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How to treat
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Hyperpigmentation
Hypopigmentation
Vitiligo and rarer
causes of
depigmentation
Case studies
The author
Disorders of
DR ALEX CHAMBERLAIN,
visiting dermatologist at The
Alfred and Royal Children’s
hospitals, and in private practice
in Armadale, Caulfield and
Hawthorn, Victoria.
PIGMENTATION
Background
THE main determinant of skin
colour across races is melanocyte
activity, not density. Melanocytes,
which are derived from the neural
crest and scattered evenly across the
basal layer of the epidermis and
outer root sheath of the hair follicle,
are principally responsible for
melanin production.
Originally synthesised from the
amino acid tyrosine, melanin is transferred to neighbouring keratinocytes
by long dendritic processes extending from each melanocyte.
The organelles within melanocytes
containing melanin are known as
melanosomes. In dark skin, melano-
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some size and number are much
greater compared with in fair skin.
The key factors that regulate
melanin production include certain
growth factors (basic fibroblast
growth factor and endothelin-1),
melanocyte-stimulating hormone and
ultraviolet light. The key immunohistochemical stain for defining
melanocytes within skin is S-100.
Disorders of pigmentation are generally divided into those characterised
by hyperpigmentation, hypopigmentation or depigmentation. Occasionally all three phases may be seen in
the one disease process (eg, trichrome
vitiligo).
However, not all alterations in
skin colour are due to disturbances
in melanin. Cutaneous vascularity
also contributes to skin colour, and
other pigments such as carotene,
haemosiderin and heavy metals may
also affect skin colour.
Occasionally accumulated dirt and
grime on skin may masquerade as a
pigmentary disturbance (terra firma
forme dermatosis).
While affected patients are seemingly unaware of the cause, the ‘dirty
keratin’ is easily wiped clean with
an alcohol wipe.
When assessing pigmentary disorders the age of onset, presence of a
preceding rash or insult, and pattern
and distribution of pigment change
can generally help define the precise
diagnosis.
Few bedside tools are required
when assessing pigmentary disorders,
except for a Wood’s lamp and a dermatoscope. The Wood’s lamp, which
emits long-wave UV light (or black
light), is particularly useful for accentuating epidermal pigment when
used in a dark room.
The dermatoscope, an illuminated
hand-held magnifying tool, is equally
invaluable in the assessment of
melanocytic lesions such as lentigines, naevi and melanoma.
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24 February 2006 | Australian Doctor |
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How to treat – disorders of pigmentation
Hyperpigmentation
TABLE 1 summarises the causes of
hyperpigmentation. Patterns of
hyperpigmentation can include diffuse, circumscribed, reticulate and
rippled forms (table 2).
Figure 1: Café-au-lait macule.
Café-au-lait macules
Café-au-lait macules affect about
25% of the population. Their significance lies in their occasional
association with a variety of multisystem genodermatoses (or genetic
skin disorders).
Generally, they are readily recognisable as well circumscribed,
coffee-coloured macules that are
usually present from birth. They
vary in size, extending up to several
centimetres in diameter (figure 1)
and may be multiple in otherwise
normal patients. Pigment laser (Qswitched Nd:YAG) offers clearance
in about 50% of cases when cosmetic treatment is requested.
These lesions may be associated
with specific conditions such as:
■ Neurofibromatosis: patients with
neurofibromatosis type 1 typically
have six or more café-au-lait macules, axillary freckling and large
numbers of neurofibromas. They
are prone to CNS and other soft
tissue malignancies (figure 2).
■ McCune-Albright syndrome:
patients typically have a large segmental café-au-lait macule (with
a jagged geographical border),
underlying osseous dysplasia and
various endocrine abnormalities
such as thyroid disease and precocious puberty.
■ Tuberous sclerosis: these patients
have café-au-lait macules associated with hypopigmentation (ashleaf, polygonal and confetti-shaped
morphology), connective tissue
naevi and various tumours (see
under Hypopigmentation). They
are at risk of seizures and mental
retardation.
Figure 2: Multiple café au lait
macules in type 1
neurofibromatosis.
Table 1: Causes of hyperpigmentation
■
Genetic — pigmentary mosaicism, incontinentia pigmenti, café-au-lait
macules
■
Infective — pityriasis versicolor, HIV
■
Solar — poikiloderma of Civatte, melasma, lentigines
■
Metabolic — endocrinopathies, acanthosis nigricans, amyloid,
haemochromatosis
■
Drugs — see table 5, page 28
■
Physical — erythema ab igne
■
Neoplastic — melanoma, mastocytosis
Table 2: Patterns of hyperpigmentation
■
Diffuse — drug-related, endocrinopathies, haemochromatosis, HIV,
melanoma
■
Circumscribed — melasma, acanthosis nigricans, post-inflammatory, fixed
drug eruption, café-au-lait macules, mastocytosis, diabetic dermopathy,
pityriasis versicolor
■
Reticulate — poikiloderma of Civatte, erythema ab igne
■
Rippled — macular amyloid, lichen amyloidosis
■
Blaschkoid — pigmentary mosaicism, incontinentia pigmenti
Common bleaching agents
include 2-4% hydroquinone cream,
(with or without 0.05% tretinoin)
and 1% hydrocortisone. The major
risk with higher-strength hydroquinone preparations is paradoxical and irreversible exogenous pigmentation known as ochronosis.
Irritant and allergic contact dermatitis may also occur so it is
advisable to test the product on a
small area of skin (eg, behind the
ear) before starting long-term therapy. Kojic acid, glycolic acid or
azelaic acid preparations may also
be of benefit.
Superficial peels (50-70% glycolic acid or Jessner’s solution) may
also be valuable in treating
melasma in people with fairer skin,
but laser has little therapeutic role
and runs a significant risk of postinflammatory pigmentation.
