Fulminant hepatic and multiple organ failure following acute viral tonsillitis: a case report
© Bechtel-Grosch et al. 2016
Received: 16 March 2015
Accepted: 30 November 2015
Published: 20 January 2016
Pyogenic tonsillitis may often be observed in the general Western population. In severe cases, it may require antibiotic treatment or even hospitalization and often a prompt clinical response will be noted. Here we present an unusual case of progressive multiple organ failure including fulminant liver failure following acute tonsillitis initially mistaken for “classic” pyogenic (that is bacterial) tonsillitis.
A 68-year-old previously healthy white man was referred with suspicion of pyogenic angina. After tonsillectomy, he developed acute liver failure and consecutive multiple organ failure including acute hemodynamic, pulmonary and dialysis-dependent renal failure. Immunohistopathological analysis of his tonsils and liver as well as serum polymerase chain reaction analyses revealed herpes simplex virus-2 to be the causative pathogen. Treatment included high-dose acyclovir and multiorgan supportive intensive care therapy. His final outcome was favorable.
Fulminant herpes simplex virus-2-induced multiple organ failure is rarely observed in the Western hemisphere and should be considered a potential diagnosis in patients with tonsillitis and multiple organ failure including acute liver failure. From a clinical perspective, it seems important to note that fulminant herpes simplex virus-2 infection may masquerade as “routine” bacterial severe sepsis/septic shock. This persevering condition should be diagnosed early and treated goal-oriented in order to gain control of this life-threatening condition.
KeywordsCritical illness Hepatitis MOF Sepsis Septic shock Viral infection
In the general Western population, pyogenic (that is bacterial) tonsillitis may often be observed and it is known to account for a large number of pre-clinical consultations. In severe cases, it may require antibiotic treatment or even hospitalization and a prompt clinical response will often be noted [1–3]. Here we present an unusual case of progressive multiple organ failure including fulminant liver failure following acute non-bacterial tonsillitis. We will furthermore report and discuss pitfalls in the clinical management of such life-threatening non-bacterial tonsillitis.
A 68-year-old white man with an insignificant past medical history (including sexual history) was referred to our tertiary care academic center with symptoms of acute tonsillitis, clinically not responding to antibiotic treatment with oral amoxicillin-clavulanic acid. Following a 2-day course of moderate fever (38 °C) and sore throat with highly elevated infection parameters of C-reactive protein 280 mg/l, white blood cell count (WBC) 4.8 G/L, and platelets 106 G/L, he was hospitalized for intravenous antibiotic treatement. An initial physical examination at admission was unremarkable. Due to a progressive elevation in his inflammatory markers along with clinical deterioration and progressive tonsillar inflammation, a left-sided tonsillectomy was performed 48 hours after his hospital admission. During his postoperative course, fulminant acute liver failure (ALF) was observed and he was transferred to our intensive care unit (ICU) for further investigations and supportive intensive care treatment.
Paraclinical presentation at intensive care unit admission. Reference ranges are indicated
Along with the development of fulminant ALF, the major clinical concern was progressive multiple organ failure. Despite initial “rescue”-steroid dosing, high doses of norepinephrine (peak dose of 0.3 μg/kg/minute) were required and progressive capillary leak was observed. Following a consecutive 48-hour trial of noninvasive ventilation, the patient required invasive mechanical ventilation as a consequence of progressive muscular exhaustion. He subsequently developed anuric acute renal failure and renal replacement therapy with intermittent hemodialysis was initiated. Due to deranged coagulation in which his platelet count was 56 G/l, prothrombin time was 38 %, and international normalized ratio (INR) was 1.82, with recurrent bleeding at the tonsillectomy site and progressive disseminated intravascular coagulation, an operative revision with ligation of tonsillar arteries was deemed necessary. High urgency liver transplantation was discussed as a therapeutic option but was refrained from due to persisting uncontrolled infection/multiple organ failure with an expected badverse outcome.
After approximately 1 month of intensive care treatment, an overall stabilization of his condition was noted. Norepinephrine was tapered and weaning from the ventilator was advanced. A diagnosis of ICU-acquired weakness was established and rehabilitative measures were initiated.
In the light of the available literature, HSV-2-induced multiple organ failure is a rare condition. HSV infection in adults is commonly associated with cutaneous facial (HSV-1) or urogenital infections (HSV-2) . Of interest, approximately 60 % of the Western population is HSV-1 colonized, whereas HSV-2 colonization occurs in approximately 12 % of cases . Oral HSV infection in adults may present as severe pharyngitis accounting for approximately 6 % of cases in young adults. However, HSV-2 seems even scarcer and accounts for approximately <0.5 % of cases . Systemic HSV infection with visceral viral dissemination may often present as ALF due to fulminant hepatic necrosis but represents less than 1 % of cases of ALF . Due to a lack of specific therapeutic options, HSV hepatitis is associated with mortality rates of up to 90 % . High-risk populations for a fatal course are immunosuppressed patients and pregnant patients (third trimester). Of interest, immunocompetency was deemed in approximately 24 % of severely affected patients . In our patient, testing for chronic viral disease including HIV testing, standard examinations including WBCs (following recovery from lymphopenia), immunoglobulins, distribution of immune cell subpopulations, and assessment of major histocompatibility complex (MHC) class II expression human leukocyte antigen- DR (HLA-DR) [8, 9] did not reveal a major immunocompromising condition. Nevertheless, in a case such as in our patient, a potential underlying immune deficiency should be ruled out.
