Evaluation of clubbing

Diseases

Summary

An important nail sign of systemic disease linked with underlying pulmonary, cardiovascular, neoplastic, infectious, hepatobiliary, mediastinal, endocrine, and gastrointestinal disorders.

Digital clubbing may also occur in isolation (e.g., familial clubbing, as an autosomal-dominant trait).

Definition

Clubbing is a bulbous uniform swelling of the soft tissue of the terminal phalanx of a digit with subsequent loss of the normal angle between the nail and nail bed.

The first stage of clubbing is a periungual erythema and a softening of the nail bed; this is followed by an increase in the Lovibond angle (the angle between the proximal nail fold and the nail plate). Eventually the depth of the distal phalanx increases and the distal interphalangeal joint may become hyperextensible.[1] [2]

The Schamroth window test can be used to identify or confirm clubbing. If 2 opposing fingers are held back to back against each other, a diamond-shaped space should normally appear between the nail beds and the nails of the 2 fingers. In clubbing, this space (or window) is missing.Images

Clubbing is usually bilateral, although unilateral clubbing does exist (e.g., axillary artery aneurysm and brachial arteriovenous malformations). It is painless unless associated with underlying conditions such as pulmonary hypertrophic osteoarthropathy. The vast majority of patients are unaware of its presence. However, an understanding of the causation and diseases associated with clubbing alerts the physician to the seriousness of this sign and the need to investigate the patient appropriately.Images

Pathophysiology

Vascular endothelial growth factor (VEGF) is key.[3] This platelet-derived factor is stimulated by hypoxia and produced in diverse malignancies and conditions that affect circulation. VEGF induces vascular hyperplasia, edema, and fibroblast or osteoblast proliferation at a peripheral level in the nails. In primary pulmonary conditions such as lung cancer, this is the operative mechanism. When there is extrapulmonary shunting of blood - for example, in cyanotic heart disease - large megakaryocytic fragments gain access to the systemic circulation and affect distal sites such as the nails. Here, these fragments release growth factors, including VEGF.[1] [4]

In cases of bronchogenic carcinoma, growth hormone has been implicated as a cause of clubbing. In hypertrophic osteoarthropathy, an additional unknown factor is considered necessary to produce this syndrome; cyanosis may also be required.[5] [6] Hypertrophic osteoarthropathy is characterized by abnormal proliferation of skin and periosteal tissues involving the extremities and is clinically evident as digital clubbing, periostosis of tubular bones, and synovial effusions.[7]

Platelet derived growth factor (PDGF) likely plays a role in the pathogenesis of clubbing.[2] [8] Platelets release PDGF in the vasculature of the fingertips. Conditions that involve chronic platelet excess (e.g., inflammatory bowel disease) result in peripheral platelet trapping and release of PDGF.[5] PDGF stimulates growth, vascular permeability, and monocyte and neutrophil chemotaxis, and leads to proliferation of vascular smooth muscle cells and fibroblasts, as is seen in clubbing.[5]

Clubbing may be stimulated by local arteriovenous anastomoses provoked by neurocirculatory stimuli. Unilateral clubbing secondary to local disorders (e.g., axillary artery aneurysm) is not due to a pulmonary circulation defect.[9] [10]

Library

Schamroth window test demonstrating a diamond-shaped window when fingers are not clubbed
Schamroth window test demonstrating lack of window with clubbed fingers
Finger clubbing
Pachydermoperiostosis: toe clubbing
Clubbing of nails showing loss of the classic Lovibond angle (normally ≤160° in a normal distal digit, but >180° with definitive clubbing)
Pachydermoperiostosis: furrowed and thickened forehead
Pachydermoperiostosis: finger clubbing
Pachydermoperiostosis: wrist joint swelling

Citations

Key Articles

Sarkar M, Mahesh DM, Madabhavi I. Digital clubbing. Lung India. 2012 Oct;29(4):354-62.[Abstract][Full Text]
Callemeyn J, Van Haecke P, Peetermans WE, et al. Clubbing and hypertrophic osteoarthropathy: insights in diagnosis, pathophysiology, and clinical significance. Acta Clin Belg. 2016 Jun;71(3):123-30.[Abstract]
Raghu G, Remy-Jardin M, Richeldi L, et al. Idiopathic pulmonary fibrosis (an update) and progressive pulmonary fibrosis in adults: an official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2022 May 1;205(9):e18-47.[Abstract][Full Text]

