Diagnostic Considerations

The importance of recognizing hypertrophic osteoarthropathy (HOA) cannot be overstated. A previously healthy individual with any manifestation of the syndrome should undergo a thorough evaluation for an underlying illness. Direct special attention toward the lungs and heart.

Other disorders to consider in the differential diagnosis include acromegaly, thyroid acropachy, and scleromyxedema, syphilitic periostitis, osteopetrosis, and Paget disease. The disfigurements in facial and skeletal appearances have been confused with leprosy and syphilis, which are especially important considerations in some developing countries.

Inflammatory arthropathy may be incorrectly diagnosed in cases of malignant lung tumors, in which painful arthropathy can be the presenting feature of HOA. HOA is more likely when the following factors are present:

Pain that extends beyond the joint into the adjacent bone
Absence of rheumatoid factor
Noninflammatory synovial fluid

Acromegaly may be suggested in cases of exuberant skin hypertrophy and enlarged hands and feet.^[95] However, in acromegaly, bones in general are larger in the face, jaw (prognathism), skull, and limbs; this is very evident in a radiographic study in the absence of signs of periostosis.Normal growth hormone levels and the absence of both prognathism and enlarged sella turcica exclude acromegaly.

Fingertip changes due to other conditions that may be confused with HOA include the following:

Spooning of nails secondary to iron deficiency anemia
Calcific deposits in distal digital pads of patients with scleroderma
Sarcoid involvement of the digit

Other diseases associated with periostitis should be included in the differential diagnosis. In HOA, the periostitis involves the distal diaphysis of long bones and metacarpal joints, while in other diseases, the involvement is as follows:

Psoriatic onycho-pachydermo periostitis - Terminal phalanx
Psoriatic arthritis - Phalanges of fingers and toes
Reactive arthritis - Phalanges of fingers and toes
Athletic overuse (running, jumping) - Upper and lower extremities
Ossifying fasciitis - Variable
Periostitis ossificans - Variable
Polyarteritis nodosa - Lower extremities
Systemic lupus erythematosus - Variable
Facial infections - Mandible, orbital
Florid reactive periostitis - Phalanges of hands and feet
Osteoblastoma - Variable
Bizarre parosteal osteochondromatous proliferation (Nora tumor) - Bones of the hands and feet
Chondrosarcoma - Variable
Treatment with interleukin-11 - Clavicle, long bones
Osteomyelitis - Variable
Chronic leg ulcers - Tibia
Synovitis-acne-pustulosis-hyperostosis (SAPHO) syndrome - Variable

Various causes of unidigital clubbing include the following:

Aortic/subclavian aneurysm
Brachial plexus injury
Shoulder subluxation
Superior sulcus (Pancoast) tumor
Median nerve injury
Trauma
Maffucci syndrome
Gout, sarcoidosis
Severe herpetic whitlow
Hemodialysis

Localized clubbing, similar to unilateral digital clubbing, has been described in association with local vascular lesions such as aneurysms; arteriovenous fistulas; and venous abnormalities of the arm, axilla, and thoracic outlet.^{[61, 62]}

Pretibial edema may be due to thrombophlebitis, venous stasis, or pretibial myxedema and may mimic periostosis.

