Prescribing in practice
Ichthyosis: guide to recognition
and current treatment options
Ann Sergeant MRCP and Colin Munro MD, FRCP
Figure 1. Scaly skin curled up at the edges is characteristic of ichthyosis vulgaris.
The mainstay of treatment is avoidance of irritants and regular use of emollients
he ichthyoses (derived from
T the Greek ‘ichthys’, meaning
‘fish’) are a heterogeneous group
of clinical disorders characterised
by rough, ‘dry’, scaling skin, usu-
ally over the whole body.
Abnormal skin scale results from
abnormalities of keratinisation,
barrier (cornified envelope) for-
mation or shedding (desquama-
tion). Most presentations in early
life are genetically determined.
Mild degrees of acquired dry skin
are common with advancing age,
but more severe acquired
ichthyosis may signal systemic dis-
ease or malignancy (see Table 1).
Inherited ichthyoses
Most genetic forms of ichthyosis
are due to defects in the formation
of the stratum corneum. The clin-
ical severity spans a broad spec-
trum from mild ichthyosis vulgaris
to the life-threatening congenital
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disorder, harlequin ichthyosis.
Ichthyosis may be a prominent fea-
ture in rare systemic syndromes,
usually due to defects in lipid
metabolism.
Ichthyosis vulgaris
Ichthyosis vulgaris is the most com-
mon inherited ichthyosis, account-
ing for more than 95 per cent of
ichthyosis cases, and is associated
with reduced expression of the
cornified envelope precursor pro-
tein filaggrin in the granular layer
of the epidermis.
Traditionally, it was thought to
be an autosomal dominant trait,
but recent research has shown that
it is pseudodominant, 1 due in
Caucasians to two common muta-
tions each of which prevents
expression of filaggrin.
In families with ichthyosis vul-
garis, severely affected individuals
were shown to be homozygous for
Ichthyoses are a collection
of disorders characterised
by dry, scaly skin. Here, the
authors discuss current
treatments for the condition
and also look at rarer condi-
tions that may be present.
a mutation or compound het-
erozygotes for these mutations, but
within the pedigrees heterozygotes
also exhibited milder dry skin.1
Ichthyosis vulgaris usually
becomes apparent during the first
year of life and, in the vast major-
ity, by the age of five years. The
extent of scaling increases until
puberty and subsequently
decreases with age. The scales are
small, flaky and white or grey, often
curling up at the edges to give the
skin a rough feel (see Figure 1).
Scaling is most pronounced on the
extensor surfaces of the arms and
lower legs and characteristically
spares the flexural creases. There
may be increased markings of the
palms and soles.
Keratosis pilaris (‘cheese
grater’ skin) is commonly associ-
ated and usually apparent on the
upper arms (see Figure 2).
Keratosis pilaris is also common in
Prescriber 19 April 2006 35
Prescribing in practice
Causes
drugs, eg nicotinic acid, hypocholesterolaemic agents
chronic hepatic disease, renal failure, thyroid and parathyroid disease
malabsorption states
AIDS
lymphoma and other malignancies
connective tissue disease, eg systemic lupus erythematosus (SLE),
dermatomyositis
sarcoidosis and leprosy
Investigations
full blood count
urea and electrolytes
calcium and phosphate
thyroid function tests
chest X-ray
Consider
antinuclear antibodies and extractable nuclear antibodies
creatinine kinase
skin biopsy
HIV test
Table 1. Causes of acquired ichthyoses and investigations used to diagnose the disease
isolation in the general popula-
tion. Signs and symptoms of
ichthyosis vulgaris may improve
during the summer months.
In general, ichthyotic skin has
poor moisture retention: transepi-
dermal water loss is increased but
stratum corneum hydration is
reduced. An impaired barrier is
prone to enhanced penetration of
topical agents and may be easily
irritated. However, the main
symptoms of isolated ichthyosis
vulgaris are roughness or dryness
of the skin and the cosmetic
defect.
Many children with atopic
eczema have ‘dr y skin’, but the
cutaneous changes of mild eczema
may mimic ichthyosis and clinical
distinction is difficult. Pruritus is
not a problem in isolated
ichthyosis vulgaris and, in patients
who also have eczema, excoriation
and flexural lichenification are
additional features. Netherton’s
Figure 2. The blocking of follicles on the upper arm with syndrome, an unusual ichthyosis
keratin is indicative of keratosis pilaris characterised by arcuate double-
36 Prescriber 19 April 2006
edged scale (ichthyosis linearis cir-
cumflexa) is accompanied by
severe atopic disease including
asthma as well as eczema.
Examples of a variety of rare
inherited disorders that present
primarily as ichthyosis are
described in Table 2. For details of
numerous other disorders of kera-
tinisation, and metabolic disorders
of which ichthyosis is a feature or
incidental finding (eg Sjögren-
Larsen, Refsum, Chanarin-
Dorfman syndromes or multiple
sulphatase deficiency), the reader
is referred to a specialist text such
as reference 2.2
Treatment
Few treatments for ichthyosis have
been subjected to rigorous or sys-
tematic trial. The approach to
treatment is largely symptomatic
and dictated by clinical signs and
symptoms, which var y between
patients and within the same indi-
vidual over time. The main aims
are to maintain barrier function
and suppleness and to improve
appearance. In the more severe
ichthyoses, it is particularly impor-
tant to acknowledge the unrelent-
ing nature of the condition and to
direct affected individuals and
their families to groups that offer
support.
Emollients
Regular and sufficient application
of emollients is critical.2,3 Lighter
water-based emollients, such as
aqueous cream, are suitable for
milder ichthyoses. Paraffin-based
(mixtures of white soft and liquid
paraffin) or cetostear yl alcohol-
containing emollients are better
for more severe cases. Table 3
shows a list of prescribable emol-
lients.
Emollients need to be applied
regularly, often several times a day.
Ideally, assistance from carers and
at school should be arranged for
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Prescribing in practice

