Since the common pathogens involved with impetigo are bacteria naturally found on the skin, most prevention (especially in children), is targeted towards appropriate hygiene, wound cleaning, and minimizing scratching (i.e. by keeping nails trimmed and short). Avoiding close contact and sharing of items such as towels with potentially infected individuals is also recommended.

The diagnosis of SSSS is made clinically. This is sometimes confirmed by isolation of "S. aureus" from blood, mucous membranes, or skin biopsy; however, these are often negative. Skin biopsy may show separation of the superficial layer of the epidermis (intraepidermal separation), differentiating SSSS from TEN, wherein the separation occurs at the dermo-epidermal junction (subepidermal separation). SSSS may be difficult to distinguish from toxic epidermal necrolysis and pustular psoriasis.

Other conditions that can result in symptoms similar to the common form include contact dermatitis, herpes simplex virus, discoid lupus, and scabies.

Other conditions that can result in symptoms similar to the blistering form include other bullous skin diseases, burns, and necrotizing fasciitis.

Histology of normal epidermal tissue through H&E. Composed of four layers, Stratum basale, Stratum spinosum, Stratum granulosum, and Stratum corneum. Normal pathology of the skin, displaying the dermis which is attached to underlying loose connective tissue which subsequently contains primary adipose tissue.

Histology of Bullous Impetigo through H&E. The cleavage plane can be found either subcorneal or within the upper stratum granulosum. The roof of the pustule is parakeratotic stratum cirneum, and the floor is formed of keratinocytes, which may or may not be acantholytic. Neutrophils begin to fill the pustule. Toxins are produced by S. "aureus" and target desmoglein, which is a desmosomal cell-cell adhesion molecule that is found in the upper levels of the epidermis. Stratum Lucidum is no longer present and can be seen infiltrated with inflammatory cells. This correlates with the subcorneal localization of the bullae.

Impetigo is usually diagnosed based on its appearance. It generally appears as honey-colored scabs formed from dried serum, and is often found on the arms, legs, or face. If a visual diagnosis is unclear a culture may be done to test for resistant bacteria.

Dempster-Shafer Theory is used for detecting skin infection and displaying the result of the detection process.

At the start of each wrestling meet, trained referees examine the skin of all wrestlers before any participation. During this examination, male wrestlers are to wear shorts; female wrestlers are only permitted to wear shorts and a sports bra. Open wounds and infectious skin conditions that cannot be adequately protected are considered grounds for disqualification from both practice and competition. This essentially means that the skin condition has been deemed as non-infectious and adequately medicated, covered with a tight wrapping and proper ointment. In addition, the wrestler must have developed no new lesions in the 72 hours before the examination. Wrestlers who are undergoing treatment for a communicable skin disease at the time of the meet or tournament shall provide written documentation to that effect from a physician. This documentation should include the wrestler’s diagnosis, culture results (if possible), date and time therapy began, and the exact names of medication for treatment. These measures aren’t always successful, and the infection is sometimes spread regardless.

A boil may clear up on its own without bursting, but more often it will need to be opened and drained. This will usually happen spontaneously within two weeks. Regular application of a warm moist compress, both before and after a boil opens, can help speed healing. The area must be kept clean, hands washed after touching it, and any dressings disposed of carefully, in order to avoid spreading the bacteria. A doctor may cut open or "lance" a boil to allow it to drain, but squeezing or cutting should not be attempted at home, as this may further spread the infection. Antibiotic therapy may be recommended for large or recurrent boils or those that occur in sensitive areas (such as the groin, breasts, armpits, around or in the nostrils, or in the ear). Antibiotics should not be used for longer than one month, with at least two months (preferably longer) between uses, otherwise it will lose its effectiveness. If the patient has chronic (more than two years) boils, removal by plastic surgery may be indicated.

Furuncles at risk of leading to serious complications should be incised and drained if antibiotics or steroid injections are not effective. These include furuncles that are unusually large, last longer than two weeks, or occur in the middle of the face or near the spine. Fever and chills are signs of sepsis and indicate immediate treatment is needed.

Staphylococcus aureus has the ability to acquire antimicrobial resistance easily, making treatment difficult. Knowledge of the antimicrobial resistance of "S. aureus" is important in the selection of antimicrobials for treatment.

