Recurrent Erythema Multiforme Research Articles

The Completion of Postoperative Radiotherapy After Breast-Conserving Surgery in a Patient With Recurrent Erythema Multiforme: A Case Report

The Completion of Postoperative Radiotherapy After Breast-Conserving Surgery in a Patient With Recurrent Erythema Multiforme: A Case Report

Immunoglobulin-E (IgE) Screening for Detecting Mouthwash Allergic Reactions with Recurrent Oral Erythema Multiforme: A Case Report

Immunoglobulin-E (IgE) Screening for Detecting Mouthwash Allergic Reactions with Recurrent Oral Erythema Multiforme: A Case Report

Recurrent bullous erythema multiforme due to oral contraceptive therapy.

Recurrent bullous erythema multiforme due to oral contraceptive therapy.

Prevention of recurrent erythema multiforme with lenalidomide: a case series.

Prevention of recurrences of erythema multiforme is a therapeutic challenge. Thalidomide is effective, but its use is limited by adverse effects, especially peripheral neuropathy. We report seven cases of recurrent severe erythema multiforme treated with lenalidomide. In six cases, the drug was effective without significant adverse effects.

Oral Manifestation of Viral-Induced Erythema Multiforme Major: A Rare Presentation.

Erythema multiforme is an acute inflammatory mucocutaneous disease manifested as macules, vesicles, bullae, erosion, and papular lesions. In the present case, a 55-year-old female patient reported painful growth in the oral cavity and difficulty in mastication. The patient gave a history of prodromal symptoms before the onset of lesions On intra-oral examination, elevated plaque-like lesions were present bilaterally on lateral borders of the tongue and buccal mucosa near the retromolar region. Extraoral examination revealed concentric erythematous target (or) bull's eye lesions in palms, forearm, and foot. Based on history, clinical examination, and laboratory investigations, recurrent herpes-associated erythema multiforme was diagnosed. We report a rare clinical presentation of recurrent herpes-associated erythema multiforme manifesting as an extensive plaque-like lesion intra-orally.

P103 A retrospective observational study of toxic epidermal necrolysis at a tertiary referral centre from 2015 to 2022

Abstract Toxic epidermal necrolysis (TEN) is associated with high mortality and morbidity. Owing to a lack of robust evidence, treatment guidelines are ambiguous and clinicians must use discretion in management decisions, specifically with regard to the use and choice of systemic agents, including immunosuppressants. We present a retrospective study of cases referred to a tertiary referral centre between 2015 and 2022. Cases were identified using histopathology coding and a database compiled by clinicians. Forty cases were categorized as follows: TEN (n = 12); Stevens–Johnson syndrome (SJS)/TEN overlap (n = 5); SJS (n = 5); unclear (n = 9); insufficient information (n = 5) and others [n = 9 (lupus, n = 4; erythema multiforme major, n = 3; burn, n = 1; recurrent erythema multiforme, n = 1)]. The median age of patients with TEN was 66 [interquartile range (IQR) 53.3–74; 33% men, 67% women]. The median percentage body surface area of epidermal loss was 40% (n = 8; IQR 30–70). Forty-two per cent of patients had an underlying malignancy. Implicated medications included nivolumab/ipilimumab (n = 2), co-trimoxazole (n = 2), carbamazepine (n = 1) and proton pump inhibitors (n = 3). Sixty-seven per cent of patients with TEN were managed by the burns centre, with a further 17% admitted to the intensive care unit. One patient presented directly to the dermatology team and 58% were transferred from other hospitals. The median time from the documented onset of rash to transfer to specialist care was 5 days (IQR 2.8–11.5). Thirty-three per cent of patients were given immunosuppression (intravenous methylprednisolone). The median duration of admission was 14 days (IQR 7.5–21.5). Fifty-eight per cent of patients (n = 7) survived. None of the five patients who died had received immunosuppression. The median time from onset of rash to receiving specialist care was 3.5 days for those who survived (n = 4) vs. 10 days for those who did not (n = 3; P = 0.03). Thirty-three per cent of patients had documented chronic complications (severe ophthalmic sequelae, n = 2; circumcision for phimosis, n = 1). This study was limited by the retrospective collection of data and the method used to identify cases. The current evidence for the treatment of TEN is primarily derived from small case series that often combine heterogeneous cases of TEN, SJS/TEN overlap and SJS. This is highly problematic as the risk–benefit dynamic varies greatly between patients with SJS, who have an excellent prognosis without treatment, and patients with TEN with a high associated mortality, who potentially have more to gain from immunosuppression. Our data support the need for patients to access specialist care promptly, to allow for early consideration of immunosuppression. Future research should focus on effective treatments for reducing mortality in cases of TEN specifically.

