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Saliva Polymerase Chain Reaction Assay for Detection and Follow-up of Herpesvirus Reactivation in Patients With Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS)

Vincent Descamps, MD, PhD; Martine Avenel-Audran, MD; Laurence Valeyrie-Allanore, MD; Benoit Bensaid, MD; Annick Barbaud, MD, PhD; Mustafa Al Jawhari; Sylvie Ranger-Rogez, MD, PhD; for the French Study Group of Cutaneous Drug Adverse Reactions
JAMA Dermatol. 2013;149(5):565-569. doi:10.1001/jamadermatol.2013.2018.
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Importance Reactivations of human herpesviruses (HHVs) contribute to the development of drug reaction with eosinophilia and systemic symptoms (DRESS). Diagnosis of HHV reactivation is conventionally based on quantitative real-time polymerase chain reaction (PCR) analysis of blood samples, but these viruses are present in the oropharynx and are shed in saliva.

Objective To evaluate the use of a saliva PCR assay for demonstrating HHV shedding in patients with DRESS.

Design Shedding of HHV in saliva was prospectively studied in patients with DRESS. Reactivations of HHV, including HHV-6, HHV-7, cytomegalovirus (CMV), and Epstein-Barr virus (EBV), were studied by performing quantitative real-time PCR analysis of blood samples obtained at admission) and serial samples of saliva obtained within the first 2 weeks of DRESS; saliva samples from controls were compared.

Participants The study included 5 patients who met definite criteria for DRESS and 15 controls (5 immunosuppressed patients and 10 healthy adults).

Main Outcome Measures DNA viral loads of HHV, including HHV-6, HHV-7, CMV, and EBV as measured with real-time PCR in blood and saliva samples from patients with DRESS and saliva samples from immunosuppressed and healthy controls.

Results The PCR assay demonstrated shedding of HHV-7, EBV, HHV-6, and CMV, listed by order of magnitude. The DNA viral loads in blood and saliva samples, also measured with real-time PCR, were found to be close. In 1 patient, reactivations in saliva preceded clinical manifestations of CMV disease. Significant production of HHV-7 and EBV was demonstrated in saliva samples from the controls, but neither HHV-6 nor CMV were detected.

Conclusions and Relevance The saliva PCR assay is a useful tool for demonstration and follow-up of HHV reactivation. The interpretation of HHV viral loads in saliva differs according to HHV type.

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Figure 1. Real-time quantitative polymerase results in blood and saliva samples from 5 patients with drug reaction with eosinophilia and systemic symptoms (DRESS), showing virus loads for cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and human herpesvirus 7 (HHV-7). A horizontal threshold line of 100 DNA copies/μg DNA is noted. B indicates blood sample; S1 through S7, saliva samples 1 through 7. When no results are shown, samples were negative.

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Figure 2. Real-time quantitative polymerase chain reaction results in saliva samples from 5 immunosuppressed patients, 10 healthy adults, and 5 patients with drug reaction with eosinophilia and systemic symptoms (DRESS; highest values within the 2-week period are presented). A horizontal threshold line of 100 DNA copies/μg DNA is noted. CMV indicates cytomegalovirus; EBV, Epstein-Barr virus; and HHV, human herpesvirus.

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