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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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Clinically, the earliest lesions may appear urticarial (like hives), but could also appear dermatitic, targetoid, lichenoid, nodular, or even without visible rash (essential pruritus). Tense bullae eventually erupt, most commonly at the inner thighs and upper arms, but the trunk and extremities are frequently both involved. Any part of the skin surface can be involved. Oral lesions are present in a minority of cases. The disease may be acute, but typically will wax and wane. Several other skin diseases may have similar symptoms. However, milia are more common with epidermolysis bullosa acquisita, because of the deeper antigenic targets. A more ring-like configuration, with a central depression or centrally collapsed bullae may indicate linear IgA disease. Nikolsky's sign is negative unlike pemphigus vulgaris where it is positive.
The most common type of eruption is a morbilliform (resembling measles) or erythematous rash (approximately 90% of cases). Less commonly, the appearance may also be urticarial, papulosquamous, pustular, purpuric, bullous (with blisters) or lichenoid. Angioedema can also be drug-induced (most notably, by angiotensin converting enzyme inhibitors).
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.
Dermatitis herpetiformis is characterized by intensely itchy, chronic papulovesicular eruptions, usually distributed symmetrically on extensor surfaces (buttocks, back of neck, scalp, elbows, knees, back, hairline, groin, or face). The blisters vary in size from very small up to 1 cm across.
The condition is extremely itchy, and the desire to scratch can be overwhelming. This sometimes causes the sufferer to scratch the blisters off before they are examined by a physician. Intense itching or burning sensations are sometimes felt before the blisters appear in a particular area.
Untreated, the severity of DH can vary significantly over time, in response to the amount of gluten ingested.
Dermatitis herpetiformis symptoms typically first appear in the early years of adulthood between 20 and 30 years of age.
Although the first signs and symptoms of dermatitis herpetiformis are intense itching and burning, the first visible signs are the small papules or vesicles that usually look like red bumps or blisters. The rash rarely occurs on other mucous membranes, excepting the mouth or lips. The symptoms range in severity from mild to serious, but they are likely to disappear if gluten ingestion is avoided and appropriate treatment is administered.
Dermatitis herpetiformis symptoms are chronic, and they tend to come and go, mostly in short periods of time. Sometimes, these symptoms may be accompanied by symptoms of coeliac disease, commonly including abdominal pain, bloating or loose stool, and fatigue.
The rash caused by dermatitis herpetiformis forms and disappears in three stages. In the first stage, the patient may notice a slight discoloration of the skin at the site where the lesions appear. In the next stage, the skin lesions transform into obvious vesicles and papules that are likely to occur in groups. Healing of the lesions is the last stage of the development of the symptoms, usually characterized by a change in the skin color. This can result in areas of the skin turning darker or lighter than the color of the skin on the rest of the body. Because of the intense itching, patients usually scratch, which can lead to the formation of crusts.
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.
Pemphigus vulgaris most commonly presents with oral blisters (buccal and palatine mucosa, especially), but also includes cutaneous blisters. Other mucosal surfaces, the conjunctiva, nose, esophagus, penis, vulva, vagina, cervix, and anus, may also be affected. Flaccid blisters over the skin are frequently seen with sparing of the skin covering the palms and soles.
Blisters commonly erode and leave ulcerated lesions and erosions. A positive Nikolsky sign (induction of blistering in normal skin or at the edge of a blister) is indicative of the disease.
Severe pain with chewing can lead to weight loss and malnutrition.
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.
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.
Some of the most severe and life-threatening examples of drug eruptions are erythema multiforme, Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), hypersensitivity vasculitis, Drug induced hypersensitivity syndrome (DIHS), erythroderma and acute generalized exanthematous pustulosis (AGEP). These severe cutaneous drug eruptions are categorized as hypersensitivity reactions and are immune-mediated. There are four types of hypersensitivity reactions and many drugs can induce one or more hypersensitivity reactions.
Bullous pemphigoid is an acute or chronic autoimmune skin disease, involving the formation of blisters, more appropriately known as bullae, at the space between the epidermis and dermis skin layers. It is classified as a type II hypersensitivity reaction, with the formation of anti-hemidesmosome antibodies.
Pemphigus vulgaris is a rare chronic blistering skin disease and the most common form of pemphigus. It is classified as a type II hypersensitivity reaction in which antibodies are formed against desmosomes, components of the skin that function to keep certain layers of skin bound to each other. As desmosomes are attacked, the layers of skin separate and the clinical picture resembles a blister. Over time the condition inevitably progresses without treatment: lesions increase in size and distribution throughout the body, behaving physiologically like a severe burn.
Before the advent of modern treatments, mortality for the disease was close to 90%. Today, the mortality rate with treatment is between 5-15%.
The forms of pemphigoid are considered to be connective tissue autoimmune skin diseases. There are several types:
- Gestational pemphigoid or Pemphigoid gestationis (PG) (formerly called Herpes gestationis)
- Bullous pemphigoid (BP) Rarely affect the mouth
- Mucous membrane pemphigoid, also known as Cicatricial pemphigoid (CP) (No skin involvement)
Bullous and Cicatricial pemphigoids usually affect persons who are over age 60. Gestational pemphigoid occurs during pregnancy, typically in the second or third trimester, and/or immediately following pregnancy.
The treatment is (1) stop the offending drug (antibiotics), (2) symptomatic (fever), and (3) for complications (hepatitis).
