A case of drug-induced hypersensitivity syndrome induced by salazosulfapyridine combined with SIADH caused by interstitial pneumonia.

We present a case of a patient with drug-induced hypersensitivity syndrome (DIHS) caused by salazosulfapyridine combined with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) caused by interstitial pneumonia (IP). A 67-year-old man with a past history of rheumatism (RA) presented with right hemiparalysis and aphasia as the chief complaints. A diagnosis of left embolic cerebral infarction following trial therapy for RA based on computed tomography findings was made, and external decompression was performed. Salazosulfapyridine was newly started on day 7. Dabigatran was started on day 37. On day 41, the patient developed fever. On day 42, edema and erythema appeared on his face, and erythema and rash appeared on his trunk and extremities, with gradual transition to erythroderma. The drug eruption was initially attributed to the dabigatran. Various symptoms of organ dysfunction (enteritis, myocarditis, interstitial pneumonia, hepatic disorder, stomatitis, and others) then appeared and persisted; hence, a diagnosis of DIHS associated with human herpes virus 6 and cytomegalovirus infection induced by salazosulfapyridine was suggested, and the oral administration of salazosulfapyridine was discontinued on day 53. Hyponatremia was observed in association with exacerbation of IP. Due to low serum osmotic pressure and prompt improvement of the serum sodium level by fluid restriction, the SIADH was attributed to IP. In this case, steroid pulse therapy followed by gradual decrease therapy prevented worsening of the condition.

Human herpesvirus 6-associated uveitis with optic neuritis diagnosed by multiplex PCR.

PURPOSE: Human herpesvirus 6 (HHV-6), which is usually responsible for exanthem subitum in children, can be reactivated from its latent state. We report a case of unilateral optic disc edema and retinal vasculitis associated with HHV-6 infection. CASE: A healthy 63-year-old man noted a decrease in the vision of his left eye. On examination, his left eye had moderate mutton-fat keratic precipitates, vitreous opacities, significant optic disc edema surrounded by yellowish-white swelling in the inner retina, retinal arteritis, and cotton-wool-like exudates. He was started on corticosteroid therapy and aspirin. After 1 month, the disc edema was reduced, the cotton wool-like exudates had decreased, and his visual acuity had improved to 10/20 OS. Multiplex polymerase chain reaction (PCR) of an aqueous humor sample revealed the presence of genomic DNA of HHV-6 but not of the other HHVs. CONCLUSIONS: The HHVs are known to infect the ocular tissues, but the differential diagnostic signs of HHV-6 are still not well known. We recommend that multiplex PCR of the aqueous humor be performed to search for the genomic DNA of HHV-6 in suspected cases of herpesviral infection.

[Human herpesvirus 6]. / Az emberi 6-os herpeszvírus.

Human herpesvirus 6 discovered in 1986 is the most ancient human herpesvirus shown by molecular characteristics. Variant B infects children under the age of 2 years by droplets from asymptomatic virus shedding adults occasionally causing exanthema subitum. The virus infects CD4+ macrophages and lymphocytes; subsequently establishes lifelong latency and persistence with occasional shedding through the saliva. This variant frequently reactivates in bone marrow and organ transplant recipients with concomitant immunosuppression causing even fatal complications. It is a cofactor in the pathogenesis of multiple sclerosis, chronic fatigue syndrome, Hodgkin and non-Hodgkin lymphomas. The direct consequences of variant A infection and latency in CD4+ cells are not known. It transactivates HIV infection in vitro and in humans, and facilitates tumor progression induced by human papilloma viruses. Pathogenic effects of both variants are mediated by altered cytokine and chemokine profiles. Serological differentiation of the two variants is unreliable; however, it is possible by using PCR. Ganciclovir, foscarnet and cidofovir can be used for treatment and chemoprophylaxis of severe complications.

A case of drug-induced hypersensitivity syndrome-like symptoms following HHV-6 encephalopathy.

