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Faust B, Parkinson A, Baumrucker SJ. Pharmacology update: pamidronate for hypertrophic pulmonary osteoarthropathy in palliative care. THERAPEUTIC ADVANCES IN RARE DISEASE 2022; 3:26330040211070298. [PMID: 37180420 PMCID: PMC10032426 DOI: 10.1177/26330040211070298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 12/07/2021] [Indexed: 05/16/2023]
Abstract
Hypertrophic pulmonary osteoarthropathy (HPOA) is a rare syndrome that causes clubbed fingers, periostitis, and synovial effusions. It can adversely impact a patient's quality of life. It occurs secondary to pulmonary disease - most commonly pulmonary malignancy. The most effective treatment for HPOA is to treat the underlying disease, usually through surgical resection, chemotherapy, or radiation. However, symptomatic treatments rather than definitive treatments (surgical, chemotherapy, or radiation) are more appropriate for the palliative care patient. Pamidronate is a promising medication for the treatment of HPOA for its safety and rapid onset of action. Further research is indicated to determine whether pamidronate is consistently effective.
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Affiliation(s)
- Bethany Faust
- Quillen College of Medicine, East Tennessee
State University, Johnson City, TN, USA
| | - Aaron Parkinson
- DeBusk College of Osteopathic Medicine, Lincoln
Memorial University, Harrogate, TN, USA
| | - Steven J. Baumrucker
- Palliative Medicine, Ballad Health System, 300
Med Tech Parkway, Johnson City, TN 37604, USA
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2
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Pain control of hypertrophic pulmonary osteoarthropathy related with lung cancer: A clinical case report. Porto Biomed J 2019; 4:e43. [PMID: 33501394 PMCID: PMC7819535 DOI: 10.1097/j.pbj.0000000000000043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2018] [Accepted: 06/18/2019] [Indexed: 11/29/2022] Open
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3
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Huang MZ, Lu XR, Yang YJ, Liu XW, Qin Z, Li JY. Cellular Metabolomics Reveal the Mechanism Underlying the Anti-Atherosclerotic Effects of Aspirin Eugenol Ester on Vascular Endothelial Dysfunction. Int J Mol Sci 2019; 20:E3165. [PMID: 31261711 PMCID: PMC6651823 DOI: 10.3390/ijms20133165] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Accepted: 06/26/2019] [Indexed: 01/29/2023] Open
Abstract
Aspirin eugenol ester (AEE) possesses anti-thrombotic, anti-atherosclerotic and anti-oxidative effects. The study aims to clarify the mechanism underlying the anti-atherosclerotic effects of AEE on vascular endothelial dysfunction. Both the high-fat diet (HFD)-induced atherosclerotic rat model and the H2O2-induced human umbilical vein endothelial cells (HUVECs) model were used to investigate the effects of AEE on vascular endothelial dysfunction. UPLC/QTOF-MS coupled with a multivariate data analysis method were used to profile the variations in the metabolites of HUVECs in response to different treatments. Pretreatment of HUVECs with AEE significantly ameliorated H2O2-induced apoptosis, the overexpression of E-selectin and VCAM-1, and the adhesion of THP-1 cells. Putative endogenous biomarkers associated with the inhibition of endothelial dysfunction were identified in HUVECs pretreated with AEE in the absence or presence of H2O2, and these biomarkers were involved in important metabolic pathways, including amino acid metabolism, carbohydrate metabolism, and glutathione metabolism. Moreover, in vivo, AEE also significantly reduced vascular endothelial dysfunction and decreased the overexpression of VCAM-1 and E-selectin. Based on our findings, the mechanism underlying the anti-atherosclerotic effects of AEE might be related to a reduction in vascular endothelial dysfunction mediated by ameliorating alterations in metabolism, inhibiting oxidative stress, and decreasing the expression of adhesion molecules.
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Affiliation(s)
- Mei-Zhou Huang
- Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China
| | - Xiao-Rong Lu
- Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China
| | - Ya-Jun Yang
- Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China
| | - Xi-Wang Liu
- Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China
| | - Zhe Qin
- Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China
| | - Jian-Yong Li
- Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China.
