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At the heart of general practice since 1960

September 2007: Disorders of keratinisation

What topical treatments can remove keratin?

How can underlying malignancy be identified?

How can I treat keratosis pilaris?

What topical treatments can remove keratin?

How can underlying malignancy be identified?

How can I treat keratosis pilaris?

Keratins are the main intermediate filaments in epithelial cells. In keratinised skin these are transformed into the dead cornified cells of the stratum corneum, which are then shed from the surface.

Normally, shedding is balanced by keratin production. When this balance is disrupted a number of different conditions can result, which vary depending on whether the disruption is local or widespread. Some of these conditions, such as corns and calluses, are very common. Others, such as ichthyosis, are rare.

1 Corns

Corns are areas of hyperkeratosis that overlie bony prominences on the hands and feet. The area of hyperkeratosis is localised over an area of pressure, with a central corn-like nodule of keratin that causes pain. They are usually sharply demarcated and take one of two forms:

• Hard corns are dry, hard masses that are most commonly found over the interphalangeal joints

• Soft corns tend to occur between the digits. They are softer and macerated as a result of being soaked in sweat.

Macroscopically, corns may look like verrucas. Paring down 1-2mm with a scalpel blade can differentiate between them: verrucas will bleed and have visible capillaries but no central keratin plug, whereas corns are avascular.

If the source of trauma is not apparent when treating a corn, remember that the cause may be intrinsic. Causative bony prominences may be detected by x ray.1

2 Hyperkeratosis

Large areas of hyperkeratosis may develop over less localised areas of pressure.

Hyperkeratosis occurs most commonly over the heel. As the layer of keratin thickens the skin may crack and a painful fissure can develop. In patients at risk, such as those with diabetes, these may become infected.

A thickened area of hyperkeratosis can be treated in a number of ways. Patients should be advised to wear shoes to prevent direct trauma from hard ground, regularly soak their feet and pare the area with a pumice stone. Topical application of salicylic acid helps to destroy the accumulated keratin.

3 Verruca

Verrucas are very common and affect 7-10% of the UK population. They are spread by direct contact, often in places such as communal showers.3 Women are more commonly affected than men and incidence is highest in children and teenagers.4

Verrucas are caused by human papillomavirus types 1, 2 and 4. These also cause hand warts, but the pressure of walking tends to cause verrucas to grow endophytically (ie inwards).

Treatment options include topical salicylic acid and cryotherapy, both of which may be more successful if the verruca is pared down. One study showed improvement with the addition of oral zinc sulphate (10mg/kg/day, maximum dose 600mg).5

Newer treatment options for resistant warts include photodynamic therapy.6

Conservative treatment is also an option.

4 Cutaneous Horns

Cutaneous horns are composed of compacted keratin. They project from the surface of the skin.

Horns will often simply separate from the skin, leaving a small firm base, and curettage and cautery can be used. However, underlying malignancy is present in 20% of cases and may be missed with this form of treatment.7

There is no reliable distinguishing feature to confirm malignancy, although tenderness around the base is more likely to occur with malignant change. Excision should be carried out if malignancy is suspected.

The majority of malignant horns arise from squamous cell carcinomas. However, they can also be caused by underlying basal cell carcinoma,8 sebaceous adenoma or a granular cell tumour.

5 Seborrhoeic Keratosis

Seborrhoeic keratoses are very common benign tumours. The cause is unknown, but in some cases there seems to be autosomal dominant inheritance.

Histologically, seborrhoeic keratoses are raised above the skin surface and show a papillomatous epithelial proliferation containing horn cysts.

Seborrhoeic keratoses do not undergo malignant change and are usually easily recognisable macroscopically. Some patients have many hundreds, and treatment can be ongoing and time consuming. Treatment options include:

• Cryotherapy

• Curettage and cautery

• Shave excision

• Electrodesiccation

• Dermabrasion surgery.

In many cases patients opt for no treatment.

6 Keratosis Follicularis (Darier's Disease)

Keratosis follicularis is also known as Darier's or Darier-White disease. It is an autosomal dominant genodermatosis characterised by greasy hyperkeratotic papules in seborrhoeic regions, nail abnormalities and mucous membrane changes.

It is most commonly detected in patients aged 6 to 20 years. There is usually a family history of the condition.

One of the main concerns patients have is the odour associated with affected areas. These areas are also at increased risk of infection with bacteria or herpes simplex.

Treatments include basic measures, such as emollients, antiseptic soaks and sunscreens. Mid-potency topical steroids, topical retinoids9 and topical 5-fluorouracil may also be used. Oral treatment with retinoids, such as acitretin and isotretinoin, may be helpful in more severe cases.

7 Subungual hyperkeratosis

Subungual hyperkeratosis is most commonly seen with fungal infections of nails and nail plates. The nails become thickened and deformed. Excess keratin collects under the nail, raising it from the nail bed and making it more difficult to cut.

When checking for the presence of fungi, collection of the hyperkeratotic material and nail clippings can be useful.

Topical treatments are of little use when nails are affected. After confirming the presence of a fungus a three-month course of an oral agent such as terbinafine is usually required.

Patients need to be advised prior to treatment that treatment failure and recurrence can occur.