Referenced Articles

1. Marrie TJ, Brown N. Clubbing of the digits. Am J Med. 2007 Nov;120(11):940-1.[Abstract]
2. Sarkar M, Mahesh DM, Madabhavi I. Digital clubbing. Lung India. 2012 Oct;29(4):354-62.[Abstract][Full Text]
3. Callemeyn J, Van Haecke P, Peetermans WE, et al. Clubbing and hypertrophic osteoarthropathy: insights in diagnosis, pathophysiology, and clinical significance. Acta Clin Belg. 2016 Jun;71(3):123-30.[Abstract]
4. Martinez-Lavin M. Exploring the cause of the most ancient clinical sign of medicine: finger clubbing. Semin Arthritis Rheum. 2007 Jun;36(6):380-5.[Abstract]
5. Dickinson CJ, Martin JF. Megakaryocytes and platelet clumps as the cause of finger clubbing. Lancet. 1987 Dec 19;2(8573):1434-5.[Abstract]
6. Silveira LH, Martinez-Levin M, Pineda C, et al. Vascular endothelial growth factor and hypertrophic osteoarthropathy. Clin Exp Rheumatol. 2000 Jan-Feb;18(1):57-62.[Abstract]
7. Yap FY, Skalski MR, Patel DB, et al. Hypertrophic osteoarthropathy: clinical and imaging features. Radiographics. 2017 Jan-Feb;37(1):157-95.[Abstract]
8. 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.[Abstract]
9. Kahtan S, Kahtan N. Unilateral finger clubbing. Lancet. 1991 Aug 31;338(8766):576.[Abstract]
10. Kinjo T, Arakaki W, Fujita J. Unilateral digital clubbing in hemiplegia due to a putaminal hemorrhage. Clin Case Rep. 2022 Mar 1;10(3):e05519.[Abstract][Full Text]
11. Sridhar KS, Lobo CF, Altman RD. Digital clubbing and lung cancer. Chest. 1998 Dec;114(6):1535-7.[Abstract][Full Text]
12. Javidan-Nejad C, Bhalla S. Bronchiectasis. Radiol Clin North Am. 2009 Mar;47(2):289-306.[Abstract]
13. Essouma M, Nkeck JR, Agbor VN, et al. Epidemiology of digital clubbing and hypertrophic osteoarthropathy: a systematic review and meta-analysis. J Clin Rheumatol. 2022 Mar 1;28(2):104-10.[Abstract]
14. Noble PW. Idiopathic pulmonary fibrosis: natural history and prognosis. Clin Chest Med. 2006 Mar;27(1 suppl 1):S11-6;v.[Abstract]
15. Raghu G, Remy-Jardin M, Richeldi L, et al. Idiopathic pulmonary fibrosis (an update) and progressive pulmonary fibrosis in adults: an official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2022 May 1;205(9):e18-47.[Abstract][Full Text]
16. Shiraishi K, Jinta T, Nishimura N, et al. Digital clubbing is associated with higher serum KL-6 levels and lower pulmonary function in patients with interstitial lung disease. Can Respir J. 2018 Jan 23;2018:3640967.[Abstract][Full Text]
17. Ungprasert P, Ryu JH, Matteson EL. Clinical manifestations, diagnosis, and treatment of sarcoidosis. Mayo Clin Proc Innov Qual Outcomes. 2019 Sep;3(3):358-75.[Abstract][Full Text]
18. American Thoracic Society. Diagnosis and initial management of nonmalignant diseases related to asbestos. Am J Respir Crit Care Med. 2004 Sep 15;170(6):691-715.[Abstract][Full Text]
19. Roggli VL, Sharma A, Butnor KJ, et al. Malignant mesothelioma and occupational exposure to asbestos: a clinicopathological correlation of 1445 cases. Ultrastruct Pathol. 2002 Mar-Apr;26(2):55-65.[Abstract][Full Text]
20. Hadda V, Khilnani GC. Lipoid pneumonia: an overview. Expert Rev Respir Med. 2010 Dec;4(6):799-807.[Abstract]
21. Mohr LC. Hypersensitivity pneumonitis. Curr Opin Pulm Med. 2004 Sep;10(5):401-11.[Abstract]
22. Fink JN, Ortega HG, Reynolds HY, et al. Needs and opportunities for research in hypersensitivity pneumonitis. Am J Respir Crit Care Med. 2005 Apr 1;171(7):792-8.[Abstract][Full Text]
