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Clinical Rheumatology

, Volume 30, Issue 1, pp 7–13 | Cite as

Review of current therapies for secondary hypertrophic pulmonary osteoarthropathy

  • Sheila Nguyen
  • Mehrnaz Hojjati
Review Article

Abstract

Hypertrophic osteoarthropathy (HOA) is a disabling condition that may occur secondarily to primary lung cancer. It is characterized by digital clubbing, arthralgia/arthritis, and periostosis of the tubular bones. The pain associated with HOA can be disabling and often refractory to conventional analgesics. We performed a comprehensive review of the literature using the PubMed database on treatment modalities available for HOA. We found 52 relevant articles—40 case reports, six case series, two review papers, and four combined case series and review papers. There were no randomized controlled trials reported. We then classified treatments used for HOA into two categories: (1) treatment of primary cause (i.e., resection of tumor, chemotherapy, radiotherapy, treatment of infection, etc.) and (2) symptomatic treatments (i.e., bisphosphonates, octreotide, NSAIDs, vagotomy, etc.). Subsequently, we summarized the main findings for each treatment. Although the clinical diagnosis of HOA has existed for over 100 years, the pathogenesis mechanism has not yet been elucidated, and treatment options for this condition remain experimental. Primary treatment is the most widely reported modality to be efficacious. In cases which primary therapy is not possible, several symptomatic treatment modalities are suggested, with various degree of success. Further research is needed to clarify the pathophysiological mechanism of HOA as to appropriately direct therapy.

Keywords

Bisphosphonates Gefetinib Octreotide Osteoarthropathy Secondary hypertrophic Therapy Treatment Vagotomy 

