Grover's may be suspected by its appearance, but since it has such a characteristic appearance under the microscope a shave skin or punch biopsy is often performed.

Patient presents with the following signs.

1. Hyperkeratotic papules present over the seborrheic area of the body.

2. V - shaped nicking present at the tip of the nails.

3. Red and white longitudinal nail lines.

Sweating causes lesions to form, but lesions aggravated by sweat usually return to "normal" fairly quicklyavoiding sweat is not a reason to avoid exercise. Minor outbreaks can be controlled with prescription strength topical cortisone creams. More severe eruptions usually clear up after treatment for one to three months with Accutane or tetracycline. If these fail or the outbreak is severe, PUVA phototherapy treatments, antifungal pills and cortisone injections are alternatives.

Some research has suggested a correlation of Grover's disease with mercury toxicity in which case Dimercaptosuccinic acid might help.

A 1992 study of 163 affected persons found that most patients had no other medical problems and most manage to lead a relatively normal life.

A doctor will take a thorough medical history, and may take blood tests as well as examining liver and kidney function. Improvements have also been reported from treating malnutrition associated with zinc deficiency and other minerals. Intracellular (red blood cell) assays are more sensitive than tests for plasma levels.

Morbidity and mortality range from both extremes as the significance correlate with the underlying systemic disease.

There seems to be beneficial responses to clindamycin therapy as the lesions regress. This leads to the hypothesis that microorganisms may be playing a role in the initial stages of Kyrle disease.

A family with Kyrle disease were examined which their skin lesions were benign. However, when three of the young adult members were closely examined, they had posterior subcapsular cataracts and two of those three developed multiple tiny yellow-brown anterior stromal corneal opacities. In order to determine if there is any correlation between Kyrle disease and the ocular observations, more cases of Kyrle disease are to be analyzed.

All in all, since Kyrle disease is relatively rare, more cases need to be studied and analyzed in order to understand the underlying pathogenesis and to improve the management of the disease.

The disease is most often diagnosed as an infant, when parents take their baby in for what appears to be bug bites. The bug bites are actually the clumps of mast cells. Doctors can confirm the presence of mast cells by rubbing the baby's skin. If hives appear, it most likely signifies the presence of urticaria pigmentosa.

Urbach–Wiethe disease is typically diagnosed by its clinical dermatological manifestations, particularly the beaded papules on the eyelids. Doctors can also test the hyaline material with a periodic acid-Schiff (PAS) staining, as the material colors strongly for this stain.

Immunohistochemical skin labeling for antibodies for the ECM1 protein as labeling has been shown to be reduced in the skin of those affected by Urbach–Wiethe disease. Staining with anti-type IV collagen antibodies or anti-type VII collagen antibodies reveals bright, thick bands at the dermoepidermal junction.

Non-contrast CT scans can image calcifications, but this is not typically used as a means of diagnosing the disease. This is partly due to the fact that not all Urbach-Wiethe patients exhibit calcifications, but also because similar lesions can be formed from other diseases such as herpes simplex and encephalitis. The discovery of mutations within the ECM1 gene has allowed the use of genetic testing to confirm initial clinical diagnoses of Urbach–Wiethe disease. It also allows doctors to better distinguish between Urbach–Wiethe disease and other similar diseases not caused by mutations in ECM1.

The diagnosis is normally made based upon the clinical appearance and history. Tissue biopsy is not usually indicated unless there are areas of ulceration or localized erythroplakia (red patches). The differential diagnosis is with other causes of white lesions (see leukoplakia for a more complete discussion). Specific conditions which can produce a similar appearance include Darier's disease, discoid lupus erythematosus, oral candidiasis, and oral lichen planus.

If a biopsy is taken, the histopathologic appearance is one of hyperkeratosis and acanthosis. There may be squamous metaplasia of excretory ducts, which results in the visible papules if the ducts become hyperplastic. Neutrophils may fill some ducts. It is characterized as a "fissured" or "dried mud" appearance from excess keratin production by cells. Dysplasia is rarely seen.

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.

There are no permanent cures for urticaria pigmentosa. However, treatments are possible. Most treatments for mastocytosis can be used to treat urticaria pigmentosa. Many common anti-allergy medications are useful because they reduce the mast cell's ability to react to histamine.

