Review

Oxford, UK
International
IJD
Blackwell
?0011-9059Science,
Journal
Ltdof Dermatology
2002

Hereditary and acquired ichthyosis vulgaris

Hereditary
Okulicz andand acquired ichthyosis vulgaris
Schwartz

Jason F. Okulicz, MD, and Robert A. Schwartz, MD, MPH

From Dermatology and Pediatrics, New Jersey Medical School, Newark,

New Jersey

Correspondence
Robert A. Schwartz, MD, MPH, Dermatology, New Jersey Medical School,
185 South Orange Avenue, Newark, NJ 07103-2714
E-mail: roschwar@umdnj.edu

childhood, scaling usually diminishes in these areas with

Introduction
age.1,3–6 A notable improvement of symptoms occurs during
Hereditary and acquired ichthyosis vulgaris are members of a the summer months and in warmer climates.3,4
group of cutaneous keratinization disorders. The hereditary Acquired ichthyosis usually appears in adulthood and is
form is an autosomal dominant disease first evident in early clinically indistinguishable from the hereditary form.7,10,16
childhood.1–6 It is by far the most common form of scaling dis- Cutaneous manifestations can be evident either before or
ease, representing over 95% of ichthyosis cases.5 Hereditary after the diagnosis of underlying disease. The severity of
ichthyosis is due to altered profilaggrin expression, which acquired ichthyosis may vary depending on the course of the
leads to scaling desquamation.2,3 It is also associated with associated disease.7
atopic manifestations, including asthma, eczema, and hay
fever.1,4–6 Acquired ichthyosis, on the other hand, is non-
Table 1 Conditions associated with acquired ichthyosis vulgaris
hereditary and extremely rare.7 It usually emerges during
adulthood in association with internal disease (Table 1).7–15
Cancer
Physicians should be particularly mindful of the many malig-
Hodgkin’s disease
nancies linked to acquired ichthyosis.7,8 Some cases have been Non-Hodgkin’s disease (including mycosis fungoides)
reported with the use of certain medications. Hereditary and Kaposi’s sarcoma
acquired ichthyosis vulgaris are virtually identical, both clin- Leiomyosarcoma
ically and histologically.7,10,16 Carcinoma
Breast
Lung
History Ovary
Cervix
The term ichthyosis is derived from “ichthys,” the ancient Leprosy
Greek root meaning fish.6 Although the resemblance is some- Sarcoidosis
Thyroid disease
what fanciful, it nonetheless describes the characteristic
Hyperparathyroidism
features of this condition. Ichthyosis has been depicted in Chronic renal failure
medical texts over 2000 years old.17 In the English literature, Nutritional disorders
the most accurate description of ichthyosis was first published Human immunodeficiency virus infection
by Robert Wilan in 1808.3,5 Subsequent modifications classi- Autoimmune diseases
Systemic lupus erythematosus
fied the disorder into hereditary and acquired categories.
Dermatomyositis
At birth, the skin in hereditary ichthyosis vulgaris looks Drugs
and feels normal.1,3–6 The skin in most patients, however, gra- Nicotinic acid
dually becomes rough and dry after 3 months of age, with the Triparanol
vast majority of cases apparent by age 5 years.4–6 The extensor Butyrophenones
Dixyrazine
surfaces of the extremities are most heavily involved, with an
Cimetidine
absence of scaling on the flexor surfaces and diaper area. Clofazimine
Although the cheeks and forehead may be affected in early 95

