Severe Hypersensitivity Syndrome Due to Sulfasalazine Associated With Reactivation of Human Herpesvirus 6

Abstract

Background: A severe adverse reaction to sulfasalazine therapy has been associated with hypersensitivity syndrome, the clinical features of which are similar to infectious mononucleosis. No serologic evidence of viral infections has been reported with this syndrome; however, human herpesvirus 6 infection has not been specifically investigated, which could cause an infectious mononucleosislike syndrome.Observations: We report 2 cases of hypersensitivity syndrome induced by the use of sulfasalazine. The clinical features of the syndrome appeared 18 and 32 days after administration of sulfasalazine. Clinical signs included a maculopapular rash progressing to exfoliative eryth-roderma, fever, and lymphadenopathy. Leukocytosis, atypical lymphocytes, liver dysfunction, and renal disturbance were also observed. In 1 patient, human herpesvirus 6 variant B was isolated from peripheral blood mononuclear cells, and in both patients anti-human herpesvirus 6 IgG titers increased considerably.Conclusions: Two cases of hypersensitivity syndrome due to sulfasalazine use were associated with the reactivation of human herpesvirus 6, which may be a required cause of hypersensitivity syndrome.

Antigenicity and immunogenicity of sulphamethoxazole: demonstration of metabolism‐dependent haptenation and T‐cell proliferation in vivo

“…However, the decision as to whether antigen presentation stimulates an immune response, seems to be determined by the extent of co-stimulation (danger), and not hapten density. These data are consistent with recent case reports where hypersensitivity to sulphasalazine was associated with the reactivation of human herpesvirus 6 (Suzuki et al, 1998;Tohyama et al, 1998).…”

Human Herpesvirus 6 Reactivation in Trichloroethylene‐exposed Workers Suffering from Generalized Skin Disorders Accompanied by Hepatic Dysfunction

“…Of these reactions, HHV-6 reactivation in adults has been reported in druginduced HS [19][20][21][22][23][24] . However, in the present study, anti-HHV-6 titers increased also in some female patients suffering from diseases of erythema multiforme spectrum.…”

“…This is the first report showing that human herpesvirus 6 (HHV-6), the causative virus of exanthema subitum [16][17][18] , the reactivation of which has been reported in patients with drug-induced HS [19][20][21][22][23][24] , can also be reactivated in those having developed skin disorders after occupational solvent exposure.…”

Skin manifestations of drug allergy

“…Published case reports and small series have pointed to oral prednisolone to treat DRESS as probably the most accepted intervention in the treatment of severe drug reactions: 1-1.5 mg kg -1 has been recommended but we have seen efficacious responses to 0.5 mg kg -1 (unpublished) with rapid resolution of rash and fever. The association with human-herpes virus-6 (HHV-6) re-activation characteristically 2 weeks after rash onset, was recognized in the late 1990s [32,54,55] and has been proposed as an explanation for the characteristic flaring seen in this condition [56] although precise explanation of the role of the virus in the disease remains unclear. Careful monitoring for potential viral reactivation is therefore essential, but it should be noted that sporadic reports have identified reactivation of other herpes viruses as well (EBV, CMV, HHV-6, HHV-7, HSV, VZV) [31].…”