Nutrition and nail disease
3 Michael W. Cashman, BA, Steven Brett Sloan, MD
4 Department of DermatologyQ1 , University of Connecticut Health Center, Farmington, CT 06030, USA
Abstract The nail is a specialized keratinous skin appendage that grows approximately 2 to 3 mm per
8 month, with complete replacement achieved in 6 to 9 months. Although this structure can be easily
9 overlooked, nail disor ders compri se approximately 10% of all dermatologic conditions. This
10 contribution first provides an overview on the basic anatomy of the nail that will delineate between
11 the nail unit (eg, hyponychium, nail bed, proximal nail fold, and matrix) and anatomic components not
12 part of the nail unit (eg, lateral nail folds, nail plate, and eponychium). The function of each nail
13 structure will also be presented. The chemical profile of the normal nail plate is reviewed with a
14 discussion of its keratin content (hair type keratin vs epithelial type keratin), sulfur content, and mineral
15 composition, including magnesium, calcium, iron, zinc, sodium, and copper. The remainder will focus
16 on nail manifestations seen in states of malnutrition. Virtually every nutritional deficiency can affect the
17 growth of the nail in some manner. Finally, the discussion will include anecdotal use of nutritional and
18 dietary supplements in the setting of brittle nail syndrome as well as a brief overview of biotin and its
19 promising utility in the treatment of nail disorders.
© 2010 Elsevier Inc. All rights reserved.
22 Although skin might encompass a large portion of the
23 field, dermatology also includes the study of its appendages,
24 namely the nails and hair. These two skin appendages are
25 often discussed together, or are at least compared with one
26 another, in the literature. The dynamics of hair and nail
27 growth control are related in several ways: both are skin
28 appendages servin g protective f unctions, and both are
29 differentiated epithelial products, which consist of tightly
30 bound cells made rigid by special intermediate filament
31 proteins, the hard keratins.
32Basic anatomy of the nail unit
33The nail is a specialized keratinous appendage produced by
34a germinative epithelium just as basal epidermal cells produce
35the stratum corneum of the skin. Nail keratinocytes contribute
36to nail cornification through the production of hard keratins,
37and hardness of the nail plate is due to a high concentration of
38sulfur matrix protein.
Q2Although it can be grossly appreciated
39and show manifestations of various underlying pathologies,
40the nail plate is, surprisingly, not considered one of the four
41anatomic structures that comprise the nail unit
42• nail bed
44• proximal nail fold
The nail plate is made of anucleate keratinocytes oriented
48so that the cells are flattened in the plane of the plate, whereas
Corresponding author. Tel.: +1 860 679 7320; fax: 860 679 1248.
E-mail address: firstname.lastname@example.org (S.B. Sloan).
0738-081X/$ – see front matter © 2010 Elsevier Inc. All rights reserved.
Clinics in Dermatology (2010) xx, xxx–xxx
ARTICLE IN PRESS
CID-06420; No of Pages 6
49 the intermediate filaments are oriented perpendicular to its
50 plane of growth. This unique orientation and the transverse
51 and longitudinal curvature of the plate are thought to provide
52 its structural rigidity.
Nail plates are roughly rectangular and
53 flat but demonstrate considerable variation within the normal
54 population. The plate is actually translucent; however, it
55 appears pink on gross examination due to the rich underlying
56 vascular network of capillaries weaving through the nail bed,
57 which firmly adheres to the nail plate above.
58 The white, crescent-shaped area on the proximal nail plate
59 is known as the lunula. It can be seen projecting from under
60 the proximal nail fold and represents the most distal portion
61 of the matrix, which ultimately determines the shape of the
62 free edge of the nail plate. As the nail plate emerges from the
63 matrix, it is bordered by three normal skin structures—two
64 lateral nail folds and a proximal nail fold. The proximal nail
65 fold is crucial in the formation of the nail plate. In fact,
66 approximately 25% of the nail plate's total surface area is
67 located under the proximal nail fold.
68 The four epithelial components that comprise the nail unit
69 serve vital functions necessary for maintaining the integrity
70 of the nail plate. The matrix is a thick epithelium situated
71 above the middle part of the distal phalanx of the digits.
