Tylosis is a rare dermatological condition characterized by excessive thickening of the skin on the palms of the hands and the soles of the feet, medically termed palmoplantar hyperkeratosis. This abnormal overgrowth is caused by an accelerated and disordered production of keratinocyte cells in the epidermis, leading to thick, firm plaques. While it is a form of palmoplantar keratoderma, tylosis often specifically refers to the inherited genetic types. Recognizing the presence of this condition is important for identifying underlying health implications that may extend beyond the skin itself.
The Clinical Manifestation of Tylosis
The physical changes associated with tylosis manifest as dense, hardened plaques of skin on the volar surfaces of the hands and feet. This hyperkeratosis can be either diffuse, covering the entire palm and sole uniformly, or focal, restricted to areas of pressure or friction. The affected skin often appears yellowish and has a waxy or firm texture, which develops progressively, sometimes beginning in early childhood.
The thickening significantly reduces the skin’s flexibility, leading to discomfort and sometimes severe pain, particularly with weight-bearing activities. Painful cracks and deep fissures can form within the thickened plaques, which are susceptible to secondary bacterial or fungal infections. Mobility and manual dexterity can be impaired due to the rigid nature of the affected skin, limiting daily activities. The condition may also be accompanied by hyperhidrosis (excessive sweating of the palms and soles), further complicating skin integrity and increasing the risk of maceration and infection.
Understanding the Underlying Causes
The development of tylosis is broadly categorized into two main groups: inherited (genetic) forms and acquired forms, each with distinct origins. Inherited tylosis is typically passed down through families in an autosomal dominant pattern, meaning a person only needs to inherit one copy of the altered gene from a parent to develop the condition. In these genetic forms, a mutation disrupts the normal lifecycle and differentiation of keratinocytes, resulting in the overproduction of keratin and the subsequent skin thickening.
A well-known inherited form is linked to the RHBDF2 gene, previously known as the TOC (Tylosis with Oesophageal Cancer) gene, which plays a part in cell signaling and proliferation. However, not all inherited forms are linked to this gene, and other genetic mutations, such as those in the GJB2 gene, can cause syndromic forms of the condition.
The acquired forms of tylosis are not genetically predetermined but result from external factors or underlying systemic health issues. Chronic mechanical stress, like repeated friction or pressure from certain occupations or ill-fitting footwear, can trigger localized hyperkeratosis that resembles tylosis. Environmental exposures or the long-term use of specific medications may also contribute to the acquired presentation of the skin thickening. Furthermore, acquired tylosis can sometimes be a cutaneous manifestation of a systemic disease, such as certain infections or underlying inflammatory conditions, making a comprehensive medical evaluation necessary for diagnosis.
Subtyping and Associated Health Concerns
Classification of tylosis is important because certain subtypes carry serious health implications that extend far beyond the skin. The most concerning hereditary form is Tylosis with Esophageal Cancer, also known as Howel-Evans Syndrome. Individuals inheriting the RHBDF2 gene mutation face a significantly elevated lifetime risk, calculated to be as high as 95% by age 65, of developing squamous cell carcinoma of the esophagus.
This cancer risk necessitates a strict medical monitoring protocol, often involving annual upper gastrointestinal endoscopy surveillance starting in early adulthood. The cutaneous features, which may also include white patches in the mouth called oral leukokeratosis, usually appear in childhood, preceding the typical onset of esophageal cancer in middle to late life.
Vohwinkel Syndrome
Another distinct hereditary form is Vohwinkel Syndrome, caused by mutations in genes like GJB2 or loricrin. It is characterized by a “honeycomb” pattern of hyperkeratosis, often accompanied by non-skin features like high-frequency hearing loss. A distinguishing feature is the formation of fibrous constricting bands around the fingers and toes, known as pseudo-ainhum, which can lead to the progressive autoamputation of the digits.
Olmsted Syndrome
A third syndromic type, Olmsted Syndrome, presents with severe palmoplantar keratoderma coupled with hyperkeratotic plaques around the mouth and nose, referred to as periorificial hyperkeratosis.
Management and Therapeutic Approaches
Management of tylosis focuses on alleviating symptoms and reducing the thickness of the hyperkeratotic skin, as a curative treatment is not available for the inherited forms. Topical treatments are a first-line approach and primarily involve the use of keratolytics, agents designed to chemically dissolve and shed the excess skin. These topical agents are often applied under occlusion to enhance penetration and effectiveness.
Common keratolytics include preparations containing high concentrations of salicylic acid, urea, or alpha-hydroxy acids. Regular application of thick emollients and moisturizers is recommended to soften the skin, improve elasticity, and prevent painful fissuring. For severe or unresponsive cases, systemic medications may be employed.
Oral retinoids, such as acitretin, are vitamin A derivatives that effectively slow the excessive proliferation of keratinocytes. Their use requires careful monitoring due to potential side effects like hypercholesterolemia, liver function abnormalities, and nasal dryness. Physical interventions, including routine mechanical debridement (where the thickened skin is manually shaved or filed down), are also incorporated to maintain function and comfort. Specialized footwear and padding are necessary for plantar involvement to distribute pressure evenly and minimize friction.