PD-L1 expression in keratinocyte and infiltration of CD4 + T lymphocyte can predict a severe type of erythema multiforme major induced by the anti-PD-1 antibody, pembrolizumab.

Skin toxicity is the most common adverse event of treatment with immune check point inhibitors. Among them, erythema multiforme is a rare occurrence with a frequency of 4%, with most of the cases developing grade 1/2 disease. We experienced high grade erythema multiforme major developing with pembrolizumab treatment for anal canal cancer with extensive skin metastases. Steroid ointment was ineffective, and the skin lesions with blisters expanded to > 45% of the body surface area. The patient was at risk for symptom aggravation, and a pulse therapy with methylprednisolone and increasing the dose of oral prednisolone (1 mg/kg) were started. The skin lesions improved in 1.8 months. Unless urgent and appropriate treatments such as high dose steroid administration were conducted, the skin toxicities could not be controlled. The presence of CD4+ T cells and PD-L1+ keratinocytes in the skin biopsy might be a predictive marker of erythema multiforme major resistant to standard steroid treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s13691-024-00676-4.

Recurrent erythema multiforme-like reaction secondary to recurrent poison ivy exposure.

A 14-year-old boy developed an erythema multiforme-like reaction following Toxicodendron radicans (poison ivy) allergic contact dermatitis three separate times over the course of 3 years. The severity of each erythema multiforme-like reaction corresponded to the severity of the allergic contact dermatitis which preceded it.

Vaping as a Risk Factor for Oral Erythema Multiforme: A Case Report and Literature Review.

Introduction: Erythema multiforme is a hypersensitivity reaction caused by various factors, such as viruses, chemicals, and drugs. Electronic cigarettes (e-cigarettes) or vape is a battery-powered nicotine delivery device that substitutes for traditional cigarettes. The chemical components of vaping, including propylene glycol and nicotine, can cause hypersensitivity reactions. Objective: To report a case of oral erythema multiforme in an e-cigarettes user, treatment, and review the literature regarding the impact of these devices on oral health. Clinical Case: A 22-year-old woman came to the Oral Medicine Department with complaints of stomatitis causing pain, eating, and drinking difficulty, which started with fever and pimple-like on the lips. She was an active vape user for one year. Extraoral examination revealed no lesions on other body parts. The serosanguinolent crusts on the lips, an erosive area on the labial commissures and tended to bleed. Intraoral examination revealed white ulcers with yellowish edges and irregular, varying sizes in several parts of the oral mucosa. The anti-HSV-1 IgG laboratory results showed non-reactive, leading to a diagnosis of oral erythema multiforme. Management of oral conditions using 0.9% NaCl compress, dexamethasone mouthwash, and hyaluronic acid, applying 2% miconazole cream on labial commissures and vaseline album cream on the dry lips, and stopping vaping. Oral condition improved in a week of therapy. Conclusion: Erythema multiforme restricted to the mouth is rare, especially associated with electronic cigarettes. Early identification of oral ulcerative disorders is crucial for accurate diagnosis and treatment, where clinicians should consider oral erythema multiforme as a possible diagnosis.

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

Background: Recurrent oral erythema multiforme (ROEM) is an uncommon subtype of erythema multiforme. Immunoglobulin E (IgE) is essential in acute allergy reactions and chronic allergic inflammatory disorders. Purpose: This report aims to describe the advantages of total IgE screening for detecting mouthwash allergic reactions associated with ROEM. Case Presentation: A 29-year-old woman came to the Oral Medicine clinic complaining of canker sores all over her mouth and swollen lips accompanied by crusts that had been bleeding easily two months prior. Complaints worsened after the patient used alcohol-containing mouthwash without a history of fever or other symptoms. Extra-oral examination showed upper and lower lip edema with hemorrhagic crusts that bleed easily. No lesions were found in other parts of the body. Intra-oral examination showed ulcers, multiple, irregular in almost the entire oral mucosa. Laboratory examination revealed non-reactive anti-HSV-1 IgG and a total IgE serum level of 612.00 IU/mL. The diagnosis based on the examination results is recurrent oral erythema multiforme. Case Management: The patient was instructed to stop using alcohol-containing mouthwash, maintain oral hygiene, a healthy lifestyle, adequate hydration, and a balanced diet. Prednisone, benzydamine HCL mouthwash, 0.025% hyaluronic acid mouthwash, multivitamins, and hydrocortisone cream were given as pharmacological therapy. The oral lesions improved in 12 days and the total IgE serum level examination showed a decrease (385 IU/mL). Conclusion: The total IgE examination can be a screening tool for mouthwash allergy-related reactions to disease and represents the response of ROEM therapy as evidenced by clinical improvement.