Poikiloderma of Civatte
Agent
Brand name
HQ 2% salicylic
acid 1.5%
John Plunkett’s Superfade cream
Poikiloderma refers to the combination of atrophy, telangiectasia,
and reticulate hyper- and hypopigmentation. Poikiloderma of Civatte
specifically refers to this appearance on the lateral aspects (figure
5) and ‘V’ of the neck, seen frequently in fairer-skinned people
living in sunny climates.
Photodynamic substances in fragrance may also play a role in the
development of this condition.
Treatment includes strict daily photoprotection, bleaching creams
(table 4) for prominent hyperpigmentation, and multiple treatments
with vascular laser or intense
pulsed light for telangiectasia.
HQ 3-5% in
aqueous cream
Compounded extemporaneously
Pigmentary mosaicism
HQ 5%/tretinoin
0.1%/HC 1% cream
Compounded extemporaneously
HQ 4-5% in tretinoin
0.025-0.05%
Compounded with Retin-A, Stieva-A or Retrieve
Lentiginoses
Tretinoin 0.01%
Retin-A gel
Solar lentigines are small, discrete,
irregularly shaped and uniformly
brown macules, usually measuring
1cm or less in diameter (figure 3),
that are often found on the upper
back, forearms and hands of sundamaged Australians, particularly
those who are fair-skinned.
Unlike freckles (or ephelides)
they are constant and do not fluctuate with sun exposure. They are
often referred to by patients as age
or liver spots but sun spots would
be a more accurate term.
An intensely black solar lentigo
is referred to as an ink-spot lentigo
and is no more dangerous than its
lighter counterpart. Occasionally,
large numbers of lentigines occur
in association with an underlying
genodermatosis such as PeutzJeghers syndrome, leopard syndrome, Carney complex or xeroderma pigmentosum (table 3).
Solar lentigines may respond to
light cryotherapy, topical tretinoin
or pigment laser (Q-switched
Nd:YAG).
Tretinoin 0.025%
Stieva-A cream
Melasma
Melasma (or chloasma) is a common
acquired form of hyperpigmentation
occurring symmetrically on sunexposed sites such as the forehead,
bridge of the nose, upper lip and
cheeks (figure 4).
Women with darker skin are
26
| Australian Doctor | 24 February 2006
Table 3: Features of syndromic lentiginoses
Peutz-Jeghers syndrome Perioral lentigines and GI polyposis with low
malignant potential
Figure 3: Biopsy-proven solar lentigo
chest (a biopsy was performed
because of the size and variegation
in colour).
Leopard syndrome
Lentigines, ECG abnormalities, ocular
hypertelorism, pulmonary stenosis, abnormal
genitalia, growth retardation and deafness
Carney complex
Lentigines, blue naevi, ephelides and atrial
myxomas
Xeroderma pigmentosum Accelerated sun damage and aggressive skin
cancers at a young age
Table 4: Locally available depigmenting agents
Figure 4: Melasma of the cheek.
Figure 5: Poikiloderma of Civatte
lateral neck.
Figure 6: Naevoid pigmentary
disorder. (Image courtesy of Dr
Maureen Rogers, Children’s
Hospital, Westmead, NSW.)
Tretinoin 0.05%
Stieva-A, Retin-A or Retrieve creams
Tretinoin 0.1%
Stieva-A forte cream
Glycolic acid 10%/
HQ 2%
Neostrata fading gel
PHA 10%/HQ 2%/
kojic acid 3%/
licorice extract
NeoCeuticals HQ skin lightening gel
Azelaic acid 15%
Finacea gel (Intendis)
Azelaic acid 20%
Skinoren cream (Schering)
Arbutin 5%/
kojic acid 2%
Skinceuticals Phyto+
Bearberry & licorice
extracts with
salicylic acid
Naturopathica Fade-Away pigmentation lotion
Ascorbic acid
Cellex-C Fade Away gel
Mulberry extract &
ascorbic acid
Neo Cosmetics whitening process cream
HQ = hydroquinone; HC = hydrocortisone; PHA = polyhydroxy acids
most prone and key aetiological
factors include sunlight and oestrogens. Melasma is sometimes
referred to as the ‘mask of pregnancy’.
Treatment includes withdrawal
of exogenous oestrogens (when
possible), strict photoprotection
and use of bleaching agents (table
4). Treatment is usually required
for at least six months, and in most
cases longer than 12 months. The
condition may recur with further
exposure to sun or oestrogen.
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Blaschko’s lines refer to a pattern
assumed by many different naevoid
and acquired skin diseases, probably determined by the migration of
skin cells during embryogenesis.
These are characterised by
whorled patterning and a sharp
midline cut-off (figure 6) and are
different to dermatomes, Langer’s
lines, Voigt’s lines and embryonic
clefts.
A variety of genetic defects (primarily chromosomal) account for
the wide range of naevoid pigmentary disorders that manifest as
blaschkoid hyperpigmentation,
hypopigmentation or an admixture
of both. At a cellular level two
populations of cells existing within
the skin (mosaicism) are responsible for the striking patterning in
pigmentation.
These disorders have previously
been designated ‘linear and
whorled hypermelanosis’ or
‘hypomelanosis of Ito’, but these
terms are best avoided as they do
not refer to any single entity.
When the disturbance is widespread, associated ocular, neurological or skeletal abnormalities
must be considered. However, in
most patients there are no other
abnormalities.
Treatment of these bizarre pigmentary disorders is limited to cosmetic camouflage. Importantly,
karyotyping of blood and skin, if
necessary to detect mosaicism, is
advocated in all patients presenting with blaschkoid pigmentary
changes (either hyperpigmentation
or hypopigmentation).
cont’d page 28
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How to treat – disorders of pigmentation
from page 26
Incontinentia pigmenti
Incontinentia pigmenti is an
important genodermatosis
with characteristic blaschkoid
hyperpigmentation and ultimately hypopigmentation
after preceding vesicular and
verrucous phases.
