Erythema Multiforme Secondary to Mumps

ABSTRACT.

Erythema multiforme (EMF), an immune-mediated disorder, presents with either cutaneous or mucosal lesions, or both. Although associated with multiple etiologies, the majority are attributed to infectious etiologies and drugs. In this case report, we describe a case of EMF secondary to a very uncommon etiology—mumps. A 22-year-old male presented with targetoid lesions on bilateral palms, the upper and lower extremities, and the trunk. He also had a few targetoid lesions on the lips and glans penis. The patient reported an episode of fever with parotid enlargement and tenderness 1 week before the onset of skin lesions. A serological investigation revealed significantly elevated IgM antibody titers to mumps. Erythema multiforme has many triggering factors, with infections such as herpes simplex virus being the most common, followed by drugs like penicillin, cephalosporins, and others. This case report shows that, in addition to the most common causes, other viral infectious etiologies should also be considered as possible triggers.

INTRODUCTION

Erythema multiforme (EMF), an immune-mediated disorder, presents with cutaneous or mucosal lesions, or both.¹ Patients may present with both typical (lesions with three concentric rings) and atypical (lesions with only two concentric rings) target lesions. Prodromal symptoms are typically absent in EMF; nevertheless, they have been observed in cases of mucocutaneous involvement.¹ Lesions usually erupt over a 72-hour period and, in some cases, produce mild pruritus or a “burning” sensation.²

Erythema multiforme is typically triggered by certain drugs and infections, most commonly the herpes simplex virus (HSV) infection.¹ In this case report, we describe a case of EMF secondary to a rare etiology—mumps.

CASE HISTORY

A 22-year-old man presented with multiple reddish raised lesions on his trunk and extremities. He had a history of itching on both palms and soles, which progressed to form target lesions with central reddish-purple discoloration on the bilateral palms (Figure 1A), bilateral soles (Figure 1B), and back (Supplemental Figure 1). Targetoid lesions were observed on both extremities, the chest, and the abdomen (Supplemental Figure 2). He developed multiple closely placed bullae and a few vesicles on the right wrist and the bilateral dorsum aspects of the feet and soles (Figure 1B, red arrow). He also had similar lesions on the lips and a few erythematous macules on the glans penis after 48 hours from the onset of the skin lesions (Supplemental Figure 3).

Figure 1.

(A) Target lesions with central reddish discoloration on the bilateral palms. (B) Targetoid lesions on the left foot with multiple closely placed bullae on the soles (red arrow).

There was no history of drug intake before the onset of the lesions. The patient experienced an episode of fever accompanied by parotid enlargement and tenderness 1 week before the lesions appeared. He was diagnosed with mumps and managed conservatively by the Ear, Nose & Throat department. Serological investigation revealed positive IgM antibody titers (6.60 index value) for mumps. The patient was treated with systemic steroids (prednisolone 0.5 mg/kg/day) along with topical corticosteroids, emollients, and antihistamines. After 6 days of treatment, he showed clinical improvement and was discharged without complications.

DISCUSSION

Mumps, which is caused by an enveloped, nonsegmented, single-stranded RNA paramyxovirus, is an important vaccine-preventable childhood viral disease. Humans are the only natural hosts, and the incubation period ranges from 12 to 25 days. The disease is transmitted via the respiratory route through inhalation or oral contact with infected respiratory droplets or secretions.³

It is characterized by pain and swelling of the parotid glands, along with nonspecific prodrome, such as fever, malaise, headache, myalgia, and anorexia. Parotid swelling is typically bilateral, occurring in over 70% of infections.⁴ Although benign, it can lead to serious complications, including encephalitis, meningitis, orchitis, myocarditis, pancreatitis, and nephritis.³

The laboratory tests include reverse transcriptase polymerase chain reaction (RT-PCR) and serum IgM antibodies. A buccal or oral swab, ideally collected within 3 days of parotid swelling, is used for RT-PCR.⁵ IgM antibodies are not detected until 5 days after the onset of symptoms in unvaccinated individuals and may not be detected in vaccinated individuals.⁶ Treatment primarily involves providing supportive care and analgesics, along with cold or warm compresses for parotid swelling.³

