Mycoplasma-Induced Rash and Mucositis (MIRM) is one of the extrapulmonary manifestations associated with Mycoplasma pneumoniae infection. Previously, mucocutaneous eruptions associated with this disease were classified within the spectrum of erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). However, a large systematic review separated MIRM as an independent disease entity.
Mycoplasma pneumoniae is an important cause of community-acquired pneumonia in children, and up to 25% of patients develop extrapulmonary symptoms. The most common extrapulmonary manifestation is mucocutaneous lesions such as MIRM. In children, Mycoplasma infection often precedes the onset of SJS.
According to a systematic review, 66% of MIRM patients are male, with an average age of 11.9 years. Ocular findings are present in 82% of cases.
The main comparative features of MIRM, erythema multiforme, and SJS/TEN are shown below.
| Feature | MIRM | Erythema multiforme (EM) | SJS/TEN |
|---|---|---|---|
| Trigger | Mycoplasma pneumoniae | Herpes simplex virus | Drugs |
| Patient population | Young males | Young males | Adults |
| Ocular disease frequency | 82% | 5–23% | 50–88% |
| Mortality rate | 3–4% | 0–6% | 25–30% |
MIRM is triggered by Mycoplasma pneumoniae, whereas SJS is mainly drug-induced. MIRM commonly occurs in young people, with predominant mucosal lesions and mild skin involvement, whereas SJS/TEN can involve widespread epidermal detachment. The mortality rate of MIRM (3–4%) is also significantly lower than that of SJS/TEN (25–30%).
Approximately one week before the appearance of mucocutaneous eruptions, the following prodromal symptoms occur.
Ocular symptoms include the following.
MIRM is characterized by prominent mucositis, typically involving an average of 2.5 mucosal sites. The eyes and oral cavity are most commonly affected.
In MIRM, bilateral conjunctivitis without conjunctival edema is common, and corneal involvement is extremely rare. In contrast, SJS/TEN has an ocular complication rate of about 70%, which can lead to severe sequelae such as corneal epithelial defects, pseudomembrane formation, and corneal opacity. Ocular sequelae in MIRM occur in only 8.9% of cases.
The cause of MIRM is infection with Mycoplasma pneumoniae. Mycoplasma pneumoniae is a common cause of mucocutaneous and respiratory infections, pneumonia, bronchitis, and upper respiratory tract infections with fever.
The diagnosis of MIRM is made by a combination of clinical and laboratory findings. It is important to have a high clinical suspicion.
The typical diagnostic criteria for MIRM are as follows.
The following tests are available for detecting Mycoplasma pneumoniae.
The following are used for anterior segment evaluation in an inpatient setting:
Collaboration with dermatology and urology departments is also important.
Since MIRM mainly occurs in children, differentiation from the following diseases is necessary.
| Differential Disease | Main Differential Points |
|---|---|
| SJS/TEN | Drug-induced, widespread epidermal detachment |
| Erythema multiforme (EM) | Herpes simplex virus-induced, acral target lesions |
| Kawasaki disease | Coronary artery lesions, fever for ≥5 days |
| Herpes zoster | Varicella-zoster virus, polymorphic rash |
| Viral exanthema | Systemic rash from various viruses |
In Japan, the diagnostic criteria for SJS require three essential findings: severe mucosal lesions at the mucocutaneous junction, erosions or blisters covering less than 10% of BSA, and fever of 38°C or higher. The frequency of ocular complications in SJS/TEN is approximately 70%.
To prove infection with Mycoplasma pneumoniae, IgM antibody testing, PCR, and confirmation of a fourfold or greater rise in IgG by paired sera are useful. Clinically, MIRM is suspected when epidermal detachment is less than 10% BSA, mucosal lesions are present at two or more sites, and atypical pneumonia findings are observed.
Currently, no standard treatment protocol for MIRM patients has been established. However, because the clinical picture is similar, treatment is given according to the SJS treatment guidelines. Systemic treatment of the underlying Mycoplasma pneumoniae infection is extremely important.