The inheritance of incontinentia pigmenti is X-linked
dominant, with only females
affected. The genetic basis is a
mutation in the NEMO
(nuclear factor-κβ essential
modulator) gene.
A range of other systems
may be affected, including the
dental, ocular, skeletal and
neurological systems and the
hair and nails, so multidisciplinary assessment is often
required.
Figure 7: Axillary acanthosis
nigricans. (Image courtesy of
Dr Adrian Mar, Monash
Medical Centre, Clayton,
Victoria.)
Figure 8: Pretibial diabetic
dermopathy.
Hyperpigmentation due to
metabolic disease
Endocrine or metabolic disorders such as Addison’s disease,
Cushing’s disease, acromegaly,
carcinoid syndrome, hyperthyroidism and porphyria
cutanea tarda can cause diffuse hyperpigmentation, with
accentuation over flexures and
pressure points. These conditions should be considered
when there is no apparent
drug cause.
Other conditions causing
hyperpigmentation include:
■ Haemochromatosis — a
unique bronzed (brown-grey
or sometimes blue-grey)
appearance associated with
glucose intolerance and iron
overload.
■ Acanthosis nigricans, which
is associated with insulin
resistance and causes hyperpigmentation and thickened
velvety skin (figure 7). It
can be treated with weight
loss, topical calcipotriol
(Daivonex), metformin or
ablative laser.
■ Paraneoplastic acanthosis
nigricans — this occurs in
GIT adenocarcinoma and
should be considered in
adults over 50 when hyperpigmentation is rapid and
involves mucosal surfaces.
■ Diabetic dermopathy, which
presents as pigmented
atrophic plaques on the
shins (figure 8) and is
thought to be due to diabetic microangiopathy and
repetitive trivial trauma.
■ Primary cutaneous amyloidosis, which has a unique
rippled hyperpigmented
appearance and is not associated with plasma cell
dyscrasias. Lichen amyloidosis shares some similarities with lichen simplex and
is seen most commonly on
the shins of people of Asian
descent (figure 9). Macular
amyloid tends to affect the
central back and is probably a response to rubbing
and scratching.
Drug
Features
Amiodarone
Slate grey (blue-grey); face and sun-exposed skin
Antimalarials
Yellow-brown to blue-black; face, mucosae and legs
Bleomycin
Linear and flagellate; sites of scratching
Carotene
Yellow-orange; palmoplantar skin most conspicuous
Chlorpromazine
Slate grey; sun-exposed skin
Chemotherapy
Brown-grey; diffuse, including mucosae and nails
Clofazamine
Red-brown to purple; lesional skin most affected
Dioxins
Brown with associated chloracne; sun-exposed skin
Heavy metals
See ‘Drug-induced hyperpigmentation’, below
Minocycline
Brown-grey to blue-black; scars, mucosae and legs (figure 10)
Oral contraceptive pill
Melasma
Phenytoin
Melasma and acquired acromelanosis
Psoralens
Enhanced tanning in conjunction with UVA (PUVA)
Thiazides
Brown-grey; sun-exposed skin
Zidovudine
Blue-grey; diffuse, including mucosae and nails
Figure 12: Erythema ab igne.
(Image courtesy of
department of dermatology,
Alfred Hospital, Prahran,
Victoria.)
Figure 13: Urticaria pigmentosa. (Image courtesy of department
of dermatology, Alfred Hospital, Prahran, Victoria.)
Figure 9: Pretibial lichen
amyloidosis. (Image courtesy
of the department of
dermatology, Alfred Hospital,
Prahran, Victoria.)
Response to
bleaching agents
takes time and
patience: it is also
prudent to treat a
test area before
committing to
larger regions.
Figure 10: Minocycline
pigmentation lower limbs.
(Image courtesy of
department of dermatology,
Alfred Hospital, Prahran,
Victoria.)
Figure 11: Fixed drug
eruption.
Drug-induced
hyperpigmentation
Skin hyperpigmentation is
associated with a large
number of drugs (table 5). It
is primarily due to increased
melanin concentration but
28
Table 5: Drugs causing pigmentation and specific features
| Australian Doctor | 24 February 2006
may also be due to deposition of exogenous pigment.
This type of photosensitivity, which is often blue-grey
and on sun-exposed sites,
occurs with amiodarone,
phenothiazines, thiazides,
certain cytotoxics and heavy
metals.
Resolution can occur after
the drug is stopped but may
take years. Pigment laser (Qswitched group, eg, Nd:YAG,
Ruby, Alexandrite) may help
in selected cases.
Heavy metals can cause
curious patterns of blue-grey
pigmentation. Silver exposure (or argyria) can cause
diffuse slate-grey pigmentation (particularly on sunexposed skin) with mucosal
involvement. Lead exposure
causes permanent mucosal
(particularly ocular and gingival) and nail pigmentation.
An unusual form of drugrelated pigmentation is the
fixed drug eruption, which
typically occurs within 24
hours of drug ingestion. The
rash recurs and is usually
seen on the hands, feet and
around the mouth or on the
glans penis.
It is characterised by burning or itch followed by an
oval inflammatory plaque
that resolves, leaving pigmentation (figure 11). The
plaques may multiply with
further exposure to the drug.
Possible triggers include
antibiotics, NSAIDs, gold,
codeine and the oral contraceptive pill.
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HIV/AIDS
Diffuse Addisonian-like pigmentation of skin, mucosae
and nails can occur in HIV
infection, for unknown reasons.
Erythema ab igne
Erythema ab igne is a distinctive, reticular, telangiectatic
pigmented dermatosis that
occurs in response to chronic
infrared radiation exposure.