Atypical Cutaneous Viral Infections Reveal an Inborn Error of Immunity in 8 Patients.

Unusual viral skin infections might be the first clinical manifestation in children with an inborn error of immunity (IEI). We performed a prospective study from 1 October 2017 to 30 September 2021, at the Department of Pediatric Infectious Diseases and Clinical Immunity of Ibn Rochd University Hospital-Casablanca. During this period, on 591 patients newly diagnosed with a probable IEI, eight of them (1.3%), from six independent families, had isolated or syndromic unusual viral skin infections, which were either profuse, chronic or recurrent infections, and resistant to any treatment. The median age of disease onset was nine years old and all patients were born from a first-degree consanguineous marriage. By combining clinical, immunological and genetic investigations, we identified GATA2 deficiency in one patient with recalcitrant profuse verrucous lesions and monocytopenia (1/8) and STK4 deficiency in two families with HPV lesions, either flat or common warts, and lymphopenia (2/8), as previously reported. We also identified COPA deficiency in twin sisters with chronic profuse Molluscum contagiosum lesions, pulmonary diseases and microcytic hypochromic anemia (2/8). Finally, we also found one patient with chronic profuse MC lesions and hyper IgE syndrome, (1/8) and two patients with either recalcitrant profuse verrucous lesions or recurrent post-herpetic erythema multiforme and a combined immunodeficiency (2/8) with no genetic defect identified yet. Raising clinicians awareness that infectious skin diseases might be the consequence of an inborn error of immunity would allow for optimized diagnosis, prevention and treatment of patients and their families.

Non-FDA-Approved Uses of Apremilast in Dermatology: A Review of Current Available literature

Introduction: Apremilast, an oral phosphodiesterase-4 inhibitor, decreases the production of pro-inflammatory cytokines including tumour necrosis factor-α, interleukin-12/23, IL-12, IL-2, and interferon-γ; while upregulating the anti-inflammatory cytokine IL-10. Its pan-immunomodulatory nature has led to its use in managing various immune-mediated dermatoses for non-FDA-approved indications. Objectives: To review and analyze the use of Apremilast in Non-FDA-approved indications in current available literature. Materials and methods: PubMed, EMBASE, SCOPUS, and Google scholar databases were searched with the parameters “Apremilast”, “Apremilast NOT Psoriasis*”, “Apremilast NOT Behçet’s*”, and “Apremilast NOT arthritis*”. A total of 45 relevant articles were chosen for review. Results: We found 22 indications in dermatology where apremilast has been used without FDA approval. The best evidence was for treatment in Atopic Dermatitis, Alopecia Areata, and Hidradenitis Suppurativa, with randomized controlled trials. Prospective open-label trials were found for Cutaneous Sarcoidosis, Lichen Planus, Rosacea, and Vitiligo. Individual case series and reports were found for Acrodermatitis Continua of Hallopeau, Dermatomyositis, Disseminated Granuloma Annulare, Erythema Nodosum Leprosum, Morphea, Pityriasis Rubra Pilaris, Hailey-Hailey Disease, Recurrent Erythema Multiforme, and Folliculitis Decalvans, Prurigo Nodularis, Perforating Dermatoses, Chronic Actinic Dermatitis, and Hand Eczema, and Epidermolysis Bullosa Simplex-Generalised Severe Type. Apremilast has shown varied efficacy despite a better safety profile and tolerability over a long duration compared to conventional immunosuppressant drugs and placebo. Conclusion: Apremilast has been used for varied non-FDA-approved indications in dermatology with variable efficacy. Better controlled, randomized studies with adequate sample size and drug comparisons are needed for better analyses.

