Syndrome characterized by abnormal proliferation of skin and osseous tissues at distal parts of the extremities causing clubbing and/or boney pain due to periostosis. Occasionally, synovial effusion of larger joints can also be present.
Primary HOA is an autosomal dominant trait with variable expression which is seen nine times more in boys than in girls in a bimodal distribution. Most patients are symptomatic in their first year of life and during puberty, but become asymptomatic as adults. Features include more disseminated skin findings such as coarsening of facial features, hypertrophy of skin. Primary HOA is less associated with pain.
Secondary HOA is either generalized or localized. The localized form results from some form of prominent endothelial injury resulting in painful swelling with associated periostosis and to a lesser degree clubbing of the affected extremity. Arterial aneurysm, infective arteritis including endocarditis or infected AV fistulas, hemiplegia and cardiac shunts such as patent ductus arteriosus are most common etiologies of secondary HOA.
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Generalized secondary HOA is the most common form of HOA and is associated with other medical conditions, most importantly primary or metastatic lung cancer or any other intrathoracic malignancy. However, many non-malignant pulmonary (cystic fibrosis, pulmonary fibrosis, chronic pulmonary infections including lung abscesses, and bronchiectasis), cardiac (infective endocarditis, congenital cyanotic diseases), hepatic (hepatocellular carcinoma, cirrhosis, hepatopulmonary syndrome), gastrointestinal (Crohn’s disease, ulcerative colitis, chronic infections, gastrointestinal malignancy), mediastinal (thymoma, esophageal carcinoma), endocrine (hyperthyroidism especially in Grave’s disease), and hematologic (thalassemias and other hemoglobinopathies) causes should be considered in the differential diagnosis as the underlying cause.
Any patient with clubbing, especially new clubbing, should have further evaluation to mainly rule out an intrathoracic malignancy. Baseline chest X-ray should be obtained on all of these patients. For patients complaining of boney pain, plain radiograph of the affected extremity should be diagnostic for evaluation of periostosis.
Since primary or metastatic lung cancer is the most frequent etiology of HOA, a thorough history regarding lung cancer risk factors including smoking history, asbestos and other environmental exposures should be obtained. HOA is mostly associated with bronchogenic adenocarcinomas and pleural tumors, and least associated with small cell carcinoma. Additionally, review of systems should elicit constitutional symptoms concerning for malignancy or chronic infection including weight loss, night sweats and fever.
Advanced clubbing of the distal digits should be easily detected on routine physical examination. However, in early clubbing the diagnosis can be difficult. Two objective measures for detecting clubbing are the phalangeal depth ratio (PDR) and the digital index, which are not commonly used maneuvers due to need for instruments for different measurements. Instead, the Shamroth Window Test is more commonly used to detect early clubbing although the validity of this test has not been well established.
Periostosis is associated with a burning and deep-seated aching pain of the affected extremity that can be exacerbated by palpation of the involved area of bone or with dependent position of the limb. Pain is improved with elevation of the affected extremity.
Although periostosis can be detected on bone scan, plain X-ray of the affected extremities should show typical lifting of the periosteum of long bones suggestive of new periosteal bone formation. As above, plain chest X-ray should be obtained to evaluate for intrathoracic malignancy or other process associated with HOA.
Primary HOA is a diagnosis of exclusion given its rare incidence. Both clubbing and radiographic evidence of periostosis of tubular bones is required for diagnosis of secondary HOA. However, presence of synovial effusion is not essential for diagnosis.
Bone scanning in setting of clear evidence of periostosis on plain radiographs will not add additional information.
Treatment of the primary etiology of HOA, such as resection of tumor, chemotherapy, radioablation or treatment of infection, has been shown to have the highest success rate and can reverse hypertrophic osteoarthropathy.
Different symptomatic treatments have been proposed in cases where primary treatment is not possible. The two mainstay modalities that have been shown to relieve pain symptoms related to HOA are non-steroidal anti-inflammatory drugs (NSAIDS) and cyclooxygenase-2 (COX-2) inhibitors as well as bisphosphonates such as pamidronate or zoledronic acid which are potent inhibitors of osteoclastic bone resorption. Octreotide and vagotomy have been used to treat HOA-associated pain with varying success and are generally reserved for resistant cases.
Jayakar, BA,, Abelson, AG,, Yao, Q.. “Treatment of Hypertrophic Osteoarthropathy with Zolendronic Acid: Case Report and Review of the Literature.”. Semin Arthritis Rheum. vol. 41. 2011. pp. 291-296.
Nguyen, S,, Hojjati, M. (Even though the exact pathophysiology of hypertrophic osteoarthropathy is still not known, several pharmacologic modalities have shown improvement of the pain syndrome associated with HOA. Bisphosphonates have emerged as the mainstay of secondary treatment with possible improved efficacy of zoledronic acid over pamidronate. Postulated mechanisms of action of bisphosphonates in the treatment of secondary HOA are inhibition of osteoclastic bone resorption and decrease in levels of plasma vascular endothelial growth factor (VEGF) which may play a role in the development of HOA. More research in elucidating the role of VEGF inhibitors is needed.)
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