INTRODUCTION — The ichthyoses are skin disorders that feature scaling and redness of the skin with or without associated systemic abnormalities. Severity can range from mild, in the case of X-linked ichthyosis and ichthyosis vulgaris, to severe and life-threatening at birth, as in the case of harlequin ichthyosis. Mutations in over 50 genes have been associated with ichthyosis, which can be inherited in an autosomal dominant, autosomal recessive, and X-linked pattern, though a small fraction of patients can manifest acquired ichthyosis in the setting of systemic autoimmune or infectious disease, nutritional deficiency, and malignancy.
This topic will review the major types of ichthyoses inherited in an autosomal recessive fashion (autosomal recessive congenital ichthyosis [ARCI]) and will utilize the consensus nomenclature adopted by the 2009 Ichthyosis Consensus Conference [1].
An overview of the inherited ichthyoses, including rare types of ARCI, and other types of ichthyosis are discussed separately.
●(See "Overview and classification of the inherited ichthyoses".)
●(See "Ichthyosis vulgaris".)
●(See "Recessive X-linked ichthyosis".)
●(See "Keratinopathic ichthyoses".)
EPIDEMIOLOGY — ARCI is rare, and individual subtypes have an average population frequency of 1:200,000 individuals, except in areas where consanguinity is more common [2].
PATHOGENESIS — The epidermis is a stratified, squamous, keratinizing epithelium, and its primary cellular component, the keratinocyte, undergoes a patterned program of gene expression tied to function. In the proliferating basal layer, genes relevant to adhesion are highly expressed, while suprabasal layers express structural proteins and components central to barrier function of the skin. In the top layers of the epidermis, the end product cell is the anucleate corneocyte, which is central both to the structural integrity of the skin and to water retention and that is shed via a process known as desquamation [3]. ARCI is characterized by compromised skin barrier function and, in most phenotypes, by accumulation of abnormal scale, although there are some disorders that feature excessive desquamation that results in a red, denuded, and scaly skin appearance.
The primary physiologic defect underlying the scaling and redness of ichthyosis is abnormal barrier function of the skin. Increased accessibility and decreased cost of whole exome sequencing (WES) has enabled the discovery of many new genetic causes of ARCI. Genetic investigation has identified mutations in genes relevant to lipid biosynthesis, intercellular adhesion, shedding of differentiated cells, and vitamin A biosynthesis, among others; all result in barrier dysfunction. In many cases, mutations in specific genes are predictive of both disease severity and risk of extracutaneous findings, though wide phenotypic variation is seen in patients with mutation in the same gene, largely determined by mutational impact on the encoded protein's structure and function. The primary disease phenotypes of nonsyndromic ARCI are caused by mutations in at least 13 genes [4]:
●ABCA12 (MIM #607800)
●ALOX12B (MIM #603741)
●ALOXE3 (MIM #607206)
●CERS3 (MIM #615276)
●CYP4F22 (MIM #611495)
●NIPAL4 (MIM #609383)
●PNPLA1 (MIM #612121)
●SDR9C7 (MIM #609767)
●SULT2B1 (MIM #604125)
●TGM1 (MIM #190195)
●LIPN (MIM #613943)
●CASP14 (MIM #617320
●SLC27A4 (MIM #608649)
Emerging evidence suggests that genetic defects underlying ARCI contribute to inflammation and shifts in the microbiome, though much research is needed to understand how mutations affecting many distinct cellular functions result in common phenotypic features [5].
CLASSIFICATION — In 2009, a group of experts convened to develop a new nomenclature for ichthyosis, moving away from commonly used phenotypic descriptors and eponyms to a system that considers inheritance, extracutaneous findings, and underlying pathobiology (table 1A-B) [1]. It is likely that classification will be further updated to consider genetic causality in the future. This topic will address the most common subtypes of syndromic and nonsyndromic ARCI.
CLINICAL PHENOTYPES
Collodion infant — The majority of ARCI patients present at birth with red, scaly skin, and many will present as collodion infants [6]. In collodion presentations, infants are born with a clear, shiny, and taut membrane covering the entire skin. Associated skin tightness often causes out-turning of the eyelids (ectropion) and lips (eclabium) (picture 1). With routine care, this membrane spontaneously sheds to reveal red, scaly skin. During the neonatal period, infants with ichthyosis are at increased risk of infection and dehydration due to impaired skin barrier function. Advances in neonatal care have led the survival rate for collodion presentation to approach near 100 percent. While no randomized, controlled trials for interventions have been enacted, there are a series of considerations to address in the neonatal period, including:
●Water loss – ARCI leads to increased insensible losses, and there is a risk of hypernatremic dehydration with abnormalities in electrolytes ensuing. Use of a humidified incubator mitigates water loss and potential problems with thermoregulation. (See "Fluid and electrolyte therapy in newborns", section on 'Hypernatremia'.)
