Human herpesvirus 6 involvement in paediatric drug hypersensitivity syndrome

Abstract

Background HHV6-positivity in context of drug hypersensitivity syndrome (DHS) may influence disease severity. Systemic corticosteroid treatment of those with DHS, testing positive for HHV6, has been speculated to prolong the duration of disease. Objectives This study's objectives are to: (1) Evaluate whether DHS patients with HHV6-positivity develop a more severe illness compared to DHS patients without presumed reactivation in the pediatric population, and (2) Evaluate the response to systemic corticosteroid treatment. Methods Retrospective case series of 29 pediatric inpatients treated for DHS and tested for HHV6. HHV6-positive and -negative patients were identified and stratified to groups treated with and without systemic corticosteroids to examine their disease severity on the basis of hospital length-of-stay (LOS), total number of febrile days (Tfeb), and days until cessation of progression (CTP). Results HHV6-positive patients had similar demographic characteristics as HHV6-negative patients, but had significantly longer hospital LOS (11.5 days v 5 days, p=0.0386), Tfeb (12.5 days v 3 days, p=0.0325), and CTP (4 days v 2 days, p=0.0141). All HHV6-positive patients and most (80%) of the HHV6-negative patients received systemic corticosteroids. Among the HHV6-negative patients, those who received corticosteroids showed significantly shorter CTP than those who did not receive corticosteroids (3 days v 2 days, p=0.043). Additionally, there was a trend towards shorter hospital LOS and Tfeb among HHV6-negative patients who received corticosteroids when compared with those who did not, though these differences were not statistically significant. The most common inciting drugs included trimethoprim-sulfamethoxazole (33%), phenytoin (10%), and amoxicillin (10%). Conclusions HHV6-positivity with DHS is associated with a more severe disease course. Treatment with systemic corticosteroids was associated with a non-statistical trend toward reduced hospital LOS and febrile days, and a statistically reduced number of days until cessation of progression.

Síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos en pediatría. Caso clínico

“…Ahluwalia et al studied in a cohort of 29 pediatric patients the relationship between VH6 and DRESS syndrome and demonstrated only 4 cases with VH6 positive, and in these they found a greater severity of the course of the disease and a greater frequency of pulmonary complications. It was also found to be associated with reactivation of other herpes viruses, including herpes virus 7, Epstein-Barr virus and cytomegalovirus 6 . On the other hand, relationships have been established between certain HLA haplotypes and a predisposition to develop DRESS syndrome with some drugs, and specific mutations have been described in genes that code for detoxifying enzymes 7 .…”

“…The exact mechanism of this reaction is unknown; type IV hypersensitivity has been proposed, but viral infections, particularly herpesvirus 6, have played a role in its pathogenesis 6 . Ahluwalia et al studied in a cohort of 29 pediatric patients the relationship between VH6 and DRESS syndrome and demonstrated only 4 cases with VH6 positive, and in these they found a greater severity of the course of the disease and a greater frequency of pulmonary complications.…”

“…The factors most frequently associated with DRESS are anticonvulsants (carbamazepine, lamotrigine, phenobarbital, phenytoin, valproic acid and zonisamide) in up to 35% of cases, alopurinol in 18%, sulphonamides (sulfasalazine) and dapsone in 12% and other antibiotics in 11% 5,6 . Initially, the condition was referred to as anticonvulsant hypersensitivity syndrome, due to its occurrence in relation to the use of these drugs; however, the diagnosis was extended to DRESS, since many other medications have been implicated 7,8 .…”

Herpesviruses dUTPases: A New Family of Pathogen-Associated Molecular Pattern (PAMP) Proteins with Implications for Human Disease

“…Reactivation of multiple herpesviruses has been reported in transplant recipients [157,158,159], patients with sepsis [160] and drug-induced hypersensitivity syndrome (DISS), also known as drug rash, or those with eosinophilia and systemic symptomology (DRESS) [161,162,163,164,165,166]. The temporal order in which these viruses are reactivated and whether they interact to contribute to symptomology remains unknown.…”

Toxidermias em idade pediátrica

“…Ainda não está determinado se esta é causa ou consequência da reação de hipersensibilidade, nem se está associada a maior gravidade da toxidermia. (36) Os principais fármacos implicados na idade pediátrica foram os antiepiléticos e os antibióticos; contrariamente aos adultos em que, para além destes, parece estar implicado o alopurinol, a dapsona e os tuberculostáticos. (37,38) …”