Skip to main content
Top
Published in: BMC Pulmonary Medicine 1/2009

Open Access 01-12-2009 | Research article

Occurrence of HSV-1-induced pneumonitis in patients under standard immunosuppressive therapy for rheumatic, vasculitic, and connective tissue disease

Authors: Matthias N Witt, Gerald S Braun, Stephan Ihrler, Holger Schmid

Published in: BMC Pulmonary Medicine | Issue 1/2009

Login to get access

Abstract

Background

Herpes simplex virus type-1 (HSV-1) has been described to cause respiratory tract infections in critically ill patients or in individuals that are immunocompromised. It is a continuing matter of debate under which circumstances HSV-1 is a relevant pathogen for pneumonitis. While its role during critical illness has been investigated by prospective interventional studies, comparatively little systematic data is available on the role of HSV-1 for pneumonitis in outpatients with autoimmune disease under a maintenance regimen of immunosuppression.

Methods

We retrospectively reviewed the charts of ~1400 patients with rheumatoid arthritis, vasculitis, and systemic lupus erythematosus (SLE) that were followed at the outpatient clinic of a German University hospital during the years 2000–2007. Episodes of admission to a ward resulting in the diagnosis of pneumonia/pneumonitis were identified, and the type of pneumonia and clinical features retrospectively studied.

Results

63 patients with rheumatoid arthritis, vasculitis, or SLE were admitted to a ward and diagnosed to have pneumonia/pneumonitis. Using bronchoscopy a total of 6 cases of pulmonary infection associated with HSV-1 in the lower respiratory tract were identified. Among those, 2 cases suggested a causative role of HSV-1 as the sole agent causing pneumonitis that proved clinically responsive to antiviral treatment. In the remaining 4 cases HSV-1 appeared as a bystander of bacterial infection. Maintenance therapy with leflunomide, which inhibits HSV-1 assembly in vitro, was associated with a milder course of pneumonitis in one patient. Detection of HSV-1 was associated with stronger immunosuppressive regimens and vasculitic disease.

