Discussion
HOA is a syndrome with stages in the disease process, most often starting with clubbing of fingers and progressing to other symptoms such as joint pain, periostosis, etc.6 These symptoms can differ in severity from patient to patient, making the diagnosis of HOA challenging.6 There are several proposed theories on the pathogenesis of HOA; the exact physiology still remains unclear. One popular theory includes release of platelet derived growth factors (PDGF), prostaglandin E, and vascular endothelial growth factor (VEGF) by megakaryocytes that have bypassed the pulmonary capillary network.7 These growth factors lead to fibroblast proliferation, distal clubbing, vascular hyperplasia, and new bone formation. Patients with HOA have been shown to have significantly higher levels of PDGF and VEGF.7 Although the diagnosis is a clinical one, bone scintigraphy is a useful adjunctive for detection. Characteristic findings on scintigraphy include bilateral increased uptake in long bones, with periostitis being the hallmark of hypertrophic pulmonary osteoarthropathy.8
Various treatments of HOA have been studied, however, treatment with surgical resection of the primary tumor results in rapid long-term remission of symptoms.9 This was evident in our case with almost complete resolution of our patient’s joint pain and swelling during her 1 week follow up. Other treatments that have shown to provide relief in HPO include bisphosphonates10 and octreotide11. One case was also treated with an EGFR inhibitor, gefitinib.12 It is important to understand that conventional analgesics, including NSAIDs have limited efficacy on HOA. Utilizing these alternative medications for refractory cases of HOA can help symptomatic relief in many patients.
HOA can also be a sign of a multitude of different organ systems being affected which makes this a syndrome that all physicians should be aware of. According to the study by Martinez-Lavin, the majority of cases will only show manifestations of clubbing in the fingers.6However, although the patient in this report did have clubbing in her fingers during examination, her main complaint, and first to manifest, was the migratory arthritis. This presentation of arthritic pain in her left knee is unusual to appear prior to clubbing of her fingers and the length of time from onset of arthritis to respiratory symptoms are unusual. This patient presentation stresses the importance of always having lung cancer on the differential diagnosis in the setting of any symptom associated with HOA. It also shows monoarthritis that spread to other joints is a potential symptom heralding adenocarcinoma of the lung.
References
  1. Cancer of the Lung and Bronchus - Cancer Stat Facts. SEER. Accessed August 25, 2022. https://seer.cancer.gov/statfacts/html/lungb.html
  2. CDCBreastCancer. An Update on Cancer Deaths in the United States. Centers for Disease Control and Prevention. Published February 28, 2022. Accessed August 25, 2022. https://www.cdc.gov/cancer/dcpc/research/update-on-cancer-deaths/index.htm
  3. Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. Lung Cancer. In: Harrison’s Manual of Medicine . 20th ed. McGraw-Hill Education; 2020. Accessed August 25, 2022. accessmedicine.mhmedical.com/content.aspx?aid=1167064169
  4. Poddar K, Pathikonda L, Villamil M. Sudden onset polyarthritis as a paraneoplastic syndrome from non-small cell lung cancer. Journal of Community Hospital Internal Medicine Perspectives . 2020;10(2):174-178. doi:10.1080/20009666.2020.1749503
  5. Cantini F, Niccoli L, Nannini C, et al. Isolated knee monoarthritis heralding resectable non-small-cell lung cancer. A paraneoplastic syndrome not previously described. Annals of the Rheumatic Diseases . 2007;66(12):1672-1674. doi:10.1136/ard.2007.075333
  6. Martínez-Lavín M. Hypertrophic osteoarthropathy. Best Pract Res Clin Rheumatol . 2020;34(3):101507. doi:10.1016/j.berh.2020.101507
  7. Davis MC. Hypertrophic Osteoarthropathy as a Clinical Manifestation of Lung Cancer. Number 5 / October 2011 . 1969;15(5):561-563. doi:10.1188/11.CJON.561-563
  8. Ito T, Goto K, Yoh K, et al. Hypertrophic Pulmonary Osteoarthropathy as a Paraneoplastic Manifestation of Lung Cancer. Journal of Thoracic Oncology . 2010;5(7):976-980. doi:10.1097/JTO.0b013e3181dc1f3c
  9. Albrecht S, Keller A. Postchemotherapeutic Reversibility of Hypertrophic Osteoarthropathy in a Patient with Bronchogenic Adenocarcinoma. Clinical Nuclear Medicine . 2003;28(6):463-466. doi:10.1097/01.RLU.0000067504.35952.10
  10. King MM, Nelson DA. Hypertrophic Osteoarthropathy Effectively Treated with Zoledronic Acid. Clinical Lung Cancer . 2008;9(3):179-182. doi:10.3816/CLC.2008.n.027
  11. Angel-Moreno Maroto A, Martínez-Quintana E, Suárez-Castellano L, Pérez-Arellano JL. Painful hypertrophic osteoarthropathy successfully treated with octreotide. The pathogenetic role of vascular endothelial growth factor (VEGF). Rheumatology . 2005;44(10):1326-1327. doi:10.1093/rheumatology/keh720
  12. Hayashi M, Sekikawa A, Saijo A, Takada W, Yamawaki I, Ohkawa SI. Successful treatment of hypertrophic osteoarthropathy by gefitinib in a case with lung adenocarcinoma. Anticancer Res . 2005;25(3c):2435-2438.
  13. Murton AJ, Maddocks M, Stephens FB, Marimuthu K, England R, Wilcock A. Consequences of Late-Stage Non–Small-Cell Lung Cancer Cachexia on Muscle Metabolic Processes. Clinical Lung Cancer . 2017;18(1):e1-e11. doi:10.1016/j.cllc.2016.06.003
  14. Lommatzsch M, Julius P, Lück W, Bier A, Virchow JC. Das Marie-Bamberger-Syndrom als Fingerzeig auf ein NSCLC: vier Fälle im Lichte der aktuellen Literatur. Pneumologie . 2012;66(02):67-73. doi:10.1055/s-0031-1291476
  15. McCormick JP, Trueick R, Connaughton J, McDonnell N. First recurrence of small cell lung cancer presenting as subacute monoarticular arthritis. BMJ Case Reports CP . 2021;14(8):e243382. doi:10.1136/bcr-2021-243382
  16. Zhang L, Zhao Q, Yuan F, Liu M. Lung cancer in patients with and without rheumatoid arthritis: A propensity score-matched survival analysis cohort study. Thoracic Cancer . 2020;11(6):1406-1413. doi:10.1111/1759-7714.13388
  17. Ong SK, Li X, Chen T. More Than Knee Pain: A Case of Hypertrophic Osteoarthropathy Secondary to Lung Cancer. Journal of Emergency Medicine . 2020;59(5):e179-e181. doi:10.1016/j.jemermed.2020.04.028
  18. Mellemkjær L, Linet MS, Gridley G, Frisch M, Møller H, Olsen JH. Rheumatoid arthritis and cancer risk. European Journal of Cancer . 1996;32(10):1753-1757. doi:10.1016/0959-8049(96)00210-9
  19. Birch E, Jenkins D, Noble S. Treatment of painful hypertrophic osteoarthropathy associated with non-small cell lung cancer with octreotide: a case report and review of the literature. BMJ Supportive & Palliative Care . 2011;1(2):189-192. doi:10.1136/bmjspcare-2011-000052
  20. Kanaji N, Watanabe N, Kita N, et al. Paraneoplastic syndromes associated with lung cancer. World J Clin Oncol. 2014;5(3):197-223. doi:10.5306/wjco.v5.i3.197