Case Report Open Access
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Feb 16, 2016; 4(2): 60-62
Published online Feb 16, 2016. doi: 10.12998/wjcc.v4.i2.60
Herpes simplex induced necrotizing tonsillitis in an immunocompromised patient with ulcerative colitis
Laura Jansen, Department of Infectious diseases, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands
Xander G Vos, Department of Gastroenterology and Hepatology, Westfries Gasthuis, 1624 NP Hoorn, The Netherlands
Mark Löwenberg, Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands
Author contributions: Jansen L and Löwenberg M designed the report; Jansen L collected the patient’s clinical information; Jansen L and Vos XG analyzed the patient; Jansen L, Vos XG and Löwenberg M wrote the paper.
Institutional review board statement: This case report was reviewed and approved by the Academic Medical Center in Amsterdam Institutional Review Board.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Laura Jansen, BSc, Department of Infectious diseases, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. laura.jansen@amc.uva.nl
Telephone: +31-20-5667621 Fax: +31-20-6917033
Received: June 15, 2015
Peer-review started: June 19, 2015
First decision: October 14, 2015
Revised: October 30, 2015
Accepted: December 3, 2015
Article in press: December 4, 2015
Published online: February 16, 2016

Abstract

We here present the case of a 22-year-old female of Suriname ethnicity with ulcerative colitis who received treatment with mercaptopurine and infliximab. She presented herself with a severe necrotizing tonsillitis due to herpes simplex virus type-1 (HSV-1). Combination therapy consisting of immunomodulators and anti-tumor necrosis factor (TNF) agents is increasingly being used. Anti-TNF therapy is associated with an increased risk of developing serious infections, and especially patients receiving combination treatment with thiopurines are at an increased risk. We here show that HSV infections can cause a severe tonsillitis in immunocompromised patients. Early recognition is essential when there is no improvement with initial antibiotic therapy within the first 24 to 72 h. HSV infections should be in the differential diagnosis of immunocompromised patients presenting with a necrotizing tonsillitis and can be confirmed by polymerase chain reaction. Early treatment with antiviral agents should be considered especially if antibiotic treatment fails in such patients.

Key Words: Herpes simplex virus, Tonsillitis, Ulcerative colitis, Immunosuppression, Anti-tumor necrosis factor agents

Core tip: Combination therapy that consists of immunomodulators and anti-tumor necrosis factor (TNF) agents is increasingly being used for patients with chronic inflammatory diseases, such as ulcerative colitis. Anti-TNF therapy is associated with an increased risk of developing serious infections, and especially patients receiving combination treatment with thiopurines are at an increased risk. This is the first report of an acute severe tonsillitis caused by herpes simplex virus in an immunocompromised patient due combination treatment with a thiopurine and an anti-TNF agent.



INTRODUCTION

Viral throat infections are a common problem and are generally self-limiting. Viral causes of a tonsillitis include: rhinovirus, respiratoir syncytial virus (RSV), Epstein-Barr virus (EBV), parainfluenza, influenza, Coxsackievirus, adenovirus, etc[1]. There are two types of the herpes simplex virus (HSV): HSV-1 and HSV-2. HSV-1 can cause primary or recurrent infections, with the most common manifestation as vesicular lesions of the oral mucosa. HSV-2 is known as genital herpes simplex. However, both HSV types can cause herpes labialis as well as genital herpes[2], which can extend into other organs, such as the hard palate, tonsils, liver, lungs and eyes. A primary HSV infection can result in an acute pharyngotonsillitis. The diagnosis of an HSV infection can usually be made based on the clinical picture. The diagnosis can be confirmed by polymerase chain reaction (PCR), which is considered as the gold standard, and with serology and/or histology.

