eMedicine Specialties > Radiology > Musculoskeletal

Hypertrophic Osteoarthropathy

Author: Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR, LRCP, Chairman of Medical Imaging, Professor of Radiology, NGHA, King Fahad National Guard Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia
Coauthor(s): Mohammed Jassim Al-Salman, MBBS, Consulting Radiologist, King Abdul Aziz Medical City, National Guard Hospital; Dare Mutiyu Seriki, MBBS, FRCR, MRCP, Staff Physician, Department of Radiology, Hope Hospital, UK; Ian Turnbull, MB, ChB, MD, DMRD, FRCR, Lecturer, Department of Radiology, University of Manchester; Consulting Neuroradiologist, Hope Hospital, Salford, Manchester and North Manchester General Hospital, UK; Sumaira MacDonald, MBChB, PhD, MRCP, FRCR, Lecturer, Sheffield University Medical School; Endovascular Fellow, Sheffield Vascular Institute
Contributor Information and Disclosures

Updated: Jul 23, 2008

Introduction

Background

Hypertrophic osteoarthropathy (HOA) is a clinical syndrome of clubbing of the fingers and toes, enlargement of the extremities, and painful, swollen joints. HOA is characterized by symmetric periostitis involving the radius and fibula and, to a lesser extent, the femur, humerus, metacarpals, and metatarsals. The syndrome can be primary or secondary.

Primary HOA, or pachydermoperiostosis, is a rare familial autosomal dominant condition. Approximately 3-5% of patients with HOA have primary HOA. The remaining 95-97% have secondary HOA, or hypertrophic pulmonary osteoarthropathy (HPOA). The term HPOA emphasizes the pulmonary problems that represent a major cause of periostitis, although conditions other than pulmonary disorders may cause HPOA. HPOA is a syndrome in which clubbing of fingers and toes, arthritis, and periostitis occur.^1,2,3,4

Pathophysiology

The precise etiology of primary hypertrophic osteoarthropathy (primary HOA, pachydermoperiostosis) is unclear, but the disease has an autosomal dominant genetic mode of transmission. It is more common in males. Finger clubbing is the result of the proliferation of fibroelastic tissue in the nailbed; subsequently, more extensive thickening of the skin and subcutaneous tissues of the digits may occur.

Numerous theories have been proposed regarding the pathogenesis of hypertrophic pulmonary osteoarthropathy (HPOA), none of which are generally accepted. An increase in peripheral blood supply may play a role. Chemical irritants and toxic substances, which initiate a periosteal response, have also been implicated. The humoral theory posits a possible role for steroids. A neurogenic mechanism has been postulated; in this model, the increase in blood supply is caused by an interruption of the vagal nerve.

Most imaging studies and histologic examinations of clubbed fingers reveal hypervascularization of the distal digits. Studies have shown that when platelet precursors fail to fragment within the pulmonary circulation, they easily become trapped in the peripheral vasculature. Platelet-derived growth factor and vascular endothelial growth factor are then released; these growth factors promote vascularity, which may eventually lead to clubbing.⁵

Secondary causes of HPOA may be further classified as pulmonary, pleural, cardiac, abdominal, and miscellaneous. Pleural causes include pleural fibroma and mesothelioma. Cyanotic heart disease with a right-to-left shunt is the only cardiac cause that has been described.

Pulmonary disorders that cause HPOA include bronchogenic carcinoma; pulmonary tuberculosis; pulmonary abscesses; blastomycosis; bronchiectasis; emphysema; Pneumocystis carinii infection in patients with AIDS; Hodgkin disease; metastases; and cystic fibrosis. Abdominal disorders that cause HPOA include liver cirrhosis, ulcerative colitis, Crohn disease, amebic and bacillary dysentery, gastrointestinal tract polyposis, gastrointestinal tract neoplasms (gastric and pancreatic), lymphoma of the bowel, Whipple's disease, and biliary atresia. Miscellaneous causes include infected aortic or axillary artery grafts, tumors of the ribs, and nasopharyngeal and esophageal carcinoma. One case resulting from each of these miscellaneous causes has been reported, in association with sarcoidosis in an adult and with malignant thymoma in a child.

HPOA is occasionally associated with nasopharyngeal lymphoepitheliomas; in these cases, HPOA may develop before or after the development of lung metastases.

An association of primary HOA with myelofibrosis has been described.^6,7

Frequency

United States

Primary hypertrophic osteoarthropathy (primary HOA, pachydermoperiostosis) is rare. Hypertrophic pulmonary osteoarthropathy (HPOA) occurs in approximately 4-17% of patients with bronchogenic carcinoma and 20-35% of patients with pleural mesothelioma. The frequency of HPOA is also increased in patients with peripheral lung tumors and in those with tumors of squamous origin.