●Infection – Collodion and harlequin presentations can lead to fissures, which increase risk of infection; monitoring for signs of infection is essential.
●Skin care – Liberal application of bland, petrolatum-based emollients can decrease water loss and improve pliability of the skin.
●Education – The unexpected appearance of an affected infant often results in fear. Prompt access to additional information for the family, caregivers, and medical team is available at the Foundation for Ichthyosis and Related Skin Types (FIRST) website. Printed material near the bedside, readily available for rotating caregivers, may be helpful. (See 'Patient support resources' below.)
Nonsyndromic autosomal recessive congenital ichthyosis — In nonsyndromic ARCI, the phenotypic expression of the disorder is seen only in the skin (table 1A).
Lamellar ichthyosis phenotype — While mutations in many genes can present with a lamellar ichthyosis (LI) phenotype, the canonical mutated gene is TGM1, which encodes transglutaminase 1 [7]. TGM1 is an enzyme necessary for cross-linking proteins that comprise the cornified envelope of differentiated keratinocytes and provides a scaffold for the elaboration of lipid. Recessive, loss-of-function mutations cause the LI phenotype.
LI presents at birth most commonly with a collodion membrane, which is shed to reveal red, scaly skin that develops large, plate-like scales that are most prominent on the trunk and lower extremities (picture 2A-C). Persistent ectropion and eclabium are common. The palms and soles can be variably affected, with some cases manifesting marked thickening (palmoplantar keratoderma) (picture 3). (See "Palmoplantar keratoderma".)
Thick scaling of the scalp can lead to peripheral scarring alopecia, as scale surrounds and pulls upon hair. Scaling occludes sweat glands, leading to anhidrosis or hypohidrosis, and many patients suffer from heat intolerance and are at risk for overheating.
Congenital ichthyosiform erythroderma phenotype — Autosomal recessive mutations in ALOXE3 and ALOX12B commonly cause congenital ichthyosiform erythroderma (CIE) [8]. These genes encode lipoxygenases, which are necessary for the formation of fatty acid precursors of the cutaneous lipid barrier.
CIE typically presents with a collodion membrane at birth that sheds to reveal red skin and fine, white, generalized scaling. Ectropion, if present, tends to be mild, and eclabium is rarely seen. There is variability in the ability to sweat, and many patients have anhidrosis. Palmoplantar keratoderma may be present but tends to be milder than when it is seen in LI.
Harlequin ichthyosis phenotype — Harlequin ichthyosis (HI) is caused by autosomal recessive mutations in ABCA12, which encodes a transporter involved in epidermal lipid transport and secretion. Loss-of-function mutations cause the severe HI phenotype, while less damaging missense mutations have been found in patients with less severe phenotypes [9,10].
HI has a dramatic, sometimes fatal, neonatal presentation. Infants are born with thick plates of scale separated with deep, red fissures that appear in geometric patterns, and they are frequently born prematurely. There is marked ectropion and eclabium, and malformation or absence of the ear (picture 4). Fingertips are tapered with loss of distal digital pulp and hyperconvexity of the nail.
Harlequin scale sheds in the first months of life to reveal deep red and scaly skin, resembling a severe CIE. While prior reports suggested that the mortality rate in the neonatal period is approximately 50 percent, with many infants with HI dying shortly after birth, improved neonatal intensive care and early treatment with oral retinoids improves the prognosis [11,12]. Neonatal demise occurs primarily from infection and respiratory compromise.
Ichthyosis prematurity syndrome — Ichthyosis prematurity syndrome (MIM #608649) is a rare subtype of ARCI associated with pathogenic variants in SLC27A4 [13]. Prenatal ultrasound findings include polyhydramnios, separation of the chorionic and amniotic membranes, sediment in the amniotic fluid, and clear chorionic fluid [14]. Patients typically present at birth with erythrodermic skin covered with a vernix caseosa-like material. Most have neonatal asphyxia and reduced Apgar score. Rapid improvement during infancy results in a mild, chronic, pruritic ichthyosis.
