EN is associated with a wide variety of conditions, including:

- Idiopathic

In about 30–50% of cases, the cause of EN is unknown.

- Infection

- Streptococcal infection which, in children, is by far the most common precipitant,

- Primary infection of Tuberculosis

- "Mycoplasma pneumoniae"

- "Histoplasma capsulatum"

- "Yersinia"

- Epstein-Barr virus

- "Coccidioides immitis" (Valley fever)

- Cat scratch disease

- Autoimmune disorders, including

- Inflammatory bowel disease (IBD)

- Behçet's disease

- Sarcoidosis

- Pregnancy

- Medications, including

- Sulfonamides

- Penicillins

- Oral contraceptives

- Bromides

- Hepatitis B vaccination

- Cancer, including

- Non-Hodgkins lymphoma (NHL)

- Carcinoid tumours

- Pancreatic cancer

EN may also be due to excessive antibody production in lepromatous leprosy leading to deposition of immune complexes.

There is an association with the HLA-B27 histocompatibility antigen, which is present in 65% of patients with erythema nodosum.

A useful mnemonic for causes is SORE SHINS (Streptococci, OCP, Rickettsia, Eponymous (Behçet), Sulfonamides, Hansen's Disease (Leprosy), IBD, NHL, Sarcoidosis.

It is very rare and estimated to affect 1 in 100,000 per year. Because of its rarity the documentation, cases and information are sparse and not a huge amount is known for certain, meaning that EAC could actually be a set of many un-classified skin lesions. It is known to occur at all ages and all genders equally. Some articles state that women are more likely to be affected than men.

Erythema nodosum is the most common form of panniculitis. It is most common in the ages of 20–30, and affects women 3–6 times more than men.

About 15 percent of patients with inflammatory bowel disease develop erythema nodosum.

Often no specific cause for the eruptions is found. However, it is sometimes linked to underlying diseases and conditions such as:

- Food (including blue cheese or tomatoes).

- Contact Dermatitis (i.e. cleaning agents, fabric softeners, etc.)

- Fungal, Bacterial and Viral infections such as sinusitis, tuberculosis, candidiasis or tinea.

- Drugs including finasteride, etizolam (and benzodiazepines), chloroquine, hydroxychloroquine, oestrogen, penicillin and amitriptyline.

- Cancer (especially the type known as erythema gyratum perstans, in which there are concentric and whirling rings).

- Primary biliary cirrhosis.

- Graves disease.

- Appendicitis.

- Lupus

- Pregnancy (EAC usually disappears/stops soon after delivery of baby).

- Hormone (Contraceptive Pill, Stress, Hormone Drugs)

- Lyme Disease

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.

Many suspected aetiologic factors have been reported to cause EM.

- Infections: Bacterial (including Bacillus Calmette-Guérin (BCG) vaccination, haemolytic "Streptococci", legionellosis, leprosy, "Neisseria meningitidis, Mycobacterium, "Pneumococcus, "Salmonella" species, "Staphylococcus" species, "Mycoplasma pneumoniae), "Chlamydial.

- Fungal (Coccidioides immitis)

- Parasitic ("Trichomonas" species, "Toxoplasma gondii), "

- Viral (especially Herpes simplex)

- Drug reactions, most commonly to: antibiotics (including, sulphonamides, penicillin), anticonvulsants (phenytoin, barbiturates), aspirin, antituberculoids, and allopurinol and many others.

- Physical factors: radiotherapy, cold, sunlight

- Others: collagen diseases, vasculitides, non-Hodgkin lymphoma, leukaemia, multiple myeloma, myeloid metaplasia, polycythemia

EM minor is regarded as being triggered by HSV in almost all cases. A herpetic aetiology also accounts for 55% of cases of EM major. Among the other infections, "Mycoplasma" infection appears to be a common cause.

Herpes simplex virus suppression and even prophylaxis (with acyclovir) has been shown to prevent recurrent erythema multiforme eruption.

Other than identifying and treating any underlying conditions in secondary livedo, idiopathic livedo reticularis may improve with warming the area.

A number of conditions may cause the appearance of livedo reticularis:

- Cutis marmorata telangiectatica congenita, a rare congenital condition

- Sneddon syndrome – association of livedoid vasculitis and systemic vascular disorders, such as strokes, due to underlying genetic cause

- Idiopathic livedo reticularis – the most common form of livedo reticularis, completely benign condition of unknown cause affecting mostly young women during the winter: It is a lacy purple appearance of skin in extremities due to sluggish venous blood flow. It may be mild, but ulceration may occur later in the summer.

