Secondary hypertrophic osteoarthropathy caused by non-pleural or pulmonary tumors.

Hypertrophic osteoarthropathy (HOA) is a rare paraneoplastic syndrome characterized by digital clubbing, periosteal reaction, polyarthralgia, arthritis, and synovitis. Herein, we report a case series of patients with secondary HOA caused by non-pleural or pulmonary tumors.The radiologic databases of 2 tertiary university hospitals were retrospectively screened for secondary HOA patients. In addition, a systemic review of the published case reports. Only HOA cases with non-pleural or pulmonary malignancies were involved into the study. HOA in primary pleural or pulmonary malignant or benign disorders, as well in inflammatory diseases were excluded. In all cases, plain radiography was performed and clinical signs were documented.In our databases, 6 patients with secondary HOA were identified. In addition, the systemic review yielded 24 eligible patients. The most prevalent primary tumors were nasopharyngeal carcinoma and esophageal cancer in 6 patients (20%), respectively. In 17 patients, (56.7%) HOA was associated with lung metastases, and in 10 patients (33.3%), no lung metastases were detected. In 14 patients (46.7%), HOA was symptomatically before a tumor diagnosis was made. Plain radiography displayed typically features with periostal enlargement in every case.This study is the first report about secondary HOA caused by non-pleural or pulmonary tumors. Various primary tumors were identified, including several rare tumors such as sarcomas. HOA is a rare disorder with typically radiologically findings, which is not only associated with lung cancer or pleural mesothelioma and can even occur in tumor patients without lung metastasis.

Digital clubbing: forms, associations and pathophysiology.

Among proposed mechanisms to explain digital clubbing, the release of cytokines, specifically vascular endothelial growth factor and platelet-derived growth factor, from aggregated platelets and megakaryocytes has emerged as the most likely explanation. This review describes these and other contributory processes.

Clubbing and hypertrophic osteoarthropathy: insights in diagnosis, pathophysiology, and clinical significance.

BACKGROUND: Digital clubbing and hypertrophic osteoarthropathy (HOA) form a diagnostic challenge. Subtle presentations of clubbing are often missed. The underlying pathophysiology remains unclear. Establishing a differential diagnosis based on nonspecific signs can be cumbersome. Finally, the prognostic value of clubbing and HOA remains unclear. OBJECTIVE: This article reviews clinical criteria and pathophysiology of clubbing and HOA. A diagnostic algorithm is proposed, based on etiology and current insights. The prognostic impact on associated diseases is discussed. METHODS: The Internet databases Medline and Embase were searched. Articles were selected based on relevance of abstract, article type and impact of the journal. RESULTS: Diagnostic criteria include Lovibond's profile sign, distal/interphalangeal depth ratio and Schamroth's sign. Three pathophysiological causes of clubbing can be distinguished: hypoxia, chronic inflammation and aberrant vascularization. A prominent role for vascular endothelial growth factor is suggested. Associated symptoms and clinical signs should guide the initial diagnostic evaluation. Finally, clubbing is a negative prognostic factor in certain pulmonary disorders, including cystic fibrosis.

Hypertrophic osteoarthropathy: what a rheumatologist should know about this uncommon condition.

This article presents an updated overview of hypertrophic osteoarthropathy and digital clubbing for the practicing rheumatologist. Discussion includes a brief historical perspective, its definition, incidence and prevalence, classification, pathology and pathophysiology, clinical manifestations, demographics, findings on physical examination, imaging techniques for its detection, differential diagnosis, and treatment modalities.

Primary hypertrophic osteoarthropathy: an update.

Digital clubbing, which has been recognized as a sign of systemic disease, is one of the most ancient diseases. However, the pathogenesis of clubbing and hypertrophic osteoarthropathy has hitherto been poorly understood. The study of a clinically indistinguishable idiopathic form (primary hypertrophic osteoarthropathy, PHO) provides an opportunity to understand the pathogenesis of hypertrophic osteoarthropathy. Current advances in the study of PHO are discussed. The impaired metabolism of prostaglandin E2 (PGE2) plays a central role in its pathogenesis.

A new hypothesis on the mechanism of digital clubbing secondary to pulmonary pathologies.

Our hypothesis concerns the chronic activation of macrophages, and the continual production of pro-fibrotic tissue repair factors, as a cause of digital clubbing in an array of pulmonary pathologies. The level of macrophage activation will differ between individuals, corresponding to the variable immune response to these pulmonary pathologies. Due to this variability, there is a corresponding inconsistency in the presentation of clubbing. Although testing of this hypothesis would be difficult, there is evidence to support our theory; including a link to chronic diseases involving granulomas, where there would be a large collection of macrophages present and pathologies in organs with large resident macrophage populations. This theory, therefore, could also be developed to include non-pulmonary causes of clubbing.

Hypertrophic osteoarthropathy effectively treated with zoledronic acid.

Hypertrophic osteoarthropathy (HOA) is a syndrome characterized by digital clubbing, arthralgias, and tissue swelling and is frequently described in association with bronchogenic carcinoma. The associated pain can be disabling, and symptoms are often resistant to conventional analgesic medications. We present a patient with HOA of the lower extremities and wrists that developed after bronchogenic carcinoma. The pain and swelling completely resolved after a single administration of 4 mg of zoledronic acid. The proposed pathogenesis of HOA and the mechanisms by which bisphosphonates might alleviate symptoms are reviewed.

