Hidrotic ectodermal dysplasia 2, or Clouston syndrome (referred to as HED2 throughout this entry) is characterized by partial or total alopecia, dystrophy of the nails, hyperpigmentation of the skin (especially over the joints), and clubbing of the fingers. Sparse scalp hair and dysplastic nails are seen early in life. In infancy, scalp hair is wiry, brittle, patchy, and pale; progressive hair loss may lead to total alopecia by puberty. The nails may be milky white in early childhood; they gradually become dystrophic, thick, and distally separated from the nail bed. Palmoplantar keratoderma may develop during childhood and increases in severity with age. The clinical manifestations are highly variable even within the same family.

Hypermelanotic nevi must be differentiated from other types of pigmented skin lesions, including:

- Lentigo simplex

- Solar lentigo

- Café au lait macule

- Ink-spot lentigo

- Mucosal melanotic macule

- Mongolian spot (dermal melanocytosis)

The term nevus is included in the names of multiple dermatologic syndromes:

- Basal cell nevus syndrome

- Blue rubber bleb nevus syndrome

- Dysplastic nevus syndrome

- Epidermal nevus syndrome

- Linear nevus sebaceous syndrome

Onychomatricoma is a cutaneous condition characterized by a distinctive tumor of the nail matrix.

This nail disease can mimic many nail problems and should be examined and biopsied by a dermatologist. In particular, a main concern is the malignant and destructive potential that may exist.

Neoplasms of the nailbed may often present with paronychia, ingrown nail, onycholysis, pyogenic granuloma, nail-plate dystrophy, longitudinal erythronychia, bleeding, and discolorations. There are various benign and malignant neoplasms that may occur in or overlying the nail matrix and in the nailbed, and symptoms may include pain, itching, and throbbing.

Benign tumors of the nails include verruca, pyogenic granuloma, fibromas, nevus cell nevi, myxoid cysts, angiofibromas (Koenen tumors), and epidermoid cysts.

Squamous cell carcinoma of the nailbed is uncommon, and often mistaken for a pyogenic granuloma initially. Subungual melanoma is frequently diagnosed late in the course of growth.

Melanonychia is a black or brown pigmentation of the normal nail plate, and may be present as a normal finding on many digits in African-Americans, as a result of trauma, systemic disease, or medications, or as a postinflammatory event from such localized events as lichen planus or fixed drug eruption.

There are two types, longitudinal and transverse melanonychia. Longitudinal melanonychia may be a sign of subungual melanoma (acral lentiginous melanoma), although there are other diagnoses such as chronic paronychia, onychomycosis, subungual hematoma, pyogenic granuloma, glomus tumour, subungual verruca, mucous cyst, subungual fibroma, keratoacanthoma, carcinoma of the nail bed, and subungual exostosis.

Dysplastic nails are a cutaneous condition, and may be a subtle finding of ridging, flaking, or poor growth of the nails, or more diffuse with nearly complete loss of nails. This condition may be seen in a number of syndromes, including Dyskeratosis congenita and Nail–patella syndrome.

According to the American Academy of Dermatology, the most common types of moles are skin tags, raised moles and flat moles. Benign moles are usually brown, tan, pink or black (especially on dark-colored skin). They are circular or oval and are usually small (commonly between 1–3 mm), though some can be larger than the size of a typical pencil eraser (>5 mm). Some moles produce dark, coarse hair. Common mole hair removal procedures include plucking, cosmetic waxing, electrolysis, threading and cauterization.

Pure hair-nail type ectodermal dysplasia is a genetic mutation in the "hair matrix and cuticle keratin KRTHB5 gene" that causes ectodermal dysplasia of hair and nail type. Manifestations of this disorder include onychodystrophy and severe hypotrichosis. It represents as an autosomal dominant trait.

The melanocytes left behind in the wound regrow in an abnormal pattern. Rather than the even and regular lace like network, the pigments tends to grow in streaks of varying width within the scar. This is often accompanied by scarring, inflammation, and blood vessel changes – giving both the clinical and histologic impression of a melanoma or a severe dysplastic nevus. When the patient is reexamined years later without the assistance of the original biopsy report, the physician will often require the removal of the scar with the recurrent nevus to assure that a melanoma is not missed.

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.