Workup

Langford CA, Mandell. Arthritis Associated with Systemic Disease, and Other Arthritides. Kasper DL, Fauci AS, Hauser FL, et al, eds. Harrison's Principles of Internal Medicine. 19th ed. New York, NY: McGraw-Hill Medical; 2015. Chapter 397.
Castori M, Sinibaldi L, Mingarelli R, Lachman RS, Rimoin DL, Dallapiccola B. Pachydermoperiostosis: an update. Clin Genet. 2005 Dec. 68(6):477-86. [Medline].
Meyer HJ, Leifels L, Bach AG, Surov A. Secondary hypertrophic osteoarthropathy caused by non-pleural or pulmonary tumors. Medicine (Baltimore). 2017 Sep. 96 (36):e7985. [Medline].
Hippocrene Books. Hippocrates: Prognostic: Regimen in Acute Diseases, Sacred Disease, Art, Breaths, Law, Decorum, Physician, Dentition (Loeb Classical Library). London, UK: Harvard University Press; 1849. Vol 1:
Bamberger E. Uber knochenveranderugen bei chronishen lungen und herzkrankheiten. Z Klin Med. 1891. 18:193-217.
Marie P. De l’osteo-arthropathie hypertrophiante pneumique. Rev Med. 1890. 4:146-8.
Manger B, Lindner A, Manger K, Wacker J, Schett G. [Hypertrophic osteoarthropathy. Bamberger-Marie disease]. Z Rheumatol. 2011 Sep. 70(7):554-60. [Medline].
Nguyen S, Hojjati M. Review of current therapies for secondary hypertrophic pulmonary osteoarthropathy. Clin Rheumatol. 2011 Jan. 30(1):7-13. [Medline].
Touraine A, Solente G, Gole L. Un syndrome osteodermopathique: La pachydermie plicaturee avec pachyperiostose des extremites. Presse Med. 1935. 43:1820-4.
Karnan S, Krishnamoorthy V, Ethiraj P, Sathyanathan BP. Touraine-Solente-Gole syndrome: The complete form needs to be recognized. Indian J Nucl Med. 2012 Jul. 27(3):201-4. [Medline]. [Full Text].
Martinez-Lavin M, Vargas A, Rivera-Vinas M. Hypertrophic osteoarthropathy: a palindrome with a pathogenic connotation. Curr Opin Rheumatol. 2008 Jan. 20(1):88-91. [Medline].
Narayanan S, Mohamed Gani VM, Sundararaju V. Primary hypertrophic osteoarthropathy with hypertrophic gastropathy. J Clin Rheumatol. 2010 Jun. 16(4):190-2. [Medline].
Toovey OT, Eisenhauer HJ. A new hypothesis on the mechanism of digital clubbing secondary to pulmonary pathologies. Med Hypotheses. 2010 Dec. 75(6):511-3. [Medline].
Padula SJ, Broketa G, Sampieri A, et al. Increased collagen synthesis in skin fibroblasts from patients with primary hypertrophic osteoarthropathy. Evidence for trans-activational regulation of collagen transcription. Arthritis Rheum. 1994 Sep. 37(9):1386-94. [Medline].
Bigler FC. The morphology of clubbing. Am J Pathol. 1958 Mar-Apr. 34(2):237-61. [Medline]. [Full Text].
Pineda C, Fonseca C, Martinez-Lavin M. The spectrum of soft tissue and skeletal abnormalities of hypertrophic osteoarthropathy. J Rheumatol. 1990 May. 17(5):626-32. [Medline].
Pineda CJ, Guerra J Jr, Weisman MH, Resnick D, Martinez-Lavin M. The skeletal manifestations of clubbing: a study in patients with cyanotic congenital heart disease and hypertrophic osteoarthropathy. Semin Arthritis Rheum. 1985 May. 14(4):263-73. [Medline].
Altman RD, Tenenbaum J. Hypertrophic osteoarthropathy. Kelley W, Harris ED Jr, Ruddy S, Sledge C, eds. Textbook of Rheumatology. 5th ed. Philadelphia, Pa: WB Saunders; 1997. 1514-20.
Rothschild BM, Rothschild C. Recognition of hypertrophic osteoarthropathy in skeletal remains. J Rheumatol. 1998 Nov. 25(11):2221-7. [Medline].
Rosenthall L, Kirsh J. Observations of radionuclide imaging in hypertrophic pulmonary osteoarthropathy. Radiology. 1976 Aug. 120(2):359-62. [Medline].
