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Nail disorders and systemic disease: What the nails tell us

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IN THIS ARTICLE
Nail disorders and systemic
disease: What the nails tell us
Here’s what you’ll see and what to suspect with these
11 nail disorders
Stamatis Gregoriou, MD,
George Argyriou, MD,
George Larios, MD, and
Dimitris Rigopoulos, MD,
PhD
University of Athens
Medical School, Dermatology
Department, Nail Clinic, Athens
drigop@hol.gr
Onycholysis
Clubbing
Koilonychia
Onychomadesis
Beau’s lines
Pitted nails
Muehrcke’s nails
Terry’s nails
Half-and-half nails
Red lunula
Splinter
hemorrhages
If you said onycholysis (left) and red lunula (right), you are correct. As for
the underlying diseases: The patient with onycholysis has hyperthyroidism
and the patient with red lunula has chronic obstructive pulmonary disease
(COPD). Onycholysis and red lunula are among the more common changes
to the morphology (shape) and color of the nail—the 2 ways by which nail
changes are classi ed.
Can you name these 2 nail conditions?
What underlying diseases do you suspect
are behind these conditions?
Nail abnormalities can be a reveal-
ing sign of underlying disease,
and because the nails are readily
examined, a convenient diagnostic tool,
as well.
This review of common—and not so
common—nail disorders shows which
changes to the nail are more likely to
occur with which underlying internal
diseases.
CONTINUED
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Eponychium
Lunula
Nail plate
Distal edge
of nail plate
Lateral
nail fold
Lateral
nail groove
Distal
phalanx
Epidermis
Hyponychium
Nail bed
Nail matrix
Proximal
nail fold
Eponychium
Onycholysis
What you’ll see: Distal separation of
the nail plate from the underlying nail
bed. Nails with onycholysis are usually
smooth,  rm, and without nail bed in-
ammation. It is not a disease of the nail
matrix, though nail discoloration may
appear underneath the nail as a result of
secondary infection.
What to suspect: Onycholysis is associ-
ated with many systemic conditions,
including thyroid disease—especially
hyperthyroidism. (See list at left.) The
nail changes seen with hyperthyroidism
usually consist of onycholysis beginning
in the fourth or  fth nail, the so-called
Plummer’s nails.1 Nakatsui and Lin2 have
suggested that patients with unexplained
onycholysis be screened for asymptom-
atic thyroid disease.
Amyloid and multiple
myeloma
Anemia
Bronchiectasis
Carcinoma (lung)
Erythropoietic porphyria
Histiocytosis X
Ischemia (peripheral)
Leprosy
Lupus erythematosus
Neuritis
Pellagra
Pemphigus vulgaris
Pleural effusion
Porphyria cutanea tarda
Psoriatic arthritis
Reiter’s syndrome
Scleroderma
Syphilis (secondary
and tertiary)
Thyroid disease
Onycholysis-associated
systemic diseases1,2
Nail anatomy
Nail changes are classi ed according
to whether they occur in the morphology
(shape) or color of the nail. Onycholysis,
clubbing, and koilonychia are some
of the most common changes in the
morphology of the nail. Red lunula is
one of the most common changes in
the color of the nail.
ILLUSTRATION © ROB FLEWELL
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Clubbing
What you’ll see: Increased transverse and
longitudinal nail curvature with  bro-
vascular hyperplasia of the soft tissue
proximal to the cuticle. With clubbing,
the Lovibond’s angle, formed between
the dorsal surface of the distal phalanx
and the nail plate, is greater than 180 de-
grees. Schamroth’s sign—the disappear-
ance of the normal window between the
back surfaces of opposite terminal pha-
langes—may also be present.3
What to suspect: Clubbing may be heredi-
tary, idiopathic, or acquired in association
with a variety of disorders. It may also be
unilateral or bilateral. Unilateral clubbing
has been associated with hemiplegia and
vascular lesions, while bilateral clubbing
has been linked to neoplastic, pulmonary,
cardiac, gastrointestinal, infectious, endo-
crine, vascular, and multisystem diseases.
Cribier et al4 studied the frequency
Koilonychia
What you’ll see: Concave thin nails with
everted edges shaped like a spoon and
capable of retaining a drop of water. It
is more common in  ngernails, but is oc-
casionally seen in toenails.
