Severe cutaneous adverse reactions | |
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Other names | SCARs |
Specialty | Dermatology |
Severe cutaneous adverse reactions are a group of potentially lethal adverse drug reactions that involve the skin and mucous membranes of various body openings such as the eyes, ears, and inside the nose, mouth, and lips. In more severe cases, SCARs also involves serious damage to internal organs. SCARs includes five syndromes: Drug reaction with eosinophilia and systemic symptoms (i.e. DRESS syndrome, also termed Drug-induced hypersensitivity syndrome [DIHS]); Stevens–Johnson syndrome (SJS); Toxic epidermal necrolysis (TEN), Stevens-Johnson/toxic epidermal necrolysis overlap syndrome (SJS/TEN); and Acute generalized exanthematous pustulosis (AGEP). The five disorders have similar pathophysiologies, i.e. disease-causing mechanisms, for which new strategies are in use or development to identify individuals predisposed to develop the SCARs-inducing effects of specific drugs and thereby avoid treatment with them. [1] Maculopapular rash (MPR) is a less-well defined and benign form of drug-induced adverse skin reactions; while not classified in the SCARs group, it shares a similar pathophysiology with SCARs and is caused by some of the same drugs which cause SCARs. [2]
Adverse drug reactions are major therapeutic problems estimated to afflict up to 20% of inpatients and 25% of outpatients. About 90% of these adverse reactions take the form of benign morbilliform rash hypersensitivity drug reactions such as MPR. However, they also include more serious reactions: a) pseudo-allergic reactions in which a drug directly stimulates mast cells, basophils, and/or eosinophils to release pro-allergic mediators (e.g. histamine); b) Type I, Type II, and Type III hypersensitivity reactions of the adaptive immune system mediated by IgE, IgG, and/or IgM antibodies; and c) SCARs and MPR which are Type IV hypersensitivity reactions of the innate immune system initiated by lymphocytes of the T cell type and mediated by various types of leukocytes and cytokines. [3]
Type IV hypersensitivity reactions are off-target drug reactions, i.e. reactions in which a drug causes toxicity by impacting a biological target other than the one(s) for which it is intended. They are T cell-initiated delayed hypersensitivity reactions occurring selectively in individuals who may be predisposed to do so because of the genetically-based types of human leukocyte antigens (i.e. HLA) or T-cell receptors they express; the efficiency with which they absorb, distribute to tissues, metabolize, and eliminate a drug or drug metabolite; or less well-defined idiosyncrasies. [1] [4] [5]
Categorizing SCARs as a group focuses on the similarities and differences in their pathophysiologies, clinical presentations, instigating drugs, and recommendations for drug avoidance.
Stevens–Johnson syndrome, toxic epidermal necrolysis, and Stevens–Johnson syndrome/Toxic epidermal necrolysis overlap syndrome are a spectrum of Type IV, Subtype IVc, delayed hypersensitivity reactions, i.e. reactions initiated by CD8+ T cells and natural killer T cells. [2] They are characterized initially by fever and flu-like symptoms followed within days by skin as well as mucous membrane blisters and denudation. Differentiation of the three disorders is based on the extent of disease with SJS involving <10%, SGS/TEN involving 10% to 30%, and TEN involving >30% of the total bodily skin area. This spectrum of disorders is complicated by inflammation in and damage to internal organs such as the liver and, less commonly, kidney and heart. More importantly, they are also complicated by sepsis due to the loss of skin and mucous membrane epithelial barriers. In one study, SJS, TEN, and SJS/TEN mortality rates were 4.8%, 19.4%, and 14.8%, respectively, with an important portion of the deaths due to bacterial sepsis, particularly in the acute, early stage of these disorders. [6] [7] The drugs most commonly triggering the SJS, TEN, and SJS/TEN spectrum of disorders are anti-infective sulfonamides, anticonvulsants (e.g. carbamazepine and lamotrigine), non-steroidal anti-inflammatory drugs, allopurinol, nevirapine, and chlormezanone. Allopurinol appears in some studies to be the most common instigator of these disorders. Any new biological or herbal remedy, it is suggested, should be considered a possible cause of these disorders under the proper clinical circumstances. [6]
The DRESS syndrome is a Type IV, Subtype IVb, hypersensitivity drug reaction, i.e. a reaction dependent on CD4(+) cells and the cell- and tissue-injuring action of eosinophils. [2] [8] Skin lesions inflict 73% to 100% of afflicted individuals; they are generally infiltrative macules and plaques. About 75% of cases exhibit facial edema. The syndrome is also associated with other maladies caused by high levels of blood eosinophils such as the various hypereosinophilia-related disorders: persistent asthma and allergic rhinitis and, more significantly, eosinophil-based and lymphocyte-based inflammation of the liver (>70% of cases), kidney (20% to 40% of cases), lung (~33% of cases), heart (4% to 27% of cases), and, uncommonly, the meninges, brain, gastrointestinal tract, and spleen. [4] The disorder is lengthened and worsened in individuals that develop reactivation of latent viruses of the herpes viruses. [4] [9] The estimated mortality rate for the DRESS syndrome is about 10%. Allopurinol and sulfasalazine account for almost 66% of DRESS syndrome cases with minocycline being the third most common cause of the disorder; Strontium ranelate, leflunomide, dapsone, and nonsteroidal anti-inflammatory drugs (diclofenac, celecoxib, ibuprofen, and phenylbutazone) are less common causes of the disorder. [10]
AGEP is a rare Type IV, subtype IVd, hypersensitivity reaction dependent on neutrophils and characterized by the rapid formation of skin pustules on an erythematous background. [2] [11] In one study of 28 patients, the disorder was complicated by involvement of the kidney (36% of cases), lung (27%), and liver (11%). [12] It is the least severe of the SCARs disorders, typically shows a mild course, and is rarely associated with severe complications although superinfection of skin lesions may be life-threatening. [2] [13] [11]
Individuals are predisposed to develop SCARs in response to a given drug based on the types of human leukocyte antigen (i.e. HLA) proteins and T-cell receptors that they express; their ability to process an instigating drug or the drug's metabolite(s); and other less well-defined factors. These predispositions are a consequence of the HLA allele and T-cell receptor variants that individuals express in their antigen presentation immune pathways; their ADME, i.e. efficiency in Absorbing, Distributing to tissues, Metabolizing, and/or Eliminating a drug or drug metabolite; and other less well-defined factors.