Syndromic autosomal recessive congenital ichthyosis — ARCI may present as syndromic diseases with involvement of the skin and other organs or systems (table 1B).
Netherton syndrome — Netherton syndrome is caused by autosomal recessive mutations in SPINK5, which encodes a protease inhibitor necessary for the regulation of desquamation [15].
Netherton syndrome is characterized by scaly skin, abnormal hair, and increased risk of atopy. Scale can assume a characteristic pattern called ichthyosis linearis circumflexa, which manifests as migratory, erythematous plaques with double-edged scale at the periphery (picture 5). Examination of the hair frequently reveals trichorrhexis invaginata, which is visible using light microscopy as a bamboo-like configuration in which the distal hair shaft invaginates into the proximal one (picture 6) [16]. Patients experience manifestations of the atopic triad including atopic dermatitis, food allergy, and asthma and often have marked elevation of serum immunoglobulin E (IgE). Itching can be severe.
Netherton syndrome is discussed in detail separately. (See "Netherton syndrome".)
Neutral lipid storage disease — Neutral lipid storage disease, also called Chanarin-Dorfman disease (MIM #275630), is caused by autosomal recessive mutations in ABHD5, which encodes a protein necessary for lipolysis of triglycerides. Loss of ABHD5 function leads to triglyceride accumulation within cells and alterations in the content of the cutaneous lipid barrier, disrupting its function.
The disease is characterized by generalized, plate-like scale of varying severity and can be associated with hepatosplenomegaly with transaminitis, fatty liver, myopathy, psychomotor delay, cataracts, and decreased hearing [17]. The disease presents at birth, often with a collodion membrane. Elevated liver function tests may be the first indication in milder ichthyosis cases. Oral retinoids must be used with care or avoided in these patients. The accumulation of lipid droplets within granulocytes on peripheral blood smear is a diagnostic finding. (See "Metabolic myopathies caused by disorders of lipid and purine metabolism", section on 'Neutral lipid storage diseases'.)
Sjögren-Larsson syndrome — Sjögren-Larsson syndrome is caused by autosomal recessive mutations in FALDH, which encodes an enzyme necessary for metabolism of fatty alcohols and other substrates. Accumulation of toxic metabolites results in skin and systemic disease.
Clinical features of Sjögren-Larsson syndrome include congenital ichthyosis, intellectual disability, and spastic di- or tetraplegic paralysis. Patients present at birth with scaling, which can be mild to moderate, and severe pruritus that persists throughout life. The skin can become thickened and brown, particularly at sites of excoriation, including flexures, the neck, and abdomen. During early development, signs of developmental delay and spastic paralysis become evident. A diagnostic finding in many patients includes the presence of macular, white dots upon ophthalmologic examination of the retina [18].
Sjögren-Larsson syndrome is discussed in greater detail separately. (See "Sjögren-Larsson syndrome".)
Trichothiodystrophy — Trichothiodystrophy (TTD; MIM #601675) is caused by a defect of DNA repair and transcription. The majority of ARCI-TTD patients have autosomal recessive mutations in the ERCC2/XPD, encoding the transcription factor TFIIH. Less frequently, TTD is associated with autosomal recessive mutations ERCC3/XPB, GTF2E2, and GTF2H5. In contrast with patients with xeroderma pigmentosum, TTD patients do not appear to be at increased risk for skin cancer. (See "Xeroderma pigmentosum".)
TTD has a highly variable presentation, characterized by scaly skin in 65 percent of cases [19]. Brittle hair that shows alternating birefringence when viewed with polarized light microscopy is considered a defining feature (picture 7A-B) [19]. This "tiger tail" appearance in the majority of hairs under polarized light is considered diagnostic. (See "Hair shaft disorders", section on 'Trichothiodystrophy'.)
Some patients present with a collodion membrane at birth. One-half of patients have dystrophic nails with findings including ridging, splitting, hypoplasia, and koilonychia (picture 8). Some patients experience thickening of the palms and soles.
Short stature and characteristic facial features, including microcephaly, protruding ears, and micrognathia, are seen in many patients. Other clinical findings, including intellectual impairment, hearing loss, photosensitivity, and cataracts, may be found with a broad spectrum of severity. Ectropion is rare.
DIAGNOSTIC APPROACH — The diagnosis of ARCI is suspected in a newborn presenting as a collodion baby. Examination by a dermatologist often reveals clinical findings central to diagnosis. This, combined with genetic testing, if available, can lead to a precise diagnosis.