What to suspect: This nail sign may result
from trauma, constant exposure of hands
to petroleum-based solvents, or nail-patella
syndrome. Koilonychia is most commonly
associated with iron de ciency anemia
and occasionally occurs in patients with
hemochromatosis. Other frequent system-
ic causes of koilonychia include coronary
disease and hypothyroidism.5 In addition,
of nail disorders in HIV-infected patients
and found that clubbing affects 5.8% of
these patients. Moreover, Cribier’s data
reinforced the notion that clubbing could
be an early sign of AIDS in pediatric pa-
tients, and thus play a role in diagnosis.
koilonychia is sometimes a normal variant
in infants; it usually disappears in the  rst
few years of life.
Koilonychia is
sometimes
a normal variant
in infants;
it usually
disappears in
the fi rst few
years of life
FAST TRACK
Onychomadesis
What you’ll see: Proximal separation of
the nail plate from the nail bed. This
typically results in shedding of the nail.
What to suspect: Trauma is the usual
cause. Less common causes include poor
nutritional status, febrile illness, or drug
sensitivity.
Wester et al6 observed the develop-
ment of onychomadesis in a critically
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Terry’s nails have
been reported
in hemodialysis
patients and renal
transplant patients
Beau’s lines
What you’ll see: Transverse depressions in
the nail plate that occur as a result of a
temporary cessation in nail growth.
What to suspect: The causes are similar
to those of onychomadesis and include
trauma, poor nutritional status, febrile
illness, and drug sensitivity.
Pitted nails
What you’ll see: Pinpoint (or larger) de-
pressions in an otherwise normal nail.
What to suspect: Pitting is usually associat-
ed with psoriasis and affects 10% to 15%
of patients with the disorder.10 Pitting has
also been reported in patients with Reiter’s
syndrome (and other connective tissue dis-
orders), sarcoidosis, pemphigus, alopecia
areata, and incontinentia pigmenti.5
Muehrcke’s nails
What you’ll see: Transverse white bands
parallel to the lunula. These bands usu-
ally occur in pairs and extend all the
way across the nail.
This nail disorder is uncommon, and
is 1 of 3 forms of leukonychia caused by
abnormalities in nail bed vascularization.
(The other 2 forms—Terry’s nails and
half-and-half nails—are described on page
513.)
What to suspect: Muehrcke’s nails ap-
pear in patients with hypoalbuminemia
and can improve if serum albumin lev-
els return to normal. They may also oc-
cur in patients with:11,12
• nephrotic syndrome,
• glomerulonephritis,
• liver disease,
• malnutrition, and
those who have undergone
chemotherapy.
Muehrcke’s lines have also been de-
scribed in a patient with Peutz-Jeghers
syndrome,13 as well as in a heart transplant
recipient.14
ill patient with a large pulmonary ab-
scess. Onychomadesis is often a clinical
manifestation of pemphigus vulgaris.7
It has also been associated with Kawa-
saki disease8 and hand, foot, and mouth
disease.9
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Terry’s nails
What you’ll see: Most of the nail plate is
white, with a narrow pink distal band.
All nails tend to be uniformly affected,
with an appearance of ground glass.15
Terry’s nails have been found in 80% of
patients with cirrhosis of the liver.15
What to suspect: One study found Terry’s
nails in 25% of 512 consecutive hospi-
tal inpatients, with researchers linking
the disorder with cirrhosis, chronic CHF,
and adult-onset diabetes mellitus.16 On
rare occasions, Terry’s nails have been re-
ported in hemodialysis patients and renal
transplant recipients.17 Terry’s nails have
also been observed in HIV patients.4
Azure lunula has
occurred in argyria
and in patients
taking medications
like 5-fl uorouracil
and azidothymidine
What you’ll see: The proximal portion on
the nail bed is white because of edema of
the nail bed and capillary network; the
distal portion is pink or reddish brown.
The nail plate is unaffected.
What to suspect: This nail disorder has
occurred in patients with renal disease as-
sociated with azotemia.18 Half-and-half
nails have also been detected in hemo-
dialysis patients, renal transplant recipi-
ents,17 and in HIV patients.4
Red lunula
What you’ll see: The lunula is red. In ad-
dition to the red lunula pictured here,
there is also the absence of lunula and
azure lunula.
What to suspect: Red lunula has been
associated with alopecia areata, and
collagen vascular disease. It has also oc-
curred in patients on oral prednisone
for rheumatoid arthritis. Red lunulae
are seen in cardiac failure, COPD, cir-
rhosis, chronic urticaria, psoriasis, and
carbon monoxide poisoning.19
Absence of lunula was the most
common nail disorder in a group of he-
modialysis patients (31.9%) and has also
been reported in renal transplant recipi-
ents (17.1%).17 Azure lunula occurs in
patients with Wilson disease. It has also
Half-and-half nails (Lindsay’s nails)
occurred in argyria and in patients tak-
ing medications like 5- uorouracil and
azidothymidine.20
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Splinter hemorrhages
What you’ll see: Extravasations of blood
from the longitudinally oriented ves-
sels of the nail bed. These hemorrhages
do not blanch. They form as a result
of the nail plate-dermis structural re-
lationship and tend to be seen in older
patients.
