case aims to raise awareness and highlights the importance of taking a comprehensive drug history including recreational drug use. This is especially important in the face of rising recreational drug usage rates.

Erythema multiforme major with swollen lips and crusted erosions

Erythema multiforme major with swollen lips and crusted erosions

Reasons for inpatient admissions to the dermatology department in Lomé, Togo: Trends between 1992 to 2005 and 2005 to 2016.

The aim of this study was to report the frequency of and reasons for dermatology admissions in Lomé (Togo) between 2005 and 2016. This retrospective study examined records from August 2005 to December 2016 from the dermatology departments of the two teaching hospitals in Lomé, Togo. During the study period, 454 (1.1%) of the 40,231 new patients who consulted in dermatology were hospitalized, with a total of 460 separate admissions (mean dermatology hospitalizations per year: 42). Patients' mean age was 43±17.6 years and the sex ratios (M/F) was 0.6. The main reasons for hospitalization were Stevens-Johnson syndrome (SJS), also known as erythema multiforme majus, and toxic epidermal necrolysis (TEN) (28.9%), followed by bullous erysipelas (21.4%), connective tissue disease (10.3%), and Kaposi sarcoma-associated herpes virus (9%). The average length of stay in hospital was 15±13.7 days. The diagnosis that accounted for the longest mean length of stay was deep fungal infections (63.5 days) (P<0.0001). We recorded 39 deaths, for a death rate of 8.6%. Death rates were highest for deep fungal infections (37.5%) and SJS/TEN (12.2%). Our study confirmed the low rate of inpatient admissions in dermatology and revealed a change in the reasons for hospitalization and a decrease in mortality in dermatology in Lomé, compared with the previous 13 years. This decrease in mortality may be attributed to the improvement of hospital care provided to patients but also by the generalization of antiretroviral treatment in Togo that began more than 10 years ago.

Abstract P-105: A COMPARATIVE STUDY ON CHILDREN WITH ERYTHEMA MULTIFORME MAJUS SYNDROME

Aims & Objectives: To compare the effect of blood purification therapy with steroid-immunoglobulin therapy in children with severe erythema multiforme majus. Methods The clinical data of 30 children admitted between 2010 and 2016 were retrospectively reviewed. These children were separated into two groups according to the therapeutic method. Results No death occurred in two groups. The results showed that the duration of fever and majus was shorter in blood-purification group comparing with steroid-immunoglobulin group, as well as the duration of mucosal lesions. Conclusions The blood purification therapy is more effective for children with severe erythema multiforme majus. It can decline the mortality.

Stevens-Johnson Syndrome

Stevens-Johnson syndrome (SJS) is an immune complex mediated hypersensitivity complex that typically involves the skin and mucous membranes. While minor presentations may occur, significant involvement of oral, nasal, eye, vaginal, urethral, gastrointestinal, and lower respiratory mucous membranes may develop in the course of the illness. GI and respiratory involvement may progress to necrosis. Stevens-Johnson syndrome is a serious systemic disorder with the potential for severe morbidity and even death. The syndrome was first described in 1922, when the American pediatricians Albert Mason Stevens and Frank Chambliss Johnson reported the cases of 2 boys aged 7 and 8 years with "an extraordinary, generalized eruption with continued fever, inflamed buccal mucosa, and severe purulent conjunctivitis". Both cases had been misdiagnosed by primary care physicians as hemorrhagic measles. Erythema multiforme (EM), originally described by Von Hebra in 1866, was part of the differential diagnosis in both cases but was excluded because of the 'character of skin lesions, the lack of subjective symptoms, the prolonged high fever, and the terminal heavy crusting". Despite the presence of leucopenia in both cases, Stevens and Johnson in their initial report suspected an infectious disease of unknown etiology as the cause. In 1950, Thomas divided EM into 2 catagories: erythema multiforme minor (Von Hebra) and Erythema multiforme major (EMM). Since 1983, erythema multiforme major and Stevens-Johnson syndrome had been considered synonymous. In the 1990s, however, Bastuji and Roujeau each proposed that Erythema multiforme major and Stevens-Johnson syndrome are 2 distinct disorders. Several investigators propose that Stevens-Johnson syndrome and Toxic epidermal necrolysis (TEN) represent the same disease at different levels of severity. Although several classification schemes have been reported, the simplest breaks the disease down as follows: * Stevens-Johnson syndrome-A "minor form of TEN", with less than 10% body surface area (BSA) detachment. * Overlapping Stevens-Johnson syndrome/Toxic epidermal necrolysis (SJS/TEN)-Detachment of 10-30% BSA. * Toxic epidermal necrolysis-Detachment of more than 30%BSA.KYAMC Journal Vol. 8, No.-2, Jan 2018, Page 31-35

