The cause of PPE is unknown. Existing hypotheses are based on the fact that only the hands and feet are involved and posit the role of temperature differences, vascular anatomy, differences in the types of cells (rapidly dividing epidermal cells and eccrine glands).

In the case of PPE caused by PLD, the following mechanism has been demonstrated: sweat deposits and spreads the drug on the skin surface; then the drug penetrates into the stratum corneum like an external agent; palms and soles have high density of sweat glands, and their stratum corneum is approximately 10 times thicker than the rest of the body, and becomes an efficient long-term reservoir for the penetrating PLD, which was deposited on the skin before.

PPE invariably recurs with the resumption of chemotherapy. Long-term chemotherapy may also result in reversible palmoplantar keratoderma. Symptoms resolve 1–2 weeks after cessation of chemotherapy (Apisarnthanarax and Duvic 2003).

Many conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle and glands. The major function of this system is as a barrier against the external environment. The skin weighs an average of four kilograms, covers an area of two square meters, and is made of three distinct layers: the epidermis, dermis, and subcutaneous tissue. The two main types of human skin are: glabrous skin, the hairless skin on the palms and soles (also referred to as the "palmoplantar" surfaces), and hair-bearing skin. Within the latter type, the hairs occur in structures called pilosebaceous units, each with hair follicle, sebaceous gland, and associated arrector pili muscle. In the embryo, the epidermis, hair, and glands form from the ectoderm, which is chemically influenced by the underlying mesoderm that forms the dermis and subcutaneous tissues.

The epidermis is the most superficial layer of skin, a squamous epithelium with several strata: the stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale. Nourishment is provided to these layers by diffusion from the dermis, since the epidermis is without direct blood supply. The epidermis contains four cell types: keratinocytes, melanocytes, Langerhans cells, and Merkel cells. Of these, keratinocytes are the major component, constituting roughly 95 percent of the epidermis. This stratified squamous epithelium is maintained by cell division within the stratum basale, in which differentiating cells slowly displace outwards through the stratum spinosum to the stratum corneum, where cells are continually shed from the surface. In normal skin, the rate of production equals the rate of loss; about two weeks are needed for a cell to migrate from the basal cell layer to the top of the granular cell layer, and an additional two weeks to cross the stratum corneum.

The dermis is the layer of skin between the epidermis and subcutaneous tissue, and comprises two sections, the papillary dermis and the reticular dermis. The superficial papillary dermis with the overlying rete ridges of the epidermis, between which the two layers interact through the basement membrane zone. Structural components of the dermis are collagen, elastic fibers, and ground substance. Within these components are the pilosebaceous units, arrector pili muscles, and the eccrine and apocrine glands. The dermis contains two vascular networks that run parallel to the skin surface—one superficial and one deep plexus—which are connected by vertical communicating vessels. The function of blood vessels within the dermis is fourfold: to supply nutrition, to regulate temperature, to modulate inflammation, and to participate in wound healing.

The subcutaneous tissue is a layer of fat between the dermis and underlying fascia. This tissue may be further divided into two components, the actual fatty layer, or panniculus adiposus, and a deeper vestigial layer of muscle, the panniculus carnosus. The main cellular component of this tissue is the adipocyte, or fat cell. The structure of this tissue is composed of septal (i.e. linear strands) and lobular compartments, which differ in microscopic appearance. Functionally, the subcutaneous fat insulates the body, absorbs trauma, and serves as a reserve energy source.

Conditions of the human integumentary system constitute a broad spectrum of diseases, also known as dermatoses, as well as many nonpathologic states (like, in certain circumstances, melanonychia and racquet nails). While only a small number of skin diseases account for most visits to the physician, thousands of skin conditions have been described. Classification of these conditions often presents many nosological challenges, since underlying etiologies and pathogenetics are often not known. Therefore, most current textbooks present a classification based on location (for example, conditions of the mucous membrane), morphology (chronic blistering conditions), etiology (skin conditions resulting from physical factors), and so on. Clinically, the diagnosis of any particular skin condition is made by gathering pertinent information regarding the presenting skin lesion(s), including the location (such as arms, head, legs), symptoms (pruritus, pain), duration (acute or chronic), arrangement (solitary, generalized, annular, linear), morphology (macules, papules, vesicles), and color (red, blue, brown, black, white, yellow). Diagnosis of many conditions often also requires a skin biopsy which yields histologic information that can be correlated with the clinical presentation and any laboratory data.

Usually, a common form of treatment for the condition is a type of hand cream which moisturises the hard skin. However, currently the condition is incurable.