Dermatitis herpetiformis (DH), or Duhring's disease, is a chronic blistering skin condition, characterised by blisters filled with a watery fluid. Despite its name, DH is neither related to nor caused by herpes virus: the name means that it is a skin inflammation having an appearance similar to herpes.
DH was first described by Louis Adolphus Duhring in 1884. A connection between DH and celiac disease was recognised in 1967, although the exact causal mechanism is not known. DH is a specific manifestation of celiac disease.
The age of onset is usually about 15-40, but DH can also affect children and the elderly. Men and women are equally affected. Estimates of DH prevalence vary from 1 in 400 to 1 in 10,000. It is most common in patients of northern European/northern Indian ancestry, and is associated with the human leukocyte antigen (HLA) haplotype HLA-DQ2 along with coeliac disease and gluten sensitivity.
AGEP is an acute febrile drug eruption characterized by numerous small, primarily non-follicular, sterile pustules, arising within large areas of red swollen skin.
The eruption follows a self-limiting course and will end before a week provided the causative agent (e.g. medication) is discarded. It is accompanied by fever, a high number of neutrophils and eosinophils in the blood, liver inflammation, and sometimes by facial swelling. The mortality rate is about 5% and the differential diagnosis includes Stevens–Johnson syndrome (SJS). Contrary to SJS, in AGEP, mucosa are not affected, which means that there are no blisters in the mouth or vagina.
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.
Bullous impetigo can appear around the diaper region, axilla, or neck. The bacteria causes a toxin to be produced that reduces cell-to-cell stickiness (adhesion), causing for the top layer of skin (epidermis), and lower layer of skin (dermis) to separate. Vesicles rapidly enlarge and form the bullae which is a blister more than 5mm across. Bullae is also known as Staphylococcal scalded skin syndrome. Other associated symptoms are itching, swelling of nearby glands, fever and diarrhea. It should also be noted that pain is very rare.
Long-term effects: once the scabs on the bullous have fallen off, scarring is minimal. Possible long-term effects are kidney disease.
Cicatricial pemphigoid (also known as "Mucous Membrane Pemphigoid", "MMP", "Benign mucosal pemphigoid," "Benign mucous membrane pemphigoid," "Ocular pemphigus," and "Scarring pemphigoid") is a rare chronic autoimmune subepithelial blistering disease characterized by erosive skin lesions of the mucous membranes and skin that results in scarring of at least some sites of involvement.
Cicatricial pemphigoid has been referred to by a variety of designations based largely on its site of involvements, with examples of such terminology including "desquamative gingivitis," "ocular pemphigus," and "benign mucous membrane pemphigoid." However, currently "...such designations are thought to be confusing or somewhat misleading (e.g., pemphigus in this context is a misnomer, and this disorder is hardly benign given the extent of morbidity it can cause)."
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.
Pemphigoid is a group of rare autoimmune blistering skin diseases. As its name indicates, pemphigoid is similar in general appearance to pemphigus, but, unlike pemphigus, pemphigoid does not feature acantholysis, a loss of connections between skin cells.
Pemphigoid is more common than pemphigus, and is slightly more common in women than in men. It is also more common in people over 60 years of age than it is in younger people.
The autoimmune reaction most commonly affects the mouth, causing lesions in the gingiva or gums, but it can also affect areas of mucous membrane elsewhere in the body, such as the sinuses, genitals and anus. When the cornea of the eye is affected, repeated scarring may result in blindness.
"Localized cicatricial pemphigoid" (also known as "Brunsting–Perry cicatricial pemphigoid") refers to a localised variant of cutaneous cicatricial pemphigoid involving the head and the neck without mucosal involvement.
Nikolsky's sign (gentle lateral pressure) on unaffected mucosa or skin raises a bulla. If no lesions are present on examination it may be useful way of demonstrating reduced epithelial adhesion. In contrast, in Pemphigus, the epithelium tends to disintegrate rather than form a bulla.
Nikolsky's sign is present in case of Pemphigus and Cicatricial Pemphigoid, but not in the case of Bullous Pemphigoid.
Although lichen planus can present with a variety of lesions, the most common presentation is as a well defined area of purple-coloured, itchy, flat-topped papules with interspersed lacy white lines (Wickham's striae). This description is known as the characteristic "6 Ps" of lichen planus: planar (flat-topped), purple, polygonal, pruritic, papules, and plaques. This rash, after regressing, is likely to leave an area of hyperpigmentation that slowly fades. That said, a variety of other lesions can also occur.
Drug-induced pruritus is itchiness of the skin caused by medication, a pruritic reaction that is generalized.
Lichen planus may be categorized as affecting mucosal or cutaneous surfaces.
- "Cutaneous" forms are those affecting the skin, scalp, and nails.
- "Mucosal" forms are those affecting the lining of the gastrointestinal tract (mouth, pharynx, esophagus, stomach, anus), larynx, and other mucosal surfaces including the genitals, peritoneum, ears, nose, bladder and conjunctiva of the eyes.
Identifying a drug allergy can sometimes be the hardest part. Sometimes drug allergies are confused with nonallergic drug reactions because they both cause somewhat similar reactions. Symptoms of a drug allergy can include, but are not limited to, the following list.
- Hives
- Itching
- Rash
- Fever
- Facial swelling
- Shortness of breath due to the short-term constriction of lung airways or longer-term damage to lung tissue
- Anaphylaxis, a life-threatening drug reaction (produces most of these symptoms as well as low blood pressure)
- Cardiac symptoms such as chest pain, shortness of breath, fatigue, chest palpitations, light headedness, and syncope due to a rare drug-induced reaction, eosinophilic myocarditis