CASE REPORT

A 22-year-old female of Suriname ethnicity with known beta thalassemia and ulcerative colitis presented herself to the family physician with a sore throat. She used infliximab, mercaptopurine, allopurinol and mesalamine enema’s. Treatment with feneticillin was started (500 mg 3 times daily) under the suspicion of a bacterial tonsillitis. After 4 d, the patient presented herself to the emergency department of our hospital because of severe dysphagia for solid and liquid foods and intermittent fever up to 39.2 Celsius. An acutely ill patient was seen with a heart rate of 135 per minute and a blood pressure of 100/60 mmHg. Her neck was diffusely swollen and painful at palpation. Cervical lymphadenopathy was seen. Oral examination revealed severely enlarged tonsils that were covered with a grey-whitish exudate. No other lesions were observed and there was no trismus. Because of a symmetric pharynx arch there was no suspicion of a peritonsillar abscess at physical examination. Laboratory investigation showed an increased C-reactive protein of 137 mg/L, Hb 4.5 mmol/L, leucocyte count of 4.7 × 109/L (leucocyte differentiation: Neutrophils 55%, eosinophils 1%, basophils 1%, lymphocytes 38%, monocytes 4%) and a thrombocyte count of 232 × 109/L. Cultures of throat and nasopharyngeal swabs as well as blood cultures were negative. Viral screening using PCR and plasma viral load measurements were negative for cytomegalovirus and EBV. A multiplex PCR analysis for respiratory viruses, including rhinovirus, adenovirus, RSV, parainfluenza and influenza was also negative. The patient was admitted and amoxicillin was started instead of feneticillin because of the immunocompromised status and the fact that she did not respond to feneticillin treatment. A computed tomography (CT)-scan showed bilateral heterogeneous contrast enhancement of both enlarged pharyngeal tonsils and arytenoids. Imaging did not reveal a peritonsillar or retropharyngeal abscess. At laryngoscopy a swollen nasopharynx was seen that was covered with grey-whitish exudate, and ulcerations of both arytenoids and in the aryepiglottic fold (see record). The patient deteriorated and became respiratory insufficient. Empirical treatment with valacyclovir was started (1000 mg 3 times daily) under the suspicion of an HSV infection. Treatment with mercaptopurine and allopurinol was stopped. The patient responded to the antiviral treatment within one day. The diagnosis of HSV type I was confirmed by PCR of the nose and throat swabs and by serology. The patient was seen at the outpatient clinic 10 d after discharge and was asymptomatic.

DISCUSSION

HSV can cause life-threatening infections in immunocompromised patients[3-5]. We here describe a patient with ulcerative colitis who received treatment with infliximab and mercaptopurine. Therapeutic efficacy of combination therapy with anti-tumor necrosis factor (TNF) agents (such as infliximab) and immunomodulators (including mercaptopurine) should be balanced against the potential risks, such as infections[6]. The use of anti-TNF therapy has been associated with serious infections and especially patients receiving combination treatment with thiopurines seem to be at an increased risk[4,7-9]. Our patient developed a severe necrotizing tonsillitis due to an infection with HSV, which was confirmed by PCR and serology. She responded promptly to antiviral treatment which was empirically started after failure of antibiotic therapy. Mercaptopurine treatment was stopped and infliximab was continued. Histological findings were reported by Wat et al[10] who described a patient with a herpes simplex infection that also caused an acute necrotizing tonsillitis. In contrast to our patient, this particular patient had a blanc medical history and was not immunocompromised. We here demonstrate that histology is not always required in order to accurately diagnose herpes simplex induced necrotizing tonsillitis.

To the best of our knowledge, this is the first report of an acute pharyngotonsillitis caused by HSV in an immunocompromised patient due combination treatment with a thiopurine and an anti-TNF agent. Hence, HSV infections should be in the differential diagnosis when immunocompromised patients present with a severe necrotizing tonsillitis, and early treatment with antiviral agents should be considered especially if antibiotic treatment fails.

COMMENTS
Case characteristics

A 22-year-old female with known ulcerative colitis presented herself to the family physician with a sore throat.

Clinical diagnosis

Herpes simplex induced necrotizing tonsillitis in an immunocompromised patient.

Laboratory diagnosis

C-reactive protein of 137 mg/L, Hb 4.5 mmol/L, leucocyte count of 4.7 × 109/L (leucocyte differentiation: Neutrophils 55%, eosinophils 1%, basophils 1%, lymphocytes 38%, monocytes 4%).

Imaging diagnosis

A computed tomography-scan showed bilateral heterogeneous contrast enhancement of both enlarged pharyngeal tonsils and arytenoids. At laryngoscopy a swollen nasopharynx was seen that was covered with grey-whitish exudate, and ulcerations of both arytenoids and in the aryepiglottic fold.