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Jenkins V, Henrique de Mello Souza C, de Lorimier LP, de Toledo-Piza E. Squamous Cell Carcinoma of the Penis with Pulmonary Metastasis and Paraneoplastic Hypertrophic Osteopathy in a Dog. J Am Anim Hosp Assoc 2017; 53:277-280. [PMID: 28792794 DOI: 10.5326/jaaha-ms-6425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Squamous cell carcinoma of the penis was diagnosed by incisional biopsy of a penile mass in a 12 yr old intact male beagle dog presenting with hemorrhagic discharge from the prepuce. Penile amputation, orchiectomy with scrotal ablation, and scrotal urethrostomy were performed. Hypertrophic osteopathy secondary to pulmonary metastatic disease occurred 10 mo after the surgery. Palliative treatment with piroxicam was administered and led to complete resolution of the clinical signs of the pain. Sixteen months following surgery, the dog presented with significant dyspnea and anorexia and was euthanized due to poor prognosis. This case report describes a rare penile tumor, squamous cell carcinoma. Consequent paraneoplastic hypertrophic osteopathy and its palliative treatment are also reviewed.
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Affiliation(s)
- Victoria Jenkins
- From the University of Florida, Gainesville, Florida (V.J., C.H.d.M.S.); Hôpital Vétérinaire Rive-Sud, Brossard, Quebec, Canada (L-P.d.L.); IPEV, Rio de Janeiro, Brazil (E.d.T-P.)
| | - Carlos Henrique de Mello Souza
- From the University of Florida, Gainesville, Florida (V.J., C.H.d.M.S.); Hôpital Vétérinaire Rive-Sud, Brossard, Quebec, Canada (L-P.d.L.); IPEV, Rio de Janeiro, Brazil (E.d.T-P.)
| | - Louis-Phillippe de Lorimier
- From the University of Florida, Gainesville, Florida (V.J., C.H.d.M.S.); Hôpital Vétérinaire Rive-Sud, Brossard, Quebec, Canada (L-P.d.L.); IPEV, Rio de Janeiro, Brazil (E.d.T-P.)
| | - Evandro de Toledo-Piza
- From the University of Florida, Gainesville, Florida (V.J., C.H.d.M.S.); Hôpital Vétérinaire Rive-Sud, Brossard, Quebec, Canada (L-P.d.L.); IPEV, Rio de Janeiro, Brazil (E.d.T-P.)
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Galuppi E, Bortoluzzi A, Govoni M, Trotta F. Hypertrophic osteoarthropathy: classification, diagnostic features, and treatment options. Expert Opin Orphan Drugs 2016. [DOI: 10.1080/21678707.2016.1205481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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6
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Voriconazole-induced periostitis: a new rheumatic disorder. Clin Rheumatol 2016; 36:609-615. [DOI: 10.1007/s10067-016-3341-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2016] [Revised: 06/22/2016] [Accepted: 06/22/2016] [Indexed: 02/04/2023]
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Pourmorteza M, Baumrucker SJ, Al-Sheyyab A, Da Silva MACP. Hypertrophic Pulmonary Osteoarthropathy: A Rare But Treatable Condition in Palliative Medicine. J Pain Symptom Manage 2015; 50:263-7. [PMID: 25701054 DOI: 10.1016/j.jpainsymman.2015.02.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2014] [Revised: 02/02/2015] [Accepted: 02/11/2015] [Indexed: 11/22/2022]
Affiliation(s)
- Mehdi Pourmorteza
- Department of Internal Medicine, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA
| | - Steven J Baumrucker
- Wellmont Cancer Institute, Wellmont Health System, Kingsport, Tennessee, USA.
