Nail Clubbing


Article Author:
Serghei Burcovschii


Article Editor:
Ayham Aboeed


Editors In Chief:
Dustin Constant
Donald Kushner


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Kyle Blair
Trevor Nezwek
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Daniyal Ameen
Altif Muneeb
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
4/2/2019 9:36:23 PM

Introduction

Clubbing of the nails is soft tissue swelling of the terminal phalanx resulting in straightening of the angle that exists between the nail bed and the nail.[1] The association of clubbing of the fingers with an underlying disease was known since the time of Hippocrates. Clubbing occurs in combination with other dermatologic and skeletal findings but can also less commonly occur in isolation. Although clubbing can present in many diverse conditions, it can be idio­pathic or familial; the familial form frequently transmits as a dominant trait.

Etiology

There are several causes of acquired nail clubbing which include infectious, neoplastic, inflammatory, and vascular diseases.[2]  Isolated nail clubbing can be a benign hereditary condition but given the multiple associated conditions underlying etiology should be ruled out.

Epidemiology

The incidence can be difficult to estimate given the numerous underlying etiologies. Further, not all patients with an underlying disease have the clinical manifestation of digital clubbing. In general, clubbing is seen in roughly 1% of all internal medicine admissions and is associated with serious underlying disease in 40% of those patients.[3]

Of the etiologies in adults, the most common pulmonary cause of clubbing is lung malignancy.[4]  Of the several different types of thoracic malignancy, 80% of these cases of clubbing are caused by lung cancer, while pleural tumors contribute to roughly 10%, and other intrathoracic and mediastinal growth account for 5% of cases.[4]  Despite being such a predominant cause of clubbing, clubbing is prevalent in only 5% to 15% of lung cancer patients.[4]  The prevalence of clubbing in other conditions like interstitial lung disease, cardiovascular disease, gastrointestinal disease, infectious disease, and other cancers has been reported but shows significant variation.

Patients with clubbing may also have hypertrophic osteo­arthropathy, a condition that characteristically presents with the subperiosteal formation of new cancellous bone at the distal ends of long bones, in particular, the radius and ulna and the tibia and fibula. Hypertrophic osteoarthropathy is almost always associated with clubbing, particularly in patients with bronchogenic carcinoma, other intrathoracic malignancies, and cystic fibrosis.

Pathophysiology

Multiple hypotheses have been proposed over the years in the attempt to describe the pathophysiology of clubbing. The main pathologic finding in clubbing is increased cap­illary density. The increased release of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) from peripheral megakaryocytes leads to increased vascularity, permeability, and ultimately connective tissue changes. The release of both PDGF and VEGF is thought to be enhanced by hypoxia.[5][6]

Numerous other signaling proteins are thought to be associated with digital clubbing including prostaglandins, bradykinin, ferritin, adenosine nucleotides, interleukin-6, von Willebrand factor, serum transforming growth factor-beta1 (TGF-beta1), tumor necrosis factor-a, growth hormone, epidermal growth factor.[1]

Shunting of blood past the capillary bed of either the lung or the liver, which suggests that a lack of metabolism of angiogenic factors that bypass a critical organ may be involved.

History and Physical

A proper history and physical exam are key to the evaluation of digital nail clubbing especially given the numerous etiologies of this physical exam finding. While conducting the patient interview, it is crucial to identify the symptoms the patient has which will guide and narrow your differential diagnosis. It is important to remember that not all patients with clubbing have an underlying pathological disease and not all with a disease will have the manifestation of digital clubbing.

Equally, it is just as important to note that clubbing itself has a large degree of variation. The assessment of clubbing by physical exam is subjective and is not always reliable, especially if the clubbing is minimal and not severe.

The most widely known physical exam sign of clubbing is the profile sign also known as Lovibond angle. The Lovibond angle is the angle found between the proximal nail fold and the nail at the location at the exit of the nail from the nail fold. Usually, this angle is less than 180 degrees in normal individuals. True digit clubbing usually can be therefore differentiated from simple nail curving when the angle is greater than 180 degrees.

The hyponychial angle is also used as an objective criterion to assess clubbing. It is where a line is drawn from the cuticle the distal digital crease and the second line is drawn from the hyponychium to the cuticle.[4] An angle of fewer than 192 degrees is normal.

