Antibody Serologies and Diagnostic Considerations in Reactive Infectious Mucocutaneous Eruption

ABSTRACT

Reactive infectious mucocutaneous eruption (RIME) is an uncommon, post‐infectious mucocutaneous condition often associated with Mycoplasma pneumoniae , but which can be triggered by other pathogens. We retrospectively reviewed eight young adult patients diagnosed with RIME over a 10‐year period, all of whom had positive Mycoplasma pneumoniae serology despite negative respiratory pathogen panel PCR results. Findings suggest serology may be more reliable than PCR testing in suspected RIME, as PCR is prone to false negatives due to timing, pathogen load, and sampling challenges. Early serology testing and consideration of empiric treatment targeting Mycoplasma pneumoniae may improve diagnosis and management, though further studies are warranted to guide standardized testing.

1. Introduction

Mycoplasma pneumoniae –induced rash and mucositis (MIRM) is an uncommon mucocutaneous eruption characterized by prominent mucositis with sparse cutaneous involvement [1]. The broader term reactive infectious mucocutaneous eruption (RIME) has been proposed to encompass similar presentations caused by non‐ Mycoplasma pneumoniae pathogens, including Chlamydia pneumoniae , metapneumovirus, parainfluenza virus 2, rhinovirus, enterovirus, influenza B virus, adenovirus, and COVID‐19 [2, 3]. Mycoplasma pneumoniae is implicated in over 90% of initial RIME cases when a preceding infection is identified, and in 66% of recurrent cases [4]. A post‐COVID‐19 pandemic resurgence of Mycoplasma pneumoniae has been reported globally [5].

RIME predominantly affects children and adolescents, with a mean age of 12 years and a male predominance [1]. The condition typically follows a nonspecific prodrome of cough, fever, and malaise, with severe mucositis developing approximately 1 week later. Three subtypes exist: (1) Classic RIME, presenting with mucositis accompanied by a transient targetoid or morbilliform rash; (2) RIME sine rash, characterized by isolated mucositis; and (3) Severe RIME, which manifests with extensive mucosal ulceration resembling drug‐induced epidermal necrolysis (DEN) (Figure 1) [6, 7]. The primary differential diagnoses for RIME include DEN, primary or secondary herpes simplex virus (HSV) infection; erythema multiforme (EM) major; and, in younger children, Kawasaki disease.

FIGURE 1.

Severe MIRM in pediatric patients displaying severe mucosal ulceration (A) and widespread eruption (B).

RIME has a favorable prognosis, with 81% of patients making a full recovery and only 4% requiring intensive care; the recurrence rate is around 8%. Mortality is rare (3%) [7]. In contrast, DEN carries a significantly higher risk of ICU admission and mortality [8]. Proposed mechanisms include polyclonal B‐cell proliferation and antibody production, perhaps induced by molecular mimicry between Mycoplasma pneumoniae P1‐adhesion molecules and a keratinocyte antigen causing skin damage [7].

Although no consensus guidelines exist for RIME diagnosis, lab testing usually includes serologic Mycoplasma pneumoniae IgG/IgM testing and PCR respiratory pathogen panels, with some reports utilizing enzyme‐linked immunoassays [1, 7]. Swab‐based testing can be challenging due to mucosal pain. Management is supportive, using corticosteroids and macrolide antibiotics [9]. We present eight serologically confirmed RIME cases and highlight the utility of combining serology with PCR testing at the onset of presentation.

2. Methods

This retrospective, single‐center series included all patients diagnosed with RIME (or alternate terms MIRM, SJS/TEN, EM) by dermatology at UVA Health from January 2015 to January 2025. All patients met diagnostic criteria for RIME (Table 1). Demographic, clinical, laboratory, treatment, and hospital course data were collected. Patients were eligible for inclusion if chart review confirmed evaluation with Mycoplasma pneumoniae antibody serologies (IgM/IgG) and PCR testing via respiratory pathogen panel (RPP) (Table 1).

3. Results

This study included eight patients diagnosed with RIME (mean [SD] age, 19.0 [8.3] years; 25% female; all non‐Hispanic white; mean [SD] hospital stay, 6.5 [3.8] days; presenting subtypes: 4 classic RIME, 3 sine rash, 1 severe). Only one patient had recurrent RIME (ages 19 and 27). All patients tested negative for RPP and HSV types 1 and 2; all had positive Mycoplasma pneumoniae IgM/IgG serologies. All received systemic corticosteroids; two stopped early (one for psychosis, one for lack of improvement). Cyclosporine was used in three patients (Table 1).

4. Discussion

Our case series highlights the diagnostic challenges of RIME and suggests that early Mycoplasma pneumoniae serology may offer greater clinical utility than PCR testing alone. All patients demonstrated positive Mycoplasma pneumoniae serology despite negative RPP results, aligning with prior reports of similar discrepancies [10]. PCR detects only active infection and is influenced by timing, bacterial load, and sampling technique. Nasopharyngeal swabs may yield false negatives from poor sampling or lower‐tract localization, risking misclassification. Serology captures both current and recent infections, which may be more relevant in an immune‐mediated post‐infectious process. When clinical suspicion for MIRM is high, early serology testing, may help guide management, avoiding repeat sampling and diagnostic delays. Empiric treatment may be reasonable even without conclusive testing [10].

This study has limitations, including its small sample size, single‐center design, and retrospective nature. The lack of PCR‐positive cases prevented comparison with serology‐only presentations, and evolving diagnostic criteria/nomenclature may have influenced case classification. Future multicenter studies with larger, stratified cohorts and extended follow‐up are warranted to refine diagnostic strategies, evaluate empiric treatment approaches, and establish evidence‐based guidelines that balance accuracy, patient comfort, and timely management of RIME.

5. Conclusion

In this case series, all eight patients with confirmed RIME had positive Mycoplasma pneumoniae serology despite negative PCR testing via RPP. Based on our findings, when clinical suspicion for Mycoplasma pneumoniae ‐associated RIME is high, empiric treatment targeting Mycoplasma pneumoniae may be reasonable even in the absence of positive PCR results and delayed receipt of serologic testing, particularly given potential delays and discomfort associated with repeated sampling. However, RPP testing remains valuable for identifying alternative infectious triggers.

Consent

Signed informed consent has been received for publication of the photographs in this article.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Table 1 Characteristics of patients with confirmed Mycoplasma pneumoniae ‐induced rash and mucositis.

Smith A. D., Cohen O., Jowdy P., Lyons C. E., Yi L., and Zlotoff B., “Antibody Serologies and Diagnostic Considerations in Reactive Infectious Mucocutaneous Eruption,” Pediatric Dermatology 43, no. 3 (2026): 662–664, 10.1111/pde.70094.

Data Availability Statement

The data that supports the findings of this study are available in the Supporting Information of this article.