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Anatomy and
physiology
Black or brown
Leukonychia
Blue or green
Yellow
Red or orange
the authors
Dr Emma Mooney
dermatology trainee, Austin
Hospital, Heidelberg, Victoria.
Dr Caroline Kronborg
medical registrar, Alfred Health,
Prahran, Victoria.
Background
CHROMONYCHIA is a common
presentation to both GPs and dermatologists. It refers to alteration in the
colour of the nail — either involving
the nail plate or subungual tissue. It
may be the result of overproduction of
pigment or melanin or deposition on
or alteration in the surface of the nail.
The nail provides a protective surface covering the fingertips while
allowing sensory discrimination and
enhanced dexterity. Further, the cosmetic appearance of the nails is of
social importance, and nail disorders
may lead to psychological distress.
Chromonychia may represent a
wide range of colours, including
black or brown (melanonychia),
white (leukonychia), red (erythronychia), or even blue, yellow or
green. The causes of chromonychia
are diverse, ranging from exogenous
dermatological conditions to infection and congenital disease. In this
article, we review the different ways
a discoloured nail may present to
general practice and their clinical
assessment and management.
cont’d next page
nail
discolouration
Associate Professor Anne
Howard
head of dermatology, Western
Hospital, Footscray, Victoria and
dermatology consultant, nail clinic,
Skin and Cancer Foundation,
Carlton, Victoria.
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Australian Doctor
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14 November 2014 | Australian Doctor |
25
How To Treat – Nail discolouration
Anatomy and physiology
FINGERNAILS grow at an average
rate of 0.1mm per day and toenails
at half this speed. Any insult to the
nail plate or matrix will result in a
deformity that may be present for
many months before growing out
completely.
The nail unit consists of the
nail plate, nail bed, lateral nail
folds, cuticle (the eponychium)
and hyponychium (figure 1). The
nail plate adheres firmly to the nail
bed, and its undersurface interdigitates longitudinally with corresponding grooves on the nail bed.
The nail unit overlies the terminal
phalanx. Due to the close proximity of the nail matrix to the distal
interphalangeal joint, any change
to the joint or bone can result in
nail-plate distortion.
About a quarter of the nail is covered by the proximal nail fold, from
which the nail plate emerges. The
nail plate is bordered on each side
by the lateral nail folds and covered
proximally by the eponychium. The
germinal epithelial matrix is responsible for the majority of nail production. The lunula is the distal aspect
of the germinal matrix and can be
identified as a white half-moon at
the proximal nail.
Nail rigidity is due to hard keratins comprised primarily of sulfur
bonds, but the nail plate also contains calcium, phosphate, zinc, iron
and copper.
Nail plate
Nail bed
Hyponychium
Lunula
Nail
plate
Figure 1: Anatomy of
the nail unit showing
the nail plate, nail bed,
lateral nail fold, cuticle
(eponychium) and
hyponychium.
Adapted from image
courtesy of R. Martell.
Lateral
nail fold
Nail
matrix
Cuticle
Proximal
nail fold
Black or brown
MELANONYCHIA — black or
brown nail discolouration — results
from melanin deposition by melanocytes; it is not age- or gender-specific
and is usually benign. These melanocytes are usually contained in the
nail matrix and normally lie dormant. Melanin production may be
increased when existing melanocytes
are activated (melanocyte activation)
or as a result of an increase in the
number of melanocytes (melanocyte
hyperplasia).
Melanonychia may present as
a tan, brown or black longitudinal streak within the nail plate that
extends from the nail fold to the free
edge of the nail (longitudinal melanonychia), may involve the entire
nail plate (complete melanonychia)
or may run transverse across the nail
(transverse melanonychia).
Table 1: Causes of melanocyte activation*
Benign racial pigmentation
Pregnancy
A
Age > 50 years old
Inflammatory
Psoriasis
Lichen planus
Chronic paronychia
Bowen’s disease
BCC
B
Brown to black, blurred irregular borders, breadth > 3mm
C
Changes of melanonychia or nail plate morphology (sudden, recent or
rapid)
D
Digit: single digit, especially thumb, great toe or index finger
Hyperthyroidism
Addison’s disease
Cushing’s syndrome
HIV
Haemosiderosis
Porphyria cutanea tarda
E
Extension of pigment into nail fold (Hutchinson’s sign of the nail)
F
Family or personal history of melanoma and/or dysplastic naevus
syndrome
Syndromes
Laugier-Hunziker
Peutz-Jeghers
Begins in a single digit during the fourth to seventh decade
Iatrogenic
Radiation exposure
Phototherapy
Drugs (eg, doxorubicin, cyclophosphamide, etoposide,
methotrexate, hydroxyurea, minocycline, chloroquine)
Systemic
Red flags for longitudinal melanonychia due to melanoma:
Involves the proximal nailfold (Hutchinson’s sign of the nail)
* Adapted from Andre and Lateur, ‘Pigmented nail disorders’, 2006.29
Melanocyte activation
Activation of existing melanocytes
leads to increased production of
melanin, which results in pigmentation of surrounding onychocytes. Melanocyte activation is
associated with many conditions
— listed in table 1. It is usually
benign.
One condition associated with
melanocyte activation is benign
racial pigmentation. This condition often occurs in multiple fingernails or toenails and is most
common in Fitzpatrick skin types
III-VI. It may be more common in
Afro-Caribbean patients, particularly in the form of longitudinal
melanonychia.1 It is unusual in
Caucasians. Figure 2 shows benign
racial pigmentation in the nails of
men of a Turkish and an Indian
ethnicity.