At least one clinical study suggested that nifedipine, a calcium channel blocker used to treat high blood pressure, may reduce mast cell degranulation in patients with urticaria pigmentosa. A 1984 study by Fairly et al. included a patient with symptomatic urticaria pigmentosa who responded to nifedipine at dose of 10 mg po tid. However, nifedipine has never been approved by the FDA for treatment of urticaria pigmentosa.

Another mast cell stabilizer Gastrocrom, a form of cromoglicic acid has also been used to reduce mast cell degranulation.

Onychauxis presents with thickened nails without deformity, and this simple thickening may be the result of trauma, acromegaly, Darier's disease, psoriasis, or pityriasis rubra pilaris, or, in some cases, hereditary.

When the appearance is caused by heat, the lesion is usually completely reversible within a few weeks if the smoking habit is stopped. This is the case even if the condition has been present for decades. Without stopping smoking, spontaneous remission of the lesion is unlikely. If the lesion persists despite stopping smoking, this is usually then considered to be a true leukoplakia rather than a reactionary keratotis, and may trigger the decision to carry out a biopsy to confirm the diagnosis. Since this condition almost always develops in the setting of long term heavy smoking, it usually indicates the need for regular observation for cancers associated with smoking, e.g. lung cancer.

Urbach–Wiethe disease is typically not a life-threatening condition. The life expectancy of these patients is normal as long as the potential side effects of thickening mucosa, such as respiratory obstruction, are properly addressed. Although this may require a tracheostomy or carbon dioxide laser surgery, such steps can help ensure that individuals with Urbach–Wiethe disease are able to live a full life. Oral dimethyl sulfoxide (DMSO) has been shown to reduce skin lesions, helping to minimize discomfort for these individuals.

Common clinical signs and symptoms of Whipple's disease include diarrhea, steatorrhea, abdominal pain, weight loss, migratory arthropathy, fever, and neurological symptoms. Weight loss and diarrhea are the most common symptoms that lead to identification of the process, but may be preceded by chronic, unexplained, relapsing episodes of non-destructive seronegative arthritis, often of large joints.

Diagnosis is made by biopsy, usually by duodenal endoscopy, which reveals PAS-positive macrophages in the lamina propria containing non-acid-fast gram-positive bacilli. Immunohistochemical staining for antibodies against "T. whipplei" has been used to detect the organism in a variety of tissues, and a PCR-based assay is also available. PCR can be confirmatory if performed on blood, vitreous fluid, synovial fluid, heart valves, or cerebrospinal fluid. PCR of saliva, gastric or intestinal fluid, and stool specimens is highly sensitive, but not specific enough, indicating that healthy individuals can also harbor the causative bacterium without the manifestation of Whipple's disease, but that a negative PCR is most likely indicative of a healthy individual.

Endoscopy of the duodenum and jejunum can reveal pale yellow shaggy mucosa with erythematous eroded patches in patients with classic intestinal Whipple's disease, and small bowel X-rays may show some thickened folds. Other pathological findings may include enlarged mesenteric lymph nodes, hypercellularity of lamina propria with "foamy macrophages", and a concurrent decreased number of lymphocytes and plasma cells, per high power field view of the biopsy.

A D-Xylose test can be performed, which is where the patient will consume 4.5g of D-xylose, a sugar, by mouth. The urine excretion of D-Xylose is then measured after 5 hours. The majority of D-Xylose is absorbed normally, and should be found in the urine. If the D-Xylose is found to be low in the urine, this suggests an intestinal malabsorption problem such as bacterial overgrowth of the proximal small intestine, Whipple's Disease, or an autoimmune with diseases such as Celiac's Disease (allergy to gluten) or Crohn's Disease (autoimmune disease affecting the small intestine). With empiric antibiotic treatment after an initial positive D-Xylose test, and if a follow-up D-Xylose test is positive (decreased urine excretion) after antibiotic therapy, then this would signify it is not bacterial overgrowth of the proximal small intestine. Since Whipple's disease is so rare, a follow-up positive D-Xylose test more likely indicates a non-infectious etiology and more likely an autoimmune etiology. Clinical correlation is recommended to rule out Whipple's disease.

It is important to include that the lesion is associated with another cancer. A biopsy will establish the diagnosis. The histology of the lesion is the same as for Paget's disease of the breast.

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.

There is no specific pathological testing or technique available for the diagnosis of the disease, although the International Study Group criteria for the disease are highly sensitive and specific, involving clinical criteria and a pathergy test. Behçet's disease has a high degree of resemblance to diseases that cause mucocutaneous lesions such as "Herpes simplex" labialis, and therefore clinical suspicion should be maintained until all the common causes of oral lesions are ruled out from the differential diagnosis.

