Skip to main content

Advertisement

SpringerLink
Log in

Helicobacter cinaedi-Associated Refractory Cellulitis in Patients with X-Linked Agammaglobulinemia

  • Original Article
  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

A Correction to this article was published on 08 March 2021

This article has been updated

Abstract

X-linked agammaglobulinemia (XLA) is characterized by severe or recurrent infections, hypogammaglobulinemia, and circulating B cell deficiency. The frequent pathogens seen in patients with XLA include Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, and enterovirus as well as Campylobacter and Helicobacter species. Here, we describe two patients with XLA who developed cellulitis and bacteremia caused by Helicobacter cinaedi even when administered an appropriate immunoglobulin replacement therapy. H. cinaedi may be difficult to isolate using a conventional blood culture system and could be identified by sequence analysis and mass spectrometry. H. cinaedi infection causes recurrent symptoms frequently, and patients require a long course of antibiotic treatment. Recently, the case of non-H. pylori Helicobacter (NHPH) infection such as H. cinaedi and H. bilis infection is increasing in number in patients with XLA. Systemic NHPH infection should be suspected, and extensive microbiological analysis should be performed to appropriately treat patients with XLA who present with fever and skin lesions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Change history

Abbreviations

GNR:

Gram-negative rod

HIV:

Human immunodeficiency virus

IVIg:

Intravenous immunoglobulin

MS:

Mass spectrometry

NHPH:

Non-Helicobacter pylori Helicobacter

PBMC:

Peripheral blood mononuclear cell

PCR:

Polymerase chain reaction

SCIg:

Subcutaneous immunoglobulin

XLA:

X-linked agammaglobulinemia

References

  1. Bruton OC. Agammaglobulinemia. Pediatrics. 1952;9:722–8.

    CAS  PubMed  Google Scholar 

  2. Tsukada S, Saffran DC, Rawlings DJ, Parolini O, Allen RC, Klisak I, et al. Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia. Cell. 1993;72:279–90.

    Article  CAS  Google Scholar 

  3. Vetrie D, Vorechovsky I, Sideras P, Holland J, Davies A, Flinter F, et al. The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases. Nature. 1993;361:226–33.

    Article  CAS  Google Scholar 

  4. Conley ME, Rohrer J, Minegishi Y. X-linked agammaglobulinemia. Clin Rev Allergy Immunol. 2000;19:183–204.

    Article  CAS  Google Scholar 

  5. Minauchi K, Takahashi S, Sakai T, Kondo M, Shibayama K, Arakawa Y, et al. The nosocomial transmission of Helicobacter cinaedi infections in immunocompromised patients. Intern Med. 2010;49:1733–9.

    Article  Google Scholar 

  6. Endo Y, Araoka H, Baba M, Okada C, Kimura M, Higurashi Y, et al. Matrix-assisted laser desorption ionization-time of flight mass spectrometry can be used to identify Helicobacter cinaedi. Diagn Microbiol Infect Dis. 2020;96:114964.

    Article  CAS  Google Scholar 

  7. Shinomiya N, Kanegane H, Watanabe A, Yamaguchi Y, Futatani T, Miyawaki T. Point mutation in intron 11 of Bruton’s tyrosine kinase in atypical X-linked agammaglobulinemia. Pediatr Int. 2000;42:689–92.

    Article  CAS  Google Scholar 

  8. Dewhirst FE, Fox JG, Mendes EN, Paster BJ, Gates CE, Kirkbride CA, et al. ‘Flexispira rappini’ strains represent at least 10 Helicobacter taxa. Int J Syst Evol Microbiol. 2000;50:1781–7.

    Article  CAS  Google Scholar 

  9. Simons E, Spacek LA, Lederman HM, Winkelstein JA. Helicobacter cinaedi bacteremia presenting as macules in an afebrile patient with X-linked agammaglobulinemia. Infection. 2004;32:367–8.

    Article  CAS  Google Scholar 

  10. Dua J, Elliot E, Bright P, Grigoriadou S, Bull R, Millar M, et al. Pyoderma gangrenosum-like ulcer caused by Helicobacter cinaedi in a patient with X-linked agammaglobulinaemia. Clin Exp Dermatol. 2012;37:642–5.

    Article  CAS  Google Scholar 

  11. Toyofuku M, Tomida J, Kawamura Y, Miyata I, Yuza Y, Horikoshi Y. Helicobacter cinaedi bacteremia resulting from antimicrobial resistance acquired during treatment for X-linked agammaglobulinemia. J Infect Chemother. 2016;22:704–6.