Altman RD. Hypertrophic osteoarthropathy. McCarty JD, Koopman WJ, eds. Arthritis and Allied Conditions. 12th ed. Philadelphia, Pa: Lea & Febiger; 1993. 1511-7.
Fam AG, Chin-Sang H, Ramsay CA. Pachydermoperiostosis: scintigraphic, thermographic, plethysmographic, and capillaroscopic observations. Ann Rheum Dis. 1983 Feb. 42(1):98-102. [Medline]. [Full Text].
Schumacher HR Jr. Articular manifestations of hypertrophic pulmonary osteoarthropathy in bronchogenic carcinoma. Arthritis Rheum. 1976 May-Jun. 19(3):629-36. [Medline].
Vidal AF, Altman RD, Pardo D, et al. Structural and immunologic changes of synovium of hypertrophic osteoarthropathy. Arthritis Rheum. 1977. 20:139.
Lauter SA, Vasey FB, Hüttner I, Osterland CK. Pachydermoperiostosis: studies on the synovium. J Rheumatol. 1978 Spring. 5(1):85-95. [Medline].
Kabashima K, Sakabe J, Yoshiki R, Tabata Y, Kohno K, Tokura Y. Involvement of Wnt signaling in dermal fibroblasts. Am J Pathol. 2010 Feb. 176(2):721-32. [Medline]. [Full Text].
Alves AP, Holanda Filha JG, Jerônimo FT. [Eyelid ptosis associated with pachydermoperiostosis: case report]. Arq Bras Oftalmol. 2005 May-Jun. 68(3):401-4. [Medline].
Kumar S, Sidhu S, Mahajan BB. Touraine-soulente-golé syndrome: a rare case report and review of the literature. Ann Dermatol. 2013 Aug. 25(3):352-5. [Medline]. [Full Text].
Gary S. Firestein MD, Ralph C. Budd MD, Sherine E. Gabriel MD, MSc, Gary A. Koretzky MD, PhD, et al. Hypertrophic Ostearthropathy. Firestein & Kelly's Textbook of Rheumatology. Eleventh Edition. Elsevier;
Martínez-Lavín M. Digital clubbing and hypertrophic osteoarthropathy: a unifying hypothesis. J Rheumatol. 1987 Feb. 14(1):6-8. [Medline].
Ginsburg J, Brown JB. Increased oestrogen excretion in hypertrophic pulmonary osteoarthropathy. Lancet. 1961 Dec 9. 2(7215):1274-6. [Medline].
Matucci-Cerinic M, Martinez-Lavin M, Rojo F, Fonseca C, Kahaleh BM. von Willebrand factor antigen in hypertrophic osteoarthropathy. J Rheumatol. 1992 May. 19(5):765-7. [Medline].
Martínez-Lavín M. Hypertrophic osteoarthropathy. Best Pract Res Clin Rheumatol. 2020 Jun. 34 (3):101507. [Medline].
Uppal S, Diggle CP, Carr IM, Fishwick CWG, Ahmed M, Ibrahim GH, et al. Mutations in 15-hydroxyprostaglandin dehydrogenase cause primary hypertrophic osteoarthropathy. Nature Genetics. 2008. 40:789-793:[Full Text].
Zhang Z, He JW, Fu WZ, Zhang CQ, Zhang ZL. Two novel mutations in the SLCO2A1 gene in a Chinese patient with primary hypertrophic osteoarthropathy. Gene. 2014 Jan 25. 534(2):421-3. [Medline].
Seifert W, Kühnisch J, Tüysüz B, Specker C, Brouwers A, Horn D. Mutations in the prostaglandin transporter encoding gene SLCO2A1 cause primary hypertrophic osteoarthropathy and isolated digital clubbing. Hum Mutat. 2012 Apr. 33 (4):660-4. [Medline]. [Full Text].
Wittenberg RH, Willburger RE, Kleemeyer KS, Peskar BA. In vitro release of prostaglandins and leukotrienes from synovial tissue, cartilage, and bone in degenerative joint diseases. Arthritis Rheum. 1993 Oct. 36 (10):1444-50. [Medline].
Yuan L, Chen L, Liao RX, Lin YY, Jiang Y, Wang O, et al. A Common Mutation and a Novel Mutation in the HPGD Gene in Nine Patients with Primary Hypertrophic Osteoarthropathy. Calcif Tissue Int. 2015 Oct. 97 (4):336-42. [Medline].
Kozak KR, Milne GL, Bentzen SM, Yock TI. Elevation of prostaglandin E2 in lung cancer patients with digital clubbing. J Thorac Oncol. 2012 Dec. 7(12):1877-8. [Medline]. [Full Text].
Nomori H, Kobayashi R, Kubo A, Morinaga S, Shintani Y, Sano T. Lung cancer containing growth hormone-releasing hormone associated with hypertrophic osteoarthropathy. Case report. Scand J Thorac Cardiovasc Surg. 1994. 28 (3-4):149-52. [Medline].
