Pediatric erythema multiforme induced by topical imiquimod: a case report.

Erythema multiforme (EM) is a rare immune-mediated reaction with mucocutaneous involvement. This case report describes the development of EM in a 9-year-old girl after treatment with imiquimod, a topical immunomodulator used in the management of some dermatologic conditions. Because imiquimod-related EM is rare, particularly in children, this article also reviews the potential adverse effects of this drug and the main characteristics of imiquimod-induced EM, especially in similar cases reported in the literature. Clinicians should be aware that topical imiquimod can induce EM, and this medication should be added to the extensive list of drugs that can trigger the condition.

Successful Treatment With Prednisolone and Mycophenolate Mofetil in a Dog With Recurrent Erythema Multiforme Minor.

A 3-year-old neutered male miniature poodle dog was referred with a 19-month history of unresolved dermatological signs despite long-term treatment. On physical examination, the dog had severe multifocal erythematous non-blanching patches and scales in the ventral trunk. Dermatological examination revealed Malassezia infection. Considering the history, clinical signs, and degree of infection, the possibility of a drug eruption appeared higher than that of Malassezia dermatitis. Therefore, bathing in lukewarm water was performed for 4 weeks without any other treatment, but there was no improvement. Subsequently, treatment for Malassezia dermatitis and differentiation from allergic dermatitis were performed, but there was still no improvement. A biopsy was performed, with the histopathology revealing lymphocytic interface dermatitis with keratinocyte apoptosis. Based on the histopathologic evaluation and clinical signs, the dog was diagnosed with erythema multiforme (EM) minor. Immunosuppressive therapy with prednisolone (1 mg/kg PO, twice daily) was initiated and had a good therapeutic effect. However, the lesion recurred after tapering the prednisolone dose (0.5 mg/kg PO, every other day). Therefore, steroid-sparing agents were added to the prednisolone regimen. Ciclosporin, azathioprine, and human intravenous immunoglobulin were administered in combination with prednisolone. Yet again, the lesion recurred when the dose of prednisolone was tapered to 0.5 mg/kg once daily. Mycophenolate mofetil (20 mg/kg PO, twice daily) was then added to the immunosuppressive regimen as a steroid-sparing agent, and complete remission was achieved and maintained even when the dose of prednisolone was tapered to 0.5 mg/kg every other day. This is the first reported case of recurrent EM successfully treated with a combination of prednisolone and mycophenolate mofetil, and this treatment option should be considered for recurrent EM.

Hyperkeratotic erythema multiforme variant in 17 dogs.

BACKGROUND: A new canine subgroup defined as 'old-dog' or 'hyperkeratotic' erythema multiforme (HKEM) with marked hyperkeratosis and parakeratosis has been proposed without any detailed description of larger case series. OBJECTIVES: We report herein the signalment, clinical signs, treatment outcome, and histopathological and immunological findings in 17 dogs with HKEM. ANIMALS: Inclusion criteria were the presence of (i) scaly skin lesions with or without crusting; and (ii) microscopic lesions typical of EM (i.e. a panepidermal cytotoxic lymphocytic dermatitis with or without basal keratinocyte apoptosis); and (iii) microscopic ortho- and/or parakeratotic hyperkeratosis affecting the interfollicular epidermis. MATERIALS AND METHODS: Clinical questionnaires and skin biopsies were reviewed. Polymerase chain reactions for epidermotropic viruses and direct immunofluorescence were performed. RESULTS: Various breeds were affected with an over-representation of males in their mid-to-late adulthood (median age 9 years). Generalised skin lesions included multifocal-to-coalescing, linear and annular macules and plaques with erythema and adherent firm crusting. Microscopic lesions were specific for EM and featured prominent superficial epidermal apoptosis with lymphocytic satellitosis and parakeratosis. No drug triggers were identified. Polymerase chain reactions for canine herpesvirus polymerase gene, canine parvovirus and canine distemper virus were negative in all HKEM and canine erosive EM (15 dogs) biopsies. Lesions failed to respond to oral and/or topical antimicrobials. Complete remission of signs was achieved in 9 of 17 dogs (53%) using immunosuppressive regimens. CONCLUSIONS AND CLINICAL RELEVANCE: Hyperkeratotic erythema multiforme (HKEM) is a chronic, persistent and clinically distinctive erythema multiforme (EM) variant that differs from 'classic' vesiculobullous erosive-to-ulcerative EM in dogs.