Disorder Protein (gene) Incidence Cutaneous signs and symptoms Other features

X-linked ichthyosis steroid sulphatase 1 in 6000 males large brown/grey scale; scaling is
MIM 308100 (ARSC) evident in the first weeks of life,
increasing throughout childhood;
scaling more prominent on
extensor surfaces and legs, but
flexures may be involved
prolonged labour; corneal opacities
on slit-lamp exam (no functional
significance); may be associated
with Kallman’s syndrome
(anosmia, hypogonadism, renal
agenesis); testicular maldescent;
inguinal hernia

Congenital arachidonate 12R- 1 in 300 000 heterogeneous; tight membrane ectropion ~ 30%; short stature, but
ichthyosiform lipoxygenase (‘collodion baby’) present in 90% may catch up with delayed growth
erythroderma (CIE) (ALOX12B); of cases; after shedding the spurt in adolescence
MIM 242100 arachidonate membrane, variable scaling and
lipoxygenase-3 erythema persists; thin, superficial
(ALOXE3); ichthyin white/grey scale affects all areas;
hyperkeratotic palms and soles;
itch; sweating absent or markedly
reduced; deteriorates in summer

Lamellar ichthyosis keratinocyte 1 in 500 000 less common cause of collodion ectropion; scarring alopecia; in
MIM 242300 transglutaminase baby than CIE; scaling occurs severely affected individuals the
(TGM1) within the first month of life and is thick, rigid scale is intermittently
typically large, dark brown or grey shed causing deep and painful
and firmly adherent; pruritus is rare fissures; limitation of joint move-
but sweating is severely impaired ment, flexion contractures and
digital sclerodactyly may result

Bullous keratins 1 and 10 <1 in 100 000 mild erythroderma at birth; blisters, hyperkeratosis of palms and soles,
ichthyosiform (KRT1, KRT10) peeling and erosions at sites of may result in painful fissures,
erythroderma (BIE) minor trauma within first few hours contractures, sclerodactyly and foot
(Epidermolytic of life; gradually the fragile skin is deformity; repeated bacterial and
hyperkeratosis) replaced by thickened yellow- fungal skin infection, with
MIM 118300 brown waxy/ridged skin; tends to associated body odour
improve with age

Netherton Syndrome LEKTI serine protease <1 in 100 000 neonatal erythema; later ichthyosis severe atopic disease
MIM 256500 inhibitor (SPINK5) with typical circumflex and double-
edged scale; trichorrhexis
invaginata (bamboo hair)

Harlequin ichthyosis ABCC12 ~5 in UK per year affected infant is usually premature,
MIM 242500 sometimes stillborn; born with a
massive horny shell of dense
plate-like scale and contraction
abnormalities of the eyes, ears,
mouth and appendages
water loss, electrolyte abnormalities,
temperature dysregulation,
infection, restricted movement,
respiratory insufficiency, absence of
effective sucking

