A presentation at the department of dermatology, Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Osun State, Nigeria

1. NAIL MANIFESTATIONS OF
SYSTEMIC DISEASES
Dr. Adesina O.A

2. Outline
• Introduction
• Nail structure
• Changes in nail plate
• Nail abnormalities of specific organ system
– Endocrine disease
– Renal disease
– Pulmonary disease
– Gastrointestinal disease
– Cardiovascular disease
– Psychological disease
– Connective tissue diseases
• Drugs and Nail abnormalities
• Conclusion
• References

3. Introduction
• The nail is a plate of keratin that covers the
dorsal aspect of the distal phalanges of the
fingers and toes.
• A change in colour, size, shape or texture of
finger- and toenails can be an indicator of
underlying systemic disease.
• An appreciation of these nail signs, and an
ability to interpret them when found, can help
guide diagnosis and management of patients.

4. Nail functions
• The nails serve multiple functions:
• Protecting the digits
• provides tactile sensation,
• aids in thermoregulation,
• assists in picking up small objects;
• it also has dense lymphatics in the
hyponychium that help resist infection.

5. Structure
• The nail plate is a hard sheet of translucent
keratin in which lie several layers of dead,
compacted cells.
• The nail bed is the tissue that lies beneath the
nail plate. It contains nerves, lymphatics and
capillaries.
• The germinal matrix, is the source of cells that
become the nail plate.
• In longitudinal sections the matrix has a wedge
shaped appearance and consists of a proximal
(dorsal) and a distal (ventral) portion.

6. Structure
• Keratinization of the proximal nail matrix cells
produces the dorsal nail plate and of the distal
nail matrix cells produces the intermediate nail
plate.
• Nail matrix melanocyte activation produces
diffuse or banded nail pigmentation
• The matrix, extends distally into the nail as the
lunula (half-moon), the whitish coloration visible
at the proximal nail, most apparent at the thumb.

7. Structure
• The eponychium is a small band of epithelium
that covers the proximal aspect of the nail; the
paronychium, around the medial & lateral
borders; the hyponychium is the thickened,
cornified layer of the epidermis beneath the free
border of the nail.
• The cuticle is a layer of epidermis that folds back
over the surface of the nail plate at its base.

9. Anatomical Location in relation to
Pathologic Changes
• Proximal Matrix:
– Beau’s Lines; Pitting; Trachyonychia (rough nails)
– Longitudinal striations/fissures/grooves
• Distal matrix: True leukonychia
• Proximal and distal matrix
– Koilonychia; Onychomadesis
• Nail bed
– Longitudinal erythronychia; Onycholysis; Splinter
hemorrhages; Apparent leukonychia
• Nail bed and hyponychium: Subungual hyperkeratosis
• Proximal nail fold: Paronychia; Periungual erythema

10. Nail Growth and Aging
• Nails grow 0.1 mm/day, with more rapid growth
in adolescence and a slower rate with aging.
• The dominant thumbnail tends to grow faster
than the non-dominant nail, and disease may
slow nail growth.
• Pregnancy and hyperthyroidism are associated
with increased rates of growth; starvation and
lactation, with slower growth.
• With aging, nails become ridged, more opaque,
greyish in color and less flexible.

11. Handedness
• The thumbnail may provide a clue to dominant
handedness.
• By measuring the comparatively larger area of
the two thumb lunulas of an individual, one can
determine that individual’s cerebral hemispheric
dominance or handedness
• The dominant thumbnail has a wider base and
the angles formed by the base and the lateral
aspects of the nail are more obtuse.

