Increased human herpes virus 6 DNA detected by real-time PCR in the saliva of two patients with drug-induced hypersensitivity syndrome

ARTICLE

ejd.2012.1703

Auteur(s) : Yoko Hara, Manabu Yoshioka, Ryutaro Yoshiki, Motonobu Nakamura motonaka@med.uoeh-u.ac.jp

Department of Dermatology, University of Occupational and Environmental Health, Iseigaoka Yahatanishi-ku, Kitakyushu 807-8555, Japan

Drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilic and systemic symptoms (DRESS) is a severe cutaneous drug adverse reaction, characterized by a limited number of causative drugs, late onset, clinical similarity to infectious mononucleosis-like syndrome, prolonged clinical course and reactivation of viruses, including human herpes virus (HHV)-6 [1]. After infection by HHV-6 in childhood, HHV-6 persists in the salivary glands, peripheral blood mononuclear cells and central nervous system [2]. In this study, we analyzed the HHV-6 DNA content in the saliva of two DIHS/DRESS patients by real-time polymerase chain reaction (PCR) technique and found elevation of HHV-6 DNA in their saliva.

Case 1 was a 65-year-old female, who was referred to our hospital due to high fever and spreading erythema. She had suffered from DIHS/DRESS four months before and her blood examination had demonstrated elevated lymphocyte proliferations with phenobarbital and phenytoin, which she had taken for a year. Although she had been advised to refrain from taking phenobarbital or phenytoin, she had mistakenly taken phenobarbital, which was prescribed by another hospital. Physical examination revealed coalescent erythema on the face, body and extremities (figure 1A) with high fever at 39.4 ̊C and cervical lymph node swellings. She had no eruptions in the mucous membranes. Blood examination showed leukocytosis (11,900/μL) with the existence of atypical lymphocytes. Histological examination of the eruption showed lymphocyte infiltration around the small blood vessels in the dermis (figure 1B). With the diagnosis of DIHS/DRESS, based on the diagnostic criteria for DIHS/DRESS [3], we initiated a steroid pulse therapy [4, 5]. Both high fever and erythema resolved after the steroid pulse therapy (methylprednisolone 1,000 mg/day for 3 days, 15-17 days after onset). To examine the amount of HHV-6 DNA in the saliva, virus DNA was isolated from the patient's saliva. The HHV-6 DNA content was assessed by real-time PCR. The HHV-6 DNA in the saliva of the patient increased on day 21 after onset (figure 1C). HHV-6 DNA was not detected in the saliva of another patient who took phenobarbital without developing DIHS/DRESS.

Case 2 was a 73-year-old male with DIHS/DRESS by allopurinol. He suffered from high fever (38.9 ̊C), erythroderma and cervical lymph node swellings, 4 weeks after the initiation of medication with allopurinol. Blood examination showed an elevated alanine amino-transferase at 106 IU/L (normal 5-33), leukocytosis (14,300/μL), and an elevated lymphocyte proliferation with allopurinol. After the administration of methylprednisolone 1,000 mg/day for 3 days (4-6 days after onset), the high fever disappeared and erythema resolved. Real-time PCR analysis of HHV-6 DNA from the saliva from this patient revealed that HHV-6 DNA was elevated on days 11 and 18 after onset, while HHV-6 DNA was not detected in the saliva of another patient who took phenobarbital without developing DIHS/DRESS (figure 1D). HHV-6 DNA was also detected from the serum of the DIHS/DRESS patient on day 18 after onset (1,180 copies/mL).

In our study, the HHV-6 DNA in saliva was increased in these two patients with DIHS/DRESS. This may be due to an important role of HHV-6 in the pathogenesis of DIHS/DRESS. Compared with examination of the amount of HHV-6 in blood, saliva is easier to obtain from the patient. Moreover, the detection of HHV-6 can be completed within a few hours when using real-time PCR analysis. Frequent analysis of the HHV-6 DNA content in saliva offers us important information for the diagnosis and follow-up of DIHS/DRESS.

Disclosure

Financial support: none. Conflict of interest: none.

References

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3. Shiohara T, Iijima M, Ikezawa Z et al. The diagnosis of a DRESS syndrome has been sufficiently established on the basis of typical clinical features and viral reactivations. Br J Dermatol 2007; 156: 1083-4.

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