Clubbing of the Nails Workup
- Author: Robert A Schwartz, MD, MPH; Chief Editor: William D James, MD more...
Because clubbing typically is secondary to an underlying pathological process, perform pertinent laboratory studies for primary medical disorders that are suggested clinically.
Radiographic changes in patients with digital clubbing vary and include bone dissolution, bone formation, or no change in the bone of the distal phalanx. The types of changes may depend on the underlying pathological processes, as well as the duration of the processes. The severity of soft tissue changes in clubbed digits has not been found to correlate with the type of bone change or the degree of radiographic change. Probably, the lysis of bone predominates in the digits of patients with congenital cyanotic heart disease, while hypertrophy predominates in the digits of patients with clubbing secondary to pulmonary conditions. As an alternate view, hypertrophy may occur earlier in the process of clubbing, and, eventually, it may change to osteolysis as the process becomes chronic.
Technetium Tc 99m skeletal imaging with good-quality views may be helpful in determining the presence and extent of bone changes in clubbed digits, which show increased uptake of the radionuclide. The increased, intense, symmetric uptake typically is localized to the nail beds and may result from increased blood flow and changes in the surrounding soft tissues.
Thermography is another imaging modality being studied for use in diagnosis and monitoring of patients with digital clubbing. Patients may show increased temperature in the distal digits, which can be attributed to an increase in blood flow secondary to vasodilation. Not all patients with clubbing have positive thermographic results.
Positron emission tomography also has been used to study the glucose metabolism of clubbed digits. An increased signal, indicating increased glucose metabolism, has been demonstrated in the distal part of the clubbed fingers. These changes are not seen in fingertips with normal morphology. The increase in signal supports the theory that clubbing is caused by the presence of a factor (eg, platelet-derived growth factor) that increases cellular metabolism.
Other imaging studies, such as computed tomography or magnetic resonance imaging, may be helpful in evaluating the patient for the primary pathological process causing the clubbing. Use of high-frequency ultrasound imaging has also been advocated for the diagnosis of clubbing. Ultrasound in primary hypertrophic osteoarthropathy may show echogenic tissue surrounding the long bones, likely a reflection of edema and inflammatory tissue.
Microscopically, the collagen fibrils and cells are separated by a distance greater than that seen in histologically normal specimens. This increased separation results in a less dense nail bed matrix. Primitive fibroblasts are seen with large nuclei, basophilic cytoplasm, and long reticular processes. Increased and scattered extravascular lymphocytes and, less often, a moderately increased number of tissue eosinophils also are noted in the nail beds of some specimens. The periosteum of the nail bed may be thickened with increased vascular penetration.
Eventually, increased collagen is laid down in all types of chronic clubbing. The mat of collagen fibers may be abnormally thick and dense. The walls of the vascular components increase in thickness and are encased in a thick fibrous sheet. At this stage of clubbing, the histologic and morphologic changes probably are irreversible.
Goyal S, Griffiths AD, Omarouayache S, Mohammedi R. An improved method of studying fingernail morphometry: application to the early detection of fingernail clubbing. J Am Acad Dermatol. 1998 Oct. 39(4 Pt 1):640-2. [Medline].
Castori M, Sinibaldi L, Mingarelli R, Lachman RS, Rimoin DL, Dallapiccola B. Pachydermoperiostosis: an update. Clin Genet. 2005 Dec. 68(6):477-86. [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 Feb 13. [Medline].
Tariq M, Azeem Z, Ali G, Chishti MS, Ahmad W. Mutation in the HPGD gene encoding NAD+ dependent 15-hydroxyprostaglandin dehydrogenase underlies isolated congenital nail clubbing (ICNC). J Med Genet. 2009 Jan. 46(1):14-20. [Medline].
Nakamura J, Halliday NA, Fukuba E, Radjenovic A, Tanner SF, Emery P, et al. The Microanatomic Basis of Finger Clubbing -- A High-resolution Magnetic Resonance Imaging Study. J Rheumatol. 2014 Mar. 41(3):523-7. [Medline].