BACKGROUND: Drug-induced hypersensitivity syndrome (DIHS) is a rare but severe disorder due to a systemic hypersensitivity reaction. We report on a case with DIHS-like symptoms following human herpes virus 6 (HHV-6) infection complicated with encephalopathy. CASE SUMMARY: An 11-month-old girl suffered from a human herpes virus 6 (HHV-6) infection (exanthema subitum) complicated with encephalopathy. We treated the patient with continuous infusion of thiopental, assisted mechanical ventilation, methylprednisolone pulse therapy, and gamma-globulin infusion therapy starting on the fifth day of the illness and started phenobarbital administration on the eleventh day. The patient developed a fever, systemic erythematous exanthema, lymphadenopathy, and eosinophilia two weeks after the start of phenobarbital administration. Steroid therapy, methylprednisolone (4 mg/kg/day) followed by oral prednisolone (1 mg/kg/day), was started on the 28th day and was tapered off on the 72nd day after admission. Serum anti-HHV-6 IgG antibody elevation and the presence of HHV-6 DNA in the peripheral blood detected by polymerase chain reaction (PCR) analysis suggested reactivation of HHV-6 after the primary infection of HHV-6. Lymphocyte transformation test for phenobarbital was positive three weeks after the DIHS crisis. DISCUSSION: HHV-6 reactivation is a unique feature in DIHS. In general one develops DIHS accompanied by reactivation of HHV-6 which has been residing in the body since the initial infection (exanthema subitum) in early childhood. This is the first report of a patient with DIHS-like symptoms which developed immediately following the primary infection of HHV-6.

Central retinal vein occlusion caused by human herpesvirus 6.

We describe a 1-year-old girl with central retinal vein occlusion caused by human herpesvirus 6. She received systemic corticosteroid therapy. Although there was retinal recovery after the therapy, the visual acuity in her left eye still could not be measured.

[Newly discovered human herpesviruses: pathogenesis and treatments for central nervous system infection due to HHV-6].

Human herpesvirus-6 (HHV-6) is the causative agent of the common childhood infectious disease, exanthem subitum. Soon after the virus was isolated from humans it was found to be closely related to human cytomegalovirus, and thus was classified within the beta subgroup of human herpesviruses. HHV-6 possesses neuro-tropism in-vitro, and it has been suggested that primary infection can cause complications of the central nervous system (CNS), including febrile seizures and encephalitis/encephalopathy. In addition, this virus has recently been associated with limbic encephalitis, which occurred in mainly immunocompromised adult patients. It is proposed that direct invasion of the virus into the CNS may play an important role in causing these neurological complications. Although pathogenesis of HHV-6 encephalitis/encephalopathy remains unclear, it is thought that two different mechanisms such as direct invasion (primary encephalitis) and immune mediated impairment (secondary encephalitis) might play important role in causing CNS manifestations. It is possible that anti-viral drugs (ganciclovir and foscarnet) might be effective to patients with primary encephalitis due to HHV-6. Therefore, rapid diagnosis of active HHV-6 infection is crucial for patient management.

Salazosulfapyridine induced hypersensitivity syndrome associated with reactivation of humanherpes virus 6.

A 22-year-old woman with ulcerative colitis developed skin eruptions, liver dysfunction, and atypical lymphocytes in the peripheral blood two weeks after she started taking salazosulfapyridine (SASP). Skin eruptions and liver damage were severe. Drug-induced lymphocyte stimulation test (DLST) for SASP was positive. She was diagnosed as having SASP-induced hypersensitivity syndrome (HS). Corticosteroid therapy was needed to suppress these reactions. The transient elevation of HHV-6 IgG titer paralleled the symptoms, which indicated that these reactions were associated with the reactivation of HHV-6. We suggest that HHV-6 IgG titer is one of the modalities for the diagnosis and the prediction of the clinical course of HS.

Selection of the same mutation in the U69 protein kinase gene of human herpesvirus-6 after prolonged exposure to ganciclovir in vitro and in vivo.

After serial passage in the presence of increasing concentrations of ganciclovir (GCV) in vitro, a human herpesvirus-6 (HHV-6) mutant exhibiting a decreased sensitivity to the drug was isolated. Analysis of drug susceptibility showed that the IC(50) of this mutant was 24-, 52- and 3-fold higher than that of the wild-type (wt) IC(50) in the case of GCV, cidofovir and foscarnet, respectively. Genotypic analysis showed two single nucleotide changes as compared to the wild-type: an A-->G substitution of the U69 protein kinase (PK) gene resulted in an M(318)V amino acid substitution and the other change, located in the C-terminal part of the U38 gene, resulted in an A(961)V amino acid substitution within the DNA polymerase. The M(318)V change was located within the consensus sequence DISPMN of the putative catalytic domain VI of the PK. This change was homologous to the M(460)V and M(460)I changes that had been reported previously within the consensus sequence DITPMN of the human cytomegalovirus (HCMV) UL97 PK and associated with the resistance of HCMV to GCV. The M(318)V change was also detected by PCR in HHV-6-infected PBMCs from an AIDS patient who had been treated with GCV for a long period of time and exhibited a clinically GCV-resistant HCMV infection. These findings provide strong circumstantial evidence that the M(318)V change of the PK gene is associated with resistance to GCV and raise the question of cross resistance to this drug among different betaherpesviruses.

