Ichthyosis differs from simple dry skin (xeroderma Xeroderma Xeroderma is dry skin that is neither inherited nor associated with systemic abnormalities. Diagnosis is clinical. Treatment involves moisturizers and other measures to keep the skin moist.... read more 
) 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
Inherited ichthyoses, which are characterized by excessive accumulation of scale on the skin surface, are classified according to clinical and genetic criteria (see table ). 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 Autosomal Recessive Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. If expression of a trait requires only one copy of a gene (one allele)... read more 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 | ||||||
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 | |
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 | |
Lamellar ichthyosis | 1:300,000 | Many, eg, TGM1, ABCA12, ALOXE3 | Birth | Large, coarse, sometimes fine | Most of body Variable palm and sole changes | Ectropion Entropion and Ectropion Entropion is inversion of an eyelid. Ectropion is eversion of the lower eyelid. This photo shows entropion, inversion of the eyelid that most commonly affects the lower eyelids of older adults... read more |
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 Leprosy Leprosy is a chronic infection usually caused by the acid-fast bacilli Mycobacterium leprae or the closely related organism M. lepromatosis. These organisms have a unique tropism... read more 
[Hansen disease], hypothyroidism Hypothyroidism Hypothyroidism is thyroid hormone deficiency. Symptoms include cold intolerance, fatigue, and weight gain. Signs may include a typical facial appearance, hoarse slow speech, and dry skin. Diagnosis... read more 
, lymphoma Overview of Lymphoma Lymphomas are a heterogeneous group of tumors arising in the reticuloendothelial and lymphatic systems. The major types are Hodgkin lymphoma Non-Hodgkin lymphoma See table Comparison of Hodgkin... read more , AIDS Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more 
, multiple myeloma Multiple Myeloma Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones that cause... read more 
). 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 Sarcoidosis Sarcoidosis is an inflammatory disorder resulting in noncaseating granulomas in one or more organs and tissues; etiology is unknown. The lungs and lymphatic system are most often affected, but... read more 
, 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 Treatment references 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... read more 
).
Moisturization and keratolytics
In any ichthyosis, there is impaired epidermal barrier function, and moisturizers Moisturizing agents Topical dermatologic treatments are grouped according to their therapeutic functions and include Cleansing agents Moisturizing agents (emollients, skin hydrators, and softeners) Drying agents... read more 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.
An emollient, preferably plain petrolatum, mineral oil, or lotions containing urea or alpha-hydroxy acids (eg, lactic, glycolic, and pyruvic acids), should be applied twice daily, especially after bathing while the skin is still wet. Blotting with a towel removes excess applied material.
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.
Other useful topical agents include urea (< 5%), dexpanthenol, ceramide-based creams, 6% salicylic acid gel, and hydrophilic petrolatum and water (in equal parts). Topical calcipotriol cream has been used with success; however, this vitamin D derivative can result in hypercalcemia when used over broad areas, especially in small children.
Retinoids are effective in treating inherited ichthyoses. Oral synthetic retinoids are effective for most ichthyoses. Acitretin is effective in treating most forms of inherited ichthyosis. In lamellar ichthyosis, 0.1% tretinoin cream or oral isotretinoin may be effective. The lowest effective dose should be used. Long-term (1 year) treatment with oral isotretinoin 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 Treatment references 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... read more ).
Infection prophylaxis
Patients with epidermolytic hyperkeratosis may need treatment with cloxacillin 250 mg orally 3 or 4 times a day or erythromycin 250 mg orally 3 or 4 times a day for as long as thick intertriginous scale is present to prevent bacterial superinfection from causing painful, foul-smelling pustules.
Regularly using soaps containing chlorhexidine may also reduce the bacteria, but these soaps tend to dry the skin.
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.