Dickinson CJ, Martin JF. Megakaryocytes and platelet clumps as the cause of finger clubbing. Lancet. 1987 Dec 19. 2(8573):1434-5. [Medline].
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 Mar 10. 6:45. [Medline].
Saigal R, Kansal A, Mittal M, Singh Y, Ram H. Pachydermoperiostosis with myelofibrosis and empty sella. J Assoc Physicians India. 2010 Apr. 58:253-5. [Medline].
Ozdemir B, Senturk T, Kaderli AA, et al. Postoperative regression of clubbing at an unexpected rate in a patient with aortic and mitral valve replacement due to infective endocarditis. Ir J Med Sci. 2008 Oct 9. [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 Feb 2. [Medline].
Pinto-Almeida T, Caetano M, Alves R, Selores M. Cutaneous lesions and finger clubbing uncovering hypocomplementemic urticarial vasculitis and hepatitis C with mixed cryoglobulinemia. An Bras Dermatol. 2013 Nov-Dec. 88(6):973-6. [Medline]. [Full Text].
Pallarés-Sanmartín A, Leiro-Fernández V, Cebreiro TL, Botana-Rial M, Fernández-Villar A. Validity and reliability of the Schamroth sign for the diagnosis of clubbing. JAMA. 2010 Jul 14. 304(2):159-61. [Medline].
Hugosson C, Bahabri S, Rifai A, al-Dalaan A. Hypertrophic osteoarthropathy caused by lipoid pneumonia. Pediatr Radiol. 1995. 25(6):482-3. [Medline].
Shneerson JM. Digital clubbing and hypertrophic osteoarthropathy: The underlying mechanisms. Br J Dis Chest. 1981 Apr. 75(2):113-31. [Medline].
Fawcett RS, Linford S, Stulberg DL. Nail abnormalities: clues to systemic disease. Am Fam Physician. 2004 Mar 15. 69(6):1417-24. [Medline].
Sridhar KS, Lobo CF, Altman RD. Digital clubbing and lung cancer. Chest. 1998 Dec. 114(6):1535-7. [Medline].
Grathwohl KW, Thompson JW, Riordan KK, Roth BJ, Dillard TA. Digital clubbing associated with polymyositis and interstitial lung disease. Chest. 1995 Dec. 108(6):1751-2. [Medline].
Kanematsu T, Kitaichi M, Nishimura K, Nagai S, Izumi T. Clubbing of the fingers and smooth-muscle proliferation in fibrotic changes in the lung in patients with idiopathic pulmonary fibrosis. Chest. 1994 Feb. 105(2):339-42. [Medline].
West SG, Gilbreath RE, Lawless OJ. Painful clubbing and sarcoidosis. JAMA. 1981 Sep 18. 246(12):1338-9. [Medline].
Loredo JS, Fedullo PF, Piovella F, Moser KM. Digital clubbing associated with pulmonary artery sarcoma. Chest. 1996 Jun. 109(6):1651-3. [Medline].
Smahi M, Lakranbi M, Choumi I, Elbiaz M, Amara B, Benjelloun MC. [Nail clubbing and lung hydatid cysts]. Rev Mal Respir. 2010. 27(1):99-101. [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].
Younis I, Sarwar S, Butt Z, Tanveer S, Qaadir A, Jadoon NA. Clinical characteristics, predictors, and survival among patients with hepatopulmonary syndrome. Ann Hepatol. 2015 May-Jun. 14 (3):354-60. [Medline].
Kitis G, Thompson H, Allan RN. Finger clubbing in inflammatory bowel disease: its prevalence and pathogenesis. Br Med J. 1979 Oct 6. 2(6194):825-8. [Medline].
Barraud-Klenovsek MM, Lübbe J, Burg G. Primary digital clubbing associated with palmoplantar keratoderma. Dermatology. 1997. 194(3):302-5. [Medline].