HED2 is suspected after infancy on the basis of physical features in most affected individuals. GJB6 is the only gene known to be associated with HED2. Targeted mutation analysis for the four most common GJB6 mutations is available on a clinical basis and detects mutations in approximately 100% of affected individuals. Sequence analysis is also available on a clinical basis for those in whom none of the four known mutations is identified.

Some sources equate the term mole with "melanocytic nevus". Other sources reserve the term "mole" for other purposes such as the animal of the same name.

Melanocytic nevi represent a family of lesions. The most common variants are:

- Location:

- Junctional nevus: the nevus cells are located along the junction of the epidermis and the underlying dermis. A junctional nevus is flat and brown to black.

- Compound nevus: a mixture of junctional and intradermal proliferation. Compound nevi are slightly raised and brown to black. Beauty marks are usually compound nevi of either the acquired variety or congenital variety.

- Intradermal nevus: the nevus cells are located in the dermis only. Intradermal nevi are raised; most are flesh-colored (not pigmented).

- Dysplastic nevus (nevus of Clark): usually a compound nevus with cellular and architectural dysplasia. Like typical moles, dysplastic nevi can be flat or raised. While they vary in size, dysplastic nevi are typically larger than normal moles and tend to have irregular borders and irregular coloration. Hence, they resemble melanoma, appear worrisome, and are often removed to clarify the diagnosis. Dysplastic nevi are markers of risk when they are numerous (atypical mole syndrome). According to the National Cancer Institute (NIH), doctors believe that, when part of a series or syndrome of multiple moles, dysplastic nevi are more likely than ordinary moles to develop into the most virulent type of skin cancer called melanoma.

- Blue nevus: It is blue in color as its melanocytes are very deep in the skin. The nevus cells are spindle shaped and scattered in deep layers of the dermis. The covering epidermis is normal.

- Spitz nevus: a distinct variant of intradermal nevus, usually in a child. They are raised and reddish (non-pigmented). A pigmented variant, called the 'nevus of Reed', typically appears on the leg of young women.

- Acquired nevus: Any melanocytic nevus that is not a congenital nevus or not present at birth or near birth. This includes junctional, compound and intradermal nevus.

- Congenital nevus: Small to large nevus present at or near time of birth. Small ones have low potential for forming melanomas, however the risk increases with size, as in the giant pigmented nevus.

- Giant pigmented nevus: these large, pigmented, often hairy congenital nevi. They are important because melanoma may occasionally (10 to 15%) appear in them.

- Intramucosal nevus: junctional nevus of the mucosa of the mouth or genital areas. In the mouth, they are found most frequently on the hard palate.

- Nevus of Ito and nevus of Ota: congenital, flat brownish lesions on the face or shoulder.

- Mongolian spot: congenital large, deep, bluish discoloration which generally disappears by puberty. It is named for its association with East Asian ethnic groups but is not limited to them.

- Recurrent nevus: Any incompletely removed nevus with residual melanocytes left in the surgical wound. It creates a dilemma for the patient and physician, as these scars cannot be distinguished from a melanoma.

Pterygium inversum unguis (also known as "Pterygium inversus unguis," and "Ventral pterygium") is characterized by the adherence of the distal portion of the nailbed to the ventral surface of the nail plate. The condition may be present at birth or acquired, and may cause pain with manipulation of small objects, typing, and close manicuring of the nail.

"Onycholysis" is from "onycho-", from Ancient Greek ὄνυξ "ónuks", meaning "nail", and Ancient Greek λύσις "lúsis", meaning "a loosening".

Also known as "true" leukonychia, this is the most common form of leukonychia, in which small white spots appear on the nails. Picking and biting of the nails are a prominent cause in young children and nail biters. Besides parakeratosis, air that is trapped between the cells may also cause this appearance. It is also caused by trauma. In most cases, when white spots appear on a single or a couple of fingers or toes, the most common cause is injury to the base (matrix) of the nail. When this is the case, white spots disappear after around eight months, which is the amount of time necessary for nails to regrow completely. The pattern and number of spots may change as the nail grows.

Longitudinal leukonychia is far less common and features smaller 1mm white longitudinal lines visible under the nail plate. It may be associated with Darier's disease.

In racquet nails (also known as brachyonychia, nail en raquette, and racquet thumb), the nail plate is flattened, the end of the thumb is widened and flattened, and the distal phalanx is abnormally short. In racquet nails, the width of the nail bed and nail plate is greater than their length. The condition is painless and asymptomatic.