| | - Ahmed Al-Sheyyab
- Department of Internal Medicine, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA
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Komatsu M, Yasuo M, Kobayashi N, Tateishi K, Ushiki A, Urushihata K, Yamamoto H, Hanaoka M, Matoba H, Honda T, Ichikawa K. Hypertrophic Pulmonary Osteoarthropathy in Anaplastic Lymphoma Kinase (ALK)-positive Lung Cancer. Intern Med 2015; 54:2045-9. [PMID: 26278300 DOI: 10.2169/internalmedicine.54.4452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
A 49-year-old man was admitted to a hospital with chest pain and polyarthralgia. Chest radiography showed abnormal findings, and chest computed tomography showed a mass in the right lung. A transbronchial lung biopsy led to a diagnosis of anaplastic lymphoma kinase (ALK)-positive adenocarcinoma. Bone scintigraphy revealed bilateral symmetrical accumulations of (99m)Technetium complexes in the long bones, suggesting co-existing hypertrophic pulmonary osteoarthropathy (HPO). The patient underwent four courses of chemotherapy with cisplatin plus pemetrexed, which led to decreased (99m)Technetium accumulations in the long bones. To the best of our knowledge, this is the first reported case of HPO associated with ALK-positive lung cancer.
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Affiliation(s)
- Masamichi Komatsu
- The First Department of Internal Medicine, Shinshu University School of Medicine, Japan
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Abstract
For patients that present with musculoskeletal symptoms, diagnostic procedures carried out by physicians and rheumatologists are primarily aimed at confirming or excluding the occurrence of primary rheumatic diseases. Another important trigger for musculoskeletal disease, however, is the presence of a tumour. Careful clinical investigation and knowledge of the gestalt of musculoskeletal syndromes related to respective tumour entities is of utmost importance for the diagnosis of paraneoplastic rheumatic diseases such as hypertrophic osteoarthropathy, paraneoplastic polyarthritis, RS3PE syndrome, palmar fasciitis and polyarthritis, cancer-associated myositis and tumour-induced osteomalacia. This places great responsibility on rheumatologists in diagnosing malignancies and referring the patient for effective treatment. The selective influence of tumours on musculoskeletal tissue is surprising and indicates that tumours alter tissues such as the periosteum, synovial membrane, subcutaneous connective tissue, fascia, muscles and bones by specific molecular processes. Some of the underlying mechanisms have been unravelled, providing valuable information on the physiologic and pathophysiologic roles of mediators such as vascular endothelial growth factor and fibroblast growth factor 23.
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Affiliation(s)
- Bernhard Manger
- Department of Internal Medicine 3, University of Erlangen-Nuremberg, Ulmenweg 18, D-91054 Erlangen, Germany
| | - Georg Schett
- Department of Internal Medicine 3, University of Erlangen-Nuremberg, Ulmenweg 18, D-91054 Erlangen, Germany
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Kanaji N, Watanabe N, Kita N, Bandoh S, Tadokoro A, Ishii T, Dobashi H, Matsunaga T. Paraneoplastic syndromes associated with lung cancer. World J Clin Oncol 2014; 5:197-223. [PMID: 25114839 PMCID: PMC4127595 DOI: 10.5306/wjco.v5.i3.197] [Citation(s) in RCA: 134] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 04/12/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
Paraneoplastic syndromes are signs or symptoms that occur as a result of organ or tissue damage at locations remote from the site of the primary tumor or metastases. Paraneoplastic syndromes associated with lung cancer can impair various organ functions and include neurologic, endocrine, dermatologic, rheumatologic, hematologic, and ophthalmological syndromes, as well as glomerulopathy and coagulopathy (Trousseau’s syndrome). The histological type of lung cancer is generally dependent on the associated syndrome, the two most common of which are humoral hypercalcemia of malignancy in squamous cell carcinoma and the syndrome of inappropriate antidiuretic hormone secretion in small cell lung cancer. The symptoms often precede the diagnosis of the associated lung cancer, especially when the symptoms are neurologic or dermatologic. The proposed mechanisms of paraneoplastic processes include the aberrant release of humoral mediators, such as hormones and hormone-like peptides, cytokines, and antibodies. Treating the underlying cancer is generally the most effective therapy for paraneoplastic syndromes, and treatment soon after symptom onset appears to offer the best potential for symptom improvement. In this article, we review the diagnosis, potential mechanisms, and treatments of a wide variety of paraneoplastic syndromes associated with lung cancer.
