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
- Cancer of the Lung and Bronchus - Cancer Stat Facts. SEER. Accessed
August 25, 2022.
https://seer.cancer.gov/statfacts/html/lungb.html
- 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
- 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
- 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
- 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
- Martínez-Lavín M. Hypertrophic osteoarthropathy. Best Pract Res
Clin Rheumatol . 2020;34(3):101507.
doi:10.1016/j.berh.2020.101507
- 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
- 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
- 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
- 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
- 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
- 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.
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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