A "Major" Complication of Pink Eye


Rachel Vetter, BS, Sean McNitt, DO, MS, Christopher J. Smith, MD, FACP


Erythema multiforme (EM) is a cutaneous hypersensitivity reaction characterized by targetoid lesions. It is caused by a cell-mediated immune response, and infections are associated with 90% of cases (1). The term erythema multiforme major (EMM) is used to describe EM with severe mucosal involvement. Although herpes simplex virus type 1 (HSV-1) is the most identified etiology of EM, HSV-2 also has been shown to cause EM. Mycoplasma pneumoniae is the second most common etiology, especially in children (1). Medications have been known to cause less than 10% of cases. EMM secondary to adenovirus, although rare, has been documented in the literature with an initial presentation of keratoconjunctivitis (2). Here, we present a case of EMM with an atypical presentation.

Case Presentation

A 32-year-old man presented with two days of rapidly progressive rash, odynophagia, and cough. His prior history was notable for bilateral conjunctivitis treated a week prior. The rash was vesiculo-papular with some pustular lesions and was located primarily on sun-exposed areas, especially his shoulders and upper arms. He also had blanching, macular lesions on his palms and soles. Other findings included ulceration and sloughing of palatal and labial mucosa. Dermatology evaluated the patient and was initially concerned for disseminated HSV and empirically started acyclovir. His rash worsened in the next 48 hours, with centripetal extension, progression of mucosal involvement, and development of targetoid lesions. The patient was started on empiric treatment for mycoplasma out of concern for EM. His respiratory panel came back positive for adenovirus. Mycoplasma IgM and IgG were positive. HSV serologies were suggestive of prior infection with negative HSV testing from skin biopsies. Given the timing of his eye infection and rash it was determined the etiology was likely adenovirus- and M. pneumoniae-related EM. The patient was started on topical and systemic steroids in addition to finishing courses of acyclovir and azithromycin. He gradually improved after five days of supportive therapy and was discharged home.


Recognition of EMM and identification of inciting factors can present a diagnostic challenge in patients with atypical presentations. In patients presenting with EMM with prodromal conjunctivitis, physicians should have a low threshold for searching for adenovirus infection in addition to more likely causes such as HSV or Mycoplasma. As adenoviruses are highly contagious, early identification of the virus and patient isolation can prevent spread of the virus throughout the community. Additionally, identification of the triggering pathogen(s) allows for more rapid patient support and treatment.


  1. Trayes KP, Love G, Studdiford JS. Erythema multiforme: recognition and management. Am Fam Physician. 2019;100:82-88. [PMID: 31305041]
  2. Calas A, Lheure C, Bernigaud C, et al. AdenovirUS-induced erythema multiforme: eye and genital mucosal involvement is specific, whereas oral and cutaneous involvement is not. Acta Derm Venereol. 2020;100:adv00181. [PMID: 32511743] doi:10.2340/00015555-3547

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