72 bordered proximally by the proximal nail fold and distally by
73 the lunula, generating the bulk of the nail plate. The proximal
74 nail fold is an invaginated, wedge-shaped fold of skin on the
75 dorsum of the distal digit
that protects much of the matrix
76 and newly forming nail plate.
77 Not considered one of the four epithelial components of
78 the nail unit, the eponychium (cuticle) is a part of the
79 proximal nail fold. It serves as a sealant and protective barrier
80 against entry of infectious organisms into the germinative
81 matrix. Disruption of the eponychium allows irritants to
82 enter, which subsequently leads to the inflammation seen in
83 chronic paronychia.
84 The hyponychium is a narrow zone of epidermis between
85 the nail bed and the distal nail groove beneath the free edge
86 of the nail plate.
Its function is very similar to that of the
87 eponychium but in an inverted manner. It seals the
88 undersurface of the nail plate, where it lifts off the tip of
89 the digit. Disruption of this area results in the creation of a
90 potential space between the nail plate and nail bed, as can be
91 appreciated in onycholysis.
92 Lastly, the nail bed begins where the distal matrix or lunula
93 ends, extending to the hyponychium, where the free edge of
94 the nail separates.
Its contribution to nail plate formation is
95 still questioned. The nail bed keratinocytes contribute about
96 20% of ventral nail plate's thickness and mass.
97 function is keeping the nail plate attached to the nail unit.
98 Chemical make-up of the nail plate
99 Most the nail plate is made of keratin and contains both
100 hair-type (“hard ”) keratin and epithelial-type (“soft”) kera-
In addition to these keratins, intermediate filament-
102associated proteins high in sulfur or tyrosine/glycine
103moieties and the protein trichohyalin are also expressed
104throughout the nail unit. Different types of keratin are
105variably expressed in separate areas of the nail unit. Keratin
106expression in the proximal nail fold and the fingertip
107epidermis consists of normal interfollicular epidermis.
108More specifically, keratins K5 and K14 are expressed in
109basal keratinocytes, K1 and K10 are expressed in suprabasal
110keratinocytes, and K2E is expressed by keratinocytes high in
111the spinous layer.
The nail matrix also expresses normal
112interfollicular keratins similar to the proximal nail fold and
113fingertip epidermis; however, unlike the proximal nail fold,
114the nail matrix sporadically expresses hard keratins and
115trichohyalin in its suprabasal layers. Finally, the nail bed
116epithelium also expresses the basal keratins, K5 and K14,
117and keratins K6, K16, and K17 are expressed in its
119Hair-type keratin constitutes 80% to 90% and the
120epithelial type keratin comprises 10% of 20% of the nail
121plate. Its overall sulfur content is approximately 10% by
122weight. The disulfide bonds of cystine in the matrix proteins
123are thought to contribute largely to nail hardness by acting as
124glue that holds the keratin fibers together, thereby creating
125the nail plate's tensile strength. Contrary to popular belief,
126calcium does not contribute to nail hardness and makes up
127only 0.2% of the nail plate by weight.
The lipid content is
128relatively low, especially compared with the amount of lipids
129found in the stratum corneum. Glycolic and stearic acids are
130types of lipids found in the nail plate, and their presence
131likely explains the nail plate's water resistance. Despite this
132feature, the nail plate's water content can vary greatly, with
133normal content being 18%.
Its hydration state is thought to
134contribute to nail hardness. For example, nails become brittle
135when the water content is less than 16% and become soft
136when greater than 25%.
Although the major contribution of
137nail plate hardness is unclear, it is likely due to both the high
138concentratio n of sulfur matrix protein and the current
140Minerals are another important aspect of the nail plate's
141composition. The principal minerals include magnesium,
142calcium, iron, zinc, sodium, and copper.
143Patients with soft, flaky nails that are inclined to break or
144split may have significantly reduced plasma and nail plate
A second study revealed that selenium is
146an essential trace element with a significant effect on nail
147health. This report described a young boy whose fingernails
148turne d white approximately 2 years after startin g tot al
149parental nutrition (TPN). Close examination of these nails
150and dermatologic consultation revealed that the nails were
151fully developed and normal, but virtually the entire nail bed
152was white except for a distal zone of normal pink. The boy's
153nail findings, of approximately 12 months' duration, resolved
154dramatically after selenium therapy was instituted.
