Ichthyosis is scaling and flaking of skin ranging from mild but annoying dryness to severe disfiguring disease. Ichthyosis can also be a sign of systemic disease. Diagnosis is clinical. Treatment involves emollients and sometimes oral retinoids.
Ichthyosis differs from simple dry skin (xeroderma) by its association with a systemic disorder or medication, inheritability, severity, or a combination. Ichthyosis can also be much more severe than xeroderma.
Inherited ichthyoses
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Inherited ichthyoses, which are characterized by excessive accumulation of scale on the skin surface, are classified according to clinical and genetic criteria (see table Clinical and Genetic Features of Some Inherited Ichthyoses). Some occur in isolation and are not part of a syndrome (eg, ichthyosis vulgaris, X-linked ichthyosis, lamellar ichthyosis, congenital ichthyosiform erythroderma [epidermolytic hyperkeratosis], harlequin ichthyosis). Other ichthyoses are part of a syndrome that involves multiple organs. For example, Sjögren-Larsson syndrome (hereditary intellectual disability and spastic paralysis caused by a defect in fatty aldehyde dehydrogenase) is an autosomal recessive condition with skin and extracutaneous organ involvement. Another example of a condition with skin and extracutaneous organ involvement is keratitis ichthyosis deafness (KID) syndrome, which is characterized by vascularizing keratitis, ichthyosis, and sensorineural hearing loss and caused by mutations in the connexin-26 gene.
Clinical and Genetic Features of Some Inherited Ichthyoses
Disorder | Prevalence | Gene Mutation | Onset | Type of Scale | Distribution | Associated Clinical Findings |
|---|---|---|---|---|---|---|
Nonsyndromic ichthyoses | ||||||
Ichthyosis vulgaris (autosomal dominant) | Prevalence varies by ethnicity: 10:792 in a study of English schoolchildren versus 1:5025 in a Russian cohort study† | FLG | Childhood | Fine | Usually back and extensor surfaces but not intertriginous surfaces Usually many markings on palms and soles | Atopy |
X-linked recessive ichthyosis | Prevalence varies by ethnicity: 1:1500 males in a United States cohort study versus about 1:4000–6000 in European cohort studies† | STS | Birth or infancy | Large, dark, usually coarse (may be fine) | Prominent on neck and trunk Normal palms and soles | Corneal opacities |
Congenital autosomal recessive ichthyoses | ||||||
Lamellar ichthyosis | 1:300,000 | Many, eg, TGM1, ABCA12, ALOXE3 | Birth | Large, coarse, sometimes fine | Most of body Variable palm and sole changes | Hypohidrosis with heat intolerance |
Congenital ichthyosiform erythroderma* | 1:300,000 | Same as lamellar ichthyosis | Birth | Thick, warty At birth: Redness and blisters In adulthood: Scaling | Most of body Especially warty in flexural creases | Bullae, frequent skin infections |
Harlequin ichthyosis | < 1:100,000 | ABCA12 | Birth | Thick, porcelain-like, body armor–like with deep fissures | Entire body | Ectropion, lip eversion (eclabion), nasal hypoplasia, polyhydramnios, flexion deformities, dehydration, severe infection, respiratory insufficiency |
* This disorder is also called bullous congenital ichthyosiform erythroderma, or epidermolytic hyperkeratosis. Mutations are spontaneous in about 50% of cases. | ||||||
† Gutiérrez-Cerrajero C, Sprecher E, Paller AS, et al: Ichthyosis. Nat Rev Dis Primers 9(1):2, 2023. doi: 10.1038/s41572-022-00412-3 | ||||||
Acquired ichthyosis
Ichthyosis may be an early manifestation of some systemic disorders (eg, leprosy [Hansen disease], hypothyroidism, lymphoma, AIDS, multiple myeloma). Some medications cause ichthyosis (eg, nicotinic acid, triparanol, butyrophenones).
The dry scale may be fine and localized to the trunk and legs, or it may be thick and widespread.
Diagnosis of Ichthyosis
Clinical evaluation
Diagnosis is based on clinical evaluation including dermatologic features, age of onset, family history, and evidence of an associated or underlying disorder.
Biopsy of ichthyotic skin is usually not diagnostic of the systemic disorder; however, there are exceptions, most notably sarcoidosis, in which a thick scale may appear on the legs, and biopsy usually shows the typical granulomas.
Genetic testing is useful in establishing or confirming specific types of ichthyosis and in genetic counseling. Test panels that can be used to detect several of the gene mutations causing inherited forms of ichthyosis are available.
A dermatologist should assist in diagnosis and management, and a medical geneticist should be consulted for genetic counseling.
Treatment of Ichthyosis
Minimization of exacerbating factors
Moisturization and keratolytics
Sometimes infection prophylaxis
When ichthyosis is caused by a systemic disorder, the underlying disorder must be treated for the ichthyosis to abate.
Other treatments of ichthyosis include emollients and keratolytics and avoiding drying (1).
Moisturization and keratolytics
In any ichthyosis, there is impaired epidermal barrier function, and moisturizers should be applied immediately after bathing. Substances that are applied to the skin may have increased absorption. For example, hexachlorophene products should not be used because of increased absorption and toxicity.
Ichthyosis typically responds well to the topical keratolytic propylene glycol. To remove scale (eg, if ichthyosis is severe), patients can apply a preparation containing 40 to 60% propylene glycol in water under occlusion (eg, a thin plastic film or bag worn overnight) every night after hydrating the skin (eg, by bathing or showering); in children, the preparation should be applied twice daily without occlusion. After scale has decreased, less frequent application is required.
Retinoidsisotretinoin has resulted in bony exostoses in some patients, and other long-term adverse effects may arise.
Research is ongoing in the development of molecular treatments for ichthyoses and related diseases, including protein and enzyme replacement, repurposed biologic agents, small-molecule agents, and gene replacement and editing (2).
Pearls & Pitfalls
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Infection prophylaxis
Treatment references
1. Mazereeuw-Hautier J, Vahlquist A, Traupe H, et al: Management of congenital ichthyoses: European guidelines of care, part one. Br J Dermatol 180(2):272–281, 2019. doi: 10.1111/bjd.17203
2. Joosten MDW, Clabbers JMK, Jonca N, et al: New developments in the molecular treatment of ichthyosis: Review of the literature. Orphanet J Rare Dis 17(1):269, 2022. doi: 10.1186/s13023-022-02430-6
Key Points
Ichthyosis may be acquired or inherited as an isolated disorder or as part of a syndrome.
Evaluate patients with gradual-onset ichthyosis for an underlying systemic disorder.
Emollients that speed the shedding of skin (keratolytics) are effective in treating ichthyosis.
