Skip to main content

Advertisement

Log in

Successful treatment of steroid-resistant methotrexate-induced interstitial pneumonia with peripherally administered ulinastatin

  • Case Report
  • Published:
Modern Rheumatology

Abstract

A 76-year-old woman with rheumatoid arthritis who had been taking methotrexate (MTX) for 9 months was admitted because of acute respiratory failure. A chest radiograph revealed diffuse ground-glass attenuation. MTX-induced interstitial pneumonia (IP) was strongly suspected. Her respiratory failure worsened in spite of steroid pulse therapy. Intravenous administration of ulinastatin, however, dramatically improved her clinical condition. The second ulinastatin treatment was also effective. This case suggests that peripherally administered ulinastatin may be effective for steroid-resistant MTX-induced IP.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Kinder AJ, Hassell AB, Brand J, Brownfield A, Grove M, Shadforth MF. The treatment of inflammatory arthritis with methotrexate in clinical practice: treatment duration and incidence of adverse drug reactions. Rheumatology (Oxford). 2005;44:61–6.

    Article  CAS  Google Scholar 

  2. Searles G, McKendry RJ. Methotrexate pneumonitis in rheumatoid arthritis: potential risk factors. Four case reports and a review of the literature. J Rheumatol. 1987;14:1164–71.

    CAS  PubMed  Google Scholar 

  3. Hilliquin P, Renoux M, Perrot S, Puechal X, Menkes CJ. Occurrence of pulmonary complications during methotrexate therapy in rheumatoid arthritis. Br J Rheumatol. 1996;35:441–5.

    Article  CAS  PubMed  Google Scholar 

  4. Newman ED, Harrington TM. Fatal methotrexate pneumonitis in rheumatoid arthritis. Arthritis Rheum. 1988;31:1585–6.

    Article  CAS  PubMed  Google Scholar 

  5. Tsujimura S, Saito K, Nakayamada S, Tanaka Y. Bolus infusion of human urinary trypsin inhibitor improves intractable interstitial pneumonia in patients with connective tissue diseases. Rheumatology (Oxford). 2008;47:907–13.

    Article  CAS  Google Scholar 

  6. Alarcon GS, Kremer JM, Macaluso M, et al. Risk factors for methotrexate-induced lung injury in patients with rheumatoid arthritis. A multicenter, case–control study. Methotrexate-Lung Study Group. Ann Intern Med. 1997;127:356–64.

    CAS  PubMed  Google Scholar 

  7. Kremer JM, Alarcon GS, Weinblatt ME, et al. Clinical, laboratory, radiographic, and histopathologic features of methotrexate-associated lung injury in patients with rheumatoid arthritis: a multicenter study with literature review. Arthritis Rheum. 1997;40:1829–37.

    Article  CAS  PubMed  Google Scholar 

  8. Grove ML, Hassell AB, Hay EM, Shadforth MF. Adverse reactions to disease-modifying anti-rheumatic drugs in clinical practice. QJM. 2001;94:309–19.

    Article  CAS  PubMed  Google Scholar 

  9. Imokawa S, Colby TV, Leslie KO, Helmers RA. Methotrexate pneumonitis: review of the literature and histopathological findings in nine patients. Eur Respir J. 2000;15:373–81.

    Article  CAS  PubMed  Google Scholar 

  10. Weinblatt ME. Methotrexate in rheumatoid arthritis: toxicity issues. Br J Rheumatol. 1996;35:403–5.

    Article  CAS  PubMed  Google Scholar 

  11. Zisman DA, McCune WJ, Tino G, Lynch JP 3rd. Drug-induced pneumonitis: the role of methotrexate. Sarcoidosis Vasc Diffuse Lung Dis. 2001;18:243–52.

    CAS  PubMed  Google Scholar 

  12. Saag KG, Kolluri S, Koehnke RK, Georgou TA, Rachow JW, Hunninghake GW. Rheumatoid arthritis lung disease. Determinants of radiographic and physiologic abnormalities. Arthritis Rheum. 1996;39:1711–9.

    Article  CAS  PubMed  Google Scholar 

  13. Kuwajima S, Matsui T, Kitahashi S, Kishida T, Noda T, Izumi Y, et al. Automated measurement of trypsin inhibitor in urine with a centrifugal analyzer: comparison with other acute phase reactants. Clin Biochem. 1990;23:167–71.

    Article  CAS  PubMed  Google Scholar 

  14. Hirose J, Ozawa T, Miura T, Isaji M, Nagao Y, Yamashiro K, et al. Human neutrophil elastase degrades inter-alpha-trypsin inhibitor to liberate urinary trypsin inhibitor related proteins. Biol Pharm Bull. 1998;21:651–6.

    CAS  PubMed  Google Scholar 

  15. Takeda J. Prevention of pulmonary damage by ulinastatin (in Japanese). Rinsho Masui. 1999;23:1703–9.

    Google Scholar 

  16. McGee DC, Gould MK. Preventing complications of central venous catheterization. N Engl J Med. 2003;348:1123–33.

    Article  PubMed  Google Scholar 

  17. Kato K, Nagao Y, Kurosawa M. Effect of human urinary trypsin inhibitor (ulinastatin) on inflammatory mediators from leukocytes: possible role in the prevention of SIRS (in Japanese). Igaku To Yakugaku. 1995;34:499–506.

    CAS  Google Scholar 

  18. Endo S, Inada K, Taki K, Hoshi S, Yoshida M. Inhibitory effects of ulinastatin on the production of cytokines: implications for the prevention of septicemic shock. Clin Ther. 1990;12:323–6.

    CAS  PubMed  Google Scholar 

  19. Selman M, Pardo A. The pathogenesis of pulmonary fibrosis. In: Fishman AP, Elias JA, Fishman JA, Grippi MA, Senior RM, Pack AI, editors. Fishman’s pulmonary diseases and disorders. 4th ed. New York: McGraw-Hill; 2008. p. 371–83.

  20. Takeuchi S, Suzuki T, Shiba T, Urita Y, Murakuni H. Application of MR-20 for pancreatitis and study of blood concentration in healthy volunteer (in Japanese). Rinsho To Kenkyu. 1985;62:626–30.

    Google Scholar 

  21. Taki K, Hirahara K, Tomita S, Totoki T. Case report: cases of recovery from paraquat poisoning without pulmonary fibrosis. Ther Res. 1995;16:1219–27.

    Google Scholar 

  22. Suwa A, Hirakata M, Satoh S, Mimori T, Utsumi K, Inada S. Rheumatoid arthritis associated with methotrexate-induced pneumonitis: improvement with i.v. cyclophosphamide therapy. Clin Exp Rheumatol. 1999;17:355–8.

    CAS  PubMed  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kenji Nagasaka.

About this article

Cite this article

Yamazaki, H., Nagasaka, K. Successful treatment of steroid-resistant methotrexate-induced interstitial pneumonia with peripherally administered ulinastatin. Mod Rheumatol 21, 79–84 (2011). https://doi.org/10.1007/s10165-010-0349-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10165-010-0349-8

Keywords

Navigation