The clinical diagnosis of ARCI is based upon evaluation of the following features:
●Skin phenotype (eg, scale pattern, quality, and color; presence of a collodion membrane at birth; presence of erythroderma; presence or absence of erosions or blistering) (see 'Clinical phenotypes' above)
●Time of onset and evolution over time
●Family history and apparent inheritance mode
●Presence of associated cutaneous manifestations (eg, photosensitivity, hair abnormalities)
●Presence of associated extracutaneous manifestations (see 'Syndromic autosomal recessive congenital ichthyosis' above)
Genetic testing is helpful for obtaining and/or confirming diagnosis and for genetic counseling. (See 'Genetic counseling' below.)
A panel type test that includes multiple well-known gene mutations causative of ichthyosis is typically used. In the United States, Clinical Laboratory Improvement Amendments (CLIA)-certified genetic testing is available from multiple providers (eg, GeneDx). Information on CLIA-certified and research-based laboratories performing disease-specific genetic testing worldwide is available through the Genetic Testing Registry. The National Registry for Ichthyosis and Related Skin Types is a resource for patients.
PRINCIPLES OF MANAGEMENT — There is no definitive treatment for ARCI. Therapy is largely symptomatic and focuses on improving skin hydration, reducing scale, and improving the comfort and appearance of the skin [20]. (See "Inherited ichthyosis: Overview of management".)
Good-quality studies on the management of ARCI are limited. Treatments are mainly based on evidence from small case series and clinical experience.
Care of the neonate with autosomal recessive congenital ichthyosis — Most neonates with ARCI present with red, scaly skin, and many will present with a collodion membrane, which appears as a glistening, translucent, cellophane-like membrane covering the entire body. They have a compromised barrier function, which is associated with increased transepidermal water loss, hypernatremic dehydration, and increased heat loss [21]. (See 'Collodion infant' above.)
These neonates are often managed in neonatal intensive care units. They should be placed in isolettes with increased humidity in the range of 50 to 70 percent and closely monitored for body temperature, vital signs, and electrolytes. Increased metabolic demand due to more rapid epidermal turnover in hyperproliferative conditions requires caloric supplementation. Close monitoring for infection is mandatory. Bland emollients, such as petrolatum, should be applied regularly. They replace in part the barrier function, permit shedding of accumulated scale, and provide a proper environment for healing of fissures or erosions.
Early consultation with a multidisciplinary team is required in the most severe cases. The team should include a dermatologist, clinical geneticist, nutritionist, physical/occupational therapist, and social worker. A national patient support organization, the Foundation for Ichthyosis and Related Skin Types (FIRST), enables medical consultations via a teledermatology program, facilitates contact between families with a newly diagnosed disorder of keratinization and other individuals/families with a similar disorder, and provides information for patients about such conditions.
Bathing — Daily, long tub soaks of at least 30 minutes are beneficial to clean the skin and soften scale. The addition of sodium bicarbonate (baking soda) in bathwater to achieve a pH of approximately 7.8 (two handfuls of baking soda in a tub of water) activates cutaneous proteases, facilitating desquamation and scale removal [22]. Scale can be removed mechanically by gentle use of a sponge or a microfiber cloth. Application of petrolatum-based emollients directly after soaking prolongs water retention and softens the skin.
Topical therapies — Topical therapies, including emollients, keratolytics, and topical retinoids, are the first-line treatments for patients with ichthyosis.
Emollients and keratolytics — Emollients and keratolytics are the mainstay of treatment for all types of ichthyosis. (See "Inherited ichthyosis: Overview of management".)
Emollients are available in many formulations, depending on the water-to-oil ratio; generally, water in oil preparations are preferred. Glycerin can be added to commercial moisturizers, if needed. They can be liberally used multiple times per day and should always be applied immediately after bathing.
Keratolytic preparations containing varying concentrations of urea, salicylic acid, propylene glycol, or alpha-hydroxy acids (eg, lactic acid, glycolic acid) alone or in combination are helpful to remove scale by enhancing desquamation. The use of all keratolytics is contraindicated in infants and small children due to irritation and systemic absorption.
Salicylic acid can be used in older children and adults for the treatment of limited, stubborn body areas. Its use is contraindicated for the treatment of large body areas due to the risk of systemic absorption and toxicity [23]. In older patients, keratolytics should be introduced gradually, with a trial to a small area first (eg, 3 cm2) since some may sting if applied too often or too liberally. The initial interval could start as once weekly and titrated up as tolerated.