RECURRENT ORAL ERYTHEMA MULTIFORME: AN UNUSUAL SUBTYPE OF ERYTHEMA MULTIFORME

Recurrent oral erythema multiforme (ROEM) is an unusual subtype of erythema multiforme, which is characterized by multiple, recurrent, self-limiting, and painful oral ulcers, evidence of herpes simplex virus (HSV) infection, and absence of cutaneous lesions. The diagnosis of ROEM is difficult and challenging, because other similar diseases should be carefully excluded. Acyclovir and/or corticoids are employed but with variable results. A 52-year-old woman presented with recurrent and painful oral ulcers in the buccal mucosa, soft palate, and gingiva in the last 12 months, with 6 to 8 recurrences during this period. The histopathologic analysis revealed an unspecified chronic lymphoplasmacytic infiltrate. Serologic tests were negative, among others, for Veneral Disease Research Laboratory (VDRL) and fluorescent treponemal antibody absorption (FTA-ABS) but positive for HSV 1/2 IgG and IgM. This report emphasizes the importance of identifying the subtypes of erythema multiforme, aiming to deal with its therapeutic and prognostic implications. Recurrent oral erythema multiforme (ROEM) is an unusual subtype of erythema multiforme, which is characterized by multiple, recurrent, self-limiting, and painful oral ulcers, evidence of herpes simplex virus (HSV) infection, and absence of cutaneous lesions. The diagnosis of ROEM is difficult and challenging, because other similar diseases should be carefully excluded. Acyclovir and/or corticoids are employed but with variable results. A 52-year-old woman presented with recurrent and painful oral ulcers in the buccal mucosa, soft palate, and gingiva in the last 12 months, with 6 to 8 recurrences during this period. The histopathologic analysis revealed an unspecified chronic lymphoplasmacytic infiltrate. Serologic tests were negative, among others, for Veneral Disease Research Laboratory (VDRL) and fluorescent treponemal antibody absorption (FTA-ABS) but positive for HSV 1/2 IgG and IgM. This report emphasizes the importance of identifying the subtypes of erythema multiforme, aiming to deal with its therapeutic and prognostic implications.

A Case Report: Clinical Efficacy of Combination Treatment of Dexamethasone and Azathioprine in Recurrent Erythema Multiforme

Recurrent erythema multiforme (REM) may have frequent episodes over a period of several years and is considered to be a hypersensitivity reaction associated with infection or medication. REM is a mucocutaneous disorder which is characterized by targetoid lesions. Most of the cases are caused by herpes simplex virus infection. Systemic corticosteroid is frequently used to treat REM due to its effects in suppressing the disease. When REM is unresponsive to systemic corticosteroid, steroid-sparing treatment needs to be instituted. We reported a case of REM in a 49-year-old male. There were complaints of burning sensations on the skin lesions, along with swelling on both hands. On physical examination, erythematous macules and targetoid lesions were found on both palms, arms, and legs. During hospitalization, dexamethasone 20 mg was administered in a tapering dose but new skin lesions still appeared. Two days after azathioprine 50 mg twice daily was added to the treatment, skin lesions and swelling on the patient’s hands were diminished and the burning sensation disappeared. No side effects of azathioprine were found in this patient and no recurrence until two weeks after hospitalization. This case report demonstrated the efficacy of combined treatment of dexamethasone and azathioprine for REM cases unresponsive to systemic corticosteroid.

Erythema Multiforme Is Not Always Erythema Multiforme

Rowell syndrome (RS) describes the rare presentation of EM like lesions found in association with a diagnosis of lupus erythematosus (LE). Major diagnostic criteria includes LE, EM, and anti-nuclear antibodies. Minor criteria includes of chilblains, anti-Ro/anti-La antibodies, and rheumatoid factor. We present a 26-year-old white male seen in consultation for chronic erythema multiforme (EM) with a duration of 6 months unresponsive to treatment. Prior to our evaluation, he had been seen by another dermatologist and was diagnosed with biopsy-proven EM. His rash did not respond to previous treatment, including corticosteroids and antifungals. Lab results showed a positive ANA and positive anti-Ro antibody. The patient met diagnostic criteria for RS and was started on hydroxychloroquine 200 mg twice daily. Improvement was noticed two weeks after beginning treatment. Our case demonstrates that an atypical presentation of recurrent erythema multiforme, which does not respond to typical EM treatment, should raise a suspicion for RS and prompt screening for autoimmune markers and lupus erythematosus.
 
