At birth this newborn was noted to have a thick, cracked collodion membrane. He developed restrictive lung disease and died at 2 weeks of age. Harlequin ichthyosis (HI) is a severe and often lethal autosomal recessive ichthyosis. If an afflicted fetus is delivered to term, the condition is often fatal within the first few weeks of life due to restrictive lung disease or sepsis. Neonates present with severe hyperkeratotic scale (collodion membrane) characterized as a plate of armor encasing the patient and restricting mobility. The limitation in movement manifests as flexion contractures of limbs as well a compromise in respiration due to restricted chest wall motion. Although hyperkeratotic, the skin of these patients forms a defective barrier resulting thermal instability, increased transepidermal water loss, and electrolyte abnormalities. Ectropion, eclabium, and ear deformities may also occur. HI may initially resemble that of other ichthyoses associated with a collodion membrane. However, the clinical course, histopathology, including the ultra-structural features, help distinguish HI from other ichthyoses.
Prenatal diagnosis is possible with 2D and 3D ultrasonography or with fetal skin biopsy. A postnatal skin biopsy of HI typically shows a thick stratum corneum with scattered lipid droplets retained in the corneocytes. An absent or thin granular layer may be present. Ultrastructural analysis may reveal abnormal or absent intracellular lamellar bodies. A uniform characteristic is the absence of inter-cellular lamellae which usually contain various lipids, ceramides, as well as proteases. In cases where lamellar bodies are present, they accumulate intracellularly suggesting defective cellular trafficking and exocytosis. Defects in other maturation markers such as profilaggrin/filaggrin as well as keratins 6 and 16 have been observed. Recently, a deletion of the distal arm of chromosome 18 was found in a fetus presenting with HI. A gene for this disorder remains to be discovered, but multiple genotypes may underlie the HI phenotype.
Treatment is largely supportive and involves optimizing fluid, electrolyte, and nutritional repletion, aggressive use of emollients, and environmental measures to decrease transepidermal water loss. Systemic retinoids have been used with limited success. The very few patients who survive develop a chronic ichthyosiform disorder resembling congenital ichthyosiform erythroderma, and have an increased risk of juvenile rheumatoid arthritis and thyroid disease.
References:
1. Chan YC, Tay WK, Tan LK et al. Harlequin ichthyosis in association with hypothyroidism and juvenile rheumatoid arthritis. Pediatr Dermatol. 2003;20(5):421.
2. Dale BA, Holbrook KA, Fleckman P, et al. Heterogeneity in harlequin ichthyosis, an inborn error of epidermal keratinization: variable morphology and structural protein expression and a defect in lamellar granules. J Invest Dermatol. 1990;94:6-18.
3. Hashimoto K, De Dobbeleer G, Kanzaki T. Electron microscopic studies of harlequin fetuses. Pediatr Dermatol. 1993;10:214-223.
4. Stewart H, Smith PT, Gaunt L, et al. De novo deletion of chromosome 18q in a baby with harlequin ichthyosis. Am J Med Genet. 2001;102:342-345.
Description
generalized thickened skin with cracks and fissures; contractures of digits