    Article  Google Scholar 

  12. Sugimoto M, Takeichi T, Muramatsu H, Kojima D, Osada Y, Kono M, et al. Recurrent cellulitis caused by Helicobacter cinaedi in a patient with X-linked agammaglobulinaemia. Acta Derm Venereol. 2017;97:277–8.

    Article  Google Scholar 

  13. Matsumoto A, Yeh I, Schwartz B, Rosenblum M, Schmidt TH. Chronic Helicobacter cinaedi cellulitis diagnosed by microbial polymerase chain reaction. JAAD Case Rep. 2017;3:398–400.

    Article  Google Scholar 

  14. Hill A, Byrne A, Bouffard D, Luong ML, Saber M, Chapdelaine H. Helicobacter cinaedi bacteremia mimicking eosinophilic fasciitis in a patient with X-linked agammaglobulinemia. JAAD Case Rep. 2018;4:327–9.

    Article  Google Scholar 

  15. Cuccherini B, Chua K, Gill V, Weir S, Wray B, Stewart D, et al. Bacteremia and skin/bone infections in two patients with X-linked agammaglobulinemia caused by an unusual organism related to Flexispira/Helicobacter species. Clin Immunol. 2000;97:121–9.

    Article  CAS  Google Scholar 

  16. Murray PR, Jain A, Uzel G, Ranken R, Ivy C, Blyn LB, et al. Pyoderma gangrenosum-like ulcer in a patient with X-linked agammaglobulinemia: identification of Helicobacter bilis by mass spectrometry analysis. Arch Dermatol. 2010;146:523–6.

    Article  Google Scholar 

  17. Turvey SE, Leo SH, Boos A, Deans GD, Prendiville J, Crawford RI, et al. Successful approach to treatment of Helicobacter bilis infection in X-linked agammaglobulinemia. J Clin Immunol. 2012;32:1404–8.

    Article  Google Scholar 

  18. Degand N, Dautremer J, Pilmis B, Ferroni A, Lanternier F, Brueau J, et al. Helicobacter bilis-associated suppurative cholangitis in a patient with X-linked agammaglobulinemia. J Clin Immunol. 2017;37:727–31.

    Article  CAS  Google Scholar 

  19. Schwarze-Zander C, Becker S, Wenzel J, Rockstroh JK, Spengler U, Yassin AF. Bacteremia caused by a novel helicobacter species in a 28-year-old man with X-linked agammaglobulinemia. J Clin Microbiol. 2010;48:4672–6.

    Article  Google Scholar 

  20. Funato M, Kaneko H, Ohkusu K, Sasai H, Kubota K, Ohnishi H, et al. Refractory chronic pleurisy caused by Helicobacter equorum-like bacterium in a patient with X-linked agammaglobulinemia. J Clin Microbiol. 2011;49:3432–5.

    Article  CAS  Google Scholar 

  21. Sharp SE. Chronic skin lesions from a patient with Bruton’s X-linked agammaglobulinemia. J Clin Microbiol. 2011;49:483–770.

    Article  Google Scholar 

  22. Fennell CL, Totten PA, Quinn TC, Patton DL, Holmes KK, Stamm WE. Characterization of campylobacter-like organisms isolated from homosexual men. J Infect Dis. 1984;149:58–66.

    Article  CAS  Google Scholar 

  23. Sacks LV, Labriola AM, Gill VJ, Gordin FM. Use of ciprofloxacin for successful eradication of bacteremia due to Campylobacter cinaedi in a human immunodeficiency virus-infected person. Rev Infect Dis. 1991;13:1066–8.

    Article  CAS  Google Scholar 

  24. Decker CF, Martin GJ, Barham WB, Paparello SF. Bacteremia due to Campylobacter cinaedi in a patient infected with the human immunodeficiency virus. Clin Infect Dis. 1992;15:178–9.

    Article  CAS  Google Scholar 

  25. Kiehlbauch JA, Tauxe RV, Baker CN, Wachsmuth IK. Helicobacter cinaedi-associated bacteremia and cellulitis in immunocompromised patients. Ann Intern Med. 1994;121:90–3.

    Article  CAS  Google Scholar 

  26. Burman WJ, Cohn DL, Reves RR, Wilson ML. Multifocal cellulitis and monoarticular arthritis as manifestations of Helicobacter cinaedi bacteremia. Clin Infect Dis. 1995;20:564–70.

    Article  CAS  Google Scholar 

  27. Sullivan AK, Nelson MR, Walsh J, Gazzard BG. Recurrent Helicobacter cinaedi cellulitis and bacteraemia in a patient with HIV infection. Int J STD AIDS. 1997;8:59–60.

