Reactive Infectious Mucocutaneous Eruption: An Entity to be Reckoned With

INTRODUCTION

Reactive infectious mucocutaneous eruption (RIME) is a recently described entity characterised by prominent mucositis, mainly affecting the oral and urogenital mucosa, following a bacterial or viral infection. The prevalence among individuals with active Mycoplasma pneumoniae infection is about 6.8%,^[1] and recurrence rates range from 8% to 38%.^[2]

RIME is a severe mucocutaneous reaction, usually in children and adolescents, though adult cases occur. Mucosal lesions are more extensive than cutaneous ones. The condition typically follows a 2–3-week incubation period with prodromal respiratory symptoms.^[3]

We report a case of RIME in a 45-year-old female to emphasise recognition of this emerging entity in adults.^[4]

A 45-year-old woman with no known comorbidities presented with an acute onset of fever followed within 24–48 h by multiple painful, fluid-filled lesions in the oral cavity, associated with tender cervical lymphadenopathy. This constituted the first episode. The vesicles ruptured spontaneously, and she was treated with oral amoxicillin-clavulanate (625 mg 3 times daily for 5 days), following which the lesions resolved completely within 4 days without residual pigmentation [Figure 1].

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Figure 1: (a) Presence of bullae on the buccal mucosa (yellow arrow). (b) Presence of an erosion on the ventral side of the tongue (yellow arrow). (c) Erosion with pseudo- membrane formation on the right side of buccal mucosa (yellow arrow). (d) Erosion on the inner aspect of the lower lip with pseudo- membrane (yellow arrow).

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After a symptom-free interval of 3 days, she developed fever and rhinitis, followed by recurrence of similar but more severe painful vesicles involving the ventral surface of the tongue and oral mucosa. These lesions ruptured to form erosions, associated with purulent discharge, severe pain, and difficulty in opening the mouth.

On examination, the patient was febrile and had multiple tense, clear vesicles, bullae, and shallow erosions with serosanguinous discharge involving the oral mucosa. Tender anterior cervical lymphadenopathy was present. Based on the clinical findings, the differential diagnoses considered included bullous pemphigoid, mucous membrane pemphigoid, and herpetic gingivostomatitis [Figure 1].

Laboratory investigations revealed haemoglobin of 12.3 g/dL (12–16 g/dL) and a total leukocyte count of 9,400/mm³ (4.5– 11 ×10³/mm³) with neutrophils 62.4% and lymphocytes 22.3%.

Histopathological examination showed denuded epithelium with subepidermal separation and dense perivascular and interstitial inflammatory infiltrates comprising lymphocytes, neutrophils, plasma cells, and melanophages. Similar perivascular inflammatory infiltrates were also noted in the subcutis [Figure 2]. The absence of full-thickness epidermal necrosis and the presence of a mixed inflammatory infiltrate favoured RIME over erythema multiforme major or Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).

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Figure 2: (a) Dermis with dense inflammatory infiltrate. (yellow arrow) (Haematoxylin and eosin: x10). (b) Denuded epidermis (yellow arrow) (Haematoxylin and eosin: x10).

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Direct immunofluorescence (DIF) was negative for immunoglobulin (Ig)G, IgM, IgA, C3, and fibrinogen. Enzyme-linked immunosorbent assays for desmoglein 1 and 3 were negative, thereby excluding pemphigus and bullous pemphigoid. Based on the clinical presentation, histopathology and immunological findings, a diagnosis of RIME was considered.

Further evaluation revealed elevated inflammatory markers, with a C-reactive protein (CRP) level of 2.63 mg/dL (<0.6 mg/ dL) and an erythrocyte sedimentation rate (ESR) of 33 mm/h (0–20 mm/h). COVID-19 reverse transcription polymerase chain reaction (RT-PCR) and herpes simplex virus serology were negative. M pneumoniae IgM was negative, while IgG was equivocal (10.6), suggestive of recent exposure.

The patient was treated with oral azithromycin (500 mg once daily for 5 days), oral acyclovir (400 mg 5 times daily for 7 days), analgesics, and supportive care, including chlorhexidine mouthwash and topical anaesthetic gel. She showed complete resolution of lesions within 7 days, with no scarring or post-inflammatory hyperpigmentation. On follow-up after 1 week, the patient was asymptomatic.

DISCUSSION

RIME is a post-infectious mucositis predominantly affecting oral, ocular, and genital mucosa, with minimal or absent cutaneous lesions. It can follow infections due to M pneumoniae, Chlamydia pneumoniae, human metapneumovirus, parainfluenza, influenza B, rhinovirus, enterovirus (including coxsackievirus), adenovirus, norovirus, and severe acute respiratory syndrome coronavirus 2.

Two mechanisms are proposed: an indirect immune-mediated response in which a distant infection triggers mucocutaneous inflammation, and a direct mechanism in which the pathogen invades mucocutaneous sites, releasing inflammatory cytokines.^[4,5]

Clinically, RIME presents with painful oral ulcers, haemorrhagic crusting of the lips, and involvement of the nasal or genital mucosa. Cutaneous lesions, when present, are usually vesiculobullous (80%), but may also be targetoid, papular or morbilliform.^[6]

Histopathology lacks pathognomonic features but shows findings overlapping erythema multiforme major and SJS/ TEN – apoptotic keratinocytes and perivascular dermal infiltrates. Laboratory investigations often reveal raised ESR and CRP. RT-PCR for COVID-19 and M pneumoniae antibody testing aid in identifying infectious triggers.

Proposed diagnostic criteria for RIME include:

1. Mucocutaneous eruption involving ≥1 mucosal site with <10% body surface area involvement

2. Presence of vesicles, bullae, or scattered atypical targetoid lesions

3. Non-contributory drug history

4. Prodromal respiratory or systemic symptoms within the previous 7–10 days

5. Laboratory or radiologic evidence of an infectious trigger.^[7]

Although the specific pathogen was not confirmed, the patient met these criteria based on prodromal symptoms, mucosal morphology, and elevated inflammatory markers, with negative DIF and desmoglein studies excluding autoimmune bullous disorders.

Management is mainly supportive, with antibiotics when bacterial infection is suspected, analgesics, and local care. Systemic corticosteroids or immunomodulators such as etanercept and cyclosporine can be considered in extensive cases.^[7] Prognosis is generally favourable, with resolution in 1–2 weeks. Recurrence occurs in about 8% of cases, and post-inflammatory sequelae such as pigmentary change or genital and ocular scarring occur in roughly 10%.^[8]

A limitation of this case report is the equivocal M pneumoniae serology, which did not allow confirmation of a definite infectious trigger.

This case highlights that RIME, though predominantly seen in younger patients, can also affect adults. Recognition of this entity is essential for distinguishing it from drug-induced reactions such as SJS/TEN and for guiding appropriate management.

CONCLUSION

Dermatologists play a major role in diagnosing RIME promptly. This case report gives a wider perspective on oral mucosal eruption which could be secondary to infection and is relatively a new entity. Proper clinical history and examination, along with laboratory investigation can help us come to a diagnosis. Increased awareness and understanding regarding RIME are crucial for enhancing diagnostic accuracy and patient outcomes.