Painful mucositis in an 8-year-old boy

Can you spot the rash?

ByMichele Khurana, MD

Fact checked byCarol L. DiBerardino, MLA, ELS

Michele Khurana

An 8-year-old boy presented to the ED with a fever and a painful rash involving his mouth, eyes and genitals.

He was in his usual state of good health until about 5 days before presentation, when he developed fevers and a persistent cough. He later developed painful blisters and erosions on his lips and within his mouth, which led to difficulty eating (Figure 1). The lesions progressed to involve his genitals, and he developed pain with urination as well. He also developed a few blisters on his face and extremities. He was otherwise healthy and did not take any medications.

Figure 1. Lips with crusted vesicles and erosions; left cheek with targetoid papule with central erosion. Image: Michele Oboite, MD.

In the ED, he was found to have multiple vesicles/erosions with overlying hemorrhagic crusting involving the lips and intraoral mucosa. His physical exam also revealed bilateral conjunctival injection, penile erosions and a few scattered targetoid eroded papules on the left cheek and distal extremities (Figure 2).

Figure 2. Targetoid papules and plaques on the left upper extremity. Image: Michele Oboite, MD.

Can you spot the rash?

A. Stevens-Johnson syndrome
B. Mycoplasma pneumoniae-induced rash and mucositis
C. Erythema multiforme
D. Staphylococcal scalded skin syndrome

Case discussion

The correct answer is B, Mycoplasma pneumoniae-induced rash and mucositis (MIRM), an entity characterized by severe mucositis involving two or more mucous membranes, along with a mild skin eruption in the setting of M. pneumoniae infection.

MIRM most commonly affects children and young adults. The pathophysiology is unknown, although genetic predisposition and molecular mimicry are thought to play a role. Although this reactive mucocutaneous phenomenon was initially named after the association with M. pneumoniae infection, other infectious etiologies have since been found to produce this eruption as well, including Chlamydia pneumoniae, group A Streptococcus, metapneumovirus, parainfluenza virus 2, rhinovirus, enterovirus, adenovirus, influenza virus and SARS-CoV-2 virus. Thus, it has since been proposed to rename this entity as reactive infectious mucocutaneous eruption (RIME) to reflect the broad variety of infections that can trigger this distinct postinfectious eruption.

MIRM/RIME classically presents as an acute mucosal-predominant eruption involving two or more sites, most commonly affecting the oral, ocular and/or urogenital mucosa. Oral involvement is nearly universal, often manifesting with significant crusting of the lips and resultant dysphagia. Ocular involvement typically presents as conjunctivitis. Patients with urogenital involvement may complain of dysuria. In contrast, skin findings are characteristically mild and may even be absent. Skin lesions can be polymorphous but most commonly manifest as blisters and/or targetoid papules. The targetoid papules often have central duskiness, blistering and/or erosions from epidermal necrosis. Lesions tend to be scattered and sparse in distribution with a predilection for the extremities. Additionally, patients often report a prodrome with cough from respiratory system involvement.

Workup for a patient with suspected MIRM/RIME should include an investigation for potential infectious triggers. This may include PCRs for M. pneumoniae as well as respiratory viruses. The cornerstone of management of MIRM/RIME is supportive care. Hospital admission for pain control is common. Although many patients with MIRM/RIME are treated with immunosuppressive agents (such as corticosteroids, intravenous immunoglobulin) and/or antibiotics for the antecedent infection, there currently are no established guidelines regarding treatment. Consultations with appropriate specialists — including dermatology, ophthalmology, oral medicine and urology — are important.

The differential diagnosis of prominent mucositis in conjunction with necrotic skin lesions should always include Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), a severe hypersensitivity reaction most commonly due to a medication that tends to occur 7 to 21 days after exposure to a suspect drug. It is more common in adults than in children. The most frequent offending agents include antibiotics (such as penicillins and sulfonamides), antiepileptics (including lamotrigine, carbamazepine, phenobarbital and phenytoin), allopurinol, and NSAIDs.

SJS/TEN represents a spectrum of the same disease and can be differentiated based upon the amount of body surface area (BSA) involved, with less than 10% BSA involvement termed SJS, more than 30% BSA termed TEN, and 10% to 30% BSA termed SJS-TEN overlap. Patients often initially present with mucositis and painful dusky erythematous and purpuric macules/patches that may appear targetoid before rapidly progressing to blistering and sloughing. In comparison to MIRM/RIME, skin involvement in SJS/TEN is usually more severe.

Furthermore, SJS/TEN is associated with more significant morbidity and mortality compared with RIME, and frequently results in permanent sequelae. Prompt discontinuation of the offending agent and aggressive supportive care are critical given the potentially life-threatening nature of this disease. Thus, it is important to obtain a thorough medication history for any patient presenting with mucositis and necrotic skin lesions and discontinue any unnecessary/potentially offending medications.

Erythema multiforme (EM) is also on the differential diagnosis for a patient presenting with mucositis with targetoid skin lesions. EM is a hypersensitivity reaction most commonly due to herpesvirus infection, which may or may not be active at the time of the eruption. It is characterized by recurrent, self-limited episodes that usually last for a few weeks before resolving without sequelae. The hallmark of EM is the presence of typical target lesions with three distinct color zones — central duskiness, then a surrounding edematous area of pallor, followed by a peripheral rim of erythema. Lesions are most prominent on acral sites with a predilection for the palms and soles. Unlike MIRM/RIME, the mucosal involvement in EM is usually mild and rare in comparison. In cases that are unclear, it could be helpful to obtain testing for HSV (such as a PCR) from mucosal lesions.

Overall, outcomes from MIRM are typically good, with most patients fully recovering. Although recurrence and long-term sequelae such as mucosal synechiae and pigmentary alteration are infrequent, it is important to monitor for this. Some features of MIRM that can help to differentiate it from SJS/TEN and EM include young age, mucosal predominance, sparse skin involvement, lack of exposure to a highly worrisome medication and generally favorable prognosis.

References:

Canavan TN, et al. J Am Acad Dermatol. 2015;doi:10.1016/j.jaad.2014.06.026.

Gámez-González LB, et al. Pediatr Dermatol. 2021;doi:10.1111/pde.14419.

Paller A, Mancini AJ. Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence. 5th ed. Edinburgh: Elsevier; 2016.

Ramien ML, et al. JAMA Dermatol. 2020;doi:10.1001/jamadermatol.2019.3589.

Song A, et al. Pediatr Dermatol. 2021; doi: 10.1111/pde.14780.