Severe Acute Respiratory Syndrome Coronavirus 2-Associated Blepharoconjunctivitis and Erythema Multiforme-Like Rash in a Young Man.

PURPOSE: The aim of this study was to describe the diagnosis and management of bilateral blepharoconjunctivitis and erythema multiforme (EM)-like illness in an otherwise healthy young man who tested positive for severe acute respiratory syndrome coronavirus (SARS-CoV)-2. METHODS: This is a case report of a 27 year-old man with a positive result for SARS-CoV-2 testing who presented with fever, eye redness, oral ulcerations, cough, sore throat, and progressive rash suspicious for EM-like illness. RESULTS: A SARS-CoV-2-positive patient presented to the emergency room with a progressing skin rash, bilateral conjunctivitis, and oropharyngeal mucosal ulcers. On initial ophthalmic examination, visual acuity was 20/25 both eyes (OU), and slit lamp examination demonstrated erythema and ulceration of the eyelid margins with fluorescein uptake at the mucocutaneous junction OU. The patient was admitted for observation and supportive treatment. During and after his hospital stay, he was treated with systemic and topical steroids, topical cyclosporine ophthalmic drops, erythromycin ophthalmic ointment, and artificial tears. At his 1-week follow-up visit after hospital discharge, the patient had complete resolution of his skin findings and improvement of his ocular and oral mucosal findings. Laboratory workup and imaging studies searching for other potential autoimmune and infectious etiologies showed negative results. CONCLUSIONS: Topical antiinflammatory drops, artificial tears, erythromycin ointment, and systemic steroids were an effective treatment for this bilateral blepharoconjunctivitis and EM-like presentation of SARS-CoV-2.

Phototherapies for erythema multiforme secondary to viral infections: A case report of a child.

INTRODUCTION: Erythema multiforme (EM) is a reactive mucocutaneous disorder typically initiated by viral infections. Although the management of EM differs according to the clinical course and trigger factor, it is not clear whether antiviral suppressive therapies may be useful in cases related to such infections. Moreover, the treatment is most often based on supportive care directed towards only the symptoms. AIM: To present a clinical case of a child in which antimicrobial photodynamic therapy (aPDT) and photobiomodulation therapy (PBMT) were used for orofacial manifestations of EM secondary to viral infections. CASE REPORT: A Brazilian 1-year-old boy was admitted to an ICU due to a severe Influenza A H3N2 infection, pneumonia with pleural effusion, and sepsis. About 10 days later, it was noted bleeding lip lesions covered by crusts and bleeding tongue lesions, diagnosed as EM secondary to both H3N2 and herpes simplex virus infections, confirmed by serology tests. A combination of an aPDT session and six PBMT sessions was proposed and resulted in almost complete resolution of the lesion on the 7th day. CONCLUSION: Given the complexity of the present case, the combination of phototherapies seems to be a promising tool for treating acute orofacial mucosal lesions of viruses-induced EM. More studies, however, are needed to reach a definite conclusion.

Erythema multiforme in children.

QUESTION: Children who present with rashes with "target" lesions are frequently diagnosed with erythema multiforme (EM). This is a self-limiting condition in most children; how should primary care providers differentiate between this and urticaria or Stevens-Johnson syndrome, and what is the recommended course of treatment? ANSWER: While EM is common in children, urticaria is also very common and tends to be more "waxing and waning" compared with EM's fixed lesions. Stevens-Johnson syndrome and toxic epidermal necrolysis are more severe and distinct conditions; they have much more substantial mucous membrane involvement and contain widespread erythematous or purpuric macules with blisters. Since EM is a self-limiting condition, treatment of EM in children is generally supportive, and rarely do children need hospital admission for rehydration. In more severe cases involving mucous membranes or substantial pain, some patients will benefit from topical steroids or antihistamines. When children present with signs of herpes infection, antiviral treatment (acyclovir) may be of benefit. Systemic steroids should be reserved for the most challenging cases.

