How should Mycoplasma pneumoniae‑induced rash and mucositis be treated, including first‑line antibiotic choice and management of mild lesions versus severe Stevens‑Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN)?

Management of Mycoplasma pneumoniae-Induced Rash and Mucositis (MIRM)

Mycoplasma pneumoniae-induced rash and mucositis should be recognized as a distinct clinical entity from drug-induced Stevens-Johnson syndrome, managed with appropriate antimicrobial therapy targeting M. pneumoniae (macrolides or fluoroquinolones), and triaged based on severity of mucosal involvement rather than extent of skin detachment. 1

Recognition as a Distinct Clinical Entity

• MIRM represents a specific infection-associated phenotype characterized by predominant mucous membrane involvement with limited or absent cutaneous lesions, distinguishing it from classic drug-induced SJS/TEN. 1
• This entity has been variably termed "M. pneumoniae-associated mucositis," "M. pneumoniae-induced rash and mucositis," and "Chlamydia pneumoniae-induced rash and mucositis." 1
• Mycoplasma pneumoniae accounts for up to 50% of infection-associated SJS/TEN cases in the pediatric population, making it the most common infectious trigger. 1

Diagnostic Approach

Clinical Features That Distinguish MIRM

• Severe erosive and hemorrhagic mucositis affecting multiple sites (oral, ocular, genital) with minimal or absent cutaneous involvement is the hallmark presentation. 1, 2
• When skin lesions are present, they are typically sparse targetoid lesions rather than the widespread purpuric macules seen in drug-induced SJS. 3, 4, 2
• Respiratory symptoms (fever, cough, upper respiratory tract infection) typically precede or accompany the mucocutaneous manifestations. 3, 4, 5

Required Diagnostic Testing

• Obtain testing for M. pneumoniae infection in all cases of severe mucositis, including PCR from respiratory specimens and/or serologic testing (IgM antibodies). 1, 5
• Discussion with the infectious disease team should be considered in all cases to guide appropriate testing and antimicrobial selection. 1
• Skin biopsy may show subepidermal cleavage similar to SJS/TEN but is not required if the clinical picture and M. pneumoniae testing are consistent with MIRM. 2

First-Line Antimicrobial Therapy

Antibiotic Selection for M. pneumoniae

• Macrolides (azithromycin) are the first-line antimicrobial choice for M. pneumoniae respiratory infection in both children and adults. 5
• Alternative agents include fluoroquinolones (levofloxacin, moxifloxacin) in adults or tetracyclines (doxycycline) in children >8 years if macrolide resistance is suspected or documented. 5
• Treatment should be initiated promptly upon clinical suspicion without waiting for confirmatory testing, as early antimicrobial therapy may reduce the severity and duration of mucocutaneous manifestations. 5

Critical Distinction from Drug-Induced SJS/TEN

• Unlike drug-induced SJS/TEN, where immediate withdrawal of the culprit medication is the most important intervention, MIRM requires active antimicrobial treatment of the underlying infection. 1
• Avoid unnecessary withdrawal of commonly used analgesics (paracetamol, ibuprofen) if infection is the likely cause, as these are often confounders given their use for prodromal symptoms. 1

Management Based on Severity

Mild MIRM (Limited Mucosal Involvement, Well-Appearing Patient)

• Patients with limited mucositis who are systemically well may be managed on an age-appropriate ward with adequate support for mucosal care. 1
• Essential supportive care includes:
  • Ophthalmologic consultation within 24 hours for assessment and management of ocular surface disease, as ocular involvement is common and can lead to long-term sequelae. 1, 6
  • Oral care with gentle debridement, topical anesthetics (lidocaine viscous), and nutritional support if oral intake is compromised. 1
  • Genital care with barrier ointments and consideration of topical corticosteroids (clobetasol propionate 0.05% ointment) for severe involvement. 1

Severe MIRM (Extensive Mucositis, Systemic Involvement, or Any Skin Detachment)

• Early transfer to a specialized unit is critical if there is extensive mucosal involvement, systemic complications, or any degree of epidermal detachment. 1
• Specialized care should include:
  • Multidisciplinary team involvement including dermatology, ophthalmology, infectious disease, and intensive care specialists. 1
  • Management in either a specialized dermatology service pediatric intensive care unit (PICU) or a pediatric burn center with on-site PICU if there is skin loss, systemic involvement, or comorbidities. 1
  • Delay in transfer to specialized care adversely affects outcomes and increases mortality risk. 1

Supportive Care Priorities

• Address eye disease aggressively with frequent ophthalmologic assessment, as ocular complications are common and can result in permanent visual impairment. 1, 6
• Ensure adequate nutritional support, as severe oral mucositis may require enteral feeding. 1
• Provide meticulous care of denuded skin and mucosa to prevent secondary bacterial infection and sepsis. 1
• Pain management is essential, as cutaneous and mucosal pain is a prominent feature. 1

Role of Immunomodulatory Therapy

• There is no reliable evidence supporting the use of systemic immunomodulatory treatments (corticosteroids, IVIG, anti-TNF biologics, ciclosporin) in MIRM or infection-associated SJS/TEN. 1
• If immunomodulatory therapy is considered, it should only be administered under the supervision of a specialist skin failure multidisciplinary team in the context of clinical research or case registry. 1
• The pathophysiology of MIRM differs from drug-induced SJS/TEN, making immunosuppression potentially counterproductive when treating an active infection. 2

Prognosis and Follow-Up

Expected Clinical Course

• MIRM typically has a more benign clinical course compared to drug-induced SJS/TEN, with lower mortality and less extensive skin involvement. 2
• Recovery is generally favorable with appropriate antimicrobial therapy and supportive care. 5

Long-Term Sequelae to Discuss

• Potential long-term complications include ocular problems (dry eye, symblepharon, corneal scarring), oral complications (dental issues, oral strictures), and urogenital problems (vaginal or urethral stenosis). 1, 6
• Recurrence risk exists with future M. pneumoniae infections, and patients should be counseled accordingly. 1
• Skin pigmentation changes and scarring are possible but typically less severe than in drug-induced SJS/TEN. 1

Critical Pitfalls to Avoid

• Do not misclassify MIRM as drug-induced SJS/TEN, as this leads to unnecessary avoidance of commonly used medications and misses the opportunity for targeted antimicrobial therapy. 1, 2
• Do not delay antimicrobial therapy while awaiting confirmatory M. pneumoniae testing if the clinical presentation is consistent with MIRM. 5
• Do not underestimate the severity of isolated mucositis—extensive mucosal involvement without significant skin detachment still requires specialized multidisciplinary care. 1
• Ensure early ophthalmologic involvement, as ocular complications can develop rapidly and lead to permanent visual impairment if not managed aggressively. 1, 6