Diagnostic Approach to Fulminant Hepatitis in the Critical Care Unit
Cheston B. Cunha, Burke A. Cunha in Infectious Diseases and Antimicrobial Stewardship in Critical Care Medicine, 2020
Human herpesvirus-6 (HHV-6) consists of a set of two closely related herpesviruses known as HHV-6A and HHV-6B that almost invariably have humans as their primary host. The seroprevalence of HHV-6 among the adult population is as high as 82%–100%, even though primary infection is rare [23]. The virus is a common cause of liver dysfunction and ALF, especially in the immunosuppressed transplant patient. The HHV-6 infection often causes exanthema subitum in infants and a mononucleosis-like syndrome in adults. Pretransplant HHV-6 infection and concurrent CMV infection are identified risk factors associated with liver dysfunction following hepatic transplantation [24]. The diagnosis of HHV-6 infection can be made based on a positive HHV-6 serum antigen test (monoclonal antibodies against specific HHV-6A and -B antigens as well as a polyclonal antibody against HHV-6 U90 protein), which detects the presence of the virus in peripheral blood mononuclear cells, the presence of HHV-6 antigens on liver biopsy, or the demonstration of HHV-6 serology (IgG or IgM anti-HHV-6) by means of indirect EIA. A greater than fourfold rise in IgG titers is considered diagnostic, as most people are seropositive for HHV-6 IgG. While anti-HHV-6 develops within 4–7 days of infection, it may be unreliable, as IgM can be falsely positive in healthy adults [23]. Foscarnet, ganciclovir, and cidofovir may be used to treat acute disease [25].
Viruses As Potential Direct or Indirect Etiological Agents for CFS
Roberto Patarca-Montero in Treatment of Chronic Fatigue Syndrome in the Antiviral Revolution Era, 2014
Herpesviruses (Epstein-Barr virus, cytomegalovirus, human herpes virus types 6 and 7, herpes simplex virus types 1 and 2) have been associated with CFS. For instance, reactivation/replication of a latent herpesvirus (such as Epstein-Barr virus) could modulate the immune system to induce CFS.85–87 In this respect, serologically proven acute infectious illness secondary to Epstein-Barr virus (EBV) is associated with a range of nonspecific somatic and psychological symptoms, particularly fatigue and malaise rather than anxiety and depression.88 Although improvement in several symptoms occurs rapidly, fatigue commonly remains a prominent complaint at four weeks, and resolution of fatigue is associated with improvement in cell-mediated immunity. A prospective cohort study of 250 primary care patients also revealed a higher incidence and longer duration of an acute fatigue syndrome and a higher prevalence of CFS after glandular fever as compared to after an ordinary upper respiratory tract infection.89 In another study, anti-EBV titers were higher among CFS patients and were associated with being more symptomatic.90 However, testing of 548 chronically fatigued, including patients with CFS, for antibodies to thirteen viruses (herpes simplex virus 1 and 2, rubella, adenovirus, human herpesvirus 6, Epstein-Barr virus, cytomegalovirus, and Coxsackie B virus, types 1 through 6) in patients found no consistent differences in any of the seroprevalences compared with controls.91
Signal Amplification-Based Techniques
Attila Lorincz in Nucleic Acid Testing for Human Disease, 2016
Neisters et al.18 found a specificity of 98.4% based on testing 15 specimens for a total of 63 results with the ultra-sensitive Hybrid Capture II HBV DNA test; similar results (99.2%; n = 134) were reported by Pawlotsky et al.53 Caliendo and co-workers54 reported a specificity of 93.2% for the Hybrid Capture CMV DNA test using uninfected buffy coat cells. Imbert-Marcille et al.55 tested this assay with 50 specimens from healthy individuals along with a panel of viruses including herpes simplex-2, Epstein–Barr, varicella zoster, and human herpesvirus-6 at concentrations of 108 to 1010 particles/ml; they found a specificity of 100%. Values for specificity derived from very limited sample sizes and from preparations not encountered in clinical settings (e.g., cell-culture derived samples) should be interpreted with caution.