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

Radiotherapy (RT) can induce dermatitis and exacerbate a patient's preexisting skin conditions. We present a case of RT in a 61-year-old Japanese woman with a history of erythema multiforme (EM). She was diagnosed with a nodule on her right breast during therapy for EM. EM was noticed on the anterior chest and upper and lower extremities. RT was initially postponed due to exacerbation of EM before postoperative RT for right breast cancer. However, considering that EM tends to recur every one to two months, RT was commenced during a period of less active dermatitis, and a total dose of 50 Gy of conventional irradiation was successfully administered. One year after RT, there was no EM recurrence, dermatitis development, obvious late effects, or radiation pneumonitis. Our experience suggests that RT can be administered relatively safely to patients with recurrent EM but should be administered with caution.

An Unusual Presentation of Erythema Multiforme Following the Administration of Pfizer-BioNTech COVID-19 mRNA Vaccine in a Pediatric Patient.

Coronavirus disease 2019 (COVID-19) caused a global calamity that forced emergency use authorization to Pfizer-BioNTech COVID-19 (BNT162b2) vaccine. It is efficacious in preventing symptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in seronegative recipients. The safety profile is still unclear; however, commonly reported symptoms post-vaccination are fatigue, headache, muscle pain, chills, and injection-site pain. COVID-19 disease elicits, to some extent, cutaneous side effects like urticaria, morbilliform rash, and chilblain-like eruption. Vaccination against COVID-19 was reported to induce similar dermatologic manifestations, such as urticarial rash, delayed large-local reaction, local injection-site reaction, and morbilliform eruption. Erythema multiforme (EM) is a rare manifestation post-vaccination, and only a few reports implicate it as a culprit in cutaneous eruptions following the BNT162b2 vaccine. This report delineates the presentation of a healthy 14-year-old girl to a dermatology clinic who developed EM post-vaccination with the first dose of BNT162b2. New-onset EM-eruption post-vaccination with BNT162b2 had been reported previously in 14 cases, and one case reported on the flare of preexisting-EM.

Bullous erythema multiforme secondary to fluconazole intake: A unique case report managed with photobiomodulation therapy.

While fluconazole use is generally considered safe and well-tolerated, there has been an increasing number of reports regarding several adverse events. Therefore, the present study aimed to present a unique case in which photobiomodulation therapy (PBMT) was employed to manage bullous erythema multiforme lesions secondary to fluconazole intake. A 32-year-old female patient sought emergency dental care due to painful orofacial lesions that had developed two days after oral fluconazole use for recurrent vulvovaginal candidiasis. Given the acute clinical features, a diagnosis of bullous erythema multiforme secondary to fluconazole was established. Prednisone 20 mg was then prescribed for five days, and fluconazole intake was immediately discontinued. As the initial treatment strategies failed to show improvement in the clinical condition, three PBMT sessions were proposed every other day. Within seven days, almost complete wound healing was observed, and any pain complaints were no longer present. The resolution of orofacial lesions within a short period suggests that PBMT could be a promising tool for managing drug-induced bullous erythema multiforme. However, more studies are needed to confirm this statement.

Evaluation of Oral Health-Related Quality of Life in Patient with Herpes-Associated Erythema Multiforme: A Unique Case Report.

Introduction: Erythema multiforme (EM) is an acute mucocutaneous hypersensitivity reaction with various etiological factors, including herpes simplex virus type 1 (HSV-1) infection, known as herpes-associated erythema multiforme (HAEM). Oral health-related quality of life (OHRQoL) is a multidimensional concept of biopsychosocial aspects related to oral health. OHRQol contains information for patient-centered treatment plan development. The OHRQoL measurement instrument widely used by clinicians is the oral health impact profile-14 (OHIP-14). This case report aimed to evaluate OHRQoL in HAEM patient, which only manifests on the lips and oral cavity. Case: A 25-year-old male patient came to the Department of Oral Medicine with the chief complaint of painful canker sores on the lips. Extra-oral examination revealed serosanguineous crusts on the lips that were painful and easily bleed. Intra-oral examination showed diffused and painful irregular erythematous lesions on the upper and lower labial mucosa. The anti-HSV1 IgG test was positive. The patient was diagnosed with HAEM. Case Management: Pharmacological therapy included triamcinolone acetonide 0.1% in orabase, acyclovir tablets, multivitamins, and 0.9% NaCl. Non-pharmacological therapy included advice on maintaining good oral hygiene, avoiding spicy and sour foods, and breaking the bad habit of licking the lips. Conclusion: The patient's physical, psychological, and social conditions showed improvement and returned to normal after 7 days of treatment. In conclusion, oral health is an important factor that can improve the quality of life of HAEM patient.