155The specific mineral content of a given individual's
156nail plate varies greatly between different populations.
2 M.W. Cashman, S.B. Sloan
ARTICLE IN PRESS
157 Higher levels of calcium and zinc are found in men,
158 higher levels of magnesium are found in women, and the
159 level of iron is equal between them. Levels of calcium are
160 higher in older people than in y ounger individuals.
161 Children have higher levels of magnesium, sodium, and
162 iron than adults, and iron is actually highest amongst
163 neonates across all groups. Children with kwashiorkor
164 disease have higher levels of calcium and sodium and
165 healthy children have higher levels of magnesium. Two
166 final examples that might seem more intuitive include
167 lower levels of iron in nail plates of patients with iron-
168 deficiency anemia and higher levels of copper in nails of
169 patients with Wilson disease.
170 Malnutrition and the nail
171 Several systemic diseases can lead to nail changes that
172 clinicians can visually appreciate; however, not all gross
173 changes are secondary to malnutrition alone. Those nail
174 changes solely due to malnutrition and other systemic
175 diseases that could manifest secondary to a deficiency in a
176 particular vitamin, mineral, or other trace element (eg, iron-
177 deficiency anemia) will be outlined systematically by which
178 part of the nail unit is affected. The exception will be the first
179 section on chromonychia, because this particular nail change
180 can affect three different parts of the nail unit.
181 Chromonychia and the nail matrix, nail bed, and
182 nail plate
183 Chromonychia can occur in the lunula (the most distal
184 portion of the nail matrix), the nail bed, or the nail plate. The
185 word is defined as a ny color (e xcluding white) that
186 abnormally discolors a part of the nail unit. Because white
187 is not necessarily considered a distinct color, whitened areas
188 of the nail unit define the term leukonychia. Chromonychia
189 of the lunula has been reported as a bluish discoloration in
190 copper overload from Wilson disease.
191 elevation of silver salts in the body—has been associated
192 with a blackish-gray discoloration of the lunula and is
193 thought to be photoinduced.
194 Color changes in the nail bed are more diffuse than focal
195 chromonychia of the lunula. For example, diffusely bluish
196 discoloration of the nail bed is characteristically associated
197 with ingestion of silver and does not need light exposure to
198 manifest itself.
The differential diagnosis of a patient who
199 presents with a bluish, discolored nail bed includes a glomus
200 tumor, especially when associated with pain. Although
201 nonspecific, pallor of the nail bed can be a sign of anemia and
202 an indication that iron body stores may be low.
203 Chromonychia of the nail plate can occur due to
204 increased melanogenesis in the matrix or to a melanocytic
Longitudinal melanonychia of the nail plate
206 secondary to increased melanin production in the matrix has
207been reported in malnutrition, vitamin D and vitamin B
208deficiencies, and hemochromatosis.
209The nail bed
210The nail bed can display signs of nutritional imbalances.
211Physical signs of nail bed disease include splinter hemor-
212rhages, Terry nails, Muehrc ke lines, and onycholysis.
213Splinter hemorrhages are formed by extravasation of red
214blood cells from longitudinally oriented nail bed vessels into
215adjacent longitudinally oriented troughs.
216cally associated with subacute bacterial endocarditis, these
217are most frequently seen as a result of trauma and have been
218associated with a slew of systemic illnesses. Among the
219nutrition-related conditions are scurvy and hemochromatosis.
220Despite its classical association with chronic liver disease,
221Terry nails can also be seen in malnutritive states, especially
222in the elderly.
Terry nails are described as any 0.5- to 3.0-
223mm wide , distal, br own-to-pi nk nail bed bands wi th
Muehrcke lines are characterized by two
225transverse white bands of pallor. When pressure is applied to
226the distal plate, the narrow transverse bands disappear,
227confirming a nail bed change.