What to suspect: While trauma is the most
common cause, they may also occur with
psoriasis and fungal infection.
Bacterial endocarditis is the most
common systemic disease associated with
splinter hemorrhages. These hemorrhages
are more common in subacute, rather
than acute, infection. Although splinter
hemorrhages in subacute bacterial endo-
carditis have been described as proximal-
ly located,21 there are no suf cient data to
con rm this—mainly because splinter le-
sions migrate distally as the nail grows.22
Splinter hemorrhages may also be
associated with mitral stenosis, vasculi-
tis, cirrhosis, trichinosis, scurvy, chronic
glomerulonephritis, and Darier’s disease.
However, due to the diverse and com-
mon causes of splinter hemorrhages, they
cannot be used as an isolated sign of ill-
ness, except when they are accompanied
by things like fever, Roth’s spots, Osler’s
nodes, Janeway’s lesions, or a heart mur-
mur, since any of the above would greatly
increase their signi cance.
Correspondence
Dimitris Rigopoulos, assistant professor of dermatology,
University of Athens Medical School, 5 Ionos Dragoumi
Street, 16121 Athens, Greece; drigop@hol.gr
Disclosure
The authors reported no potential con ict of interest rel-
evant to this article.
References
1. Jabbour SA. Cutaneous manifestations of endo-
crine disorders: a guide for dermatologists. Am J
Clin Dermatol. 2003;4:315-331.
2. Nakatsui T, Lin AN. Onycholysis and thyroid dis-
ease: report of three cases. J Cutan Med Surg.
1998;3:40-42.
3. Spicknall KE, Zirwas, MJ, English, JC III. Club-
bing: an update on diagnosis, differential diagno-
sis, pathophysiology, and clinical relevance. J Am
Acad Dermatol. 2005;52:1020-1028.
4. Cribier B, Mena ML, Rey D, et al. Nail changes in
patients infected with human immunode ciency vi-
rus. A prospective controlled study. Arch Dermatol.
1998;134:1216-1220.
5. Zaiac MN, Daniel CR III. Nails in systemic disease.
Dermatol Ther. 2002;5:99-106.
6. Wester JP, van Eps RS, Stouthamer A, Girbes AR.
Critical illness onychomadesis. Intensive Care Med.
2000;26:1698-700.
7. Engineer L, Norton LA, Ahmed AR. Nail involve-
ment in pemphigus vulgaris. J Am Acad Dermatol.
2000;43:529-535.
8. Ciastko AR. Onychomadesis and Kawasaki dis-
ease. CMAJ. 2002;166:1069.
9. Clementz GC, Mancini AJ. Nail matrix arrest fol-
lowing hand-foot-mouth disease: a report of  ve
children. Pediatr Dermatol. 2000;17(1):7-11.
10. Mayeaux, EJ Jr. Nail disorders. Prim Care. 2000;
27:333-351.
11. Muehrcke RC. The  ngernails in chronic hypoalbu-
minemia. BMJ. 1956;1:1327.
12. D’Alessandro A, Muzi G, Monaco A, Filiberto S,
Barboni A, Abbritti G. Yellow nail syndrome: does
protein leakage play a role? Eur Respir J. 2001;
87:5435-5441.
13. Skoog S, Boardman L. Muehrcke’s nails in Peutz-
Jeghers syndrome with hepatic adenoma. Clin
Gastroenterol Hepatol. 2004;2:XXIV.
14. Nabai H. Nail changes before and after heart trans-
plantation: personal observation by a physician.
Cutis. 1998;61:31-32.
15. Dupont AS, Magy N, Humbert P, Dupond JL. Nail
manifestations of systemic diseases. Rev Prat.
2000;50:2236-2240.
16. Holzberg M, Walker HK. Terry’s nails: revised de -
nition and new correlations. Lancet. 1984;2:896.
17. Saray Y, Seckin D, Gulec AT, Akgun S, Haberal M.
Nail disorders in hemodialysis patients and renal
transplant recipients: a case-control study. J Am
Acad Dermatol. 2004;50:197-202.
18. Dyachenko P, Monselise A, Shustak A, et al. Nail
disorders in patients with chronic renal failure and
undergoing haemodialysis treatment: a case control
study. J Eur Acad Dermatol Venereol. 2007;21:340-
344.