23. Duyuler S, Bayir PT, Tüfekçioğlu O. Differential clubbing in an adult patient with patent ductus arteriosus and small ventricular septal defect. Anadolu Kardiyol Derg. 2012 Apr 20;12(3):E14-5.[Abstract][Full Text]
24. Mylonakis E, Calderwood SB. Infective endocarditis in adults. N Engl J Med. 2001 Nov 1;345(18):1318-30.[Abstract]
25. Habib G, Erba PA, Iung B, et al. Clinical presentation, aetiology and outcome of infective endocarditis. Results of the ESC-EORP EURO-ENDO (European infective endocarditis) registry: a prospective cohort study. Eur Heart J. 2019 Oct 14;40(39):3222-32.[Abstract][Full Text]
26. Sun Y, Haapanen K, Li B, et al. Women and primary biliary cirrhosis. Clin Rev Allergy Immunol. 2015 Jun;48(2-3):285-300.[Abstract][Full Text]
27. Pritchard E. Familial clubbing of fingers and toes. Br Med J. 1938;1:752.[Full Text]
28. Seaton DR. Familial clubbing of digits. Br Med J. 1938 Mar 19;1(4028):614-5.[Abstract][Full Text]
29. 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.[Abstract]
30. Chan CW. Evaluation of digital clubbing. Aust Fam Physician. 2015 Mar;44(3):113-6.[Abstract][Full Text]
31. 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.[Abstract][Full Text]
32. Ahmmed MF, Shazzad MN, Ferdous S, et al. Polyarthritis is a rare manifestation of pachydermoperiostosis: a case report. Mymensingh Med J. 2017 Oct;26(4):939-43.[Abstract]
33. Torgutalp M, Durmaz CD, Karabulut HG, et al. Primary hypertrophic osteoarthropathy mimicking juvenile idiopathic arthritis: a novel SLCO2A1 mutation and imaging findings. Cytogenet Genome Res. 2019;158(3):126-32.[Abstract][Full Text]
34. Ishizuka T, Fujioka K, Mori I, et al. Primary hypertrophic osteoarthropathy with severe arthralgia identified by gene mutation of <i>SLCO2A1</i>. Mod Rheumatol Case Rep. 2021 Jan 18;:1-7.[Abstract][Full Text]
35. Bozzao F, Bernardi S, Dore F, et al. Hypertrophic osteoarthropathy mimicking a reactive arthritis: a case report and review of the literature. BMC Musculoskelet Disord. 2018 May 14;19(1):145.[Abstract][Full Text]
36. Karkucak M, Erturk E, Capkin E, et al. Primary hypertrophic osteoarthropathy (pachydermoperiostosis): a case report. Rheumatol Int. 2007 Feb;27(4):403-5.[Abstract]
37. Barraud-Klenovsek MM, Lübbe J, Burg G. Primary digital clubbing associated with palmoplantar keratoderma. Dermatology. 1997;194(3):302-5.[Abstract][Full Text]
38. Santiago MB, Lima I, Feitosa AC, et al. Pseudoclubbing: is it different from clubbing? Semin Arthritis Rheum. 2009 Jun;38(6):452-7.[Abstract]
39. Pandita KK, Afaq S, Singh D, et al. Finger clubbing in a patient of myelofibrosis with renal cell carcinoma. J Assoc Physicians India. 2012 Feb;60:124-6.[Abstract]
40. Markowitz SB, Levin SM, Miller A, et al. Asbestos, asbestosis, smoking, and lung cancer. New findings from the North American insulator cohort. Am J Respir Crit Care Med. 2013 Jul 1;188(1):90-6.[Abstract][Full Text]
41. Charlton OA, Dickison P, Smith SD, et al. Nail clubbing in laxative abuse: case report and review of the literature. J Eat Disord. 2019;7:6.[Abstract][Full Text]
42. Suzuki K, Otsuka H. Clubbing due to laxative abuse. Intern Med. 2022 May 1;61(9):1473-4.[Full Text]
43. Sperling B, Marschall J, Kennedy R, et al. Thymoma: a review of the clinical and pathological findings in 65 cases. Can J Surg. 2003 Feb;46(1):37-42.[Abstract][Full Text]