Erythema multiforme in a young adult following COVID-19 infection and vaccination in Tanzania.

We report the case of a young female adult in her early 20s, who had COVID-19 infection for 8 weeks and COVID-19 vaccination 4 weeks prior to presentation with an extensive rash associated with erythema multiforme, resembling varicella zoster on initial presentation. After initial acyclovir therapy with no improvement, systemic corticosteroid treatment dramatically resolved the patient's skin rash.

Erythema multiforme associated with anti-plakin antibodies: a multicentric retrospective case series.

BACKGROUND: Erythema multiforme (EM) is a muco-cutaneous inflammatory disease mainly triggered by herpes simplex virus (HSV) recurrences. Association of EM and circulating auto-antibodies against plakins (anti-PLK-Abs [EM-PLK+]) has been reported. However, little is known about this subset of EM. OBJECTIVES: We aimed to describe the clinical and immunological features and response to treatment of EM-PLK+. METHODS: We conducted a retrospective multicentric study of EM-PLK+ selected from the database of the immunological laboratory of Bichat hospital, Paris, France, from January 2009 to December 2020. Anti-PLK-Abs were detected in ≥1 immunological tests: immunofluorescence assay, immunoblotting and/or ELISA. Patients with alternative diagnoses were excluded. RESULTS: We included 29 patients (16 women, median age 25 [range 2-58] years). EM-PLK+ were mostly major (EM with ≥2 mucosal involvements; n = 24, 83%) and relapsing (≥2 flares; n = 23, 79%). Cutaneous lesions were target (n = 13, 54%) and target-like lesions (n = 9, 38%) with usual topography (acral, n = 19, 79%; limbs, n = 21, 88%). Mucosal lesions affected the mouth (n = 27, 96%) and genitalia (n = 19, 68%), with a median of 2 [range 0-5] mucous membranes. EM-PLK+ were suspected as certain or possible postherpetic (EM-HSV) in 19 cases (65.5%); no triggering factors were detected in 9 (31%) patients. Desmoplakin-I/II Abs were the most frequent anti-PLK-Abs (n = 20, 69%); envoplakin and periplakin Abs were detected in 11 and 9 cases. Relapsing EM-PLK+ (n = 23) were still active (≥1 flare within 6 months) in 13 (57%) patients despite immunosuppressive therapy (n = 8, 62%). Antiviral drugs were ineffective in preventing relapse in 15/16 (94%) EM-HSV. CONCLUSION: The rationale for anti-PLK-Ab detection in EM is not elucidated. More systematic research of anti-PLK-Abs is warranted to better understand whether this association reflects humoral immune activity in a subset of EM or is fortuitous, related to an epitope spreading process. However, EM-PLK+ seems to be associated with major and relapsing subtypes, and difficult-to-treat cases.

Oral erythema multiforme after Pfizer-BioNTech COVID-19 vaccination: a report of four cases.

BACKGROUND: The 2019 Coronavirus disease (Covid-19) has affected thousands of people worldwide. To date, vaccines appear to be the only method to prevent and reduce mortality. Four vaccinations have been outwardly approved by European Medicine Agency (EMA) in Europe: BNT162b2 (Comirnaty-BioNTech/Pfizer), mRNA-1273 (Spikevax-Moderna), ChAdOx1 (VaxzevriaAstrazeneca), and Ad26.COV2-S (Janssen-Johnson&Johnson). After vaccination, local and systemic adverse effects can occur. Cutaneous reactions like urticaria, local injection site pain, morbilliform rash have been documented after vaccination. CASES PRESENTATION: We report four cases of oral erythema multiforme flare arising after BNT162b2 vaccination administration. All the patients denied previous erythema-like and herpetic manifestations history. Two of the reported cases (number 1 and 2) presented with both oral and cutaneous lesions, while cases 3 and 4 showed only oral manifestations. Three of the cases presented the erythema after the first vaccination dosage administration, only one case reported lesions after the second vaccination dosage administration. All the cases were treated with prednisone via oral administration and topical 0.05% clobetasol ointment. CONCLUSIONS: The present reports represent some of the few cases of erythema multiforme occurring as a side effect of the BNT162b2 COVID-19 vaccination. The causal role of the vaccine for the erythema multiforme has not been proven yet; nevertheless, it is not uncommon for medications to trigger this disease. The vaccine could surface a silent herpes virus infection, which would induce the erythema multiforme instead.