The prognosis of SSSS in children is excellent, with complete resolution within 10 days of treatment, and without significant scarring. However, SSSS must be differentiated carefully from toxic epidermal necrolysis, which carries a poor prognosis. The prognosis in adults is generally much worse, and depends upon various factors such as time to treatment, host immunity, and comorbidities.

Because it is a rare disease, diagnosis is often complicated and takes a long time. Early in the disease patients may have erosions in the mouth or blisters on the skin. These blisters can be itchy or painful. Theoretically, the blisters should demonstrate a positive Nikolsky's sign, in which the skin sloughs off from slight rubbing, but this is not always reliable. The gold standard for diagnosis is a punch biopsy from the area around the lesion that is examined by direct immunofluorescent staining, in which cells are acantholytic, that is, lacking the normal intercellular connections that hold them together. These can also be seen on a Tzanck smear. These cells are basically rounded, nucleated keratinocytes formed due to antibody mediated damage to cell adhesion protein desmoglein.

Pemphigus vulgaris is easily confused with impetigo and candidiasis. IgG4 is considered pathogenic. The diagnosis can be confirmed by testing for the infections that cause these other conditions, and by a lack of response to antibiotic treatment.

Unlike most other manifestations of Tinea dermatophyte infections, Kerion is not sufficiently treated with topical antifungals and requires systemic therapy. Typical therapy consists of oral antifungals, such as griseofulvin or terbinafine, for a sustained duration of at least 6-8 weeks depending on severity. Successful treatment of kerion often requires empiric bacterial antibiotics given the high prevalence of secondary bacterial infection.

According to the NCAA Wrestling Rules and Interpretations, used by all high schools in the United States: "Infection control measures, or measures that seek to prevent the spread of disease, should be utilized to reduce the risks of disease transmission. Efforts should be made to improve wrestler hygiene practices, to utilize recommended procedures for cleaning and disinfection of surfaces, and to handle blood and other bodily fluids appropriately. Suggested measures include: promotion of hand hygiene practices; educating athletes not to pick, squeeze, or scratch skin lesions; encouraging athletes to shower after activity; educating athletes not to share protective gear, towels, razors or water bottles; ensuring recommended procedures for cleaning and disinfection of wrestling mats, all athletic equipment, locker rooms, and whirlpool tubs are closely followed; and verifying clean up of blood and other potentially infectious materials." More ways of prevention include wearing long sleeve shirts and sweatpants to limit

the amount of skin to skin contact. A wrestler should also not share their

equipment with other teammates and should regularly check their skin for any lesions or other signs of outbreaks. Body wipes are also common to see Coaches must also enforce the disinfecting and sanitary cleansing of the wrestling mats and other practice areas. This can greatly limit the spread of skin infections that can infect an individual indirectly.

One high school wrestling coach from Southern California described his methods of prevention using three simple procedures. “Keep the mats [clean]…you’ve got to bleach and mop them every day before practice. Along the same lines, gear should also be washed regularly, especially headgear…Most importantly, the wrestlers need to shower immediately after practices. If one kid doesn’t, and he gets [infected], it can spread to everyone else on the team within a week. I’ve had it happen before, to the point where some schools won’t allow any of our guys to wrestle in a meet. When this happens, it’s a huge blow to the school’s record and reputation. In the future, we are less likely to be invited to exclusive tournaments in the coming year.”

Whilst usually a straightforward diagnosis at times the appearance can raise concern that the rash could be due to herpes simplex; however, the latter generally has a more clustered and vesicular appearance.

In uncertain cases, a scraping of a lesion can be taken and the fluid examined under the microscope. Herpes lesions will have a positive direct fluorescent antibody test. The fluid from erythema toxicum lesions will show many eosinophils. If blood samples are taken, they may show a high level of circulating eosinophils; however, this is not usually required.

Differential diagnosis may include Herpes simplex virus, Impetigo, neonatal sepsis, Listeria and Varicella (chicken pox).

Diagnosis is based on two biopsies of the skin, one submitted for routine H&E staining and one for immunofluorescence studies.

Diagnostic techniques:

- antibodies (IgG) precipitates complement (C3) in the lamina lucida of the basement membrane.

- Circulating auto-antibodies to BP-1 antigen (located in hemidesmosome). 50% have BP-2.

- Positive Nikolsky sign.

- IgG, C3 deposition at BM creating smooth line in immunofluorescent analysis.

Patients with high concentration of antibodies show intercellular, intraepidermal antibodies as well as along the dermoepidermal junction. Patients with low concentration of antibodies only present with them inside the cells (intercellular).

