Erythema nodosum is diagnosed clinically. A biopsy can be taken and examined microscopically to confirm an uncertain diagnosis. Microscopic examination usually reveals a neutrophilic infiltrate surrounding capillaries that results in septal thickening, with fibrotic changes in the fat around blood vessels. A characteristic microscopic finding is radial granulomas, well-defined nodular aggregates of histiocytes surrounding a stellate cleft.

Additional evaluation should be performed to determine the underlying cause of erythema nodosum. This may include a full blood count, erythrocyte sedimentation rate (ESR), antistreptolysin-O (ASO) titer and throat culture, urinalysis, intradermal tuberculin test, and a chest x-ray. The ESR is typically high, the C-reactive protein elevated, and the blood showing an increase in white blood cells.

The ESR is initially very high, and falls as the nodules of erythema nodosum. The ASO titer is high in cases associated with a streptococcal throat infection. A chest X-ray should be performed to rule out pulmonary diseases, in particular sarcoidosis and Löfgren syndrome.

A skin biopsy can be performed to test for EAC; tests should be performed to rule out other possible diseases such as: pityriasis rosea, tinea corporis, psoriasis, nummular eczema, atopic dermatitis, drug reaction, erythema migrans and other rashes.

No treatment is usually needed as they usually go away anywhere from months to years. The lesions may last from anywhere between 4 weeks to 34 years with an average duration of 11 months. If caused by an underlying disease or malignancy, then treating and removing the disease or malignancy will stop the lesions. It usually doesn't require treatment, but topical corticosteroids may be helpful in reducing redness, swelling and itchiness.

Some supported and not supported methods of having an effect on EAC include:

- Photosensitive so it can be moved/reduced with appropriate sunlight.

- Vitamin D

- Immune system - hence it will increase in size/number when the immune system is low or overloaded.

- Hormone Drugs

- Disulone

- Stress reduction

- Topical calcipotriol - a topical vitamin D derivative has been known to be beneficial

Discontinuing contact with the heat source is the initial treatment of erythema ab igne. If the area is only mildly affected with slight redness, the condition may resolve itself in a few months. If the condition is severe and the skin pigmented and atrophic, resolution is unlikely. In this case, there is a possibility that a squamous cell carcinoma or a neuroendocrine carcinoma such as a Merkel cell carcinoma may form. If there is a persistent sore that does not heal or a growing lump within the rash, a skin biopsy should be performed to rule out the possibility of skin cancer. If the erythema ab igne lesions demonstrate pre-cancerous changes, the use of 5-fluorouracil cream has been recommended. Abnormally pigmented skin may persist for years. Treatment with topical tretinoin or laser may improve the appearance.

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).

In all cases of suspected NEH, a skin biopsy should be performed, because the clinical symptoms are non specific, but the histopathological findings on the biopsy are specific. The biopsy shows characteristic changes of the eccrine glands, the major sweat glands of the body.

In NEH, eccrine gland necrosis, and neutrophils surroundings the eccrine glands, are typical findings on biopsy. If the chemotherapy has recently been administered, chemotherapy induced neutropenia may be present, and, as a result, the neutrophils may be absent. But the other characteristic finding, i.e. eccrine gland necrosis, can still be seen. A vacuolar interface dermatitis also is visible in glands and ducts, along with necrosis of the lining cells.

In addition, in patients receiving chemotherapy, keratinocyte atypia can be seen.

Erythema nodosum is self-limiting and usually resolves itself within 3–6 weeks. A recurring form does exist, and in children it is attributed to repeated infections with streptococcus. Treatment should focus on the underlying cause. Symptoms can be treated with bedrest, leg elevation, compressive bandages, wet dressings, and nonsteroidal anti-inflammatory agents (NSAIDs). NSAIDs are usually more effective at the onset of EN versus with chronic disease.

Potassium iodide can be used for persistent lesions whose cause remains unknown. Corticosteroids and colchicine can be used in severe refractory cases. Thalidomide has been used successfully in the treatment of Erythema nodosum leprosum, and it was approved by the U.S. FDA for this use in July 1998.

Erythema multiforme is frequently self-limiting and requires no treatment. The appropriateness of glucocorticoid therapy can be uncertain, because it is difficult to determine if the course will be a resolving one.

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

The diagnosis is confirmed by a skin biopsy and a positive culture for acid-fast bacilli. A PPD test may also result positive.

Erythema induratum is a panniculitis on the calves. It occurs mainly in women, but it is very rare now. Historically, when it has occurred, it has often been concomitant with cutaneous tuberculosis, and it was formerly thought to be always a reaction to the tuberculum bacillus. It is now considered a panniculitis that is not associated with just a single defined pathogen. The medical eponym Bazin disease was historically synonymous, but it applies only to the tuberculous form and is dated.

Palmar erythema has no specific treatment. Management is based on the underlying cause. When its cause is treated then patients get relief. If it is attributable to a particular drug then the drug should be withdrawn.

The medieval "Bald's Leechbook" recommended treating chilblains with a mix of eggs, wine, and fennel root.

A common tradition of Hispanic America recommends warm garlic on the chilblains.

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.

