COVER ARTICLE CARING FOR COMMON SKIN CONDITIONS Nail Abnormalities: Clues to Systemic Disease ROBERT S. FAWCETT, M.D., M.S., Thomas M. Hart Family Practice Residency Program, York Hospital, York, Pennsylvania SEAN LINFORD, M.D., and DANIEL L. STULBERG, M.D., Utah Valley Family Practice Residency Program, Provo, Utah The visual appearance of the fingernails and toenails may suggest an underlying systemic disease. Clubbing of the nails often suggests pulmonary disease or inflammatory bowel disease. Koilonychia, or “spoon-shaped” nails, may stimulate a work-up for hemochromatosis or anemia. In the absence of trauma or psoriasis, onycholysis should prompt a search for symptoms of hyperthyroidism. The find- ing of Beau’s lines may indicate previous severe illness, trauma, or exposure to cold temperatures in patients with Raynaud’s disease. In patients with Muehrcke’s lines, albumin levels should be checked, and a work-up done if the level is low. Splinter hemorrhage in patients with heart murmur and unex- plained fever can herald endocarditis. Patients with telangiectasia, koilonychia, or pitting of the nails may have connective tissue disorders. (Am Fam Physician 2004;69:1417-24. Copyright© 2004 American Academy of Family Physicians.) areful examination of in ridging or splitting. A transient prob- the fingernails and toe- lem causing growth disturbance may lead nails can provide clues to the formation of transverse lines across to underlying systemic the nail plate, as in Mees’, Muehrcke’s, diseases (Table 1). Club- and Beau’s lines (Figure 2). Changes in Cbing, which is one example of a nail the configuration of the capillaries in manifestation of systemic disease, was the proximal nail bed are responsible first described by Hippocrates in the fifth for some of the alterations that occur in century B.C.1 Since that time, many more patients with connective tissue disorders, nail abnormalities have been found to be while abnormalities in the periosteal ves- clues to underlying systemic disorders. sels contribute to clubbing.2 The nail plate is the hard keratin cover The nail is bound proximally by the of the dorsal portion of the distal pha- eponychium (the skin just proximal to lanx. The nail plate is generated by the the cuticle), laterally by the nail folds, and nail matrix at the proximal portion of distally by the distal nail fold (defined by the nail bed (Figure 1). As the nail grows, the separation created by the anterior the distal part of the matrix produces ligament between the distal nail bed and the deeper layers of the nail plate, while the nail plate; Figure 1). the proximal portion makes the super- Localized bacterial and fungal infec- ficial layers. This production is impor- tions of the nail, the most common nail tant, because a disruption of function problems seen by family physicians, have in the proximal matrix (as may occur in been reviewed elsewhere.3,4 patients with psoriasis) results in more superficial nail problems (e.g., pitting). A Growth Disturbances disruption of the distal matrix may cause yellow nail syndrome problems with the deeper layers, resulting A 1964 study5 described “yellow nail syndrome,” in which nails grow more slowly and develop a “heaped-up” or Superficial nail problems are caused by proximal matrix disrup- thickened appearance. The lateral sides of the nail plate show exaggerated convex- tion, while deeper nail abnormalities are caused by distal matrix ity, the lunula (i.e., the white half-moon disruption. at the proximal edge of the nail bed) disappears, and the nail takes on a yel- Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright© 2004 American Academy of Family Physicians. For the private, noncommercial use of one individual user of the Web site. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests. TABLE 1 Nail Findings and Associated Systemic Conditions Nail finding Associated systemic conditions Shape or growth change Clubbing Inflammatory bowel disease, pulmonary malignancy, asbestosis, chronic bronchitis, COPD, cirrhosis, congenital heart disease, endocarditis, atrioventricular malformations, fistulas Koilonychia Iron deficiency anemia, hemochromatosis, Raynaud’s disease, SLE, trauma, nail-patella syndrome Onycholysis Psoriasis, infection, hyperthyroidism, sarcoidosis, trauma, amyloidosis, connective tissue disorders Pitting Psoriasis, Reiter’s syndrome, incontinentia pigmenti, alopecia areata Beau’s lines Any severe systemic illness that disrupts nail growth, Raynaud’s disease, pemphigus, trauma Yellow nail Lymphedema, pleural effusion, immunodeficiency, bronchiectasis, sinusitis, rheumatoid arthritis, nephrotic syndrome, thyroiditis, tuberculosis, Raynaud’s disease Color change Terry’s (white) nails Hepatic