What is Palmoplantar keratodermas (PPK)?

Palmoplantar keratodermas are a group of disorders characterized by thickening of the skin on the palms of the hands and soles of the feet of affected individuals. The various forms of PPK can be divided into hereditary forms with only skin problems, hereditary syndromes with PPK as an associated feature, and acquired forms. The more commonly seen hereditary PPKs are discussed here. Hereditary forms may be localized to the hands and feet, or they may be associated with a more generalized skin disorder. Classification of hereditary PPK is frequently confusing. A simple classification incorporates 3 factors:

1. specific form and structure and distribution of the palmoplantar keratosis,
2. presence of associated skin and other tissue (such as nails, hair, mucous membranes) disease in sites other than the palms and the soles, and
3. presence or absence of fragile or blistering skin.

Diffuse Hereditary PPK without associated features:

1) Diffuse non-epidermolytic palmoplantar keratoderma

(also known as diffuse NEPPK, or PPK diffusa circumscripta).

Mode of inheritance: Diffuse non-epidermolytic palmoplantar keratoderma is an autosomal dominantly inherited condition traced to KRT1 and KRT16 keratins. Onset of clinical features usually presents within the first two years of life.

What are the Signs & Symptoms?

•  Even, widespread thickened skin (keratosis) over the palms and soles.
•  A red band at the edges of the keratosis is frequent.
•  Other keratotic lesions may appear on the tops of the hands, feet, knees, and elbows.
•  Excessive perspiration.
•  Nails may be thickened.

What is the Treatment?

• Topical keratolytics, such as 6% salicylic acid in white soft paraffin, or a gel of 6% salicylic acid in 70% propylene glycol.
• Benzoic acid compounds.
• Oral retinoids.

2) Diffuse epidermolytic palmoplantar keratoderma

(Also known as diffuse EPPK, Vorner disease, PPK cum degenerations granulose)
Diffuse epidermolytic PPK is the most common type of hereditary PPK. It has an autosomal dominant inheritance traced to KRT9 keratin.
Onset of clinical features usually takes place within the first year.

What are the Signs & Symptoms?

• Similar to diffuse non-epidermolytic PPK but the skin is fragile and may blister.

What is the Treatment?

•  Topical keratolytics
•  Oral retinoids.
•  Topical calcipotriol.

3) Progressive Palmoplantar Keratoderma

(Also known as PPPK, Greither disease, PPK transgrediens et progrediens)

Progressive PPK is transmitted through an autosomal dominant inheritance.
Onset of clinical features usually appears between ages 8 and 10.

What are the Signs & Symptoms?

•  The widespread thickened skin spreads from the palms and the soles to the tops of the hands and feet and up the Achilles tendon (back of the heel).
•  Excessive perspiration and variations in signs and symptoms between affected family members are common.
•  Signs and symptoms tend to be worse during childhood, static after puberty, and improve in middle age.

What is the Treatment?

• Topical keratolytics, such as 6% salicylic acid in white soft paraffin, or a gel of 6% salicylic acid in 70% propylene glycol.
• Benzoic acid compounds.
• Oral retinoids.

Diffuse Hereditary PPK with associated features

(Diffuse PPK is associated with extra palmoplantar skin involvement in several inherited disorders of cornification. The more common conditions are outlined below.)

1) Mal de Meleda

(Also know as Keratosis extremitatum hereditaria transgrediens et progrediens)
Mal de Meleda is a rare disorder seen in approximately 1 in 100,000 people. It was initially observed in inhabitants of the Adriatic island of Meleda (Miljet). It is transmitted through an autosomal recessive inheritance. Clinical features of the disorder usually appear in early infancy. Palmoplantar keratoderma is often the only manifestation.

What are the Signs & Symptoms?

• Widespread thickened skin with a prominent red border, which spreads onto the tops of the hands and feet. The widespread hyperkeratosis may resemble gloves or stockings on the hands and feet.
• Tight constricting bands around the fingers and toes, which result in spontaneous amputation, have been reported.
• Individuals may have well defined psoriasis-like plaques or lichenoid patches (small firm lesions set very close together) on the knees and elbows.
• Excessive sweating.
• Reddened and thickened skin around the eye socket.
• Nail changes.
• A ridged tongue, webbed fingers or toes, hair on the palms or soles, a high arched palate (roof of the mouth), and left-handedness are associated features.

What is the Treatment?