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Myint TMM, Vucak-Dzumhur M, Ebeling PR, Elder GJ. A case report of disabling bone pain after long-term kidney transplantation. Osteoporos Int 2014; 25:769-72. [PMID: 23800747 DOI: 10.1007/s00198-013-2425-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2013] [Accepted: 06/03/2013] [Indexed: 11/30/2022]
Abstract
A 77-year-old man, who received a renal transplant 13 years before for IgA glomerulonephritis, was referred after he developed bilateral mid-tibial aching pain that did not improve with simple analgesia. He had recently been changed from low-dose cyclosporine to tacrolimus, but the pain did not improve when this was reversed. He had a history of focal prostatic adenocarcinoma, cryptococcal lung infection, osteoporosis treated with alendronate for 2 years and multiple squamous cell carcinomas, including one requiring left neck dissection and radiotherapy. Upon physical examination, he had gouty tophi and marked bilateral tibial tenderness but had no other clinical findings. Laboratory investigations included an elevated intact parathyroid hormone value of 7.9 pmol/L (1.6 to 6.9), bone specific alkaline phosphatase of 22 µg/L (3.7 to 20.9), urinary deoxypyridinoline/creatinine ratio of 7.2 nmol/mmol (2.5 to 5.4) and C-reactive protein. Chest X-ray and tibial X-rays were normal, but there was marrow oedema and a prominent periosteal reaction on magnetic resonance imaging. A radionuclide bone scan showed increased symmetrical, linear uptake in both tibiae and the left femur, and uptake was also noted in both clinically asymptomatic humeri. Tibial bone biopsy disclosed small deposits of poorly differentiated metastatic cancer and a follow-up chest CT revealed a lung lesion. It was concluded that the bone pain and periostitis was caused by primary lung cancer with metastatic disease to bone, and an associated hypertrophic osteoarthropathy.
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Affiliation(s)
- T M M Myint
- Department of Renal Medicine, Westmead Hospital, Westmead, NSW, Australia
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Abstract
Platelets are causally involved in coronary artery obstruction in acute coronary syndromes (ACS). This cell type is unique to mammals and its production, which is unlike that of any other mammalian cell, involves polyploid nuclear change in the mother cell (megakaryocyte) and the production of anucleate cells with a log Gaussian distribution of volume. Platelets vary more in cellular volume than any other circulating blood element in mammals. Larger platelets are denser, contain more secretory granules, and are more reactive than their smaller counterparts. A causal relationship between the presence of large, dense, reactive platelets in the circulation and ACS is supported by many clinical studies. Furthermore, the results of two large, prospective, epidemiological studies have demonstrated that mean platelet volume was the strongest independent predictor of outcome in patients with acute myocardial infarction. Notably, evidence indicates that an increase in mean platelet volume in the pathogenesis of ACS can potentially overwhelm current therapeutics. The control system for the physiological and pathophysiological production of large platelets should, therefore, be researched. An understanding of this system might give rise to new therapeutics that could control platelet reactivity and thereby comprehensively prevent ACS.
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Abstract
Digital clubbing is an ancient and important clinical signs in medicine. Although clubbed fingers are mostly asymptomatic, it often predicts the presence of some dreaded underlying diseases. Its exact pathogenesis is not known, but platelet-derived growth factor and vascular endothelial growth factor are recently incriminated in its causation. The association of digital clubbing with various disease processes and its clinical implications are discussed in this review.
