You are in: eMedicine Specialties > Radiology > MUSCULOSKELETAL Hypertrophic OsteoarthropathyArticle Last Updated: Jul 23, 2008AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  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 Ali Nawaz Khan is a member of the following medical societies: American Institute of Ultrasound in Medicine, Radiological Society of North America, Royal College of Physicians, Royal College of Physicians and Surgeons of the United States, Royal College of Radiologists, and Royal College of Surgeons of England 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, MD, Lecturer, Department of Radiology, University of Manchester; Consulting Neuroradiologist, Hope Hospital, Salford, Manchester and North Manchester Hospital; Sumaira MacDonald, MBChB, PhD, MRCP, FRCR, Lecturer, Sheffield University Medical School; Endovascular Fellow, Sheffield Vascular Institute Editors: Giuseppe Guglielmi, MD, Associate Professor of Radiology, Department of Radiology, Scientific Institute Hospital; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Wilfred CG Peh, MD, MBBS, FRCP(Glasg), FRCP(Edin), FRCR, Clinical Professor, Faculty of Medicine, National University of Singapore; Senior Consultant Radiologist, Alexandra Hospital, Singapore; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Felix S Chew, MD, MBA, EdM, Professor, Department of Radiology, Vice Chairman for Radiology Informatics, Section Head of Musculoskeletal Radiology, University of Washington Author and Editor Disclosure Synonyms and related keywords: hypertrophic osteoarthropathy, primary hypertrophic osteoarthropathy, hypertrophic pulmonary osteoarthropathy, pachydermoperiostosis, secondary hypertrophic osteoarthropathy, HOA, HPOA, primary HOA, secondary HOA, idiopathic hypertrophic osteoarthropathy, generalized hyperostosis with pachydermia, idiopathic familial generalized osteophytosis, Touraine-Solente-Gole syndrome, periostitis, periosteal response, pachydermia, cutis vertices gyrata INTRODUCTIONSection 2 of 10
  BackgroundHypertrophic 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 PathophysiologyThe 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. 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. An association of primary HOA with myelofibrosis has been described.6, 7 FrequencyUnited StatesPrimary 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. InternationalThe international frequency of hypertrophic osteoarthropathy is similar to that in the United States. Mortality/Morbidity
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Clinical DetailsPrimary 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. Preferred ExaminationPlain 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 TechniquesNeither 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. DIFFERENTIALSSection 3 of 10
Caffey Disease Fibrous Dysplasia Paget Disease Other Problems To Be ConsideredPrimary hypertrophic osteoarthropathy (primary HOA, pachydermoperiostosis) Congenital syphilis Hypertrophic pulmonary osteoarthropathy (HPOA) Acromegaly RADIOGRAPHSection 4 of 10
FindingsPrimary hypertrophic osteoarthropathy (HOA, pachydermoperiostosis) The predominant radiographic feature of primary hypertrophic osteoarthropathy (HOA) is periostitis, which is depicted as symmetric osseous thickening. Periostitis mostly affects the tubular bones of the limbs, especially the radius, ulna, tibia, and fibula, although the pelvis, carpus, tarsus, metacarpals, metatarsals, and phalanges may be involved (see Images 1-11). Periosteal proliferation is usually shaggy and is associated with irregular excrescences and diaphyseal expansion. Periosteal proliferation begins in the epiphyseal region at the tendon-muscle attachment. Rarely, thickening of the calvarium and skull base is seen. Hypertrophic pulmonary osteoarthropathy (HPOA) HPOA usually involves diaphyseal and metaphyseal periostitis. Periosteal proliferation is usually single or laminated and is either regular or irregular. Laminated periostitis may have an onionskin appearance. Initially, periostitis is symmetric and involves the tibia, fibula, radius, ulna, and, less commonly, the femur, humerus, metacarpals, metatarsal, and phalanges on both sides. Eventually, periosteal proliferation extends into the metaphysis. Periosteal proliferation rarely extends into the epiphysis except in