Ichthyosis

The ichthyoses are a group of skin conditions characterised by a diffuse, generally uniform and persistent pattern of scaling (the term ichthyosis is derived from the ancient Greek root ichthys, meaning fish). There are at least 20 varieties of ichthyosis, which can be genetic, acquired or form part of an ichthyosiform syndrome. 

This chapter, which is set out as below, provides a brief overview on ichthyosis, with a focus on the more common and/or important types.

• The inherited forms of ichthyosis occur as a result of genetic mutations that alter the appearance and behaviour of keratinocytes in the stratum corneum 

• The cause of acquired ichthyosis can be idiopathic or secondary to underlying systemic condition, including occasionally malignancy - refer to the section below on investigations 

Ichthyosis vulgaris (IV)

• Is the most common form of ichthyosis. In one study it affected 1 in 250 school children

• It is caused by altered profilaggrin expression leading to scaling and desquamation, and is inherited as autosomal dominant

• IV Is more common in temperate climates and Caucasians, and symptoms tend to improve in warm and sunny weather  

• Clinical features
• Chronology - the skin may appear dry or normal at birth, however, fine scaling is usually apparent by two months of age, although occasionally the diagnosis does not become apparent until the age of five years 
• Distribution - a symmetrical involvement of the extensor aspects of the arms and legs, with sparing of the flexural creases and nappy area. The trunk, and in particular the abdomen, is mildly affected. The forehead and cheeks may be involved early on, but scaling usually diminishes in these areas with age. There is often fine scaling of the scalp 
• Morphology - scales are small (upto 1 cm), fine, irregular, and polygonal in shape, often curling up at the edges. The scaling, which is semi-adherent, is often much more pronounced on the shins. The scale is usually white-grey, although dark-skinned individuals often have darker scales

• Associations - up to 50% of patients with ichthyosis vulgaris have features of atopic eczema, and many have keratosis pilaris

• Skin creases on the palms and soles are more prominent and there can be painful fissuring

• Prognosis - many will have a gradual improvement through adolescence, although a few cases become worse 

X-linked recessive ichthysosis 

• Is the second most common type of ichthyosis with an estimated prevalence of 1 in 2000 to 1 in 6000 males

• It is caused by an epidermal lipid metabolism anomaly due to inactivating mutations or deletions in the steroid sulfatase STS gene, and is transmitted as an X-linked recessive trait ie it affects males and is inherited through female carriers. Female patients have rarely been reported

• Onset often occurs within the first days of life, although is occasionally delayed. Scaling increases throughout childhood

• The clinical features differ from ichythosis vulgaris in that:
• There can be involvement of the flexural creases (which can be marked on the neck)
• There is sparing of the palms and soles
• The scaling evolves into grey-black, medium-large, adherent scales, which are most pronounced on the trunk and limbs, particularly on the extensor surfaces of the legs and upper outer arms (both XLRI and ichthyosis vulgaris have extensor involvement, especially of the shins). There can also be significant pre-auricular involvement 

• Scaling improves during summer and with age 

• Extracutaneous features / associations  
• Undescended testicles in 5–20%
• Corneal opacities affect many patients but are rarely of clinical significance 
• Kallmann's syndrome describes the association between XLRI, hypogonadotropic hypogonadism, and neurological deficits 

• Prognosis
  • Although the condition persists through adult-life, up to 80% of patients report that symptoms become less troublesome

Autosomal recessive congenital ichthyosis (encompasses non-bullous congenital ichthyosiform erythroderma (NCIE), lamellar ichthyosis (LI), and harlequin ichthyosis)

• Autosomal recessive congenital ichthyosis (ARCI) is a rare, heterogeneous group of disorders of keratinisation characterised primarily by abnormal scaling over the whole body

• These disorders are limited to skin, with approximately two-thirds of patients presenting severe symptoms

• The main skin phenotypes are non-bullous congenital ichthyosiform erythroderma (NCIE) and lamellar ichthyosis (LI), although phenotypic overlap within the same patient or among patients from the same family can occur. Neither histopathologic findings nor ultrastructural features clearly distinguish between NCIE and LI. In addition, mutations in several genes have been shown to cause both lamellar and non-bullous ichthyosiform erythrodermal phenotypes. Consequently the term 'autosomal recessive congenital ichthyosis' (ARCI) was designated to encompass non-bullous congenital ichthyosiform erythroderma, lamellar ichthyosis, and harlequin ichthyosis  

• Most cases are born encased by a collodion membrane, a glistening, yellow, tight film; which cracks and is then shed, usually fully within the first few weeks of life. Such cases require intensive, supportive care. Mortality rates have reduced significantly, with one reported rate of 11%

Non-bullous congenital ichthyosiform erythroderma (NCIE) 

• 90% of cases are born with a collodion membrane 

• Once the membrane is shred the condition is characterised by prominent erythroderma (extensive redness) and fine scaling 

• In early childhood the erythroderma may lessen, while scaling increases. The scales are white-grey, superficial, semiadherent, and cover almost the entire body surface including the flexural folds 

• Hands and feet - 70% of cases develop palmoplantar hyperkeratosis, which can lead to digital contractures. In half of the cases a nail dystrophy including ridging, subungual hyperkeratosis, or hypoplasia has been described 

• Other features can include ectropion (with the potential for eye complications in persisting cases), loss of eyebrows and eyelashes (appears to be more frequent in NCIE than in lamellar ichthyosis), eclabium, and scalp involvement, sometimes with scarring alopecia. Severe anhidrosis is common in childhood, but often improves with adolescence. Growth can be delayed. Psychological problems are common

Lamellar ichthyosis (LI) 