- Secondary livedo reticularis:

- Vasculitis autoimmune conditions:

- Livedoid vasculitis – with painful ulceration occurring in the lower legs

- Polyarteritis nodosa

- Systemic lupus erythematosus

- Dermatomyositis

- Rheumatoid arthritis

- Lymphoma

- Pancreatitis

- Chronic pancreatitis

- Tuberculosis

- Drug-related:

- Adderall (side effect)

- Amantadine (side effect)

- Bromocriptine (side effect)

- Beta IFN treatment, "i.e." in multiple sclerosis

- Livedo reticularis associated with rasagiline

- Methylphenidate and dextroamphetamine-induced peripheral vasculopathy

- Gefitinib

- Obstruction of capillaries:

- Cryoglobulinaemia – proteins in the blood that clump together in cold conditions

- Antiphospholipid syndrome due to small blood clots

- Hypercalcaemia (raised blood calcium levels which may be deposited in the capillaries)

- Haematological disorders of polycythaemia rubra vera or thrombocytosis (excessive red cells or platelets)

- Infections (syphilis, tuberculosis, Lyme disease)

- Associated with acute renal failure due to cholesterol emboli status after cardiac catheterization

- Arteriosclerosis (cholesterol emboli) and homocystinuria (due to Chromosome 21 autosomal recessive Cystathionine beta synthase deficiency)

- Intra-arterial injection (especially in drug addicts)

- Ehlers-Danlos syndrome – connective tissue disorder, often with many secondary conditions, may be present in all types

- Pheochromocytoma

- Livedoid vasculopathy and its association with factor V Leiden mutation

- FILS syndrome (polymerase ε1 mutation in a human syndrome with facial dysmorphism, immunodeficiency, livedo, and short stature)

- Primary hyperoxaluria, oxalosis (oxalate vasculopathy)

- Cytomegalovirus infection (very rare clinical form, presenting with persistent fever and livedo reticularis on the extremities and cutaneous necrotizing vasculitis of the toes)

- Generalized livedo reticularis induced by silicone implants for soft tissue augmentation

- As a rare skin finding in children with Down syndrome

- Idiopathic livedo reticularis with polyclonal IgM hypergammopathy

- CO angiography (rare, reported case)

- A less common skin lesion of Churg-Strauss syndrome

- Erythema nodosum-like cutaneous lesions of sarcoidosis showing livedoid changes in a patient with sarcoidosis and Sjögren's syndrome

- Livedo vasculopathy associated with IgM antiphosphatidylserine-prothrombin complex antibody

- Livedo vasculopathy associated with plasminogen activator inhibitor-1 promoter homozygosity and prothrombin G20210A heterozygosity

- As a first sign of metastatic breast carcinoma (very rare)

- Livedo reticularis associated with renal cell carcinoma (rare)

- Buerger's disease (as an initial symptom)

- As a rare manifestation of Graves hyperthyroidism

- Associated with pernicious anaemia

- Moyamoya disease (a rare, chronic cerebrovascular occlusive disease of unknown cause, characterized by progressive stenosis of the arteries of the circle of Willis leading to an abnormal capillary network and resultant ischemic strokes or cerebral hemorrhages)

- Associated with the use of a midline catheter

- Familial primary cryofibrinogenemia.

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.

Acral erythema is a common adverse reaction to cytotoxic chemotherapy drugs, particularly cabozantinib, cytarabine, doxorubicin, and fluorouracil and its prodrug capecitabine.

Targeted cancer therapies, especially the tyrosine kinase inhibitors sorafenib and sunitinib, have also been associated with a high incidence of acral erythema. However, acral erythema due to tyrosine kinase inhibitors seems to differ somewhat from acral erythema due to classic chemotherapy drugs.

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

Erythema multiforme major (also known as "erythema multiforme majus") is a form of rash with skin loss or epidermal detachment.

The term "erythema multiforme majus" is sometimes used to imply a bullous (blistering) presentation.

According to some sources, there are two conditions included on a spectrum of this same disease process:

- Stevens–Johnson syndrome (SJS)

- Toxic epidermal necrolysis (TEN) which described by Alan Lyell and previously called Lyell syndrome[5].

In this view, EM major, SJS and TEN are considered a single condition, distinguished by degree of epidermal detachment.

However, a consensus classification separates erythema multiforme minor, erythema multiforme major, and SJS/TEN as three separate entities.