The incidence of mumps in the United States dropped by 99% after the introduction of the vaccine.⁵ The mumps vaccine is available as part of a trivalent measles, mumps & rubella (MMR) vaccine, which is scheduled to be administered in two doses: the first dose at the age of 1 and the second between the ages of 4 and 6 years. It is a live attenuated vaccine that is contraindicated in pregnancy and in individuals with immunosuppression.⁶

Erythema multiforme is an immune-mediated condition that typically presents with discrete target lesions and can affect both mucosal and cutaneous sites.¹

Erythema multiforme has many triggering factors, with HSV infection and Mycoplasma pneumonia infection being the most common, followed by drugs such as penicillins, cephalosporins, sulfonamides, and others. Erythema multiforme is also triggered by contact with heavy metals, herbal agents, topical therapies, and poison ivy.⁷

Although it is associated with multiple etiologies, the majority are attributed to infectious etiologies, with HSV infection being the most common, followed by Mycoplasma pneumoniae infection. Drug triggers contribute to less than 10% of cases.⁷ A more recent association between EMF and the severe acute respiratory syndrome coronavirus 2 pathogen, the novel coronavirus responsible for the recent pandemic, has been described.⁸ Medications implicated in causing EMF include nonsteroidal anti-inflammatory drugs, sulfonamides, antiepileptics, and antibiotics.¹

A few cases of EMF secondary to vaccination have been reported, including MMR, diphtheria pertusis tetanus, coronavirus disease 2019, and hepatitis B vaccinations.^9–11 Bernardini et al. reported a case of EMF secondary to the MMR vaccine in an 18-month-old boy. The proposed pathogenetic mechanism is similar to that of viropathic effects mediated by HSV proteins (DNA polymerase) and the immunological reaction to viral antigens.⁹

Prodromal symptoms such as fever, myalgias, and malaise are not common in most cases of EMF but are typical in cases with mucosal involvement. These symptoms may appear 1 week or more before EMF manifests.²

Round, erythematous, edematous papules surrounded by blanching patches that mimic insect bites or papular urticaria are typically the initial signs of EMF. The well-known target lesions of EMF can arise from the enlargement of these papules and the development of concentric changes in morphologic characteristics and color. The morphologic features of a target lesion include a central area of epidermal necrosis that may appear as a dusky area or blister. Immediately outside this central area is a dark red inflammatory zone, which is surrounded by a lighter edematous ring and an erythematous zone at the extreme periphery.¹²

Over the course of an episode of EMF, lesions may change, resulting in modifications in the concentric morphologic characteristics and the development of annular, polycyclic, and geographic patterns.¹³ Patients with EMF may also present with atypical lesions. These areas manifest as circular, palpable, edematous lesions with either only two zones or a weakly defined border, or both, in contrast to the conventional target symptoms.²

Lesions in classical EMF are typically symmetrically distributed on the acral extremities, with a predilection for the extensor surfaces. Although lesions may ultimately spread in a centripetal fashion, the trunk is usually far less affected than the extremities.¹

Erythema multiforme prognosis depends on the underlying cause; however, most viral triggers in immunocompetent patients are self-limited. Acute EMF cases typically resolve spontaneously within 7 to 21 days, with treatment strategies primarily being supportive, such as corticosteroids and antihistamines. Proper follow-up and the avoidance of exacerbating factors are crucial for determining prognostic outcomes in EMF cases. The recurrence rate of EMF is <5%, with most recurrences associated with HSV infections.¹⁴

Mucosal erosion-related pain, burning and itching of the skin, edema in the hands and feet, and inadequate hydration and oral intake are major causes of morbidity in EMF. Although the skin lesions do not lead to scarring, post-inflammatory hyperpigmentation may persist for months after disease resolution.¹³ To the best of our knowledge, EMF secondary to mumps has not yet been recorded.

CONCLUSION

This case report demonstrates that, in addition to the common causes, other viral infectious etiologies should also be investigated. Although EMF has frequently been reported secondary to HSV infection or drugs, other uncommon viral etiologies, such as mumps, should also be considered.

A prompt diagnosis and early management, leading to better outcomes, can be achieved in patients with EMF by anticipating these uncommon etiologies.

Note: Supplemental materials appear at www.ajtmh.org.