12. Changes in the nail plate
• Beau lines are transverse depressions in the
nail as indicative of a systemic illness or
condition of sufficient severity to interfere with
the metabolic proliferative function, thus
temporarily arresting growth of the matrix.
• Systemic conditions associated with beau lines
– High fever; Viral illness (hand-foot-and-mouth
disease; measles); Diarrhea; Kawasaki
syndrome; Peripheral ischemia; Drugs

13. Changes in the nail plate
• Onychomadesis also results from a temporary
arrest in nail matrix activity and the proximal nail
plate is detached from the proximal nail fold by a
whole-thickness sulcus.
• Causes of onychomadesis are the same as
those for Beau’s lines but are more severe.
• Multiple Beau’s lines or onychomadesis in the
same nail indicates repetitive insults.
• Measuring the distance of the groove from the
proximal nail fold can date the time of the insult
leading to Beau’s lines

15. Onychomadesis

16. Changes in the nail plate
• Longitudinal ridging of the nails could be seen
in normal aging, gout, PVD, viral infections.
• In this condition, the ridges start at the cuticle
and run the entire length of the nail. Often due to
lack of moisture, and decrease in nutrient
absorbtion

18. Clubbing
• Clubbing of the nails refers to the enlarged
curvature of the horizontal and longitudinal
orientation of the nails with bulbous enlargement
of the distal digit.
• May be associated with increased nail-plate
mobility
• Observed grossly, also by measuring the
Lovibond’s angle- the angle formed by the
proximal nail fold and the emerging nail plate.
• Normally ~160 degrees. When this angle is
enlarged, it is indicative of pathologic signs.

19. Clubbing
• Pathophysiology is unknown, though different
theories abound.
• One theory is that clubbing is a response to
arterial hypoxaemia, in which release of an
humoral substance causes dilation of the
vessels of the fingers and toes.
• Another is that clubbing results from a
neurovascular (vagal) abnormality.
• PDGF release from trapped megakaryocytes

20. Clubbing
• May be idiopathic/primary (5-10%), or acquired
(90%).
• Idiopathic clubbing, is linked to AD disorders
such as pachydermoperiostosis (Integumentary
and skeletal hyperproliferation seen primarily in
men), familial clubbing, and hypertrophic
osteoarthropathy.

21. Clubbing
• Acquired cases of clubbing in:
– Chronic suppurative lung diseases, bronchial
carcinoma, asbestosis, idiopathic pulmonary fibrosis;
cyanotic congenital heart diseases, infective
endocarditis, endomyocardial fibrosis, atrial
myxomas; steatorrhoeas, ulcerative colitis, Crohn’s
disease; liver/ biliary cirrhosis; schistosomiasis.
• Unilateral clubbing is reflective of aneurysms or
arteriovenous fistulas.

23. Koilonychia
• Koilonychia describes the state where the nail
loses its normal contour to become flat or spoon
shaped.
• It is the classic nail disorder found in iron
deficiency anemia. Also in:
– hemochromatosis, raynaud’s syndrome, porphyria,
scleroderma, thyrotoxicosis, diabetes mellitus,
syphilis, and Plummer-Vinson syndrome.

24. Koilonychia
• Mechanisms:
• oxygen deprivation causing atrophy of the distal
connective tissue, in turn causing the matrix to
assume a plantargrade attitude
• Possible causal relationship between low cystine
content in nails associated with severe anemia
to nail weakness and flexibility, thus giving rise
to koilonychia.

26. Pitting
• Pitting describes shallow depressions in the nail
plate approx 1mm in diameter and manifest
either a random or linear arrangement.
• When >6 on all the nails, or if the diameter is
unusually large, further evaluation is indicated.
• Pitting has been most closely linked with
– connective tissue and collagen disorders:
Reiter’s syndrome, rheumatoid arthritis, and
systemic lupus erythematosus

28. Onycholysis
• Onycholysis is the separation of the nail plate
from the nail bed at the distal aspect of the digit.
• Associated with hyperthyroidism (fourth finger>
fifth finger> remaining fingers> thumb> toenails).
• Also in, amyloidosis, multiple myeloma,
raynaud’s disease, diabetes mellitus, Porphyria
cutanea tara, Syphilis, Histiocytosis X, Hansen’s
disease, Hypothyroidism, Pregnancy,
Bronchogenic carcinoma, Bronchiectasis,
Systemic lupus erythematosus, Reiter’s
syndrome, Tabes dorsalis, Acute anterior
poliomyelitis, Systemic sclerosis