A chronic EBV infection causing persistent facial erythema multiforme and a retrospective literature review: A case report.

RATIONALE: Epstein-Barr virus (EBV) infection is associated with a variety of diseases and can involve multiple organs and systems, with complex and nonspecific clinical manifestations that are easily misdiagnosed. Chronic EBV infection with persistent erythema multiforme (EM) on the cheek as the main manifestation is very rare and has been reported rarely. PATIENT CONCERNS: This article reports a case of an adolescent female with chronic EBV infection who presented with chronic symmetrical erythema lesions on the face for 4 years, exacerbated with photophobia, lacrimation, Henoch-Schonlein purpura (HSP)-like rash, decline in granulocyte and erythrocyte lineages, hematuria, and proteinuria for 1 week. DIAGNOSES: The disease was initially misdiagnosed as systemic lupus erythematosus (SLE) and later confirmed as chronic EBV infection by skin biopsy. In the case, EBV infection not only caused chronic facial EM, but also induced acute HSP and purpura nephritis (hematuria and proteinuria type). INTERVENTIONS: The child was treated with 1 week of glucocorticosteroids in adequate doses combined with acyclovir antiviral therapy and 3 sessions of hemoperfusion. After discharge, she took prednisone acetate (15 mg twice a day) orally for 1 month and then discontinued. OUTCOMES: She was discharged with her rash relieved and normal blood routine test and urine routine test. After 13 months of long-term follow-up, her facial erythema and hyperpigmentation became lighter, and there was no new rash on the whole body, and no abnormality in continuous monitoring of complete blood count and urine test. LESSONS: This case suggests the need to be alert for chronic EBV infection in adolescent females with chronic facial EM rash and multiple organs and systems injury, in addition to connective tissue diseases such as SLE.

Evaluation of Thalidomide Treatment of Patients With Chronic Erythema Multiforme: A Multicenter Retrospective Cohort Study.

IMPORTANCE: Erythema multiforme (EM) may become long term, with a recurrent or persistent course. First-line treatment for chronic EM is valaciclovir. There is no consensus for selection of second-line treatment of chronic EM. OBJECTIVE: The aim of this study was to assess the effectiveness of treatment with thalidomide for patients with chronic EM. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective national multicenter cohort study, among 68 French hospital dermatology departments contacted by e-mail, 10 reported having eligible cases. All adults aged 18 years or older under dermatology care for chronic EM (including recurrent and persistent forms) who had received thalidomide between 2010 and 2018 were included. Analyses were conducted from June 24, 2019, to December 31, 2019. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients who did not experience an EM flare within 6 months of initiating thalidomide treatment for recurrent EM or with complete clearance at 6 months for persistent EM (complete remission). RESULTS: Overall, 35 patients with chronic EM (median [range] age, 33 [15-65] years; 20 [57%] female) experienced failure of at least 1 previous treatment prior to initiating treatment with thalidomide. After 6 months of continuous thalidomide treatment, 23 (66%) were in complete remission, 5 (14%) had stopped the treatment, and 7 (20%) experienced at least 1 flare. The median (IQR) initial dose followed by remission was 50 (50-100) mg/d. Main adverse effects were asthenia (16 [46%]) and neuropathy (14 [40%]). Twenty-five (71%) of patients stopped thalidomide treatment after a median (IQR) of 12 (8-20) months owing to lack of effect (7/25 [28%]), neuropathy or another adverse effect (14/25 [56%]), or long-term complete remission (4/25 [16%]). Low-dose thalidomide, less than 50 mg every other day was sufficient in 9 of 23 (39%) of responders and was associated with less neuropathy and longer treatment duration. CONCLUSIONS AND RELEVANCE: In this cohort study, second-line therapy with thalidomide was associated with complete remission in two-thirds of the 35 patients with chronic EM. However, adverse events were a common cause of thalidomide withdrawal. In the long term, dose reduction when possible may allow for continuation by improving tolerance.