Reactive Infectious Mucocutaneous Eruption Associated With SARS-CoV-2 Infection | Dermatology | JAMA Dermatology | JAMA Network
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April 7, 2021

Reactive Infectious Mucocutaneous Eruption Associated With SARS-CoV-2 Infection

Author Affiliations
  • 1Harvard Combined Dermatology Residency Program, Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts
  • 2Dermatology Program, Boston Children's Hospital, Boston, Massachusetts
JAMA Dermatol. 2021;157(5):603-605. doi:10.1001/jamadermatol.2021.0385

As COVID-19, caused by SARS-CoV-2, spreads worldwide, various patterns of associated dermatologic diseases continue to emerge. Early reports classified multiple cutaneous manifestations of SARS-CoV-2 infection.1 In this article, we report the observation of a newly associated mucocutaneous eruption in a pediatric patient with confirmed SARS-CoV-2 infection.

Report of a Case

A previously healthy 17-year-old male presented to the emergency department with 3 days of mouth pain and nonpainful penile erosions. One week prior, he experienced transient anosmia and ageusia that had since spontaneously resolved. At that time, he was tested for SARS-CoV-2 infection via nasopharyngeal polymerase chain reaction (PCR), the results of which were positive. He denied fever, cough, dyspnea, rhinorrhea, and gastrointestinal symptoms at any time. Although he had taken acetaminophen and ibuprofen before presenting to the emergency department, he took no medications before the onset of his mucocutaneous eruption.

At initial presentation, the patient did not have a fever and was in no distress. His vital signs were normal, including a respiratory rate of 16 breaths per minute and an oxygen saturation of 97%. Physical examination revealed shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and 5 small vesicles on the trunk and upper extremities (Figure 1). The remainder of the mucocutaneous (including palms and soles), cervical lymphatic, and cardiopulmonary examinations were unremarkable. Laboratory testing results revealed a normal white blood cell count (7030 leukocytes/μL [to convert to ×109/L, multiply by 0.001]; reference: 5240-9740 leukocytes/μL) with mild absolute lymphopenia (930 lymphocytes/μL; reference: 1030-2180), slightly elevated creatinine level (1.2 mg/dL [to convert to μmol/L, multiply by 88.4]; reference: 0.3-1.0 mg/dL), normal liver function, slightly elevated C-reactive protein level (3.0 mg/dL [to convert to mg/L, multiply by 10]; reference: <0.5 mg/dL), normal D-dimer level (0.37 μg/mL [to convert to nmol/L, multiply by 5.476]; reference: <0.5 mg/dL), and normal ferritin level (180 ng/mL [to convert to μg/L, multiply by 1]; reference: 10-320 μg/L). Microbiological testing results revealed positive repeated SARS-CoV-2 nasopharyngeal PCR and negative nasopharyngeal PCR testing for Mycoplasma pneumoniae, adenovirus, Chlamydophila pneumoniae, human metapneumovirus, influenza A/B, parainfluenza 1 to 4, rhinovirus, and respiratory syncytial virus. Titers of Mycoplasma pneumoniae IgM levels were negative, but Mycoplasma pneumoniae IgG levels were elevated. A diagnosis of SARS-CoV-2–associated reactive infectious mucocutaneous eruption (RIME) was made.

Figure 1.  Initial Presentation 3 Days After Onset of Mucocutaneous Symptoms and 1 Week After Initial Anosmia and Ageusia
Initial Presentation 3 Days After Onset of Mucocutaneous Symptoms and 1 Week After Initial Anosmia and Ageusia

A, Shallow erosions of the vermilion lips and hard palate. B, Periurethral erythema and shallow erosions on the glans penis. C, Few small vesicles on the upper extremities.

The patient was prescribed betamethasone valerate, 0.1%, ointment for the lips and penis, intraoral dexamethasone solution, viscous lidocaine, acetaminophen, and ibuprofen. However, he noted progressively worsening oral pain over the subsequent 3 days, prompting initiation of oral prednisone, 60 mg (approximately 1 mg/kg), daily for 4 consecutive days (Figure 2A). This was followed by drastic improvement in his mucositis (Figure 2B). He did have brief recurrence of oral mucositis 3 months later, but this also resolved quickly with prednisone, 80 mg, for 6 days.