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Affiliation(s)
- Malay Sarkar
- Department of Pulmonary Medicine, Indira Gandhi Medical College, Shimla, India
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Marengo MF, Suarez-Almazor ME, Lu H. Neoplastic and Paraneoplastic Synovitis. Rheum Dis Clin North Am 2011; 37:551-72. [DOI: 10.1016/j.rdc.2011.09.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Kilaru M, Vitale C, Montagnini M. Pain management in hypertrophic pulmonary osteoarthropathy: an illustrative case and review. Am J Hosp Palliat Care 2011; 29:302-7. [PMID: 21998443 DOI: 10.1177/1049909111421608] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Hypertrophic pulmonary osteoarthropathy (HOA) is a condition associated with lung cancer and many other diseases. Pain associated with HOA can be disabling, unremitting, and refractory to conventional analgesic medications. We present a challenging case of HOA in a patient with nonsmall cell lung cancer and review specific therapies for management of HOA-related pain.
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Affiliation(s)
- Malathy Kilaru
- Henry Ford Hospice, Henry Ford Health System, Detroit, MI, USA
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16
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Huang CH, Jeng CR, Lin CT, Yeh LS. Feline hypertrophic osteopathy: a collection of seven cases in Taiwan. J Am Anim Hosp Assoc 2010; 46:346-52. [PMID: 20810556 DOI: 10.5326/0460346] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Between October 2003 and May 2004, seven cats were diagnosed with severe and extensive hypertrophic osteopathy of the appendicular skeleton without detectable underlying causes. All cats showed similar clinical signs of pain with progressive lameness of the limbs. One cat died shortly after presentation, whereas conditions of the others resolved after medical treatment and a change in diet. Regression of the bone lesions was observed radiographically in all surviving six cases.
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Affiliation(s)
- Chiung-Hui Huang
- Department of Veterinary Medicine, Graduate Institute of Veterinary Medicine and Veterinary Teaching Hospital, National Taiwan University, Number 1, Section 4, Roosevelt Road, Taipei City 106, Taiwan
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Wang TF, Wang T, Altman R, Eshaghian P, Lynch JP, Ross DJ, Belperio JA, Weigt SS, Saggar R, Gregson A, Kubak B, Saggar R. Periostitis secondary to prolonged voriconazole therapy in lung transplant recipients. Am J Transplant 2009; 9:2845-50. [PMID: 19845595 DOI: 10.1111/j.1600-6143.2009.02837.x] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
We report five cases of possible drug-induced periostitis associated with long-term use of voriconazole therapy after lung transplantation (LT). The diagnosis of periostitis was made by the documentation of bone pain, elevation of serum alkaline phosphatase and characteristic findings on radionuclide bone imaging in the absence of any identifiable rheumatologic disease. This periostitis appears similar to hypertrophic osteoarthopathy (HOA) but does not meet all criteria for HOA. In all patients, the symptoms resolved rapidly after discontinuation of voriconazole therapy. Awareness of this potential syndrome, which manifests as bone pain, elevated serum alkaline phosphatase and a bone scan suggestive of periostitis, is necessary in LT recipients on long-term voriconazole.
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Affiliation(s)
- T F Wang
- Division of Internal Medicine, Department of Medicine, Ronald Reagan University of California Los Angeles Medical Center, Los Angeles, CA, USA
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Periostitis and hypertrophic pulmonary osteoarthropathy: report of 2 cases and review of the literature. Semin Arthritis Rheum 2008; 38:458-66. [PMID: 18760449 DOI: 10.1016/j.semarthrit.2008.07.001] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2007] [Revised: 06/19/2008] [Accepted: 07/08/2008] [Indexed: 02/06/2023]
Abstract
OBJECTIVES To demonstrate the clinical spectrum of hypertrophic osteoarthropathy (HOA). METHODS We report 2 cases of HOA and performed a computer-assisted search of Medline/PubMed for the medical literature from 1960 to June 2008 using the keywords HOA, periostitis, and clubbing. These were also combined with the text words cancer, rheumatic disease, etiology, pathogenesis, hypothesis, transplant, and treatment. Only the English language literature, with pertinent information, was included. RESULTS Our 2 cases include 1 HOA case with clubbing, in a patient with a right to left shunt from cryptogenic cirrhosis and interstitial lung disease, and 1 HOA case without apparent clubbing, in a patient with chronic lung transplant rejection secondary to tobacco smoking and related emphysema. Review of the literature has shown that HOA is associated with a wide variety of disorders, approximately 80% are found with primary or metastatic pulmonary malignancies. Various rheumatic diseases, such as systemic vasculitis, can also be associated with HOA. With respect to the pathogenesis, vascular endothelial growth factor, platelet-derived growth factor, and platelets may play crucial roles. Therapeutically, bisphosphonates, such as pamidronade or octreotide, may be tried to relieve symptoms in refractory cases. CONCLUSIONS HOA, especially periostitis without clubbing, may go unrecognized. Involvement of vascular endothelial growth factor, platelet-derived growth factor, and platelets in the pathogenesis of HOA has been postulated and supported by recent data. HOA may present as a partial syndrome without clubbing and about 20% of cases have HOA without detectable malignancy. One of our cases represents the first report of the association of HOA with lung transplantation.
