Diagnosis of Herpes Simplex Virus-Induced Erythema Multiforme Confounded by Previous Infection With Mycoplasma Pneumonia
June 2013 | Volume 12 | Issue 6 | Case Reports | 707 | Copyright © June 2013
Barry Ladizinski MD,a Joi B Carter MD,b Kachiu C. Lee MD MPH,c Denise M. Aaron MDd
aDepartment of Dermatology, Duke University Hospital, Durham, NC
bDepartment of Dermatology, Mass General Hospital, Boston, MA
cDepartment of Dermatology, Brown University Hospital, Providence, RI
dDepartment of Dermatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH
Erythema multiforme (EM) is an immune-mediated hypersensitivity reaction often related to viral infection or medications. Infection-induced
EM is typically self-limited and commonly caused by herpes simplex virus (HSV) or Mycoplasma pneumoniae (MP); recurrent
EM is almost always associated with HSV. We present a concise overview of diagnostic techniques for HSV and MP, as repeatedly
elevated MP titers in our case led to a delayed diagnosis of HSV-induced EM. J Drugs Dermatol.
An 18 year-old male presented with 1 week of painful oral lesions accompanied by fever, cough and photophobia.
Physical examination revealed an ill appearing
male with bilateral conjunctivitis and hemorrhagic crusting on the lips (Figure 1). There were no lesions on the hands or genitalia. Blood, eye, sputum and throat cultures were unremarkable. Mycoplasma pneumoniae (MP) serology showed elevated IgM (1.51 g/l) and IgG (4.92 g/l), and he was successfully
treated with azithromycin and prednisone for presumed MP-induced erythema multiforme (EM).
One year later, he presented with oral ulcers and targetoid macules on the penis. MP IgM and IgG were again elevated at 1.68 g/l and 6.03 g/l, respectively. HSV serologies were normal except for elevated HSV-1 IgG, suggesting previous exposure or infection, and he responded to treatment with azithromycin and prednisone for presumed recurrent MP-induced EM.
One month later, he returned with bilateral conjunctivitis, clustered
vesicles on the lips (Figure 2), oral white plaques (Figure 3), and targetoid macules on the penis (Figure 3). Repeat HSV serologies were normal except for elevated HSV-1 IgG and HSV-1 direct fluorescent antibody (DFA) testing from a lip lesion was positive. A diagnosis of recurrent HSV-induced EM was made and he was treated with valacyclovir without further recurrences.
Erythema multiforme is an immune-mediated hypersensitivity reaction usually due to infection (up to 90% of cases) or rarely, medications (less than 10% of cases). Infection-induced EM is typically self-limited and commonly caused by HSV or MP; recurrent EM is almost always associated with HSV. However,
identifying the causal factor can be sometimes challenging given variations in diagnostic methods. Herein, we present a concise overview of diagnostic techniques for HSV and MP (Tables
1 and 2), as repeatedly elevated MP titers with normal HSV IgM in our case led to a delayed diagnosis of HSV-induced EM.
Diagnosis of herpes simplex virus
Serology can aid in the diagnosis of primary HSV infection, but is less helpful with distinguishing recurrences. HSV IgM becomes positive within 9 to 14 days of initial infection and remains elevated
up to 7 weeks. However, IgM may not be produced during HSV recurrence, leading to missed diagnoses. HSV IgG becomes positive within 4 weeks and remains elevated indefinitely. Sensitivity
and specificity are presented in Table 1.1
HSV culture becomes positive within 2 to 5 days, but samples must be obtained from active vesicles during viral shedding, which lasts an average of 4 days. Cultures may be negative in over 50% of recurrent lesions, resulting in gross underdiagnoses.2, 3
Direct Fluorescent Antibody (DFA)
A comparison between DFA and viral culture found a sensitivity of 85% for DFA analysis.3 For recurrent lesions, multiple samples
are recommended to maximize collection of viral particles. DFA has a rapid turnaround time and allows for differentiation between HSV and varicella zoster virus (VZV).
Polymerase Chain Reaction (PCR)
PCR detects DNA from ocular, oral and genital lesions, with superior
specificity to culture.4 PCR can also detect viral copies during