Diffuse hereditary palmoplantar keratodermas

What are diffuse hereditary palmoplantar keratodermas?

Diffuse hereditary palmoplantar keratodermas are the palmoplantar keratodermas that affect most of the palms and soles and are caused by a genetic abnormality. Several family members may be affected. Some types of keratoderma are associated with abnormalities of internal organs.

They may be inherited from one affected parent (known as autosomal dominant inheritance) or from both parents, who are generally unaffected (known as autosomal recessive inheritance). The affected gene has been specificaly identified for many of these keratodermas.

Clinical features

Diffuse hereditary palmoplantar keratodermas present in early childhood with redness of the palms and soles. The palms and soles gradually become thicker and develop a yellowish, waxy appearance. There is a clear cut-off between affected and unaffected skin and the edge of the thickening is often red. This is usually obvious by the age of 3 to 4.

Increased sweating (hyperhidrosis) is quite common and there is a tendency to fungal and bacterial infections of the feet.

Diffuse hereditary palmoplantar keratoderma

‘Transgradient’ is a term used to describe the extent of the skin thickening:

• Non-transgradient keratodermas do not extend beyond the palms on the hands and the sole on the feet. They may affect the knuckle pads and nails but do not involve the thin skin on the top of the feet or hands.
• Transgradient keratodermas extend beyond the palms and soles onto the back of the hands and feet and in some cases up the wrists and ankles. Skin around the mouth, eyes, nose, and over the elbows and knees may also be affected.

Non-transgradient diffuse palmoplantar keratodermas

The non-transgradient diffuse inherited keratodermas are known as Vorner's disease and Unna-Thost disease. They are inherited as autosomal dominant conditions. There are no associated abnormalities. They look the same but have slightly different findings on skin biopsy.

Unna-Thost palmoplantar keratoderma

Transgradient diffuse palmoplantar keratodermas

Olmsted syndrome	Most likely to have autosomal recessive inheritance Associated with scaly rash around the mouth and nose Lines of skin thickening occur the inner aspects of the forearms Fingers may be lost due to tight bands of skin around the fingers
Mal-de Meleda	Autosomal recessive inheritance Associated with a mild rash around the mouth and nose Atopic dermatitis Marked increase in sweating
Huriez syndrome	Autosomal dominant inheritance Tightening of the skin over the fingers Squamous cell carcinoma may arise in affected skin

Diffuse palmoplantar keratoderma associated with other abnormalities

Deafness

• Vohwinkel syndrome is an autosomal dominant keratoderma associated with ‘starfish’-shaped thickening over knuckles, tight bands forming around fingers which sometimes result in amputation of the finger or toe affected (pseudoainhum), and deafness.
• Loricrin keratoderma is a variant of Vohwinkel syndrome which also results in dry, scaly skin over the rest of the body (ichthyosis).
• Bart-Pumphrey syndrome is an autosomal dominant keratoderma, similar to Vohwinkel syndrome, with thickened knuckle pads, white nails and deafness.
• Diffuse palmoplantar keratoderma with deafness is due to a mutation in mitochondria (inherited by a different method than autosomal dominant or recessive patterns).

Hair, nail and teeth abnormalities

• Hidrotic ectodermal dysplasia is an autosomal dominant keratoderma associated with very sparse or absent hair on the head, face and body and thickened, short nails which are easily lost. Skin thickening may also affect knuckles, knees and elbows.
• Papillon-Lefevre syndrome is an autosomal recessive keratoderma associated with inflammation of the gums and loss of teeth, sparse hair and recurrent bacterial infections of the skin and internal organs.
• Diffuse PPK with woolly hair and arrythmogenic cardiomyopathy is an autosomal recessive condition associated with congenital heart disease and coarse, unruly hair.

Treatment of diffuse palmoplantar keratoderma

The following treatments soften the thickened skin and make them less noticeable.

• Emollients
• Keratolytics (e.g. 6% salicylic acid in 70% propylene glycol)
• Topical retinoids
• Topical vitamin D ointment (calcipotriol)
• Systemic retinoids (acitretin)

What is the prognosis?

These conditions persist for life and may be passed on to the next generation.