 

Recent Updates in the Treatment of Erythema Multiforme.

Erythema multiforme (EM) is an immune-mediated condition that classically presents with discrete targetoid lesions and can involve both mucosal and cutaneous sites. While EM is typically preceded by viral infections, most notably herpes simplex virus (HSV), and certain medications, a large portion of cases are due to an unidentifiable cause. EM can be confused with other more serious conditions like Stevens–Johnson syndrome (SJS); however, clinical research has provided significant evidence to classify EM and SJS as separate disorders. Treatment of EM is highly variable, depending on the etiology, the involvement of mucosal sites, and the chronicity (acute vs. recurring) of the disease. If the etiology or causal medication/infection is identified, then the medication is stopped and/or the infection is treated prior to initiating symptomatic treatment. Treatment for acute EM is focused on relieving symptoms with topical steroids or antihistamines. Treatment for recurrent EM is most successful when tailored to individual patients. First line treatment for recurrent EM includes both systemic and topical therapies. Systemic therapies include corticosteroid therapy and antiviral prophylaxis. Topical therapies include high-potency corticosteroids, and antiseptic or anesthetic solutions for mucosal involvement. Second-line therapies for patients who do not respond to antiviral medications include immunosuppressive agents, antibiotics, anthelmintics, and antimalarials

Recurrent erythema multiforme: A therapeutic proposal for a chronic disease.

Recurrent erythema multiforme is a chronic relapsing disease that represents a therapeutic challenge. Our objective was to retrospectively evaluate the clinical-epidemiological characteristics and therapeutic response of patients with recurrent erythema multiforme and suggest a therapeutic protocol. We included patients with recurrent erythema multiforme diagnosed between January 2000 and December 2019. Clinical symptoms and a positive serology for herpes simplex virus were the inclusion criteria to initiate acyclovir in monotherapy or a combined treatment with dapsone, thalidomide, or immunosuppressants in refractory cases. Thirty-five patients were included and 71.4% were female. The median disease onset age was 35.7years and the mean follow-up was 7.58years. The skin was the most affected site (91.4%). Herpes simplex virus immunoglobulin (Ig)G serology was positive in 91.1% of cases. Acyclovir treatment was used in 33 of 35 patients, and complete remission was achieved in 22 of 33 after the first therapeutic course; 16 of 22 relapsed and required a second acyclovir cycle. Combined treatment with dapsone was required in nine of 33 due to partial response to acyclovir; thalidomide was an adjuvant drug in four of 33 due to adverse effects to dapsone. After the first cycle of acyclovir with or without combined therapy, 19 of 33 patients relapsed and received 2-6 additional cycles. Our results suggest that recurrent erythema multiforme presents a good response to acyclovir in monotherapy or in combined therapy with dapsone or thalidomide in the majority of patients. We propose a long-term therapeutic protocol to enable disease remission.

Interventions for erythema multiforme: a systematic review.

Treatment of erythema multiforme (EM) is not codified. We performed a systematic review of the effect of any topical or systemic treatment on time to healing and frequency of episodes with acute and chronic forms of EM in adults. Four databases (MEDLINE, CENTRAL, EMBASE and LILACS) and other sources were searched for articles published up to 20 March 2018. Randomized control trials (RCTs), observational studies and case series (n ≥ 10) were considered. From 1558 references, we included one RCT and six case series. The RCT (n = 20) showed a significant difference in complete remission of EM with continuous acyclovir vs. placebo over 6 months. One case series found a mean reduction in flare duration with thalidomide for recurrent EM (5.1 vs. 16.2 days; n = 20). Adverse events were poorly or not reported in included studies. Quality of life was never assessed. One limitation of our study is that we excluded the cases of isolated mucosal EM in order to prevent inclusion of Stevens-Johnson syndrome cases. In conclusion, there is low-level evidence for continuous acyclovir treatment for recurrent EM (one RCT). Evidence for other treatments is only based on retrospective case series. Results for thalidomide, in particular, encourage further research. Data concerning safety are insufficient. PROSPERO registration no. CRD42016053175.