Topical retinoids — Due to their antiproliferative and antikeratinizing effects, topical retinoids such as tazarotene or tretinoin can be used for the treatment of focal areas of hyperkeratosis. They are applied in small amounts three times weekly and up to daily until therapeutic benefit is seen [24]. Some patients prefer an even less frequent interval of once weekly. The primary side effect of such therapy is local irritation, which may require a reduction in frequency or amount of application. Unlike emollients, applying retinoids to wet skin may make them more irritating.
Systemic retinoids — Systemic retinoids, including isotretinoin and acitretin, can dramatically reduce scaling in many ARCI patients. They modulate keratinocyte proliferation and differentiation and reduce tissue infiltration by inflammatory cells.
Both are oral medications administered at doses ranging from 0.2 to 1.5 mg/kg/day. It is advisable to start with a low dose and titrate gradually to efficacy, with the goal of using the lowest dose possible to achieve efficacy [25]. Continued administration is necessary to maintain therapeutic benefit. (See "Inherited ichthyosis: Overview of management", section on 'Retinoids'.)
Dryness of the skin, lips, and eyes is a common adverse effect of systemic retinoids. Other adverse effects include myalgias, visual changes, idiopathic intracranial hypertension, hepatotoxicity, hyperlipidemia, and ectopic calcification of tendons and ligaments. The risk versus benefit ratio must be weighed in every patient. While adverse effects can be concerning to patients and their families/caregivers, systemic retinoids can lead to significant improvement of skin appearance, quality of life, and ability to conduct activities of daily living [26]. Some considerations for initiating treatment include the presence or absence of keratoderma-related hand contractures that impair ability to work or hold a pencil, which may soften with use of retinoids. Serial photographs to monitor progress and establish ideal dosing are helpful.
Monitoring for hypertriglyceridemia and hepatotoxicity are required with retinoid therapy. Systemic retinoids are teratogenic and must not be used during pregnancy. Pregnancy is contraindicated for three years after discontinuing acitretin. In women of childbearing potential, isotretinoin is preferred to acitretin because of its shorter half-life; pregnancy is contraindicated for one month after discontinuing isotretinoin.
Special situations
Eye and ear complications — In patients with lamellar ichthyosis (LI), management of ectropion is of primary importance to prevent lagophthalmos and corneal damage and scarring. Frequent use of ocular lubricants, such as lipid-containing eye drops, is helpful in improving signs and symptoms of eye dryness [27]. Ectropion improvement with topical tazarotene has been reported in both adult and pediatric patients with LI [24,28].
Ear complications are mainly due to scale build-up in the external ear canal. Excessive scale accumulation in the auditory canal, if left untreated, can lead to hearing impairment and speech delay in children. Regular hearing evaluation and cleaning by an ear, nose, and throat (ENT) specialist is recommended.
Hypohidrosis and heat intolerance — Patients with ARCI may have hypohidrosis and reduced heat tolerance due to mechanical plugging of sweat gland ducts by hyperkeratosis. Topical therapy with emollients and keratolytics may be helpful in improving the thermoregulation in these patients. There is an isolated report of hypohidrosis improvement in a patient with LI treated with oral retinoids [29].
Children with hypohidrosis may have a tendency to become overheated, which can be worsened in direct sunlight and can occur regardless of ambient temperature. In general, individuals with ichthyosis learn over time what can and cannot be tolerated. In school activities, it is important for children with hypohidrosis to have ready access to water and a cool environment when needed. One of the first signs of overheating is increased redness of the skin. Some children have used a "buddy system" at school so that all students in the class can be aware that an affected child is becoming overheated and can help by suggesting water or a cool environment if they notice signs of overheating, such as increased redness.
Fungus infection — Ichthyosis increases the risk of dermatophyte infection of the skin and scalp, and fungal infections may account for acute episodes of localized or generalized scaling. Itch and loss of hair can be associated. Scraping of scale for microscopic examination with potassium hydroxide, chlorazol black stain, or culture can confirm the diagnosis. (See "Office-based dermatologic diagnostic procedures", section on 'Potassium hydroxide preparation' and "Office-based dermatologic diagnostic procedures", section on 'Fungal culture'.)