The most classic site of
involvement is the lower legs
(figure 12) or back. A typical
patient will give a history of
exposure to heat at close
range from open fires,
portable heaters under desks
or hot water bottles.
The clinician should consider hypothyroidism in
patients with this condition,
which may present as cold
intolerance. The major differential diagnosis is livedo reticularis.
Paraneoplastic
hyperpigmentation
Very rarely, patients with
advanced metastatic melanoma develop diffuse bluegrey hyperpigmentation due
to dermal melanin. Dark
urine (melanogenuria) often
coexists and is usually preterminal.
Mastocytosis
Mastocytosis is a reactive disorder of mast cells characterised by multisystem infiltration and a benign course in
young patients.
The most common subtype, urticaria pigmentosa,
features widespread redbrown papules and plaques
(figure 13) that urticate on
rubbing (Darier’s sign), and
may be mistaken for
melanocytic naevi in adultonset mastocytosis. Patients
often complain of pruritus,
and an elevated serum
tryptase level helps in reaching the diagnosis.
Treatment is symptomatic
using topical corticosteroids,
antihistamines, oral sodium
cromoglycate (Nalcrom),
which is available through the
Special Access Scheme, and
phototherapy, but pigmentation often persists. More
recently, imatinib (Glivec), a
tyrosine kinase inhibitor, has
shown promise in treatment
of systemic mastocytosis.
Post-inflammatory
hyperpigmentation
All severe inflammatory dermatoses are prone to leaving
post-inflammatory hyperpigmentation or staining in
people with darker skin.
Antecedents include:
■ Acne.
■ Superficial burns.
■ Insect bites.
■ Contact dermatitis.
■ Lichen planus.
■ Discoid lupus erythematosus.
Disorders featuring apoptotic damage at the dermoepidermal interface, such as
lichen planus, are especially
vulnerable to pigmentation.
Although slow resolution over
months to years is usual, some
patients have persistent
dermal pigmentation.
If the pigment is epidermal
(enhances under Wood’s
lamp), bleaching agents,
superficial peels and strict
photoprotection may help.
Dermal pigment sometimes
responds to pigment laser but
should only be considered in
severe disabling cases because
laser treatment may trigger
further pigmentation.
Treatment principles
Treat any active skin or systemic disease first, then
emphasise the importance of
strict photoprotection with
physical measures (shade and
hats with a broad brim) plus
broad-spectrum anti-UVA and
UVB sunscreens applied frequently.
Response to bleaching
agents takes time and
patience: it is also prudent to
treat a test area before committing to larger regions.
Superficial chemical peels
benefit epidermal pigmentation, such as melasma and
freckling.
Pigment laser or intense
pulsed light have a limited
role in treating superficial
pigment and pose the real
risk of aggravating the problem. For many patients cosmetic camouflage is the most
realistic treatment.
Pityriasis versicolor
See next section.
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Hypopigmentation
HYPOPIGMENTATION generally
occurs in a circumscribed fashion
(unlike patterns of hyperpigmentation)
and may be localised or widespread.
Major causes include genetic, infective, inflammatory/autoimmune, solar,
chemical, physical and neoplastic
processes (table 6).
Pityriasis alba
Pityriasis alba is the most common
cause of facial hypopigmentation presenting to the dermatologist. It is seen
most often in prepubertal children
and is especially noticeable in those
with darker skin.
The hypopigmentation of pityriasis
alba is poorly defined and frequently
lightly scaly and is thought to represent low-grade eczema. Erythema
may occur in early lesions. The face
is the most common site (figure 14)
but it is occasionally seen on the
trunk or limbs.
Treatment (as for eczema) is with
emollients and weak topical corticosteroids, such as 1% hydrocortisone
ointment. Permanent resolution generally occurs after puberty.
Table 6: Causes of hypopigmentation
Genetic — tuberous sclerosis, pigmentary mosaicism, naevus
depigmentosus
■ Infective — pityriasis versicolor, leprosy, syphilis
■ Inflammatory — pityriasis alba, lichen sclerosus, psoriasis, discoid lupus,
sarcoidosis, pityriasis lichenoides chronica
■ Solar — idiopathic guttate hypomelanosis
■ Chemical — chemical leukoderma
■ Physical — cryotherapy, laser, ionising radiation
■ Neoplastic — cutaneous T-cell lymphoma
■
Figure 14: Pityriasis alba of the face.
(Image courtesy of Dr David
Orchard, Royal Children’s Hospital,
Parkville, Victoria.)
Tuberous sclerosis complex
Figure 22: Scattered hypopigmentation
and connective tissue naevi in
tuberous sclerosis. (Image courtesy
of Dr Adrian Mar, Monash Medical
Centre, Clayton, Victoria.)
Figure 15: Hyperpigmented pityriasis
versicolor lower back.
Figure 16: Hypopigmentation
resulting from pityriasis versicolor.
Figure 18: Idiopathic guttate
hypomelanosis of the outer arm.
(Image courtesy of Dr Adrian Mar,
Monash Medical Centre, Clayton,
Victoria.)
Figure 23: Hypopigmentation in
psoriasis. (Image courtesy of Dr
Maureen Rogers, Children’s Hospital,
Westmead, NSW.)
Figure 19: Naevus depigmentosus.
Figure 24: Hypopigmentation in
pityriasis lichenoides chronica.
(Image courtesy of Dr Maureen
Rogers, Children’s Hospital,
Westmead, NSW).
Figure 20: Lichen sclerosus.
Idiopathic guttate hypomelanosis
Idiopathic guttate hypomelanosis is a
very common finding on the limbs
and especially the outer arms of Australian women (figure 18). It is most
obvious in darker-skinned people,
especially in older age.