Conclusion

The present study analyzed the frequency and hallmarks of cases of HSV-1 associated pneumonitis that occurred in a comparatively large cohort of patients with rheumatologic autoimmune diseases. In an area of controversy, this study provides further evidence that HSV-1 causes isolated pneumonitis in the immunocompromised. The study may provide an estimate on the frequency of relevant HSV-1 infection and bacterial agents in outpatients with autoimmune disease.
Appendix
Available only for authorised users
Literature
1.
go back to reference Whitley RJ, Roizman B: Herpes simplex virus infections. Lancet. 2001, 357 (9267): 1513-1518. 10.1016/S0140-6736(00)04638-9.CrossRefPubMed Whitley RJ, Roizman B: Herpes simplex virus infections. Lancet. 2001, 357 (9267): 1513-1518. 10.1016/S0140-6736(00)04638-9.CrossRefPubMed
2.
go back to reference Tunback P, Bergstrom T, Claesson BA, Carlsson RM, Lowhagen GB: Early acquisition of herpes simplex virus type 1 antibodies in children – a longitudinal serological study. J Clin Virol. 2007, 40 (1): 26-30. 10.1016/j.jcv.2007.06.002.CrossRefPubMed Tunback P, Bergstrom T, Claesson BA, Carlsson RM, Lowhagen GB: Early acquisition of herpes simplex virus type 1 antibodies in children – a longitudinal serological study. J Clin Virol. 2007, 40 (1): 26-30. 10.1016/j.jcv.2007.06.002.CrossRefPubMed
3.
go back to reference Schuller D, Spessert C, Fraser VJ, Goodenberger DM: Herpes simplex virus from respiratory tract secretions: epidemiology, clinical characteristics, and outcome in immunocompromised and nonimmunocompromised hosts. Am J Med. 1993, 94 (1): 29-33. 10.1016/0002-9343(93)90116-7.CrossRefPubMed Schuller D, Spessert C, Fraser VJ, Goodenberger DM: Herpes simplex virus from respiratory tract secretions: epidemiology, clinical characteristics, and outcome in immunocompromised and nonimmunocompromised hosts. Am J Med. 1993, 94 (1): 29-33. 10.1016/0002-9343(93)90116-7.CrossRefPubMed
4.
go back to reference Ramsey PG, Fife KH, Hackman RC, Meyers JD, Corey L: Herpes simplex virus pneumonia: clinical, virologic, and pathologic features in 20 patients. Ann Intern Med. 1982, 97 (6): 813-820.CrossRefPubMed Ramsey PG, Fife KH, Hackman RC, Meyers JD, Corey L: Herpes simplex virus pneumonia: clinical, virologic, and pathologic features in 20 patients. Ann Intern Med. 1982, 97 (6): 813-820.CrossRefPubMed
5.
go back to reference Bruynseels P, Jorens PG, Demey HE, Goossens H, Pattyn SR, Elseviers MM, Weyler J, Bossaert LL, Mentens Y, Ieven M: Herpes simplex virus in the respiratory tract of critical care patients: a prospective study. Lancet. 2003, 362 (9395): 1536-1541. 10.1016/S0140-6736(03)14740-X.CrossRefPubMed Bruynseels P, Jorens PG, Demey HE, Goossens H, Pattyn SR, Elseviers MM, Weyler J, Bossaert LL, Mentens Y, Ieven M: Herpes simplex virus in the respiratory tract of critical care patients: a prospective study. Lancet. 2003, 362 (9395): 1536-1541. 10.1016/S0140-6736(03)14740-X.CrossRefPubMed
6.
go back to reference Linssen CF, Jacobs JA, Stelma FF, van Mook WN, Terporten P, Vink C, Drent M, Bruggeman CA, Smismans A: Herpes simplex virus load in bronchoalveolar lavage fluid is related to poor outcome in critically ill patients. Intensive Care Med. 2008, 34 (12): 2202-9. 10.1007/s00134-008-1231-4.CrossRefPubMed Linssen CF, Jacobs JA, Stelma FF, van Mook WN, Terporten P, Vink C, Drent M, Bruggeman CA, Smismans A: Herpes simplex virus load in bronchoalveolar lavage fluid is related to poor outcome in critically ill patients. Intensive Care Med. 2008, 34 (12): 2202-9. 10.1007/s00134-008-1231-4.CrossRefPubMed
7.