Hypertrophic osteoarthropathy: a palindrome with a pathogenic connotation.

PURPOSE OF REVIEW: The review seeks to update advances on the pathogenesis of hypertrophic osteoarthropathy, describe a previously unrecognized palindrome that occurs in hypertrophic osteoarthropathy and that may have pathogenic implications, and review the role of bisphosphonates in the treatment of this condition. RECENT FINDINGS: Some patients with primary hypertrophic osteoarthropathy display an interesting palindrome. Many years after the onset of the osteoarthropathy, they develop diseases that in other circumstances are known to generate secondary hypertrophic osteoarthropathy. This palindrome has been reported in cases of patent ductus arteriosus, Crohn's disease and myelofibrosis. Additionally, primary hypertrophic osteoarthropathy and POEMS syndrome share important clinical features. The many diseases associated with hypertrophic osteoarthropathy have in common abnormal production of vascular endothelial growth factor. This cytokine has been proposed to play a major role in the pathogenesis of Crohn's disease, myelofibrosis and POEMS syndrome. A controlled study showed that vascular endothelial growth factor is abnormally expressed in cases of hypertrophic osteoarthropathy. The biologic effects of vascular endothelial growth factor may explain hypertrophic osteoarthropathy histological features. Several isolated reports suggest that pamidronate is effective in relieving painful osteoarthropathy. SUMMARY: Hypertrophic osteoarthropathy is a palindromic syndrome. Anomalous vascular endothelial growth factor expression may explain this phenomenon. Bisphosphonates may have a role in the symptomatic treatment of hypertrophic osteoarthropathy.

Effective symptomatic relief of hypertrophic pulmonary osteoarthropathy by video-assisted thoracic surgery truncal vagotomy.

Various modalities for the treatment of hypertrophic pulmonary osteoarthropathy (HPOA) associated with lung cancer have been suggested since 1958. Although the etiology remains speculative, unilateral vagotomy on the side of the lung cancer achieves symptomatic relief. We report a case of a 50-year-old woman with disabling HPOA and inoperable lung cancer who experienced effective pain relief and regained full mobility after video-assisted thoracoscopic surgery was used to perform truncal vagotomy. This relatively safe and simple procedure should be considered for terminal lung cancer patients with intractable HPOA.

Digital clubbing in tuberculosis--relationship to HIV infection, extent of disease and hypoalbuminemia.

BACKGROUND: Digital clubbing is a sign of chest disease known since the time of Hippocrates. Its association with tuberculosis (TB) has not been well studied, particularly in Africa where TB is common. The prevalence of clubbing in patients with pulmonary TB and its association with Human Immunodeficiency Virus (HIV), severity of disease, and nutritional status was assessed. METHODS: A cross-sectional study was carried out among patients with smear-positive TB recruited consecutively from the medical and TB wards and outpatient clinics at a public hospital in Uganda. The presence of clubbing was assessed by clinical signs and measurement of the ratio of the distal and inter-phalangeal diameters (DPD/IPD) of both index fingers. Clubbing was defined as a ratio > 1.0. Chest radiograph, serum albumin and HIV testing were done. RESULTS: Two hundred patients (82% HIV-infected) participated; 34% had clubbing by clinical criteria whilst 30% had clubbing based on DPD/IPD ratio. Smear grade, extensive or cavitary disease, early versus late HIV disease, and hypoalbuminemia were not associated with clubbing. Clubbing was more common among patients with a lower Karnofsky performance scale score or with prior TB. CONCLUSION: Clubbing occurs in up to one-third of Ugandan patients with pulmonary TB. Clubbing was not associated with stage of HIV infection, extensive disease or hypoalbuminemia.

Hypertrophic osteoarthropathy in two children with cholestatic hepatic disease.

AIM: To describe two children with hypertrophic osteoarthropathy associated with cholestatic hepatic disease. Both patients suffered from chronic progressive cholestatic liver disease and developed digital clubbing, polyarthritis and periosteal reaction. In one of them, clinical and radiological features normalized after liver transplant. CONCLUSION: Hepatic hypertrophic osteoarthropathy is a rare disabling condition that responds poorly to conservative management, while liver transplantation appears to be the only effective therapeutic intervention.

Hypertrophic osteoarthropathy may be a marker of underlying sympathetic bias.

Hypertrophic osteoarthropathy (HOA) is a condition that accompanies many seemingly unrelated diseases. It is commonly associated with various clinical conditions such as pregnancy, aging, pulmonary diseases, cancers, and other systemic illnesses. The condition has been attributed to various causes such as platelet abnormalities, hormonal disturbances, and cytokine dysfunction, but the exact underlying mechanism has been elusive. We propose a unifying hypothesis that activation of the adrenergic system is the common thread that links all of the disparate clinical associations of hypertrophic osteoarthropathy. In diseased states, autonomic stimulation may occur as a result of chemoreceptor activation in response to acidosis, hypoxia, or hypercapnia. Examples include sleep apnea, congestive heart failure, renal failure, and tumor-induced hypoxia. In this setting, clinical signs of HOA may be a marker of underlying autonomic dysfunction. Autonomic stimulation may also occur as a normal part of pregnancy or as an abnormal component of aging. The exact pathway linking adrenergic excess to HOA remains to be clarified, but a plausible scenario based on current molecular evidence is offered.