The principal lesion is a widely scattered, small hypopigmented macule
that does not usually repigment. It can
be thought of as a surrogate marker of
chronic sun damage. Tanning may
accentuate the contrast, and artificial
tanning agents may be useful for
camouflage.
Naevus depigmentosus
Naevus depigmentosus, or naevus
achromicus, is a common pigmentary
abnormality that occurs in more than
1% of the population and typically
appears early in life as a solitary area
of hypopigmentation with an irregular margin (figure 19). This pigmentary abnormality can also be considered a manifestation of mosaicism
(see Pigmentary mosaicism, page 26).
Naevus anaemicus, caused by a
paucity of cutaneous vasculature,
inhibitors, such as pimecrolimus
(Elidel), have also been shown to
have some effect in small case series.
Circumcision should be considered
in men and is often curative.
The tuberous sclerosis complex is an
autosomal dominant genodermatosis comprising hamartomas in the
skin (figure 22), CNS, eyes, heart and
kidneys. Recognising the various
cutaneous features allows diagnosis
at an early age, with earlier cosmetic
treatment of the facial angiofibromas
and screening for tumours.
Hypopigmentation is characteristically either ash-leaf, polygonal or
confetti-like in shape and the so
called ‘ash-leaf macule’ is the earliest
pigmentary finding. Fortunately the
pigmentary changes are rarely cosmetically significant.
Hypomelanosis of Ito
Pityriasis versicolor
Pityriasis versicolor is a common and
often asymptomatic scaly eruption
found on the upper trunk and shoulders. It is caused by the lipophilic
yeast Malassezia furfur and infections
are most common in summer or
humid climates.
When infection is active, the
plaques are lightly scaly — best
appreciated by stretching the skin.
The colour of pityriasis versicolor
is reddish-brown in fair skin (figure
15) and more hypopigmented in
darker skin types (figure 16). In the
latter, the rash usually resolves leaving hypopigmentation that persists
for months.
Skin scrapings of Malassezia furfur
have a ‘spaghetti and meatballs’
appearance on potassium hydroxide
examination (figure 17).
Treatment includes topical antifungals as shampoos, foaming solutions
or creams. Occasionally the infection
may be difficult to clear with topical
therapy alone and require combined
treatment with oral antifungals such
as ketoconazole (Nizoral).
Figure 17: Malassezia furfur on KOH
microscopy.
Figure 21: Abdominal wall morphoea
with central hypopigmentation.
Hypomelanosis of Ito is another rare
example of pigmentary mosaicism,
appearing at birth or shortly afterwards. The term is probably best
avoided because blaschkoid
hypopigmentation occurs in a wide
variety of genetic abnormalities (see
Pigmentary mosaicism, page 26).
Leprosy
Leprosy, or Mycobacterium leprae
infection, has a broad spectrum of
clinical expressions, including
hypopigmented macules, patches and
plaques.
This diagnosis should be considered is cases with unexplained nerve
palsies or hypo-anaesthetic skin with
lesions, especially patients from
developing countries and particularly
the Indian subcontinent.
Psoriasis
A white halo, known as Woronoff’s
ring, may surround plaques of psoriasis, particularly after treatment with
UV phototherapy or topical therapy.
The ring is probably vascular rather
than pigmentary in nature.
Small-plaque psoriasis in darkskinned patients may be particularly
hypopigmented (figure 23) and may
masquerade as a primary pigmentary
disorder. The white overlying scale
(which enhances after scratching the
plaques) is the key clue to the diagnosis.
Pityriasis lichenoides chronica
may also appear as a solitary pale
patch but can be distinguished
from naevus depigmentosus by
compressing the edge with a glass
slide (diascopy), which diminishes
the demarcation between normal
and lesional skin in the former.
Naevus anaemicus also has a characteristically vague border, often
with a surrounding blush of erythema. Under Wood’s lamp the distinction between hypopigmented
and normal skin is accentuated in
naevus depigmentosus but lost with
naevus anaemicus.
Distinguishing between theses
two lesions allows a precise diagnosis for the patient, but there is
no effective treatment for either.
Lichen sclerosus
Lichen sclerosus is a chronic inflammatory and possibly autoimmune
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dermatosis that affects anogenital
(most often) and extra-genital skin,
seen as porcelain-white and atrophic
plaques with follicular plugging and
occasional purpura.
Genital lichen sclerosus is intensely
pruritic and can lead to scarring and
architectural distortion of the vulva
in women or phimosis in men.
Secondary squamous cell carcinoma occasionally complicates genital lichen sclerosus and justifies longterm monitoring.
Extragenital lichen sclerosus is
usually asymptomatic and can
occur in a guttate form or coexist
with localised scleroderma (morphoea) (figures 20, 21).
Management of genital lichen sclerosus includes ultrapotent topical corticosteroids, which have been shown
to improve symptoms and signs of
the disease. Topical calcineurin
Pityriasis lichenoides chronica is an
inflammatory skin disorder that
sometimes mimics psoriasis. The rash
is known to be polymorphic and presents as crops of reddish-brown macules and papules with variable surface scaling, which resolve primarily
with hypopigmentation (figure 24).
The duration of the eruption is
generally weeks to months. For
symptomatic cases, treatment
includes topical corticosteroids,
antibiotics (erythromycin or tetracycline) or phototherapy.
Progression to T-cell lymphoma
has only been noted rarely.
Chronic cutaneous lupus
erythematosus
Chronic cutaneous lupus includes
discoid and subacute forms that both
carry a small chance (5% and 15%,
respectively) of progression to SLE.
Discoid lupus is characterised by
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24 February 2006 | Australian Doctor |
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How to treat – disorders of pigmentation
from previous page
scaly erythematous plaques with follicular plugging, which ultimately
resolve, leaving atrophy, scarring and
a mix of hyper- and hypopigmentation (figure 25).