RECURRENT ERYTHEMA MULTIFORME, RESOLVED AFTER IMMULOGLOBULIN REPLACEMENT THERAPY IN A PATIENT WITH NORMAL IMMUNOGLOBULIN LEVELS

Introduction While immunoglobulin has been used for Stevens-Johnson syndrome (SJS), its use in erythema multiforme (EM) is limited. Our case describes recurrent EM after SJS with antibiotic exposure and Mycoplasma pneumoniae infection, with normal immunoglobulin levels, which failed standard treatment but resolved following immunoglobulin replacement therapy (IRT). Case Description A 13-year-old boy developed fever, cough, and rash progressing to generalized sloughing bullae, with dyspnea that deteriorated to emphysematous lung changes. The lesions were targetoid with erythematous base, dusky center, including mucosa. Symptoms developed after treatment for presumed pneumonia with amoxicillin-clavulanate. He was admitted with SJS and Mycoplasma pneumoniae. Steroids, azithromycin, and acyclovir were given. Biopsy was consistent with EM. He was discharged on azithromycin, doxycycline, and valacyclovir for persistent lesions, although HSV titers and cultures were negative. Immune work-up was unremarkable. He lacked immunity to multiple pathogens, despite vaccination, but responded to re-immunization. Immunoglobulins remained normal. Lesions recurred frequently, with minimal response to steroids, and flares with weaning. IRT was administered during re-admission with near resolution. He was then started on IRT therapy. Steroids were weaned without recurrence. Discussion Traditionally described secondary to HSV, Mycoplasma and medications are implicated frequently in pediatric EM. Standard treatment includes prolonged antivirals, antibiotics, and steroids. With treatment failure, immunosuppressants, anti-malarials, and IRT are used. However, controlled trials and consistent data are lacking. As our patient demonstrates, IVIG's immunomodulatory effect can facilitate resolution of recurrent EM. Furthermore, prophylactic use for infections may prevent recurrence. Finally, IVIG represents an alternative to immunosuppressants in pediatric patients with recalcitrant EM despite normal immunoglobulins.

The effect of levamisole in the treatment of recalcitrant recurrent erythema multiforme major: An observational study

BackgroundErythema multiforme major (EMM) is an immune-mediated mucocutaneous eruption mostly triggered by herpes simplex virus (HSV) infection. A vicious circle of recurrence may be developed due to HSV reactivation and prolonged use of systemic corticosteroids to control EMM. Levamisole is an immunomodulator and has been applied to prevent relapses of recurrent HSV infection. ObjectiveTo evaluate the clinical efficacy and safety of levamisole in patients with recalcitrant recurrent EMM. MethodsWe enrolled 23 patients with recurrent EMM treated with levamisole and 24 controls, and analyzed the demographics, treatments and outcomes. ResultsPatients with recurrent EMM for years (mean 3.99 ± 2.71) showed significantly reduced recurrences after various durations of levamisole treatment (recurrences after and before treatment: 3.98 ± 1.04 vs 6.75 ± 1.45 times per year, p = 1.33x10−8). The recurrences of EMM also significantly reduced after levamisole treatment comparing to that of patients without levamisole treatment (p = 3.77x10−9). No patient was reported to have severe side effects during or after levamisole treatment. ConclusionsLevamisole was effective in reducing recurrences of recalcitrant recurrent EMM and can thus be considered an alternative or add-on therapy for this disorder.

Current Perspectives on Erythema Multiforme.

