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The condition varies from a mild, self-limited rash (E. multiforme minor) to a severe, life-threatening form known as erythema multiformer major (or erythema multiforme majus) that also involves mucous membranes.
Consensus classification:
- Erythema multiforme minor—typical targets or raised, edematous papules distributed
- Erythema multiforme major—typical targets or raised, edematous papules distributed acrally with involvement of one or more mucous membranes; epidermal detachment involves less than 10% of total body surface area (TBSiA)
- SJS/TEN—widespread blisters predominant on the trunk and face, presenting with erythematous or pruritic macules and one or more mucous membrane erosions; epidermal detachment is less than 10% TBSA for Stevens-Johnson syndrome and 30% or more for toxic epidermal necrolysis.
The mild form usually presents with mildly itchy (but itching can be very severe), pink-red blotches, symmetrically arranged and starting on the extremities. It often takes on the classical "target lesion" appearance, with a pink-red ring around a pale center. Resolution within 7–10 days is the norm.
Individuals with persistent (chronic) erythema multiforme will often have a lesion form at an injury site, e.g. a minor scratch or abrasion, within a week. Irritation or even pressure from clothing will cause the erythema sore to continue to expand along its margins for weeks or months, long after the original sore at the center heals.
Erythema (redness) multiforme (EM) is usually a reaction of the skin and mucous membranes that occurs suddenly. It appears as a symmetrical rash and may include the mucous membrane lesions. This means that the body is sensitive to something that causes the skin and mucous membranes to react. The more common mild form is refer to as EM minor. It consists of a skin rash that involve no more than one mucosal surface. The sudden onset will progress rapidly as symmetrical lesions with circular color changes in some or all of the lesions. Rash will spread towards center or trunk of the body. Evenly distributed bumps on the skin become classic iris or target lesions. They have bright red borders and small white bumps in the center.
The cause of EM appears to be a highly sensitive reaction that can be triggered by a variety of causes. The causes can include bacterial, viral or chemical products, such as antibiotics – specifically penicillins or cephalosporins. This reaction is an allergic reaction and is in no way contagious.
Erythema multiforme minus is sometimes divided into papular and vesiulobullous forms.
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.
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).
The rash is composed of small papular lesions, each on a separate reddened base.
Erythema nodosum is characterised by nodules (rounded lumps) below the skin surface, usually on the shins. These subcutaneous nodules can appear anywhere on the body, but the most common sites are the shins, arms, thighs, and torso. Each nodule typically disappears after around two weeks, though new one may continue to form for up to six or eight weeks. A new nodule usually appears red and is hot and firm to touch. The redness starts to fade and it gradually becomes softer and smaller until it disappears. Each nodule usually heals completely without scarring over the course of about two weeks. Joint pain and inflammation sometimes continues for several weeks or months after the nodules appear.
Less common variants of erythema nodosum include:
- Ulcerating forms, seen in Crohn's disease
- Erythema contusiforme, when a subcutaneous hemorrhage (bleeding under the skin) occurs with a erythema nodosum lesion, causing the lesion to look like a contusion (bruise)
- Erythema nodosum migrans (also known as subacute nodular migratory panniculitis), a rare form of chronic erythema nodosum characterized by asymmetrical nodules that are mildly tender and migrate over time.
Urticarial erythema multiforme is an unusual reaction virtually always associated with antibiotic ingestions, characterized by skin lesions that consist of urticarial papules and plaques, some of which clear centrally forming annular lesions, but with no true urticarial lesions.
Erythema toxicum neonatorum (also known as erythema toxicum, urticaria neonatorum and toxic erythema of the newborn) is a common rash in neonates. It appears in up to half of newborns carried to term, usually between day 2–5 after birth; it does not occur outside the neonatal period.
Erythema toxicum is characterized by blotchy red spots on the skin with overlying white or yellow papules or pustules. These lesions may be few or numerous. The eruption typically resolves within first two weeks of life, and frequently individual lesions will appear and disappear within minutes or hours. It is a benign condition thought to cause no discomfort to the baby.
Urticarial allergic eruption is a cutaneous condition characterized by annular or gyrate urticarial plaques that persist for greater than 24 hours.
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.
The rings are barely raised and are non-itchy. The face is generally spared.