Sorafenib-Induced Erythema Multiforme Major and Severe Hepatic Failure in Metastatic Hepatocellular Carcinoma: A Case Report.

Sorafenib, a kinase inhibitor, is known to cause skin toxicity, which sometimes leads to treatment interruption or drug dose reduction. Erythema multiforme (EM) is one of these dermatologic toxicities induced by sorafenib. We report the case of a 28-year-old male with hepatocellular carcinoma (HCC). Two months after surgery, the patient presented with multiple metastases to the retroperitoneal lymph nodes and lungs. Therefore, systemic therapy with sorafenib was indicated. While receiving the medication, the patient presented signs compatible with EM. The signs occurred on the torso and then spread to the rest of the body. Sorafenib treatment was interrupted the same day when skin lesions appeared and moisturizers with topical steroids and oral antihistamines were prescribed. The skin lesions decreased in size but without significant cutaneous improvement. The patient showed biologically severe liver failure and radiological progression. Because of the severe hepatic failure, initiation of intravenous steroids and establishment of another line of chemotherapy following tumor progression were contraindicated. The decision of the multidisciplinary staff with patient consent was to proceed with the best supportive care. The patient died in ambulatory care 12 days after discharge and local treatment. This report highlights the possibility of developing severe EM while receiving sorafenib. Patients with HCC who have liver resection without liver dysfunction should not be administered sorafenib, or it must be used with caution at very low doses and accompanied by close and regular follow-ups to avoid disease progression and deaths.

Exploring the association between erythema multiforme and HIV infection: some mechanisms and implications.

Erythema multiforme (EM) is an immune-mediated mucocutaneous condition characterized by hypersensitivity reactions to antigenic stimuli from infectious agents and certain drugs. The most commonly implicated infectious agents associated with EM include herpes simplex virus (HSV) and Mycoplasma pneumoniae. Other infectious diseases reported to trigger EM include human immunodeficiency virus (HIV) infection and several opportunistic infections. However, studies focusing on EM and human immunodeficiency virus (HIV) infection are scarce. even though the incidence of EM among HIV-infected individuals have increased, the direct and indirect mechanisms that predispose HIV-infected individuals to EM are not well understood. In turn, this makes diagnosing and managing EM in HIV-infected individuals an overwhelming task. Individuals with HIV infection are prone to acquiring microorganisms known to trigger EM, such as HSV, Mycobacterium tuberculosis, Treponema pallidum, histoplasmosis, and many other infectious organisms. Although HIV is known to infect CD4 + T cells, it can also directly bind to the epithelial cells of the oral and genital mucosa, leading to a dysregulated response by CD8 + T cells against epithelial cells. HIV infection may also trigger EM directly when CD8 + T cells recognize viral particles on epithelial cells due to the hyperactivation of CD8 + T-cells. The hyperactivation of CD8 + T cells was similar to that observed in drug hypersensitivity reactions. Hence, the relationship between antiretroviral drugs and EM has been well established. This includes the administration of other drugs to HIV-infected individuals to manage opportunistic infections. Thus, multiple triggers may be present simultaneously in HIV-infected individuals. This article highlights the potential direct and indirect role that HIV infection may play in the development of EM and the clinical dilemma that arises in the management of HIV-infected patients with this condition. These patients may require additional medications to manage opportunistic infections, many of which can also trigger hypersensitivity reactions leading to EM.

Erythema Multiforme in an HIV+ Patient on Highly Active Antiretroviral Therapy After Starting Paxlovid (Nirmatrelvir-Ritonivir).

In this report, we present a case of a woman currently on HIV antiretroviral therapy who presented with oral mucosal and cutaneous skin lesions with a target-like appearance following completion of a five-day course of Paxlovid™ for symptomatic COVID-19 infection. The patient was treated with intravenous steroids and oral antihistamines with mild improvement. However, she returned in one week with worsening skin lesions. The biopsy and infectious workup were non-contributory. It was determined that the patient had developed erythema multiforme (EM), secondary to Paxlovid™.

Erythema Multiforme-Like Fixed Drug Eruption During Azathioprine and Hydroxychloroquine Treatment for Systemic Lupus Erythematosus Mimicking Rowell Syndrome: A Rare and Challenging Clinical Scenario.