Shifts in the number of pityriasis rosea diagnoses during the COVID-19 pandemic: Insights on a viral etiology?
Published in Baylor University Medical Center Proceedings, 2023
Pityriasis rosea (PR) is an acute papulosquamous exanthem that classically begins with an enlarging, salmon-colored, scaly papule or plaque on the trunk. This “herald patch” is followed by similar smaller lesions, whose long axes are oriented along skin cleavage lines, resulting in a Christmas tree pattern.1 A viral etiology has been proposed, with much focus on human herpesvirus-6 (HHV-6), a ubiquitous beta-herpesvirus.1,2 Despite being a self-limited eruption, PR has been associated with pregnancy complications, especially when onset occurs in early gestation.2 Given the associations of PR with HHV-6B viral load and adverse events in pregnancy,2 clarifying the viral etiology of PR to assess the potential role of antivirals in vulnerable populations (i.e., pregnant patients) may be of clinical benefit.
Clozapine-related drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: a systematic review
Published in Expert Review of Clinical Pharmacology, 2020
Renato de Filippis, Pau Soldevila-Matías, Pasquale De Fazio, Daniel Guinart, Inmaculada Fuentes-Durá, Jose M. Rubio, John M. Kane, Georgios Schoretsanitis
The clinical features of DRESS invariably include cutaneous eruption, fever, hematologic abnormalities with eosinophilia and/or atypical lymphocytosis, involvement of at least one internal organ and/or generalized lymphadenopathy [10,11]. The multi-visceral involvement differentiates DRESS from other cutaneous drug reactions [12,13]. The debate regarding the diagnosis of DRESS syndrome has evolved in recent years and various diagnostic criteria have been suggested [14]. There are two major assessment tools for DRESS: the first was developed by a multinational registry study group investigating severe cutaneous adverse reactions (RegiSCAR), the RegiSCAR criteria [15]. The second diagnostic tool was developed by a Japanese group and contains similar criteria with RegiSCAR, but also considers the role of the reactivation of human herpesvirus 6 (HHV-6) [16].
Pharmacovigilance approaches to study rare and very rare side-effects: the example of clozapine-related DiHS/DRESS syndrome
Published in Expert Opinion on Drug Safety, 2022
Renato de Filippis, Pasquale De Fazio, John M. Kane, Georgios Schoretsanitis
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) refers to a rare but potentially life-threatening drug hypersensitivity reaction with incidence estimates for antiepileptic-induced DRESS ranging between 0.001% and 0.0001% in general population and 0.0004% in hospital settings [4–6]. DRESS is classified within severe cutaneous adverse reactions (SCARs), which include a broad group of delayed hypersensitivity reactions, such as Stevens–Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, and drug-induced hypersensitivity syndrome (DiHS) [7]. Specifically, as DiHS and DRESS are clinically very similar, with overlapping pathogenetic mechanisms, they are frequently referred to as DiHS/DRESS [7]. For example, the role of Human Herpesvirus 6 (HHV-6) reactivation has been included among the proposed diagnostic criteria for DiHS, but not for DRESS [7]. Among the mechanisms underlying DiHS/DRESS, the role of CD4 and CD8 and cytomegalovirus (CMV), Epstein–Barr virus (EBV), or HHV-6/-7 infections with autoimmune sequelae has been considered. Ultimately, complex interactions between small-molecule drugs, human leukocyte antigens (HLAs) genes, and T-cell receptors (TCRs) take place for most SCARs [7,8]. More specifically, HLA-genotyping could essentially contribute to the assessment of the SCARs’ risk [9,10]. Pharmacogenomic data for several clozapine-related ADRs are available [11], but not for DRESS, for which future pharmacovigilance studies should provide evidence.
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