Alpha-1 antitrypsin deficiency panniculitis is a panniculitis associated with a deficiency of the α-antitrypsin enzyme.

Annular erythema of infancy is a skin condition reported in children roughly six months in age, characterized by transitory skin lesions that resolved without treatment within eleven months.

Erythema marginatum is a type of erythema (redness of the skin or mucous membranes) involving pink rings on the torso and inner surfaces of the limbs which come and go for as long as several months. It is found primarily on extensor surfaces.

An association with bradykinin has been proposed in the case of hereditary angioedema.

Lipodermatosclerosis is a form of panniculitis associated with chronic venous insufficiency that presents with brown indurations on the front of the shins. It may be associated with pain and other signs of chronic venous insufficiency. The exact cause is unknown.

Other forms include:

- Subcutaneous fat necrosis of the newborn, a form of panniculitis occurring in newborns that is usually self-resolving, that may be a result of hypoxic injury to relatively high levels of brown fat.

- Sclerema neonatorum, affecting premature births.

- Weber–Christian disease, a symmetrical form of the disease of unknown origin occurring in middle-aged women.

- Lupus erythematosus panniculitis, panniculitis associated with lupus erythematosus.

- Forms associated with use of high doses of systemic corticosteroids during rapid corticosteroid withdrawal, and from the injection of silicone or mineral oils.

Erythema multiforme (EM) is a skin condition of unknown cause; it is a type of erythema possibly mediated by deposition of immune complexes (mostly IgM-bound complexes) in the superficial microvasculature of the skin and oral mucous membrane that usually follows an infection or drug exposure. It is an uncommon disorder, with peak incidence in the second and third decades of life. The disorder has various forms or presentations, which its name reflects ("multiforme", "", from "" + ""). Target lesions are a typical manifestation. Two types, one mild to moderate and one severe, are recognized (erythema multiforme minor and erythema multiforme major).

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.

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

It occurs in less than 5% of patients with rheumatic fever, but is considered a major Jones criterion when it does occur. The four other major criteria include carditis, polyarthritis, Sydenham's Chorea, and subcutaneous nodules. In this case, it is often associated with Group A streptococcal infection, otherwise known as "Streptococcus pyogenes" infection, which can be detected with an ASO titer.

It is an early feature of rheumatic fever and not pathognomonic of it. It may be associated with mild myocarditis (inflammation of heart muscle). It is also seen in conditions like allergic drug reactions, sepsis and glomerulonephritis.

It often occurs as a harbinger of attacks in hereditary angioedema. In this case it may occur several hours or up to a day before an attack.

It can be caused by infection, massage, electrical treatment, acne medication, allergies, exercise, solar radiation (sunburn), cutaneous radiation syndrome, mercury toxicity, blister agents, niacin administration, or waxing and tweezing of the hairs—any of which can cause the capillaries to dilate, resulting in redness. Erythema is a common side effect of radiotherapy treatment due to patient exposure to ionizing radiation.

Septal panniculitis is a condition of the subcutaneous fat affecting the layer of adipose tissue that lies between the dermis and underlying fascia, of which there are two forms: acute erythema nodosum and chronic erythema nodosum.

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.

Urticaria is a vascular reaction of the skin characterized by the appearance of wheals, which are firm, elevated swelling of the skin. Angioedema, which can occur alone or with

urticaria, is characterized by a well-defined, edematous swelling that involves subcutaneous tissues, abdominal organs, or upper airway.

- Acquired C1 esterase inhibitor deficiency

- Acute urticaria

- Adrenergic urticaria

- Anaphylaxis

- Aquagenic urticaria

- Cholinergic urticaria

- Chronic urticaria (ordinary urticaria)

- Cold urticaria

- Dermatographism (dermographism)

- Episodic angioedema with eosinophilia (Gleich's syndrome)

- Exercise urticaria (exercise-induced urticaria)

- Galvanic urticaria

- Heat urticaria

- Hereditary angioedema (Quincke's edema)

- Localized heat contact urticaria

- Mast cell-independent urticaria

- Physical urticaria

- Primary cold contact urticaria

- Pressure urticaria (delayed pressure urticaria)

- Reflex cold urticaria

- Schnitzler syndrome

- Secondary cold contact urticaria

- Solar urticaria

- Systemic capillary leak syndrome

- Urticarial allergic eruption

- Urticaria-like follicular mucinosis

- Vibratory angioedema

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.