    Article  CAS  Google Scholar 

  28. Hung CC, Hsueh PR, Chen MY, Teng LJ, Chen YC, Luh KT, et al. Bacteremia caused by Helicobacter cinaedi in an AIDS patients. J Formos Med Assoc. 1997;96:558–60.

    CAS  PubMed  Google Scholar 

  29. Murakami H, Iwata M, Goto M, Takahashi T, Ono E, Sawabe E, et al. Isolation of Helicobacter cinaedi from blood of an immunocompromised patient in Japan. J Infect Chemother. 2003;9:344–7.

    Article  Google Scholar 

  30. Araoka H, Baba M, Kimura M, Abe M, Inagawa H, Yoneyama A. Clinical characteristics of bacteremia caused by Helicobacter cinaedi and time required for blood cultures to become positive. J Clin Microbiol. 2014;52:1519–22.

    Article  Google Scholar 

  31. Imafuku A, Araoka H, Tanaka K, Marui Y, Sawa N, Ubara Y, et al. Helicobacter cinaedi bacteremia in four renal transplant patients: clinical features and an important suggestion regarding the route of infection. Transpl Infect Dis. 2016;18:132–6.

    Article  CAS  Google Scholar 

  32. Kawamura Y, Tomida J, Morita Y, Fujii S, Okamoto T, Akaike T. Clinical and bacteriological characteristics of Helicobacter cinaedi infection. J Infect Chemother. 2014;20:517–26.

    Article  Google Scholar 

  33. Araoka H, Baba M, Okada C, Kimura M, Sato T, Yatomi Y, et al. First evidence of bacterial translocation from the intestinal tract as a route of Helicobacter cinaedi bacteremia. Helicobacter. 2018;23:10.

    Article  Google Scholar 

  34. Tomida J, Tsurunaga M, Hosoda T, Hayakawa S, Suematsu H, Sawamura H, et al. Evaluation of automated blood culture systems about the detection capability for Helicobacter cinaedi. J Jpn Soc Clin Microbiol. 2012;22:233 [in Japanese].

    Google Scholar 

  35. Kitamura T, Kawamura Y, Ohkusu K, Masaki T, Iwashita H, Sawa T, et al. Helicobacter cinaedi cellulitis and bacteremia in immunocompetent hosts after orthopedic surgery. J Clin Microbiol. 2007;45:31e8.

    Article  Google Scholar 

  36. Araoka H, Baba M, Okada C, Kimura M, Sato T, Yatomi Y, et al. Risk factors for recurrent Helicobacter cinaedi bacteremia and the efficacy of selective digestive decontamination with kanamycin to prevent recurrence. Clin Infect Dis. 2018;67:573–8.

    Article  CAS  Google Scholar 

  37. Orange JS, Grossman WJ, Navickis RJ, Wilkes MM. Impact of trough IgG on pneumonia incidence in primary immunodeficiency: a meta-analysis of clinical studies. Clin Immunol. 2010;137:21–30.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank the staff of the Central Clinical Laboratory at Shiga University of Medical Science Hospital and that of the Central Clinical Laboratory at Tokyo Medical and Dental University Hospital for identifying Helicobacter cinaedi. We also thank Enago (www.enago.jp) for the English language review.

Funding

This work was supported by MEXT/ JSPS KAKENHI Grant Number JP17K10099 to H. K.

Author information

Author notes

  1. Kento Inoue and Saeko Sasaki contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan

    Kento Inoue & Tomohiro Morio

  2. Department of Pediatrics, Shiga Medical Center for Children, Moriyama, Shiga, Japan

    Saeko Sasaki & Takashi Kusunoki

  3. Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Takahiro Yasumi

  4. Department of Community Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan

    Kohsuke Imai

  5. Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan

    Hirokazu Kanegane

Authors
  1. Kento Inoue
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Saeko Sasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takahiro Yasumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kohsuke Imai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takashi Kusunoki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tomohiro Morio
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hirokazu Kanegane
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

K. Inoue, S.S., and H. K. wrote the manuscript. K. Inoue, S. S., and T. K. collected patient data. Y. T., K. Imai, and T. M. provided critical discussion. H. K. conceptualized the study.

Corresponding author

Correspondence to Hirokazu Kanegane.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material

ESM 1

(DOCX 537 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Inoue, K., Sasaki, S., Yasumi, T. et al. Helicobacter cinaedi-Associated Refractory Cellulitis in Patients with X-Linked Agammaglobulinemia. J Clin Immunol 40, 1132–1137 (2020). https://doi.org/10.1007/s10875-020-00830-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10875-020-00830-6

Keywords

Search

Navigation