Leukonychia, the term
228used to describe whitened areas of the nail unit, can be
229applied to Muehrcke lines. In fact, leukonychia can be
230further classified as true or apparent. Muehrcke lines are an
231example of the latter, as evidenced by disappearing white
232bands with applied pressure to the distal plate. Although
233Muehrcke initially associated this finding with hypoalbumi-
234nemia, this nail change has also been associated with
235malnutrition and acrodermatitis enteropathica, an autosomal-
236recessive metabolic disorder that affects zinc absorption.
237Onycholysis is defined as separation of the nail plate from
238the underlying nail bed, causing a proximal extension of free
It is the third most common nail disorder seen, after
240onychomycosis and verrucae vulgaris.
241ly a sign of thyroid disease, the correlation of onycholysis
242with systemic illness is overrated and more likely to be
243associated with common local conditions such as trauma,
244allergic contact dermatitis, or irritant reactions.
245lysis may be due to exogenous or endogenous causes, with
246the former representing most cases seen in the clinic. Some
247endogenous causes of onycholysis related to nutritional
248imbalances include iron-deficiency anemia, pellagra, and
249Cronkhite-Canada syndrome, an extremely rare nonfamilial
250syndrome characterized by marked epithelial disturbances in
251the gastrointestinal tract and epider mis. The a bnormal
252mucosal proliferation leads to fluid and electrolyte abnor-
253malities, malabsorption, and malnutrition.
254The nail plate
255The nail plate is the last portion of the nail apparatus
256affected by nutritional imbalances that often result in grossly
257visible signs. Examples of observed nail plate changes
3Nutrition and nail disease
ARTICLE IN PRESS
258 include transverse leukonychia, clubbing, koilonychia,
259 hapalonychia, Beau lines, onychomadesis, onychorrhexis,
260 and trachyonychia. Transverse leukonychia is distinguished
261 by transverse, opaque white bands that tend to occur in the
262 same relative position in multiple nails.
These bands mimic
263 the contour of the lunula and grow out with the nail plate
264 (Figure 1). Measuring the distance of the line from the
265 proximal nail fold gives the clinician a time reference from
266 when nail insult occurred, because fingernails grow about
267 0.10 to 0.15 mm/d. Although transverse leukonychia is
268 typically associated with deficiency states like acrodermatitis
269 enteropathica, pellagra (deficient niacin/vitamin B
), and low
270 calcium levels, it is additionally associated with overabun-
271 dant states such as the increased blood iron levels that occur
272 in hemochromatosis.
273 Mees line is a descriptive term used to specify transverse
274 leukonychia with arsenic deposition in the plate secondary to
275 arsenic poisoning.
Mees line is a classic example of true
276 leukonychia, because the transverse white bands are truly
277 deposited in the nail plate and will not disappear with applied
278 pressure to the distal plate, unlike Muehrcke lines (apparent
279 leukonychia), whose lines do disappear.
280 Clubbing (Figure 2) is a long-recognized nail sign that
281 Hippocrates first described in 5th century BCE .
The term is
282 used when the Lovibond angle (the normal 160° angle
283 between the proximal nail fold and the nail plate) exceeds
284 180°. Clubbing can be inherited or acquired. An inherited
285 type of clubbing that falls under the purview of nutritional
286 imbalances includes citrullinemia, a rare autosomal-reces-
287 sive disorder of the hepatic urea cycle that leads to an
288 accumulation of nitrogenous waste compounds and other
289 toxic substances, including citrulline, in the blood.
290 Acquired clubbing secondary to nutritional imbalances
291 may be due to several different combinations of substances
292 and pathologies, including phosphorus, arsenic, alcohol,
293 mercury or beryllium poisoning, hypervitaminosis A, and
294 cretinism caused by iodine deficiency.
295 Koilonychia is defined as spoon-shaped nail plates. It is
296 thought to occur due to a relatively low-set distal matrix
297 compared with the proximal matrix that causes nail plate
298 growth to occur in a downward direction as it grows toward
299 the nail bed.
When present, it is usually more severe on the
300 index and third fingernails.
Almost all cases of koilonychia
301are acquired, but it also may be idiopathic or inherited.