Pregnancy may also cause melanocyte activation, affecting the
skin and the nails. It may result
in dark bands of pigment through
one or multiple nails. It usually
resolves following delivery.
Local causes
Local inflammatory conditions
may cause melanocyte activation — most commonly seen with
psoriasis, chronic paronychia and
lichen planus. While these conditions may present with melanonychia, they are also associated with
a variety of other nail changes,
including red, orange and yellow
discolouration. On resolution or
26
| Australian Doctor | 14 November 2014
Features concerning for melanoma of the nail unit
(The ABCDEF mnemonic8)
Physiologic
A
Figure 2:
Benign racial
pigmentation:
A: in the
toenails of
a Turkish
male. B: in the
fingernails of
an Indian male.
B
control of the inflammatory condition, chromonychia often resolves.
Carcinoma may invade and disrupt the germinal matrix, resulting in melanonychia. Squamous
cell carcinoma in situ (Bowen’s
disease) and basal cell carcinoma
of the nail are uncommon. Such
malignant processes will often
cause identifiable surrounding
cutaneous change and secondary
nail distortion. Treatment is surgi-
cal; Mohs’ micrographic surgery is
often utilised to achieve adequate
local clearance while minimising
loss of digital function.
Systemic and syndromic causes
Systemic diseases or syndromes
can present with melanonychia.
Toenails and fingernails are often
involved and may present as multiple bands of longitudinal melanonychia. Endocrine disorders, such
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Develops abruptly in a previously normal nail
Becomes suddenly darker or wider
Occurs in a person who gives a history of digital trauma
Has blurred, not straight lateral borders
Is accompanied by nail dystrophy
Has a wider base of the band (proximally) than distally
as hyperthyroidism, Addison’s
disease and Cushing’s syndrome,
have been associated with melanonychia in some patients. Other
associated conditions include HIV,
haemosiderosis and porphyria
cutanea tarda.
There are a few rare syndromes
associated with melanonychia.
Laugier-Hunziker syndrome is
a benign, sporadic disorder of
unknown cause characterised
by macular pigmentation of the
buccal mucosa, lips and melanonychia. It may be of cosmetic
concern but is not associated with
internal malignancy. This differs
from Peutz-Jeghers syndrome,
which is an autosomal dominant
condition associated with an
increased risk of gastrointestinal
malignancy. It too may result in
melanocytic macules of the oral
mucosa as well as the hands, feet
and nails.
Iatrogenic causes
Iatrogenic causes of melanonychia
include drugs, phototherapy and
both systemic and local irradiation. Cytotoxic agents are often
implicated and include cyclophosphamide, etoposide, methotrexate,
doxorubicin and hydroxyurea.2-4
Cyclophosphamide may cause
a diffuse or longitudinal black
melanonychia or a grey dyschromia at the proximal nail plate.
Doxorubicin may cause transverse
bands of dark brown and white
dyschromia, and hydroxyurea
may produce a dark brown band
of pigmentation distally. Chloroquine may cause diffuse blue-black
dyschromia. 26 The antiretroviral
agent zidovudine may cause longitudinal melanonychia. 27
Minocycline is known to cause
diffuse blue-black chromonychia
with relative sparing of the
lunula.28 Following cessation of
the causative agent, chromonychia
will often resolve, but resolution
may take months.
Melanocyte hyperplasia
Melanocytic hyperplasia refers
to an increase in the number of
melanocytes in the nail matrix.
The process may occur in benign
conditions (lentigo or subungual
melanocytic naevi) or malignant
conditions (melanoma). It is sometimes difficult to differentiate
between a benign and a malignant
process clinically, resulting in diagnostic delay and subsequent poor
prognosis. A high index of suspicion is required, and concerning
features warrant prompt specialist referral (see ‘Features concerning for melanoma of the nail’ and
‘Red flags for longitudinal melanonychia due to melanoma’).
cont’d page 28
How To Treat – Nail discolouration
from page 26
Benign causes
Subungual naevi may be acquired
or congenital and are more common in children (figure 3). They
differ from lentigo because of the
nested nature of melanocytes. Subungual naevi can present de novo in
childhood or teenage years. Lentigo
is more common in adults.
If a new linear band of blackbrown pigment occurs in an adult,
a biopsy may be required. Serial
photography can be helpful if the
history of evolution is unclear,
especially in conjunction with dermoscopic images. Dermoscopic
evaluation of naevi will reveal regular parallel lines of pigment often
on a brown background.
Melanoma
Melanoma involving the nail plate
is most commonly seen in the
fourth to seventh decade. It represents 1-3% of melanoma in the
Caucasian population and 15-20%
of melanomas in the African-American population.5,6 Between 45%
and 60% of subungual melanomas
arise in the hand and 40-55% in
the foot. The thumb and great toe
are more commonly affected.
Melanoma is thought to originate from the nail matrix and not
from the nail bed itself.7 Acral
lentiginous melanoma is the most
common cause of malignant melanocyte hyperplasia; superficial
spreading or nodular melanoma
may also cause melanonychia.
Subungual melanoma is classically
seen as new-onset longitudinal melanonychia. It may also present with
change in width or colour of exist-
Figure 3:
Benign
subungual
naevus of the
middle finger
that had been
present since
childhood.
Figure 4:
Surgery
exposing
melanoma
extending
into the nail
fold, clinically
identified by
Hutchinson’s
sign of the nail.
ing longitudinal melanonychia. It
should be noted that longitudinal
melanonychia is most commonly
caused by physiological conditions,
even though it may suggest an
underlying subungual melanoma.