19. Cohen PR. Red lunulae: case report and literature
review. J AM Acad Dermatol. 1992;26:292.
20. Tanner LS, Gross DJ. Generalized argyria. Cutis.
1990;45:237.
21. Saccente M, Cobbs CG. Clinical approach to infec-
tive endocarditis. Cardio Clin. 1996;14:351-362.
22. Swartz MN, Weiburg AN. Infections due to gram-
positive bacteria. In: Fitzpatrick TB, Elsen AZ, Wolff
K, Freedberg IM, Austen KF, eds. Dermatology in
General Medicine. 4th ed. New York: McGraw-Hill;
1993: 2309-2334.
23. Lawry M, Daniel CR. Nails in systemic disease.
In: Scher RK, Daniel CR III, eds. Nails: Diagnosis,
Therapy, Surgery. 3rd ed. Philadelphia: Elsevier
Saunders; 2005:147-176.
DID YOU KNOW?
Systemic disease
typically affects more
than 1 nail.5,23
Fingernails usually
provide more accurate
information than toenails
because clinical signs
on toenails are often
modifi ed by trauma.23
Fingernails grow at a
rate of 0.1 mm/day and
toenails grow at a rate
of 0.03 mm/day.5,23 Thus,
you can estimate the time
at which an initial insult
occurred by measuring
the distance between the
cuticle and the leading
edge of any pigmentation
change.
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... Clubbing (Figure 2(g)) is the incrassation of the soft organization beneath the proximal nail plate, leading to increased curvature of the nails. Diagnostic findings include Lovibond's angle, and the Schamroth sign [44]. This condition may indicate cyanotic congenital heart disease, pulmonary fibrosis, bronchial carcinoma, inflammatory bowel disease, cirrhosis and thyroid acropachy. ...
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Background: The skin is a major target organ for extrahepatic manifestations of liver diseases, and dermatologic abnormalities are common in patients with hepatic disorders. Clinical examination of the skin, nails and hair can allow for appropriate recognition, early diagnosis and treatment of liver diseases, and improvement in the quality of life and life expectancy of affected patients. Methods: We searched 3 databases (Pubmed,Medline and Embase) and selected studies about cirrhosis related skin manifestations and their pathophysiology. Results: A total of 73 articles were included in the review. Studies displayed the spectrum of cutaneous manifestations related to hormonal and vascular changes as well as nail and hair changes in patients with cirrhosis and/or portal hypertension. Conclusion: Cutaneous alterations are important clues or potential indications in the diagnosis of liver cirrhosis. Familiarity with skin conditions can be promptly diagnosed and appropriate management initiated. • KEY MESSAGES • Manifestations of the liver and skin disorders are interrelated in various ways. Cutaneous changes may be the first clue that a patient has liver disease. • The skin is a major target organ for extrahepatic manifestations of liver diseases. A broad range of cutaneous alterations can be present in patients with cirrhosis, such as vascular, nail, hair, hormonal changes, etc. • Recognizing these signs is crucial so that potential underlying diseases including liver disease can be promptly diagnosed and appropriate management timely initiated.
... Другой симптом -онихолизис, который характеризуется отслоением ногтевой пластинки от ногтевого ложа в его дистальной части, по данным литературы, встречается в 80-94% у пациентов с псориазом [20]. ...
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Psoriatic onychodystrophy affects up to 50% of patients with psoriasis and up to 80% of patients with psoriatic arthritis, with an estimated lifetime risk of nail plate changes in this patient population of up to 90%. Nail psoriasis is characterised by a variety of morphological changes resulting from the inflammation in the nail matrix or nail bed, leading to functional impairment and negative impact on patient’s quality of life. Psoriatic onychodystrophy is a distinct therapeutic problem, as its localization is torpid to the current treatment. The limited penetration of topical agents through the nail plate together with the poor adherence to treatment make them typically ineffective. Systemic therapy is often regarded by dermatologists as inappropriate for patients with limited cutaneous lesions. Many systemic drugs, especially biologics, are effective in treating nail psoriasis, but with delayed and less pronounced effects compared to the improvement of skin manifestations. Efficacy for nail changes should be evaluated after 3–6 months of therapy. Recent studies demonstrate that the best effect is achieved after 1 year of treatment. This article presents the main clinical features of psoriatic onychodystrophy and provides information about the interleukin 17A (IL-17A) inhibitor drug netakimab as a promising therapeutic agent for patients with nail psoriasis. It also describes our own clinical experience of using netakimab in the therapy of patients with psoriasis coupled with onychodystrophy. Our experience of using netakimab in two cases of resistant psoriasis accompanied by nail lesions demonstrates its high efficacy in treatment of patients with both plaque psoriasis and psoriasis with “difficult”, hard-to-treat locations, such as nail plate lesions.