The centre of the plaques is usually
hypopigmented, with a margin of
hyperpigmentation. Although the
erythema and scaling respond to
treatment (with photoprotection,
topical steroids, antimalarials or
methotrexate), hypopigmentation is
often permanent.
Figure 25: A. Hypopigmentation of the right cheek after treatment of discoid
lupus erythematosus. B. Hypopigmentation of the hands resulting from
subacute cutaneous lupus. (Images courtesy of Dr Adrian Mar, Monash
Medical Centre, Clayton, Victoria.)
B
A
Chemical leukoderma
Physical factors
Chemical leukoderma, or contact
vitiligo, occurs without preceding
inflammation.
A large number of chemicals,
including hydroquinone, monobenzyl
ether of hydroquinone (MBEH),
paratertiary butylphenol (PTBP),
arsenic, mercurial compounds, azelaic acid and corticosteroids may be
responsible.
Phototherapy has limited treatment potential.
Injury to melanocytes by cryotherapy, laser or radiotherapy often
causes persistent hypopigmentation,
so cryotherapy is a less suitable therapy in dark-skinned patients.
The 1064nm Nd:YAG laser,
which is deeply penetrating and less
well absorbed by melanin, has less
risk of dyspigmentation than other
pigment lasers.
Syphilis
Sarcoidosis
Sarcoidosis is a systemic disorder
of unknown origin. About onethird of patients have cutaneous
manifestations that can present in
myriad ways ranging from yellowor red-brown papules, nodules or
plaques to infiltrated scars, alopecia,
erythroderma, ulcers and panniculitis.
Hypopigmentation is an uncommon feature but there is likely to be a
link to multisystem disease (most
often pulmonary involvement, arthritis or cytopenias) when it does occur.
Hypopigmentation may be seen
rarely in secondary syphilis, and the
diagnosis should be considered
whenever a widespread scaly rash
involves the palms. Other rare nonvenereal treponematoses such as
pinta and yaws may also cause
hypopigmentation.
Cutaneous T-cell lymphoma
Rarely, mycosis fungoides or cutaneous T-cell lymphoma may present as hypopigmented plaques.
These are lightly scaly, atrophic
and occur more often in darkskinned people.
The poikilodermatous variant
shows a mixture of hyper- and
hypopigmentation (in addition to
atrophy and telangiectasia).
Vitiligo and rarer causes of depigmentation
VITILIGO is an acquired and
progressive disorder characterised by macular depigmentation or complete amelanosis,
as distinct from disorders
characterised by hypopigmentation or partial pigment loss
(figure 26).
It affects 1-2% of the general population and the cause
is likely to be multifactorial
and polygenic.
In vitiligo, depigmentation
is sharply circumscribed and
may be induced by trauma to
normal skin (the Koebner
response). Sites of predilection
include the face, axillae, nipples, groin, hands, feet and
genitalia, although occasionally vitiligo may be localised in
a segmental distribution.
Whitening of hairs (leukotrichia, or poliosis) and follicular repigmentation are
valuable clues to the diagnosis (figure 27).
Vitiligo is frequently stable
or slowly progressive over
many years. Complete repigmentation is rarely observed.
The disfigurement and psychological burden are often
greatest in darker-skinned
patients. Patients should be
made aware of the rare association between vitiligo and
diabetes or thyroid disease.
Treatment of vitiligo is
unpredictable and generally
Figure 26: Extensive vitiligo
over the trunk and limbs.
topical immunomodulators in
conjunction with sunscreens
when treating exposed areas.
Calcipotriol, a synthetic vitamin D analogue, has also been
shown to have additional benefit in the treatment of vitiligo
when combined with phototherapy (either narrow-band
UVB or PUVA) or ultrapotent
topical corticosteroids.
Figure 27: Vitiligo with poliosis.
Oculocutaneous albinism
disappointing, although there
have been advances in recent
years. The benefits of cosmetic
camouflage and protection
from sunburn should be considered in all patients before
the risks and benefits of active
intervention are contemplated.
Traditional treatments for
vitiligo have included potent
topical corticosteroids, psoralen phototherapy (PUVA)
and depigmentation therapy
in widespread cases (with topical 20% monobenzyl ether of
hydroquinone).
Newer treatments include
topical immunomodulators,
narrow-band UVB phototherapy (311nm), targeted phototherapy with the excimer
laser (308nm) and calcipotriol
(Daivonex) in conjunction
with phototherapy.
Narrow-band UVB phototherapy is probably the
treatment of choice for widespread vitiligo — it offers
equivalent efficacy to that of
PUVA, with less toxicity. A
typical course is often more
than six months, as improvement is slow.
Targeted phototherapy with
the excimer laser is effective
in treating localised areas of
vitiligo by delivering high
doses of light, and works well
in combination with other
topical agents such as tacrolimus or 8-methoxypsoralen
(Oxsoralen lotion).
The two topical immunomodulators are tacrolimus
ointment (available in Europe
and the US as Protopic but
must be compounded in Australia) and pimecrolimus
cream. These agents offer an
advantage on the face and
flexures as, unlike potent topical corticosteroids, they do
not cause cutaneous atrophy
when used long term.
Because these agents are
reasonably new there are no
long-term safety data for their
use in vitiligo. Clinicians
should also be aware of black
box warning labels issued by
the US Food and Drug
Administration in March
2005 for both agents due to
concerns over increased frequency of skin cancer and
lymphoma in animal studies
and the small numbers of
patients using the drugs.
It is prudent therefore to use
Oculocutaneous albinism
refers to a group of inherited
disorders characterised by
abnormal melanin synthesis in
the skin, hair and eyes.
