P. Fleckman, MD
Department of Medicine (Dermatology), University of Washington, Seattle, WA
The ichthyoses are a heterogeneous group of inherited scaling skin disorders that can also affect other organs. Management should be directed at both the skin and other sites. Skin therapy is not specific at this time, although new products may offer more directed therapy in the future. Moisturizers and keratolytics are the mainstay of topical therapy. Calcipotriene, retinoids, and for select types, anti inflammatories such as topical steroids and calcineurin inhibitors have also been used. Systemic therapy is limited to the retinoids. Superinfection of the skin should be anticipated and treated. Pruritus can be disabling. Failure to sweat normally may result in heat intolerance. Eye care should seek to prevent corneal changes resulting from ectropion and more specific changes associated with specific disorders. Hearing can be impaired by the accumulation of material in the external auditory canal. Severely affected children may require caloric supplementation to avoid growth retardation. Affected individuals and their family should be counseled about the long term outlook and the genetic nature of their disorder, and informed of FIRST, the Foundation for Ichthyosis and Related Skin Types, the lay foundation that offers support and information.
Key Words: ichthyoses
The ichthyoses are a heterogeneous group of inherited scaling skin diseases (this article excludes acquired ichthyosis, although treatment is much the same with the exception that an underlying cause should be sought). In some cases, other organs are also involved.1 Although recent studies have revealed that mutations underlie many of the ichthyoses,2 specific treatments have yet to follow. Current therapy should be aimed at the skin, other organ involvement, and secondary conditions related to the underlying disorder. Perhaps equally important is to acknowledge the unrelenting nature of the ichthyoses and to direct affected individuals and their families to groups who offer support.
Past and Current Therapies
“The treatment of ichthyosis is essentially external… removal of the scaliness and the maintenance of a soft and pliable condition of the skin.”3 Unfortunately, efficacy of treatment has paralleled neither the understanding of the molecular basis of the disorders nor the expansion of topical treatments seen since this time (Table 1). Moisturizers are the mainstay of therapy of the ichthyoses. They work by increasing the flexibility of the epidermis, hydrating and restoring epidermal barrier function, and by covering and removing scale.4 Moisturizers are complex. They have been reviewed recently in this forum.5 If one talks with a group of individuals affected with different ichthyoses, it becomes clear that everyone has his/her “best” moisturizer. My interpretation is that these differences reflect not only the way different disorders affect the skin, but also differences between individuals. One approach is to offer general dry skin care along with a list of moisturizers and suggest that affected individuals compare several until the “best” product for that person is identified (see Table 2). Keratolytics and humectants are worth singling out from the moisturizers because published, double-blind controlled clinical trials of topical therapy demonstrate efficacy.6,7 However, the trials are short, the numbers of treated individuals are small, irritation is common, and high plasma urea levels have been reported.8,9
The retinoids and calcipotriene have been used as topical therapy for ichthyosis in a small number of trials.10-12 Their use has been, for the most part, anecdotal.
Elias and coworkers recently espoused topical therapy based on the underlying defect of specific ichthyoses.13 Anecdotal reports support successful use of “a patented ceramide dominant ratio of epidermal lipids [ceramides, fatty acids, and cholesterol]” in some disorders (Elias PM, personal communication, 10.8.2002).
Topical steroids have not been effective in the treatment of the ichthyoses, with the exception of eczema in ichthyosis vulgaris and Netherton syndrome. The inflammation that is present likely results from the underlying barrier defect. Topical tacrolimus is contraindicated in Netherton disease because of the risk of systemic absorption.14 We have had anecdotal success using topical tacrolimus in Hailey-Hailey and Darier disease, however systemic levels have not been measured.
Systemic therapy with oral retinoids is the most effective therapy available for most of the ichthyoses.15 It is said that the aromatic retinoids are more effective than 13-cis retinoic acid, but convincing support for this statement is lacking. Although the retinoids have profound effects on epidermal differentiation, the most likely mechanism of action is thinning of the stratum corneum and accelerated loss of scale. The retinoids have significant guaranteed and potential sideeffects.16 Many severely affected individuals use the retinoids chronically, but this should occur only after thoughtful discussion with a physician about the risks and benefits.