The phalangeal depth ratio, which is the ratio of digit’s depth measured at the nail and the distal interphalangeal joint, is another objective criterion used to assess clubbing. The depth at the DIP joint is normally greater than that of the nail. A ratio of greater than 1, therefore, supports clubbing.

In 1976, Schamroth reported a clinical sign associated with clubbing demonstrating obliteration in clubbed fingers of the diamond-shaped window normally produced when the dorsal surfaces of the corresponding finger of each hand are opposed and now called Schamroth sign.

Of these features, the nail cuticle angle straightening appears to be the most sensitive measurement.[2]

A noteworthy feature of clubbing is the speed with which it can develop, about 2 weeks in patients with new-onset empyema, and how quickly it can reverse, also about 2 weeks in patients after corrective cardiac surgery.

Evaluation

The evaluation of digital clubbing is primarily during initial patient evaluation. A thoroughly taken history including attention to characteristic features of the many possible etiologies of clubbing should be taken into account. The history is followed by the physical exam where digital clubbing is assessed based on the features mentioned above, and measurements. Acquired clubbing is most often associated with pulmonary or cardiovascular diseases so obtaining chest radiography is very reasonable during initial workup. If plain films demonstrate no abnormality, a CT scan is a next step to look for a pulmonary neoplasm or other lesions which may still be localized and curable.

Treatment / Management

Treatment and management of digital clubbing are not focused on the clubbing finding itself but rather on the underlying etiology behind clubbing if it exists. Response to treatment will have a significant degree of variation depending on the underlying disease process. Data for the reversibility of clubbing is sparse. Clubbing reversibility has been reported in particular in patients undergoing prostaglandin therapy for liver disease who developed clubbing which reversed with the cessation of therapy.[1]

Differential Diagnosis

Neoplastic intrathoracic disease associated with clubbing includes bronchogenic carcinoma, malignant and benign pleural tumors, metastatic cancers, Hodgkin lymphoma, thymoma, pulmonary artery sarcoma, nasopharyngeal carcinoma, rhabdomyosarcoma, primary lymphosarcoma of the lung, and esophageal cancer.

Suppurative intrathoracic disease associated with clubbing includes lung abscess, bronchiectasis, cystic fibrosis, empyema, and chronic lung cavitary mycobacterial or fungal infection.

Diffuse pulmonary disease associated with clubbing includes idiopathic pulmonary fibrosis, asbestosis, Langerhans cell histiocytosis, lipoid pneumonia, and pulmonary arteriovenous malformations.

Cardiovascular disease associated with clubbing includes cyanotic congenital heart disease, infective endocarditis, arterial graft sepsis, brachial arteriovenous fistula, aortic aneurysm, atrial myxoma, and hemiplegic stroke.

Gastrointestinal disease associated with clubbing includes inflammatory bowel disease, celiac disease, amoebiasis, ascariasis, and lymphoma of the gastrointestinal tract.

Hepatobiliary disease including biliary cirrhosis and juvenile cirrhosis also correlates with nail clubbing.

Metabolic diseases such as thyroid acropathy and severe secondary hyperparathyroidism too may present with the finding of clubbing.

Medication-induced cases also exist, including laxative overuse, interferon alfa-2A, and prostaglandin infusion.[4][7]

Prognosis

As with the treatment and management of digital clubbing, the prognosis is highly dependent on the underlying etiology. If the etiology is reversible, then clubbing will reverse. But if the condition is chronic or associated with a malignancy, clubbing is long term.

Complications

Clubbing as an individual entity results in aesthetic changes which can lead to complications especially surrounding the psychosocial aspects of everyday life. Although the data is sparse, reports indicate that acquired clubbing is reversible with successful treatment of the underlying condition.[8] Furthermore, it is vital to establish the etiology of clubbing as the underlying condition responsible may itself result in further complications if left untreated.

Deterrence and Patient Education

Patients, in general, benefit greatly from adequate information provided to them by healthcare workers, especially regarding a condition they may have. As with other medical conditions, information on clubbing should be given to patients, and they should be encouraged to ask questions to prompt further their insight into their situation. When acceptable, patients should receive reassurance especially if the cause of their clubbing is not due to the underlying pathology.