The box, ‘Red flags for longitudinal melanonychia due to melanoma’, lists features that should
arouse suspicion for further invest-
alteration in the nail matrix nor the
nail bed; rather, it refers to an exogenous process affecting the more
superficial layers of the nail plate,
such as in white superficial onychomycosis or nail varnish.
Occupational history, family history, drug history and history of
possible exposure to heavy metals should be elicited. Examination
should be targeted, looking for signs
of liver or renal failure, malnutrition
and signs of systemic disease. Screening blood tests may include an FBC,
a metabolic panel, liver function
tests, albumin, iron studies, nail clippings for fungal microscopy, culture
and sensitivities and, if indicated on
history, a heavy metal screen.
Treatment of the identified underlying aetiology can lead to resolution
of the nail changes with time. Diligent nail care, limitation of exposure
to irritants and frequent moisturising can all assist in the return to a
normal nail. For example, onycholysis as a cause of pseudoleukonychia
may be managed by keeping the nails
trimmed short and avoiding moist
environments, trauma and contact
irritants. Mechanical cleaning under
the nails should be discouraged to
prevent introduction of infection.
trauma to the matrix (eg, overzealous manicuring) and a subsequent
fault in keratinisation. It is not due
to zinc or calcium deficiency as is
often believed. Punctate leukonychia
has also been described in association with alopecia areata. About half
of the lesions will disappear as the
nail grows towards the free edge.
igation and referral. Definitive
diagnosis of subungual melanoma
requires biopsy.
Clinical examination
Dermoscopic features of melanoma involving the nail plate may
include brown pigmentation with
various darker bands within the
lesion. These bands are often more
irregular in spacing and width than
in naevi and lentigo.9 Hutchinson’s
sign of the nail refers to extension
of pigment onto the proximal or
lateral nail fold and is a concerning sign requiring further investigation. It can occur in subungual
naevi but is more commonly seen
in melanoma (figure 4). Change
in longitudinal melanonychia,
which should be closely monitored,
should prompt specialist referral
for urgent consultation.
discolouration of the skin and nails
of fingers used to hold cigarettes.
Smoking cessation may result in a
clear line of demarcation with tar
staining evident in the distal nail
and absent proximally (also known
as ‘quitter’s nail’). Henna, used for
cultural and cosmetic purposes,
may also cause brown staining of
the skin and nails.
Following prolonged use of nail
varnish, a light-brown or yellow
discolouration may occur in the
affected nails if it is not removed
frequently. This is temporary and
will grow out.
Haematoma
Exogenous pigment is a common
cause of brown chromonychia.
Nicotine may cause brown-orange
Traumatic nail injury causing subungual haemorrhage may result in
red-brown dyspigmentation in the
acute phase or brown-black discolouration if chronic as a result
of haemosiderin deposition. The
patient may or may not be aware
of a history of trauma.
Dermoscopically, haemorrhage
may appear red, brown or black
and has central pigment homogeneity. Round droplets may be
present near the edges of the nail
plate, and splinter haemorrhages
may also be seen. In the event of a
large traumatic haematoma, pressure can be released though the
slow insertion of a sharp, heated
sterile implement (such as the end
of a paperclip) just distal to the
lunula. No treatment expedites
clearance of haemosiderin.
The affected nail will migrate distally at the same rate as normal nail
growth (0.1mm/day), eventually
separating and falling off by itself
or being intentionally clipped.
be a common incidental finding in
children and adolescents who do
not notice minor injury to nails. The
abnormality is transient and grows
out with the growth of new nail.
treatment for the leukonychia seen
in Darier’s and Hailey-Hailey disease although it may improve with
management of aggravating factors
and prevention of complications.
Longitudinal leukonychia
Apparent leukonychia
Longitudinal leukonychia is a permanent greyish-white longitudinal
streak 1mm wide. It may develop as
a single streak on a single nail, affect
two or three nails, or present as several striae down one nail. Isolated
longitudinal leukonychia is uncommon and may reflect an underlying
nail-bed tumour, such as a subungual filamentous tumour. A horny
pearl of keratinous substance will be
seen under the free edge of the nail
in a subungual filamentous tumour.
If pain or nail splitting develops,
surgical excision may be required,
wherein the nail bed is exposed and
the lesion is excised before the plate
is repositioned.
Longitudinal leukonychia may
also be seen together with longitudinal erythronychia in Darier’s disease
(keratosis follicularis), which is a
rare autosomal dominant dermatosis. Hailey-Hailey disease (familial
benign chronic pemphigus) may also
cause longitudinal leukonychia. This
rare inherited condition is associated
with the gene ATP2C1 and may present in the second to fourth decade as
a painful erosive rash occurring primarily in the flexures. It may become
hyperkeratotic and develop secondary bacterial infection, resulting in
an associated malodour. There is no
Apparent leukonychia, in contrast
to true leukonychia, does fade
with pressure and does not move
distally with nail growth. This is
due to the fact that apparent leukonychia is the result of changes
in the nail bed rather than the
nail matrix itself. Apparent leukonychia may be a sign of systemic
disease causing vascular changes,
nail-bed hyperkeratosis or interspersed onycholysis. The most
commonly seen forms of apparent leukonychia are half-and-half
nails, Muehrcke’s nails and Terry’s nails. Anaemia may also manifest with apparent leukonychia
if the haemoglobin is sufficiently
low. Raynaud’s phenomenon may
cause apparent leukonychia due to
vasoconstriction.
Treatment and prognosis
Following the diagnosis of melanoma, treatment will depend on
tumour thickness but will often
involve amputation of the digit.