go back to reference Tuxen DV, Wilson JW, Cade JF: Prevention of lower respiratory herpes simplex virus infection with acyclovir in patients with the adult respiratory distress syndrome. Am Rev Respir Dis. 1987, 136 (2): 402-405.CrossRefPubMed Tuxen DV, Wilson JW, Cade JF: Prevention of lower respiratory herpes simplex virus infection with acyclovir in patients with the adult respiratory distress syndrome. Am Rev Respir Dis. 1987, 136 (2): 402-405.CrossRefPubMed
8.
go back to reference Camps K, Jorens PG, Demey HE, Pattyn SR, Ieven M: Clinical significance of herpes simplex virus in the lower respiratory tract of critically ill patients. Eur J Clin Microbiol Infect Dis. 2002, 21 (10): 758-759. 10.1007/s10096-002-0809-y.CrossRefPubMed Camps K, Jorens PG, Demey HE, Pattyn SR, Ieven M: Clinical significance of herpes simplex virus in the lower respiratory tract of critically ill patients. Eur J Clin Microbiol Infect Dis. 2002, 21 (10): 758-759. 10.1007/s10096-002-0809-y.CrossRefPubMed
9.
go back to reference Luyt CE, Combes A, Deback C, Aubriot-Lorton MH, Nieszkowska A, Trouillet JL, Capron F, Agut H, Gibert C, Chastre J: Herpes simplex virus lung infection in patients undergoing prolonged mechanical ventilation. Am J Respir Crit Care Med. 2007, 175 (9): 935-942. 10.1164/rccm.200609-1322OC.CrossRefPubMed Luyt CE, Combes A, Deback C, Aubriot-Lorton MH, Nieszkowska A, Trouillet JL, Capron F, Agut H, Gibert C, Chastre J: Herpes simplex virus lung infection in patients undergoing prolonged mechanical ventilation. Am J Respir Crit Care Med. 2007, 175 (9): 935-942. 10.1164/rccm.200609-1322OC.CrossRefPubMed
10.
go back to reference Liebau P, Kuse E, Winkler M, Schlitt HJ, Oldhafer K, Verhagen W, Flik J, Pichlmayr R: Management of herpes simplex virus type 1 pneumonia following liver transplantation. Infection. 1996, 24 (2): 130-135. 10.1007/BF01713317.CrossRefPubMed Liebau P, Kuse E, Winkler M, Schlitt HJ, Oldhafer K, Verhagen W, Flik J, Pichlmayr R: Management of herpes simplex virus type 1 pneumonia following liver transplantation. Infection. 1996, 24 (2): 130-135. 10.1007/BF01713317.CrossRefPubMed
11.
go back to reference Francois-Dufresne A, Garbino J, Ricou B, Wunderli W: ARDS caused by herpes simplex virus pneumonia in a patient with Crohn's disease: a case report. Intensive Care Med. 1997, 23 (3): 345-347. 10.1007/s001340050339.CrossRefPubMed Francois-Dufresne A, Garbino J, Ricou B, Wunderli W: ARDS caused by herpes simplex virus pneumonia in a patient with Crohn's disease: a case report. Intensive Care Med. 1997, 23 (3): 345-347. 10.1007/s001340050339.CrossRefPubMed
12.
go back to reference Kim EA, Lee KS, Primack SL, Yoon HK, Byun HS, Kim TS, Suh GY, Kwon OJ, Han J: Viral pneumonias in adults: radiologic and pathologic findings. Radiographics. 2002, 22 (Spec No): S137-149.CrossRefPubMed Kim EA, Lee KS, Primack SL, Yoon HK, Byun HS, Kim TS, Suh GY, Kwon OJ, Han J: Viral pneumonias in adults: radiologic and pathologic findings. Radiographics. 2002, 22 (Spec No): S137-149.CrossRefPubMed
13.
go back to reference Taplitz RA, Jordan MC: Pneumonia caused by herpesviruses in recipients of hematopoietic cell transplants. Semin Respir Infect. 2002, 17 (2): 121-129. 10.1053/srin.2002.33447.CrossRefPubMed Taplitz RA, Jordan MC: Pneumonia caused by herpesviruses in recipients of hematopoietic cell transplants. Semin Respir Infect. 2002, 17 (2): 121-129. 10.1053/srin.2002.33447.CrossRefPubMed
14.