Papular mucinosis is chronic and may be progressive. The dermal layer of the skin breaks out into small and solid bumps, usually conical in shape and measured from 2 to 4 mm or sometimes flat-topped papules. Unlike pustules, these bumps do not contain pus. Instead they contain mucin, a substance of mucus, the body's natural and protective lubricant found in saliva and epithelial cells in lungs and the sensitive part of the nose. They usually come in clusters such as linear arrays. Less frequently, urticarial, nodular, or sometimes annular lesions may be appreciated. The dorsal aspect of the hands, face, elbows, and extensor portions of the extremities are most frequently affected. Mucosal lesions are absent. The coalescence of papules on the face, particularly on the glabella, results in longitudinal folding and gives the appearance of a leonine facies.
In scleromyxedema, symptoms can occur on larger part of the body. Erythema and scleroderma-like induration occurs on the skin. In addition, the mobility of the lips, hands, arms, and legs is reduced. Proximal myopathy, inflammatory polyarthritis, central nervous system symptoms, esophageal aperistalsis, and hoarseness are among the notable systemic symptoms. If viscera is involved, the disease will be fatal. The dermatoneuro syndrome is a rare neurological complication of the disease presenting with fever, seizures and altered mental status.
Id reactions (also known as "disseminated eczema," and "generalized eczema") are types of acute dermatitis developing after days or weeks at skin locations distant from the initial inflammatory or infectious site. They can be localised or generalised. This is also known as an 'autoeczematous response' and there must be an identifiable initial inflammatory or infectious skin problem which leads to the generalised eczema. Often, intensely itchy, the red papules and pustules can also be associated with blisters and scales and are always remote from the primary lesion. It is most commonly a blistering rash with itchy vesicles on the sides of fingers and feet as a reaction to fungal infection on the feet, athlete's foot. Stasis dermatitis, Allergic contact dermatitis, Acute irritant contact eczema and Infective dermatitis have been documented as possible triggers, but the exact cause and mechanism is not fully understood. Several other types of id reactions exist including erythema nodosum, erythema multiforme, Sweet's syndrome and urticaria.
The first signs of erythema nodosum are often flu-like symptoms such as a fever, cough, malaise, and aching joints. Some people also experience stiffness or swelling in the joints and weight loss.
Urticarial dermatoses are distinct from urticaria, which examples being drug-induced urticaria, eosinophilic cellulitis and bullous pemphigoid. It is important to distinguish urticaria from urticarial dermatoses. The individual wheals of urticaria are ‘here today and gone tomorrow’ (i.e. they last less than 24 hours), whereas with urticarial dermatoses, the individual lesions last for days or longer.
Fever and a non specific skin eruption – with reddening (erythema) and swelling (oedema) of the skin – are the most common symptoms of NEH. Patients usually present with the skin eruption 1-2 weeks after use of the cytotoxic drug. Sometimes, the skin eruption can be painful. Skin eruptions can be located on the extremities, trunk, and face. Severe lesions are rare, and can mimic cellulitis. Generalised lesions resembling erythema multiforme have been reported.
Autoimmune estrogen dermatitis presents as a cyclic skin disorder, that may appear eczematous, papular, bullous, or urticarial. with pruritus typically present, skin eruptions that may be chronic but which are exacerbated premenstrually or occur immediately following menses.
Papular mucinosis (also known as "Scleromyxedema," "Generalized lichen myxedematosus," and "Sclerodermoid lichen myxedematosus") is a rare skin disease. Localized and disseminated cases are called papular mucinosis or lichen myxedematosus while generalized, confluent papular forms with sclerosis are called scleromyxedema. Frequently, all three forms are regarded as papular mucinosis. However, some authors restrict it to only mild cases. Another form, acral persistent papular mucinosis is regarded as a separate entity.
Although there are a multitude of varying appearances, the id reaction often presents with symmetrical red patches of eczema with papules and vesicles, particularly on the outer sides of the arms, face and trunk which occur suddenly and are intensely itchy occur a few days to a week after the initial allergic or irritant dermatitis. Most commonly, athletes foot can lead to localised vesicles on hands, bacterial infections to erythema nodosum and herpes simplex virus to erythema multiforme.
The diagnosis is frequently made by treating the initial triggering skin problem and observing the improvement in the eczematous rash. Both the initial skin problem and the id reaction must be observed to make the diagnosis.
All dyshidrotic rashes are not id reactions, but id reactions are often dishydrotic-like.
Initial tests may include isolating a fungus by taking a swab and sending it for culture. Patch testing may be considered if there is suspicion of allergic contact dermatitis.
A skin biopsy is rarely necessary, but if done mostly shows an interstitial granulomatous dermatitis, some lesions being spongiotic. Id reactions cannot be distinguished from other skin diseases by histopathology. However, they can be distinguished from other id reactions by histopathology.