... Treatments include topical or intralesional corticoids; topical agents such as vitamin D3 analogues, tacrolimus, fluorouracil, cyclosporine, and tazarotene; phototherapy; radiotherapy; systemic agents such as acitretin, methotrexate, and cyclosporine; and biologic agents such as etanercept, infliximab, or adalimumab (Langley et al. 2012). -Differential diagnosis: Onychorrhexis, longitudinal nail fissure, nail sarcoidosis, nail pemphigus, alopecia areatarelated, eczema-related, and Reiter's syndrome (Gregoriou et al. 2008). ...
... Other causes of splinter hemorrhage include trauma, vasculitis, cirrhosis, trichinellosis, scurvy, chronic glomerulonephritis, and Darier's disease. [16] The presence of periungual telangiectasia is an important clue to underlying SLE, systemic sclerosis, and dermatomyositis. Other causes include diabetes mellitus, COPD, and rheumatoid arthritis. ...
... In meiner Studie war dies am Beispiel des Glomustumors zu beobachten. Obwohl diese Erkrankungen wie die zuvor erwähnte periphere arterielle Verschlusskrankheit[182,90,105,272,257,273] oder die Einnahme von bestimmten Arzneimitteln[60,33,210].Sowohl für Kliniker als auch Dermatologen ist es oft schwierig, allein anhand des klinischen Erscheinungsbildes eine Diagnose zu erstellen. Die histopathologische Untersuchung kann in zahlreichen Fällen helfen und zur Ursachenklärung und genauen Diagnose beitragen. ...
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Background Moulds are often wrongly considered contaminants, not very sensitive to conventional antifungal treatments, but they may cause ungual hyphomycosis, particularly Aspergillus. Due to the lack of precise diagnostic criteria, their real impact is underestimated. Objectives Retrospective descriptive analysis of all ungual hyphomycosis cases diagnosed at Montpellier Hospital from 1991 to 2019 to: (i) determine the incidence of onychomycosis by pseudo-dermatophytes and moulds; (ii) perform an epidemiological analysis of nail aspergillosis; (iii) provide simple criteria for mould involvement in onychopathy. Patients/Methods: Data concerning 4053 patients were collected: age, sex, onychomycosis location, direct examination results, species(s) identified, and fungal co-infections. Moreover, clinical data of patients with nail aspergillosis were analysed to identify potential contributing factors, and the classical criteria for mould involvement in onychopathy were critically reviewed. Results A pseudo-dermatophyte or a mould was involved in nail colonization in 17.25% of patients (men/women ratio: 0.70; mean age: 53.1 years). The identified hyphomycetes belonged mainly to the genera Fusarium (45.68%), Scopulariopsis (30.23%) and Aspergillus (16.94%). Analysis of the clinical reports of 102 patients with ungual aspergillosis (men/women ratio: 0.67; mean age: 56.3 years) identified cardiovascular (43.9%), endocrine (25.8%), cancer (19.7%) and skin (18.2%) diseases as contributing factors. Conclusions The adoption of simple and reliable criteria (i.e. characteristic filaments on direct microscopic examination after periodic acid-Schiff staining, growth at seeding points in culture) allows determining the formal involvement of a mould in chronic onychopathies and avoiding possible side effects and costs of empirical or inappropriate and repetitive treatments.
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Objective: To present our observation of the development of a rare nail deformity in the prolonged course of disease of a critically ill patient with a pulmonary abscess. Design: Case report. Setting: Tertiary referral, 16-bed, level I surgical ICU in an academic hospital. Patient: A 48-year-old Caucasian male was treated with penicillin for a pneumococcal meningitis and pneumonia. He developed a large pulmonary abscess of the right upper lobe and needed prolonged mechanical ventilation. Extensive surgical treatment was successful eventually. A remarkable feature concerned the occurrence of onycholysis of all finger nails and toe nails resulting in complete shedding of the nails (onychomadesis). This phenomenon can be regarded as an extreme manifestation of Beau's lines precipitated by a severe systemic insult. Conclusion: We observed the development of onychomadesis in a critically ill patient with a large pulmonary abscess. This association has not been described before.
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Thumb nails with asymptomatic red lunulae were noted in a 54-year-old woman with testosterone propionate-responsive vulvar lichen sclerosus et atrophicus of 4 years' duration and localized vitiligo that had been treated with topical corticosteroids for 15 months. Cutaneous and systemic disorders in which red lunulae have been observed are reviewed.
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