Prognosis is variable depending
on the time of detection and the
depth of the tumour. As a result of
the delayed diagnosis, the tumour
subtype (acral lentiginous, superficial spreading or nodular) is not
significantly associated with prognosis. Melanoma in the toenail is
typically identified later than melanoma in the fingernail, resulting in
a worse prognosis on diagnosis.
Brown staining
Leukonychia
LEUKONYCHIA describes an
opaque white discolouration of the
nail and is the most common form
of chromonychia. While there are
a variety of classifications reported,
there are three broad subtypes: true
leukonychia, apparent leukonychia
and pseudoleukonychia.1,10
True leukonychia is the result of
matrix dysfunction and resulting
defective keratinisation. Light is diffracted abnormally so that normal
transparency of the nail is lost, giving it an opaque white appearance.
The discolouration moves distally
as the nail grows and does not fade
with applied pressure.
True leukonychia may be categorised, depending on extent and
pattern, as complete or total leukonychia; and incomplete or subtotal
leukonychia, which includes punctate, transverse and longitudinal leukonychia. Complete leukonychia is
rare. It may be inherited or acquired,
involve one or multiple digits, and a
rare inherited form can involve all
20 nails, appearing porcelain-white
in colour. Acquired complete leukonychia is commonly the result of
superficial onychomycosis but may
rarely be seen in association with
peptic ulcer disease, cholelithiasis
and ulcerative colitis. The subcategories of incomplete leukonychia are
discussed later in this section.
Apparent leukonychia is due to an
abnormality in the nail bed rather
than the nail matrix and therefore
does resolve with pressure. Pseudoleukonychia is neither the result of
28
| Australian Doctor | 14 November 2014
Punctate leukonychia
Punctate leukonychia is the most
common form of true leukonychia.
It describes the presence of white
spots on the nail plate and is found
most commonly in the fingernails. It
is thought to be due to local micro-
Transverse leukonychia
Mees’ lines
Mees’ lines are transverse homogenous white bands, 1-2mm wide,
across the entire nail. First described
by Mees in 1919 in association with
arsenic toxicity, transverse leukonychia can develop on one or several nails. It occurs at the same level
in each nail, and the proximal and
distal borders are parallel throughout their width. The distance from
the cuticle helps determine the time
of the insult. The magnitude of the
band indicates disease severity. Any
acute systemic illness can cause
transverse leukonychia, as can heavy
metal toxicity or chemotherapy.
Acute rejection of a renal allograft
has also been recognised as a cause.11
Leukonychia variegata
This is a variant of transverse leukonychia. The white transverse bands
are not uniform and result from
repeated microtrauma to the nail
matrix (eg, from a distally impinged
shoe on an untrimmed nail). These
striae are less homogeneous than
the transverse leukonychia caused
by endogenous pathology and can
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Half-and-half nail
Half-and-half nail (‘Lindsay nail’) is
associated with chronic renal failure
— in particular, uraemia. The proximal half of the nail is pale or white
and obscures the lunula while the
nail is erythematous distally. There
is a red/pink or brown band at the
junction of the colour change due to
increased lipochrome pigment deposition. The nail discolouration may
cont’d page 30
How To Treat – Nail discolouration
from page 28
resolve with correction of renal function and often resolves within weeks
of renal transplantation in affected
individuals.12,13
Terry’s nail
Terry’s nail was first described in
patients with cirrhosis.14 Like halfand-half nails, all nails tend to be
affected uniformly, with proximal
opaque white discolouration that
obscures the lunula and extends distally to end 1-2mm from the distal
edge, leaving an area of normallooking nail. In some patients, the
proximal nail bed is light pink rather
than white. These changes are attributed to alterations in the underlying
vascularity and are seen in cirrhosis, hepatic metastases, congestive
cardiac failure and type 2 diabetes
mellitus. In contrast to half-and-half
nails, there is no brown band at the
junction between the white discolouration and the distal area of erythema.
Treatment of the underlying disease process may alter the appearance of the nail, but the vascular
changes often persist.
Muehrcke’s lines
Muehrcke’s lines are a double band
of white lines running parallel to the
lunula and are separated by pink
bands of normal-looking nail. They
are classically seen in association
with conditions that cause hypoalbuminaemia (<2g/dL), such as
nephrotic syndrome, hepatic failure
and malnutrition.31 Muehrcke’s lines
have also been reported in patients
receiving systemic chemotherapy
and patients with zinc deficiency. It
is thought to be the result of oedema
of the connective tissue in front of
the lunula, below the epidermis.
Figure 5:
Onycholysis due to
psoriasis causing
pseudoleukonychia in
the distal fingernails.
Recovery of serum albumin level
leads to a return to normal nails;
thus, correction of the underlying
disorder and/or replacement of albumin is the treatment of choice.
Pseudoleukonychia
Pseudoleukonychia occurs following alteration of the nail plate
rather than the matrix by external
causes. It can be seen in onychomycosis (superficial or subungual)
or granulation of the nail keratin
after the long-term application of
nail enamel.
Onycholysis may also masquerade
as leukonychia. Separation of the
nail plate from the nail bed allows
air to pass beneath the nail plate and
may cause the onycholytic portion
of the nail plate to appear white.
