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Why has a 6-year-old boy with no previous health problems suddenly developed swollen eyelids and reddened patches of skin along with vesicles and erosions on his face, trunk, and limbs, and also blisters on his anal mucosa? That was the diagnostic challenge Yuanyuan Xiao, MD, of Beijing Children's Hospital in China, and colleagues recently described in .

The boy's caregivers noted that he was not taking any medications before developing these severe skin symptoms 3 days previously. In recounting his recent history, they explained that he had become feverish and developed a cough over 2 weeks prior and then developed multiple vesiculobullous lesions on the palms of his hands and soles of his feet about a week later.

On presenting to hospital, the patient's temperature was 38.7°C (101.7°F), his heart rate 125 bpm, his blood pressure 98/50 mm Hg, and oxygen saturation 98% on room air.

A full physical exam revealed exudative conjunctivitis affecting both eyes and white exudates on his tongue, at the back of his throat, and inner lining of his cheeks. Erosions around his eyes, lips, and anal mucosa were coated with dried blood. They also noted targetoid erythematous papules on his face and vesiculobullous lesions scattered on his torso, arms, and legs.

On auscultation, clinicians noted crackles in both the patient's lungs.

Lab test results included:

• White blood cell count of 15,000/μL (82% neutrophils)
• Erythrocyte sedimentation rate of 39 mm/h
• C-reactive protein level of 57.1 mg/L

A CT scan of the chest revealed lower lobe infiltrates in both lungs. Xiao's team started the boy on IV azithromycin at 10 mg/kg daily.

Making the Diagnosis

The team suspected the patient had reactive infectious mucocutaneous eruption (RIME) after ruling out differential diagnoses, including Behcet disease and Kawasaki syndrome. Behcet disease was deemed unlikely because the child had pneumonia, which is not generally associated with Behcet disease, and did not have a history of recurrent oral and genital ulcerations that are characteristic of that disease. Kawasaki syndrome was unlikely given the patient's cough and presence of vesiculobullous lesions, which the group noted are not typical of Kawasaki syndrome.

To confirm their presumptive diagnosis of reactive infectious mucocutaneous eruption (RIME), clinicians tested for serum levels of Mycoplasma pneumoniae immunoglobulin (Ig) M and IgG. Total M. pneumoniae antibody (IgM + IgG) level was elevated at 1:1280, they noted. And findings of polymerase chain reaction (PCR) testing of nasopharyngeal aspirate were found to be positive for M. pneumoniae and negative for respiratory viruses, including two common serotypes of enterovirus associated with hand, foot, and mouth disease.

The team added IV immunoglobulin (1 g/kg daily) for 3 days and dexamethasone (0.5 mg/kg, for a total of 10 mg daily) to the IV azithromycin the patient was receiving. After consulting with ophthalmology, they also applied chlortetracycline ointment in and around his eyes.

On hospital day 4, the patient's fever had fully resolved, his cough had lessened, and the blisters and erosions on his body were beginning to heal.

On hospital day 7, clinicians prescribed prednisone (1.5 mg/kg, for a total 30 mg daily), to be tapered slowly over the next month, and discharged the patient to home.

A follow-up examination at the dermatology clinic 1 year later found the patient's mucocutaneous symptoms were completely resolved and his skin had returned to normal.

Discussion

Clinicians presenting this case explained that "the key to the correct diagnosis is recognition that the combination of pneumonia; oral, ocular, and anal mucositis; and cutaneous lesions in a child is suggestive of RIME, which is most commonly associated with Mycoplasma pneumoniae infection."

Up to one in three children hospitalized for community-acquired pneumonia have M. pneumoniae, the group wrote, an infection that frequently results in mucocutaneous disease. They cited that found that mucocutaneous lesions affected approximately 23% of pediatric patients with community-acquired pneumonia due to M. pneumoniae.

"The pathophysiology of these lesions may involve immune complex deposition and complement activation due to polyclonal B-cell proliferation and antibody production in response to infection," Xiao's group explained.

They noted that "the term 'reactive infectious mucocutaneous eruption' (RIME) was established to incorporate MIRM (M pneumoniae–induced rash and mucositis) with similar mucosal-predominant eruptions caused by other pathogens, including Chlamydophila pneumoniae, human metapneumovirus, human parainfluenza virus 2, rhinovirus, enterovirus, adenovirus, and influenza A and B."

Recently, the condition has also been described in adolescents with in the setting of influenza A, "a newly reported infectious trigger," wrote authors of that 2021 , with "the initial episode likely triggered by Mycoplasma pneumoniae (MP) infection."

Case authors described the diagnostic criteria for RIME, which includes evidence of respiratory infection with cough, fever, malaise, and arthralgias in the preceding 7 to 10 days, along with at least two of the following:

• Erosive mucositis affecting two or more sites
• Vesiculobullous or atypical (often bullous) lesions involving less than 10% of the body surface area
• No potentially contributing medications

RIME due to M. pneumoniae infection causes erosions, ulcers, and vesiculobullous lesions which affect the oral mucosa in 94% of patients, the ocular mucosa in 82% of patients, and the urogenital mucosa in 63% of patients.

Other symptoms of RIME include weight loss and dehydration, visual changes, and depression, Xiao's team noted. Most of those who develop RIME have a complete recovery, although 3% of patients with M. pneumoniae-associated RIME die, mostly as a result of pulmonary complications, authors noted. The condition recurs in about 8% of patients, often as a result of a of M. pneumoniae or another respiratory infection.

The team noted that diagnostic testing for suspected RIME includes blood tests for M. pneumoniae IgM and IgG levels, and PCR testing of a nasopharyngeal or oropharyngeal aspirate for M. pneumoniae, Chlamydia pneumoniae, respiratory viruses, SARS-CoV-2, enterovirus, and herpes simplex virus.

Case authors said that, while standardized guidelines for RIME have not been developed, treatment should include supportive care, behavioral support, dermatology consultation, and ophthalmologic evaluation in case the eyes are affected.

And while antibiotics do not seem to improve the course of mucocutaneous eruptions, their use is advisable in patients with RIME who have severe community-acquired pneumonia, the team wrote: "For patients with severe mucocutaneous involvement, use of anti-inflammatory medications, such as glucocorticoids, intravenous immunoglobulin used alone or with glucocorticoids, cyclosporine, and tumor necrosis factor inhibitors, may decrease healing time, although evidence from randomized clinical trials for these treatment options is lacking."

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