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King MM, Nelson DA. Hypertrophic osteoarthropathy effectively treated with zoledronic acid. Clin Lung Cancer 2008; 9:179-82. [PMID: 18621629 DOI: 10.3816/clc.2008.n.027] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
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.
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Affiliation(s)
- Melissa M King
- Department of Hematology/Oncology, Wilford Hall Medical Center, Lackland Air Force Base, San Antonio, TX 78236, USA.
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22
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Rendina D, De Filippo G, Viceconti R, Soscia E, Sirignano C, Salvatore M, Della Monica M, Scarano G, Mossetti G. Interleukin (IL)-6 and receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) are increased in the serum of a patient with primary pachydermoperiostosis. Scand J Rheumatol 2008; 37:225-9. [PMID: 18465459 DOI: 10.1080/03009740701772457] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Primary pachydermoperiostosis (PDP) is a rare syndrome, characterized by digital clubbing, periostosis, and pachydermia. We have evaluated biochemical bone turnover markers, including components of interleukin-6 (IL-6) and osteoprotegerin/receptor activator of nuclear factor (NF)-kappaB ligand (OPG/RANKL) systems, in an 18-year-old man affected by primary PDP. The acute phase of the disease was characterized in our patient by high serum levels of IL-6 and RANKL. The observed high serum levels of these parameters are associated with increased values in markers of bone resorption (degradation products of C-terminal telopeptides of type-I collagen and urinary hydroxyproline/creatinine ratio) and reduced serum levels of bone alkaline phosphatase, a marker of bone formation. Serum levels of osteotrophic hormones were in the normal range. Our data suggest that, despite the radiographic findings, the acute phase of primary PDP is characterized by increased bone resorption, probably mediated by IL-6 and RANKL.
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Affiliation(s)
- D Rendina
- Department of Clinical and Experimental Medicine, 'Federico II' University Medical School, Naples
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Spicknall KE, Zirwas MJ, English JC. Clubbing: an update on diagnosis, differential diagnosis, pathophysiology, and clinical relevance. J Am Acad Dermatol 2006; 52:1020-8. [PMID: 15928621 DOI: 10.1016/j.jaad.2005.01.006] [Citation(s) in RCA: 109] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Finger clubbing can be a striking physical finding. At other times, the presence of clubbing is difficult to establish by subjective examination alone and the profile angle or distal phalangeal to interphalangeal depth ratio are needed to confirm the finding. Most microscopic and imaging studies of clubbed fingers reveal hypervascularization of the distal digits. Recent research shows that when platelet precursors fail to become fragmented into platelets within the pulmonary circulation, they are easily trapped in the peripheral vasculature, releasing platelet-derived growth factor and vascular endothelial growth factor, promoters of vascularity and, ultimately, clubbing. Clinically, clubbing is associated with a number of neoplastic, pulmonary, cardiac, gastrointestinal, infectious, endocrine, psychiatric, and multisystem diseases. In narrowing the differential diagnosis, we recommend a detailed history and physical examination accompanied by focused laboratory and imaging studies. An algorithm for the evaluation of newly diagnosed clubbing is suggested.