Notes

Disclosures

None

References

  1. 1.
    Yao Q, Altman RD, Brahn E (2009) Periostitis and hypertrophic pulmonary osteoarthropathy: report of 2 cases and review of the literature. Semin Arthritis Rheum 38:458–466CrossRefPubMedGoogle Scholar
  2. 2.
    Bazar KA, Yun AJ, Lee PY (2004) Hypertrophic osteoarthropathy may be a marker of underlying sympathetic bias. Med Hypotheses 63:357–361CrossRefPubMedGoogle Scholar
  3. 3.
    Ntaios G, Adamidou A, Karamitsos D (2008) Hypertrophic pulmonary osteoarthropathy secondary to bronchial adenocarcinoma and coexisting pulmonary tuberculosis: a case report. Cases Journal 1:221CrossRefPubMedGoogle Scholar
  4. 4.
    Ooi A, Saad RA, Moorjani N, Amer KM (2007) Effective symptomatic relief of hypertrophic pulmonary osteoarthropathy by video-assisted thoracic surgery truncal vagotomy. Ann Thorac Surg 83:684–685CrossRefPubMedGoogle Scholar
  5. 5.
    Rassam JW, Anderson G (1975) Incidence of paramalignant disorders in bronchogenic carcinoma. Thorax 30:86–90CrossRefPubMedGoogle Scholar
  6. 6.
    Martínez-Lavín M, Bobadilla M, Casanova J, Attié F, Martínez M (1982) Hypertrophic osteoarthropathy in cyanotic congenital heart disease: its prevalence and relationship to bypass of the lung. Arthritis Rheum 25:1186–1193CrossRefPubMedGoogle Scholar
  7. 7.
    Botton E, Saraux A, Laselve H, Jousse S, Le Goff P (2003) Musculoskeletal manifestations in cystic fibrosis. Joint Bone Spine: Rev Rhum 70:327–335CrossRefGoogle Scholar
  8. 8.
    Shih W (2004) Pulmonary hypertrophic osteoarthropathy and its resolution. Semin Nucl Med 34:159–163CrossRefPubMedGoogle Scholar
  9. 9.
    Yeo W, Leung SF, Chan AT, Chiu KW (1996) Radiotherapy for extreme hypertrophic pulmonary osteoarthropathy associated with malignancy. Clin Oncology (R Coll Radiol (Great Brit)) 8:195–197Google Scholar
  10. 10.
    Morita M, Sakaguchi Y, Kuma S, Kajiyama K, Sugio K, Yasumoto K (2003) Hypertrophic osteoarthropathy associated with esophageal cancer. Ann Thorac Surg 76:1744–1746CrossRefPubMedGoogle Scholar
  11. 11.
    Pallecaros A, Ross BA, Gates L, Webb FW (1992) Oesophago-gastrectomy for Marie-Bamberger syndrome. J R Soc Med 85:635–636PubMedGoogle Scholar
  12. 12.
    Ullal SR (1972) Hypertrophic osteoarthropathy and leiomyoma of the esophagus. Am J Surg 123:356–358CrossRefPubMedGoogle Scholar
  13. 13.
    Collier DH, Zulman JI (1986) Hypertrophic osteoarthropathy associated with achalasia. Am J Med 81:355–360CrossRefPubMedGoogle Scholar
  14. 14.
    Suzuma T, Sakurai T, Yoshimura G, Umemura T, Tamaki T, Yoshimasu T, Naito Y (2001) Pamidronate-induced remission of pain associated with hypertrophic pulmonary osteoarthropathy in chemoendocrine therapy-refractory inoperable metastatic breast carcinoma. Anticancer Drugs 12:731–734CrossRefPubMedGoogle Scholar
  15. 15.
    Atkinson MK, McElwain TJ, Peckham MJ, Thomas PP (1976) Hypertrophic pulmonary osteoarthropathy in Hodgkin’s disease: reversal with chemotherapy. Cancer 38:1729–1734CrossRefPubMedGoogle Scholar
  16. 16.
    Frand M, Koren G, Rubinstein Z (1982) Reversible hypertrophic osteoarthropathy associated with cyanotic congenital heart disease. Am J Dis Child (1960) 136:687–689Google Scholar
  17. 17.
    Dickinson CJ, Martin JF (1987) Megakaryocytes and platelet clumps as the cause of finger clubbing. Lancet 2:1434–1435CrossRefPubMedGoogle Scholar
  18. 18.
    Letts M, Pang E, Simons J (1994) Prostaglandin-induced neonatal periostitis. J Pediatr Orthop 14:809–813PubMedGoogle Scholar
  19. 19.
    Alonso-Bartolomé P, Martínez-Taboada VM, Pina T, Blanco R, Rodriguez-Valverde V (2006) Hypertrophic osteoarthropathy secondary to vascular prosthesis infection: report of 3 cases and review of the literature. Medicine 85:183–191CrossRefPubMedGoogle Scholar
  20. 20.
    Amital H, Applbaum YH, Vasiliev L, Rubinow A (2004) Hypertrophic pulmonary osteoarthropathy: control of pain and symptoms with pamidronate. Clin Rheumatol 23:330–332CrossRefPubMedGoogle Scholar
  21. 21.
    Garske LA, Bell SC (2002) Pamidronate results in symptom control of hypertrophic pulmonary osteoarthropathy in cystic fibrosis. Chest 121:1363–1364CrossRefPubMedGoogle Scholar
  22. 22.
    Augarten A, Goldman R, Laufer J, Szeinberg A, Efrati O, Barak A, Miller MS, Yahav Y (2002) Reversal of digital clubbing after lung transplantation in cystic fibrosis patients: a clue to the pathogenesis of clubbing. Pediatr Pulmonol 34:378–380CrossRefPubMedGoogle Scholar
  23. 23.
    Taillandier J, Alemanni M, Samuel D, Bismuth H (1998) Hepatic hypertrophic osteoarthropathy: the value of liver transplantation. Clin Exp Rheumatol 16:80–81PubMedGoogle Scholar