30. Splinter hemorrhages
• Splinter hemorrhages are small, linear
subungual structures, normally red, purple or
brown in colour, frequently located in the distal
third of the nail plate.
• caused by damage to capillaries within the nail
bed, which have a longitudinal orientation,
leading to their linear appearance.
• Occurs in subacute bacterial endocarditis,
antiphospholipid syndrome, scurvy, sarcoidosis,
rheumatoid arthritis, mitral stenosis, severe
anemia, SLE, and is seen in patients on dialysis,
Buerger’s thromboangiitis obliterans.

32. Nail color changes
• ‘‘yellow nail syndrome’’ associated with
lymphedema, chronic pulmonary infection and
sinus infection with bronchiectasis and
subsequent fibrosis.
• Other conditions:
– Diabetes mellitus, Hypothyroidism, Raynaud’s
disease, Rheumatoid arthritis, Pulmonary and hepatic
tuberculosis, Extremely hard ear wax, Anaplastic
sarcoma, Hodgkin’s disease, Laryngeal carcinoma,
Adenocarcinoma, Hypogammaglobulinemia

34. Nail color changes
• Leukonychia, or white nail, may be complete,
partial, spotted, or banded.
• It is postulated to be the result of light diffraction
caused by retained nuclei in the nail plate.
• Leukonychia may be congenital or acquired.
• Associated with: Cirrhosis, Typhoid fever,
Tuberculosis, Leprosy, Nephritis, Hodgkin’s
disease, Colitis, Chilblains, Metastatic disease

35. Nail color changes
• Terry nail/three-quarter, one-quarter nail with a
pale, proximal portion and a narrow, deep-red
distal portion, frequently seen in liver cirrhosis;
also in PVD, Raynaud phenomenon, SLE and
other connective tissue disorders.
• Half-and-half nail, where the proximal portion of
the nail is white, and the distal portion is pink or
brown.
• associated with azotemia and chronic renal
failure.

36. Nail color changes
• Mees nail characterized by a single, transverse,
narrow whitish line that runs the width of the nail
plate and is seen on multiple nails. Seen in:
– septicemia, aortic dissection, ARF, sickle cell
anemia in crisis and poisoning with heavy
metals particularly arsenic.
• The number of days since the serious event
occurred can be approximated by measuring
from the cuticle to the transverse line, adding 3
to 4mm for that portion of the nail which is
hidden between the matrix and the cuticle, then
dividing by the 0.1mm.

37. Nail color changes
• Muehrcke’s lines taking place as a result of nail
bed changes, where a pair of horizontal white
bands transverse the width of the nail.
• Found particularly when serum albumin < 2.2
g/dL, e.g in nephrotic syndrome, advanced liver
disease. Also seen in zinc deficiency.

40. Melanonychia
• Melanonychia describes a brown to black colour
of the nails due to the presence of melanin in the
nail plate.
• It can be caused by activation or proliferation
(benign or malignant) of nail matrix melanocytes.
• The pigmentation may involve the whole nail
(total melanonychia) or may be banded, as in
transverse melanonychia (rare) or commonly
longitudinal melanonychia.
• Associated systemic disorders include:
– HIV infection, Addison syndrome, post-bilateral
adrenalectomy, small cell lung CA producing ACTH,
MSH.

41. Nail color changes
• Red: Lupus erythematosus, Polycythemia,
Darier’s disease, Cardiac failure, Raynaud’s
disease
• Orange: Diabetes mellitus, Hyperbilirubinemia,
Syphilis
• Blue: Wilson’s disease
• Black: Peutz-Jeghers syndrome
• Gray: Malaria, Hemochromatosis
• Nail bed pallor is seen in patients with anaemia

42. Nail peculiarities in Systemic
Diseases
• In systemic diseases, nail manifestations usually
involve most or all nails.
• Recurrent nail infections and chronic paronychia
can be a sign of underlying immunosuppression.
• Beau’s lines located at the same level in all
digits or onychomadesis occurring
simultaneously in all digits is strongly diagnostic
for nail matrix damage from a systemic cause.