The histological and ultrastructural features of Ledderhose and Dupuytren's disease are the same, which supports the hypothesis that they have a common cause and pathogenesis. As with Dupuytren's disease, the root cause(s) of Ledderhose's disease are not yet understood. It has been noted that it is an inherited disease and of variable occurrence within families, i.e. the genes necessary for it may remain dormant for a generation or more and then surface in an individual, or be present in multiple individuals in the same generation with varying degree.

There are certain identified risk factors. The disease is more commonly associated with -

- A family history of the disease

- Higher incidence in males

- Palmar fibromatosis 10-65% of the time.

- Peyronie's disease

- Epilepsy patients

- Patients of diabetes mellitus

There is also a suspected, although unproven, link between incidence and alcoholism, smoking, liver diseases, thyroid problems, and stressful work involving the feet.

NBCCS has an incidence of 1 in 50,000 to 150,000 with higher incidence in Australia. One aspect of NBCCS is that basal-cell carcinomas will occur on areas of the body which are not generally exposed to sunlight, such as the palms and soles of the feet and lesions may develop at the base of palmar and plantar pits.

One of the prime features of NBCCS is development of multiple BCCs at an early age, often in the teen years. Each person who has this syndrome is affected to a different degree, some having many more characteristics of the condition than others.

Disseminated superficial actinic porokeratosis (DSAP) is a non-contagious skin condition with apparent genetic origin in the SART3 gene. It most often presents in sun-exposed areas of the body. Some DSAP cases have been reported in patients with acute immune compromised situations, particularly in the elderly. For those with sun damaged skin, the lesions usually begin to appear in the patient's 20s and increase in number and visibility in the 40s or 50s. Commonly, though not always, the number and visibility of lesions is in direct proportion to the amount of sun damage to the affected area.

Lesions generally are characterized by an irregularly shaped thread-like ring that is usually the size of a pencil eraser, though lesions vary and may be half or double that size. The thread-like ring is very thin, much like fabric thread for sewing, and raised such that it is both palpable and visible. The interior of the ring may be rough like sandpaper, or smooth. The interior is often discolored, though colors vary from patient to patient. Lesions, due to their vascular nature, can also vary according to body temperature, environmental temperatures, and other external stimuli. The internal ring color is most often reddish, purplish, pink, or brown.

Some patients report itching and irritation associated with the condition, and many report no notable sensation. Although no known hormonal link has been found, DSAP occurs more commonly in women.

A study in 2000 was done on a Chinese family, in which a locus for a gene was located.

Pachyonychia congenita may be divided into these types:

- Pachyonychia congenita type I (also known as "Jadassohn–Lewandowsky syndrome") is an autosomal dominant keratoderma that principally involves the plantar surfaces, but also with nails changes that may be evident at birth, but more commonly develop within the first few months of life.

- Pachyonychia congenita type II (also known as "Jackson–Lawler pachyonychia congenita" and "Jackson–Sertoli syndrome") is an autosomal dominant keratoderma presenting with a limited focal plantar keratoderma that may be very minor, with nails changes that may be evident at birth, but more commonly develop within the first few months of life.

HPV is spread by direct and indirect contact from an infected host. Avoiding direct contact with infected surfaces such as communal changing rooms and shower floors and benches, avoiding sharing of shoes and socks and avoiding contact with warts on other parts of the body and on the bodies of others may help reduce the spread of infection. Infection is less common among adults than children.

As all warts are contagious, precautions should be taken to avoid spreading them. Recommendations include:

- cover them with an adhesive bandage while swimming

- wear flip-flops when using communal showers

- should not share towels.

Plantar warts are not prevented by inoculation with HPV vaccines because the warts are caused by different strains of HPV. Gardasil protects against strains 6, 11, 16, and 18, and Cervarix protects against 16 and 18, whereas plantar warts are caused by strains 1, 2, 4, and 63.

Reticulate acropigmentation of Kitamura consists of linear palmar pits and pigmented macules 1 to 4 mm in diameter on the volar and dorsal aspects of the hands and feet, usually inherited in an autosomal-dominant fashion.

Xanthoma disseminatum (also known as "Disseminated xanthosiderohistiocytosis" and "Montgomery syndrome") is a rare cutaneous condition that preferentially affects males in childhood, characterized by the insidious onset of small, yellow-red to brown papules and nodules that are discrete and disseminated.

It is a histiocytosis syndrome.

Porokeratosis is a specific disorder of keratinization that is characterized histologically by the presence of a cornoid lamella, a thin column of closely stacked, parakeratotic cells extending through the stratum corneum with a thin or absent granular layer.