failure, cirrhosis, diabetes mellitus, CHF, hyperthyroidism, malnutrition Azure lunula Hepatolenticular degeneration (Wilson’s disease), silver poisoning, quinacrine therapy Half-and-half nails Specific for renal failure Muehrcke’s lines Specific for hypoalbuminemia Mees’ lines Arsenic poisoning, Hodgkin’s disease, CHF, leprosy, malaria, chemotherapy, carbon monoxide poisoning, other systemic insults Dark longitudinal streaks Melanoma, benign nevus, chemical staining, normal variant in darkly pigmented people Longitudinal striations Alopecia areata, vitiligo, atopic dermatitis, psoriasis Splinter hemorrhage Subacute bacterial endocarditis, SLE, rheumatoid arthritis, antiphospholipid syndrome, peptic ulcer disease, malignancies, oral contraceptive use, pregnancy, psoriasis, trauma Telangiectasia Rheumatoid arthritis, SLE, dermatomyositis, scleroderma COPD = chronic obstructive pulmonary disease; SLE = systemic lupus erythematosus; CHF = congestive heart failure. Distal edge Lateral of nail plate Onycholysis nail fold Cuticle Longitudinal band Nail bed Eponychium Lunula Nail plate Nail plate Beau’s lines Cuticle Distal nail Pitting fold Mees’ or Eponychium Muehrcke’s lines Anterior ligament Posterior ligament Nail matrix ILLUSTRATIONS BY DAVID KLEMM BY DAVID ILLUSTRATIONS FIGURE 1. Anatomic structures of the nail. FIGURE 2. Pathologic findings in the nail. 1418-AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 69, NUMBER 6 / MARCH 15, 2004 Nail Abnormalities The finding of clubbing without obvious associated disease should prompt a search for bronchogenic carcinoma or another occult disease. FIGURE 3. Clubbing. This condition may accompany neoplastic and other lung dis- eases, atrioventricular malformations, con- genital heart disease, celiac disease, and inflammatory bowel disease. low hue. This syndrome may be seen in patients with FIGURE 4. Schamroth sign. This finding, which chronic bronchiectasis or sinusitis, pleural defines clubbing, is the obliteration of the effusions, internal malignancies, immunode- normal diamond-shaped space at the proxi- ficiency syndromes, and rheumatoid arthritis.6 mal end of the nail when the distal phalanges When it occurs in patients with rheumatoid are opposed. arthritis, yellow nail syndrome commonly is found in the patients treated with thiol drugs filtration in the pulmonary bed and have (e.g., bucillamine and gold sodium thioma- entered the systemic circulation. Platelets then late); these medications are thought to play a may release platelet-derived growth factor at role in the nail condition.7 the nail bed, causing periosteal changes.10 The Because yellow nail syndrome often affects angle between the finger proximal to the nail patients with impaired lymphatic drainage and the proximal nail plate is straightened, of the extremities or face, there may be an creating the “Schamroth sign,” which is an etiologic mechanism, although this theory obliteration of the normally diamond-shaped has not been substantiated.8 Others research- space formed when dorsal sides of the distal ers suspect that the cause of yellow nail syn- phalanges of corresponding right and left dig- drome may be related to protein leakage from its are opposed (Figure 4). increased microvascular permeability, which Clubbing occurs in patients with neoplastic would account for its common association diseases, particularly those of the lung and with hypoalbuminemia, pleural effusion, and pleura. It also may accompany other pulmo- lymphedema.9 nary diseases, including bronchiectasis, lung abscess, empyema, pulmonary fibrosis, and CLUBBING cystic fibrosis. Arteriovenous malformations Clubbing of the nails (Figure 3) is a thicken- or fistulas have been associated with clubbing, ing of the soft tissue beneath the proximal nail as have celiac disease, cirrhosis, and inflamma- plate that results in sponginess of the proximal tory bowel disease. Clubbing also may occur plate and thickening in that area of the digit.1 in patients with congenital heart disease and The cause of clubbing is poorly understood; endocarditis. The finding of clubbing without the condition may result from megakaryo- an obvious associated disease should prompt a cytes and platelet clumps that have escaped search for bronchogenic carcinoma or another MARCH 15, 2004 / VOLUME 69, NUMBER 6 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN-1419 depressions in the nail plate. Pitting usually is occult reason for the finding. associated with psoriasis, affecting 10 to 50 per- cent of patients with that disorder.13 Pitting also KOILONYCHIA may be caused by a variety of systemic diseases, Koilonychia is represented by transverse including Reiter’s syndrome and other connec- and longitudinal concavity of the nail, result-