44. Martínez-Lavín M. Hypertrophic osteoarthropathy. Best Pract Res Clin Rheumatol. 2020 Jun;34(3):101507.[Abstract]
45. Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis. 2017 Jan 15;64(2):e1-e33.[Abstract][Full Text]
46. Shen KR, Bribriesco A, Crabtree T, et al. The American Association for Thoracic Surgery consensus guidelines for the management of empyema. J Thorac Cardiovasc Surg. 2017 Jun;153(6):e129-46.[Abstract][Full Text]
47. Chambers HF, Bayer AS. Native-valve infective endocarditis. N Engl J Med. 2020 Aug 6;383(6):567-76.[Abstract][Full Text]
48. Petty TL. The early diagnosis of lung cancer. Dis Mon. 2001 Jun;47(6):204-64.[Abstract]
49. Rivera MP, Mehta AC, Wahidi MM. Establishing the diagnosis of lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013 May;143(5 suppl):e142S-65.[Abstract][Full Text]
50. Hill AT, Sullivan AL, Chalmers JD, et al. British Thoracic Society guideline for bronchiectasis in adults. Thorax. 2019 Jan;74(suppl 1):1-69.[Abstract][Full Text]
51. de Hoyos A, Sundaresan S. Thoracic empyema. Surg Clin North Am. 2002 Jun;82(3):643-71;viii.[Abstract]
52. Farrell PM, White TB, Ren CL, et al. Diagnosis of cystic fibrosis: consensus guidelines from the cystic fibrosis foundation. J Pediatr. 2017 Feb;181S:S4-15;e1.[Abstract][Full Text]
53. Wong LJ, Wang J, Zhang YH, et al. Improved detection of CFTR mutations in Southern California Hispanic CF patients. Hum Mutat. 2001 Oct;18(4):296-307.[Abstract]
54. Pipavath S, Godwin JD. Imaging of interstitial lung disease. Clin Chest Med. 2004 Sep;25(3):455-65;v-vi.[Abstract]
55. Lynch DA. High-resolution CT of idiopathic interstitial pneumonias. Radiol Clin North Am. 2001 Nov;39(6):1153-70.[Abstract]
56. du Bois RM. Evolving concepts in the early and accurate diagnosis of idiopathic pulmonary fibrosis. Clin Chest Med. 2006 Mar;27(1 suppl 1):S17-25;v-vi.[Abstract]
57. Mihailovic-Vucinic V, Jovanovic D. Pulmonary sarcoidosis. Clin Chest Med. 2008 Sep;29(3):459-73;viii-ix.[Abstract]
58. Noth I, Martinez FJ. Recent advances in idiopathic pulmonary fibrosis. Chest. 2007 Aug;132(2):637-50.[Abstract]
59. Popat S, Baas P, Faivre-Finn C, et al. Malignant pleural mesothelioma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up(☆). Ann Oncol. 2022 Feb;33(2):129-42.[Full Text]
60. Boutin C, Rey F. Thoracoscopy in pleural malignant mesothelioma: a prospective study of 188 consecutive patients. Part 1: diagnosis. Cancer. 1993 Jul 15;72(2):389-93.[Abstract]
61. Ali MS, Light RW, Maldonado F. Pleuroscopy or video-assisted thoracoscopic surgery for exudative pleural effusion: a comparative overview. J Thorac Dis. 2019 Jul;11(7):3207-16.[Abstract][Full Text]
62. Pistolesi M, Rusthoven J. Malignant pleural mesothelioma: update, current management, and newer therapeutic strategies. Chest. 2004 Oct;126(4):1318-29.[Abstract]
63. Geldmacher H, Taube C, Kroeger C, et al. Assessment of lymph node tuberculosis in northern Germany: a clinical review. Chest. 2002 Apr;121(4):1177-82.[Abstract]
64. Weir MR, Thornton GF. Extrapulmonary tuberculosis. Experience of a community hospital and review of the literature. Am J Med. 1985 Oct;79(4):467-78.[Abstract]
65. Baydur A. The spectrum of extrapulmonary tuberculosis. West J Med. 1977 Apr;126(4):253-62.[Abstract][Full Text]
66. Centers for Disease Control and Prevention. Updated guidelines for the use of nucleic acid amplification tests in the diagnosis of tuberculosis. Jan 2009 [internet publication].[Full Text]