  24. 24.
    Katsicas M, Ciocca M, Rosanova M, Russo R (2005) Hypertrophic osteoarthropathy in two children with cholestatic hepatic disease. Acta Paediatr (Oslo, Norway: 1992) 94:1152–1155CrossRefGoogle Scholar
  25. 25.
    Huaux JP, Geubel A, Maldague B, Michielsen P, de Hemptinne B, Otte JB, de Deuxchaisnes CN (1987) Hypertrophic osteoarthropathy related to end stage cholestatic cirrhosis: reversal after liver transplantation. Ann Rheum Dis 46:342–345CrossRefPubMedGoogle Scholar
  26. 26.
    Pitt P, Mowat A, Williams R, Hamilton E (1994) Hepatic hypertrophic osteoarthropathy and liver transplantation. Ann Rheum Dis 53:338–340CrossRefPubMedGoogle Scholar
  27. 27.
    Treasure T (2006) Hypertrophic pulmonary osteoarthropathy and the vagus nerve: an historical note. J R Soc Med 99:388–390CrossRefPubMedGoogle Scholar
  28. 28.
    Martinez-Lavin M, Vargas A, Rivera-Viñas M (2008) Hypertrophic osteoarthropathy: a palindrome with a pathogenic connotation. Curr Opin Rheumatol 20:88–91CrossRefPubMedGoogle Scholar
  29. 29.
    Kozak KR, Milne GL, Morrow JD, Cuiffo BP (2006) Hypertrophic osteoarthropathy pathogenesis: a case highlighting the potential role for cyclo-oxygenase-2-derived prostaglandin E2. Nat Clin Pract Rheumatol 2:452–456, quiz following 456CrossRefPubMedGoogle Scholar
  30. 30.
    Martinez-Lavin M (2007) Exploring the cause of the most ancient clinical sign of medicine: finger clubbing. Semin Arthritis Rheum 36:380–385CrossRefPubMedGoogle Scholar
  31. 31.
    Atkinson S, Fox SB (2004) Vascular endothelial growth factor (VEGF)-A and platelet-derived growth factor (PDGF) play a central role in the pathogenesis of digital clubbing. J Pathol 203:721–728CrossRefPubMedGoogle Scholar
  32. 32.
    Akizuki M, Homma M (1991) Amelioration of secondary hypertrophic osteoarthropathy following tumor resection in a patient with primary lung cancer. Ryūmachi [Rheum] 31:311–316, discussion 316–317Google Scholar
  33. 33.
    Poantă L, Parasca I, Fazakas E, Porojan M, Pais R, Boian L (2009) Paraneoplastic hypertrophic osteoarthropathy: evaluation at 25 years after pneumectomy. Pol archiwum medycyny wewnȩtrznej 119:603–606Google Scholar
  34. 34.
    Kishi K, Nakamura H, Sudo A, Kobayashi K, Yagyu H, Oh-ishi S, Matsuoka T (2002) Tumor debulking by radiofrequency ablation in hypertrophic pulmonary osteoarthropathy associated with pulmonary carcinoma. Lung Cancer (Amsterdam, Neth) 38:317–320Google Scholar
  35. 35.
    Braude S, Kennedy H, Hodson M, Batten J (1984) Hypertrophic osteoarthropathy in cystic fibrosis. Br Medical Journal (Clin Research Ed) 288:822–823CrossRefGoogle Scholar
  36. 36.
    Kaymakcalan H, Sequeria W, Barretta T, Ghosh BC, Steigmann F (1980) Hypertrophic osteoarthropathy with myogenic tumors of the esophagus. Am J Gastroenterol 74:17–20PubMedGoogle Scholar
  37. 37.
    Flavell G (1956) Reversal of pulmonary hypertrophic osteoarthropathy by vagotomy. Lancet 270:260–262CrossRefPubMedGoogle Scholar
  38. 38.
    Yacoub MH (1966) Vagotomy through mediastinoscopy for pulmonary osteoarthropathy. Br J Dis Chest 60:144–147CrossRefPubMedGoogle Scholar
  39. 39.
    Reardon G, Collins AJ, Bacon PA (1976) The effect of adrenergic blockade in hypertrophic pulmonary osteoarthropathy (HPOA). Postgrad Med J 52:170–173CrossRefPubMedGoogle Scholar
  40. 40.
    Blackwell N, Bangham L, Hughes M, Melzack D, Trotman I (1993) Treatment of resistant pain in hypertrophic pulmonary arthropathy with ketorolac. Thorax 48:401CrossRefPubMedGoogle Scholar
  41. 41.
    Leung FW, Williams AJ, Fan P (1985) Indomethacin therapy for hypertrophic pulmonary osteoarthropathy in patients with bronchogenic carcinoma. West J Med 142:345–347PubMedGoogle Scholar
  42. 42.
    Johnson SA, Spiller PA, Faull CM (1997) Treatment of resistant pain in hypertrophic pulmonary osteoarthropathy with subcutaneous octreotide. Thorax 52:298–299CrossRefPubMedGoogle Scholar
  43. 43.
    Penson RT, Rudd RM (1997) Commentary: octreotide and hypertrophic pulmonary osteoarthropathy. Thorax 52:297–298CrossRefPubMedGoogle Scholar
  44. 44.
    Penn RD, Paice JA, Kroin JS (1992) Octreotide: a potent new non-opiate analgesic for intrathecal infusion. Pain 49:13–19CrossRefPubMedGoogle Scholar
  45. 45.
    Angel-Moreno Maroto A, Martínez-Quintana E, Suárez-Castellano L, Pérez-Arellano J (2005) Painful hypertrophic osteoarthropathy successfully treated with octreotide. The pathogenetic role of vascular endothelial growth factor (VEGF). Rheumatol (Oxf, Engl) 44:1326–1327CrossRefGoogle Scholar
  46. 46.