302Koilonychia is classically a sign of iron-deficiency anemia
303and has not been observed in any other type of anemia
304however, a few published cases have reported koilonychia in
305postgastrectomy patients and in patients diagnosed with
306Plummer-Vinson syndrome. These clinical syndromes still
307fall under the purview of iron-deficiency anemia (eg, iron
308malabsorption in postgastrectomy patients and iron-defi-
309ciency anemia as one criterion of the Plummer-Vinson
310syndrome clinical triad) and support the notion that
311koilonychia is observed only in sideropenic anemia and not
312in other anemias. Iron-deficiency anemia may be the only
313anemia strongly correlated with koilo nychia, but other
314nutrition states such as riboflavin deficiency, pellagra, and
315more commonly, vitamin C deficiency have all been
316implicated in the development of koilonychia.
317Hapalonychia, or soft nails, have been associated with
318occupational diseases, eczematous dermatides, and certain
319systemic diseases. Female gender and advancing age are two
320predisposing factors that influence the development of
321hapalonychia. Some systemic causes include hypochromic
322anemia, rheumatoid arthritis, and arsenic poisoning. Nutri-
323tional deficiencies involving vitamins A, B
324and D, in addition to low serum calcium, have all been
325implicated in causing hapalonychia.
326Beau lines are defined as transverse grooves or depression
327of the nail plate seen in acute systemic disorders.
It is one
328of the most common signs encountered in clinical practice,
329but is the least specific. Acute illnesses are thought to cause a
330temporary arrest of the matrix. The width of the furrow is an
331indicator of the given ailment's duration.
332distance from the furrow to proximal nail fold gives an
333approximate time that the insult may have occurred, as can
334also be done with transverse leukonychia. If the entire
335activity of the matrix is inhibited for 1 to 2 weeks, a Beau line
336will reach its maximum depth, causing a total division of the
337nail plat e (ie, onychomadesis).
338associated with Beau lines include protein deficiency and
339pellagra. Dysregulated blood mineral levels, such asFig. 1 Apparent leukonychiaQ5 .
Fig. 2 Clubbing.
4 M.W. Cashman, S.B. Sloan
ARTICLE IN PRESS
340 hypocalce mia, chronic alcoh olism (anothe r source of
341 malnutrition and malabsorption), and arsenic toxicity, can
342 also play a role in the development of Beau lines.
343 Onychomadesis (Figure 3) is the term used to describe
344 complete onycholysis, beginning at the nail plate's proximal
345 end, which is also known as complete nail shedding. The
346 most common cause of onychomadesis is neurovascular
347 change. Examples would be repeated episodes of drops in
348 blood calcium levels or a chronic state of hypocalcemia with
349 arteriolar spasm. This underlying pathophysiology leads to
350 an abrupt separation of the nail plate from the underlying
351 nail matrix and nail bed and results in the clinical
352 manifestation of onychomadesis. Other associations that
353 can lead to the development of onychomadesis include
354 arsenic and lead poisoning.
355 Onychorrhexis, or senile nail, describes longitudinal
356 ridges in the nail plate that are most often associated with
357 the aging process. This nail change can be inherited, and the
358 pattern has been described as specific enough to distinguish
359 between identical twins and can be useful in forensic
It is most strongly correlated with rheuma-
361 toid arthritis, but other systemic disturbances can also
362 contribute to its development. Mineral imbalances leading
363 to onychorrhexis include iron-deficiency anemia, arsenic
364 poisoning, and zinc deficiency.
365 The term trachyonychia (Figure 4) describes rough nail
366 plates with a characteristic gray opacity, brittle (fragilitas
367 unguium) and split free ends, longitudinal ridging, and a
368 rough sandpaperlike surface.
Brittle nails and trachyony-
369 chia are relatively common in persons aged older than 60
370 years. Causes often include repeated cycles of hydration and
371 dehydration as occur in excessive domestic wet work and
372 overuse of dehydrating agents such as nail enamel and
373 cuticle removers. Another typical offender is poor or
374 decreased dietary water and food intake, an especially
375 common phenomenon in the elderly. Any of these may
376contribute to and precipitate brittle nails and subsequent
377trachyonychia seen in the elderly.
378Nutritional supplements and the nail
379Little information is available on how nutritional supple-
380ments can affect different nail disorders; however, brittle nail
381syndrome is one nail disorder often found in what minimal
382literature exists. Brittle nail syndrome is a disease character-
383ized by soft, dry, weak, easily breakable nails that show
384onychorrhexis and onychoschizia.