Kroll MH, Afshar-Kharghan V. Platelets in pulmonary vascular physiology and pathology. Pulm Circ. 2012 Jul. 2 (3):291-308. [Medline]. [Full Text].
Spicknall KE, Zirwas MJ, English JC 3rd. Clubbing: an update on diagnosis, differential diagnosis, pathophysiology, and clinical relevance. J Am Acad Dermatol. 2005 Jun. 52 (6):1020-8. [Medline].
Vazquez-Abad D, Martinez-Lavin M. Macrothrombocytes in the peripheral circulation of patients with cardiogenic hypertrophic osteoarthropathy. Clin Exp Rheumatol. 1991 Jan-Feb. 9(1):59-62. [Medline].
Wiedermann CJ, Kob M, Benvenuti S, et al. Digital clubbing in primary intestinal lymphangiectasia: a case report. Wien Med Wochenschr. 2010 Aug. 160(15-16):431-6. [Medline].
Shin KC, Chung WJ, Lee KY, et al. Pachydermoperiostosis accompanied by heart failure. J Cardiovasc Ultrasound. 2009 Dec. 17(4):135-7. [Medline]. [Full Text].
Miller RE, Illing RO, Whelan JS. Lung carcinoma with hypertrophic osteoarthropathy in a teenager. Rare Tumors. 2011 Mar 30. 3(1):e8. [Medline]. [Full Text].
Arikan S, Sen I, Bahceci M, Tuzcu A, Ayli M. An interesting case of pachydermoperiostosis with idiopathic myelofibrosis associated with monosomy 22. Int J Dermatol. 2009 Aug. 48(8):882-5. [Medline].
Yacoub MH. Cervical Vagotomy for Pulmonary Osteoarthropathy. Br J Dis Chest. 1965 Jan. 59:28-31. [Medline].
Bazar KA, Yun AJ, Lee PY. Hypertrophic osteoarthropathy may be a marker of underlying sympathetic bias. Med Hypotheses. 2004. 63(2):357-61. [Medline].
Kut C, Mac Gabhann F, Popel AS. Where is VEGF in the body? A meta-analysis of VEGF distribution in cancer. Br J Cancer. 2007 Oct 8. 97 (7):978-85. [Medline]. [Full Text].
Hara Y, Matsuura Y, Takiguchi H, et al. [Reversal of pulmonary hypertrophic osteoarthropathy in surgically treated lung cancer]. Nihon Kokyuki Gakkai Zasshi. 2010 Dec. 48(12):966-71. [Medline].
Toovey OT, Eisenhauer HJ. A new hypothesis on the mechanism of digital clubbing secondary to pulmonary pathologies. Med Hypotheses. 2010 Dec. 75(6):511-3. [Medline].
da Costa FV, de Magalhaes Souza Fialho SC, et al. Infliximab treatment in pachydermoperiostosis: a rare disease without an effective therapeutic option. J Clin Rheumatol. 2010 Jun. 16(4):183-4. [Medline].
Martinez-Ferrer A, Peris P, Alos L, Morales-Ruiz M, Guanabens N. Prostaglandin E2 and bone turnover markers in the evaluation of primary hypertrophic osteoarthropathy (pachydermoperiostosis): a case report. Clin Rheumatol. 2009 Oct. 28(10):1229-33. [Medline].
Jajic I. Epidemiology of hypertrophic osteoarthropathy. Clin Exp Rheumatol. 1992 May-Jun. 10 Suppl 7:13. [Medline].
Martínez-Lavín M, Bobadilla M, Casanova J, Attié F, Martínez M. Hypertrophic osteoarthropathy in cyanotic congenital heart disease: its prevalence and relationship to bypass of the lung. Arthritis Rheum. 1982 Oct. 25 (10):1186-93. [Medline].
Martinez-Lavin M, Pineda C, Valdez T, et al. Primary hypertrophic osteoarthropathy. Semin Arthritis Rheum. 1988 Feb. 17(3):156-62. [Medline].
Nakajima M, Hirano T, Itoh K, Uchino M. Atherothrombotic brain infarction in a patient with pachydermoperiostosis. Mod Rheumatol. 2008. 18(3):281-4. [Medline].
Martínez-Lavín M, Matucci-Cerinic M, Jajic I, Pineda C. Hypertrophic osteoarthropathy: consensus on its definition, classification, assessment and diagnostic criteria. J Rheumatol. 1993 Aug. 20(8):1386-7. [Medline].