Type I is characterised by
white hair and skin, blue-grey
irides, nystagmus and reduced
visual acuity. Skin and hair
colour do not improve with
age, and vision frequently
worsens. These patients are at
risk of solar keratoses and all
forms of skin cancer, particularly squamous cell carcinoma
and amelanotic melanoma.
Type II is sometimes
referred to as ‘partial albinism’
and is characterised by cream
or pink skin, with cream to
yellow hair. A variety of pigmented lesions, such as naevi,
freckles and lentigines,
develop with age and ocular
problems are the same as for
patients with type I. Types III
and IV are far less common.
Sun protection is clearly
vital for these patients, as are
regular dermatological surveillance and ophthalmological assessment.
Piebaldism
Piebaldism is a rare autosomal dominant genodermatosis characterised by a white
forelock and vitiligo-like
depigmentation. The genetic
defect responsible for piebaldism is a mutation in the c-kit
proto-oncogene on chromosome 4q.
Piebaldism has a stable and
chronic course, with changes
evident from birth. The depigmented macules can be difficult to distinguish from
vitiligo, but the presence of
hyperpigmented islands within
the white areas or normal skin
are very suggestive of the disorder.
The most characteristic sites
of absent pigment are the
anterior trunk and mid
extremities. The hands and
feet are usually spared, unlike
some cases of vitiligo, and a
skin biopsy demonstrates an
absence of melanocytes. The
mainstay of treatment is sun
protection, cosmetic camouflage and possibly bleaching
of the remaining skin with
monobenzyl ether of hydroquinone.
Author’s case study
MISS M, 35, presented five years
ago, unhappy because of dark brown
pigmentation over her cheeks and
forehead (figure 28).
She tanned easily, was in good
health and had been using the combined oral contraceptive pill since
her mid-20s. Miss M was nulliparous but recognised a similar
appearance in friends during pregnancy.
The pigmentation was more
noticeable in summer and she was
already in the habit of applying a
daily moisturiser with high-factor
sunscreen.
There was no history of preceding
inflammation or rash before the pigmentation began and the patient had
already inquired into the benefits of
laser to improve her complexion.
30
| Australian Doctor | 24 February 2006
Figure 28: Melasma affecting the
forehead.
Comment
Melasma, or chloasma, is a common
diagnosis in women. Investigations are
generally not required to confirm the
diagnosis, provided the pigmentation is
not felt to be post-inflammatory, such
as that seen in acne or discoid lupus.
Punctate melasma must be distinguished from solar lentigines (or solar
freckling) but this is usually not difficult, as the latter have a moth-eaten
border and are usually lighter.
The importance of hormonal factors and solar exposure were explained
to Miss M, and the type of sunscreen
she used was checked: a combined
anti-UVA and anti-UVB agent is
most important to provide adequate
protection.
Because it was not convenient for
her to change contraceptive measures
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she was treated with depigmenting
agents but responded poorly to 5%
hydroquinone cream and even hydroquionone-tretinoin combinations.
Glycolic acid preparations, eg, Neostrata fading gel, were slightly more
successful in lightening the pigment
when used consistently over many
months with strict photoprotection,
but were even more successful in
combination with superficial peels,
courtesy of a local cosmetic dermatologist.
Superficial peels with higher
strengths of glycolic acid or trichloroacetic acid usually improve melasma
but it must always be emphasised that
even a short period of sun exposure
(several days) can undo any improvements seen with months of bleaching
agents.
Online resources
eMedicine — melasma:
www.emedicine.com/derm/
topic260.htm
n DermNet NZ — chloasma:
dermnetnz.org/colour/
melasma.html
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How to treat – disorders of pigmentation
GP’s contribution
Case study
DR MARCIA MANNING
Greenwich, NSW
TR, a 50-year-old health
professional, had been going
through major conflict
related to separation and
divorce for the previous two
years. She first noticed vulval
itching and soreness about
nine months ago and had
treated herself twice with
clotrimazole cream.
Swabs grew Candida albicans and group B streptococcus. A single dose of fluconazole and a course of
amoxycillin gave short-term
respite.
On examination about
two months later, I suspected TR had vulval skin
disease but a repeat swab
grew group B streptococcus
and a further attempt was
made to eradicate this
apparent pathogen.
A few weeks later the
vulva looked ‘soggy’ and
there were distinct white
areas and two small fissures.
There were also several 5mm
atrophic-looking ovoid
patches on the skin over the
inguinal ligaments, which on
biopsy proved to be lichen
sclerosus.
A short course of Advantan ointment gave tremendous relief but the vulval
pain recurred shortly after it
was stopped, so several further brief courses were used.
autoantibodies to extracellular matrix protein 1
(ECM1), a possible target
antigen.
Psychological stress is not
known to trigger LS but may
magnify symptoms. Infection
may exacerbate LS but has
never been substantiated as
directly causal.
Trauma is well known to
exacerbate LS also, which
can appear within surgical
scars (Koebner phenomenon).
A dermatologist also saw her
because of continuing distress and prescribed a more
intensive steroid regimen and
regular review.
By this time, TR had
become severely distressed
and anxious. She had also
very tentatively started a
new relationship, but was
thinking that intercourse
would be impossible.
She was fearful of the
amount of strong steroid she
needed to control the symptoms and was also alarmed
to discover she had already
suffered some atrophy of the
labia minora by the time all
her symptoms had come
under control.
To add another layer of
stress, a routine thyroid screen
revealed mild hypothyroidism,
although tests for thyroid
auto-antibodies, antinuclear
antibodies, DNA antibodies,
C-reactive protein and extractable nuclear antigen were all
negative.
Questions for the author
Is lichen sclerosus definitely
autoimmune and does psychological distress trigger it,
especially in someone at this
age? (I have three other
patients with this condition
but they are much older).
Are there other triggers?