Brittle fingernails are an
385all-too-common complaint seen in the dermatologist's office.
386As many as 60 million people in the United States of
387America may experience this disorder, with women
The causes are believed to be
389traumatic, vascular, or physical. Damage to the nails because
390of deficient production of intercellular cement substance may
391also be related to systemic diseases, nutritional deficiencies,
392endocrine or metabolic disorders, and dermatologic condi-
The intercellular cement substance is mostly made
394of phospholipids, mucopolysaccharides, and acid phospha-
395tases, and is found in high concentrations around cell
396junctions, known as the zonula occludens and gap junctions,
397and firmly adheres nail cells together.
398A multitude of regimens exist for treatment of brittle nails,
399including buffing and moisturizing, application of essential
400fatty acids, and ingestion of vitamin C and pyridoxine, iron,
401vitamin D, calcium, amino acids, and gelatin.
402nutritional supplement that has been seriously investigated
403and has recently shown promise is biotin, or vitamin H.
404Biotin use to abate pathologic horse hoofs in veterinary
405medicine suggested it could be used to treat human nail
A role for biotin in nail disorders is also indicated
407by its favorable effect on other skin disorders, such as
408seborrheic dermatitis, Leiner disease, and disorders of hair
409growth. Biotin deficiency may be caused by insufficient
410intake, ingestion of raw eggs, absorption disorders, produc-
411tion of biotin antagonists by intestinal bacteria, or distur-
412bance in th e intestinal flora by or al therapy wi th
413sulfonamides, antibiotics, or anticonvulsant agents.
Fig. 3 Onychomadesis.
Fig. 4 Trachyonychia Q6.
5Nutrition and nail disease
ARTICLE IN PRESS
414 One study demonstrated a 25% increase in the thickness of
415 the nail plate in patients diagnosed with brittle nails of
416 unknown cause and treated with biotin (2.5 mg dailyQ4 ) for 6 to
417 15 months.
Another study showed that biotin was not
418 equally effective in all patients, but a definite trend toward
419 benefit was noted in most of those who took between 1.0 and
420 3.0 mg daily, with 2 months being the average time before
421 clinically noticeable results. This same study also showed that
422 approximately 10 weeks after biotin was discontinued, nail
423 ridging gradually returned and the nail brittleness recurred.
424 Both studies provide clinical evidence that biotin is possibly
425 effective in treating patients with nail brittleness. The next
426 step in biotin investigation is to determine whether vitamin H
427 supplementation is legitimately correcting an underlying
428 deficiency or whether improvement in nail brittleness is
429 through some other mechanism that has yet to be elucidated.
431 Nails as a skin appendage are considered ancillary and
432 may be neglected by the nondermatologist in an examination;
433 however, there are a myriad of recognizable patterns that can
434 alter each individual part of the nail apparatus. Because
435 systemic illness can manifest through subtle changes in the
436 nail, clinicians may need to be reminded of these physical
437 findings in determining the cause of nail complaints.
439 1. Stenn K, Fleckman P. Hair and nail physiology. In: Hordinsky MK,
440 Sawaya ME, Scher RK, editors. Atlas of hair and nails. Philadelphia:
441 Churchill Livingstone; 2000. p. 1-7.
442 2. Conejo-Mir JS. Nail. In: Sternberg SS, editor. Histology for
443 pathologists. New York: Raven Press; 1992. p. 399-420.
444 3. Zaias N. The nail in health and disease. 2nd ed. Norwalk (Conn):
445 Appleton & Lange; 1990. p. 250.
446 4. Forslind B. Biophysical studies of the normal nail. Acta DermVenereol
448 5. Stone M, Styles AR, Cockerell CJ. Histology of the normal nail unit. In:
449 Hordinsky MK, Sawaya ME, Scher RK, editors. Atlas of hair and nails.
450 Philadelphia: Churchill Livingstone; 2000. p. 18-23.
451 6. Tosti A, Piraccini BM. Biology of nails and nail disorders. In: Wolff K,
452 Goldsmith LA, Katz SI, et al, editors. Fitzpatrick's dermatology in
453 general medicine. 7th ed. New York: McGraw Hill Medical; 2003.
