Ichthyoses

Newborns (0–2 Months)

Newborns with ichthyosis can present with a range of phenotypes including collodion membrane, widespread erosions, armor-like scale, red/scaly skin, or normal skin that subsequently develops scaling and erythema. In recessive ichthyosis, collodion membrane presentations are common and are characterized by a taut, translucent layer of skin, which sheds within a month of birth to reveal scaly and/or red skin. A minority of collodion babies heal spontaneously, leaving mild scaling. In severe cases, morbidity is possible due to increased TEWL, difficulties in thermoregulation, and increased infection risk, especially with Staphylococcus aureus and dermatophytes. It is also important to recognize that other disorders such as Omenn syndrome and neonatal Gaucher disease can also cause collodion membrane. Therefore, genetic testing is the cornerstone of diagnostic workup.

It is common practice to place collodion babies in a 40–60% humidified incubator to minimize dehydration and prevent fissures. Since eclabium can interfere with oral feeding, newborns may require modified bottle nipples or nasogastric feeding. Newborn care also includes pain control, ophthalmologic attention to prevent conjunctivitis and keratitis secondary to ectropion, and close monitoring for infection and fluid and electrolyte imbalances, especially hypernatremia. Prophylactic antibiotics are discouraged given a lack of evidence supporting their efficacy. Medicated ointments, such as salicylic acid, lactic acid, and sulfadiazine cream, should be avoided, given the risk of percutaneous absorption. Bland emollients including white petrolatum and Aquaphor are preferred.

Newborns with epidermolytic ichthyosis (EI) can present with widespread blistering, so epidermolysis bullosa and staphylococcal scalded skin infection are in the differential. A biopsy can distinguish among these diagnoses because suprabasal vacuolar degeneration, coarse keratohyalin granules, and hyperkeratosis are pathognomonic for EI. Treatment includes use of a humidified incubator, pain control, infection surveillance, and nutritional intervention to compensate for increased metabolic demands.

Harlequin ichthyosis (HI) has a severe neonatal presentation and while formerly often lethal, advances in intensive care have enabled survival in a large fraction of infants who are born encased in a thick stratum corneum separated by deep, red fissures that form geometric plates of skin. Surviving infants ultimately shed the hyperkeratosis to evolve to an ichthyosiform erythroderma phenotype. Upon birth, coordinated care with attention to fluid and electrolyte balance, signs of infection, and respiratory compromise is appropriate. Treatment recommendations include pain control, nutritional supplementation, and daily bathing with hypochlorite baths followed by application of bland emollients every 4–6 hours. Those surviving the neonatal period should be monitored for achievement of developmental milestones since many are at risk for growth and developmental delay.

Oral retinoids are employed in HI if there is evidence that the thick scale is causing respiratory compromise. Retinoids, including isotretinoin and acitretin, promote desquamation, improving motion, respiration, ectropion, and eclabium. Acitretin is preferred for its fewer side effects and shorter half-life. Dosing should be 0.5–1 mg/kg/day. Retinoids are discontinued when the scale sheds and respiration improves. If oral retinoids cannot be tolerated, topical retinoids such as 0.1% tazarotene cream are also beneficial if used in limited areas, such as around the eyes, to relieve ectropion.

Infants (2 Months–1 Year)

Ichthyosis vulgaris (IV) and X-linked ichthyosis (XLI) are among the most common forms of ichthyosis. IV typically develops during infancy, revealing fine, rough, white scales most prominent on the extensor surfaces of the extremities with flexural sparing. XLI is sex-linked recessive and only affects males; the translucent, loosely adherent scales seen at birth are quickly replaced by adherent brown scales, most notably on the abdomen and extensor surfaces of lower limbs with flexural sparing. Baths and daily application of bland emollients to reduce scaling are preferred.