While the aetiology of
lichen sclerosus (LS) is not
entirely clear, evidence for
an autoimmune basis is
emerging.
An association with certain HLA subtypes and
other autoimmune diseases
has been recognised for
some time. More recently,
studies have shown that
most patients with LS have
How to Treat Quiz
INSTRUCTIONS
Disorders of pigmentation —
24 February 2006
FAX BACK
Photocopy form
and fax to
(02) 9422 2844
1. Which THREE factors are most likely to
help in the diagnosis of conditions affecting
pigmentation?
❏ a) Age of onset
❏ b) Sex
❏ c) Preceding rash
❏ d) Pigment distribution
2. Linda presents with her only child,
Sophie, who is eight years old and has some
large pigmented lesions consistent with
café-au-lait macules. Which TWO features
would be suggestive of underlying
neurofibromatosis?
❏ a) More than six macules
❏ b) Axillary freckling
❏ c) Variable size
❏ d) Associated hair
3. Which TWO findings would make you
consider McCune-Albright syndrome as the
cause of a café-au-lait macule?
❏ a) A pathological fracture
❏ b) Precocious puberty
❏ c) A small regular lesion
❏ d) A positive family history of the condition
4. Geraldine, 37, complains of pigmentation
affecting her face. If she has melasma,
exposure to which THREE factors is most
likely to be significant in causing her
symptom?
❏ a) Perfume
❏ b) Oestrogen
❏ c) Sunlight
❏ d) Phenytoin
5. Which TWO of the following treatments
are most likely to be beneficial?
❏ a) Narrow-band UVB therapy
❏ b) Hydroquinone plus tretinoin cream
❏ c) Azelaic acid cream or gel
❏ d) Laser
6. Geraldine sees you a year later after a
visit to her son in Scotland. She has
noticed a new rash on her back and legs.
A ‘Yes’ response to which ONE question
What would have helped to
make the correct diagnosis
more quickly? Should
biopsy be considered in
lichen simplex?
Lichen sclerosus has a distinct appearance — generally
with pallor, atrophy (wrinkled, shiny skin with telangiectasia) and ecchymoses,
with or without fissures in a
‘figure of 8’ distribution over
anogenital skin. The ivory
white colour change is perhaps the most distinct feature.
Lichen simplex, on the
other hand (which is also
pruritic), is distinguished by
erythema, exaggerated skin
markings and skin thickening rather than atrophy.
Lichen simplex is more likely
to occur in patients with a
history of atopic dermatitis
or exposure to irritants.
When there is difficulty in
distinguishing the entities
clinically, a small punch
biopsy will usually help to
do so.
How much does this disease
usually affect sexual functioning?
There is no doubt that
lichen sclerosus affects psychosexual wellbeing. Dyspareunia may be a prominent
symptom and both anxiety
and loss of libido may stem
from this.
It has now been demonstrated that ultrapotent topical steroids will completely
reverse the signs of the disease in about 20% of
women, so this forms the
cornerstone of treatment.
When scarring is severe,
surgery is occasionally of
benefit.
Washing with soap substitutes, avoiding irritants, and
the use of lubricants (eg,
Sylk or even vegetable oil)
all help to allow more comfortable intercourse.
Counselling and psychological support may also
help women in coming to
terms with this disease.
The UK-based National
Lichen Sclerosus Support
Group web site can be found
at www.lichensclerosus.org.
Complete this quiz to earn 2 CPD points and/or 2 PDP points by marking the correct answer(s)
with an X on this form. Fill in your contact details and return to us by fax or free post.
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would support a diagnosis of erythema
ab igne?
❏ a) Does Geraldine also have a malar rash?
❏ b) Does she have joint pain?
❏ c) Has she had repeated exposure to a
heater or open fire?
❏ d) Has she had palpitations, tremor and
lost weight?
7. Nine-year-old Simone has had
hypopigmented circumscribed patches on
her face for six months. There is no scale
or pruritus. Which ONE condition is the
most likely cause?
❏ a) Naevus depigmentosus
❏ b) Lichen sclerosus
❏ c) Psoriasis
❏ d) Pityriasis alba
8. Which TWO characteristics would favour
a diagnosis of vitiligo causing Simone’s
lesions?
❏ a) Partial pigment loss only in the lesions
❏ b) History of lesions induced by skin trauma
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❏ c) Whitening of hairs
❏ d) History of topical corticosteroid use
9. Maria, 62, was born in Greece. She
complains of small pale spots on her arms
and legs. If she has idiopathic guttate
hypomelanosis, what advice can you give
her (choose ONE)?
❏ a) Sun exposure will make the lesions less
obvious
❏ b) The lesions are unlikely to repigment
❏ c) They will improve as she gets older
❏ d) Topical retinoids may lead to
pigmentation
10. Maria returns six months later with new
skin lesions. Which THREE characteristics
would make you think she has pityriasis
versicolor?
❏ a) Scaly rash on elbows and knees
❏ b) Lightly scaly plaques on the trunk
❏ c) Hypopigmentation persisting after
treatment
❏ d) Onset during summer
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HOW TO TREAT Editor: Dr Lynn Buglar
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Quiz: Dr Lynn Buglar
The mark required to obtain points is 80%. Please note that some questions have more than one correct answer. Your CPD activity will be updated on your RACGP records every January, April, July and October.
NEXT WEEK The next How to Treat tackles assessment, management and prevention of falls in the elderly. The authors are Dr Jacqueline Close, staff specialist in geriatric medicine at Prince of Wales
Hospital, conjoint senior lecturer at the University of NSW, and senior research associate at the Prince of Wales Medical Research Institute, Randwick, Sydney, NSW; and Associate Professor Stephen Lord,
NHMRC principal research fellow at the Prince of Wales Medical Research Institute.
32
| Australian Doctor | 24 February 2006
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