454 p. 778-94.
455 7. Fleckman P. Basic science of the nail unit. In: Scher RK, Daniel CR,
456 editors. Nails: therapy, diagnosis, surgery. 2nd ed. Philadelphia: WB
457 Saunders; 1997. p. 37-54.
4588. Fistarol SK, Itin PH. Nail changes in genodermatoses. Eur J Dermatol
4609. Scheinfeld N, Dahdah MJ, Scher RK. Vitamins and minerals: their role
461in nail health and disease. J Drugs Dermatol 2007;6:782-6.
46210. Singh G, Haneef NS, Uday A. Nail changes and disorders among the
463elderly. Indian J Dermatol Venereol Leprol 2005;71:386-92.
46411. Cohen PR, Scher RK. Aging. In: Hordinsky MK, Sawaya ME, Scher
465RK, editors. Atlas of hair and nails. Philadelphia: Churchill Living-
466stone; 2000. p. 213-25.
46712. Bauer F, Stevens B. Investigations of trace metal content of normal and
468diseased nails. Australas J Dermatol 1983;24:127-9.
46913. Kien CL, Ganther HE. Manifestations of chronic selenium deficiency in
470a child receiving total parenteral nutrition. Am J Clin Nutr 1983;37:
47214. Greenberg RG, Berger TG. Nail and mucocutaneous hyperpigmen-
473tation with azidothymidine therapy. J Am Acad Dermatol 1990;22:
47515. Plewig G, Lincke H, Wolff HH. Silver-blue nails. Acta Derm Venereol
47716. Holzberg M. Nail signs of systemic disease. In: Hordinsky MK, Sawaya
478ME, Scher RK, editors. Atlas of hair and nails. Philadelphia: Churchill
479Livingstone; 2000. p. 59-70.
48017. Scher RK, Daniel CR. therapy, diagnosis, surgery. Philadelphia: WB
481Saunders; 1990. p. 389.
48218. Muehrcke RC. The fingernails in chronic hypoalbuminemia. BMJ
48419. Rabinowitz SS, Sheth M. Cronkhite-canada syndrome [updated Apr 1
4852008]. Available at: http://emedicine.medscape.com/article/928489-overview.
486Accessed: Oct 31, 2009.
48720. Marino MT. Mees' lines. Arch Dermatol 1990;126:827-8.
48821. Mendlowitz M. Measurements of blood flow and blood pressure in
489clubbed fingers. J Clin Invest 1941;20:113.
49022. Roth KS. Citrullinemia [updated Mar 26. 2009]. Available at: http://
491emedicine.medscape.com/article/942435-overview. Accessed: Oct 13,
49323. Stone OJ. Spoon nails and clubbing. Cutis 1975;16:235-41.
49424. Sato S. Iron deficiency: structural and microchemical changes in hair,
495nails, and skin. Semin Dermatol 1991;10:313-9.
49625. Weismann K. Beau and his descriptions of transverse depression on
497nails. Br J Dermatol 1977;97:571-2.
49826. Baran R, Dawber RPR. Diseases of the nails and their management.
4992nd ed. Oxford: Blackwell Scientific; 1994. p. 656.
50027. Tosti A, Fanti PA, Morelli R, et al. Trachyonychia associated with
501alopecia areata: a clinical and pathologic study. J Am Acad Dermatol
50328. Hochman LG, Scher RK, Meyerson MS. Brittle nails: response to daily
504biotin supplementation. Cutis 1993;51:303-5.
50529. Colombo VE, Gerber F, Bronhofer M, et al. Treatment of brittle
506fingernails and onychoschizia with biotin: scanning electron microsco-
507py. J Am Acad Dermatol 1990;23:1127-32.
50830. Hashimoto K. Cementsome, a new interpretation of the membrane-
509coating granule. Arch Dermatol Res 1971;240:349-64.
51031. Reilly JD, Cottrell DF, Martin RJ, et al. Effect of supplementary dietary
511biotin on hoof growth and hoof growth rate in ponies: a controlled trial.
512Equine Vet J 1998;26:51-7.
6 M.W. Cashman, S.B. Sloan
ARTICLE IN PRESS