Many conditions are associated with
onycholysis, including psoriasis (figure 5), eczema, thyrotoxicosis, lichen
planus and pregnancy.1,15 Local irritation or injury to the nail can cause
onycholysis, such as excessive local
trauma from manicuring, allergic or
irritant contact dermatitis, chemical
overexposure with cosmetic manicures or prolonged exposure to wet
environments. Drugs can also irritate
the nail and precipitate onycholysis
— in particular, chemotherapeutic
agents, oral retinoids, the oral contraceptive pill, antipsychotics (olanzapine and aripiprazole) and those
that interact with sunlight, such as
the tetracyclines.1,3 Onycholysis predisposes nails to secondary subungual infections from dermatophytes,
yeasts or bacterial infections, including Pseudomonas aeruginosa and
Staphylococcus aureus.7
Blue or green
Pseudomonal infection
GREEN-BLACK discolouration of
the nail plate is often indicative of
infection with P. aeruginosa (figure
6). Any insult that disrupts the nail
architecture may allow this organism to colonise under the nail plate.
The green tinge is due to accumulation of pyocyanin and pyoverdin, a
pigment that adheres to the undersurface of the nail plate. It is often
seen in conjunction with onycholysis
or chronic paronychia, and may also
be associated with onychomycosis.
The management of pseudomonal
nail infection should begin with
treating any underlying disorder,
such as onychomycosis or paronychia. Pseudomonal infection often
coexists with candida and aspergillus, especially in the diabetic patient.
If candida is cultured from the nail
plate, oral antifungals should be
administered.
The general treatment of paronychia includes good skin care and
Figure 6:
Characteristic
green-black
chromonychia of
pseudomonal nail
infection.
once or twice daily. Cutting the
detached portion of the nail may
be necessary to expose the infected
area and to keep the nail dry. Topical tobramycin drops (using the eye
formulation) have been reported
to successfully treat subungual
pseudomonal infection.16 Failure
of conservative management may
necessitate removal of the nail plate.
Argyria
general hand/foot hygiene. Avoid
the use of soap and detergents and
wear protective gloves for all wet
and contaminated work. Regular
application of hand moisturiser to
maintain the skin barrier function is
recommended. In the event of nailfold inflammation, the daily application of a topical steroid (short term),
such as mometasone ointment, is
beneficial. Systemic antibiotics are
often ineffective in the treatment of
the pseudomonal infection.
Pseudomonas thrives in a wet
alkaline environment. Daily acetic
acid (1%) soaks may help suppress
pseudomonal growth: the patient
should be advised to dilute white
vinegar with water to 1:20, soak
the affected hand or foot for 10-15
minutes in the solution and then dry
thoroughly. This should be done
Argyria is a rare condition characterised by blue discolouration of
the skin and nails following chronic
ingestion of silver. Currently, silver
ingestion is rare because the amount
of elemental silver in oral medications such as antibiotics has been
reduced.
However, recently, reported cases
of colloidal silver toxicity have
occurred in relation to alternative
health practices and some commercial water-sterilising devices. Following ingestion, the silver granules are
deposited in the skin and lunula of
the nail bed, causing a slate-grey blue
pigmentation — particularly in sunexposed areas. The pigmentation is
permanent. It is important to distinguish argyria from other conditions
such as Wilson’s disease, Addison’s
disease, haemochromatosis or drugrelated pigmentary changes. Skin
biopsy is often necessary. Avoiding
sun exposure and using UV-protective measures may reduce further
darkening of pigmented skin.
Wilson’s Disease
Hepatolenticular
degeneration
occurs secondary due to copper
accumulation and may cause a profound blue discolouration of the nail
lunula. A golden-brown ring is visible around the corneoscleral junction of the eye in most patients with
Wilson’s disease and may distinguish
this disease from other causes of
blue nails. Traces of copper may be
detected in nail clippings and urine.
Yellow
Onychomycosis
ONYCHOMYCOSIS is exceedingly
common in toenails and may present
with yellow dyschromia of the nail
(figure 7). Nail clippings and scrapings of the subungual debris should
be sent for fungal microscopy, culture and sensitivities.
Management options for onychomycosis include application of
topical antifungal agents, often in
combination with a urea-based
agent to soften the nail. Onychomycosis is notoriously difficult to treat,
and oral antifungal therapy is often
required to eradicate infections (see
table 2). Therefore, intense followup is imperative.
Psoriasis
Psoriasis can result in nail pitting
and ridging, onycholysis, subungual
hyperkeratosis and yellow discolouration. Psoriatic nail changes may
be seen in 50-60% of patients with
psoriasis.1 The fingernails are more
commonly affected than the toenails.
Severe nail involvement may occur
without severe skin disease; however, psoriatic nail changes do have
an increased association with psori-
30
| Australian Doctor | 14 November 2014
Figure 7: Yellow
discolouration of the
toenails as a result of
onychomycosis.
atic arthritis. Management options
for psoriatic nail changes are unfortunately often ineffective (see table 3,
next page).
Diabetes
Diabetic patients may develop
thickened nails with yellow discolouration. This is thought to
be the result of microangiopathic
changes seen in the extremities of
diabetic patients. Diabetic patients
experience a three fold increased
risk of onychomycosis.17 There is
no specific treatment once concur-
rent onychomycosis has been ruled
out.
Yellow nail syndrome
Yellow nail syndrome is an uncommon condition of unclear aetiology
characterised by a triad of thickened
yellow nails, lymphoedema and respiratory manifestations.30 This condition presents in adults but may
rarely be seen in children. Characteristically, the nails are thick, slowgrowing with diffuse yellow-green
discolouration and obscuration of
the lunulae (figure 8, see next page).
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Table 2. Oral antifungal agents used to treat
onychomycosis in adults
Oral antifungal agent
Details of administration
Terbinafine
250mg daily with 42 tablets supplied and one repeat.
The second course of tablets may be taken twice a
week instead of daily, prolonging therapy while still
providing adequate dosing.