Table 2. Some rarer genetic disorders that present primarily as ichthyosis

38 Prescriber 19 April 2006 www.escriber.com


severely affected children.
Individual preference is important
in optimising compliance. If pro-
vided with samples of a variety of
suitable preparations, patients can
choose the most acceptable. Low
humidity environments, common
in winter, exacerbate the problem.
Conversely, bathing too often may
also be an irritant. Bubble baths
and detergents should be avoided,
and use of soaps and shampoos
minimised.
Preparations such as aqueous
cream, emulsifying ointment and
solid moisturiser bars can be used
as soap substitutes. Emollient bath
oils are useful; again, establishing
individual preference is important
for compliance. After bathing,
patients’ emollients should be
applied before the skin fully dries
to retain hydration.
Prescribers often fail to appre-
ciate just how much emollient is
needed. Liberal application
should be encouraged – 500g per
week for adults and two weeks for
children is recommended.
Pruritus associated with
ichthyosis is often mild and may
respond to emollients alone, but
nonspecific antipruritic agents are
included in many creams and bath
oils. These tend to be more expen-
sive. Response to topical steroids
suggests an undiagnosed low-grade
eczema.
Keratolytic agents
The cosmetic effect of excessive
scale is important to patients.
Keratolytic agents such as 1-5 per
cent salicylic acid may be added to
emollient cream bases to encour-
age exfoliation of scale, but are
often too irritant for regular use.
Their widespread application
should be avoided due to the risk
of systemic absorption and toxicity
(salicylate poisoning), especially in
young children with a high surface
area relative to body size.
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Nonproprietary preparations
aqueous cream, BP
emulsifying ointment, BP
liquid and white soft paraffin
ointment, NPF
Proprietary preparations
Aveeno cream and lotion
Cetraben cream
Decubal Clinic cream
Dermamist spray
Diprobase cream and ointment
Doublebase gel
E45 cream, wash and lotion
Epaderm ointment
Hydromol cream and ointment
Emollient bath additives
Alpha Keri Bath
Aveeno
Balneum
Cetraben
Dermalo
Diprobath
Preparations containing alpha-hydroxy acid
LactiCare lotion (lactic acid 5%)
Calmurid cream (lactic acid 5%)
(many more are available from
Preparations containing urea
Aquadrate cream (urea 10%)
Balneum Plus cream (urea 5%)
Calmurid cream (urea 10%, also
contains lactic acid)
Source: BNF. No 50, September 2005
Table 3. Emollients currently available that may be used in ichthyosis management
Alpha-hydroxy acids Alpha-
hydroxy (‘fruit’) acids (eg lactate,
glycolic, malic or other organic
acids) in oil, lotion, cream or
ointment bases are widely avail-
able as exfoliants. They are
humectants that increase the stra-
tum corneum’s water-holding
capacity, and are keratolytic at
higher concentrations. 4 They
may be less irritant, although
Prescribing in practice
hydrous ointment, BP
paraffin, white soft, BP
paraffin, yellow soft, BP
Lipobase cream
Neutrogena Dermatological Cream
Oilatum cream
Ultrabase cream
Unguentum M cream
Vaseline Dermacare cream and lotion
Zerobase cream
Dermol cream and lotion (contains
antiseptic)
E45
emollient medicinal bath oil
Hydromol Emollient
Oilatum
(there are further bath additives
containing antiseptics if required)
cosmetic counters in pharmacies and
department stores)
E45 Itch Relief Cream cream (urea 5%)
Eucerin cream and lotion (urea 10%)
Nutraplus cream (urea 10%)
more expensive, than salicylic
acid compounds. See Table 3 for
available preparations.
Urea Emollients containing
urea (5-10 per cent: see Table 3
for available preparations) also
have a humectant and keratolytic
effect. 4 In practice, keratolytic
and urea treatments should be
applied as tolerated for a couple
of weeks or so to produce a mild
Prescriber 19 April 2006 39
Prescribing in practice

General measures Treatment is often lifelong.

Patients with severe ichthyosis are
avoid dry or cold environments reluctant to discontinue treatment,
avoid irritants and many have been taking oral
retinoids for 20 or more years. 6
Emollients
Retinoids have important adverse
find the ‘best’ product for the individual by providing samples effects on bone, liver and serum
apply emollient soon after bathing lipids, and their teratogenic poten-
apply regularly tial should be borne in mind in any
use soap substitute and bath oil woman of, or approaching, child-
prescribe sufficient quantities! bearing age. Due to its long half-
life, pregnancy should be avoided
Keratolytics, alpha-hydoxy acids and urea for two years after discontinuing
acitretin. Mandatory contraception
consider addition of salicylic acid, alpha-hydroxy acids or urea to aid
following oral isotretinoin is only
exfoliation and increase hydration
four weeks, but this agent is gener-
may be irritant
ally less effective. In the UK, pre-
avoid applying to large areas of inflamed skin (systemic absorption can occur)
scription of oral retinoids is
Antiseptics and antibiotics restricted to hospital specialists.
Topical retinoids used in psori-
not generally required in the ichthyoses but used to treat secondary infections asis, such as tazarotene (Zorac
in fissured sites (and particularly in BIE to control repeated cutaneous gel)7 and vitamin D analogues, eg
infections and associated body odour) calcipotriol (Dovonex), 8 have
been reported to be of benefit but,
Retinoids
in practice, irritancy is a problem
oral retinoids (acitretin and isotretinoin) are sometimes helpful in the more and widespread and continuous
severe ichthyoses, but should only be used under the supervision of a use carries the risk of systemic tox-
dermatologist; side-effects include teratogenicity, hepatotoxicity, icity.
triglyceridaemia, and chronic skeletal toxicity in long-term use
The role of the GP
Table 4. Summary of ichthyosis management The diagnosis of mild ichthyosis
vulgaris can be made on the char-
exfoliation, which can then be Retinoids acteristic clinical signs (see figures
maintained with less frequent The systemic retinoids acitretin 1 and 2) and may be supported by
application. (Neotigason) and isotretinoin a family histor y of dr y skin. In
Mechanical exfoliation can be (Roaccutane) reduce scaling, pru- more severe male cases, it is impor-
achieved with a loofah or bath ritus and er ythema in most tant to consider the possibility of
mitt while bathing. In patients patients with severe congenital X-linked recessive ichthyosis
with prominent inflammator y ichthyosis.5 For many patients, the (XLRI) due to steroid sulphatase
lesions of keratosis pilaris, er y- effect of oral retinoids is life- deficiency, which has implications
thema may be reduced with a changing, allowing normal partic- for obstetric care of female carri-
potent topical steroid ointment ipation in school, sports and ers due to prolongation of labour
applied for 7-10 days. socialising. in affected male children.