Erythema Multiforme in Children and Mycoplasma pneumoniae Aetiology.

Erythema multiforme (EM) in children is understudied and confused with Stevens-Johnson syndrome (SJS) despite their being separate diseases with unique aetiologies and clinical presentations. The goal of this study was to determine the prevalence of Mycoplasma pneumoniae in paediatric patients with EM minor, EM major (EMM), and SJS. This retrospective cohort at The Hospital for Sick Children accrued all cases of EM minor, EMM, and SJS from 1999 to 2013. Sixty-five cases were identified: 20 of EM minor, 23 of EMM, and 22 of SJS. Aetiologies were attributed in 58% of cases: 79% infection and 21% drug aetiology. Sixty-one percent of patients with EMM were M pneumoniae positive, compared with 14% of those with SJS and 22% of those with EM minor (P < .01). M pneumoniae patients were older at presentation (P = .03) and more frequently had sore throat (P < .01) and atypical targets with central blistering (P < .01). These findings suggest that M pneumoniae should be suspected and treated until laboratory confirmation becomes available in patients presenting with atypical target lesions with central blistering.

Herpes iris of Bateman.

An 11-year-old boy presented with mildly painful erythematous rash and vesiculobullous lesions over the trunk and in the oral cavity of three days duration. One day prior, he started developing vesiculobullous lesions over his arms. Ten days prior, he had an episode of sore throat and mild fever, for which he received azithromycin. There was no history of similar lesions in the past or family history of similar lesions. On examination, ‘target’ lesions were noted over the trunk, oral cavity and genitalia [Figure 1a]. The arms were notable for a distinctive type of lesion, characterized by central bulla over an erythematous background and a ring of vesicles at the margin [Figure 1b]. Systemic examination did not reveal any abnormality. Routine blood examination revealed mild leukocytosis and elevated ESR. Based on classical target lesions and mucosal involvement, clinical diagnosis of erythema multiforme major (EMM) was made. Our case was notable for ‘Herpes iris of Bateman’ lesions over the upper extremities. The boy was treated conservatively and all lesions subsided within 2 weeks with mild hyperpigmentation.

Erythema Multiforme in a Patient with Recurrent Non-Hodgkins Lymphoma/Chronic Lymphocytic Leukemia

Erythema multiforme major (EMM) is a hypersensitivity reaction usually secondary to medications, viruses or other infections. Its presentation is fairly typical with a symmetrical distribution of vesicles, bullae or targeted lesions on the upper body, arms, legs, palms, feet and oral mucosa. The authors present a delineated case of EMM in association with chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma (NHL) with a very unusual clinical presentation evolving overtime into a unique, almost dermatomal distribution. Typical therapies were not initially helpful and intravenous immunoglobulin antibody had to be administered.

