When we think of inherited skin disorders, psoriasis is probably the first that comes to mind as many cases are familial but there is one skin conditions which affects about 1 in 250 people. Ichthyosis is a group of disorders characterised by scaling, dryness and sometimes thickening of the skin. It is the scale from which the condition gets is name from the Latin “Ichthys” (fish). In most cases the condition is purely a skin problem, but some types can affect other organ systems.
Figure 1: Ichthyosis vulgaris affecting the plantar surface.
The condition arises as a result of mutations in a range of genes responsible for the manufacture and construction of structural proteins within the epidermis. The most common form of the disease is ichthyosis vulgaris which is caused by a loss of function to the filaggrin gene (on chromosome 1). Filaggrin is an important molecule within the skin providing natural moisturising factors to the epidermis and affecting skin structure. It is a large polyprotein which is dephosphorylated in the epidermis into filaggrin. It has several important effects. Firstly, it causes compaction and flattening of the keratinocytes as they ascend from the stratum granulosum into the stratum corneum. It does this by tightly binding together keratin bundles producing squames. Additionally, it degrades into urocanic acid, pyrrolidone carboxylic acid and natural moisturising factors. Combined, these chemicals maintain the acid mantle protect the skin from microbes and photosensitivity while improving the skins elasticity.
Figure 2: Functions of Profilaggrin & FiIlaggrin (From Brown & McLean (2012))
Lack of filaggrin increases the skin fragility and due to the reduced presence of natural moisturising factors the skin is very dry and loses pliability. In addition, a raised pH affects the normal keratinisation process and the patient becomes more prone to allergens and the risk of developing atopic dermatitis along other atopic features such as asthma and skin infection with staphylococcus aureus and other microbes. Microscopically, epidermis lacking in filaggrin has an absent stratum granulosum.
Ichthyosis vulgaris (IV) which is inherited by as an autosomal dominant trait [2], affects around 1:250 patients and most patients with the mutation will exhibit features by the age of 5 years. Patients with this form are also more susceptible to developing atopic dermatitis. The palms and the soles may exhibit hyperkeratosis, with the creases of the palms exhibiting hyperlinearity. Many patients have no reported symptoms other than persistently dry skin others may exhibit small or large scales on the skin (see figure 2). Homozygotes showing more severe symptoms than heterozygotes.
Complications associated with IV include reduced ability within the skin to naturally produce vitamin D which in children can lead to rickets if undetected. Eye problems have also been reported in other studies. Excessive scale in the auditory canal can lead to reduce hearing. Some variants of the disease can also carry an increased risk for fungal skin infection.
Treatment for patients with ichthyosis consists of strategies to soften and hydrate the epidermis and so consequently emollients are the mainstay of any treatment. Agents such as urea, lactic or glycolic acid based can enhance the effectiveness of treatment and regular application can lead to reduction of scaling and in improvement in epidermal function. Using emollients under occlusion has a potentiating effect. Keratolytics such as salicylic acid can reduce scale and add water to the epidermis. Systemic retinoid therapy for some types of the disease can be beneficial although careful consideration is required before prescribing due the known side effects which include dry mouth, nose bleeds, headaches and more serious effects such as hyperostosis, arthralgia, elevation of liver enzymes and raised cholesterol. Moreover, retinoids are teratogenic and so women of childbearing age must ensure contraception is in place before commencement and for up to 3 years after ceasing treatment with some types of prescribed retinoid.
References / Further reading
1. Brown, S.J. and W.H. McLean, One remarkable molecule: filaggrin. J Invest Dermatol, 2012. 132(3 Pt 2): p. 751-62.
2. Jaffar, H., et al., Ichthyosis vulgaris: An updated review. Skin Health and Disease, 2023. 3(1): p. e187.