Human herpesvirus-6 and -7 infections in children: agents of roseola and other syndromes.

Human herpesvirus-6 (HHV-6) and -7 (HHV-7) infections typically are silent or manifested as mild febrile illnesses including classic roseola. In addition, case reports and epidemiologic data support the rare occurrence of HHV-6 encephalitis in immunocompromised as well as immunocompetent subjects. Although many other diseases have been putatively associated with HHV-6 or HHV-7, these associations are not well documented due to small numbers, use of tests incapable of distinguishing latent from replicating virus, potential virus cross-reactivity, or contradictory results. Further careful studies are needed to confirm these disease associations. Laboratory tests for diagnosing active HHV-6 and HHV-7 infections include virus culture, antigen detection, and polymerase chain reaction of cell-free biologic fluid. Although HHV-6 and HHV-7 are inhibited by several antiviral drugs in the laboratory, including ganciclovir and foscarnet, no clinical trials have assessed their benefit. Nevertheless, treatment may be considered for patients with serious HHV-6- or HHV-7-associated disease confirmed with accurate virologic tests.

[Macrophage activation syndrome in primary human herpes virus-6 infection: a rare condition after liver transplantation in infants]. / Syndrome d'activation macrophagique au cours de la primo-infection pat le 6e virus herpétique humain: une affection certainement méconnue au cours de la transplantation hépatique chez l'enfant.

Human herpes virus-6 primary infection generally occurs during the first three years of childhood and is generally asymptomatic. The virus has been identified as the causal agent of exanthemum subitum in children or mononucleosis-like disease in adults, and may also cause several disorders in immunocompromised patients. We report a clinical case of acute rejection observed 29 days after orthotopic liver transplantation in a 22-month-old child associated with acute hepatitis and a hemophagocytic syndrome on day 38. Human herpes virus-6 primary infection was identified based on several virological tests: seroconversion, detection of viral DNA in bone marrow and peripheral blood after polymerase chain reaction, and detection of viral replication in peripheral blood. Tests for Epstein-Barr virus, cytomegalovirus or Parvovirus B19 infections were negative. After treatment by ganciclovir (Cymévan(R)), clinical status improved.

A practitioner's guide to human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7).

Human herpesvirus-6 (HHV-6) and HHV-7 are newly recognized ubiquitous human viruses first discovered in patients with AIDS or lymphoproliferative disorders. Much more information is available about the clinical characteristics of infection with HHV-6 than HHV-7. Primary infection with HHV-6 occurs in early childhood and is most commonly manifested as an undifferentiated highly febrile illness, with seizures noted to be the most common complication. A subset of children develop the classic manifestations of roseola infantum or exanthem subitum. Other neurologic diseases in adults such as encephalitis and multiple sclerosis also have been linked to HHV-6; however, the role of HHV-6 in these clinical entities has not been fully elucidated. Although HHV-6 and HIV are both tropic for CD4+ lymphocytes and interact in vitro, there is no evidence at present that HHV-6 plays a role in HIV disease. HHV-7 is similar to HHV-6 in genetic organization and structure. Little is known of the clinical characteristics of infection with HHV-7 or its ability to cause disease in children or reactivation in adults.

Acute encephalopathy and status epilepticus associated with human herpes virus 6 infection.

A previously healthy 22-month-old boy presented in status epilepticus with high fever. He was comatose, with upper respiratory-tract infection. The seizures responded to anticonvulsant therapy. The boy's temperature returned to normal within 24 hours and he recovered slowly from his encephalopathy. On the third hospital day, he exhibited the characteristic rash of reseola infantum. Acute infection with human herpes virus 6 (HHV-6) was established serologically by enzyme immunoassay. HHV-6 DNA was not detected by polymerase chain reaction in CSF or serum at the onset of illness, but was found three months later in the child's saliva. The pathogenesis of the patient's encephalopathy is discussed. It is concluded that HHV-6 infection should be considered in infants and young children with febrile status epilepticus.