    Speden D, Nicklason F, Francis H, Ward J (1997) The use of pamidronate in hypertrophic pulmonary osteoarthropathy (HPOA). Aust NZ J Med 27:307–310Google Scholar
  47. 47.
    King MM, Nelson DA (2008) Hypertrophic osteoarthropathy effectively treated with zoledronic acid. Clin Lung Cancer 9:179–182CrossRefPubMedGoogle Scholar
  48. 48.
    Olán F, Portela M, Navarro C, Gaxiola M, Silveira LH, Ruiz V, Martínez-Lavín M (2004) Circulating vascular endothelial growth factor concentrations in a case of pulmonary hypertrophic osteoarthropathy. Correlation with disease activity. J Rheumatol 31:614–616PubMedGoogle Scholar
  49. 49.
    Hayashi M, Sekikawa A, Saijo A, Takada W, Yamawaki I, Ohkawa S (2005) Successful treatment of hypertrophic osteoarthropathy by gefitinib in a case with lung adenocarcinoma. Anticancer Res 25:2435–2438PubMedGoogle Scholar
  50. 50.
    Hung GU, Kao CH, Lin WY, Wang SJ (2000) Rapid resolution of hypertrophic pulmonary osteoarthropathy after resection of a lung mass caused by xanthogranulomatous inflammation. Clin Nucl Med 25:1029–1030CrossRefPubMedGoogle Scholar
  51. 51.
    Lopez-Majano V, Layon J, Britt T (1982) Pulmonary hypertrophic osteoarthropathy: its modification by therapy. Eur J Nucl Med 7:419–421PubMedGoogle Scholar
  52. 52.
    Armstrong DJ, McCausland EM, Wright GD (2007) Hypertrophic pulmonary osteoarthropathy (HPOA) (Pierre Marie-Bamberger syndrome): two cases presenting as acute inflammatory arthritis. Description and review of the literature. Rheumatol Int 27:399–402CrossRefPubMedGoogle Scholar
  53. 53.
    Campeau RJ, Rosales OR, Garcia OM, Correa OA (1989) Resolution of hypertrophic pulmonary osteoarthropathy after radiotherapy in the absence of lung tumor response. Clin Nucl Med 14:453–455CrossRefPubMedGoogle Scholar
  54. 54.
    Rao GM, Guruprakash GH, Poulose KP, Bhaskar G (1979) Improvement in hypertrophic pulmonary osteoarthropathy after radiotherapy to metastasis. AJR Am J Roentgenol 133:944–946PubMedGoogle Scholar
  55. 55.
    Roos DE (1996) Hypertrophic pulmonary osteoarthropathy: is there a role for radiotherapy to symptomatic sites? Case report and literature review. Acta Oncologica (Stockh, Sweden) 35:101–103CrossRefGoogle Scholar
  56. 56.
    Albrecht S, Keller A (2003) Postchemotherapeutic reversibility of hypertrophic osteoarthropathy in a patient with bronchogenic adenocarcinoma. Clin Nucl Med 28:463–466CrossRefPubMedGoogle Scholar
  57. 57.
    Dalgleish AG (1983) Hypertrophic pulmonary osteoarthropathy: response to chemotherapy without documented tumour response. Aust NZ J Med 13:513–516Google Scholar
  58. 58.
    Evans WK (1980) Reversal of hypertrophic osteoarthropathy after chemotherapy for bronchogenic carcinoma. J Rheumatol 7:93–97PubMedGoogle Scholar
  59. 59.
    Uchiyama G, Ishizuka M, Sugiura N (1985) Hypertrophic pulmonary osteoarthropathy inactivated by antitumor chemotherapy. Radiat Med 3:25–28PubMedGoogle Scholar
  60. 60.
    Vickers C, Herbert A, Neuberger J, Elias E (1988) Improvement in hypertrophic hepatic osteoarthropathy after liver transplantation. Lancet 2:968CrossRefPubMedGoogle Scholar
  61. 61.
    Shapiro LM, Mackinnon J (1980) The resolution of hypertrophic pulmonary osteoarthropathy following treatment of subacute infective endocarditis. Postgrad Med J 56:513–515CrossRefPubMedGoogle Scholar
  62. 62.
    Dam WH, Hagelsten JO (1964) Blocking of the vagus nerve relieving osteoarthropathy in lung diseases. Dan Med Bull 11:131–133PubMedGoogle Scholar
  63. 63.
    DINER WC (1962) Hypertrophic osteoarthropathy. Relief of symptoms by vagotomy in a patienh qihh pulmonary metastases from a lympho-epithelioma of the nasopharynx. JAMA, J Am Med Assoc 181:555–557Google Scholar
  64. 64.
    Mauricio O, Francis L, Athar U, Shah C, Chaudhary M, Gajra A (2009) Hypertrophic osteoarthropathy masquerading as lower extremity cellulitis and response to bisphosphonates. J Thoracic Oncology: Official Publication Int Assoc Study Lung Cancer 4:260–262Google Scholar
  65. 65.
    Slobodin G, Rosner I, Feld J, Rimar D, Rozenbaum M, Boulman N, Odeh M (2009) Pamidronate treatment in rheumatology practice: a comprehensive review. Clin Rheumatol 28:1359–1364CrossRefPubMedGoogle Scholar

Copyright information

© Clinical Rheumatology 2010

Authors and Affiliations

  1. 1.University of Minnesota Medical SchoolMinneapolisUSA
  2. 2.Department of Medicine, Division of Rheumatic and Autoimmune DiseasesUniversity of MinnesotaMinneapolisUSA
  3. 3.Medicine Rheumatology OfficeUniversity of MinnesotaMinneapolisUSA

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