patients with congenital cyanotic heart disease, in whom the epiphysis may be affected. In rare cases, periostitis affects the ribs, clavicles, and scapula. Periarticular soft tissue swelling, clubbing, and clinical and radiologic features of an underlying primary lesion are often depicted. Digital clubbing associated with soft tissue swelling may be depicted on plain radiographs. Occasionally, focal areas of tuft hypertrophy or bone resorption may be seen. Clinically, joint involvement (eg, in the wrists, knees, ankles, and small joints of the hands) in patients with HPOA may mimic inflammatory arthritis. The presence of soft tissue swelling, joint effusion, and juxta-articular osteoporosis accentuate the clinical difficulty in making a diagnosis. However, synovial inflammation associated with HPOA is usually mild, and erosive change and loss of joint cartilage space are not features of HPOA. Chest radiographs may reveal the underlying cause of HPOA. Degree of ConfidenceRadiography remains the mainstay of imaging in patients with primary hypertrophic osteoarthropathy (HOA, pachydermoperiostosis) or hypertrophic pulmonary osteoarthropathy (HPOA), but the differential diagnosis includes many conditions. False Positives/NegativesAlthough similar osseous changes may occur in both primary hypertrophic osteoarthropathy (HOA) and hypertrophic pulmonary osteoarthropathy (HPOA), periostitis in HOA more commonly extends into the epiphysis. Poorly defined bony outgrowths are more characteristic of HOA. These outgrowths may also affect the axial skeleton. In patients with HOA, these changes occur at an earlier age because of the familial nature of the disease. Differences in the pattern of bone involvement in HOA and HPOA are partly related to the earlier age of onset in patients with HOA and the resulting longer duration of the bony changes. In patients with HPOA, changes develop at a later age, except in patients with conditions such as cyanotic heart disease; in these patients, the changes more closely resemble those of HOA. The irregular periosteal proliferation in the metaphysis and epiphysis among patients with HOA is not usually seen in patients with HPOA. The patient's family history, the early appearance of osseous changes, and the absence of joint pain help in differentiating HOA from HPOA. Patients with diffuse idiopathic skeletal hyperostosis (DISH) occasionally have diaphyseal periostitis, particularly in the femur and humerus. Occasionally, the metacarpals are involved; this finding mimics that of HOA. Thyroid acropachy is an unusual complication of thyrotoxicosis, which is associated with periostitis; it can mimic HOA on radiographs. However, the clinical features are distinct; exophthalmos, soft tissue swelling, pretibial myxedema, and clubbing are present. The condition is usually observed in patients with thyrotoxicosis after having undergone treatment; patients may be euthyroid or hypothyroid. Periostitis in thyroid acropachy appears fluffy and spiculated. It mostly affects the periosteal bone in the hands and feet and is rarely seen elsewhere. Hypervitaminosis A may cause periosteal proliferation, but the clinical and radiographic features enable one to distinguish this disease from HOA. Periostitis is usually diaphyseal, with undulating contour; it is often associated with epiphyseal abnormalities, soft tissue nodules, and intracranial hypertension. Endosteal hyperostosis (van Buchem disease) is characterized by thickening of the skull vault and tubular bones, but clubbing is not observed. Skin changes, thickening of the paranasal sinuses, and extension of periosteal proliferation into the epiphysis are features of HOA and do not occur in endosteal hyperostosis. Acromegaly and HOA share some clinical and radiographic features, but the 2 conditions are seldom confused. In patients with chronic venous stasis, periosteal proliferation is confined to the lower limbs. The condition is characterized by undulating periosteal contour and cortical thickening; it is associated with soft tissue swelling, ulceration, and calcified phleboliths. Infantile cortical hyperostosis (Caffey disease) typically affects the young; it is usually associated with extreme proliferative periostitis of the mandible, clavicle, scapula, ribs, and tubular bones. Cranial destruction, bone deformities, and soft tissue nodules may occur in infantile cortical hyperostosis. The clinicoradiologic features of infantile cortical hyperostosis are distinct, and it is usually not confused with HPOA or HOA. The radiographic features of Paget disease, fluorosis, fibrous dysplasia, macrodystrophia lipomatosa, and Proteus syndrome are sufficiently distinct not to cause confusion with HPOA or HOA. CT SCANSection 5 of 10
