A healthy 28 year-old man with isolated oral candidiasis at 17 and 26 years, on no medications, and having a recent URI 1 week before, presented with acute-onset progressive, painful oral mucositis and odynophagia (Fig. 1). His temperature was 101.6°F. The white blood cell count was 19.5, with 4.4% lymphocytes, 226CD4. Oral nystatin and IV caspofungin were started. Subsequently, the patient developed injected sclera with bilateral subconjunctival hemorrhages (Fig. 2) and marginated, erythematous, targetoid genital papules with vesicular centers (Fig. 3). His oral, ocular and genital lesions corresponded to the classic distribution of Behçet’s syndrome, initially placing this at the top of the differential diagnosis, followed by erythema multiforme (EM) and herpes simplex. However, generalized oral mucositis, conjunctivitis and, most importantly, targetoid lesions are not common in Behcet’s syndrome. Behcet’s syndrome frequently presents with aphthous ulcers sparing the outer lips, genital ulcers and uveitis. Subsequent biopsy of the targetoid lesions demonstrated EM, with vacuolizing keratinocytes and tagging lymphocytes. Skin lesions and pain resolved after 1 week of high-dose methylprednisolone without complications. Repeat complete blood count (CBC) showed resolution of the lymphocytopenia. EM is a self-limited hypersensitivity reaction to external triggers, most notably HSV, Mycoplasma pneumoniae and medications1,2. In this patient, HIV, HSV, M.pneumonia and Legionella studies were negative. Traditionally, EM has been placed within the hypersensitivity reaction spectrum, which includes Stevens-Johnson syndrome and toxic epidermal necrolysis3. However, there is suggestive evidence that EM may be a distinct entity. Treatment targets underlying infection and removing offending agents. Currently, systemic steroids are frequently used, but remain controversial.

Figure 1
figure 1

Oral ulcerations.

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Figure 2
figure 2

Subconjunctival hemorrhages and ocular ulcerations.

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Figure 3
figure 3

Scrotal and penile shaft ulcerations.

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