• As with NCIE, most patients are born with a collodion membrane, however, once the membrane is shred the degree of erythroderma is less 

• Scaling develops early, usually within the first month, and can be generalised or localised. The scales are large, dark and adherent 

• Other cutaneous features similar to those seen in NCIE can be found in the more severe cases 

• Severe anhidrosis is usually the case 

• As with NCIE there is a spectrum of severity, some patients are much less severely affected than others. Milder cases are less symptomatic and improve during the summer months. Whereas, the cutaneous features seen in the more severe cases tend to persist into adult life 

Harlequin ichthyosis 

• Children with harlequin ichthyosis are born with a severe collodion membrane, ectropion, out-turned lips and contractures

• Despite the dramatic and distressing appearance at birth, an increasing number of babies with harlequin ichthyosis now survive, and go on to develop the characteristic ichthyotic skin, which can be treated in the same way as the other ichthyotic conditions (refer to the section on management) 

Epidermolytic ichthyosis (syn. bullous ichthyosiform erythroderma)

• Epidermolytic ichthyosis is a rare inherited condition characterised by erythema and widespread formation of epidermal blisters developing at birth. Later, bullous erythema is replaced by progressive hyperkeratosis 

• EHK is usually transmitted following an autosomal dominant inheritance pattern, although it arises from sporadic mutations in up to 50% of cases

• The blisters are flaccid and give way to widespread erosions in the first few hours of life

• Hyperkeratosis becomes more apparent from the third month. The scale is typically generalised and is often more prominent at flexures and overlying joints. The scale is classically described as corrugated in appearance

• Palmoplantar hyperkeratosis develops in almost 60% of cases

• As with other autosomal dominant skin conditions, EHK tends to improve with age

Ichthyosis hystrix

• This term is used to encompass a group of rare conditions characterised by spiny hyperkeratotic scale (hystrix meaning like a porcupine) 

• Transmission is autosomal dominant but some sporadic cases have been reported

• The skin is usually normal at birth. The condition starts in early childhood with severe hyperkeratosis of yellow-brown or grey colour, and of spiky, cobblestone-like or verrucous appearance. Hyperkeratosis is often diffuse and more pronounced on extensor areas of the limbs, the extremities and the trunk. Lesions may also be naevoid, following the lines of Blaschko

• Patients are also affected by striae or diffuse palmoplantar keratoderma 

Netherton's syndrome

• Netherton's syndrome is the most common of the multisystem ichthyosiform syndromes

• It is likely to have an autosomal recessive inheritance

• Cutaneous changes 
  • Generalised erythema (erythroderma) is usually present at or shortly after birth. This is not associated with a collodion membrane. Desquamation develops soon after 
  • In time, children have variable degrees of erythema, with episodic skin peeling
  • Ichthyosis linearis circumflexa is a characteristic serpiginous migratory annular/polycyclic rash with double-edged scale, it is pathognomonic for Netherton's syndrome
  • Some improvement is noted in most patients with age
  • There appears to be an increased risk of cutaneous squamous cell carcinoma

• Other features 
  • Trichorrhexis invaginata - slow-growing, short, brittle, lustreless hair
  • Atopic diathesis - a predisposition to allergy 

• The majority of patients will have an inherited ichthyosis, and depending on the type genetic testing may be needed

• Patients with acquired ichthyosis require thorough investigation to look for an underlying cause, which includes:
• Malignancy 
• Drugs - several medications have been associated including allopurinol, hydroxyurea, nicotinic acid, cimetidine and clofazimin
• Hypothyroidism 
• Renal failure 
• Bowel conditions causing malabsorption 
• Other nutritional deficiencies
• Infection - HIV, leprosy
• Lupus erythematosus
• Graft‐versus‐host disease
• Idiopathic 

• A more sudden onset of acquired ichthyosis similar to the pattern of ichthyosis vulgaris in adult life or with a generalized eczema craquelé appearance suggests the possibility of internal malignancy, particularly if it occurs in a younger age group. Paraneoplastic ichthyosis is typically very extensive, affecting the trunk and having quite prominent fissuring. Other paraneoplastic signs have been reported to be present in conjunction with acquired ichthyosis, including erythema gyratum repens, Bazex syndrome and dermatomyositis. The strongest association is with Hodgkin disease (accounting for over 70% of cases) and other lymphoreticular tumours, including T‐cell lymphomas, leukaemias, myelodysplastic syndrome, multiple myeloma and polycythaemia vera. Cases linked with solid tumours are also well documented, including cancers of the ovary, kidney, liver and breast, as well as leiomyosarcoma. A course paralleling that of an underlying lymphoma (including resolution related to treatment) is usual

• Provide appropriate patient information
• Provide a patient information leaflet  
• Direct to the Ichthyosis Support Group

• Check vitamin-D levels twice a year as vitamin D deficiency is common

• Good skin care

• Avoid soaps and provide a soap substitute 

• Moisturisers - a urea-based moisturiser, such as Calmurid® cream, or Balneum®, is preferable, although patient choice is paramount ie the one they like the best

• In order to reduce scale (and the malodour that is often associated) patients should soak the skin once a day in a warm bath using an emollient bath additive, and wash the skin with a topical antiseptic (eg Octenisan® wash or Hibiscrub®). Other options include sodium bicarbonate (baking soda) - refer to the following link for more information on the various options

• In moderate-severe disease specialists use systemic retinoids (eg acitretin, isotretinoin). These work for some better than others. Topical retinoids can be used for local disease such as the face

• Psychological support may be required

• The Ichthyosis Support Group has produced a document that can help children when starting school - Coping with ichthyosis at Pre-School and Primary School