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With no particular affinity to any particular ethnic group, seen in all age groups and equally amongst males and females, the precise prevalence is not known.
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.
Other rashes that occur in a widespread distribution can look like an id reaction. These include atopic dermatitis, contact dermatitis, dyshidrosis, photodermatitis, scabies and drug eruptions.
Very rarely seen in children, bullous pemphigoid most commonly occurs in people 70 years of age and older. Estimated frequency is seven to 14 cases per million per year, but has been reported to be as high as 472 cases per million per year in Scottish men older than 85. At least one study indicates the incidence might be increasing in the United Kingdom. Some sources report it affects men twice as frequently as women, while others report no difference between the sexes.
Many mammals can be afflicted, including dogs, cats, pigs, and horses, as well as humans. It is very rare in dogs; on average, three cases are diagnosed around the world each year.
Bullous pemphigoid may be self-resolving in a period ranging from several months to many years even without treatment. Poor general health related to old age is associated with a poorer prognosis.
The culprit can be both a prescription drug or an over-the-counter medication.
Examples of common drugs causing drug eruptions are antibiotics and other antimicrobial drugs, sulfa drugs, nonsteroidal anti-inflammatory drugs (NSAIDs), biopharmaceuticals, chemotherapy agents, anticonvulsants, and psychotropic drugs. Common examples include photodermatitis due to local NSAIDs (such as piroxicam) or due to antibiotics (such as minocycline), fixed drug eruption due to acetaminophen or NSAIDs (Ibuprofen), and the rash following ampicillin in cases of mononucleosis.
Certain drugs are less likely to cause drug eruptions (rates estimated to be ≤3 per 1000 patients exposed). These include: digoxin, aluminum hydroxide, multivitamins, acetaminophen, bisacodyl, aspirin, thiamine, prednisone, atropine, codeine, hydrochlorothiazide, morphine, insulin, warfarin, and spironolactone.
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.
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.
Hospital wards and, nurseries, and can be passed from person to person. Also many close contact sports. Therefore, it is advised that the patient has to try to limit as much human contact as possible to limit transmission of infection.
After 48 hours the disease is considered no longer contagious assuming the proper antibiotic treatments have been administered.
Dermatitis herpetiformis generally responds well to medication and changes in diet. However, it is an autoimmune disease, and patients with DH are more likely than others to have thyroid problems and intestinal lymphoma.
Dermatitis herpetiformis does not usually cause complications on its own, without being associated with another condition. Complications from this condition, however, arise from the autoimmune character of the disease, as an overreacting immune system is a sign that something does not work well and might cause problems to other parts of the body that do not necessarily involve the digestive system.
Gluten intolerance and the body's reaction to it make the disease more worrying in what concerns the possible complications. This means that complications that may arise from dermatitis herpetiformis are the same as those resulting from coeliac disease, which include osteoporosis, certain kinds of gut cancer, and an increased risk of other autoimmune diseases such as thyroid disease.
The risks of developing complications from dermatitis herpetiformis decrease significantly if the affected individuals follow a gluten-free diet. The disease has been associated with autoimmune thyroid disease, insulin-dependent diabetes, lupus erythematosus, Sjögren's syndrome, sarcoidosis, vitiligo, and alopecia areata.
Pemphigoid is usually considered to be mediated by IgG, but IgA-mediated forms have also been described.
IgA-mediated immunobullous diseases can often be difficult to treat even with usually effective medications such as rituximab.
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.
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%.
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.
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.
Pemphigus is an autoimmune disease caused by antibodies directed against both desmoglein 1 and desmoglein 3 present in desmosomes. Loss of desmosomes results in loss of cohesion between keratinocytes in the epidermis, and a disruption of the barrier function served by intact skin. The process is classified as a type II hypersensitivity reaction (in which antibodies bind to antigens on the body's own tissues). On histology, the basal keratinocytes are usually still attached to the basement membrane leading to a characteristic appearance called "tombstoning." Transudative fluid accumulates in between the keratinocytes and the basal layer (suprabasal split), forming a blister and resulting in what is known as a positive Nikolsky's sign. This is a contrasting feature from bullous pemphigoid, which is thought to be due to anti-hemidesmosome antibodies, and where the detachment occurs between the epidermis and dermis (subepidermal bullae). Clinically, pemphigus vulgaris is characterized by extensive flaccid blisters and mucocutaneous erosions. The severity of the disease, as well as the mucosal lesions, is believed to be directly proportional to the levels of desmoglein 3. Milder forms of pemphigus (like foliacious and erythematoses) are more anti-desmoglein 1 heavy.
The disease arises most often in middle-aged or older people, usually starting with a blister that ruptures easily. It can also start with blisters in the mouth. The lesions can become quite extensive.
Risk factors for drug allergies can be attributed to the drug itself or the characteristics of the patient. Drug-specific risk factors include the dose, route of administration, duration of treatment, repetitive exposure to the drug, and concurrent illnesses. Host risk factors include age, sex, atopy, specific genetic polymorphisms, and inherent predisposition to react to multiple unrelated drugs (multiple drug allergy syndrome).
A drug allergy is more likely to develop with large doses and extended exposure.
The treatment is (1) stop the offending drug (antibiotics), (2) symptomatic (fever), and (3) for complications (hepatitis).
Photosensitive drug reaction (or drug-induced photosensitivity) secondary to medications may cause phototoxic, photoallergic, and lichenoid reactions, and photodistributed telangiectasias, as well as pseudoporphyria.
Drugs involved include naproxen and doxycycline.
In 2016, interferon gamma/CXCL10 axis was hypothesized to be a target for treatments that reverse inflammation. Apremilast is undergoing investigation as a potential treatment .
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)."
Drug-induced pruritus is itchiness of the skin caused by medication, a pruritic reaction that is generalized.
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.
When a medication causes an allergic reaction, it is called an allergen. The following is a short list of the most common drug allergens:
- Antibiotics
- Penicillin
- Sulfa drugs
- Tetracycline
- Analgesics
- Codeine
- Non-steroidal anti-inflammatory drugs (NSAIDs)
- Antiseizure
- Phenytoin
- Carbamazepine