Swartz MH. Textbook of Physical Diagnosis: History and Examination. 2nd ed. Philadelphia, Pa: WB Saunders; 1994. 76-8.
Branwood AW. Clubbing of the fingers. Edinb Med J. 1949 Mar. 56(3):105-20. [Medline].
Kaditis AG, Nelson AM, Driscoll DJ. Takayasu's arteritis presenting with unilateral digital clubbing. J Rheumatol. 1995 Dec. 22(12):2346-8. [Medline].
Pallares-Sanmartin A, Leiro-Fernandez V, Cebreiro TL, Botana-Rial M, Fernandez-Villar A. Validity and reliability of the Schamroth sign for the diagnosis of clubbing. JAMA. 2010 Jul 14. 304(2):159-61. [Medline].
Martinez-Lavin M. Hypertrophic osteoarthropathy. Klippel JH, Dieppe PA, eds. Rheumatology. 2nd ed. London, UK: Mosby; 1998. 8.46.1-4.
Vazquez-Abad D, Pineda C, Martinez-Lavin M. Digital clubbing: a numerical assessment of the deformity. J Rheumatol. 1989 Apr. 16(4):518-20. [Medline].
Resnick D. Enostosis, hyperostosis, and periostitis. Resnick D, Kransdorf MJ, eds. Bone and Joint Imaging. 3rd ed. Philadelphia, Pa: Elsevier Saunders; 2005. 1433-35.
Poormoghim H, Hosseynian A, Javadi A. Primary hypertrophic osteoarthropathy. Rheumatol Int. 2012 Mar. 32(3):607-10. [Medline].
Kumar U, Bhatt SP, Misra A. Unusual associations of pachydermoperiostosis: a case report. Indian J Med Sci. 2008 Feb. 62(2):65-8. [Medline].
Ghosn S, Uthman I, Dahdah M, Kibbi AG, Rubeiz N. Treatment of pachydermoperiostosis pachydermia with botulinum toxin type A. J Am Acad Dermatol. 2010 Dec. 63(6):1036-41. [Medline].
Bergmann C, Wobser M, Morbach H, et al. Primary hypertrophic osteoarthropathy with digital clubbing and palmoplantar hyperhidrosis caused by 15-PGHD/HPGD loss-of-function mutations. Exp Dermatol. 2011 Jun. 20(6):531-3. [Medline].
Diggle CP, Carr IM, Zitt E, et al. Common and recurrent HPGD mutations in Caucasian individuals with primary hypertrophic osteoarthropathy. Rheumatology (Oxford). 2010 Jun. 49(6):1056-62. [Medline].
Saghafi M, Azarian A, Nohesara N. Primary hypertrophic osteoarthropathy with myelofibrosis. Rheumatol Int. 2008 Apr. 28(6):597-600. [Medline].
Vogl A, Blumenfeld S, Gutner LB. Diagnostic significance of pulmonary hypertrophic osteoarthropathy. Am J Med. 1955 Jan. 18(1):51-65. [Medline].
Ito T, Goto K, Yoh K, et al. Hypertrophic pulmonary osteoarthropathy as a paraneoplastic manifestation of lung cancer. J Thorac Oncol. 2010 Jul. 5(7):976-80. [Medline].
Izumi M, Takayama K, Yabuuchi H, Abe K, Nakanishi Y. Incidence of hypertrophic pulmonary osteoarthropathy associated with primary lung cancer. Respirology. 2010 Jul. 15(5):809-12. [Medline].
Moralidis E, Gerasimou G, Theodoridou A, Hilidis I, Mylonaki E, Gotzamani-Psarrakou A. Hypertrophic osteoarthropathy manifested with isolated calcaneal periostitis in bone scintigraphy. Ann Nucl Med. 2010 May. 24(4):313-7. [Medline].
Poanta L, Parasca I, Fazakas E, Porojan M, Pais R, Boian L. Paraneoplastic hypertrophic osteoarthropathy: evaluation at 25 years after pneumectomy. Pol Arch Med Wewn. 2009 Sep. 119(9):603-6. [Medline].
Izumi M, Takayama K, Yabuuchi H, Abe K, Nakanishi Y. Incidence of hypertrophic pulmonary osteoarthropathy associated with primary lung cancer. Respirology. 2010 Jul. 15(5):809-12. [Medline].
Aissa I, Messadi A, Boudaya S, El Mezni F, Kilani T, Ghedira H. [Hypertrophic osteoarthropathy associated with pulmonary tuberculosis]. Rev Pneumol Clin. 2011 Apr. 67(2):101-4. [Medline].
Jayakar BA, Abelson AG, Yao Q. Treatment of hypertrophic osteoarthropathy with zoledronic acid: case report and review of the literature. Semin Arthritis Rheum. 2011 Oct. 41(2):291-6. [Medline].
