Table of Contents
Ichthyosis vulgaris is a cutaneous dermatological disease of abnormal keratinization characterized by scaling of skin that usually subsides during summer. It is the most common inherited ichthyosis, being inherited in an autosomal dominant fashion with variable penetrance. Atopic disease has been associated with this condition, with 37-50 % of those with ichthyosis vulgaris exhibiting signs of atopic disease.
- Among keratinization disorders, ichthyosis vulgaris is the most common withan incidence of 1 in 250. It is commonly seen in Caucasians living in temperate climates.
- Males and females are equally affectedwith no racial predisposition. The commonest age of onset is 3-12 years.
- Hereditary ichthyosis is the most common variety accounting for 95% of ichthyosis cases. It is present at birth and presents within the first year in most cases.
Etiology of Ichthyosis Vulgaris
Ichthyosis vulgaris can be:
- Hereditary ichthyosis vulgaris which is inherited in an autosomal dominant fashion with variable penetrance. There is mutation in the genes that encode skin barrier formation. Ichthyosis vulgaris is caused by loss-of-function mutations of the filaggrin gene (it codes for filaggrin protein). Loss-of-function mutations are the type of mutations in genes in which the function for which it encodes is lost. Filaggrin (filament aggregating protein) is a 37-kD peptide that forms a main part of the keratohyaline granule present in the granular layer. Normally, it binds to keratin filaments, resulting in their aggregation, thus causing flattening of the stratum corneum corneocytes(keratinocytes). The normal function of this gene has a crucial role in the integumentary barrier function. Filaggrin gene has been mapped to chromosome 1q21. Mutations of this gene predispose the affected individual to atopic eczema, atopic asthma, and even psoriasis. Other factors that determine the severity of scaling include deficiency of amino acid break-down products of filaggrin that are water-retentive and defects in serine proteases. A mutation in the steroid sulfatase gene can also lead to more severe ichthyosis.
- Acquired ichthyosis : which is a disease of adulthood that is seen following an internal pathology such as malignancy or medication use.
Pathology and Pathophysiology of Ichthyosis Vulgaris
Filaggrin mutations result in disorganized lamellar bilayers and impaired lamellar bilayer maturation. Filaggrin proteolysis is important for skin homeostasis. It is usually fully degraded into constituent amino acids, namely, glutamine, arginine and histidine, and subsequently hydrolyzed further into acidic, polycarboxylic acid osmolytes that are responsible for maintaining the stratum corneum hydration (the “natural moisturizing factors”).
Filaggrin metabolites are reduced in patients with ichthyosis vulgaris, resulting in reduced levels of “natural moisturizing factors” that in turn results in a reduction in skin hydration, an elevated skin surface pH, and increased transepidermal water loss (TEWL). These are responsible for the xerotic skin seen in ichthyosis vulgaris.
Reduction in filaggrin also decreases the ability of the squames to maintain their hydration as they move up progressively through the stratum corneum; this results in the characteristic excessive scale.
The abnormal barrier function leads to compensatory repair mechanisms, including epidermal hyperplasia; this results in hyperkeratosis. Lower levels of flagging proteins is also associated with reduced epidermal urocanic acid (a major ultraviolet-absorbing chromophore that) levels and has been shown to have an increased sensitivity to ultraviolet light. This may be the reason for the higher prevalence of non-melanoma skin cancer seen in patients with atopic dermatitis.
Symptoms and Signs of Ichthyosis Vulgaris
At birth the skin feels and looks normal, however in the neonatal period, the skin may present a dry and scaly appearance. However, scaling is obvious from two months onwards, usually. The scale is typically white or grey, small, flaky, or branny in texture, and semi-adherent with edges that are turned up. The typical location is on the extensor aspects of the arms as well as the lower legs; flexural creases are usually spared. The nappy or diaper area is typically spared.
Regarding the trunk involvement, the back may be more affected than the abdominal wall. Mild dandruff and involvement of the pinnae may be seen in some patients. Palmoplantar hyperlinearity (linear grooves that cross perpendicularly to the thenar and hypothenar eminences), which is a reflection of mild hyperkeratosis, is a helpful feature in many ichthyosis vulgaris patients, though the soles and palms are usually free of scaling.
Keratosis pilaris (keratotic elevations located around hair follicle orifices) is seen in both atopic eczema and ichthyosis vulgaris, and is usually seen on the extensor aspects of the arms and thighs.
Symptoms include mainly dryness or roughness of the skin and the cosmetic blemishes. Pruritus is not present in isolated ichthyosis vulgaris; however, it may be present in those who have co-existent eczema. Marked seasonal variation is seen in most patients, with amelioration of symptoms in warm and sunny weather. A significant proportion of patients (38 %) report a gradual improvement during adolescence; however, some patients worsen with age.
Bathing suit ichthyosis is an entity typically present in congenital ichthyosis that is inherited in an autosomal recessive fashion. The main feature of this condition is substantial scaling present along the bathing suit areas. The extremities and the center of the face are typically spared. Transglutaminase-1 deficiency is responsible for this condition.