Because of an unspecific clinical presentation, a diagnosis of HSV-induced hepatitis may frequently be missed and data demonstrate that the majority (that is 58 %) of patients are diagnosed post-mortem . Improved survival rates are reported following early initiation of antiviral treatment. Retrospective analyses of patients with HSV hepatitis demonstrate significantly lower mortality rates following early acyclovir treatment when compared to controls (51 % versus 88 %). Treatment delay is associated with higher need for liver transplantation and higher mortality rates . Thus, early initiation of antiviral therapy may be regarded mandatory to prevent fatal outcomes. Orthotopic liver transplantation (OLT) in the context of disseminated HSV infection should be evaluated carefully, as the risk for HSV recurrence seems increased and lifelong treatment with acyclovir may be needed following OLT . Although there is a lack of conclusive data, intensivists should consider treating this life-threatening condition with antiviral medication over a sustained period of time until profound clinical improvement is observed. However, optimal dosage, especially in the presence of acute renal failure, and optimal timing of treatment for HSV-2-induced multiple organ failure remains elusive. In addition, it should be kept in mind that serum PCR levels (that is, respective assessment of viral load) may reveal positive results for a sustained period in time. This may be due to amplification of non-live viral particles and may be misleading in this clinical scenario.
In conclusion, this case demonstrates that HSV-2-induced multiple organ failure may develop in immunocompetent hosts following HSV-2 infectious tonsillitis. The clinical picture may masquerade as “routine” bacterial septic shock induced by bacterial tonsillitis and may lead to fatal clinical decisions if not recognized early and treated accordingly.
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
The authors thank the patient for kindly providing informed consent to the publication of the data. Furthermore, the authors thank all ICU nurses and laboratory personnel for their dedicated care and efforts. The authors thank PD Dr P. Sendi, Dept. of Infectious Diseases, Inselspital, Bern, for expert advice/consultations. The authors also thank PD Dr med. S. Zimmerli, Dept. of Infectious Diseases, Inselspital, Bern, for expert advice/consultations and provision of photographs.
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- [Sore throat and chronic tonsillitis (an analytical review)]. Vestnik otorinolaringologii 2012(1):68–76.Google Scholar
- Bathala S, Eccles R. A review on the mechanism of sore throat in tonsillitis. J Laryngol Otol. 2013;127(3):227–32.View ArticlePubMedGoogle Scholar
- Bird JH, Biggs TC, King EV. Controversies in the management of acute tonsillitis: an evidence-based review. Clin Otolaryngol. 2014;39(6):368–74.View ArticlePubMedGoogle Scholar
- Rosenthal SL, Stanberry LR, Biro FM, Slaoui M, Francotte M, Koutsoukos M, et al. Seroprevalence of herpes simplex virus types 1 and 2 and cytomegalovirus in adolescents. Clin Infect Dis. 1997;24(2):135–9.View ArticlePubMedGoogle Scholar
- McMillan JA, Weiner LB, Higgins AM, Lamparella VJ. Pharyngitis associated with herpes simplex virus in college students. Pediatr Infect Dis J. 1993;12(4):280–4.View ArticlePubMedGoogle Scholar
- Schiodt FV, Davern TJ, Shakil AO, McGuire B, Samuel G, Lee WM. Viral hepatitis-related acute liver failure. Am J Gastroenterol. 2003;98(2):448–53.View ArticlePubMedGoogle Scholar
- Norvell JP, Blei AT, Jovanovic BD, Levitsky J. Herpes simplex virus hepatitis: an analysis of the published literature and institutional cases. Liver Transpl. 2007;13(10):1428–34.View ArticlePubMedGoogle Scholar
- Schefold JC. Measurement of monocytic HLA-DR (mHLA-DR) expression in patients with severe sepsis and septic shock: assessment of immune organ failure. Intensive Care Med. 2010;36(11):1810–2.View ArticlePubMedGoogle Scholar
- Schefold JC, Hasper D, Reinke P, Monneret G, Volk HD. Consider delayed immunosuppression into the concept of sepsis. Crit Care Med. 2008;36(11):3118.View ArticlePubMedGoogle Scholar
- Riediger C, Sauer P, Matevossian E, Muller MW, Buchler P, Friess H. Herpes simplex virus sepsis and acute liver failure. Clin Transplant. 2009;23 Suppl 21:37–41.View ArticlePubMedGoogle Scholar