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Affiliation(s)
- Kerith E Spicknall
- Department of Dermatology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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Ddungu H, Johnson JL, Smieja M, Mayanja-Kizza H. Digital clubbing in tuberculosis--relationship to HIV infection, extent of disease and hypoalbuminemia. BMC Infect Dis 2006; 6:45. [PMID: 16529654 PMCID: PMC1462994 DOI: 10.1186/1471-2334-6-45] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2005] [Accepted: 03/10/2006] [Indexed: 11/29/2022] Open
Abstract
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.
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Affiliation(s)
- Henry Ddungu
- Department of Medicine, Makerere University and Mulago Hospital, Kampala, Uganda
| | - John L Johnson
- Department of Medicine, Division of Infectious Diseases, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio, USA
| | - Marek Smieja
- Departments of Pathology and Molecular Medicine, Medicine, and Clinical Epidemiology and Biostatistics, McMaster University, Hamilton ON, Canada
- L424 St. Joseph's Hospital, 50 Charlton Ave. E., Hamilton ON L8N 4A6, Canada
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Abstract
Pachydermoperiostosis (PDP) is a rare genodermatosis, characterized by pachydermia, digital clubbing, periostosis and an excess of affected males. Although an autosomal dominant model with incomplete penetrance and variable expression has been proved, both autosomal recessive and X-linked inheritance have been suggested. However, at present, genetic heterogeneity is not fully supported. The aim of this study is to review the clinical and pedigree data of 68 published PDP families, including 204 patients. This analysis has confirmed an autosomal dominant mutation in 37 families and suggested the existence of an autosomal recessive form in the remaining families. The two forms may differ in clinical severity, intrafamilial variability and prevalence of some features. Additionally, the marked skewed sex ratio could not be easily explained by an X-linked mutation, but alternative explanations (i.e. testosterone promoting proliferation) are discussed.
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Affiliation(s)
- M Castori
- IRCCS-CSS San Giovanni Rotondo and CSS-Mendel Institute, Rome, Italy
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Amital H, Applbaum YH, Vasiliev L, Rubinow A. Hypertrophic pulmonary osteoarthropathy: control of pain and symptoms with pamidronate. Clin Rheumatol 2004; 23:330-2. [PMID: 15293094 DOI: 10.1007/s10067-004-0941-4] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2004] [Accepted: 04/06/2004] [Indexed: 02/06/2023]
Abstract
This case presents a patient with hypertrophic osteoarthropathy of the lower extremities that developed secondary to congenital cyanotic heart disease. The major clinical manifestation was severe bilateral leg pain. The pain that was debilitating in nature completely resolved following a single administration of 60 mg pamidronate. Hypertrophic osteoarthropathy (HOA) is an acquired, uncommon disorder of obscure etiology. It has been described mainly in association with chronic suppurative pulmonary diseases, bronchogenic carcinoma and lung metastases, cystic fibrosis, and cyanotic congenital malformations of the heart.
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Affiliation(s)
- Howard Amital
- Rheumatology Unit, Department of Radiology and Division of Internal Medicine, Hadassah-Hebrew University School of Medicine, Ein-Karem, POB 12000, 91120 Jerusalem, Israel.