Diagnosis of Ichthyosis Vulgaris
Both light as well as electron microscopy may be employed to examine skin biopsy samples. It is recommended to procure samples for biopsy from areas that have maximal hyperkeratosis. Areas that have minimal scaling are best not taken for histopathologic examination. The preferred site for biopsy is the lower leg (anterior surface) as the thickest scales/stratum corneum are found here.
Histological similarity exists between acquired and hereditary ichthyosis. Compact hyperkeratosis is usually present in the stratum corneum although some involved regions may have a laminated appearance. Follicular plugging if present may represent co-existent keratosis pilaris. Another characteristic histological finding is the presence of one-layered granular layer or it may be absent altogether. Sarcoidosis may present with features of ichthyosis, called ichthyosiform sarcoid, which characteristically has multiple non-caseating dermal granulomas.
The other diagnoses to be considered are
- Ichthyosiform sarcoid.
- Allergic contact dermatitis
- Asteatotic eczema
- Drug eruptions
- Irritant contact dermatitis
- Lamellar ichthyosis
- Pediatric atopic dermatitis
- X-linked ichthyosis.
Therapy of Ichthyosis Vulgaris
There is no total cure for ichthyosis. Morbidity reduction and complication prevention are the goals of pharmacotherapy in this condition. The defective integumentary barrier in this condition allows allergens access beyond the epidermis to come into contact with the antigen-presenting cells. Hence, an important prophylactic approach would be to restore the barrier function of the skin using emollients and Moisturizers.
Moisturizers are very beneficial in patients suffering from ichthyosis vulgaris and atopic dermatitis.
Management of ichthyosis vulgaris involves hydration of the skin and application of an ointment to prevent evaporation thus cause disaggregation of corneocytes by loss of adhesion between cells leading to the formation of a new stratum corneum.
Topical retinoids, such as tretinoin are useful skin hydrating medications. However, they are irritating or cause stinging to the skin following topical application. They are contraindicated in pregnant women due to teratogenicity. A topical retinoid that is receptor-selective, Tazarotene, is beneficial especially in patients who find tretinoin irritating.
Over-the-counter product available for the treatment of ichthyosis vulgaris usually contains propylene glycol or urea as their main constituent. Both urea and propylene glycol are called as humectants. These agents retain the moisture/hydration level in the skin. Urea acts by maintaining the hydration levels of the skin by forming water inclusions in the skin. It may also help in the epidermal gene regulation, thus improving the barrier function of the skin. In contrast, propylene glycol acts by withdrawing water via stratum corneum due to the presence of a water gradient. Shedding of thick skin is seen following hydration.
A humectants lotion, ammonium lactate (12%), is the commercially available form of lactic acid. This agent may be applied twice daily and has been very beneficial in the control of ichthyosis vulgaris. It has superior action compared to creams that are petrolatum-based. It reduces the excessive keratinization in the ichthyosis vulgaris afflicted skin. Its exact mechanism of action is not known.
Other useful methods of management include:
- Salicylic acid may be used for scale removal. It is also called as keratolytic or keratolytic agent. It acts by promoting the shedding or peeling of corneocytes. Also, it induces disaggregation of the corneocytes situated in the upper layers. However, excessive use should be avoided due to risk of systemic toxicity following topical administration over a large surface area especially pediatric patients.
- Over-the-counter product available for the treatment of ichthyosis vulgaris usually contains propylene glycol or urea as their main constituent. Both urea and propylene glycol are called as humectants. These agents retain the moisture/hydration level in the skin. Urea acts by maintaining the hydration levels of the skin by forming water inclusions in the skin. It may also help in the epidermal gene regulation, thus improving the barrier function of the skin.
- In contrast, propylene glycol acts by withdrawing water via stratum corneum due to the presence of a water gradient. Shedding of thick skin is seen following hydration.
- Topical retinoids, such as tretinoin can be useful. However, they are irritating or cause stinging to the skin following topical application. They are contraindicated in pregnant women due to teratogenicity. A topical retinoid that is receptor-selective, Tazarotene, is beneficial especially in patients who find tretinoin irritating.
- Steroids are not indicated as the mainstay of treatment; however, pruritus may be alleviated by the topical use of a mild steroid agent.
The co-existent systemic disease should be treated in cases of acquired ichthyosis vulgaris.
Ichthyosis vulgaris improves during summer and in humid climates. The hereditary variety improves during adulthood. Thus, the disease runs a predictable course.
However, the most common causes of morbidity and mortality include:
- Cosmetic blemish among adolescents.
- Secondary infections of the skin lesions.
- An underlying disease in the acquired variety.
Review Questions on Ichthyosis Vulgaris
The correct answers can be found below the references.
1. Which of the following areas is spared in ichthyosis vulgaris?
- Lower limbs
- Diaper area
- Extensor surfaces
2. Regarding the inheritance pattern of hereditary ichthyosis vulgaris, which of the following is true?
- Autosomal dominant with variable penetrance
- Autosomal dominant with fixed penetrance
- Autosomal recessive
- X-linked dominant
- Mitochondrial inheritance
3. Which of the following is a treatment modality for ichthyosis vulgaris?
- Local heat
- Three doses of methylprednisolone
- Systemic retinoids