Treatment

Valacyclovir (1000 mg 3 times daily).

Experiences and lessons

Herpes simplex virus infections should be in the differential diagnosis when immunocompromised patients present with a severe necrotizing tonsillitis, and early treatment with antiviral agents should be considered especially if antibiotic treatment fails.

Peer-review

An highly interesting case report.

Footnotes

Video Record: Laryngoscopy from a 22-year-old female with ulcerative colitis who presented herself with a severe necrotizing tonsillitis. 00:00-00:07 s: A swollen nasopharynx covered with a grey-whitish exudate; 00:25-00:32 s: Ulcerations of both arytenoids and in the aryepiglottic fold.

P- Reviewer: Bock CT S- Editor: Qi Y L- Editor: A E- Editor: Liu SQ

References
1.  Putto A. Febrile exudative tonsillitis: viral or streptococcal? Pediatrics. 1987;80:6-12.  [PubMed]  [DOI]  [Cited in This Article: ]
2.  Taylor TJ, Brockman MA, McNamee EE, Knipe DM. Herpes simplex virus. Front Biosci. 2002;7:d752-d764.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 84]  [Cited by in F6Publishing: 99]  [Article Influence: 4.5]  [Reference Citation Analysis (0)]
3.  Arduino PG, Porter SR. Herpes Simplex Virus Type 1 infection: overview on relevant clinico-pathological features. J Oral Pathol Med. 2008;37:107-121.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 205]  [Cited by in F6Publishing: 188]  [Article Influence: 11.8]  [Reference Citation Analysis (0)]
4.  Brooke AE, Eveson JW, Luker J, Oakhill A. Oral presentation of a novel variant of herpes simplex infection in a group of bone marrow transplant patients: a report of five cases. Br J Dermatol. 1999;141:381-383.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 10]  [Cited by in F6Publishing: 10]  [Article Influence: 0.4]  [Reference Citation Analysis (0)]
5.  Gonen C, Uner A, Cetinkaya Y, Hascelik G, Haznedaroglu I. Tonsillar abscess formation due to herpes simplex type-1 in a severely immunocompromised stem cell transplant patient with chronic myeloid leukemia. Transpl Infect Dis. 2006;8:166-170.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 7]  [Cited by in F6Publishing: 7]  [Article Influence: 0.4]  [Reference Citation Analysis (0)]
6.  Hoentjen F, van Bodegraven AA. Safety of anti-tumor necrosis factor therapy in inflammatory bowel disease. World J Gastroenterol. 2009;15:2067-2073.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 76]  [Cited by in F6Publishing: 72]  [Article Influence: 4.8]  [Reference Citation Analysis (0)]
7.  Lichtenstein GR, Feagan BG, Cohen RD, Salzberg BA, Diamond RH, Price S, Langholff W, Londhe A, Sandborn WJ. Serious infection and mortality in patients with Crohn’s disease: more than 5 years of follow-up in the TREAT™ registry. Am J Gastroenterol. 2012;107:1409-1422.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 536]  [Cited by in F6Publishing: 503]  [Article Influence: 41.9]  [Reference Citation Analysis (0)]
8.  Toruner M, Loftus EV, Harmsen WS, Zinsmeister AR, Orenstein R, Sandborn WJ, Colombel JF, Egan LJ. Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology. 2008;134:929-936.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 719]  [Cited by in F6Publishing: 751]  [Article Influence: 46.9]  [Reference Citation Analysis (0)]
9.  Rahier JF, Ben-Horin S, Chowers Y, Conlon C, De Munter P, D’Haens G, Domènech E, Eliakim R, Eser A, Frater J. European evidence-based Consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis. 2009;3:47-91.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 374]  [Cited by in F6Publishing: 397]  [Article Influence: 26.5]  [Reference Citation Analysis (0)]
10.  Wat PJ, Strickler JG, Myers JL, Nordstrom MR. Herpes simplex infection causing acute necrotizing tonsillitis. Mayo Clin Proc. 1994;69:269-271.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 28]  [Cited by in F6Publishing: 27]  [Article Influence: 0.9]  [Reference Citation Analysis (0)]