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Moreira JDS, Porto NDS, Moreira ALS. Avaliação objetiva do hipocratismo digital em imagens de sombra de dedo indicador: estudo em pacientes pneumopatas e em indivíduos normais. J Bras Pneumol 2004. [DOI: 10.1590/s1806-37132004000200009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
INTRODUÇÃO: O diagnóstico do hipocratismo digital é clínico, mas pode tornar-se mais acurado pelo uso de critérios objetivos de determinação. OBJETIVO: Mostrar um método simples de obtenção de imagens de dedos para estudo do hipocratismo digital. MÉTODO: Em imagens de dedos indicadores em perfil, obtidas praticamente sem distorção em folha de papel comum, projetadas através de lâmina de vidro, determinaram-se os ângulos do perfil e hiponiquial, e a relação entre as espessuras falangeana distal e interfalangena. Estudaram-se 306 pneumopatas adultos, clinicamente com hipocratismo presente, ausente ou duvidoso, e 452 indivíduos adultos normais. Eram fumantes 71,0% dos pacientes e 33,4% dos controles. RESULTADOS: Os valores encontrados nos indivíduos normais e nos pacientes nos quais havia a presença clínica de hipocratismo foram, respectivamente, 172,8 ± 5,3º e 183,4 ± 5,0º para ângulo de perfil, 181,5 ± 4,8º e 201,4 ± 6,5º para ângulo hiponiquial, e 0,904 ± 0,029 e 1,014 ± 0,062 para a relação entre as espessuras falangeana distal e interfalangeana. As diferenças foram significativas. Os casos duvidosos também tiveram valores maiores que os verificados nos controles. No grupo controle, observou-se que os fumantes masculinos apresentaram os três valores significativamente superiores aos exibidos pelos não fumantes, enquanto que nas mulheres fumantes desse grupo apenas a relação entre as espessuras falangeana distal e interfalangeana se mostrou superior. CONCLUSÃO: Imagens nítidas de dedos indicadores foram facilmente obtidas pelo método empregado. O ângulo hiponiquial, determinado a partir das imagens, foi a medida que se mostrou com maior capacidade para discriminar casos com e sem hipocratismo (sensibilidade de 76,7%, especificidade de 83,2%, valores preditivos positivo de 95,8% e negativo de 96,9%).
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Brouwers AAM, Vermeij-Keers C, van Zoelen EJ, Gooren LJG. Clubbed fingers: the claws we lost? Med Hypotheses 2004; 62:321-4. [PMID: 14975497 DOI: 10.1016/s0306-9877(03)00300-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2003] [Accepted: 10/11/2003] [Indexed: 10/26/2022]
Abstract
Clubbed digits resemble the human embryonic fingers and toes, which look like the digits of a claw. Clubbed digits, thus, may represent the return of the embryonic claw and may even represent the claws man has lost during evolution, if ontogenesis really recapitulates phylogenesis. We put forward the hypothesis that secondary clubbing, like gynecomastia, is caused by a pathologic condition, which alters hormone levels in the blood, leading to the activation of 'dormant' genes, resulting in the development of an organ. However, the nature of the diseases that cause clubbing suggests that these hormones may actually be cytokines, acting as hormones. The nature of these cytokines is not known. They may be identified by comparing their blood levels or the combination of their blood levels to the presence or absence of clubbing, but also to the degree of clubbing and its disappearance after treatment of the primary disease.
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Affiliation(s)
- A A M Brouwers
- Department of Internal Medicine, Gelderse Vallei Hospital, Ede, Hindelaan 5, 6705CV Wageningen, The Netherlands.
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Silveri F, De Angelis R, Poggi A, Muti S, Bonapace G, Argentati F, Cervini C. Relative roles of endothelial cell damage and platelet activation in primary Raynaud's phenomenon (RP) and RP secondary to systemic sclerosis. Scand J Rheumatol 2002; 30:290-6. [PMID: 11727844 DOI: 10.1080/030097401753180372] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/16/2022]
Abstract
OBJECTIVE To evaluate the relative roles of endothelium and platelets in the pathogenesis of primary RP and RP secondary to SSc. METHODS Endothelial derived ET-1, t-PA, PAI-1, and platelet derived beta-TG, PDGF, TGF-beta were measured in 36 patients with primary RP, 14 patients with RP secondary to SSc and 30 age and sex matched controls. RESULTS A significative increase of ET-1, t-PA, PAI-1, TGF-beta, and beta-TG were the most relevant changes in patients with RP secondary to SSc with respect to the controls. Less relevant increases of t-PA, PAI-1, PDGF, and beta-TG levels were observed in patients with primary RP vs controls. CONCLUSIONS These data seem to confirm the involvement of endothelial cells and platelets in the pathogenesis of RP, with mild changes in primary RP and more relevant changes in RP secondary to SSc.
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Affiliation(s)
- F Silveri
- Department of Rheumatology, Ancona University, Ospedale A. Murri, Jesi, Italy.
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