Rarely, infants may have normal skin at birth and subsequently develop ichthyosis. Disorders within the erythrokeratodermia variabilis et progressiva (EKVP) spectrum can present with migratory erythema and fixed, well-demarcated, hyperkeratotic plaques or symmetrically distributed, transient stationary, keratotic plaques on an erythematous base with palmoplantar keratoderma (PPK). Lesions appear on the extensor surfaces of extremities, buttocks, and face and can become confluent.

It is also essential to monitor growth and development because failure to thrive (FTT) is common among ichthyosis patients. Appropriate consults and a gastrostomy feeding tube (G-tube) may be required. Infection and extracutaneous symptoms such as spastic diplegia in Sjögren–Larsson syndrome can also arise.

Children and Adults

Ichthyosis treatment in adults and children is tailored to age-specific needs. In infants and young children, treatment is focused on improving function and quality of life. In older children and adults, the significant impact of a visible disease motivates therapy. In such cases, first-line therapy includes baths and topical agents to reduce scaling and improve comfort. Since the skin of ichthyosis patients is susceptible to bacterial superinfection, dilute bleach baths can decrease risk of infection and improve odor. Bathing with two handfuls of baking soda is especially effective at removing scales, because the increased alkalinity may increase serine protease activity and promote desquamation. Despite its strong odor, topical 10% N -acetylcysteine with 5% urea has also demonstrated efficacy for scaling and ectropion and is another therapeutic option.

Emollients applied two to four times daily, ideally after bathing, can help retain moisture. Although discouraged in children because of stinging, adults can apply keratolytics including urea (≥10%) and alpha-hydroxyacids (5–12%) to remove scale more effectively. Salicylic acid (>2%) and topical tazarotene should be used on localized areas and can also relieve scaling.

Systemic retinoids, especially acitretin, are third-line therapeutics for scale-predominant disorders. For children and adults, we seek the lowest effective dose, and most respond to a dose between 0.5 and 1 mg/kg/day. Common side effects include dry lips, dry eyes, and photosensitivity. Rare side effects include long-term musculoskeletal effects, dyslipidemia, and liver injury. Therefore, serum vitamin D, lipid, and liver function tests are obtained at baseline, 1 month after initiating retinoids, and every 3 months afterwards. Retinoids should be used with caution in females of child-bearing potential; acitretin is relatively contraindicated in this population given the risk of retinoid embryopathy if conception occurs within 3 years of the last dose.

For epidermolytic ichthyoses, first-line therapies include emollients and bicarbonate baths to facilitate desquamation. Thick scales harbor a myriad of microorganisms, but antibiotics, antibacterial soaps, and bleach baths can control odor and reduce infection risk. Keratolytics and topical retinoids are second-line strategies that further reduce hyperkeratosis. Tolerance of keratolytics varies, and usage is limited to adolescents and adults. While topical retinoids and third-line systemic retinoids decrease infections and greatly improve skin appearance and function, they can exacerbate skin fragility. Therefore, it is important to initiate retinoids at a low dose and gradually increase to efficacy.

Exfoliative scale is seen in Netherton syndrome (NS) and treatment with emollients and focal use of topical steroids is standard of care. While corticosteroids can alleviate inflammation, impaired skin barrier increases risk of systemic toxicity of topical agents such as iatrogenic Cushing syndrome, especially among children. Therefore, monitoring serum drug levels is imperative, especially if using the topical immunomodulator, tacrolimus, to treat NS. Third-line therapies include biologics such as infliximab, a TNF-α inhibitor that targets inflammatory markers such as thymic stromal lymphopoietin (TSLP), interleukin-6, and interleukin-8 in the skin, resulting in clinical improvement in isolated case reports. Retinoids exacerbate desquamation and are contraindicated.

Psychosocial Management

The appearance of ichthyosis can be striking and intimidating, and families may feel guilty and reproachful. Without proper psychosocial support and education, there is a risk of delayed parental–infant bonding and child neglect after discharge. The ichthyoses profoundly impact quality of life from childhood to adulthood, and there is a high prevalence of depression and anxiety among affected individuals. Psychological assessment, support, and intervention is therefore crucial.