Evidence for Reactivation of Human Herpesvirus 6 in Generalized Lymphadenopathy in a Patient with Drug-Induced Hypersensitivity Syndrome

Abstract

The present case provides direct evidence of human herpesvirus 6 reactivation in resected lymph node tissue in a patient with drug-induced hypersensitivity syndrome. This case clearly demonstrates that appropriate pathological evaluation of lymphadenopathy for drug-induced hypersensitivity syndrome, which mimics malignant lymphoma in clinical, radiological, and pathological findings, is required. CASE REPORTA 57-year-old woman was referred to our department because of generalized erythema involving mainly her face and upper trunk, with a morbilliform eruption for a week, persistent pyrexia, and a sore throat for the preceding 3 weeks. She had been treated for bipolar disorder and had a history of atopic dermatitis and bronchial asthma in her childhood. She had been on lorazepam, famotidine, and loxoprofen for a decade, and carbamazepine had been started 1 month prior to coming to our department ( Fig. 1, day 1). She was allergic to soybeans, corn, eggs, and rice. She had not been in contact with any sick persons. At her first visit to our department (day 34), physical examination showed mild periorbital edema and expanding erythema from her face to both lower legs, with a morbilliform eruption, but no mucosal ulcers or erosions were noted. Thus, she was tentatively diagnosed as having an adverse cutaneous reaction to carbamazepine; therefore, carbamazepine was stopped, and oral prednisolone therapy was started at a dose of 20 mg/day. One week after starting the prednisolone therapy (Fig. 1, day 43), her sore throat and high-grade fever had almost disappeared, and some aspects of the cutaneous lesions, such as pigment deposition and nonpalpable purpura, had improved. Of note, at this time, she noticed generalized lymphadenopathy and returned to our department.At her 2nd visit to our department (day 43), physical examination showed generalized superficial lymphadenopathy (supraclavicular, cervical, axillary, and inguinal), and each node was 20 mm in size, firm, nonfixed, circumscribed, and rubbery, suggesting lymphoma. Laboratory examination revealed marked elevations of her white blood cell count (37,400/l, with 1% basophils, 7% eosinophils, 25% neutrophils, 44% lymphocytes, 14% atypical lymphocytes, and 3% monocytes), lactate dehydrogenase (1,657 IU/liter), and soluble interleukin 2 receptor (11,600 U/ml). Moderate elevations of serum hepatic biliary enzymes were also noted (aspartate aminotransferase, 81 IU/liter; alanine aminotransferase, 144 IU/liter; alkaline phosphatase, 264 IU/liter; ␥-glutamyl transpeptidase, 371 IU/liter). Two sets of blood cultures were negative, and no evidence of a recent infectious mononucleosis (IM) syndrome (Epstein-Barr virus) or IM-like syndrome (cytomegalovirus, Toxoplasma gondii, human immunodeficiency virus) was detected (Fig.

Bronchoscopic Investigation of Atypical Drug-induced Hypersensitivity Syndrome Showing Viral Lung Involvement

“…Many members of the Hepeviridae family have been reported to be reactivated in DIHS patients. A few reports demonstrated these latent viruses pathologically: HHV-6 in monocytes of skin lesions (2), atypical Reed-Sternberg-like cells of lymph nodes (20), and Treg cells of lymph nodes (21); and CMV in skin lesions (22). The present case showed inclusion bodies and multinucleated giant cells in the lung specimens, which suggest that the causal virus might have been a member of the Herpesviridae family, which are commonly found in latent infections in humans.…”

Multiple Drug Induced Hypersensitivity Syndrome Reactions in a Patient with Drugs that Have Known HLA Associations for Reactions

“…It is possible that herpes virus reactivation, most notably HHV-6, was the common underlying factor for the multiple drug reactions [38][39][40][41][42], although that was not proven in our case. We conclude that the HLA-B*58 haplotype may be a risk factor for drug hypersensitivity syndrome with imatinib therapy in patients who react to allopurinol, but this needs to be confirmed in further studies.…”

Evidence for human herpesvirus-6B infection of regulatory T-cells in acute systemic lymphadenitis in an immunocompetent adult with the drug reaction with eosinophilia and systemic symptoms syndrome: A case report

“…Although lymphadenopathy is very common among the patients with DRESS syndrome, so far there have been a few immunohistochemical studies of the lymphadenopathy [13,14]. A previous study demonstrated the presence of HHV-6-infected cells in the lymph node in a case of DRESS syndrome [14].…”

“…A few cases of HHV-6-associated acute lymphadenitis have been reported in pathological studies, including one in a patient with DRESS syndrome [13,14]. The expression of CD25 and FoxP3 is known to be induced by infections with viruses including the human T-lymphotropic virus 1 [15], and HHV-6 [16,17], but there have been no reports so far describing HHV-6 activation in Tregs or CD25(+)/FoxP3(+) cells.…”