McGuire MM, Demehri S, Kim HB, Kamin D. Hypertrophic osteoarthropathy in intestinal transplant recipients. J Pediatr Surg. 2010 Nov. 45(11):e19-22. [Medline].
McGuire MM, Demehri S, Kim HB, Kamin D. Hypertrophic osteoarthropathy in intestinal transplant recipients. J Pediatr Surg. 2010 Nov. 45(11):e19-22. [Medline].
Suppiah R, McQueen F. Hypertrophic osteoarthropathy associated with a left ventricular tumour. Rheumatology (Oxford). 2008 Sep. 47(9):1277. [Medline].
Murphy C, Syahizul Nuhairy Mohd Sharial M, Brennan N, Lee G, Moylan E, O' Reilly S. Hypertrophic osteoarthropathy leading to the diagnosis of primitive neuroectodermal tumour (PNET). Acta Oncol. 2008. 47(5):983-6. [Medline].
Cathebras P, Gaultier JB, Charmion S, Guichard I. Hypertrophic osteoarthropathy of the lower limbs. J Rheumatol. 2011 Apr. 38(4):775-6. [Medline].
Moule B, Grant MC, Boyle IT, May H. Thyroid acropachy. Clin Radiol. 1970 Jul. 21(3):329-33. [Medline].
Kinsella RA Jr, Back DK. Thyroid acropachy. Med Clin North Am. 1968 Mar. 52(2):393-8. [Medline].
Chen L, Mulligan ME. Medication-induced periostitis in lung transplant patients: periostitis deformans revisited. Skeletal Radiol. 2011 Feb. 40(2):143-8. [Medline].
Ayub A, Kenney CV, McKiernan FE. Multifocal nodular periostitis associated with prolonged voriconazole therapy in a lung transplant recipient. J Clin Rheumatol. 2011 Mar. 17(2):73-5. [Medline].
Pracht M, Le Roux C, Kerjouan M, Boucher E, Audrain O, Raoul JL. Clubbing and hypertrophic osteoarthropathy in two patients taking long-term bevacizumab for metastatic colorectal cancer. J Gastrointest Cancer. 2011 Sep. 42(3):176-8. [Medline].
Ede K, McCurdy D, Garcia-Lloret M. Hypertrophic osteoarthropathy in the hepatopulmonary syndrome. J Clin Rheumatol. 2008 Aug. 14(4):230-3. [Medline].
Shah NN, Price MR, Loeb DM. Cardiac metastasis and hypertrophic osteoarthropathy in recurrent infantile fibrosarcoma. Pediatr Blood Cancer. 2012 Jul 15. 59(1):179-81. [Medline].
Utine EG, Yalcin B, Karnak I, et al. Childhood intrathoracic Hodgkin lymphoma with hypertrophic pulmonary osteoarthropathy: a case report and review of the literature. Eur J Pediatr. 2008 Apr. 167(4):419-23. [Medline].
Mauricio O, Francis L, Athar U, Shah C, Chaudhary M, Gajra A. Hypertrophic osteoarthropathy masquerading as lower extremity cellulitis and response to bisphosphonates. J Thorac Oncol. 2009 Feb. 4(2):260-2. [Medline].
Karimova MM, Halimova ZY, Urmanova YM, Korbonits M, Cranston T, Grossman AB. Pachydermoperiostosis Masquerading as Acromegaly. J Endocr Soc. 2017 Feb 1. 1 (2):109-112. [Medline]. [Full Text].
Diggle CP, Carr IM, Zitt E, et al. Common and recurrent HPGD mutations in Caucasian individuals with primary hypertrophic osteoarthropathy. Rheumatology (Oxford). 2010 Jun. 49(6):1056-62. [Medline].
Moreira AL, Porto NS, Moreira JS, Ulbrich-Kulczynski JM, Irion KL. Clubbed fingers: radiological evaluation of the nail bed thickness. Clin Anat. 2008 May. 21(4):314-8. [Medline].
Jajic I, Pecina M, Krstulovic B, Kovacevic D, Pavicic F, Spaventi S. Primary hypertrophic osteoarthropathy (PHO) and changes in the joints. Clinical, X-ray, scintigraphic, arteriographic and histologic examination of 19 patients. Scand J Rheumatol. 1980. 9(2):89-96. [Medline].
Bleyen I, White VA, Dolman PJ. Floppy eyelid syndrome and ptosis in a patient with pachydermoperiostosis. Ophthal Plast Reconstr Surg. 2010 Jul-Aug. 26(4):293-5. [Medline].