© 2003 The International Society of Dermatology International Journal of Dermatology 2003, 42, 95 – 98
96 Review Hereditary and acquired ichthyosis vulgaris
Epidemiologic characteristics
Ichthyosis vulgaris is found in all races worldwide.1 Heredi-
tary ichthyosis vulgaris is by far the most common form,
whereas acquired ichthyosis is extremely rare. During a study
of hereditary ichthyosis vulgaris, Wells and Kerr5 found an
incidence of 1 per 5300 people living in five counties sur-
rounding Oxford, England, in 1966. When considering only
school-aged children in the same study, a strikingly different
incidence of 1 per 250 was found. These differences can most
likely be attributed to the general improvement of symptoms
with age. In addition, varying degrees of penetrance confound
estimates, especially when trying to identify cases within the
same family.3 People with milder symptoms may not bring
them to the attention of physicians.1 Thus, the overall fre-
quency of hereditary ichthyosis vulgaris is probably greater
than expected due to the general improvement of symptoms
with age and the variable degree of penetrance.
Etiology
Ichthyosis vulgaris is classified as a retention hyperkeratosis
due to the delayed removal of scales.2,3 The expression of the
molecular marker profilaggrin, a high-molecular-weight
filaggrin precursor, is altered in hereditary ichthyosis vulgaris.
Profilaggrin is synthesized in the granular layer of the epi-
dermis and is a major component of keratohyalin granules.
It undergoes various post-translational modifications to
become filaggrin, which assembles keratin intermediate
filaments in the lower stratum corneum.2 The proteolysis and
metabolism of filaggrin produce free amino acids that may
play a critical role as water-binders in the upper stratum
corneum.18,19
The normal expression of the profilaggrin gene can be first
identified in the granular layer. In ichthyosis vulgaris, dimin-
ished or absent expression of profilaggrin occurs in the epi-
dermis. The reduction of keratohyalin granules and the
clinical severity of the condition are correlated with this bio-
chemical abnormality.20 The analysis of cultured keratino-
cytes from affected individuals shows reduced profilaggrin
messenger RNA (mRNA).21,22 Compared to normal levels, a
study found only 50% of the profilaggrin mRNA and 10% of
the profilaggrin protein present.22 Further research has deter-
mined that defective post-transcriptional regulation of the
gene leads to the decreased stability of profilaggrin mRNA.2
Studies using mouse models are currently underway to dis-
cover the underlying mechanisms of this instability.23
The pathophysiologic mechanism responsible for acquired
ichthyosis vulgaris is far from clear. One study postulates that
the condition may be due to impaired lipogenesis. The incor-
poration of radiolabeled glucose into lipids was performed to
assess lipid biosynthesis in the dermis and epidermis. One
patient with acquired ichthyosis and Hodgkin’s disease had
International Journal of Dermatology 2003, 42, 95 – 98
Okulicz and Schwartz
almost undetectable labeling of lipids.24 Additional research is
needed to determine the role of lipogenesis in the pathophys-
iology of this disease. The mechanism relating to acquired ich-
thyosis following therapy with certain medications has not
been illustrated.
Clinical manifestations
Ichthyosis vulgaris, both hereditary and acquired, involves
symmetric scaling of the skin, which ranges from minor
roughness and dryness to the desquamation of large plates
(Fig. 1).1 The scales are usually small, irregular, and fine, with
curled up edges that give the skin a rough feel.3,4,6 Their color
varies from white to dirty gray to brown, with a diameter of
1 mm to 1 cm. Darker scales are usually present in dark-
skinned individuals.6 Different types of scaling can be
observed in different areas of the same person.1
Scaling is most extensive on the extensor surfaces of the
extremities, with a sharp demarcation between normal flexor
surfaces and the surrounding affected areas.1,3,6 In general,
the lower extremities are more affected than the upper
extremities. The shins characteristically have the thickest and
darkest scales, often arranged in a mosaic fashion.6 Patients
may complain of “lizard skin” in these areas, especially dur-
ing the winter.3 If the trunk is involved, scaling is usually more
pronounced on the back rather than the abdomen.4 The face
is relatively spared, most likely due to elevated sebaceous
secretions, although the cheeks and forehead may be affected
during early childhood in the hereditary form.3,5,6 Dry scaling
may be observed uniformly over the scalp.1,5 Sparing of the
flexor surfaces, including the neck, axillae, and the antecu-
bital and popliteal fossae, is related to the increased temper-
ature and humidity in these areas.3 Likewise, improvement of
symptoms generally occurs during the summer months or in
warm climates.4
Figure 1 Photograph of an African-American patient with
hereditary ichthyosis vulgaris showing thickened, scaly skin on
the upper thigh
© 2003 The International Society of Dermatology
Okulicz and Schwartz
In addition to scaling, hyperkeratosis of the palms and soles
creates a “dirty” appearance.3 Skin creases are more pro-
nounced in these areas, leading to painful fissuring.3,5 Kera-
tosis pilaris or follicular hyperkeratosis can be present on the
side of the cheek and neck, upper arms, buttocks, and
thighs.1,3,6 Palpation of these areas resembles a cheese grater
due to many spiny parafollicular papules. Dry skin is often