The side effects of oral antifungal agents, while
rare, include agranulocytosis and liver function
abnormalities; therefore it is recommended to monitor
white cell count and liver function during treatment.
Itraconazole
Pulse therapy with 100-200mg twice daily for the
first week of each month for three months. A new
formulation is available in 50mg tablets.
Fluconazole
150mg weekly for three months. It should be taken
until the new nail grows.
Griseofulvin
1g daily may be used but is not as effective as other
agents. It has a 50% cure rate. It is not a fungicidal
agent and thus relapse is common.
Cuticles are absent, and increased
lateral curvature may be observed
along the thickened nail plate with
associated subungual hyperkeratosis. A marked bulge is often seen halfway between the distal and proximal
nail folds, and the nail plate may not
reach the free edge of the digit. It is
thought that the yellow colour is due
to a combination of hyperkeratosis
and lipochrome accumulation and
that the structural nail changes are a
result of dense stromal sclerosis that
replaces the subungual stroma.18
Lymphoedema is the presenting
symptom and commonly affects
the lower limbs. Patients often present with cough and tachypnoea,
Figure 8: Yellow
nail syndrome
showing
characteristic
thick nails
with diffuse
yellow-green
discolouration,
obscuration
of the lunulae
and increased
lateral
curvature.
which result from a wide range of
pathologies — including pneumonia, bronchiectasis, pleural effusions
and sinusitis. Yellow nail syndrome
has also been reported in association
with immunodeficiency states, TB,
breast cancer, cholangiocarcinoma,
mycosis fungoides, obstructive sleep
apnoea, thyroid disease and rheumatoid arthritis.30
Some patients may experience
spontaneous recovery. Topical
(twice-daily application to the nail
plate) or oral vitamin E (800 units
daily for 12-18 months) has been
reported to be beneficial in some
patients and may lead to clinical
improvement.19 Vitamin E is thought
to scavenge free radicals and may
reduce the accumulation of lipofuscin. The addition of itraconazole
or fluconazole may produce better
results than oral vitamin E alone.20
Oral zinc replacement may be of
benefit. Intralesional triamcinolone
to the proximal nail matrix has been
reported to be partially effective.
(see box, ‘Drugs that may cause yellow chromonychia’). Penicillamine,
gold, lithium and antimalarial
agents, such as quinacrine and chloroquine, have been reported to cause
a diffuse yellow chromonychia in
some patients. 14 Tetracycline doses
greater than 1g per day may cause
fluorescent lunulae and a yellow nail
plate.21 Lithium may cause a golden
discolouration of the distal nail bed,
most commonly affecting the great
toe.1 Medication cessation may
allow for gradual improvement, but
in some cases, yellow chromonychia
may persist for many years.
Drugs
Onychogryphosis
Drugs may cause yellow dyschromia
Onychogryphosis
Table 3. Management options for psoriatic nail changes
Type of agent and
administration
Details and explanation
Potent topical steroids
applied to the proximal nail
fold under occlusive dressing
Diprosone ointment rubbed in to the nail fold nocte may be of benefit over a number of
months. The fingernail can be covered in plastic wrap for 2-3 hours at a time for a period
of one week to enhance absorption.
Intralesional steroids
Intralesional triamcinolone is sometimes used in those individuals suffering from psoriatic
nail changes but with minimal cutaneous psoriasis elsewhere. It is painful and variably
effective; as such it is not usually a first-line treatment
Oral agents in patients with
widespread, cutaneous
psoriasis; some oral agents
may improve associated nail
changes
Methotrexate. This is a potent competitive antagonist of dihydrofolate reductase,
altering DNA synthesis and T-cell proliferation and migration, resulting in
immunosuppressive and anti-inflammatory effects. Possible adverse effects include
hepatotoxicity, pulmonary toxicity (especially pneumonitis and fibrosis), nausea,
diarrhoea, myelosuppresion, nephrotoxicity and potential immunosuppression-induced
malignancy. It is teratogenic and spermatogenic and should be discontinued at least
three months prior to conception.
Drugs that may cause yellow
chromonychia
Acitretin. This is a second-generation mono-aromatic oral retinoid that elicits its
biological effect through the activation of nuclear receptors and regulation of gene
transcription. It is used in the treatment of psoriasis in men of all ages and women who
are not of childbearing age. Like all other retinoids, side effects include dry mucous
membranes, hyperlipidaemia, teratogenicity, depression and reduced night vision.
Tetracycline
Penicilliamine
Gold
Antimalarial agents: quinacrine and
chloroquine
Cyclosporine. Cyclosporine is a calcineurin inhibitor that reduces T-cell proliferation and
may improve cutaneous psoriasis more rapidly than other oral agents. Adverse effects
include hypertension, renal toxicity, tremor, headache, hypertrichosis, hyperkalaemia and
hyperlipidaemia. Often long-term use is limited by its nephrotoxicity.
Lithium
describes
the
Biologic agents. These agents have revolutionised the treatment of severe, recalcitrant
psoriasis. The PBS provides rebates for patients over 18 years of age, who have had
symptoms for more than six months from the time of initial diagnosis and have failed
to achieve adequate response (based on PASI score) to three systemic treatments (ie,
methotrexate, cyclosporine, narrow band ultraviolet B phototherapy) following a minimum
trial of six weeks of each treatment.