Gardasil 6 is an HPV vaccine aimed at preventing cervical cancers and genital warts. Gardasil is designed to prevent infection with HPV types 16, 18, 6, and 11. HPV types 16 and 18 currently cause about 70% of cervical cancer cases, and also cause some vulvar, vaginal, penile and anal cancers. HPV types 6 and 11 are responsible for 90% of documented cases of genital warts.

Gardasil 9, approved in 2014 protects against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.

HPV vaccines do not currently protect against the virus strains responsible for plantar warts (verrucas).

Pachyonychia congenita follows an autosomal dominant pattern of inheritance, which means the defective gene is located on an autosome, and only one copy of the gene is required to inherit the disorder from a parent who has the disorder. On average, 50% of the offspring of an affected person will inherit the disorder, regardless of gender.

Occasionally, however, a solitary case can emerge in a family with no prior history of the disorder due to the occurrence of a new mutation (often referred to as a sporadic or spontaneous mutation).

Odonto–tricho-ungual–digital–palmar syndrome is an autosomal dominant skin condition with salient clinical features of natal teeth, trichodystrophy, prominent interdigital folds, simian-like hands with transverse palmar creases, and ungual digital dystrophy.

Epidermolytic palmoplantar keratoderma has been associated with keratin 9 and keratin 16.

Nonepidermolytic palmoplantar keratoderma has been associated with keratin 1 and keratin 16.

It is associated with various physiological as well as pathological changes, or may be a normal finding:

- Portal hypertension

- Chronic liver disease (including chronic hepatitis)

- Pregnancy

- Polycythemia

- Thyrotoxicosis

- Rheumatoid arthritis (especially in patients with polycythaemia)

- Eczema and psoriasis

- Deep telangiectasias

- Coxsackievirus A infection (Hand, foot and mouth disease)

- Rocky Mountain spotted fever

- Secondary syphilis

- Kawasaki disease

- Adverse drug reaction: palmoplantar erythrodysesthesia (acral erythema)

Because circulating levels of estrogen increase in both cirrhosis and pregnancy, estrogen was thought to be the cause for the increased vascularity. More recently, nitric oxide has been implicated in the pathogenesis of palmar erythema.

Hemihyperplasia–multiple lipomatosis syndrome is a cutaneous condition characterized by multiple lipomas in association with asymmetric (but non-progressive and non-distorting) overgrowth, cutaneous capillary malformations, and thickened plantar skin with prominent creases.

Warts are caused by the human papilloma virus (HPV). There are about 130 known types of human papilloma viruses. HPV infects the squamous epithelium, usually of the skin or genitals, but each HPV type is typically only able to infect a few specific areas on the body. Many HPV types can produce a benign growth, often called a "wart" or "papilloma", in the area they infect. Many of the more common HPV and wart types are listed below.

- Common warts – HPV types 2 and 4 (most common); also types 1, 3, 26, 29, and 57 and others.

- Cancers and genital dysplasia – "high-risk" HPV types are associated with cancers, notably cervical cancer, and can also cause some vulvar, vaginal, penile, anal and some oropharyngeal cancers. "Low-risk" types are associated with warts or other conditions.

- Plantar warts (myrmecia) – HPV type 1 (most common); also types 2, 3, 4, 27, 28, and 58 and others.

- Anogenital warts (condylomata acuminata or venereal warts) – HPV types 6 and 11 (most common); also types 42, 44 and others.

- Flat warts – HPV types 3, 10, and 28.

- Butcher's warts – HPV type 7.

- Heck's disease (Focal epithelial hyperplasia) – HPV types 13 and 32.

Normally, exfoliation is restricted to a particular area and normal skin will replace the exfoliated parts, so no treatment is needed. Since keratolysis exfoliativa is caused by friction, detergents, and solvents, these factors should be avoided. Creams, especially those with silicone and lactic acid are also helpful. In severe cases, photochemotherapy is an option.

Palmar erythema is reddening of the palms at the thenar and hypothenar eminences.

In most cases exfoliation resolves spontaneously and no lasting damage is seen. On the other hand, some patients experience cracking and even bleeding in extreme cases.

Infection-related cutaneous conditions may be caused by bacteria, fungi, yeast, viruses, or parasites.

Black heel and palm (also known as "Calcaneal petechiae," "Chromidrose plantaire," "Post-traumatic punctate intraepidermal hemorrhage," "Tache noir," and "Talon noir") is a skin condition characterized by a sudden shower of minute, black, punctate macules occurring most often on the posterior edge of the plantar surface of one or both heels.

A number of treatments have been found to be effective. A 2012 review of different treatments for skin warts in otherwise healthy people concluded modest benefit from salicylic acid and cryotherapy appears similar to salicylic acid.