go back to reference Ferrari A, Luppi M, Potenza L, Riva G, Morselli M, Imovilli A, Volzone F, Rossi G, Codeluppi M, Guaraldi G, et al: Herpes simplex virus pneumonia during standard induction chemotherapy for acute leukemia: case report and review of literature. Leukemia. 2005, 19 (11): 2019-2021. 10.1038/sj.leu.2403893.CrossRefPubMed Ferrari A, Luppi M, Potenza L, Riva G, Morselli M, Imovilli A, Volzone F, Rossi G, Codeluppi M, Guaraldi G, et al: Herpes simplex virus pneumonia during standard induction chemotherapy for acute leukemia: case report and review of literature. Leukemia. 2005, 19 (11): 2019-2021. 10.1038/sj.leu.2403893.CrossRefPubMed
15.
go back to reference Cunha BA, Eisenstein LE, Dillard T, Krol V: Herpes simplex virus (HSV) pneumonia in a heart transplant: diagnosis and therapy. Heart Lung. 2007, 36 (1): 72-78. 10.1016/j.hrtlng.2006.07.005.CrossRefPubMed Cunha BA, Eisenstein LE, Dillard T, Krol V: Herpes simplex virus (HSV) pneumonia in a heart transplant: diagnosis and therapy. Heart Lung. 2007, 36 (1): 72-78. 10.1016/j.hrtlng.2006.07.005.CrossRefPubMed
16.
go back to reference Gooskens J, Templeton KE, Claas EC, van Bussel MJ, Smit VT, Kroes AC: Quantitative detection of herpes simplex virus DNA in the lower respiratory tract. J Med Virol. 2007, 79 (5): 597-604. 10.1002/jmv.20861.CrossRefPubMed Gooskens J, Templeton KE, Claas EC, van Bussel MJ, Smit VT, Kroes AC: Quantitative detection of herpes simplex virus DNA in the lower respiratory tract. J Med Virol. 2007, 79 (5): 597-604. 10.1002/jmv.20861.CrossRefPubMed
17.
go back to reference Reichenberger F, Dickenmann M, Binet I, Soler M, Bolliger C, Steiger J, Brunner F, Thiel G, Tamm M: Diagnostic yield of bronchoalveolar lavage following renal transplantation. Transpl Infect Dis. 2001, 3 (1): 2-7. 10.1034/j.1399-3062.2001.003001002.x.CrossRefPubMed Reichenberger F, Dickenmann M, Binet I, Soler M, Bolliger C, Steiger J, Brunner F, Thiel G, Tamm M: Diagnostic yield of bronchoalveolar lavage following renal transplantation. Transpl Infect Dis. 2001, 3 (1): 2-7. 10.1034/j.1399-3062.2001.003001002.x.CrossRefPubMed
18.
go back to reference Aisenberg G, Torres H, Tarrand J, Safdar A, Bodey G, Chemaly RF: Herpes simplex virus lower respiratory tract infection in patients with solid tumors. Cancer. 2009, 115 (1): 199-206. 10.1002/cncr.24011.CrossRefPubMed Aisenberg G, Torres H, Tarrand J, Safdar A, Bodey G, Chemaly RF: Herpes simplex virus lower respiratory tract infection in patients with solid tumors. Cancer. 2009, 115 (1): 199-206. 10.1002/cncr.24011.CrossRefPubMed
19.
go back to reference Groeneveld AB, Vandenbroucke-Grauls CM: One swallow does not make a summer: can herpes simplex virus-1 cause pneumonia and acute lung injury?. Am J Respir Crit Care Med. 2007, 175 (9): 865-866. 10.1164/rccm.200701-133ED.CrossRefPubMed Groeneveld AB, Vandenbroucke-Grauls CM: One swallow does not make a summer: can herpes simplex virus-1 cause pneumonia and acute lung injury?. Am J Respir Crit Care Med. 2007, 175 (9): 865-866. 10.1164/rccm.200701-133ED.CrossRefPubMed
20.
go back to reference Kang I, Park SH: Infectious complications in SLE after immunosuppressive therapies. Curr Opin Rheumatol. 2003, 15 (5): 528-534. 10.1097/00002281-200309000-00002.CrossRefPubMed Kang I, Park SH: Infectious complications in SLE after immunosuppressive therapies. Curr Opin Rheumatol. 2003, 15 (5): 528-534. 10.1097/00002281-200309000-00002.CrossRefPubMed
21.
go back to reference Doran MF, Crowson CS, Pond GR, O'Fallon WM, Gabriel SE: Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum. 2002, 46 (9): 2287-2293. 10.1002/art.10524.CrossRefPubMed Doran MF, Crowson CS, Pond GR, O'Fallon WM, Gabriel SE: Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum. 2002, 46 (9): 2287-2293. 10.1002/art.10524.CrossRefPubMed
22.
