Management of Ichthyosis: A Brief Review

Allison L. Limmer, BS, BA; Crystal E. Nwannunu, BS; Ravi R. Patel, MD; Uyen N. Mui, MD; Stephen K. Tyring, MD, PhD

Disclosures

Skin Therapy Letter. 2020;25(1):5-7. 

In This Article

Management

Topical Agents

Ichthyosis management should incorporate hydration and lubrication with the addition of keratolytics and modulators of keratinocyte differentiation depending on scale severity.[8] Hydration can be accomplished with creams and ointments containing low concentrations of salt, urea, or glycerol. Such topical therapies are employed to increase the water-binding capacity of the stratum corneum. Hydrophobic ointments such as petroleum jelly are effective for adequate lubrication. Of note, evidence does not support the use of skin-lipid-containing creams over the aforementioned plain creams and ointments in ichthyosis. When disease is characterized by markedly thickened stratum corneum, topical keratolytics such as alpha-hydroxy acids (lactic acid, glycolic acid), salicylic acid, N-acetylcysteine, propylene glycol, and high-dose urea allow for desquamation while keratinocyte differentiation modulators such as the retinoids (tretinoin, adapalene, tazarotene) and calcipotriol limit epidermal proliferation.[8]

Oral Medications

Although generally not necessary in the management of the common ichthyoses (ichthyosis vulgaris and X-linked recessive ichthyosis), oral retinoids are a mainstay in the systemic management of severe disease.[8] Patients suffering from lamellar ichthyosis, epidermolytic hyperkeratosis, or congenital ichthyosiform erythroderma can benefit from retinoids as the drug's keratolytic effects allow shedding and prevent further hyperproliferation. It is recommended that these agents be administered in low, effective doses as their use could be lifelong in ichthyosis patients.[8] Additionally, retinoids are well-known teratogens.[9] Retinoic acid plays a significant role in transcription regulation by binding retinoic acid response elements (RAREs) that are located proximally to numerous genes. RAREs have been found to inhibit Fgf8, homeobox genes, and other genes integral to neuron and organ development, thereby causing major craniofacial, thymic, cardiac, and central nervous system malformations in addition to spontaneous abortion.[9,10] In an effort to increase awareness and reduce birth defects associated with isotretinoin use, US-based physicians prescribing isotretinoin should be certified in and patients taking the medication should be registered with the iPLEDGE Program.[11] For female patients of child-bearing potential, this program mandates regular pregnancy tests and requires two forms of contraception.[11] Providers and patients in other countries should adhere strictly to local pregnancy avoidance programs and policies. In a patient considering pregnancy, isotretinoin may actually be preferred to acitretin due to its shorter half-life and resultant shorter washout period.[8] At this time, data suggest oral retinoids are safe to use in reproductively active men.[12]

While retinoids share many features, some agents may be more effective than others situationally.[8] For example, isotretinoin and aromatic retinoids (such as etretinate, acitretin) appear equally efficacious in the treatment of lamellar ichthyosis, whereas the propensity of acitretin to act on volar skin makes it the preferred therapy in palmoplantar hyperkeratosis.[8]

Lifestyle Considerations

The majority of ichthyosis therapies aim to improve the barrier function of the skin. Important aspects of an ichthyosis patient's daily routine include bathing and proper application of the bland creams and ointments discussed previously.[13] Daily bathing with water or mild cleanser and the application of plain emollients directly after bathing, as well as frequently throughout the day, help to seal in moisture.[14] It is thought that bathing aids to hydrate and promote shedding of the stratum corneum, therefore reducing the thickness of scaling and improving overall skin appearance.[13] Many emollients are not covered by insurance; in addition, patients self-report applying topical agents as time-consuming.[3] Thus, it is important to be aware of the possible financial and lifestyle stresses with which these therapies may burden the ichthyosis patient population.

In addition, patients diagnosed with ichthyosis should be aware of the lifelong course of this group of disorders, as there is currently no cure. Patients who are carriers of the FLG gene mutation may be at increased risk of developing atopic disorders, such as atopic dermatitis and asthma.[1] To decrease potential risks for the development of atopic disorders, individuals diagnosed with ichthyosis vulgaris should be advised to avoid certain environmental risk factors including professions involving wet work or excessive metal and contact irritant exposure.[1] Smoking tobacco should also be discouraged as an interaction between FLG mutations and tobacco smoking has been shown to favor the development of asthma in patients with ichthyosis vulgaris.[1,15]

Finally, it is important to acknowledge lifestyle factors that commonly influence the quality of life in ichthyoses patients. Patients self-report suffering from altered skin and eye appearance, including pain, pruritus, and "smelly" skin, that worsen in relation to environmental and psychological changes.[3] To accommodate these changes, most patients refrain from activities that risk exacerbating their condition by avoiding hot atmospheres and activities in which they cannot hide their skin.[3] As affected patients consistently express dissatisfaction with their medical care, it is prudent for physicians to advocate for the development of strategies and therapeutic programs targeted at improving the care and quality of life of these individuals.[3]

Genetic Counseling

Gene therapy is not yet a reality in ichthyosis therapy; however, genetic counseling remains an integral aspect of disease management. As mentioned previously, the most common forms of ichthyosis are ichthyosis vulgaris and X-linked recessive ichthyosis, which are inherited in autosomal (pseudo-) dominant and X-linked recessive patterns, respectively, via well-characterized genetic mutations. Although the diagnosis of ichthyosis vulgaris in particular may be evident from biopsy alone, the diagnosis of X-linked recessive ichthyosis requires polymerase chain reaction analysis, Southern blot, or fluorescent in situ hybridization analysis.[4,8] A positive male-only family history of scaly skin, the detection of low estriol on the prenatal triple screen, and/or low estrogen and nonhydrolyzed sulfated steroids in maternal urine can point toward a diagnosis of X-linked recessive ichthyosis, thus prompting analysis of chorionic villi or amniotic fluid using the aforementioned techniques.[4] Additionally, a recent case report suggests that a rare and extreme form of fetal ichthyosis, harlequin ichthyosis, can be detected on ultrasonography as early as the second trimester with subsequent genetic screening to elucidate mutations in ABCA12.[2,16] A referral to a genetic counselor can serve to answer questions and alleviate anxiety regarding the diagnosis of a congenital ichthyosis as well as assist parents in consideration of future pregnancies.

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