Distinguishing between erythema multiforme major and Stevens–Johnson syndrome/toxic epidermal necrolysis immunopathologically

The early clinical presentations of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are similar to that of erythema multiforme major (EMM). Cytotoxic molecules, especially granulysin, are expressed in the skin lesions of SJS/TEN and cause extensive keratinocyte death. It is postulated that the function of regulatory T cells (Treg) in SJS/TEN is inadequate. This study examined whether an immunohistological examination of cytotoxic molecules and the immunophenotype of Treg is useful for discriminating SJS from EMM in the early period. Over the past 9 years, the lesional skin of 14 patients with SJS/TEN and 16 patients with EMM was biopsied. Double immunofluorescence labeling of CD8 and granulysin, perforin, or granzyme B was performed, and immunohistochemical analyses of granulysin, perforin, granzyme B, CD1a, CD3, CD4, CD8, CD68 and Foxp3 were conducted using a highly sensitive indirect immunoperoxidase technique. The number of cells positive for each antibody per five high-power fields was counted. The proportions of granulysin(+) cells/CD8(+) cells (P = 0.012) and perforin(+) cells/CD8(+) cells (P = 0.037) in SJS/TEN were significantly higher than in EMM. The number of Foxp3(+) cells/five high-power fields in SJS/TEN was significantly lower than in EMM (P = 0.004). Similarly, the number of CD4(+) cells/five high-power fields in SJS/TEN was significantly lower than in EMM (P = 0.0017). These data suggest that these panels of antibodies for labeling cytotoxic molecules, CD4 and Treg are useful for discriminating early SJS/TEN and EMM with a skin biopsy.

Critical factors differentiating erythema multiforme majus from Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN)

Erythema multiforme majus (EMM) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are severe cutaneous reactions characterised by targetoid erythematous lesions and mucocutaneous involvement. The initial skin manifestations are similar, making early diagnosis difficult. We retrospectively reviewed 36 cases of EMM and 18 cases of SJS/TEN and also evaluated 6 patients with unclassified EMM. 13 patients in the EMM group and 16 patients in the SJS/TEN group presented with a high fever (>38.5̊C; p&#60;0.001). Two or more mucous membranes were affected in 6 patients in the EMM group and 18 patients in the SJS/TEN group. Significantly more SJS/TEN than EMM patients had high levels of C-reactive protein and severe hepatic dysfunction. Thirteen EMM and 13 SJS/TEN cases were caused by medications/drugs. Skin biopsy samples showed stronger mononuclear cell infiltration in the EMM than in the SJS/TEN group (p&#60;0.001). The mean dose of initial systemic corticosteroid used to treat EMM was lower than that used to treat SJS/TEN. No patients died in either group. Clinically, the unclassified cases mostly behaved like EMM. The results of our investigation suggest that EMM and SJS/TEN are distinct conditions and they help in differentiating these syndromes at an early stage.

The Ophthalmologist's Role in the Management of Acute Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Stevens-Johnson syndrome (SJS) and its more severe variant, toxic epidermal necrolysis (TEN), are relatively rare but have high mortality rates. Survivors are frequently afflicted with severe blinding ocular surface diseases. Recent literature in the areas of ophthalmology and dermatology illustrate that the ophthalmologist's role should no longer be considered secondary in the acute management of SJS/TEN. Accurately differentiating SJS or TEN from erythema multiforme majus (EMM) at the onset of the disease is important, because the management approach to these disease entities differs. Systemic cyclosporine and intravenous immunoglobulin have shown some potential as treatments for SJS/TEN, but their efficacies remain controversial. Amniotic membrane transplantation and intravenous corticosteroid pulse therapy at the acute stage have shown promise for preventing late sight-threatening cicatricial complications. An improved staging system for the ocular surface involvement of acute SJS/TEN, as well as better understanding of the underlying destructive pathogenic mechanism, should further improve our ability to predict ocular involvement and develop new therapeutics to abort destructive processes at the acute stage.

Ciprofloxacin-induced Stevens-Johnson syndrome: First report from Bangladesh

Stevens-Johnson syndrome, otherwise known as erythema multiforme majus, was first described in 1922 by Stevens and Johnson as a febrile illness with stomatitis, purulent conjunctivitis, and skin lesions. Case report: We report a 28-year-old married woman who presented with fever and was advised ciprofloxacin tablet. After taking two doses of the tablet, she developed papulo-vesicular rash involving the trunk and the upper and lower limbs, including mucous membranes. She also developed a painful red eye. She eventually developed jaundice and her case was ultimately diagnosed as ciprofloxacin-induced Stevens-Johnson syndrome. Discussion: Medications appear to be the most common cause of Stevens-Johnson syndrome. It commonly affects multiple organs. Treatment for Stevens-Johnson syndrome is as diverse as the symptoms and it should be begun by withdrawing any offending agent identified. Conclusion: Stevens-Johnson syndrome is a potentially fatal multiorgan disease. This aspect of the condition is best addressed by early involvement of medical specialists.