Figure 2.  Mucositis
Mucositis

A, The patient experienced worsening mucositis and pain 10 days after initial anosmia and ageusia, at which time prednisone treatment was initiated. B, The mucositis had essentially resolved on follow-up 3 weeks after starting prednisone.

Discussion

Formerly known as Mycoplasma-induced rash and mucositis, RIME has arisen as the preferred terminology to include mucocutaneous eruptions that are caused by other infectious agents.2 This case describes RIME secondary to SARS-CoV-2 infection, details its resolution with systemic steroids, and notes the potential for recurrence with subsequent milder symptoms, as has been previously reported.3 The combination of anosmia and ageusia, multiple positive SARS-CoV-2 PCR tests, and no other identified contemporaneous infections (the elevated Mycoplasma pneumoniae IgG titer with low IgM titer and negative nasopharyngeal PCR likely indicated prior exposure) suggests SARS-CoV-2 as the infectious trigger. The sparse cutaneous involvement and lack of dusky targetoid lesions also distinguish RIME from Stevens-Johnson syndrome and erythema multiforme (which has been described in association with SARS-CoV-2 infection).4,5 Furthermore, RIME can be distinguished from the newly described multisystem inflammatory syndrome in children, which is associated with Kawasaki disease–like features, including mucocutaneous involvement, systemic symptoms, and dramatically elevated systemic inflammatory markers.6 This case highlights what is to our knowledge the first report of SARS-CoV-2–induced RIME and distinguishes this entity from other mucocutaneous eruptions with substantially different prognoses and treatment algorithms.

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Article Information

Corresponding Author: Zachary E. Holcomb, MD, Dermatology Program, Boston Children’s Hospital, 300 Longwood Ave, Boston, MA 02115 (zholcomb09@gmail.com).

Published Online: April 7, 2021. doi:10.1001/jamadermatol.2021.0385

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank the patient’s mother for granting permission to publish this information.

References
1.
Galván Casas  C, Català  A, Carretero Hernández  G,  et al.  Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases.   Br J Dermatol. 2020;183(1):71-77. doi:10.1111/bjd.19163 PubMedGoogle ScholarCrossref
2.
Ramien  ML, Bruckner  AL.  Mucocutaneous eruptions in acutely ill pediatric patients—think of mycoplasma pneumoniae (and other infections) first.   JAMA Dermatol. 2020;156(2):124-125. doi:10.1001/jamadermatol.2019.3589 PubMedGoogle ScholarCrossref
3.
Mazori  DR, Nagarajan  S, Glick  SA.  Recurrent reactive infectious mucocutaneous eruption (RIME): Insights from a child with three episodes.   Pediatr Dermatol. 2020;37(3):545-547. doi:10.1111/pde.14142 PubMedGoogle ScholarCrossref
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Jimenez-Cauhe  J, Ortega-Quijano  D, Carretero-Barrio  I,  et al.  Erythema multiforme-like eruption in patients with COVID-19 infection: clinical and histological findings.   Clin Exp Dermatol. 2020;45(7):892-895. doi:10.1111/ced.14281 PubMedGoogle ScholarCrossref
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Demirbaş  A, Elmas  ÖF, Atasoy  M, Türsen  Ü, Lotti  T.  A case of erythema multiforme major in a patient with COVID 19: The role of corticosteroid treatment.   Dermatol Ther. 2020;33(6):e13899. Published online July 13, 2020. doi:10.1111/dth.13899PubMedGoogle Scholar
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Whittaker  E, Bamford  A, Kenny  J,  et al; PIMS-TS Study Group and EUCLIDS and PERFORM Consortia.  Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2.   JAMA. 2020;324(3):259-269. doi:10.1001/jama.2020.10369PubMedGoogle ScholarCrossref
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