Racquet nails usually occur on one or both thumbs, but may appear on all fingers and toes. It may be genetic, inherited as an autosomal-dominant trait, or acquired. Genetic disorders associated with racquet nail include Larsen syndrome, Brooke–Spiegler syndrome, Rubinstein–Taybi syndrome, Hajdu–Cheney syndrome, cartilage–hair hypoplasia, pycnodysostosis, acrodysostosis, and brachydactylia.

Acquired racquet nail is associated with acroosteolysis and psoriatic arthropathy. Acquired racquet nail may also be diagnostic of bone resorption in hyperparathyroidism.

Racquet nail often presents with other nail conditions such as onycholysis, koilonychia, pachyonychia, Muehrcke's lines, leuconychia, and half-and-half nails. Cosmetic surgery can be used to improve the appearance of the nails.

Pseudomelanoma (also known as a "recurrent melanocytic nevus", and "recurrent nevus") is a cutaneous condition in which melantic skin lesions clinically resemble a superficial spreading melanoma at the site of a recent shave removal of a melanocytic nevus.

Onycholysis is a common medical condition characterized by the painless detachment of the nail from the nail bed, usually starting at the tip and/or sides. On the hands, it occurs particularly on the ring finger but can occur on any of the fingernails. It may also happen to toenails.

Onycholysis can occur in many conditions, including psoriasis. In thyrotoxicosis it is thought to be due to sympathetic overactivity. It may also be seen in infections or trauma.

Bowenoid papulosis is a cutaneous condition characterized by the presence of pigmented verrucous papules on the body of the penis. They are associated with human papillomavirus, the causative agent of genital warts. The lesions have a typical dysplastic histology and are generally considered benign, although a small percentage will develop malignant characteristics.

It is considered as a pre-malignant condition. Other terms used to describe the condition are: Erythroplasia of Queyrat, Squamous cell carcinoma in situ and Bowen’s disease. The term "Bowenoid papulosis" was coined in 1977 by Kopf and Bart and is named after dermatologist John Templeton Bowen.

The term “intraepithelial neoplasia” defines a premalignant intraepithelial change.

On the vulva it is termed VIN (vulvar or vulval intraepithelial neoplasia); on the penis, PIN (penile intraepithelial neoplasia); and on or around the anus, AIN (anal intraepithelial neoplasia). The terminology has been very confusing and it is now recommended that the terms Bowen’s disease, erythroplasia of Queyrat, and bowenoid papulosis should not be used for lesions in the anogenital area. However, dermatologists still recognize a distinct clinical variant, bowenoid papulosis, characterized by discrete papules in a younger age group and a tendency for spontaneous regression. Additionally, some authorities believe that erythroplasia of Queyrat and Bowen’s disease remain useful terms in men.

Longitudinal erythronychia presents with longitudinal red bands in the nail plate that commence in the matrix and extend to the point of separation of the nail plate and nailbed, and may occur on multiple nails with inflammatory conditions such as lichen planus or Darier's disease.

Often, this disease evolves from a precursor lesion, usually a dysplastic nevus. Otherwise it arises in previously normal skin. A prolonged radial growth phase, where the lesion remains thin, may eventually be followed by a vertical growth phase where the lesion becomes thick and nodular. As the risk of spread varies with the thickness, early SSM is more frequently cured than late nodular melanoma.

The microscopic hallmarks are:

- Large melanocytic cells with nest formation along the dermo-epidermal junction.

- Invasion of the upper epidermis in a pagetoid fashion (discohesive single cell growth).

- The pattern of rete ridges is often effaced.

- Invasion of the dermis by atypical, pleomorphic melanocytes

- Absence of the 'maturation' typical of naevus cells

- Mitoses

Drug-induced nail changes are caused by drug administration which may result in a large number of nail abnormalities, usually with multiple nails being affected at the same time.

They tend to be painful due to the pressure applied to the nail bed and plate. They can involve destruction of the nail bed. These lesions are not true osteochondromas, rather it is a reactive cartilage metaplasia. The reason it occurs on the dorsal aspect is because the periosteum is loose dorsally but very tightly adherent volarly.

Subungal malignant melanomas can also occur in canines.

They are distinct from subungual osteochondroma.