Reactive infectious mucocutaneous eruption (RIME), a term describing blistering skin and mucosal lesions, is a term coined by a group of Pediatric Dermatology Research Alliance (PeDRA) researchers and first published in 2021. Since that time, the literature has grown with reports of diverse infectious triggers, management strategies, and complications. This expert opinion PeDRA perspective, developed by a group conducting a consensus process on management of RIME, is an interim update on the current state of diagnosis and management of RIME with a focus on practical information for the busy clinician.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare life-threatening mucocutaneous reactions that remain poorly characterized in pediatric populations. Using the Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Database (KID), the prevalence of SJS/TEN hospitalizations declined from 0.02% in 2016 to 0.009% in 2022, with an overall prevalence of 0.014%. Mortality rates among hospitalized patients remained relatively stable, ranging from 1.8% in 2016 to 1.1% in 2019 and 2022. These findings suggest encouraging trends in pediatric SJS/TEN prevalence and survival while emphasizing the importance of comprehensive supportive management.

Carbamazepine (brand names include Carbatrol, Epitol, Equetro, and Tegretol) is an effective antiseizure drug that is often used as a first-line agent in the treatment of epilepsy. Carbamazepine is also used to treat bipolar disorder and to relieve pain in trigeminal neuralgia. Hypersensitivity reactions associated with carbamazepine can occur in up to 10% of patients, and typically affect the skin. Some of these reactions are mild, as in the case of maculopapular exanthema (MPE); however, conditions such as Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) are potentially life-threatening. The risk of hypersensitivity is increased by the presence of specific human leukocyte antigen (HLA) alleles. The HLA-B*15:02 allele is strongly associated with carbamazepine-induced SJS/TEN in populations where this allele is most common, such as in Southeast Asia. According to the FDA-approved drug label for carbamazepine, testing for HLA-B*15:02 should be done for all patients with ancestry in populations with increased frequency of HLA-B*15:02, prior to initiating carbamazepine therapy (Table 1). The label states that greater than 15% of the population is reported HLA-B*15:02 positive in Hong Kong, Thailand, Malaysia, and parts of the Philippines, compared to about 10% in Taiwan and 4% in North China. The label states that South Asians, including Indians, appear to have intermediate prevalence of HLA-B*15:02, averaging 2 to 4%, but higher in some groups. In Japan and Korea, the HLA- B*15:02 is present in less than 1% of the population. In individuals not of Asian origin (e.g., Caucasians, African-Americans, Hispanics, and Native Americans), the HLA-B*15:02 allele is largely absent. These prevalence rates of HLA-B*15:02 may be used to guide which patients should be screened. However, the FDA cautions to keep in mind the limitations of prevalence rate data when deciding which patients to screen. This is because of the wide variability in HLA-B*15:02 rates (even within ethnic groups), the difficulty in ascertaining ethnic ancestry, and the likelihood of mixed ancestry (1). The FDA label also states that carbamazepine should not be used in patients who are positive for HLA-B*15:02 unless the benefits clearly outweigh the risks. Tested patients who are found to be negative for the allele are thought to have a low risk of SJS/TEN. The HLA-A*31:01 allele may also be a risk factor for SJS/TEN but is more strongly associated with other carbamazepine-induced reactions, such as DRESS and MPE. HLA-A*31:01 is found in most populations, worldwide. HLA-B*15:11 is another allele that has been linked with SJS/TEN. The FDA states that the risks and benefits of carbamazepine therapy should be weighed before considering carbamazepine in patients known to be positive for HLA-A*31:01, but does not discuss HLA-B*15:11 (1). Carbamazepine dosing guidelines based on HLA genotype have been published by the Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Association for the Advancement of Pharmacy (KNMP), the Clinical Pharmacogenetics Implementation Consortium (CPIC), and the Canadian Pharmacogenomics Network for Drug Safety (CPNDS) (2-5). DPWG recommendations include avoiding the use of carbamazepine and selecting an alternative, if possible, for individuals positive for HLA-B*15:02, HLA-A*31:01 and HLA-B*15:11 (Table 2). CPIC recommendations include not using carbamazepine in carbamazepine-naïve patients who are positive for HLA-B*15:02 and any HLA-A*31:01 genotype (or HLA-A*31:01 genotype unknown) (Table 3). CPNDS recommends genetic testing for all carbamazepine-naïve patients before they start treatment, with a moderate level of evidence for HLA-A*31:01 testing, and strong to optional evidence for HLA-B*15:02 testing (based on the frequency of HLA-B*15:02 in the population the patient originates from, and if this is known or not) (Table 4).