Biologic agents available in Australia include:
Anti-TNF agents
• Etanercept
• Infliximab
• Adalimumab
Ani-IL12/23 agents
• Ustekinumab
thickening and lengthening of the
nail plate that may result in distortion of the nail mimicking a ram’s
horn. Such distortion may result
in an apparent chromonychia with
a yellow-brown appearance. The
elderly and neglected are commonly
affected, but it may also be associ-
Red or orange
Online resources
THE red nail, or erythronychia,
is the result of inflammation, vascular proliferation or thinning of
the nail plate, all rendering the
vasculature of the nail bed more
visible. Nails can be affected individually or collectively. Fingernails
are more commonly affected than
toenails.
Figure 9:
Longitudinal
erythronychia
in the finger.
The underlying
cause turned
out to be
a benign
pseudomyxoid
cyst.
Splinter haemorrhage
Splinter haemorrhages are common, resulting from longitudinal
haemorrhage in the nail bed. They
often occur distally and may affect
one or multiple nails. Trauma is
the most common cause, which
explains why they are often seen
on the dominant hand. Other conditions associated with splinter
haemorrhages include onychomycosis, psoriasis and dermatitis.
Extensive involvement of multiple
digits of the hands and feet may
be caused by systemic conditions
such as bacterial endocarditis or
antiphospholipid syndrome. Recognition of associated stigmata
may facilitate the diagnosis.
Splinter haemorrhages may
also be associated with the use of
thrombolytics, anticoagulants, the
oral contraceptive pill, tetracyclines, ganciclovir and taxanes.22
Longitudinal erythronychia
Longitudinal erythronychia is a
linear red band along the nail plate
originating proximally (figure 9).
It occurs as a result of thinning of
ated with trauma or psoriasis. Treatment involves hand hygiene and
good nail care; however, nails may
remain hyperkeratotic for months.
New monodactylous
longitudinal
erythronychia require
close monitoring, and
if evolving, a biopsy
of the nail fold should
be performed to
investigate for local
malignancy.
the overlying nail plate because of
a focal defect in the germinal nail
matrix. This allows the underlying vasculature to be more visible, resulting in a longitudinal red
band. It may occur directly as a
result of nail matrix disease or secondary to pressure on the matrix
— as seen with myxoid cyst, glomus tumour or onychopapilloma.
More than one nail may have longitudinal erythronychia, and more
than one band may develop in a
single nail.
Polydactylous
longitudinal
erythronychia is suggestive of a
systemic disorder, such as lichen
planus, Darier’s disease, amyloidosis or coeliac disease. Monodactylous longitudinal erythronychia
may be caused by an underlying systemic disease but is more
commonly the result of a benign
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tumour (verruca, glomus tumour,
myxoid cyst) or a malignant process, such as squamous cell carcinoma in situ, melanoma in situ or
basal cell carcinoma. New monodactylous longitudinal erythronychia require close monitoring,
and if evolving, a biopsy of the nail
fold should be performed to investigate for local malignancy.
Darier’s disease
Darier’s disease, or keratosis follicularis, is a rare autosomal dominant condition causing greasy
hyperkeratotic papules in seborrhoeic regions. About 90% of
patients with Darier’s disease will
have nail involvement, with the
fingernails more affected than the
toenails.23
There may be subungual hyperkeratosis, and V-shaped notches
classically develop in the distal free
edge of the nail. Keratotic papules
may be found over the proximal
nail fold along with palmar pits.
Several bands of red and white
longitudinal striae are frequently
seen in the nail plate.
Glomus tumour
The glomus body of the nail acts
as a thermoregulatory shunt in the
peripheries between the arterioles
and venules. Glomus tumours are
rare benign hypervascular neoplasms arising from the glomus
body. It frequently affects adults
cont’d next page
• www.dermnetnz.org
• www.emedicine.com/derm/
• www.aafp.org
• www.bad.org.uk
References
Available on request from
[email protected]
Declaration of interest
statement
There are no conflicts of interest
to declare.
Acknowledgement
The authors thank Mr Rodrigo
Martell for the production of the
medical illustration in figure 1.
Photographic images were the
author’s own.
14 November 2014 | Australian Doctor |
31
How To Treat – Nail discolouration
from previous page
between 20 and 40 years of age.
It most commonly occurs subungually but may be seen on the finger or toe pulps. Women are more
frequently affected than men, and
75% of cases involve the hand.1
The tumour causes a light-red or
blue discolouration of the overlying nail with linear erythronychia
extending distally (figure 10). It
may be extremely painful, and
local application of ice will exacerbate the pain.
Ultrasound or MRI may confirm the clinical suspicion and
assess size preoperatively. Glomus tumours are benign; however, surgical treatment is often
mandated because of pain. Histological examination of the excised
tumour is required to confirm the
diagnosis.
Red lunulae
Red lunula may be caused by many
cutaneous or systemic disorders
and usually affects the thumb (see
table 4). Dotted red lunulae may
be seen in patients with psoriasis
and alopecia areata. The pathogenesis remains undetermined.
Conclusion
A
DISCOLOURATION of the nails
is a common presentation in general practice. Its causes are numerous and while often benign, may
be a sign of underlying systemic
disease or malignancy. Identification of a concerning presentation,
such as new longitudinal melanonychia or Hutchinson’s sign of the
nail, requires prompt referral to
a dermatology service for biopsy
and further management. For
patients who live in communities
without good access to dermatologists, consideration may be given
to taking a biopsy locally in consultation with a dermatologist.
Orange chromonychia
Kawasaki disease is a rare febrile
vasculitis of childhood classically
affecting children under five years
of age. Following the acute febrile
phase, transverse orange-red dyschromia may be seen in multiple
nails followed by the development
of Beau’s lines.24,25 These areas do
not blanch under pressure and
usually resolve over a period of
weeks.