Enhancing Healthcare Team Outcomes

Nail clubbing is a physical exam finding that often correlates with a serious underlying disease. Proper recognition of clubbing, therefore, plays a vital outcome in the progression of the disease. The initial physical exam in the case of clubbing may be at either an inpatient or outpatient setting depending on the underlying cause. Clubbing is identifiable by anyone conducting the physical exam including medical students, nurses, nurse practitioners, physician assistants, and physicians. Regardless of who recognizes the clubbing first, an interprofessional team approach is the ideal way to evaluate and manage a patient with clubbing.

In many cases, depending on the underlying cause of the clubbing, evaluation by specialists may be required. These include pulmonologists, oncologists, infectious disease specialists, cardiologists, gastroenterologists, endocrinologists, and/or radiologists. Cases where clubbing results in increased stress due to impaired physical appearance may warrant intervention from a behavioral therapist.

 

 


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Nail Clubbing - Questions

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A patient with a long history of a congenital heart disorder is found to have an increased Lovibond angle. This usually indicates the development of which of the following?



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In which medical disorder do providers use the Schamroth window to assess disease?



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In a patient with new onset clubbing, what is the study of choice?



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Which of the following lung diseases can be associated with finger clubbing?



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Digital clubbing can be seen in which of the following conditions?



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Which of the following would be the most appropriate investigation in an individual with digital clubbing?



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What is the most common cause of digital clubbing?



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At what angle between the nail bed and the cuticula is considered clubbing of the fingernail?



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Which disease process is associated with clubbing?



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Which of the following is associated with nail clubbing?



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Unilateral clubbing and unidigital clubbing of the nails suggest the diagnosis of:



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What is the single most reliable clinical finding to establish the diagnosis of clubbing?



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On physical exam, you are asked to point to the Lovibond angle. What organ do you point at?



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Which congenital heart disorder will present with a positive Schamroth sign?



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A nurse is rounding on the cardiology floor and enters the room of a child with a congenital heart defect. While conducting the physical assessment, the nurse notes the following feature (see image). Such a pathological finding may be found in patients with which of the following? Select all that apply.

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A 47-year-old man presents to the emergency department complaining of cough, subjective fevers, and night sweats for the past week. He has recently immigrated to the United States from Russia where he worked as a computer programmer. He eats a diet high in fish and reports drinking one to two beers once a week during the weekend. On physical examination, he is noted to have abnormally enlarged fingertips and curvature of the nails. Which of the following is the most likely cause of this physical exam finding?



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A 39-year-old woman is seen in a primary care clinic for the first time after moving from out of state complaining of diffuse abdominal pain, cramping, and non-bloody diarrhea for the past week. She was previously on sulfasalazine for Crohn disease but since moving 3 months ago ran out of her medication and has not been taking it. On physical examination, she is noted to have abnormally enlarged fingertips and curvature of the nails. Which of the following is the most likely cause of this physical exam finding?



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Nail Clubbing - References

References

Dubrey S,Pal S,Singh S,Karagiannis G, Digital clubbing: forms, associations and pathophysiology. British journal of hospital medicine (London, England : 2005). 2016 Jul;     [PubMed]
Myers KA,Farquhar DR, The rational clinical examination. Does this patient have clubbing? JAMA. 2001 Jul 18;     [PubMed]
Sarkar M,Mahesh DM,Madabhavi I, Digital clubbing. Lung India : official organ of Indian Chest Society. 2012 Oct;     [PubMed]
Vandemergel X,Renneboog B, Prevalence, aetiologies and significance of clubbing in a department of general internal medicine. European journal of internal medicine. 2008 Jul;     [PubMed]
McPhee SJ, Clubbing 1990;     [PubMed]
Tucker JR, Nail Deformities and Injuries. Primary care. 2015 Dec     [PubMed]
Baran R, [The use of nails to diagnosis diseases]. Presse medicale (Paris, France : 1983). 2014 Nov     [PubMed]
Charlton OA,Dickison P,Smith SD,Roger SD, Nail clubbing in laxative abuse: case report and review of the literature. Journal of eating disorders. 2019     [PubMed]

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