Bullous drug reaction (also known as a "bullous drug eruption", "generalized bullous fixed drug eruption", and "multilocular bullous fixed drug eruption") most commonly refers to a drug reaction in the erythema multiforme group. These are uncommon reactions to medications, with an incidence of 0.4 to 1.2 per million person-years for toxic epidermal necrolysis and 1.2 to 6.0 per million person-years for Stevens–Johnson syndrome. The primary skin lesions are large erythemas (faintly discernible even after confluence), most often irregularly distributed and of a characteristic purplish-livid color, at times with flaccid blisters.
Although a clear understanding of the various skin lesions in IgG4-related disease is a work in progress, skin lesions have been classified into subtypes based on documented cases:
- Angiolymphoid hyperplasia with eosinophilia (or lesions that mimic it) and cutaneous pseudolymphoma
- Cutaneous plasmacytosis
- Eyelid swelling (as part of Mikulicz's disease)
- Psoriasis-like eruptions
- Unspecified maculopapular or erythematous eruptions
- Hypergammaglobulinemic purpura and urticarial vasculitis
- Impaired blood supply to fingers or toes, leading to Raynaud's phenomenon or gangrene
Note:
In addition, Wells syndrome has also been reported in a case of IgG4-related disease.
TEN ultimately results in extensive skin involvement with redness, necrosis, and detachment of the top (epidermal) layer of the skin and mucosa. Before these severe findings develop, people often have a flu-like prodrome, with a cough, runny nose, fever, decreased appetite and malaise. A history of drug exposure exists on average 14 days (ranging from 1–4 weeks) prior to the onset of symptoms, but may result as early as 48 hours if it is a reexposure.
Initial skin findings include red-purple, dusky, flat spots known as macules that start on the trunk and spread out from there. These skin lesions then transform into large blisters. The affected skin can then become necrotic or sag from the body and peel off in great swaths.
While the presence of lesions is the denominator among patients with PNP, the characteristics of the lesions differ. The five clinical presentations of lesions associated with PNP include:
- "Pemphigus-like": Flaccid blister (discrete), crusts over the raw exuding skin lesions
- "Pemphigoid-like": Tense blister(s) on brick red erythema
- "Erythema multiforme-like": Severe polymorphic skin and/or mucous membrane lesions
- "Graft-vs.-host disease-like": Widespread lichenoid eruption with severe mucous membrane involvement
- "Lichen planus-like": Small red flat-topped scaly papules
It is most common that mucous membrane lesions of the oral cavity are presented first. They can involve the oropharynx, nasopharynx, tongue, and vermilion (red portion) of the lips. They are also known to develop in the conjunctiva of the eye, anogenital (perineum) region, and esophagus. Cutaneous lesions tend to follow the onset of mucosal lesions. The blisters often erupt in waves, usually affecting the upper trunk, head, neck, and proximal extremities. Pemphigoid-like lesions are seen more often on the extremities. Lichenoid lesions are more common among children, presenting on the trunk and limbs, ranging from small red scaly papules to extensive violet to brown papules extending to the face and neck. Within the spectrum of lichenoid presentations are wounds that have features of erythema multiforme and graft-vs.-host disease. Scaly lesions on the palms of the hand and soles of the feet have been noted to coincide with the lichenoid lesions. Lesions of varying morphology may present simultaneously and transform from one type to another as the disease progresses.
Generally, the areas affected are exposed skin not usually protected by clothing; however it can also occur in areas covered by clothing. Areas constantly subjected to the sun's rays may only be slightly affected if at all. People with extreme cases will also have reactions to light bulbs that emit a UV wavelength (any bulb that is not an LED). Parts of the body only thinly covered can also potentially be subjected to an outbreak.
Life with SU can be difficult. Patients are subject to constant itching and pain, as within minutes of the initial exposure to UV radiation a rash will appear. The urticarial reaction begins in the form of pruritus, later progressing to erythema and edema in the exposed areas of the skin. If vast areas of the body are affected, the loss of fluid into the skin could lead to light-headedness, headache, nausea, and vomiting. Extremely rarely, patients have been reported to experience an increase in heart rate that can cause a stroke or heart attack due to the body cavity swelling. Other rare side effects can be bronchospasm and glucose instability issues. Also, if a large area of the body is suddenly exposed the person may be subject to an anaphylactic reaction. Once free of exposure, the rash will usually fade away within several hours; rare and extreme cases can take a day or two to normalize depending on severity of the reaction.