1 Introduction

Paraneoplastic rheumatic manifestations are vascular immune-mediated and musculoskeletal conditions that arise due to the presence of underlying malignancy. The secondary form of hypertrophic pulmonary osteoarthropathy (HPOA) is one such paraneoplastic rheumatic manifestation which can be associated with pulmonary malignancy, among a diverse array of conditions involving the lungs, pleura, mediastinum, and the digestive system.¹ This rare condition presents with digital clubbing, periostitis of tubular bones, and non-inflammatory arthritis of large joints in the setting of a pulmonary condition, most commonly malignancy.²

2 Case report

This is the case of a 63 year old man with no known past medical history, as he had gone 40 years without seeing a provider, who presented to the emergency department for acute on chronic dyspnea and dysphagia. The patient reported having these symptoms of dyspnea on exertion and dysphagia for the past year with episodes occurring intermittently, but acutely worsening over the last week. Secondarily, the patient expressed increasing difficulty accomplishing activities of daily living which were limited by both his shortness of breath and increasing bilateral knee pain.

He was a smoker of 2.5 packs per day for 35 years, admitted to drenching night sweats for the last year and a half, and 30 pounds of unintentional weight loss over the previous year. Most notably on physical exam, the patient was found to have decreased breath sounds of the right middle and lower lobes, as well as clubbing of all 10 upper extremity digits.

Radiographs of the chest (Fig. 1) were performed which displayed a large right lung mass extending from the hilar region, which was particularly concerning for malignancy given the patients history. A CT scan of the chest (Fig. 2) was then performed which identified a large heterogeneous hilar mass predominantly in the right lower lobe, extending into the right middle and right upper lobes measuring approximately 10.4cm by 10.4cm. Bronchoalveolar lavage of the right middle lobe was performed, indicating the presence of malignant epithelial cells on the cytology report.

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Fig. 1 A: Fig. 1 B: Anteroposterior and lateral chest radiographs displaying a large right lung mass extending from the hilar region.

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Fig. 2 A: Fig. 2B: Fig. 2C: CT scan of the lungs reveal a large heterogeneous hilar mass predominantly in the right lower lobe, extending into the right middle and right upper lobes. The mass measured approximately 10.4cm by 10.4cm.

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The patient had bilateral radiographs of his knees (Fig. 3) taken during his admission due to his increasing knee pain. These radiographs showed bilateral, non-aggressive appearing periosteal reactions along the distal femur with no changes seen in the tibia or fibula. No signs of significant arthritic change, acute or healing fractures, or joint effusion were present in these radiographs. Based on this constellation of symptoms: bilateral, non-aggressive periosteal reactions of the upper leg with sparing of the lower leg, in the setting of lung malignancy and digital clubbing, a diagnosis of hypertrophic pulmonary osteoarthropathy secondary to lung malignancy was made as the cause of the patient's knee pain.

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Fig. 3 A: Fig. 3B: Anteroposterior and lateral radiographs were taken of the right and left knees. All images revealed non-aggressive appearing periosteal reactions along the distal femur. Osteopenia with no signs of acute healing fractures were noted. No evidence of joint effusion, arthritic changes.

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3 Discussion

There are two forms of hypertrophic osteoarthropathy (HOA), the secondary form as presented in this case study and a primary, idiopathic form of HOA also termed pachydermoperiostosis. The primary form of this condition is much less common, consisting of only 3–5% of all HOA cases and presenting around the time of puberty as the result of an inherited autosomal dominant trait without underlying disease.³ To avoid confusion between the two forms, the rest of the discussion will be restricted to hypertrophic pulmonary osteoarthropathy (HPOA), the secondary form of this condition.

HPOA is a condition which is characterized by hypertrophic osteoarthropathy (HOA) secondary to underlying pulmonary disease.² The majority of cases of HPOA arise secondary to paraneoplastic syndromes, with studies showing this occurring at a rate of over 80%.^4,5 Of these cases, adenocarcinoma is the most common form of malignancy with small cell carcinoma being the least common.⁶ In a retrospective study of 6151 lung cancer patients, 115 (1.87%) demonstrated characteristics that were identified as HPOA.⁷ Chronic infections have also been associated with HOA, such cystic fibrosis, subacute bacterial endocarditis, syphilis, acquired immunodeficiency syndrome, pulmonary tuberculosis, and even vascular graft infections.^8–13 Currently, the underlying pathophysiology of this systemically mediated HOA is poorly understood and likely multifactorial.

Clinically, patients with HPOA present with digital clubbing, painful swelling and tenderness of the extremities with adjacent joint pain, joint effusions, and periosteal reactions of the tubular bones of the extremities, all typically in the setting of pulmonary disease.¹ The pain is a non-inflammatory large joint pain that is typically resistant to analgesic medication. HOA tends to be more pronounced distally with common involvement of the hands, feet, knees and elbows, with rare involvement of the shoulders and hips. When diagnosing these patients, it is important to have high clinical suspicion for HPOA, as the symptoms of HOA may precede those of an underlying pulmonary condition.

On radiographic imaging, as seen in Fig. 3, the tubular long bones of the appendicular skeleton will display a symmetric, bilateral non-aggressive appearing periosteal reaction. This bilateral periostitis of the appendicular skeleton is the hallmark of HPOA, and when seen, should raise suspicion for this condition. Bilateral periostitis is seen in a small number of conditions, including juvenile idiopathic arthritis, hypervitaminosis A, and venous stasis which should all be ruled out with physical examination and laboratory testing.

The use of radionuclide bone scintigraphy has also been reported in literature, with HPOA having the characteristic features of diffuse, symmetrically increased uptake along cortical margins of the diaphysis of tubular bones, which is described as the “parallel tract” or “double stripe” sign.¹⁴ Notably, uptake may also be seen in the distal phalanges and juxta-articular to long bones due to digital clubbing and synovitis respectively. In a series of 48 cases in which radionuclide bone scintigraphy was performed, bones of the extremities exhibited typical changes of HPOA in every case, though asymmetric and irregular involvement of long bones was see in rare cases.¹⁴

Treatment for HPOA revolves primarily around treatment of the underlying cause. In many cases, clinical symptoms may regress upon removal of causative lung cancer or treatment of other causative condition, though this is not always effective.^15,16 In cases in which treatment of the primary condition alone is ineffective, bisphosphonates have been reported to be an effective second line therapy.^17,18

4 Conclusion

Although hereditary pulmonary osteoarthropathy is a relatively rare condition, it should be considered in the setting of bilateral, symmetric periostitis of long bones, digital clubbing, and pulmonary malignancy. This case is an excellent example of the classic presentation of symptoms seen in HPOA. Though as a condition that can, on occasion, present with musculoskeletal symptoms and digital clubbing prior to the symptoms of pulmonary neoplasm, a high index of clinical suspicion is warranted. In these rare cases, early work-up and identification of the underlying cause is of utmost importance.

Funding declaration

The authors received no financial support for the research, authorship, and/or publication of tthis aricle.

Author contribution statement

The authors confirm contribution from all authors in the conception of this manuscript. All authors reviewed and approved the final version of the manuscript.

Informed patient consent

Complete informed consent was obtained from the patient for the publication of this study and accompanying images.