• Oral retinoids

2) PPK Mutilans Vohwinkel

(Also know as mutilating keratoderma, Vohwinkel syndrome, and palmoplantar keratoderma mutilans)
PPK Mutilans Vohwinkel is a rare disorder that can be transmitted through an autosomal dominant inheritance or an autosomal recessive inheritance. The genetic defect has been traced to the GJB2 gene and connexin 26. Clinical features usually appear in infancy.

What are the Signs & Symptoms?

• Presents in infants as a honeycomb-like thickening of the skin on the palms and the soles.
• Later-forming, constricting, fibrous bands on the fingers and toes lead to progressive strangulation and autoamputation.
• Starfish-shaped thickened skin may occur on the tops of the fingers and knees.
• Baldness, deafness, spastic impairment of the muscles, nearsightedness, scaly skin, and nail abnormalities are associated

  What is the Treatment?

Currently the recommended treatment for PPK is Oral retinoids.

3) Mutilating Palmoplantar keratoderma with periorificial keratotic plaques

(Also known as Olmstead Syndrome)
A rare disorder transmitted through an autosomal dominant inheritance. Clinical features usually appear within the first year of life.

What are the Signs & Symptoms?

• Symmetrical, sharply defined palmoplantar keratoderma surrounded by reddened skin and deformities of the joints that lead to constriction and spontaneous amputation.
• Horny growths around the eyes and mouth.
• Nail abnormalities.
• White thickened patches of skin around the anus and in the mouth.
• Sparse hair.

What it the Treatment?

• Oral retinoids.
• Topical retinoids.

4) Palmoplantar Keratoderma with sclerodactyly (hardening and thickening of the connective tissues of the fingers and toes).

(Also known as Huriez syndrome)
A rare disorder transmitted through an autosomal dominant inheritance. Clinical symptoms are visible in infancy.

What are the Signs & Symptoms?

• Sclerodactyly – scleroderma or hardening and thickening of the connective tissues of the fingers and toes.
• Widespread thickened skin more marked on the soles than on the palms.
• Nail abnormalities.
• Decreased sweating.
• Associated with squamous cell carcinoma.

5) Palmoplantar Keratoderma with peridontitis (inflammation of the gums)

(Also known as Papillon-Lefevre Syndrome)
A rare disease transmitted through an autosomal recessive inheritance. The disorder results from mutations in cathepsin C. It occurs equally among males and females. Clinical features usually appear within the first and fifth years of life.

What are the Signs & Symptoms?

• Widespread or focal thickened skin on the palms and the soles.
• Unless treated, periodontitis results in severe gum disease and loss of teeth by age 5.
• Patients may exhibit an increased susceptibility to infection.
• Scaly, red lesions over knees, elbows, and knuckles are occasionally observed.
• Excessive sweating and body odor.

What is the Treatment?

• Dental care and appropriate antibiotic therapy for periodontitis.
• Oral retinoids.

Treatment of all types of hereditary and nonhereditary keratodermas can be difficult. Most treatment options only result in short-term improvement and are compounded frequently by side effects. Treatment tends to address the symptoms and can vary from saltwater soaks and paring down of the thickened skin, to topical keratolytics, oral retinoids, or reconstructive surgery of the hyperkeratotic skin followed by grafting. Common treatments include:

• Topical keratolytics including 5 – 10% salicylic acid, 10% lactic acid, or 10% urea in a neutral base.
• Topical retinoids, such as tretinoin (0.05% gel and 0.1% cream), are effective, but treatment can cause irritation of the surrounding skin.
• Topical steroids can be considered, with or without keratolytics, in conditions where there is an inflammatory component.
• Treatment with 5% 5-fluorouracil has produced dramatic results in spiny keratoderma, but its use in other keratodermas has not been evaluated.
• Oral retinoids are effective, especially in some hereditary PPKs such as Mal de Meleda, Papillon-Lefevre syndrome, and erythrokeratodermia variabilis (a form of ichthyosis that often includes palmoplantar keratoderma). Most hereditary PPKs require long-term treatment. Caution is advised if the patient has a blistering form, since large erosions may occur with oral retinoids therapy. Patients should be started on a low dose, and dosage should be increased should be carefully increased to avoid flaring the disease and/or causing erosions.
• Regular foot care, careful selection of footwear, and treatment of fungal infections are important.
• Dermabrasion may help topical agents penetrate, and carbon dioxide laser treatment may be beneficial in limited keratodermas.
• For severe, difficult to treat keratoderma, surgery may need to be considered. Total excision of hyperkeratotic skin followed by grafts has been successful in a number of cases.

Adapted from eMedicine.com, Keratosis Palmaris et Plantaris.   Copyright 2002, eMedicine.com, Inc.