International

The international frequency of hypertrophic osteoarthropathy is similar to that in the United States.

Mortality/Morbidity

• Primary hypertrophic osteoarthropathy (primary HOA, pachydermoperiostosis) may have an insidious onset involving the hands and feet. It usually progresses for 10 years before arresting spontaneously.
• Complications include stiffness and restricted motion in the axial and appendicular skeleton; kyphosis; and neurologic manifestations caused by osseous compression of the spinal cord, nerve roots, and cranial nerves.
• Life expectancy of patients with HOA is similar to that in persons without HOA.

Race

• Primary hypertrophic osteoarthropathy (primary HOA, pachydermoperiostosis) is more common in blacks than in whites.
• Hypertrophic pulmonary osteoarthropathy (HPOA) has no racial predominance because it is caused by an underlying pathology.

Sex

• Primary hypertrophic osteoarthropathy (primary HOA, pachydermoperiostosis) is predominant and more severe in men than in women.
• Hypertrophic pulmonary osteoarthropathy (HPOA) has no sex predominance.

Age

• Primary hypertrophic osteoarthropathy (primary HOA, pachydermoperiostosis) usually occurs in adolescents, but it can affect prepubescents as well.
• Persons aged 3-38 years are affected, with progression of the disease late into the 20s and 30s.
• Hypertrophic pulmonary osteoarthropathy (HPOA) can occur in persons of any age.

Presentation

Primary hypertrophic osteoarthropathy (primary HOA, pachydermoperiostosis)

The clinical manifestations of patients with primary HOA vary. The manifestations include those of the complete form (pachydermia, periostitis, cutis vertices gyrata) and those of the incomplete form (sparing of the scalp, forme fruste, pachydermia with minimal or absent periostitis). Enlargement of the hands and feet, clubbing of the distal fingers and toes, coarsening of the skin of the face and scalp with ptosis, furrowing and oiliness of cutaneous tissue, excessive sweating, fatigability, pain in bones and joints, hepatosplenomegaly anemia, and endocrine abnormalities may be seen.

Hypertrophic pulmonary osteoarthropathy (HPOA)

The clinical manifestations of HPOA are not uniform. Not unexpectedly, they depend on the underlying lesion.

HPOA caused by a pulmonary neoplasm is associated with an acute onset of digital clubbing and warmth and burning of the fingertips, occasionally with skin thickening and hyperhidrosis. Other types of HPOA may be characterized by an insidious onset of digital clubbing, arthritis, and skin thickening. In HPOA, digital clubbing is common but not inevitable. The presence of clubbing does not constitute the full syndrome. Initially, the fibroelastic tissue in the nailbed thickens. This is followed by increased fluctuance, prominence, striations, shininess, and increased curvature of the nail.

Limb skin thickening may also occur. Articular signs and symptoms are apparent in 30-40% of patients at some time; these signs and symptoms may be the presenting manifestations. Pain and tenderness occur in many joints; these symptoms are usually more severe during the night and are exacerbated by movement. The knees, ankles, wrists, elbows, and metacarpophalangeal joints are most often involved. Involvement of the joints is usually symmetric, with synovial effusions. This finding may resemble rheumatoid arthritis.

Preferred Examination

Plain radiography is the mainstay of radiology-aided diagnosis, although the exact sensitivity of plain radiography is unknown. Nuclear medicine studies reveal early evidence of disease. Its sensitivity is greater than that of other modalities. The role of MRI is currently exploratory; information regarding its use is anecdotal. CT is useful in elucidating the cause of hypertrophic pulmonary osteoarthropathy (HPOA), such as intrathoracic pathology or infected vascular grafts.^8,9,10

Limitations of Techniques

Neither radiographic results nor radionuclide findings are specific for hypertrophic osteoarthropathy (HPOA), and the differential diagnosis includes many entities. However, a specific diagnosis can usually be achieved with clinical input.

Differential Diagnoses

Caffey Disease
Fibrous Dysplasia
Paget Disease

Other Problems to Be Considered

Primary hypertrophic osteoarthropathy (primary HOA, pachydermoperiostosis)

Congenital syphilis
Diaphyseal dysplasia (Camurati-Engelmann disease)
Infantile cortical hyperostosis
Caffey disease
Hypervitaminosis A

Hypertrophic pulmonary osteoarthropathy (HPOA)

Acromegaly
Thyroid acropachy
Venous stasis
Endosteal hyperostosis (van Buchem disease)
Macrodystrophia lipomatosa
Proteus syndrome
Paget disease
Fibrous dysplasia

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