If the results are negative, perform the additional assays regardless. Cases have been confirmed that reported with initial negative DIF and IDIF tests.

Immunoprecipitation, immunoblotting and enzyme-link immunosorbent assay (ELISA)

Poot et al. 2013 determined that immunoprecipitation for antibodies against envoplakin and periplakin or alpha2-macroglobulin-like–1 is the most sensitive test. However, alpha2-macroglobulin-like-1 can also be detected in patients with toxic epidermal necrosis.

Often a diagnosis of exclusion, skin biopsy shows a neutrophillic inflammatory infiltrate.

Other causes include poor immune system function such as from HIV/AIDS, diabetes, malnutrition, or alcoholism. Poor hygiene and obesity have also been linked. It may occur following antibiotic use due to the development of resistance to the antibiotics used. An associated skin disease favors recurrence. This may be attributed to the persistent colonization of abnormal skin with "S. aureus" strains, such as is the case in persons with atopic dermatitis.

Boils which recur under the arm, breast or in the groin area may be associated with hidradenitis suppurativa (HS).

To help with cradle cap, parents can gently massage their baby's scalp with their fingers or a soft brush to loosen the scales. They may want to shampoo the baby's hair more frequently (no more than once a day), and after shampooing gently brush the baby's scalp with a soft brush or a terrycloth towel. Oil remedies can be used by rubbing a small amount of pure, plant-derived oil (coconut oil, pure olive oil, almond oil) on the baby's scalp and leaving it on for 15 minutes. After 15 minutes, gently comb out the flakes with a fine tooth comb or brush. Be sure to wash out all of the oil to avoid making the cradle cap worse.

For infants: in cases that are related to fungal infection, such as Tinea capitis, doctors may recommend a treatment application of clotrimazole (commonly prescribed for jock itch or athlete's foot) or miconazole (commonly prescribed for vaginal yeast infections).

For toddlers: doctors may recommend a treatment with a mild dandruff shampoo such as Selsun Blue or Neutrogena T-gel, even though the treatment may cause initial additional scalp irritation. A doctor may instead prescribe an antifungal soap such as ketoconazole (2%) shampoo, which can work in a single treatment and shows significantly less irritation than over-the-counter shampoos such as selenium disulfide shampoos, but no adequate and controlled study has been conducted for pediatric use as of 2010.

For adults: see the article on seborrheic dermatitis (the adult version of cradle cap).

Lichen planus has a unique microscopic appearance that is similar between cutaneous, mucosal and oral. A Periodic acid-Schiff stain of the biopsy may be used to visualise the specimen. Histological features seen include:

- thickening of the stratum corneum both with nuclei present (parakeratosis) and without (orthokeratosis). Parakeratosis is more common in oral variants of lichen planus.

- thickening of the stratum granulosum

- thickening of the stratum spinosum (acanthosis) with formation of colloid bodies (also known as Civatte bodies, Sabouraud bodies) that may stretch down to the lamina propria.

- liquefactive degeneration of the stratum basale, with separation from the underlying lamina propria, as a result of desmosome loss, creating small spaces (Max Joseph spaces).

- Infiltration of T cells in a band-like pattern into the dermis "hugging" the basal layer.

- Development of a "saw-tooth" appearance of the rete pegs, which is much more common in non-oral forms of lichen planus.

It is estimated that 2—3 percent of hospitalised patients are affected by a drug eruption, and that serious drug eruptions occur in around 1 in 1000 patients.

The differential diagnosis for OLP includes:

- Other oral vesiculo-ulcerative conditions such as Pemphigus vulgaris and Benign mucous membrane pemphigoid

- Lupus erythematosus, with lesions more commonly occur on the palate and appear as centrally ulcerated or erythematous with radiating white striae. In contrast, OLP and lichenoid reactions rarely occur on the palate, and the striae are randomly arranged rather than radial.

- Chronic ulcerative stomatitis

- Frictional keratosis and Morsicatio buccarum (chronic cheek biting)

- Oral leukoplakia

- Oral candidiasis

Research into using genetically modified T-cells to treat pemphigus vulgaris in mice was reported in 2016. Rituximab indiscriminately attacks all B cells, which reduces the body's ability to control infections. In the experimental treatment, human T cells are genetically engineered to recognize only those B cells that produce antibodies to desmoglein 3.

Because the eruption is transient and self-limiting, no treatment is indicated.