8 Keratosis Pilaris

Keratosis pilaris is a very common condition that affects 50-80% of all adolescents and 40% of adults. Up to 50% of those affected have a positive family history with autosomal dominant inheritance.10

Keratosis pilaris is a disorder of hyperkeratosis. Discrete 1mm diameter folliculocentric nodules develop, predominantly over the outer aspects of the upper arms, the fronts of the thighs and the face. In some cases this may be associated with mild erythema. Women are twice as likely to be affected than men.

Although the condition causes few symptoms, its cosmetic appearance usually leads patients to seek medical help.

The condition improves with age. There is no effective treatment, although exfoliating regimens, regular moisturising and the use of salicylic acid compounds, topical steroids and tretinoin cream may be useful.10

9 Ichthyosis Vulgaris

Ichthyosis, derived from the Greek ichthys, meaning fish, is so called because of the scaly, fish-like appearance of the skin of affected patients.

There are two forms. The hereditary form is an autosomal dominant condition that is usually apparent by the age of five years. The acquired form is extremely rare. It may occur at any time of life and is usually secondary to an internal condition, such as malignancy.11

A biopsy may be required to confirm the diagnosis. This should be taken from the areas of most significant hyperkeratosis (usually the anterior lower legs), as in less affected areas histology may differ little from normal skin.

The mainstay of treatment is the regular use of emollients, application of keratolytics and, if required, topical retinoids. Topical steroids have little effect, but may help with irritation.

10 Keratoacanthoma

Keratoacanthoma is a relatively common low-grade tumour arising from the pilosebaceous unit. It closely resembles squamous cell carcinoma.

Typically, keratoacanthomas grow rapidly over a period of a few weeks and then, if untreated, undergo a period of regression and resolution. In the majority of cases they tend to be excised so that they can be differentiated from the more serious squamous cell carcinoma.

Incidence increases with age, and the lesion is rare in patients under the age of 20. Men are twice as likely to be affected than women. The lesion usually occurs on the face, neck, dorsum and on upper extremities.

The underlying cause remains unclear, but several potentiating factors have been identified. The similarity of the site of the lesion with squamous cell carcinoma and Bowen's disease and the age and sex of patients affected suggest a link with ultraviolet light exposure.

Incidence seems to be higher in industrial workers exposed to pitch and tar,12 and a recent study has suggested a strong association with cigarette smoking.13

11 Palmoplantar keratoderma

The palmoplantar keratodermas are a group of heterogeneous disorders characterised by hyperkeratosis of the palms and soles. They are divided into acquired and inherited forms and then subdivided according to their clinical form:

• Inherited forms are categorised as diffuse, focal and punctate palmoplantar keratodermas.

• The acquired form may be caused by:

– Infection

– Drug therapy (for example lithium, methyldopa and gold)

– Inflammation.2

In all cases treatment can be difficult. Options include topical keratolytics, topical retinoids, potent topical steroids, dermabrasion and psoralen combined with exposure to ultraviolet light A (PUVA).

12 Hyperkeratotic Squamous Cell Carcinoma

Squamous cell carcinomas have a predilection for the upper pinna, as shown in the picture. In this patient there is hyperkeratosis on the surface, which may lead to an incorrect diagnosis of seborrhoeic wart in some patients.

Any lesions excised from the pinna should be sent for histology to avoid missing malignancy. The increased risk of malignancy in this area is thought to be caused by the increased exposure to ultraviolet light.

Once a lesion has been excised, education regarding protection from sunlight is essential. Patients should be advised to wear a hat when outside. .

Author

Dr Nigel Stollery
MB BS
GP, Kibworth, Leicestershire and clinical assistant in dermatology, Leicester Royal Infirmary

Corns are areas of hyperkeratosis that overlie bony prominences on the hands and feet Figure 1: Corns Hyperkeratosis occurs most commonly over the heel. In patients at risk, such as those with diabetes, cracks and fissures may become infected Figure 2: Hyperkeratosis Verrucas are very common. Treatment options include salicylic acid and cryotherapy Figure 3: Verruca A cutaneous horn. Underlying malignancy is present in 20% of cases Figure 4: Cutaneous horns Seborrhoeic keratoses are common, easily recognisable and do not undergo malignant change Figure 5: Seborrhoeic keratosis Keratosis follicularis. Patients are often concerned by the odour associated with affected areas Figure 6: Keratosis follicularis Subungual hyperkeratosis is commonly linked to fungal infection. Patients should be advised that treatment failure and recurrence can occur Figure 7: Subungual hyperkeratosis Keratosis pilaris affects 50-80% of all adolescents Figure 8: Keratosis pilaris Ichthyosis vulgaris is characterised by the scaly, fish-like appearance of the skin Figure 9: Ichthyosis vulgaris Keratoacanthomas typically grow rapidly over a period of a few weeks and then undergo a period of regression and resolution Figure 10: Keratoacanthoma Palmoplantar keratoderma may be inherited or acquired Figure 11: Palmoplantar keratoderma Squamous cell carcinoma. Any lesions excised from the pinna should be sent for histology to avoid missing malignancy Figure 12: Hyperkeratotic squamous cell carcinoma

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