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Hypertrophic osteoarthropathy pathogenesis: a case highlighting the potential role for cyclo-oxygenase-2-derived prostaglandin E2

Nature Clinical Practice Rheumatology volume 2, pages 452–456 (2006)Cite this article

Abstract

Background A 65-year-old woman presented with weakness, 9 kg weight loss, dysphagia, facial and bilateral upper-extremity swelling, and debilitating, bilateral lower-extremity pain. The patient had undergone a right upper lobectomy for a 5 mm, poorly differentiated adenocarcinoma of the lung 4 years previously. Medical history included chronic obstructive pulmonary disease (emphysema), hypertension, cerebrovascular disease and multinodular goiter. Surgical history included a right carotid endarterectomy. The patient's history was remarkable for 50+ pack-years of smoking.

Investigations Physical examination, comprehensive metabolic panel and complete blood counts, CT, bone scintigraphy, quantification of urinary 11a-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (also known as PGE-M).

Diagnosis Recurrent non-small-cell lung cancer with adrenal metastasis, hypertrophic osteoarthropathy associated with non-small-cell lung cancer, and hyperprostaglandinuria.

Management Rofecoxib 25 mg daily for hypertrophic osteoarthropathy, palliative external-beam radiation (44 Gy in 22 fractions) for mediastinal mass, palliative external-beam radiation (30 Gy in 12 fractions), followed 2 years later with radiofrequency ablation, for left adrenal metastasis.

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Figure 1: Features of hypertrophic osteoarthropathy.

References

  1. Murphey LJ et al. (2004) Quantification of the major urinary metabolite of PGE2 by a liquid chromatographic/mass spectrometric assay: determination of cyclooxygenase-specific PGE2 synthesis in healthy humans and those with lung cancer. Anal Biochem 334: 266–275

    Article  CAS  Google Scholar 

  2. Gross ND et al. (2005) Levels of prostaglandin E metabolite, the major urinary metabolite of prostaglandin E2, are increased in smokers. Clin Cancer Res 11: 6087–6093

    Article  CAS  Google Scholar 

  3. Martinez-Lavin M (1997) Hypertrophic osteoarthropathy. Curr Opin Rheumatol 9: 83–86

    Article  CAS  Google Scholar 

  4. Martinez-Lavin M (1998) Hypertrophic osteoarthropathy. In Rheumatology, 8.46.1–8.46.4 (Eds Klippel JH and Dieppe PA) London: Mosby

    Google Scholar 

  5. Naschitz JE et al. (1999) Rheumatic syndromes: clues to occult neoplasia. Semin Arthritis Rheum 29: 43–55

    Article  CAS  Google Scholar 

  6. Vandemergel X et al. (2004) Periostitis and hypertrophic osteoarthropathy: etiologies and bone scan patterns in 115 cases. Eur J Intern Med 15: 375–380

    Article  Google Scholar 

  7. Dickinson CJ and Martin JF (1987) Megakaryocytes and platelet clumps as the cause of finger clubbing. Lancet 2: 1434–1435

    Article  CAS  Google Scholar 

  8. Olan F et al. (2004) Circulating vascular endothelial growth factor concentrations in a case of pulmonary hypertrophic osteoarthropathy. Correlation with disease activity. J Rheumatol 31: 614–616

    PubMed  Google Scholar 

  9. Silveira LH et al. (2000) Vascular endothelial growth factor and hypertrophic osteoarthropathy. Clin Exp Rheumatol 18: 57–62

    CAS  PubMed  Google Scholar 

  10. Maroto AA et al. (2005) Painful hypertrophic osteoarthropathy successfully treated with octreotide. The pathogenetic role of vascular endothelial growth factor (VEGF). Rheumatology 44: 1326–1327

    Article  Google Scholar 

  11. Piper PJ et al. (1970) Inactivation of prostaglandins by the lungs. Nature 225: 600–604

    Article  CAS  Google Scholar 

  12. Seyberth HW et al. (1975) Prostaglandins as mediators of hypercalcemia associated with certain types of cancer. New Engl J Med 293: 1278–1283

    Article  CAS  Google Scholar 

  13. Martinez-Lavin M and Castillejos G (1986) Reply to: Ferritin and prostaglandins in hypertrophic osteoarthropathy. J Rheumatol 13: 834–836

    Google Scholar 

  14. Lemen RJ et al. (1978) Relationships among digital clubbing, disease severity, and serum prostaglandins F2α and E concentrations in cystic fibrosis patients. Am Rev Respir Dis 117: 639–646

    CAS  PubMed  Google Scholar 

  15. Frolich JC et al. (1975) Urinary prostaglandins. Identification and origin. J Clin Invest 55: 763–770

    Article  CAS  Google Scholar 

  16. Suzuma T et al. (2001) Pamidronate-induced remission of pain associated with hypertrophic pulmonary osteoarthropathy in chemoendocrine therapy-refractory inoperable metastatic breast carcinoma. Anticancer Drugs 12: 731–734

    Article  CAS  Google Scholar 

  17. Garske LA and Bell SC (2002) Pamidronate results in symptom control of hypertrophic pulmonary osteoarthropathy in cystic fibrosis. Chest 121: 1363–1364

    Article  Google Scholar 

  18. Amital H et al. (2004) Hypertrophic pulmonary osteoarthropathy: control of pain and symptoms with pamidronate. Clin Rheumatol 23: 330–332

    Article  Google Scholar 

  19. Guyot-Drouot MH et al. (2000) Rheumatologic manifestations of pachydermoperiostosis and preliminary experience with bisphosphonates. J Rhemumatol 27: 2418–2423

    CAS  Google Scholar 

  20. Johnson SA et al. (1997) Treatment of resistant pain in hypertrophic pulmonary osteoarthropathy with subcutaneous octreotide. Thorax 52: 298–299

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank Timothy P Padera and Torunn I Yock for advice and critical review of the manuscript. This study was supported by NIH grants DK48831, GM15431, CA77839 and RR00095 (JDM).

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Authors and Affiliations

  1. Physician at the Harvard Radiation Oncology Program at Massachusetts General Hospital, Boston, MA

    Kevin R Kozak

  2. Research Assistant Professor,

    Ginger L Milne & Jason D Morrow

  3. Professor of Medicine and Pharmacology at Vanderbilt University Medical Center, Nashville, TN

    Ginger L Milne & Jason D Morrow

  4. Attending Medical Oncologist and Hematologist at Brockton Hospital, Brockton, MA, USA

    Barry P Cuiffo

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  1. Kevin R Kozak
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Correspondence to Kevin R Kozak.

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Kozak, K., Milne, G., Morrow, J. et al. Hypertrophic osteoarthropathy pathogenesis: a case highlighting the potential role for cyclo-oxygenase-2-derived prostaglandin E2. Nat Rev Rheumatol 2, 452–456 (2006). https://doi.org/10.1038/ncprheum0252

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