43. Nail signs in Diabetes and other
endocrinopathies
• Many of the abnormalities and adverse reactions
in the lower extremeties in diabetics are related
to:
– Impaired peripheral circulation due to diabetic
angiopathy
– Loss of sensation of the lower extremity
because of diabetic peripheral neuropathy
– Impaired wound healing related to diabetic
immunopathies
– Unrecognized trauma resulting in a breach in
cutaneous integrity

44. Nail signs in Diabetes and other
endocrinopathies
• Diabetes mellitus:
– Periungal erythema and telangiectasia in the
nail folds
– Thickening of the skin of the dorsal hands and
feet and proximal nail folds
– Yellow, thickened, fragile, ridged, and brittle
nails in long-standing diabetes
– Onychogryphosis (Ram’s Horn Nails)
– Vesicles and bulla on the toes
– Onychomycosis.

45. Yellowish hue in diabetics nails

46. onychomychosis

47. onychogryphosis

48. Nail signs in Diabetes and other
endocrinopathies
• Hyperthyroidism:
– Onycholysis beginning in the fourth and fifth nail
(Plummer’s nails)
– Yellow nail syndrome, characterized by yellow, slow-
growing nails and absent lunulae and cuticles
– Finger clubbing
• Hypothyroidism:
– Slow growth, hapalonychia (thin nails), longitudinal
sulcus, and brittle nails
– Chronic mucocutaneous candidiasis

49. Plummer’s nails

50. Hapalonychia

51. Nail signs in Diabetes and other
endocrinopathies
• Hypoparathyroidism:
– Brittle, thin, and fragile nails affecting the
distal half of the nail
– Finger clubbing
• Hyperparathyroidism:
– Pseudoracquet nail (broader and shorter
because of acro-osteolysis of the distal
phalanx due to calcium mobilization)

52. Racquet nails

53. Nail signs in Diabetes and other
endocrinopathies
• Estrogen states
– Nail growth increased in pregnancy and
decreased during lactation
– Longitudinal pigmented bands sometimes in
pregnancy
– Thinner, and more brittle nails at menopoause

54. Nail signs in Diabetes and other
endocrinopathies
• Acromegaly:
– Absent lunulae, koilonychia, macronychia
• Hypopituitarism
– Absent lunulae
• Cushing’s syndrome
– Candida paronychia
• Chronic adrenal insufficiency:
– Hyperpigmented longitudinal bands in multiple
nail plates

55. Nail signs in Renal Diseases
• The nail patella syndrome (hereditary osteo-
onychodysplasia, HOOD)
– with absent or underdeveloped, discoloured,
split, ridged or pitted nails, triangular lunula
– Fingernails affectation > toenails
• Azotemia: Half-and-half nail
• In nephrotic syndrome: Muercke bands
• Multiple splinter hemorrhages have been noted
in patients undergoing hemodialysis.

56. Nail patella syndrome

57. Nail signs in GIT/Liver Diseases
• Liver cirrhosis: leuchonychia, Terry nail
• Wilson disease: Bluish lunulae
• Hemochromatosis: blackish pigment, presumably
melanin, appears on the nails as it does on the
skin.
• Upper GIT cancer: acrokeratosis paraneoplastica
(Bazex syndrome) - keratosis of the palms and
acral skin. Featuring nail plate thickening,
subungual hyperkeratosis, longitudinal ridging,
discolouration, nail plate loss

58. bazex syndrome

59. Nail signs in Cardiac Diseases
• Congestive heart failure
– A reddish lunula.
• Congenital heart disease
– Digital clubbing
• Bacterial endocarditis
– Splinter haemorrhages; Osler's nodes

60. Nail signs in Respiratory Diseases
• Superficial yellow-brown staining of the nail plate
is commonly observed in smokers.
• If a patient quits suddenly, there will be a sharp
demarcation in colour as the nail grows out,
otherwise known as ‘quitter's nail’.
• Clubbing
• Yellow nail syndrome