white in the central portions which can be mistaken for pus.3
Keratosis pilaris, sometimes present without scaling, may be
the only finding in family members with hereditary ichthyosis
vulgaris.1,3
Acquired ichthyosis vulgaris is associated with many sys-
temic diseases, such as cancer, leprosy, sarcoidosis, thyroid
disease, hyperparathyroidism, chronic renal failure, nutri-
tional disorders, bone marrow transplant, and human immu-
nodeficiency virus infection.7,8,10,12,14 Autoimmune disorders,
such as dermatomyositis and systemic lupus erythematosus,
are also linked.9,15 The most common types of cancer include
Hodgkin’s disease, non-Hodgkin’s lymphoma (including
mycosis fungoides), Kaposi’s sarcoma, myeloma, leiomyosa-
rcoma, and carcinomas of the breast, lung, ovary, and cer-
vix.7,11,13 Rare cases have been observed following therapy
with certain medications, namely nicotinic acid, triparanol,
butyrophenones, dixyrazine, cimetidine, and clofazimine.14
Atopic manifestations, such as asthma, eczema, and hay
fever, are associated with the hereditary form.1,3–6 Nearly one-
half of the patients in one study had atopic symptoms, with
41% having at least one family member affected as well.5
Diagnosis
The diagnosis of ichthyosis vulgaris is primarily based on
history and clinical findings. Hereditary ichthyosis vulgaris
has a history of scaling after 3 months of age, with general
improvement in the summer months and as the patient gets
older.4 The presence of hyperkeratosis, keratosis pilaris, and
atopic manifestations may also be found. A family history of
scaling supports the diagnosis. Acquired ichthyosis vulgaris is
almost entirely observed in adults.7 New-onset ichthyosis at
any age, however, should prompt further investigation due to
associated internal disease. The progression of systemic dis-
ease or malignancy can result from a delay in diagnosis.
Histopathology
Hereditary and acquired ichthyosis vulgaris are practically
identical in histologic appearance.7,10,16 Basket-weave hyperk-
eratosis is present in the stratum corneum, although some
areas may be compacted and laminated.1,6,10,18 Patchy para-
keratosis and occasional follicular plugging are also present.1,25
The diminished granular layer is either one cell layer thick or
absent altogether.1,3,16 Although usually intact, the stratum
malpighii has a decreased rete-papillae pattern.6,25 When
© 2003 The International Society of Dermatology
Hereditary and acquired ichthyosis vulgaris Review 97
present, the sebaceous and eccrine glands are atrophic and
reduced in number.1,4,6,25 Sweat glands and hair follicles
remain intact.6 The dermis contains a perivascular lympho-
histiocytic infiltration in most cases.6,25
Ultrastructural studies reveal diminished or absent kerato-
hyalin granules housed in the granular layer.3,10,26 They have
a crumbly or spongy appearance, most likely caused by
defective keratohyalin synthesis. A normal keratin pattern
is observed in the hyperkeratotic portions of the stratum
corneum.26
Biopsies should be obtained from areas of maximal hyper-
keratosis, because areas of mild scaling have been shown to be
less reliable for histopathologic analysis and may be indistin-
guishable from normal skin. The anterior aspect of the lower
leg is often the most favorable location due to the presence of
thick scales.6,25
Management
Although hereditary ichthyosis vulgaris often improves in
most patients with age, it is a chronic disease that requires
continuous therapy for many patients.3 The severity of
acquired ichthyosis may depend on the course and severity of
internal disease.7 Treatment of the underlying condition
generally results in improvement of acquired ichthyosis.3 The
main approach in treating both disorders includes hydration
of the skin and prevention of evaporation.3,4 Hydration
promotes desquamation by increasing the susceptibility to
mechanical forces and the elevation of hydrolytic enzymes.
Pliability of the stratum corneum is also increased.3
Hydration of the skin can be achieved by the application
of alpha-hydroxy acids, such as lactic, glycolic, and pyruvic
acids. They work in the newly formed lower layers of the stra-
tum corneum by causing the disaggregation of corneocytes.3
Lactic acid is commercially available in a 12% ammonium
lactate cream or lotion, or it can be compounded at a concen-
tration of 5–10% in a suitable vehicle.27 Studies have shown
that twice-daily applications are superior to the application of
petrolatum-based creams.3,27
Keratolytics, such as salicylic acid, can aid in the removal of
scales by inducing keratinocyte disaggregation in the upper
stratum corneum. A 6% salicylic acid gel is available commer-
cially and can be used as needed.3 Many products on the
market contain urea or propylene glycol.3,28 Moisturizers
containing urea at lower concentrations of 10–20% have
humectant properties. Propylene glycol, a common vehicle
in topical preparations, promotes the movement of water
through the stratum corneum by establishing a gradient.
Effective hydration of the skin is followed by the shedding of
thick skin in affected areas.3
Tretinoin and other topical retinoids may also be beneficial.
They stimulate mitosis and turnover, reduce cohesiveness,
and suppress keratin synthesis.3 The topical receptor-selective
International Journal of Dermatology 2003, 42, 95– 98
98 Review Hereditary and acquired ichthyosis vulgaris
retinoid tazarotene was found to be effective in one small
trial.29 Ichthyosis vulgaris does not improve following steroid
treatment.3
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© 2003 The International Society of Dermatology