Bernardo SG, Emer JJ, Burnett ME, Gordon M. Hypertrophic osteoarthropathy presenting as unilateral cellulitis with successful treatment using pamidronate disodium. J Clin Aesthet Dermatol. 2012 Sep. 5(9):37-46. [Medline]. [Full Text].
Langer CJ. Role of zoledronic acid in the setting of bone metastases from non-small-cell lung cancer. Clin Lung Cancer. 2005 Mar. 6(5):314-6. [Medline].
King MM, Nelson DA. Hypertrophic osteoarthropathy effectively treated with zoledronic acid. Clin Lung Cancer. 2008 May. 9(3):179-82. [Medline].
Sonthalia N, Mukherjee K, Saha A, Talukdar A. Treatment of hypertrophic osteoarthropathy in the case of pulmonary metastasis secondary-to-nasopharyngeal carcinoma with zoledronic acid: an enlightening experience. BMJ Case Rep. 2012 Nov 11. 2012:[Medline].
Angel-Moreno Maroto A, Martinez-Quintana E, Suarez-Castellano L, Perez-Arellano JL. Painful hypertrophic osteoarthropathy successfully treated with octreotide. The pathogenetic role of vascular endothelial growth factor (VEGF). Rheumatology (Oxford). 2005 Oct. 44(10):1326-7. [Medline].
Marino WD, Harigopalan JA, Bangar M. A 49-year-old smoker with a lung mass and diffuse bone pain. Chest. 2011 Feb. 139(2):460-3. [Medline].
Thornton J, Rangaraj S. Anti-inflammatory drugs and analgesics for managing symptoms in people with cystic fibrosis-related arthritis. Cochrane Database Syst Rev. 2016 Jan 21. CD006838. [Medline]. [Full Text].
Shakya P, Pokhrel KN, Mlunde LB, Tan S, Ota E, Niizeki H. Effectiveness of non-steroidal anti-inflammatory drugs among patients with primary hypertrophic osteoarthropathy: A systematic review. J Dermatol Sci. 2017 Dec 28. [Medline].
Yuan L, Liao RX, Lin YY, Jiang Y, Wang O, Li M, et al. Safety and efficacy of cyclooxygenase-2 inhibition for treatment of primary hypertrophic osteoarthropathy: A single-arm intervention trial. J Orthop Translat. 2019 Jul. 18:109-118. [Medline].
Atkinson S, Fox SB. Vascular endothelial growth factor (VEGF)-A and platelet-derived growth factor (PDGF) play a central role in the pathogenesis of digital clubbing. J Pathol. 2004 Jun. 203 (2):721-8. [Medline].
Cerny J, Licho R, Simkin P, Walsh WV. Hypertrophic pulmonary osteoarthropathy disappearance despite lung cancer relapse. South Med J. 2008 Sep. 101(9):970-1. [Medline].
Kikuchi R, Itoh M, Tamamushi M, Nakamura H, Aoshiba K. Hypertrophic Osteoarthropathy Secondary to Lung Cancer: Beneficial Effect of Anti-vascular Endothelial Growth Factor Antibody. J Clin Rheumatol. 2017 Jan. 23 (1):47-50. [Medline].
Hayashi M, Sekikawa A, Saijo A, Takada W, Yamawaki I, Ohkawa S. Successful treatment of hypertrophic osteoarthropathy by gefitinib in a case with lung adenocarcinoma. Anticancer Res. 2005 May-Jun. 25(3c):2435-8. [Medline].
Poanta L, Parasca I, Fazakas E, Porojan M, Pais R, Boian L. Paraneoplastic hypertrophic osteoarthropathy: evaluation at 25 years after pneumectomy. Pol Arch Med Wewn. 2009 Sep. 119(9):603-6. [Medline].
Huaux JP, Geubel A, Maldague B, Michielsen P, de Hemptinne B, Otte JB, et al. Hypertrophic osteoarthropathy related to end stage cholestatic cirrhosis: reversal after liver transplantation. Ann Rheum Dis. 1987 Apr. 46 (4):342-5. [Medline].
Frand M, Koren G, Rubinstein Z. Reversible hypertrophic osteoarthropathy associated with cyanotic congenital heart disease. Am J Dis Child. 1982 Aug. 136 (8):687-9. [Medline].
Ooi A, Saad RA, Moorjani N, Amer KM. Effective symptomatic relief of hypertrophic pulmonary osteoarthropathy by video-assisted thoracic surgery truncal vagotomy. Ann Thorac Surg. 2007 Feb. 83 (2):684-5. [Medline].