Recognition and timely adequate treatment of erythema multiforme remain a major challenge. In this review, current diagnostic guidelines, potential pitfalls, and modern/novel treatment options are summarized with the aim to help clinicians with diagnostic and therapeutic decision-making. The diagnosis of erythema multiforme, that has an acute, self-limiting course, is based on its typical clinical picture of targetoid erythematous lesions with predominant acral localization as well as histological findings. Clinically, erythema multiforme can be differentiated into isolated cutaneous and combined mucocutaneous forms. Atypical erythema multiforme manifestations include lichenoid or granulomatous lesions as well as lesional infiltrates of T cell lymphoma and histiocytes. Herpes simplex virus infection being the most common cause, other infectious agents like-especially in children-Mycoplasma pneumoniae, hepatitis C virus, Coxsackie virus, and Epstein Barr virus may also trigger erythema multiforme. The second most frequently identified cause of erythema multiforme is drugs. In different studies, e.g., allopurinol, phenobarbital, phenytoin, valproic acid, antibacterial sulfonamides, penicillins, erythromycin, nitrofurantoin, tetracyclines, chlormezanone, acetylsalicylic acid, statins, as well as different TNF-α inhibitors such as adalimumab, infliximab, and etanercept were reported as possible implicated drugs. Recently, cases of erythema multiforme associated with vaccination, immunotherapy for melanoma, and even with topical drugs like imiquimod have been described. In patients with recurrent herpes simplex virus-associated erythema multiforme, the topical prophylactic treatment with acyclovir does not seem to prevent further episodes of erythema multiforme. In case of resistance to one virostatic drug, the switch to an alternative drug, and in patients non-responsive to virostatic agents, the use of dapsone as well as new treatment options, e.g., JAK-inhibitors or apremilast, might be considered.

Characteristics of pediatric recurrent erythema multiforme.

Erythema multiforme (EM) is an acute condition characterized by distinctive target lesions of the skin often accompanied by mucosal ulcers. A subset of individuals experience frequent episodes of recurrent EM, which is rare and poorly understood, especially in children. To characterize clinical features, laboratory findings, and treatment responses of pediatric recurrent EM. A retrospective chart review was conducted at the Children's Hospital of Wisconsin in Milwaukee, Wisconsin (2000-2015) and the Mayo Clinic in Rochester, Minnesota (1990-2015). Inclusion criterion was a diagnosis before age 18 years with recurrent EM, defined as a symmetrically distributed, fixed eruption, including target lesions, with or without mucous membrane involvement, occurring on at least three occasions. A literature review was conducted to include individuals who met the inclusion criterion. Twenty-six patients were included, of whom 16 (62%) were male. The median age of onset was 9.1years (range 0-15.7years). Nine patients (35%) required hospitalization. Herpes simplex virus testing was positive in 9 of 17 (65%) patients. Remission was achieved in 5 of 16 (31%) patients while taking suppressive antivirals. Eight patients received continuous anti-inflammatory treatment, two (25%) of whom experienced remission. This study of pediatric recurrent EM found a greater male predominance, more hospitalizations, fewer cases caused by herpes simplex virus, and alower response to immunosuppression in children than in the general population.

Apremilast for treatment of recurrent erythema multiforme

Recurrent erythema multiforme with oralinvolvement is therapeutically challenging.Apremilast has been used with success in resolvingthe oral aphthae of Behçet disease, prompting theuse of the drug in patients with oral erosions fromerythema multiforme. Three patients with oralerythema multiforme were given apremilast at dosesof 30-60mg daily. Complete clearance of the lesionswere observed in all three patients, including thoserefractory to other standard therapies. Apremilast maypresent an effective option for recurrent erythemamultiforme for patients who have failed trials antiviraland immunosuppressive therapies.

Paediatric Erythema Multiforme: Epidemiological, Clinical and Laboratory Characteristics.

Erythema multiforme (EM) is an immune-mediated reaction presenting as acrofacial target lesions. Most studies utilize the outdated classification, which includes EM, Stevens-Johnson syndrome and toxic epidermal necrolysis as related entities. We describe here epidemiological, aetiological, clinical, laboratory and treatment characteristics of paediatric EM. This is a retrospective single-centre study, performed between 2000 and 2013. Of 119 children given a diagnosis of EM, only 30 met clinical criteria and were included in this study. Most misdiagnosed cases were non-specific eruptions and urticaria multiforme. Mean age was 11.3 years. Fifty percent had mucosal involvement. An aetiology was observed in half of the patients. Seventy percent of patients were admitted to hospital, 46.7% were treated with systemic steroids. Sixteen percent had recurrent EM. The most common identified infectious agent associated with EM in this study was Mycoplasma pneumonia and the cases associated with this infection may represent the recent entity, mycoplasma-induced rash and mucositis. Association with herpes simplex virus was not observed. Despite being a benign, self-limiting condition, children were over-treated in terms of hospitalization and therapy.