Mullins GM, Lenhard RE Jr. Digital clubbing in Hodgkin's disease. Johns Hopkins Med J. 1971 Mar. 128(3):153-7. [Medline].
Dispenzieri A, Gertz MA. Treatment options for POEMS syndrome. Expert Opin Pharmacother. 2005 Jun. 6(6):945-53. [Medline].
Miest RY, Comfere NI, Dispenzieri A, Lohse CM, El-Azhary RA. Cutaneous manifestations in patients with POEMS syndrome. Int J Dermatol. 2013 Apr 4. [Medline].
Grekas D, Avdelidou A. Digital clubbing as an unusual complication associated with severe secondary hyperparathyroidism: report of two cases. Hemodial Int. 2007 Apr. 11(2):193-7. [Medline].
Helvaci MR, Gokce C, Davran R, Acipayam C, Akkucuk S, Ugur M. Tonsilectomy in sickle cell diseases. Int J Clin Exp Med. 2015. 8 (3):4586-90. [Medline].
Schuller A, Cottin V, Hot A, Cordier JF. Finger clubbing and altered carbon monoxide transfer capacity in cannabis smokers. Eur Respir J. 2008 Feb. 31(2):473-4. [Medline].
El Bakkal A, Idrissi R, Meziane M, Mikou O, Sekal M, Belghiti H, et al. [Tripe palms and a hypertrophic osteoarthropathy syndrome revealing a neuroendocrine carcinoma of the lung]. Ann Dermatol Venereol. 2011 Oct. 138(10):668-72. [Medline].
Thompson MA, Warner NB, Hwu WJ. Hypertrophic osteoarthropathy associated with metastatic melanoma. Melanoma Res. 2005 Dec. 15(6):559-61. [Medline].
Lommatzsch M, Julius P, Lück W, Bier A, Virchow JC. [Hypertrophic Pulmonary Osteoarthropathy as a Cue for NSCLC: Four Cases in the Light of the Current Literature]. Pneumologie. 2012 Feb. 66(2):67-73. [Medline].
Tajbakhsh R, Dehghan M, Azarhoosh R, Haghighi AN, Sadani S, Zadeh SS, et al. Mucocutaneous manifestations and nail changes in patients with end-stage renal disease on hemodialysis. Saudi J Kidney Dis Transpl. 2013 Jan. 24(1):36-40. [Medline].
Salem A, Al Mokadem S, Attwa E, Abd El Raoof S, Ebrahim HM, Faheem KT. Nail changes in chronic renal failure patients under haemodialysis. J Eur Acad Dermatol Venereol. 2008 Nov. 22(11):1326-31. [Medline].
Rush PJ, Giorshev C, Shore A, Levinson H. The use of thermography in clubbing. Respir Med. 1992 May. 86(3):257-9. [Medline].
Ward RW, Chin R Jr, Keyes JW Jr, Haponik EF. Digital clubbing. Demonstration with positron emission tomography. Chest. 1995 Apr. 107(4):1172-3. [Medline].
Roy HS, Wang Z, Ran H, Song W, Zheng Y. Diagnosis of digital clubbing by high-frequency ultrasound imaging. Int J Dermatol. 2013 Jan. 52(1):1-5. [Medline].
Adams B, Amin T, Leone V, Wood M, Kraft JK. Primary hypertrophic osteoarthropathy: ultrasound and MRI findings. Pediatr Radiol. 2016 May. 46 (5):727-30. [Medline].
Li ZT, Wang D, Wang S. Successful treatment of pachydermoperiostosis with etoricoxib in a patient with a homozygous splice-site mutation in the SLCO2A1 gene. Br J Dermatol. 2016 Feb 15. [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].
Saghafi M, Azarian A, Nohesara N. Primary hypertrophic osteoarthropathy with myelofibrosis. Rheumatol Int. 2008 Apr. 28(6):597-600. [Medline].