61. Quitter’s nails

62. Nail signs in psychiatric Diseases
• Nail tic disorders
– Onychophagia, onychotillomania, habit tic deformity;
bidet nails
• Longitudinal ridging
• Dystrophic nails
• Hang nails
• Paronychia
• Longitudinal melanonychia

64. Hang nails

65. Nail signs in Hematological Diseases
• Anemia: nail bed pallor
• Iron deficiency anemia: koilonychia.
• Leukemia and bleeding diatheses: Hemorrhages
under the nail plate

66. Connective tissue diseases
• An informative site of nail change in connective
tissue disease is the proximal nail fold, which
can develop erythema, telangiectasia and nail
fold infarcts
• Scleroderma and dermatomyositis:
– Giant capillary loops adjacent to areas with no
capillaries in the proximal nail fold.
• Pterygium inversum unguis, periungal
hemorrhages and ulceration in scleroderma
• Erythema of the distal nail folds; hyperkeratotic
thickening and roughening of the cuticles in
Dermatomyositis

67. Connective tissue diseases
• Systemic lupus erythematous:
– periungual erythema and telangiectasia;
Cuticular and subungal hyperkeratosis,
splinter hemorrhages, transverse leuconychia,
pitting, and onychorrhexis.
• In rheumatoid arthritis, splinter hemorrhages are
most commonly seen at the nail folds. Small nail
fold and finger pulp petechiae secondary to
necrotising vasculitis in rheumatoid arthritis
(Bywaters lesions).

68. pterygium inversum unguis

69. periungal erythema

70. bywaters' lesions

71. Nail signs in HIV
• Untreated HIV or AIDs can present with nail
infections; bacterial, viral and fungal.
• Proximal onychomycosis, particularly with
Trichophyton rubrum
• Candida species can also lead to acute and
chronic onychomycosis and paronychia
(inflammation of the periungual skin).
• Nail bed squamous cell carcinoma in younger
patients can occur with HIV and is associated
with human papillomavirus infection.

72. Nail signs in HIV
• Melanonychia, particularly longitudinal
melanonychia
• Digital clubbing
• Onycholysis
• Terry’s nails
• Anolunula

73. Nail signs with drugs
• Tetracycline: yellowish nail
• Chloroquine: blue-black nail
• Adreamycin and cyclophosphamide: blackish
nails.
• Argyria (silver exposure): slate grey nails.
• Zidovudine, Azathioprine: melanonychia
• Indinavir: pyogenic granuloma
• Chemotherapy: Beau’s lines, Onychomadesis,
muehrcke’s lines, hemorrhagic onycholysis,
pyogenic granulomas, melanonychia

74. Nail signs with drugs
• Hydroquinone: Ochronosis (yellow-brown
discoloration)
• B-blockers: digital ischemia, pincer nail deformity
• PUVA phototherapy: photo-oncholysis,
melanonychia
• Retinoids: nail fragility, pyogenic granuloma,
paronychia

75. Conclusion
• As we have seen, a patient’s nails,
although by no means pathognomonic,
can provide various clues leading to either
the detection or confirmation of systemic
illnesses.
• As diagnosticians, we are obliged to make
use of these information, which, are
readily available.

76. References
• Abraham J. Herzberg, Clin Podiatr Med Surg 21 (2004)
631–640
• Bean WB: Nail growth: 30 years of observation. Arch
Intern Med 134:497-502, Sep 1974
• Cutler AG. Stedman’s medical dictionary. 23rd edition.
Baltimore (MD): Williams & Wilkins; 1976. p. 679
• Phoebe Rich: Nail changes due to diabetes and other
endocrinopathies. Dermatologic therapy, Vol. 15, 2002,
107-110
• Shearn MA: Nails and systemic disease (Medical Infor-
mation). West J Med 129:358-363. Oct 1978
• Zaias N. The nails in health and disease. Norwalk (CT):
Appleton & Lange; 1990.

77. Thanks for listening