Bullous Pemphigoid, Cicatricial Pemphigoid, Drug Eruptions. Epidermolysis Bullosa, Epidermolysis Bullosa Acquisita, Erythema Multiforme, Lichen Planus, pemphigus vulgaris, Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

PNP is most commonly mistaken for pemphigus vulgaris, due to the extreme similarities of the lesions that develop. However, the difference lies in the specificity of the autoreactive antibodies in each case.

Painful red swelling of the hands and feet in a patient receiving chemotherapy is usually enough to make the diagnosis. The problem can also arise in patients after bone marrow transplants, as the clinical and histologic features of PPE can be similar to cutaneous manifestations of acute (first 3 weeks) graft-versus-host disease. It is important to differentiate PPE, which is benign, from the more dangerous graft-versus-host disease. As time progresses, patients with graft-versus-host disease progress to have other body parts affected, while PPE is limited to hands and feet. Serial biopsies every 3 to 5 days can also be helpful in differentiating the two disorders (Crider et al., 1986).

Erythema ab igne was once commonly seen in the elderly who stood or sat closely to open fires or electric heaters; however, erythema ab igne has been reported in both young and elderly individuals. Women have a higher incidence of erythema ab igne than men. Although wide use of central heating has reduced the overall incidence of erythema ab igne, it is still sometimes found in people exposed to heat from other sources such as heating pads, space heaters, hot water bottles, and electronic devices.

Predisposing factors include abnormal amount of subcutaneous fat, thick ankles and abnormally poor arterial supply. Abnormal arterial supply causes low-grade ischemia of ankle region. The ankle skin becomes sensitive to temperature changes. When weather is cold, ankle is cold, blue and often tender. In hot weather, ankle becomes hot, edematous, swollen and painful. Chilblains may be present. On palpation, small superficial and painful nodules are felt. They break down to form small and multiple ulcers. Fresh crops of nodules appear in periphery of ulcer and ultimately break down. In nodular stage, pain is present; while it subsides in ulcerative stage.

A single case report suggested that oral dapsone may be useful for prevention. However, the efficacy of oral dapsone as prevention has not been demonstrated very clearly until now.

The cooling of hands and feet during chemotherapy may help prevent PPE (Baack and Burgdorf, 1991; Zimmerman et al., 1995). Support for this and a variety of other approaches to treat or prevent acral erythema comes from small clinical studies, although none has been proven in a randomised controlled clinical trial of sufficient size.

Lucio's phenomenon is treated by anti-leprosy therapy (dapsone, rifampin, and clofazimine), optimal wound care, and treatment for bacteremia including antibiotics. In severe cases exchange transfusion may be helpful.

Chilblains — also known as pernio, chill burns and perniosis — is a medical condition that occurs when a predisposed individual is exposed to cold and humidity, causing tissue damage. It is often confused with frostbite and trench foot. Damage to capillary beds in the skin causes redness, itching, inflammation, and sometimes blisters. Chilblains can be reduced by keeping the feet and hands warm in cold weather, and avoiding extreme temperature changes. Chilblains can be idiopathic (spontaneous and unrelated to another disease), but may also be a manifestation of another serious medical condition that must be investigated. A history of chilblains suggests a connective tissue disease (such as lupus). In infants, chilblains together with severe neurologic disease and unexplained fevers occurs in Aicardi–Goutières syndrome, a rare inherited condition.

The differential diagnosis includes oral lichen planus, erythematous candidiasis, leukoplakia, lupus erythematosus, glossitis, and chemical burns. Atrophic glossitis is usually distinguished from benign migratory glossitis on the basis of the migrating pattern of the lesions and the presence of a whitish border, features which are not present in atrophic glossitis, which instead shows lesions which enlarge rather than migrate. Rarely, blood tests may be required to distinguish from glossitis associated with anemia or other nutritional deficiencies. Since the appearance and the history of the condition (i.e. migrating areas of depapillation) are so striking, there is rarely any need for biopsy. When biopsy is taken, the histopathologic appearance is quite similar to psoriasis:

- Hyperparakeratosis.

- Acanthosis.

- Subepithelial T lymphocyte inflammatory infiltrate.

- Migration of neutrophilic granulocytes into the epithelial layer, which may create superficial microabscesses, similar to the Munro's microabscesses described in pustular psoriasis.

A careful history is of utmost importance when the diagnosis of pseudoporphyria is being considered. A personal and family history of hepatitis, porphyria, or photosensitivity disorder must be sought.

Although a genetic factor has not been considered in pseudoporphyria, one case of monozygotic twins developing pseudoporphyria after excessive UV-A exposure from long-term tanning bed use has been documented.

The patient should be thoroughly questioned regarding any symptoms of connective tissue disorder, which may be the underlying pathology of the photosensitivity. Recent reports suggest that a connective tissue disorder may be a predisposing factor in patients using nonsteroidal anti-inflammatory drugs (NSAIDs) who develop pseudoporphyria.

Erythema disappears on finger pressure (blanching), while purpura or bleeding in the skin and pigmentation do not. There is no temperature elevation, unless it is associated with the dilation of arteries in the deeper layer of the skin.