Hypertrophic Osteoarthropathy: A Secondary Manifestation of Malignant Melanoma

Background Hypertrophic osteoarthropathy (HOA) is a rare finding in the setting of metastatic melanoma. A majority of cases of secondary HOA involve lung malignancies. Evaluation of presenting symptoms such as polyarthralgia and clubbing followed by review of imaging studies are diagnostic steps for HOA. Case Presentation. We present a 60-year-old female with a history of metastatic melanoma who presented with bilateral and symmetric polyarthralgia and clubbing. A plain film radiograph demonstrated periosteal thickening involving the metacarpals and proximal phalanges as well as the distal radius and ulna, consistent with HOA. The patient was treated with nonsteroidal anti-inflammatory agents for supported care. Conclusion HOA may be a secondary manifestation of metastatic melanoma. Recognition and supportive care of this condition may lead to improved quality of life for patients.


Introduction
Hypertrophic osteoarthropathy (HOA) is characterized by digital clubbing, periostosis, and arthralgia of extremities.
is condition is secondary to abnormal proliferation of osseous and soft tissue.
ere are two forms of HOA: a primary genetic form, which accounts for approximately 3% of cases, and a secondary form, mainly attributed to paraneoplastic syndrome from non-small cell lung cancer and to a lesser degree, from pulmonary diseases such as sarcoidosis, pulmonary tuberculosis, and cystic fibrosis [1,2]. e proposed pathophysiology involves the release of plateletderived growth factor and vascular endothelium-derived growth factor [3]. ese growth factors lead to increased bone production and vascular hyperplasia, which leads to clinical signs of digital clubbing.

Case Presentation
We present the case of a 60-year-old female with a medical history of B-RAF wild-type metastatic melanoma with metastasis to the liver and lung, presenting with swelling over the fingers and toes. e patient reported the presence of edema for years and was told it was related to an autoimmune condition given a previously positive ANA result. e patient stated that the swelling was also associated with symmetric polyarthralgia of the upper and lower extremities. She denied any alleviating or aggravating factors. On physical exam, clubbing was present on bilateral distal phalanges ( Figure 1). Additionally, when placing the pads of bilateral terminal phalanges in dorsal opposition, disappearance of the normal diamond-shaped window was found, indicating a positive Schamroth sign (Figure 2). e patient underwent lab work, which revealed an alkaline phosphatase level of 146.
Plain film radiography of the upper extremities demonstrated periosteal thickening involving the metacarpals and proximal phalanges as well as the distal radius and ulna, consistent with hypertrophic osteoarthropathy (Figure 3). Given patient's terminal malignancy, no further oncological or surgical treatments were available. e patient was started on a nonsteroidal anti-inflammatory agent, ibuprofen, for symptomatic relief. She demonstrated significant improvement of arthralgias during her three-week follow-up. e patient went on to hospice care and shortly passed.

Discussion
e proposed pathophysiology of HOA involves the release of platelet-derived and vascular endothelium-derived growth factors. e exact mechanism of disease in HOA is uncertain. is diagnosis should be considered in the setting of clubbing with imaging findings supportive of periosteal thickening. In the setting of HOA with no underlying cause, a plain film radiograph of the chest should be indicated to rule out pulmonary etiology [3]. ere are no specific or reliable lab tests available for the diagnosis of HOA. A plain radiograph is the most telling diagnostic modality for HOA. e presence of periosteal thickening is the most specific radiographic finding associated with HOA. is finding may be generalized to include more than one specific region of the bone or localized to a specific site of the bone [4,5].
Treatment of the underlying disease process is key for secondary HOA. Supportive care with nonsteroidal antiinflammatory agents as well as bisphosphonates may provide relief. VEGF inhibitors have also been proposed as therapeutic options for alleviating pain symptoms in secondary HOA [6].
is case exhibits the importance of both, a thorough clinical history and physical examination.
is diagnosis should be considered in patients presenting with polyarthralgia and appropriate imaging findings. Early diagnosis of this condition combined with appropriate management and therapy may result in improved quality of life for affected patients.

Data Availability
All data in this case report are taken from the clinical records.

Conflicts of Interest
e authors declare no conflicts of interest.    Case Reports in Rheumatology