FindingsCT is useful in elucidating the cause of hypertrophic pulmonary osteoarthropathy (HPOA), such as intrathoracic pathology or infected vascular grafts. MRISection 6 of 10
FindingsMRI findings in patients with hypertrophic pulmonary osteoarthropathy (HPOA) were described in a solitary case in which 2 main features were observed: soft tissue changes and periostitis. The soft tissue component appeared as an area of high signal intensity on T2-weighted and short-tau inversion recovery (STIR) images. The findings consisted of muscular and septal edema associated with extensive soft tissue swelling that surrounded the femur and the attached cortex but not the bone. These features were believed to be consistent with an inflammatory process, which probably was highly vascularized, similar to reactive edema or fibrovascular proliferation. MRI depiction of periostitis is not usually reliable, but in the reported case, periostitis was easily identified through use of a surface coil; periostitis appeared as a wavy, thin, hypointense line surrounding the cortex.11, 12 Degree of ConfidenceExperience is insufficient for assessing the reliability of MRI in the diagnosis of hypertrophic osteoarthropathy (HOA). Apparently, the reported case indicated that the soft tissue component of the disease is depicted better on MRIs than on other images. False Positives/NegativesThe improved sensitivity of MRI in the detection of soft tissue edema may suggest an erroneous diagnosis of hypertrophic osteoarthropathy (HOA) if MRI is the initial modality used, because many inflammatory, posttraumatic, and neoplastic conditions have features similar to those of HOA. NUCLEAR MEDICINESection 7 of 10
FindingsIsotope bone scanning with technetium-99m–labeled diphosphonate shows evidence of hypertrophic pulmonary osteoarthropathy (HPOA) early in the course of disease; in addition, the sensitivity of isotope bone scans is greater than that of other imaging methods. Isotope uptake is symmetrically increased in the tubular bones along the cortical margins of the diaphysis and metaphysis. Uptake may be irregular, or it may create a double-stripe or parallel-track sign. Periarticular radionuclide uptake may be increased as a result of associated synovitis. Isotope bone scans show high rates of mandibular involvement (40% of patients) and scapular involvement (>60% of patients); these rates are considerably higher than the rates of such involvement as determined with the use of radiographs. Radionuclide uptake findings may be normal after a month of successful therapy (see Image 12).13 Degree of ConfidenceScintigraphic findings in patients with hypertrophic pulmonary osteoarthropathy (HPOA) appear earlier than radiographic findings do, and they correspond well to the clinical findings. Activity decreases with successful therapeutic measures, such as surgery or radiation therapy. Tumor recurrence may be associated with recurrent findings of increased radionuclide uptake. False Positives/NegativesAlthough isotope bone scanning is a highly sensitive means of assessing hypertrophic pulmonary osteoarthropathy (HPOA), its findings are nonspecific, and similar findings can occur with other forms of periosteal proliferation. INTERVENTIONSection 8 of 10
If hypertrophic pulmonary osteoarthropathy (HPOA) is secondary to an intrathoracic disease process, thoracotomy frequently leads to remission of the joint symptoms and signs within 24 hours. Vagotomy, neurectomy, and occlusion of the ipsilateral pulmonary artery cause clinical manifestations to regress. Radiotherapy and chemotherapy may lead to similar improvement. Regrowth of the neoplasm is associated with an increase in clinical and radiologic findings. Patients with HPOA secondary to chronic liver disease may benefit from liver transplantation. MULTIMEDIASection 9 of 10
REFERENCESSection 10 of 10
Hypertrophic Osteoarthropathy excerpt Article Last Updated: Jul 23, 2008 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
