Introduction

 

Ichthyoses are disorders of cornification in which abnormal differentiation and abnormal desquamation of the epidermis result in a defective epidermal barrier. Ichthyoses features permanent and generalized visible scaling affecting the whole integument.

Generally, icthyosis results in abnormal differentiation and/or abnormal desquamation showing impaired corneocyte shedding (retention hyperkeratosis) or accelerated keratinocyte production (epidermal hyperplasia/ hyper proliferative hyperkeratosis). The development of hyperkeratosis in these diseases may be understood as a homeostatic repair response aimed at compensating for an abnormal epidermal barrier.

Keratolytic agents and moisturizers for topical treatment of ichthyoses.

Agent	Concentration (%)	Comment
Urea	5–10	Classical humectant and keratolytic. Better avoided during first year of life because of possible systemic absorption
Lactic acid	5–12	Alternative to urea. Commercial preparations are often optimized by buffering
Glycerol	10–15	Moisturizer
Vitamin E acetate	5	Moisturizer
Calcipotriol	0.05 × 10−3	High risk of systemic absorption, treat less than 10% of body surface

 

 

COMMON ICHTHYOSES

 

 

Ichthyosis vulgaris

 

Epidemiology

Ichthyosis vulgaris is the most common disorder of cornification, with an estimated prevalence of 1 in 250 individuals.

Pathophysiology

Ichthyosis vulgaris is due to filaggrin mutations (FLG), which are inherited as an autosomal semidominant trait. About two thirds of IV patients actually have two FLG mutations leading to complete filaggrin deficiency and present with more severe ichthyosis and one third of heterozygotes patients who have only one FLG mutation, have mild ichthyosis.

Loss-of-function mutations in the filaggrin gene (FLG) underlie ichthyosis vulgaris. FLG encodes profilaggrin, a major component of the keratohyalin granules located in the granular layer of the epidermis. Filaggrin mutations result in impaired epidermal barrier formation and a marked reduction of natural moisturizing factors (NMF) which play a critical role in hydration of the stratum corneum. During keratinocyte terminal differentiation, profilaggrin is cleaved into filaggrin peptides, which aggregate keratin intermediate filaments in the lower stratum corneum. These complexes are cross-linked to the cornified cell envelope and are responsible for proper formation of compact squamous cells. Filaggrin is eventually degraded into water-retaining amino acids including urocanic and pyrrolidone carboxylic acids called natural moisturizing factors (NMF) which play a critical role in hydration of the stratum corneum. Filaggrin deficiency results in impaired cornification, increased transepidermal water loss leading to xerosis, enhanced penetration of allergens and irritants, and a propensity to develop inflammatory responses upon exposure to the latter; this explains the association of FLG mutations with atopic dermatitis as well as ichthyosis vulgaris. Irrespective of the presence of IV, FLG mutations predispose to atopic eczema (AE), allergic rhinitis, asthma, food allergies, hand eczema, nickel sensitization and eczema herpeticatum in AE.

 

 

Clinical features

Ichthyosis vulgaris in FLG heterozygotes is usually not evident at birth. Onset is between 3-12 months of life. Dry skin and mild to moderate scaling appear during infancy or early childhood. Scales are most prominent on the extensor surfaces of the extremities, particularly on the pretibial and lateral aspects of the lower leg, where the scales are larger with an adherent at the center and detached, outward-turning with cracking (superficial fissuring through the stratum corneum) at the edges and quadriangular and plate-like, resembling fish scales. This turning up at the edges can lead to the skin feeling rough. In other areas, small, white, translucent, bran-like scales may be seen. Scales tend to be darker on dark-skinned individuals. The scales tend to be smaller than in RXLI and do not encroach on the axillae, groin, and fossae and diaper area because of increased humidity in those regions. Mild hyperkeratosis of the palms and soles leading to accentuated skin markings (hyperlinearity) is common.

In more severe disease due to a complete lack of filaggrin, ichthyosis vulgaris may present at birth with mild erythema and generalized scaling or peeling. Later, large scales reminiscent of lamellar ichthyosis may develop and the trunk, scalp, forehead, and cheeks can be affected in addition to the extremities. Palmoplantar involvement is also more pronounced and often results in furrows or painful fissures of the heels. A considerable number of patients indicate that they suffer from hypohidrosis and cannot perspire well.

Clinical symptoms (e.g. pruritus) and severity depend on season and climate, improving during the summer and with higher humidity, and worsening in a cold and dry weather. Although the ichthyosis may be progressive during childhood, it usually improves with age.

Ichthyosis vulgaris is frequently associated with keratosis pilaris and the atopic triad of asthma, hay fever and atopic dermatitis. The latter is encountered in at least 25–50% of patients with ichthyosis vulgaris and can obscure the characteristic sparing of the flexures. Conversely, approximately 10–15% of individuals with atopic dermatitis also have moderate to severe ichthyosis vulgaris.

Distribution of ichthyosis vulgaris. Dots indicate keratosis pilaris.

 

 

Pathology

 

Mild orthokeratotic hyperkeratosis is seen. A reduced or absent granular layer in biopsy specimen may help to differentiate ichthyosis vulgaris from other forms of ichthyosis. Immunohistochemistry demonstrates diminished or absent filaggrin staining in most patients.

 

Differential diagnosis

The border between dry skin (xerosis) and mild ichthyosis vulgaris is not clear-cut. In male patients, X-linked ichthyosis may be differentiated by larger, darker scales and involvement of the neck and other flexures; a maternal history of delayed or prolonged labor, cryptorchidism and the inheritance pattern can represent additional clues. Chromosomal microarray or fluorescence in situ hybridization (FISH) testing can exclude steroid sulfatase deficiency.

 

 

Treatment

 

The mainstay of treatment is reduction of scaling through the use of emollients and humectants, and those containing ceramides together with other lipids may be especially effective. In those patients without concomitant AE, application of 12% ammonium lactate lotion or cream (Lacsoft) or 10% urea cream is very effective.