Diagnosis: M pneumoniae-associated mucositis
The patient was admitted for observation to rule out Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). We felt that the degree of mucositis (extensive) compared to the number of targetoid papules on the hands (minimal) suggested a diagnosis of Mycoplasma pneumoniae-associated mucositis (MPAM), a subtype of erythema multiforme (EM) major. The patient’s prodrome of fever, cough, and malaise also supported a “walking pneumonia” diagnosis, such as MPAM.
Further testing. The patient had a normal chest x-ray and a negative respiratory virus polymerase chain reaction (PCR), but IgM serologies for Mycoplasma were elevated. Although the patient developed targetoid lesions on his hands during his first 24 hours in the hospital, he felt his constitutional symptoms had improved.
Exposure to Mycoplasma leads to an immune response
MPAM (also known as Fuchs’ syndrome and mycoplasma-associated mucositis with minimal skin manifestations) appears at some point during infection with M pneumoniae and causes severe ocular, oral, and sometimes genital symptoms with minimal skin manifestations.
MPAM is primarily seen in young males. In one systemic review of 202 cases, the average age of the patients was 11.9 years and 66% were male.1 Exposure to M pneumoniae is theorized to result in the production of autoantibodies to mycoplasma p1-adhesion molecules and to molecular mimicry of keratinocyte antigens located in the mucosa.1-3
Mycoplasma organisms have not been isolated from the cutaneous lesions of patients with MPAM; they have only been isolated from the respiratory tract, supporting the theory that MPAM is the body’s immune response to Mycoplasma, rather than a direct pathologic effect.4 This pathogenesis is distinct from that of SJS/TEN, which is thought to involve CD8+ T-cell-mediated keratinocyte apoptosis (programed cell death). In addition, SJS/TEN is almost always drug induced.
First up in the differential: Rule out SJS/TEN
When evaluating a patient like ours with a blistering eruption, the most important diagnosis to exclude is SJS/TEN. This condition is usually triggered by a medication, which was absent in this case. SJS/TEN begins with a host of constitutional symptoms and an erythematous blistering eruption, which may be preceded by atypical targetoid (2-zoned) flat papules along with erosions on 2 or more mucosal surfaces.
Patients with SJS/TEN are usually critically ill and may have a guarded prognosis. Patients with MPAM have a more favorable prognosis and are unlikely to be critically ill—as was the case with our patient.
EM major is often associated with Mycoplasma infections. Patients with EM major may have fever and arthralgias, as well as extensive mucous membrane involvement including that of the lips/mouth, eyes, and genitals.
Experts agree that EM is separate from the SJS/TEN continuum, and that patients with EM major, including those with MPAM, are not at risk of developing SJS/TEN.5 EM is characterized by the presence of the more characteristic ‘target’ or ‘iris’ 3-zoned lesion—a central dusky purpura, surrounded by an elevated edematous pale ring, rimmed by a red macular outer ring. EM major is defined as EM along with involvement of one or more mucosal regions.
In this case, the patient had acral target lesions and oral and ocular mucosal involvement characteristic of EM major, without widespread skin erosions or sloughing commonly seen with SJS/TEN.
Kawasaki’s disease occurs in young children and presents with conjunctivitis and oral changes. However, patients with Kawasaki’s disease generally have a fever for >5 days, a strawberry tongue (not a part of the morphology of EM major or MPAM), and palmoplantar erythema and desquamation that are not common with EM major or MPAM.1
Pemphigus vulgaris is uncommon in children and young adults. The disease does not present with diffuse mucositis nor diffuse blistering of the skin, but rather with discrete shallow erosions on the mucosa and the trunk along with flaccid bullae and erosions on the skin.
The morphologies of a fixed drug eruption (round purpuric patch) and toxic shock syndrome (diffuse macular erythema and widespread skin sloughing) are inconsistent with this patient’s diffuse mucositis, conjunctivitis, and targetoid lesions.