Polyarthritis is a relatively common complaint in both outpatient and inpatient settings. The patient in this case presented with polyarthritis that did not respond to NSAIDs and was diagnosed with hypertrophic osteoarthropathy secondary to Non-small-cell lung cancer. Different from most rheumatologic diseases, the evidence shows that steroids are not beneficial in this condition and the main treatment is tumor resection. Bisphosphonates are an option in non-operative candidates.

This case highlights the importance of having a high index of suspicion for malignancy in certain patient populations, but also the importance of ordering chest imaging in patients presenting with arthritic symptoms of unclear cause. This patient did not have chest imaging until day two of hospitalization since he did not have respiratory or chest symptoms.

Hypertrophic osteoarthropathy (HOA) is a rare paraneoplastic disease that can be extremely debilitating and usually resolves with treatment of the underlying lung pathology or with bisphosphonates. It develops due to underlying pulmonary pathology, most commonly a malignancy [1]. Eighty percent of cases are caused by a paraneoplastic syndrome, more commonly by non-small-cell lung cancer and less often by small-cell lung cancer [2]. The remaining 20% of cases can be caused by chronic respiratory disease, congenital cyanotic heart disease, chronic inflammation, or congenital pachydermoperiostosis [3,4]. It is sometimes the first sign of malignancy, so physicians should maintain a high index of suspicion when encountered with sudden arthritis, especially in a smoker [5,6].

Currently, three theories prevail regarding the pathophysiology of HOA. First, the neurogenic theory proposes direct nerve involvement. As early as 1965, several case reports were published of symptom relief following vagotomy on the side of the tumor [7–9]. The second theory, the mechanical hypothesis, proposes arteriovenous shunting within the pulmonary system to be the main culprit. Pulmonary capillaries are normally responsible for the degradation of inflammatory cytokines. With AV shunting secondary to chronic hypoxia, vasoactive compounds are not degraded in the pulmonary endothelium and instead are released systemically, leading to increased inflammation, tissue hypoxia, and peripheral clubbing, as well as pain [10].

The third theory is currently the most widely accepted and supported by evidence. Named the biochemical hypothesis, it posits increased systemic inflammation as a direct result of biochemical compound release from the primary tumor. Multiple studies have demonstrated elevated levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) in patients with HOA, even when compared to other patients with chronic lung disease [11,12]. VEGF and PDGF are both pro-inflammatory cytokines which increase vascular permeability, cell permeability, angiogenesis, and bone formation. Tumor production of these cytokines is thought to lead to widespread inflammation, connective tissue, and bone proliferation, and the symptoms of HOA. In one study, removal of the lung tumor resulted in normalization of VEGF and PDGF levels and a remission of symptoms [13].

HOA is important to recognize because the treatment of the primary tumor often leads to rapid improvement in symptoms. In some cases, the improvement was seen in as little as 24 h to 2 weeks [14]. In the case of a debilitated patient who cannot tolerate surgery or chemotherapy, palliative treatment with bisphosphonates and octreotide is an option. However, the best treatment is cure of the underlying malignancy.