go back to reference Aquino SL, Dunagan DP, Chiles C, Haponik EF: Herpes simplex virus 1 pneumonia: patterns on CT scans and conventional chest radiographs. J Comput Assist Tomogr. 1998, 22 (5): 795-800. 10.1097/00004728-199809000-00024.CrossRefPubMed Aquino SL, Dunagan DP, Chiles C, Haponik EF: Herpes simplex virus 1 pneumonia: patterns on CT scans and conventional chest radiographs. J Comput Assist Tomogr. 1998, 22 (5): 795-800. 10.1097/00004728-199809000-00024.CrossRefPubMed
23.
go back to reference Umans U, Golding RP, Duraku S, Manoliu RA: Herpes simplex virus 1 pneumonia: conventional chest radiograph pattern. Eur Radiol. 2001, 11 (6): 990-994. 10.1007/s003300000696.CrossRefPubMed Umans U, Golding RP, Duraku S, Manoliu RA: Herpes simplex virus 1 pneumonia: conventional chest radiograph pattern. Eur Radiol. 2001, 11 (6): 990-994. 10.1007/s003300000696.CrossRefPubMed
24.
go back to reference Miller WT, Shah RM: Isolated diffuse ground-glass opacity in thoracic CT: causes and clinical presentations. AJR Am J Roentgenol. 2005, 184 (2): 613-622.CrossRefPubMed Miller WT, Shah RM: Isolated diffuse ground-glass opacity in thoracic CT: causes and clinical presentations. AJR Am J Roentgenol. 2005, 184 (2): 613-622.CrossRefPubMed
25.
go back to reference Boivin G, Goyette N, Sergerie Y, Keays S, Booth T: Longitudinal evaluation of herpes simplex virus DNA load during episodes of herpes labialis. J Clin Virol. 2006, 37 (4): 248-251. 10.1016/j.jcv.2006.09.006.CrossRefPubMed Boivin G, Goyette N, Sergerie Y, Keays S, Booth T: Longitudinal evaluation of herpes simplex virus DNA load during episodes of herpes labialis. J Clin Virol. 2006, 37 (4): 248-251. 10.1016/j.jcv.2006.09.006.CrossRefPubMed
26.
go back to reference Knight DA, Hejmanowski AQ, Dierksheide JE, Williams JW, Chong AS, Waldman WJ: Inhibition of herpes simplex virus type 1 by the experimental immunosuppressive agent leflunomide. Transplantation. 2001, 71 (1): 170-174. 10.1097/00007890-200101150-00031.CrossRefPubMed Knight DA, Hejmanowski AQ, Dierksheide JE, Williams JW, Chong AS, Waldman WJ: Inhibition of herpes simplex virus type 1 by the experimental immunosuppressive agent leflunomide. Transplantation. 2001, 71 (1): 170-174. 10.1097/00007890-200101150-00031.CrossRefPubMed
27.
go back to reference Afessa B: Mycobacterial and nonbacterial pulmonary complications in hospitalized patients with human immunodeficiency virus infection: a prospective, cohort study. BMC Pulm Med. 2001, 1: 1-10.1186/1471-2466-1-1.CrossRefPubMed Afessa B: Mycobacterial and nonbacterial pulmonary complications in hospitalized patients with human immunodeficiency virus infection: a prospective, cohort study. BMC Pulm Med. 2001, 1: 1-10.1186/1471-2466-1-1.CrossRefPubMed
28.
go back to reference Simoons-Smit AM, Kraan EM, Beishuizen A, Strack van Schijndel RJ, Vandenbroucke-Grauls CM: Herpes simplex virus type 1 and respiratory disease in critically-ill patients: Real pathogen or innocent bystander?. Clin Microbiol Infect. 2006, 12 (11): 1050-1059. 10.1111/j.1469-0691.2006.01475.x.CrossRefPubMed Simoons-Smit AM, Kraan EM, Beishuizen A, Strack van Schijndel RJ, Vandenbroucke-Grauls CM: Herpes simplex virus type 1 and respiratory disease in critically-ill patients: Real pathogen or innocent bystander?. Clin Microbiol Infect. 2006, 12 (11): 1050-1059. 10.1111/j.1469-0691.2006.01475.x.CrossRefPubMed
Metadata
Title
Occurrence of HSV-1-induced pneumonitis in patients under standard immunosuppressive therapy for rheumatic, vasculitic, and connective tissue disease
Authors
Matthias N Witt
Gerald S Braun
Stephan Ihrler
Holger Schmid
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2009
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/1471-2466-9-22

Other articles of this Issue 1/2009

BMC Pulmonary Medicine 1/2009 Go to the issue