67. World Health Organization. WHO consolidated guidelines on tuberculosis: module 3: diagnosis: rapid diagnostics for tuberculosis detection. Mar 2024 [internet publication].[Full Text]
68. Bjerrum S, Schiller I, Dendukuri N, et al. Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in people living with HIV. Cochrane Database Syst Rev. 2019 Oct 21;10(10):CD011420.[Abstract][Full Text]
69. World Health Organization. WHO operational handbook on tuberculosis: module 3: diagnosis: rapid diagnostics for tuberculosis detection, 2021 update. Jul 2021 [internet publication].[Full Text]
70. Mangiameli G, Cioffi U, Alloisio M, et al. Lung metastases: current surgical indications and new perspectives. Front Surg. 2022 Apr 29;9:884915.[Abstract][Full Text]
71. Acebo E, Val-Bernal JF, Gómez-Román JJ, et al. Clinicopathologic study and DNA analysis of 37 cardiac myxomas: a 28-year experience. Chest. 2003 May;123(5):1379-85.[Abstract]
72. Butany J, Nair V, Naseemuddin A, et al. Cardiac tumors: diagnosis and management. Lancet Oncol. 2005 Apr;6(4):219-28.[Abstract]
73. Nayak B, Hodak SP. Hyperthyroidism. Endocrinol Metab Clin North Am. 2007 Sep;36(3):617-56;v.[Abstract]
74. Clemmons DR. IGF-I assays: current assay methodologies and their limitations. Pituitary. 2007;10(2):121-8.[Abstract]
75. Katznelson L, Laws ER Jr, Melmed S, et al. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014 Nov;99(11):3933-51.[Abstract][Full Text]
76. Ben-Shlomo A, Melmed S. Acromegaly. Endocrinol Metab Clin North Am. 2008 Mar;37(1):101-22;viii.[Abstract][Full Text]
77. Melmed S. Medical progress: acromegaly. N Engl J Med. 2006 Dec 14;355(24):2558-73. [Erratum in: N Engl J Med. 2007 Feb 22;356(8):879.][Abstract][Full Text]
78. Hodgson DC. Hodgkin lymphoma: the follow-up of long-term survivors. Hematol Oncol Clin North Am. 2008 Apr;22(2):233-44;vi.[Abstract]
79. Silver RT. Chronic myeloid leukemia. Hematol Oncol Clin North Am. 2003 Oct;17(5):1159-73;vi-vii.[Abstract]
80. Mayo MJ. Natural history of primary biliary cirrhosis. Clin Liver Dis. 2008 May;12(2):277-88;viii.[Abstract]
81. Mendes F, Lindor KD. Antimitochondrial antibody-negative primary biliary cirrhosis. Gastroenterol Clin North Am. 2008 Jun;37(2):479-84;viii.[Abstract]
82. Kim SJ, Seo JH, Choi CW, et al. Unusual presentation of thymic carcinoma: hypertrophic osteoarthropathy. Korean J Intern Med. 2003 Jun;18(2):125-8.[Abstract][Full Text]
83. Lee KS, Kim EA. High-resolution CT of alveolar filling disorders. Radiol Clin North Am. 2001 Nov;39(6):1211-30.[Abstract]
84. Camus P, Bonniaud P, Fanton A, et al. Drug-induced and iatrogenic infiltrative lung disease. Clin Chest Med. 2004 Sep;25(3):479-519;vi.[Abstract]
85. Yi ES. Tumors of the pulmonary vasculature. Cardiol Clin. 2004 Aug;22(3):431-40;vi-vii.[Abstract]
86. Kauczor HU, Schwickert HC, Mayer E, et al. Pulmonary artery sarcoma mimicking chronic thromboembolic disease: computed tomography and magnetic resonance imaging findings. Cardiovasc Intervent Radiol. 1994 Jul-Aug;17(4):185-9.[Abstract]
87. Pardanani A, Guglielmelli P, Lasho TL, et al. Primary myelofibrosis with or without mutant MPL: comparison of survival and clinical features involving 603 patients. Leukemia. 2011 Dec;25(12):1834-9.[Abstract]
88. Tefferi A, Lasho TL, Finke CM, et al. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia. 2014 Jul;28(7):1472-7.[Abstract]