Érythème polymorphe majeur et infection à Chlamydia pneumoniae

Erythema multiforme majus of infectious origin is an acute eruptive syndrome seen more commonly in young subjects and characterised by an appearance of round target lesions. In most cases, it is associated with infection involving Herpes simplex virus or Mycoplasma pneumoniae. We report an original case of erythema multiforme majus subsequent to infection with Chlamydia pneumoniae. An 18 year-old man was hospitalised for management of generalised skin rash comprising lesions in rings, associated with bullous and post-bullous lesions, chiefly in the oral (preventing eating) and genital areas in a setting of febrile cough. Various bacterial agents (Mycoplasma pneumoniae, Chlamydia pneumoniae) and viral agents were suspected, but serological testing for Chlamydia pneumoniae alone was positive with IgM of 128 IU and IgG of 64 IU. The outcome was favourable within several days following administration of symptomatic treatment (rehydration, mouthwashes, etc.) and aetiological treatment (acyclovir: 30 mg/kg/d, ofloxacine: 400 mg/d). At D15, serologic tests for Mycoplasma pneumoniae continued to be negative. Anti-Chlamydia pneumoniae IgM and IgG were 256 IU. At D30, IgM was 128 IU while IgG remained at 256 IU. The existence of a systematic skin rash comprising typical target lesions and mucosal lesions in the oral and genital areas suggested to us a diagnosis of erythema multiforme majus. Screening for the agents generally responsible was negative and drug-induced rash was ruled out. Serological tests for Chlamydia pneumoniae were positive at various times, resulting in diagnosis of erythema multiforme majus secondary to infection with Chlamydia pneumoniae. Following demonstration of the presence of Chlamydia pneumoniae using reliable methods and the elimination of other causes of erythema multiforme majus, dermatologists should opt for this aetiology in order to optimise treatment.

Correlations between clinical patterns and causes of erythema multiforme majus, Stevens-Johnson syndrome, and toxic epidermal necrolysis: results of an international prospective study.

It was proposed that Stevens-Johnson syndrome and toxic epidermal necrolysis differed from erythema multiforme majus by the pattern and localization of skin lesions. To evaluate the validity of this clinical separation. Case-control study. Active survey from 1989 to 1995 of 1800 hospital departments in Europe. A total of 552 patients and 1720 control subjects. Cases were sorted into 5 groups (erythema multiforme majus, Stevens-Johnson syndrome, Stevens-Johnson syndrome-toxic epidermal necrolysis overlap, toxic epidermal necrolysis, and unclassified erythema multiforme majus or Stevens-Johnson syndrome) by experts blinded as to exposure to drugs and other factors. Etiologic fractions for herpes and drugs obtained from case-control analyses were compared between these groups. Erythema multiforme majus significantly differed from Stevens-Johnson syndrome, overlap, and toxic epidermal necrolysis by occurrence in younger males, frequent recurrences, less fever, milder mucosal lesions, and lack of association with collagen vascular diseases, human immunodeficiency virus infection, or cancer. Recent or recurrent herpes was the principal risk factor for erythema multiforme majus (etiologic fractions of 29% and 17%, respectively) and had a role in Stevens-Johnson syndrome (etiologic fractions of 6% and 10%) but not in overlap cases or toxic epidermal necrolysis. Drugs had higher etiologic fractions for Stevens-Johnson syndrome, overlap, or toxic epidermal necrolysis (64%-66%) than for erythema multiforme majus (18%). Unclassified cases mostly behaved clinically like erythema multiforme. This large prospective study confirmed that erythema multiforme majus differs from Stevens-Johnson syndrome and toxic epidermal necrolysis not only in severity but also in several demographic characteristics and causes.