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40 Prescriber 19 April 2006 www.escriber.com

Prescribing in practice
In the presence of extracuta-
neous features (especially devel-
opmental delay), even with mild
childhood ichthyosis, specialist
opinion should be sought to
exclude metabolic causes.
In marked ichthyosis develop-
ing in adulthood, causes of
acquired ichthyosis (see Table 1)
should be excluded.
As with any chronic disease,
patients with genetically deter-
mined ichthyosis require support
and encouragement to empower
the family and individual to man-
age their condition. More practi-
cally, patients require huge
quantities of emollients, and they
will appreciate repeat prescrip-
tions for an emollient that they
both use and like. The greasy
nature of many effective prepara-
tions may have implications for
clothing, bedding and laundry.
Conclusion
Mild degrees of genetically deter-
mined ichthyosis are common,
and merge into normality. For
the majority of patients, treat-
ments are directed at relieving
symptoms due to dr y skin, and
avoidance of irritants and regular
emollients are the mainstay of
treatment.
Patient choice is important to
ensure compliance. Samples of sev-
eral nonbranded or branded prod-
ucts may need to be provided
before the ideal preparation is
found, and this may change over
time. The addition of salicylic acid,
alpha-hydroxy acids or urea to a
moisturising base may help to
remove scale, but these prepara-
tions are usually more expensive
and can be irritants.
For more severe ichthyosis, par-
ticularly if not present from
infancy or of late onset, specialist
opinion is recommended. Oral
retinoids under specialist supervi-
sion are valuable in the manage-
42 Prescriber 19 April 2006
ment of the more severe genetic
ichthyoses.
References
1. Smith FJD, Ir vine AD, Terron-
Kwiatkowski A, et al. Semidominant
loss-of-function mutations in the filag-
grin gene cause ichthyosis vulgaris.
Nature Genetics 2006;38:337-42.
2. Judge MR, McLean WHI, Munro CS.
Disorders of keratinisation. In: Burns T,
Breathnach S, Cox N, Griffiths C(eds).
Rook’s textbook of dermatology. Seventh
edition. Malden, Mass; Oxford:
Blackwell Science, 2004.
3. Fleckman P. Management of the
ichthyoses. Skin Therapy Lett 2003;8:
3-7.
4. Williams ML, Elias PM. Enlightened
therapy of the disorders of cornifica-
tion. Clin Dermatol 2003;21:269-73.
5. Lacour M, Mehta-Nikhar B,
Atherton DJ, et al. An appraisal of
acitretin therapy in children with
inherited disorders of keratinisation.
Br J Dermatol 1996;134:1023-9.
6. Katugampola RP, Finlay AY.Oral
retinoid therapy for disorders of kera-
tinization: single-centre retrospective
25 years’ experience on 23 patients. Br
J Dermatol. 2006;154:267-76.
7 Hofmann B, Stege H, Ruzicka T, et
al. Effect of topical tazarotene in the
treatment of congenital ichthyoses. Br
J Dermatol 1999;141:642-6.
8. Kragballe K, Steijlen PM, Ibsen HH,
et al. Efficacy, tolerability, and safety of
calcipotriol ointment in disorders of
keratinisation. Results of a random-
ized, double-blind, vehicle-controlled,
right/left comparative study. Arch
Dermatol 1995;131:556-60.
Resources
The Ichthyosis Support Group
(ISG) is a UK registered charity
that provides support and infor-
mation. ISG, PO Box 7913,
Reading RG6 4ZQ. Tel: 0845 602
9202; website: www.ichthyosis.
org.uk.
Dr Sergeant is specialist registrar and
Professor Munro is consultant in der-
matology at the Southern General
Hospital, Glasgow
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