B
Table 4. Conditions that may cause red lunulae1
Clinical system
Conditions
Cardiovascular
Atherosclerosis, hypertension, congestive cardiac failure
Pulmonary
Chronic obstructive pulmonary disease
Haematological
Hodgkin’s disease, myeloid leukaemia, polycythemia
rubra vera
Dermatological
Alopecia areata, chronic urticaria, psoriasis, trachyonichia,
vitiligo
Endocrine
Diabetes, hyperthyroidism
Hepatic
Cirrhosis
Infectious
Pneumonia, tuberculosis
Other
Alcohol abuse, carbon monoxide poisoning
Figure 10: Subungual glomus tumour in the finger. A: Initial presentation of
the tumour showing a discrete erythematous area under the nail plate with
overlying onycholysis. B: The glomus tumour exposed on removal of the nail
plate and retracting the nail fold.
Instructions
How to Treat Quiz
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Nail discolouration
— 14 November 2014
1. Which TWO statements are correct
regarding the anatomy and physiology of
the nail unit?
a) Toenails grow at an average rate of 0.1mm
per day
b) The nail bed is responsible for the majority of
nail production
c) The lunula is the distal aspect of the germinal
matrix
d) Nail rigidity is due to hard keratins comprised
primarily of sulfur bonds
2. Which TWO statements are correct
regarding melanonychia?
a) Melanonychia is usually malignant
b) Malignant melanonychia can only be caused
by melanoma not other types of skin cancers
c) Systemic causes of melanonychia include
hyperthyroidism, Addison’s disease and
Cushing’s syndrome
d) Antibiotics can cause melanonychia
3. Which THREE clinical characteristics of
longitudinal melanonychia are red flags for
melanoma?
a) It begins in a single digit during the fourth to
seventh decade of life
b) It is associated with Hutchinson’s sign of the
nail
c) It has blurred not straight lateral borders
d) It is wider distally than proximally
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4. W
hich TWO statements are correct
regarding melanoma as a cause of
melanonychia?
a) M
elanoma involving the nail plate is most
commonly seen in late teenage years or early
adulthood
b) D
ermoscopically observed dark bands in
melanonychia are often more irregular in
spacing and width than in naevi and lentigo
c) T
reatment of melanoma in the nail often
involves amputation of the digit
d) P
rognosis of melanoma in the nail depends
on the tumour subtype
hepatic metastases, congestive cardiac
failure and type 2 diabetes mellitus
c) Muehrcke’s lines are a double band of white
lines running parallel to the lunula typically
associated with onychomycosis
d) Onycholysis as a cause of
pseudoleukonychia may be managed
by keeping the nails trimmed short and
avoiding moist environments, trauma and
contact irritants
5. W
hich TWO statements are correct
regarding true leukonychia?
a) T
rue leukonychia is caused by an abnormality
in the nail bed and resolves with pressure
b) P
unctate leukonychia is due to zinc or calcium
deficiency
c) T
ransverse leukonychia may be caused by an
acute systemic illness
d) Isolated longitudinal leukonychia may reflect
an underlying subungual filamentous tumour
7. Which THREE statements are correct
regarding the clinical approach to
leukonychia?
a) History-taking should include occupational
history, family history, drug history and
history of exposure to heavy metals
b) Examination should look for signs of liver or
renal failure
c) Screening tests may include an FBC and
iron studies
d) First-line treatment of true leukonychia is a
strong topical corticosteroid daily for three
months
6. W
hich THREE statements are correct
regarding apparent leukonychia and
pseudoleukonychia?
a) H
alf-and-half nail is associated with chronic
renal failure and uraemia
b) T
erry’s nails are associated with cirrhosis,
8. Which ONE statement is correct
regarding blue-green chromonychia?
a) Green-black chromonychia is usually caused
by hepatolenticular degeneration
b) Pseudomonal infection causing nail
discolouration should be treated initially with
systemic antibiotics
c) Wilson’s disease causes blue discolouration
of the lunula only
d) Nail discolouration caused by argyria is
reversible by chelation therapy
9. Which TWO statements are correct
regarding yellow chromonychia?
a) Yellow nail discolouration may be caused
by onychomycosis, onychogryphosis and
psoriasis in the nails
b) Diabetic patients with yellow chromonychia
should be started on a high-protein diet
c) Yellow nail syndrome is a benign racial
pigmentary syndrome with no associated
comorbidities
d) Drugs that may cause yellow chromonychia
include tetracyclines and lithium
10. Which TWO statements are correct
regarding conditions associated with
red or orange chromonychia?
a) Splinter haemorrhages are diagnostic for
bacterial endocarditis
b) Longitudinal erythronychia in multiple fingers
may suggest underlying amyloidosis or
coeliac disease
c) Dotted red lunulae are caused by basal cell
carcinoma
d) Transverse orange-red chromonychia may
be associate with Kawasaki disease
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Next
week
32
how to treat Editor: Dr Steve Liang
Email: [email protected]
Chronic obstructive pulmonary disease is a common condition seen in general practice and causes significant morbidity and mortality. The next How to Treat reviews the clinical approach
to COPD with particular focus on information given by the soon-to-be-published COPD-X Concise Guide for Primary Care developed by Lung Foundation Australia in conjunction with the
Thoracic Society of Australia and New Zealand. The authors are members of the Lung Foundation Australia COPD Coordinating Committee, and Writing Committee for the COPD Concise
Guide: Associate Professor Ian Yang, Professor Peter Frith, Dr Kerry Hancock, Professor Christine McDonald, Elizabeth Harper, and Professor Michael Abramson.
| Australian Doctor | 14 November 2014
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