Visual acuity, or color vision loss with concurrent mucocutaneous lesions or systemic Behçet's disease symptoms should raise suspicion of optic nerve involvement in Behçet's disease and prompt a work-up for Behçet's disease if not previously diagnosed in addition to an ocular work-up. Diagnosis of Behçet's disease is based on clinical findings including oral and genital ulcers, skin lesions such as erythema nodosum, acne, or folliculitis, ocular inflammatory findings and a pathergy reaction. Inflammatory markers such ESR, and CRP may be elevated. A complete ophthalmic examination may include a slit lamp examination, optical coherence tomography to detect nerve loss, visual field examinations, fundoscopic examination to assess optic disc atrophy and retinal disease, fundoscopic angiography, and visual evoked potentials, which may demonstrate increased latency. Optic nerve enhancement may be identified on Magnetic Resonance Imaging (MRI) in some patients with acute optic neuropathy. However, a normal study does not rule out optic neuropathy. Cerebrospinal fluid (CSF) analysis may demonstrate elevated protein level with or without pleocytosis. Imaging including angiography may be indicated to identify dural venous sinus thrombosis as a cause of intracranial hypertension and optic atrophy.

Extramammary Paget's disease is usually seen in isolation and is associated with an underlying invasive malignancy about 12% of the time. It is associated with an underlying adnexal malignancy about 24% of the time. Paget's disease of the breast is almost always associated with an underlying invasive malignancy, i.e. breast cancer (e.g. mammary ductal carcinoma).

Treatment is with penicillin, ampicillin, tetracycline, or co-trimoxazole for one to two years. Any treatment lasting less than a year has an approximate relapse rate of 40%. Recent expert opinion is that Whipple's disease should be treated with doxycycline with hydroxychloroquine for 12 to 18 months. Sulfonamides (sulfadiazine or sulfamethoxazole) may be added for treatment of neurological symptoms.

According to the International Study Group guidelines, for a patient to be diagnosed with Behçet's disease, the patient must have oral (aphthous) ulcers (any shape, size, or number at least 3 times in any 12 months period) along with 2 out of the following 4 "hallmark" symptoms:

- eye inflammation (iritis, uveitis, retinal vasculitis, cells in the vitreous)

- genital ulcers (including anal ulcers and spots in the genital region and swollen testicles or epididymitis in men)

- pathergy reaction (papule >2 mm dia. 24–48 hrs or more after needle-prick). The pathergy test has a specificity of 95 percent to 100 percent, but the results are often negative in American and European patients

- skin lesions (papulo-pustules, folliculitis, erythema nodosum, acne in post-adolescents not on corticosteroids)

Despite the inclusive criteria set forth by the International Study Group, there are cases where not all the criteria can be met and therefore a diagnosis cannot readily be made. There is however a set of clinical findings that a physician can rely upon in making a tentative diagnosis of the disease; essentially Behçet's disease does not always follow the International Study Group guidelines and so a high degree of suspicion for a patient who presents having any number of the following findings is necessary:

- arthritis/arthralgia

- cardio-vascular problems of an inflammatory origin

- changes of , psychoses

- deep vein thrombosis

- epididymitis

- extreme exhaustion

- inflammatory problems in chest and lungs

- mouth ulcers

- nervous system symptoms

- problems with hearing or balance

- stomach or bowel inflammation

- superficial thrombophlebitis

- any other members of the family with a diagnosis of Behçet's disease.

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.

Acrokeratosis verruciformis (also known as "Acrokeratosis verruciformis of Hopf" is a rare autosomal dominant disorder appearing at birth or in early childhood, characterized by skin lesions that are small, verrucous, flat papules resembling warts along with palmoplantar punctate keratoses and pits. However sporadic forms, whose less than 10 cases have been reported, presents at a later age, usually after the first decade and generally lack palmoplantar keratoses.

Whether acrokeratosis verruciformis and Darier disease are related or distinct entities has been controversial, like Darier's disease, it is associated with defects in the ATP2A2 gene. however the specific mutations found in the ATP2A2 gene in acrokeratosis verruciformis have never been found in Darier's disease.

The diagnosis is clinical, not based upon serology. At least seven sets of diagnostic criteria have been devised, however the Yamaguchi criteria have the highest sensitivity. Diagnosis requires at least five features, with at least two of these being major diagnostic criteria.