Reactive infectious mucocutaneous eruption (RIME) is a recently defined mucocutaneous manifestation associated with respiratory infections, most commonly reported secondary to Mycoplasma pneumoniae. The core diagnostic criteria of RIME involve greater than or equal to two mucosal areas with erosive mucositis, minimal cutaneous lesions, a recent infectious prodrome, and exclusion of drug-induced etiologies. RIME presents with acute mucositis involving the oral, ocular, and genital mucosa, with presentations similar to other mucocutaneous disorders such as Stevens-Johnson syndrome (SJS), erythema multiforme (EM), and multisystem inflammatory syndrome in children (MIS-C) secondary to SARS-CoV-2 infection. This case report describes a unique presentation of RIME secondary to a Mycoplasma infection, highlighting diagnostic challenges and therapeutic approaches. A 16-year-old male, previously healthy with no significant past medical history, was accepted for transfer to our hospital for evaluation of persistent fever, worsening left lower lobe pneumonia, oral mucositis, and conjunctivitis. On examination, extensive erythema and inflammation throughout the oral cavity, exudative pharyngitis, clear ocular discharge with conjunctival injection, and sloughing of the scrotal skin were noted. The patient's medical history and clinical examination raised initial suspicion of Kawasaki disease or possible MIS-C. Lab studies showed elevated CRP, ESR, and B-type natriuretic peptide (BNP), indicating extensive systemic inflammation; however, the PCR was negative for respiratory syncytial virus (RSV), influenza A and B, and SARS-CoV-2. Further investigations revealed a positive Group A Streptococcus PCR on throat swab, felt to be colonization, and elevated Mycoplasma pneumoniae IgG titers suggested previous or recent exposure; however, acute infection could not be confirmed due to negative PCR and IgM. The patient improved over the following several days after initiation of azithromycin, continuation of clindamycin, and wound care for scrotal and oral mucosal lesions. Differentiating RIME from other mucocutaneous disorders is vital to prescribing proper treatment and preventing further systemic effects. This case underscores the importance of considering Mycoplasma as a potential etiology in patients presenting with mucocutaneous lesions and conjunctivitis following a previous respiratory infection.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threate-ning mucocutaneous reactions characterized by extensive epidermal detachment and systemic complications. Wound management is central to survival and long-term outcomes, yet standardiz-ed care pathways remain controversial and in-consistently implemented. This study aimed to systematically synthesize the best available evidence on wound management for patients with SJS/TEN to support clinical decision-making and optimize clinical outcomes. A comprehensive search of major international and Chinese databases and authoritative websites was conducted from January 2010 to May 2025 to collect relevant clinical decisions, guidelines, expert consensus, systematic reviews, and evidence summaries. Two reviewers independently screened and evaluated the literature, and then extracted and summarized evidence using the JBI grading system. A total of 14 high-quality publications met the inclusion criteria, yielding 28 pieces of best evidence across seven7 domains: wound assessment, conservative management, surgical approach, dressing selection, pain management, infection prevention and surveillance, and hospital setting. Among them, 11 recommendations were graded as strong and 17 as weak. This evidence-based synthesis provides practical guidance for wound management in SJS/TEN and supports the development of standardized care protocols to promote epithelial recovery, reduce complications, and improve quality of life.

We report a case of erythema multiforme (EM) associated with atazanavir/ritonavir in a patient with HIV-1 infection. The patient was receiving tenofovir, lamivudine, and dolutegravir; however, owing to a supply chain issue, dolutegravir was substituted with atazanavir/ritonavir. The patient subsequently developed pruritic erythematous papules and plaques with characteristic target lesions over the face and a hemorrhagic crust on the lower lip, without epidermal detachment or systemic symptoms. The Naranjo probability score indicated a probable adverse drug reaction. This case highlights the importance of recognizing EM as a potential adverse reaction to atazanavir and of early drug withdrawal to prevent progression to more severe cutaneous adverse reactions, including Stevens-Johnson syndrome.

Reactive infectious mucocutaneous eruption (RIME) is a para-infectious syndrome characterised by prominent mucositis with limited cutaneous involvement, typically following a respiratory illness. Diagnostic uncertainty is common because RIME may mimic erythema multiforme and drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), particularly when antibiotics have been initiated shortly before onset. We report a 25-year-old woman presenting with fever, generalised maculopapular rash, severe oral erosions with odynophagia, genital involvement, eyelid and lip oedema, and haemorrhagic lip erosions. Chest radiography demonstrated a right lower lobe opacity consistent with pneumonia despite minimal respiratory symptoms. The eruption developed five days after initiation of oral cefuroxime for a presumed respiratory tract infection. There was no epidermal detachment and the Nikolsky sign was negative; ophthalmologic assessment showed no ocular involvement. Mycoplasma pneumoniae infection was confirmed by sputum multiplex PCR and supported by serology. The clinical phenotype and microbiologic confirmation supported RIME rather than drug-induced SJS/TEN. The patient improved with intravenous corticosteroids, azithromycin, and supportive care, with complete resolution at one-month follow-up. This case-based review summarises diagnostic clues, highlights the role of multiplex PCR in aetiologic attribution, and outlines pragmatic management principles to reduce morbidity and avoid misclassification as a severe drug reaction.