Do We Recognize Mycoplasma-associated RIME as Often as Stevens-Johnson Syndrome in Children?

To the Editors: Reactive infectious mucocutaneous eruption (RIME) is a severe yet underrecognized mucocutaneous reaction that primarily affects children and adolescents, most commonly following Mycoplasma pneumoniae infections.1,2 It is characterized by prominent oral mucositis, conjunctivitis, and urethral involvement and typically resolves spontaneously. Clinically, RIME shares similarities with Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN); however, it differs significantly due to its infectious etiology, milder disease course, and more favorable prognosis.2,3 Nevertheless, RIME is often initially misidentified as SJS, leading to unnecessary concern among clinicians. With this case, we aim to highlight the diagnostic challenges of RIME, emphasize its distinction from SJS, and raise awareness among clinicians to ensure timely and accurate diagnosis. A 12-year-old male patient was referred to our center for further evaluation and treatment due to persistent fever, ocular redness, and mucocutaneous lesions on the lips. The patient had initially presented to another hospital, where SJS or drug eruption was considered as a preliminary diagnosis. Before being referred to our center, the patient was evaluated as having SJS and was started on intravenous immunoglobulin along with steroid therapy. The patient’s medical history revealed that he had been experiencing fever for approximately 1 week. In response to the fever, he was started on amoxicillin-clavulanic acid at a dose of 50 mg/kg/d. However, despite antibiotic treatment, the fever persisted. Apart from intermittent paracetamol use, he had not received any other medications. Two days before admission, he developed mucocutaneous lesions involving the lips and oral cavity, along with ocular redness and cough, which prompted hospitalization at our center. Importantly, there were no skin lesions elsewhere on the body. There was no family history of mucocutaneous eruptions. On physical examination, the patient appeared ill and fatigued, with reduced oral intake. Bilateral rales were present on lung auscultation, but there were no signs of tachypnea or tachycardia. Conjunctival hyperemia and mucocutaneous lesions affecting only the lips and oral mucosa were noted (Fig. 1). The patient had dark-colored urine, which raised suspicion of hematuria. Due to the patient’s findings, consultations with ophthalmology, otolaryngology, and pediatric allergy specialists were obtained with a preliminary diagnosis of SJS. As a result of the multidisciplinary approach, the patient was diagnosed with Reactive Infectious Mucocutaneous Eruption (RIME). Due to the absence of significant progression in the patient’s lesions, RIME was considered as the primary diagnosis. The patient’s laboratory results revealed a white blood cell count of 10,550/µL, with an absolute neutrophil count of 8000/µL and an absolute lymphocyte count of 1200/µL. The platelet count was 183,000/µL, and the eosinophil count was 360/µL. Inflammatory markers showed an elevated C-reactive protein level of 161 mg/L, while the erythrocyte sedimentation rate was 11 mm/h. Viral serologies were negative. The nasal swab polymerase chain reaction (PCR) test was found to be negative. Chest radiograph was normal. Nasopharyngeal swab and blood serologies were obtained for M. pneumoniae testing. While M. pneumoniae nasopharyngeal PCR was negative, serological testing was positive, with an IgM level >10 RU/mL and an IgG level of 108 RU/mL. The cultures were sterile. Urinalysis revealed 200 red blood cells per high-power field. The patient was closely monitored in our center. Laryngopharyngeal examination was normal, and there was no oxygen desaturation. Due to conjunctival involvement, local ocular treatment was initiated. Oral care and enteral nutrition solutions were provided for caloric support. Azithromycin was added to the treatment regimen. Following consultation with the pediatric allergy department, prednol treatment was continued at a dose of 2 mg/kg/day. By the 6th day of hospitalization, improvement in oral lesions was observed. Given the patient’s good general condition, steroid treatment was gradually tapered and discontinued after 1 week. Ophthalmologic follow-up was planned to continue. Multidisciplinary follow-up was recommended, and the patient was discharged in good general condition. Follow-up visits are ongoing.FIGURE 1.: The clinical features and progression through treatment. Conjunctivitis (A), hemorrhagic crusted lip (A, B) and posttreatment healing appearance of eyes and lips (C).Mucocutaneous eruptions associated with M. pneumoniae have been previously documented, and other viral pathogens may also contribute to its development.4,5 However, the exact pathogenesis of these eruptions remains unclear. Clinically, RIME closely resembles SJS and TEN; however, it is a postinfectious condition, and no fatal cases have been reported in recent years. In addition, long-term sequelae are rare, distinguishing it from SJS, which carries a 15% mortality rate.2,3 In RIME, the affected body surface area is typically less than 10%, and in some cases, cutaneous involvement may be absent. In a study by Joseph et al.2 cutaneous lesions were present in 7 of 13 pediatric cases, while the remaining patients did not exhibit skin involvement. However, oral mucosal involvement was reported in all 13 cases.2 Similarly, in our patient, there were no skin lesions, but mucosal involvement was prominent. In addition to, in our case, mucosal eye involvement, urinary involvement was also present. The primary etiologic agent was Mycoplasma; however, other viral agents (such as adenovirus and COVID-19) should also be investigated in the etiology.4,5 In our patient, M. pneumoniae was identified as the causative agent through serology, while other pathogens tested negative. The nasal swap PCR was negative, we think this may be due to the azithromycin treatment we used. Supportive care is the cornerstone of treatment, and a multidisciplinary approach is recommended. Antibiotic therapy does not alter the clinical course of RIME. In addition, the benefit of immunosuppressive therapy in improving clinical outcomes remains uncertain.2,3,5 Systemic treatment should be considered only in cases where the differentiation between SJS/TEN and RIME remains unclear or if new and progressive skin lesions develop after 5–7 days of conservative treatment, emphasizing the importance of close clinical monitoring.2,5 Most cases resolve within 14 days.2 In our case, the patient achieved complete recovery by day 10 of hospitalization. No complications were observed in our patient, and respiratory symptoms were completely resolved. Our patient was initially given a preliminary diagnosis of SJS and referred to our hospital after receiving intravenous immunoglobulin and steroid therapy. SJS is a serious condition with a high mortality rate, poor prognosis, and risk of sequelae, often necessitating intensive care in severe cases. Therefore, clinicians are understandably concerned about the severity of the clinical course in patients diagnosed with SJS. However, our patient was ultimately diagnosed with RIME, a condition with milder clinical features and a lower mortality risk. With this case, we aim to emphasize that RIME follows a more stable clinical course compared with SJS. Increasing awareness of RIME will help facilitate more rational treatment decisions and prevent unnecessary concerns. Early recognition and multidisciplinary collaboration are essential for accurate diagnosis and appropriate management.