Congenital ichthyosiform erythroderma: A rare neonatal dermatoses responding to acitretin.

Congenital ichthyosiform erythroderma is a rare and severe form of ichthyosis manifesting in the neonatal age group. We report a child with diffuse peeling of skin and erythroderma presenting on the 2nd day of birth. With aseptic nursing care along with emollients and oral acitretin, the child's quality of life improved remarkably, hence highlighting the point of early and judicious use of acitretin in reducing disease morbidity. Copyright:

Introduction

Congenital ichthyosiform erythroderma (CIE) is a rare and severe autosomal recessive inflammatory ichthyosis. Together with lamellar ichthyosis (LI), it has been classified under autosomal recessive congenital ichthyosis (ARCI).[1] CIE presents as a collodion baby appearance at birth in around 90% of cases gradually progressing to erythroderma. With a paucity of data on the incidence of ARCI, it is estimated to be 1 in 300,000 persons.[2] The severity of this genetic disease precludes the importance of prenatal diagnosis. However, any specific biochemical or molecular markers or ultrasonographic evidence for prenatal diagnosis of this condition are still lacking. Mutations in transglutaminase-1, loricrin, and few other genes have been identified. Recently, lipoxygenase pathway has been linked to various ARCI. Fetal skin biopsy during pregnancy at 17–23 weeks to look for premature or abnormal keratinization helps in some cases. There is currently no cure for the condition, and the management is mainly supportive. Topical emollients, keratolytics, and topical and systemic retinoids form the mainstay of therapy. We present a case of CIE showing good follow-up response to systemic acitretin.

Case Report

A 4-day-old male child, late preterm appropriate for gestational age, born out of nonconsanguineous marriage with 2 kg weight and uneventful perinatal period was referred with chief complaints of diffuse peeling of skin since 2nd day of birth. On examination [Figure 1a], there was diffuse superficial scaling from the whole body with the underlying erythematous skin. There were no vesicles or bullae. Minimal erosion was noted on handling sites such as forearms and back secondary to friction. Palms and soles appeared normal to dry, and hair and mucosa examination was normal. The baby was otherwise active, alert, euthermic, euglycemic with stable vital parameters and required initial tube feeding. All routine blood parameters were within normal limits. The initial septic screen was done which was negative, and the baby did not require any form of respiratory support after birth. The child was advised aseptic nursing care along with bland emollients. In addition, the child was started on oral acitretin (0.2 mg/kg) in view of impending erythroderma and diffuse scaling involving more than 80% of the total body surface area. The child was followed up monthly with routine blood monitoring [Table 1]. At 3 months follow-up [Figure 1b], the erythema had subsided, leaving behind dry skin all over the body.

Figure 1

(a) Diffuse peeling of skin with underlying erythema. (b) Decrease in scaling after 3 months of acitretin therapy

Table 1

Blood parameters at the baseline, 1-month, and 3-month follow-up visit

Investigation	Baseline (at birth)	1 month	3 months
Hb (g/dl)	17.2	13.7	12.8
TWBC (/µl)	14,600	11,200	10,500
TPC (lakhs/µl)	3.78	4.12	3.90
AST/ALT (U/L)	57/39	45/37	50/42
Serum urea/creatinine (mg/dl)	11.2/0.7	11/0.7	12.5/0.8
Lipid profile (total cholesterol/LDL/HDL/triglycerides) (mg/dl)	140.3/64.1/49.7/126.4	142.2/65/49.3/133.1	145.6/70.7/47.3/135.8

Hb=Hemoglobin, TWBC=Total white blood cell, TPC=Total platelet count, AST=Aspartate aminotransferase, ALT=Alanine aminotransferase, LDL=Low-density lipoprotein, HDL=High-density lipoprotein

Discussion

The term ichthyosis is derived from the Greek word ichthys, meaning fish. Ichthyosis is a heterogeneous group of disorders characterized by fish-like scales on the skin. It can be congenital or acquired in etiology. The severity of scaling seen in congenital ichthyosis can range from milder ichthyosis vulgaris to severe life-threatening Harlequin ichthyosis. CIE as the name suggests presents with nonbullous erythroderma in the neonatal period. At birth, most of the cases present with collodion membrane (dipped in hot wax appearance). Soon, the membrane ruptures give rise to dry scaling on underlying diffuse erythema involving the whole body. The nature of scales are fine white, feathery scales all over the body except brownish thick, plate-like scales on the lower limbs.[3] Ectropion and eclabium are frequently seen but less severe than LI. Hair and teeth are normal and the mucosa is spared. Other associated features reported are hypoplasia of nasal and aural cartilage, decreased sweating with heat intolerance, palmoplantar hyperkeratosis, and nail dystrophy.[4] Histopathological findings are nonspecific with hyperkeratosis, acanthosis, and variable parakeratosis. There is markedly increased epidermal cell turnover in CIE in contrast to LI. The various complications seen in the neonatal period are cutaneous infections, aspiration pneumonia, hypothermia, hypernatremic dehydration, and sometimes, acute renal failure.

The goal of therapy in CIE is to maintain body temperature, assist shedding of the collodion membrane, and to take care of the xerosis without irritating the skin. Nonocclusive emollients form the mainstay of therapy. The neonates should be nursed in humidified incubators with frequent application of emollients, temperature monitoring, fluid and electrolyte correction, and special attention to the aseptic environment. The various topical preparations used include emollients, keratolytics, and retinoids. The milder keratolytics are preferred such as alpha-hydroxy acids (lactic and glycolic), urea (10%–20%), and propylene glycol (40%–60%). They help in increasing hydration along with the desquamation of scales. In severe cases, oral retinoid therapy with acitretin is the drug of choice at doses of 0.1–0.75 mg/kg/day. It helps in reducing the scaling, pruritus, and erythema and can be used as intermittent therapy.

Acitretin is a second-generation retinoid. The absorption of acitretin increases on intake with fatty food. Its bioavailability is around 60% on oral intake. Retinoids help in reducing hyperkeratosis in ichthyosis patients but do not correct the keratinization defect. Hence, indefinite therapy is needed in severe cases to keep the disease under control. Apart from mucocutaneous dryness, the main concern while using oral acitretin in children is its long-term side effects such as bone toxicity. Premature epiphyseal closure, skeletal hyperostosis, and extraosseous calcification have been reported with etretinate therapy. Hepatotoxicity and hyperlipidemia are other less commonly encountered side effects in children with retinoid therapy which return to normal on drug discontinuation. The relative safety and efficacy of acitretin has been well documented in neonates and in many instances can be a life-saving drug.[56]

In severe ichthyotic disorders such as CIE presenting in neonatal age, judicious and intermittent therapy with acitretin along with other supportive therapy helps in reducing the disease-related morbidity to a great extent. In our case, there was an excellent response to acitretin markedly improving the infant's quality of life and at the same time giving relief to the anxious parents.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that name and initials will not be published and due efforts will be made to conceal patient identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.