In the Gregory classification, severity is determined based on the location and extent of conjunctival and corneal epithelial detachment 1). The criteria for severe are as follows.
In severe cases or above, amniotic membrane transplantation (AMT) is required in addition to topical therapy1).
Topical therapy according to the SJS treatment protocol is as follows.
Acute Phase Treatment
Systemic treatment: antibiotics for Mycoplasma pneumoniae
Steroid pulse therapy: systemic steroid administration for ocular surface anti-inflammation
Topical therapy: Antibiotic, steroid, and cyclosporine eye drops
Amniotic membrane transplantation: Performed within 7–10 days after epithelial detachment in severe cases
Chronic phase treatment
Dry eye management: Frequent artificial tears, rebamipide eye drops, punctal plugs
Trichiasis management: Regular epilation, oculoplastic surgery
Low-dose steroid eye drops: Suppression of chronic inflammation, prevention of cicatricial progression
Management of corneal opacity: Cultivated mucosal epithelial transplantation, scleral-supported hard contact lens
In the acute phase treatment of SJS/TEN, systemic steroid pulse therapy plus frequent instillation of topical steroid eye drops is necessary. Whether adequate anti-inflammatory treatment can preserve corneal epithelial stem cells during the acute phase greatly affects subsequent corneal transparency and visual prognosis.
In the chronic phase, the following ocular surface management is important.
Amniotic membrane transplantation (AMT) is the main treatment for severe cases. AMT should be performed within 7 to 10 days of epithelial detachment; beyond this period, effectiveness decreases.
According to Gregory’s classification, when the condition is severe or worse—i.e., involvement of one-third or more of the eyelid margin, or involvement of the bulbar conjunctiva with a diameter of 10 mm or more—amniotic membrane transplantation (AMT) is indicated in addition to local therapy 1). It is recommended to perform the procedure within 7 to 10 days of epithelial detachment.
The exact pathophysiology of MIRM has not been fully elucidated. The following two mechanisms have been proposed.
MIRM (Immune Complex Type)
Polyclonal B-cell proliferation: Mycoplasma infection non-specifically activates B cells.
Immune complex deposition: Following antibody production, immune complexes deposit in tissues.
Complement activation: Deposited immune complexes activate the complement system, causing skin damage.
Molecular mimicry: Molecular mimicry between the Mycoplasma P1 adhesin and host keratinocytes may also be involved.
EM/SJS type (cytotoxic type)
Perforin/granzyme pathway: Direct keratinocyte damage by cytotoxic T cells.
Fas ligand: Keratinocyte necrosis via apoptosis induction1).
Granulysin: Involvement of granulocyte-derived cytotoxic molecules.
Type IV delayed-type hypersensitivity: The delayed-type hypersensitivity mechanism traditionally proposed1).
Since MIRM and EM/SJS types have different pathophysiology, differences in clinical presentation and prognosis are thought to occur. The immune complex-type mechanism of MIRM may explain why tissue damage is more localized compared to the cytotoxic mechanism in SJS/TEN.
The ophthalmic prognosis of MIRM has been shown to be better than that of SJS/TEN. In a systematic review, ophthalmic sequelae of MIRM (corneal ulcer, conjunctival shrinkage, blindness, adhesions, dry eye, eyelash loss, etc.) occurred in only 8.9% of cases.
In a recent case series, with appropriate local treatment, most patients recovered to a best-corrected visual acuity (BCVA) of 20/25 (equivalent to 0.8) or better, and only one case had residual scarring of the eyelid margin.
Shanbhag et al. (2019) reported the long-term effects of a treatment protocol based on severity classification for SJS/TEN. The group treated with strict severity-based classification had significantly fewer long-term complications compared to the non-strict treatment group. Additionally, in 9 out of 10 ultra-severe cases, early AMT resulted in a final BCVA of 20/201).
Currently, there are no large-scale prospective studies or randomized controlled trials specifically for MIRM, and establishing an optimal treatment protocol remains a future challenge. Further validation of the efficacy and safety of applying SJS/TEN treatment protocols to MIRM is required.