|Moisturizers5||Mild-moderate, variable||Varies widely||Contact dermatitis, can be messy, folliculitis, acne|
|Keratolytics and Humectants5||Mild-moderate, varies with disorder6,7||Varies widely||Similar to moisturizers, burning a common complaint|
|Tretinoin 0.1% cream Tazarotene (Tazorac®) 0.05% gel||Mild, varies with disorder10||45g $83.10USD;|
|Adapalene (Differin®) gel, 0.1% (45 g)||Mild, varies with disorder11||100g $232.01USD||Irritation, photosensitivity|
|Calcipotriene (Dovonex®) 0.005%ointment||Mild, varies with disorder||45g $71.69USD||Irritation, photosensitivity|
|TriCeram® “a ceramide dominant|
ratio of epidermal lipids” (www.osmotics.com/triceram.com)
|Mild, varies with disorder12||100g $162.13USD||Irritation|
|Topical steroids – a large variation in strengths is available||Moderate relief in some ichthyoses (uncontrolled)||$30USD/100 ml||Cost, ? other|
|Tacrolimus (Protopic®) 0.1% ointment||Not efficacious, with the exception of eczema associated with ichthyosis vulgaris and Netherton sydrome||Varies widely||Local atrophy, telangiectasia, striae, superinfection|
|13-cis retinoic acid (Accutane®)||Hailey-Hailey, Darier disease (anecdotal experience)||60g tube $116.25 USD||Irritation, sytemic absorption a possible issue (not studied, but documented in Netherton syndrome14)|
|Acetretin (Soriatane®)||Varies with disorder. Makes some disorders (e.g., Netherton syndrome) worse||60mg $18.22USD day||Many – mucocutaneous, GI, CNS, lipid, WBC, musculoskeletal16|
|Unavailable at this time||Varies with disorder. Makes some disorders (e.g., Netherton syndrome) worse||35mg $20.61USD day||Similar to 13-cis16|
Consideration of the management of the ichthyoses is incomplete without a review of aspects beyond primary skin involvement. Specifics of individual disorders (e.g., the corneal changes in KID syndrome, etc.) are beyond the scope of this discussion. Barrier function in ichthyotic skin is impaired, which often leads to secondary infection. In addition to bacterial infection, viral and fungal (especially dermatophyte) infections are common but can easily be missed in the setting of an underlying blistering or scaling dermatosis if a high index of suspicion is not present.15 Pruritus can be incapacitating. Sweating is often impaired, perhaps due to eccrine duct occlusion, and precautions against overheating should be advised. The eye is commonly affected in the setting of ectropion; a corneal ophthalmologist should be involved in care. Ears often plug with cellular debris and require periodic cleaning. Hair and scalp care should address scaling, scaring alopecia, and hair shaft abnormalities leading to fragility. Children with severe erythroderma may display severe growth retardation. This may be the result of increased energy loss caused by evaporative water loss,17 and may respond to topical treatments and to addressing the nutritional needs of the child. See Table 3. FIRST offers “Fact Sheets” on overheating, retinoids, scalp scaling, ear wax & scale, and itching.
Lubricants (All are available over the counter at your local pharmacy. There are many more than those listed here).
Everyone is different. What suits you may not work for someone else. The best lubricant is the one you like the best – you are more likely to use it.
|Secondary skin changes|
|Maintain a high index of suspicion.|
Culture, KOH, Tzanck, wet prep where appropriate.
|• Pruritus||Exclude secondary infection/ infestation.||Treat erosions and fissures by excluding infection and “sealing” with polysporin ointment. Moisturizers and judicious use of antihistamines may help.|
|• Decreased sweating||Inquire about perspiration, heat intolerance.||Avoid exposure to excessive heat. Use water|
“spritzers”, cooling vests.
|Eye||Observe for ectropion. Inquire about eyelids that do not close during sleep.||Refer to a corneal ophthalmologist.|
|Ear||Inquire about fluctuating hearing.||Refer to otolaryngology for ear cleaning and|
|Scalp scaling & hair loss||Examine hair, scalp. Inquire about hair loss. Exclude dermatophyte infection.||Overnight humectants and mild keratolytics with occlusion. Gentle shampoo of scalp with soft rubber bristle brush. Use of hair conditioner. Avoid combing hair until it is dry (the force exerted is much greater than that exerted on dry hair due to increased resistance). Treat tinea capitis if present.|
|Growth retardation||Determine where the child fits on the growth chart and whether s/he is growing.||Refer to dietician for caloric needs.|
Consider GI evaluation.
|The individual and their family||Determine an accurate diagnosis.|
Ask what questions you can answer.
|Refer to an interested “expert” for confirmation of the diagnosis.|
Inform about FIRST and the National Registry for Ichthyosis and Related Disorders
Time and thought should be given to affected individuals and their families in order to inform them accurately of the diagnosis and prognosis of their disorder. If the diagnosis is in question, referral to a dermatologist with particular interest in these disorders may be helpful. Work with the individual and family to identify the most effective therapy. FIRST, the Foundation for Ichthyosis and Related Skin Types, is a lay foundation that supports affected individuals and their family members (650 N. Cannon Avenue, Lansdale, PA 19446, 800 545-3286, 215 631-1411, 215 631-1413 [FAX], email@example.com, www.scalyskin.org). The National Registry for Ichthyosis and Related Disorders, 1-800-595- 1265, firstname.lastname@example.org, www.skinregistry.org/, offers one means of “empowerment” and may be able to help with the diagnosis.
Conflict of interest: the author participated in the clinical trial of Lac-Hydrin® cream (Westwood).