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
mineral oil |
Fleet, Kondremul, Liqui-Doss, Muri-Lube |
urea |
Aluvea , BP-50% Urea , BP-K50, Carmol, CEM-Urea, Cerovel, DermacinRx Urea, Epimide-50, Gord Urea, Gordons Urea, Hydro 35 , Hydro 40, Kerafoam, Kerafoam 42, Keralac, Keralac Nailstik, Keratol, Keratol Plus, Kerol, Kerol AD, Kerol ZX, Latrix, Mectalyte, Nutraplus, RE Urea 40, RE Urea 50 , Rea Lo, Remeven, RE-U40, RYNODERM , U40, U-Kera, Ultra Mide 25, Ultralytic-2, Umecta, Umecta Nail Film, URALISS, Uramaxin , Uramaxin GT, Urea, Ureacin-10, Ureacin-20, Urealac , Ureaphil, Uredeb, URE-K , Uremez-40, Ure-Na, Uresol, Utopic, Vanamide, Xurea, X-VIATE |
salicylic acid |
Akurza , Aliclen, Bensal HP, Clear Away, Clear Away Liquid, Clear Away One Step, Clear Away Plantar, Clearasil Rapid Rescue Deep Treatment, Compound W, Compound W Total Care Wart & Skin, Corn/Callus Remover, Curad Mediplast, DermacinRx Atrix, Dermarest Psoriasis Moisturizer, Dermarest Psoriasis Overnight Treatment, Dermarest Psoriasis Scalp Treatment, Dermarest Psoriasis Shampoo plus Conditioner, Dermarest Psoriasis Skin Treatment, Dr. Scholl's Callus Removers, Dr. Scholl's Corn Removers, Dr. Scholl's Extra Thick Callus Remover, Dr. Scholl's One Step Callus Remover, Dr. Scholl's One Step Corn Removers, Dr. Scholl's Ultra, Dr.Scholl's Dual Action FREEZE AWAY, Dr.Scholl's Duragel, DuoFilm Wart Remover, Freezone, Gold Bond Psoriasis Relief, Gordofilm , Hydrisalic, Ionil, Ionil Plus, Keralyt, Keralyt 5, Keralyt Scalp Complete, MOSCO Callus & Corn Remover, MOSCO One Step Corn Remover, Neutrogena Acne Wash, Neutrogena T/Sal Scalp, Occlusal-HP, P&S, RE SA , SalAC, Salactic Film , Salacyn, Salex, Salimez, Salimez Forte, Salisol , Salisol Forte , Salitech, Salitech Forte, Salitop , Salkera, Salvax, Scalpicin 2 in 1 Anti-Dandruff, Selsun Blue, Thera-Sal , Trans-Ver-Sal, UltraSal-ER, VIRASAL, Wart-Off, XALIX |
vitamin d |
Calcidol, Calciferol, D3 Vitamin, DECARA, Deltalin, Dialyvite Vitamin D, Dialyvite Vitamin D3, Drisdol, D-Vita, Enfamil D-Vi-Sol, Ergo D, Fiber with Vitamin D3 Gummies Gluten-Free, Happy Sunshine Vitamin D3, MAXIMUM D3, PureMark Naturals Vitamin D, Replesta, Replesta Children's, Super Happy SUNSHINE Vitamin D3, Thera-D 2000, Thera-D 4000, Thera-D Rapid Repletion, THERA-D SPORT, UpSpring Baby Vitamin D, UpSpring Baby Vitamin D3, YumVs, YumVs Kids ZERO, YumVs ZERO |
acitretin |
Soriatane |
tretinoin |
Altinac, Altreno, Atralin, AVITA, Refissa, Renova, Retin-A, Retin-A Micro, Tretin-X, Vesanoid |
isotretinoin |
Absorica, Absorica LD, Accutane, Amnesteem , Claravis , MYORISAN, Sotret, ZENATANE |
erythromycin |
A/T/S, Akne-mycin, E.E.S., Emcin Clear , EMGEL, E-Mycin, ERYC, Erycette, Eryderm , Erygel, Erymax, EryPed, Ery-Tab, Erythra Derm , Erythrocin, Erythrocin Lactobionate, Erythrocin Stearate, Ilosone, Ilotycin, My-E, PCE, PCE Dispertab , Romycin, Staticin, T-Stat |
chlorhexidine |
Betasept, Chlorostat, Hibiclens, Oro Clense , Peridex, Periogard, PerioRx , Perisol |