Background. Fixed drug eruption and Rowell syndrome stand as intriguing entities with overlapping clinical and pathological features. Case Presentation. A 32-year-old female patient presented with a tender and pruritic rash on the left upper chest for 3 days. Clinical examination revealed a flaring rash on the chest, under her left eye, tongue, and lips. The patient had a significant past medical history of systemic lupus erythematous with positive (ANA, Sm, dsDNA, ribosomalP, RNP) antibodies, hypocomplementemia, inflammatory arthritis, discoid lupus, leukopenia, thrombocytopenia, and immune thrombocytopenic purpura, and avascular necrosis affecting both hips and her right knee. At the time of presentation, the patient was on azathioprine 150 mg daily and hydroxychloroquine 200 mg twice daily. Skin biopsy of the left upper chest revealed interface dermatitis with necrotic keratinocytes at the dermal-epidermal junction. Superficial and, in some areas, deep perivascular and peri adnexal lymphocytic infiltrates were observed, accompanied by eosinophils. CD123 staining highlighted 16% of the inflammatory cells. Direct Immunofluorescence for IgG, IgA, IgM, C3, and fibrinogen revealed positive linear basement membrane staining for IgG and fibrinogen, with no significant staining for the remaining immunoreactants. Considering the patient's history of medicine usage, and negative SS-A and SS-B antibody, a fixed drug eruption was favored. Discussion. This article discusses the clinical presentations, pathophysiological mechanisms, and diagnostic criteria for fixed drug eruption and Rowell syndrome. Conclusion. Awareness of the distinct clinical and histopathologic features of fixed drug eruption and Rowell syndrome, particularly when sharing cutaneous manifestations, underscores the importance of a comprehensive diagnostic approach and laboratory testing.

Acute Cytomegalovirus Infection Associated With Erythema Multiforme-Like Eruption: A Case Report.

Human cytomegalovirus infection usually proceeds asymptomatically in immunocompetent patients. In symptomatic forms, mononucleosis syndrome is the most common manifestation. However, atypical cases of cytomegalovirus infections in immunocompetent subjects are reported in the literature. Here, we describe a case of cytomegalovirus-related mononucleosis syndrome that presented with an atypical erythema multiforme-like skin rash and high fever. Very few cases have been described in the literature previously. In our case, the diagnosis was supported by specific serology, and human cytomegalovirus DNA was detected in the blood sample. The clinical picture resolved without the administration of antiviral therapy.

Systemic lupus erythematosus associated with erythema multiforme: A rare case report of Rowell's syndrome.

Key Clinical Message: Although it is very uncommon, SLE may initially present with recurrent episodes of EM-like rash. Despite the various possibilities underlying their association, prompt identification, and treatment of SLE in patients presenting with EM is important to prevent death or serious organ damage. Abstract: Rowell's syndrome (RS) is an uncommon presentation of systemic lupus erythematosus (SLE) with erythema multiforme (EM)-like lesions associated with specific serological changes, including positive rheumatoid factor (RF), speckled antinuclear antibody (ANA), positive rheumatoid factor, or anti-La antibodies in the serum. Our case, a 41-year-old male, presented with features of EM. Upon investigation, we identified underlying systemic lupus erythematosus, marking a rare instance of SLE presenting for the first time as EM. Classical or true EM is precipitated by trigger factors such as infective agents like the herpes simplex virus, Mycoplasma pneumoniae, drugs like anticonvulsants, antibiotics, and non-steroid anti-inflammatory drugs, any underlying malignancy, or connective tissue disorders, and is not associated with any specific serological abnormalities. EM cases associated with LE lesions where an EM trigger factor is missing are considered an RS diagnostic criterion. In this case report, the importance of considering SLE in patients presenting initially with recurrent episodes of EM-like rash is emphasized. RS should be considered, especially when there is no evidence of triggering factors. Early diagnosis and prompt treatment of SLE are crucial to preventing death and irreversible organ damage.

Cases from a Community Hospital JCHIMP Series #2: 66-Year-old Man with Recurrent Painful Rashes and Oral Ulcerations.

This is part of a series of case reports detailing scenarios from our community hospital. The cases are selected to feature clinical dilemmas, provide a review on what is currently known about the topic with expert perspective. A 66-year-old black man presented to the primary care clinic with his fourth episode of generalized painful rash and oral ulcerations without a diagnosis despite two emergency room (ED) visits alongside doxycycline treatment. Symptoms interfered with daily activities with skin exam notable for widespread erythematous patches and plaques. In office biopsies were obtained with final diagnosis of erythema multiforme. Etiologic workup revealed positive HSV 1 IgG and active untreated hepatitis C infection. He was treated with prednisone, and acyclovir with resolution of lesions and no further recurrences over a nine-month follow up period. This case depicts an unusual presentation of a common skin disorder. It highlights the challenge of recognizing atypical target lesions in skin of color and the important role of primary care in bridging access to dermatological care.