Topical antifungal therapy can be sufficient, but follow-up examination to confirm response is needed. Oral medication for treatment may be necessary to ensure complete resolution. (See "Dermatophyte (tinea) infections".)
Neonates with harlequin ichthyosis — Neonates with harlequin ichthyosis should be admitted to a neonatal intensive care unit. Management includes supportive care and treatment of hyperkeratosis and skin barrier dysfunction.
Intubation is often required until nares are patent and armor-like plates of scale are shed from the thorax. Nutritional support with tube feeds is essential until eclabium resolves and infants can begin nursing. Ophthalmology consultation can be helpful in the early management of ectropion, which is initially pronounced and improves as scale is shed. To avoid digital ischemia, careful debridement of constrictive bands of hyperkeratosis should be performed.
Systemic retinoids have a central role in the neonatal period for some patients, particularly in cases with scale preventing full respiratory effort, but are less commonly used in childhood and adulthood [11,12].
As many infants and children suffer from failure to thrive, particular attention must be paid to growth and development with focus on nutrition and caloric supplementation.
GENETIC COUNSELING — Patients diagnosed with ARCI may benefit from genetics consultation to better understand the inheritance pattern and impact on family members. Parents are almost always unaffected, but each parent has a 50 percent likelihood of transmitting the pathogenetic mutation, so there is a 25 percent probability that an offspring will inherit two mutated alleles (figure 1). (See "Inheritance patterns of monogenic disorders (Mendelian and non-Mendelian)".)
PROGNOSIS — While ARCI can have a significant impact on quality of life, most individuals with nonsyndromic forms have normal lifespan and intelligence. Skin symptoms require lifelong management, and advances in neonatal intensive care unit care have improved neonatal outcomes.
PATIENT SUPPORT RESOURCES — Patient support organizations, such as the Foundation for Ichthyosis and Related Skin Types (FIRST), can provide resources for affected individuals and their families/caregivers. FIRST provides patient information resources, opportunities to interact with other affected individuals and their caregivers, and an expert physician-led telemedicine platform to assist clinicians in the care of patients with ichthyosis.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ichthyosis".)
SUMMARY AND RECOMMENDATIONS
●Definition and clinical phenotypes – Autosomal recessive congenital ichthyosis (ARCI) represents a group of rare, recessive disorders that can present with skin scaling and redness with or without erythema. ARCI encompasses cutaneous phenotypes of varying severity, including (see 'Nonsyndromic autosomal recessive congenital ichthyosis' above):
•Lamellar ichthyosis
•Congenital ichthyosiform erythroderma
•Harlequin ichthyosis
Congenital ichthyosis may also be part of a number of autosomal recessive syndromic disorders with manifestations involving every organ system. (See 'Syndromic autosomal recessive congenital ichthyosis' above.)
●Management – There is no definitive treatment for ARCI. Therapy is largely symptomatic and focuses on improving skin hydration, reducing scale, and improving the comfort and appearance of the skin (see 'Principles of management' above and "Inherited ichthyosis: Overview of management"):
•Newborns – Neonates with ARCI presenting with red, scaly skin; with a collodion membrane; and who have a compromised barrier function resulting in increased transepidermal water loss, hypernatremic dehydration, and increased heat loss are often managed in neonatal intensive care units. (See 'Care of the neonate with autosomal recessive congenital ichthyosis' above.)
•Adults and older children – Emollients and keratolytic preparations containing varying concentrations of urea, salicylic acid, or propylene glycol alone or in combination are the mainstay of treatment in adults and older children. The use of all keratolytics is contraindicated in infants and small children due to irritation and systemic absorption. (See 'Principles of management' above and 'Emollients and keratolytics' above.)
Systemic retinoids, including isotretinoin and acitretin, can dramatically reduce scaling in many ARCI patients, but continued administration is necessary to maintain therapeutic benefit. Due to their multiple adverse effects (eg, mucocutaneous disorders, myalgias, idiopathic intracranial hypertension, hyperlipidemia, hepatotoxicity, teratogenicity), the risk-benefit ratio of systemic retinoid therapy should be weighed in the individual patient. (See 'Systemic retinoids' above.)
●Prognosis – While ARCI can have a significant impact on quality of life, most individuals with nonsyndromic forms have normal lifespan and intelligence. Patient support organizations, such as the Foundation for Ichthyosis and Related Skin Types (FIRST), can provide resources for affected individuals and their families/caregivers. (See 'Prognosis' above.)