Media Gallery

Clubbing associated with hypertrophic osteoarthropathy can be classified into 3 topographical groups (ie, symmetrical, unilateral, unidigital). This is symmetrical clubbing; it involves all the fingers.
Joint symptoms of hypertrophic osteoarthropathy range from mild to severe arthralgias that involve the metacarpal joints, wrists, elbows, knees, and ankles. The range of motion of affected joints may be slightly decreased. When effusions are present, they usually involve the large joints (eg, knees, ankles, wrists).
For hypertrophic osteoarthropathy diagnosis, radionuclide bone scan using technetium Tc 99m polyphosphate shows increased uptake of the tracer in the periosteum, often appearing pericortical and linear in nature. These findings can be present even when findings from plain radiographs are doubtful. The clubbed digits may also show increased uptake in early passage flow studies.
In adulthood, 90% of generalized hypertropic osteoarthropathy cases are associated with an intrathoracic infectious or neoplastic condition.

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Author

Vishnuteja Devalla, MD Fellow, Department of Rheumatology, Dartmouth-Hitchcock Medical Center

Vishnuteja Devalla, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology

Disclosure: Nothing to disclose.

Coauthor(s)

Stephanie Danielle Mathew, DO Fellowship Program Director, Dartmouth-Hitchcock Medical Center

Stephanie Danielle Mathew, DO is a member of the following medical societies: American College of Physicians, American College of Rheumatology, American Osteopathic Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Lawrence H Brent, MD Associate Professor of Medicine, Sidney Kimmel Medical College of Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center

Lawrence H Brent, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, American College of Rheumatology

Disclosure: Stock ownership for: Johnson & Johnson.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

Additional Contributors

Bryan L Martin, DO Associate Dean for Graduate Medical Education, Designated Institutional Official, Associate Medical Director, Director, Allergy Immunology Program, Professor of Medicine and Pediatrics, Ohio State University College of Medicine

Bryan L Martin, DO is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Osteopathic Association

Disclosure: Nothing to disclose.

Richa Dhawan, MD, CCD Associate Professor, Director of Osteoporosis Clinic, Center of Excellence for Arthritis and Rheumatology, Louisiana State University Health Science Center at Shreveport

Richa Dhawan, MD, CCD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American College of Rheumatology, American Association of Physicians of Indian Origin

Disclosure: Nothing to disclose.

Mehwish Amir Khan, MD Fellow in Rheumatology, Louisiana State University Health Science Center at Shreveport

Mehwish Amir Khan, MD is a member of the following medical societies: American College of Rheumatology

Disclosure: Nothing to disclose.

Acknowledgements

Mohammed Mubashir Ahmed, MD Associate Professor, Department of Medicine, Division of Rheumatology, University of Toledo College of Medicine

Mohammed Mubashir Ahmed, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, and American Federation for Medical Research

Disclosure: Nothing to disclose.

Henri Andre Menard, MD, FRCPC Professor of Medicine, Director of Rheumatology, Department of Medicine, Division of Rheumatology, McGill University Health Center (MUHC) and McGill University Faculty of Medicine; Director, The McGill Arthritis Center; Senior Physician, Shriner's Hospital for Crippled Children, Montreal; Leader, MSK Research Axis, MUHC Research Institute

Henri Andre Menard, MD, FRCPC is a member of the following medical societies: American College of Rheumatology, Canadian Medical Association, Canadian Rheumatology Association, and Quebec Medical Association

Disclosure: Nothing to disclose.

Fahd Saeed, MD Rheumatology Fellow, Louisiana State University Health Sciences Center, Shreveport

Disclosure: Nothing to disclose.