Drugs can cause SCARs by subverting the antigen presentation pathways which recognize and trigger immune responses to non-self epitopes (i.e. antigens) on foreign proteins. These proteins are taken up by antigen-presenting cells (APC) and degraded into small peptides. The peptides are inserted into a groove on HLA proteins that are part of major histocompatibility complexes (i.e. MHC) and presented to T-cell receptors (TCR) on nearby cytotoxic T cells (i.e. CD8+ T cells) or T helper cells (i.e. CD4+ T cells). T-cell receptors are heterologous; only a small fraction of them can bind a particular epitope on presented peptides and this binding is restricted to non-self epitopes. Upon binding a non-self epitope on a presented peptide, a T-cell receptor becomes active in stimulating its parent cell to mount one of two types of immune responses based on whether the APC presenting the peptide is professional or non-professional in type. Non-professional APC include all nucleated cells; these cells load the processed peptides onto MHC class I (i.e. HLA-A, HLA-B, or HLA-C) proteins and thereon present the peptides to CD8+ T cells. Those CD8+ T cells whose T-cell receptors bind a non-self epitope on the peptides are stimulated to attack cells or pathogens expressing this epitope. Professional APC are dendritic cells, macrophages, and B cells. They load processed peptides onto MHC class II (i.e. HLA-DM, HLA-DO, HLA-DP, HLA-DQ, or HLA-DR) proteins and thereon present the peptides to CD4+ T cells. Those CD4+ T cells whose T-cell receptors bind a non-self epitope on presented peptides are stimulated to orchestrate various immune reactions that attack soluble proteins, pathogens, and host cells and tissues that express the non-self epitope. SCARs-inducing drugs can act through these pathways to cause CD8+ or CD4+ T cells to mount immune responses that are inappropriately directed against bodily tissues. Four models propose the underlying mechanisms by which SCARs-inducing drugs may activate T cells to mount immune responses against self: [3] [13]
HLA genes are highly polymorphic, i.e. have many different serotypes (i.e. alleles) while T-cell receptor genes receptors are edited. i.e. altered to encode proteins with different amino acid sequences. Humans, it is estimated, express more than 10,000 different HLA class I proteins, 3,000 different HLA class II proteins, and 100 trillion different T-cell receptors. An individual, however, expresses only a fraction of these polymorphic or edited gene products. Since a SCARs-inducing drug interacts with only one or a few types of HLA proteins or T-cell receptors, its ability to induce a SCARs disorder is limited to those individuals who express those HLA proteins that make the appropriate HLA/non-self peptide or the T cell that expresses the T-cell receptor that recognize the non-self epitope created by the drug. [3] [13] Thus, only rare individuals are predisposed to develop a SCARs disorder in response to a particular drug on the bases of their expression of specific HLA protein or T-cell receptor types. [5]
SCARs disorders are triggered by wide range of drugs [4] with the most commonly reported offenders being Carbamazepine, allopurinol, abacavir, phenytoin, and nevirapine. [3] These drugs evoke SCARs by interacting with one or just a few HLA proteins. The following table list drugs repeatedly implicated in eliciting SCARs; it also gives the drugs' therapeutic targets, HLA serotypes through which they act, the types of SCARs disorders they trigger, the negative and positive predictive values for the drugs (where known), and the populations afflicted. [1] [3] Positive predictive values give the true percentages of individuals with the indicated HLA gene allele (identified as a serotype) that develop the cited drug-induced SCARs; negative predictive values give the percentage of individuals without the indicated serotype that fail to develop the cited drug-induced SCARs. For example, Chinese, Korean, Japanese, and European individuals that express the HLA-A31:01 allele have a 1% true chance of developing the DRESS syndrome while HLA-A31:01 negative individuals in these specific populations have a 99.9% true chance of not developing the DRESS syndrome when treated with carbamazepine. In this particular example, the HLA-A31:01 allele is virtually necessary but clearly not sufficient for developing the DRESS syndrome in response to carbamazepine. The table also shows that: positive predictive values lie between 0.59-55%, i.e. far below 100%; positive as well as negative predictive values vary with the population tested; a drug may cause more than one type of SCARs disorder or interact with more than one HLA serotype to cause SCARs; and the level of susceptibility to a drug varies between populations. These findings indicate that other factors, generally regarded as due to unspecified population-related genetic differences, contribute decisively to developing SCARs. [3] [4] [13] [14]
Drug | Drug action | HLA gene and allele | SCARs disorder triggered | Positive predictive value | Negative predictive value | Populations afflicted |
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Carbamazepine | anticonvulsant | HLA-A*31:01 | DRESS syndrome | 1% | 99.9% | Chinese, Koreans, Japanese, European |
Carbamazepine | anticonvulsant | HLA-A*31:01 | SJS, TEN, SJS/TEN | 0.89% | 99.98% | European |
Carbamazepine | anticonvulsant | HLA-A*31:01 | SJS, TEN, SJS/TEN | 0.59% | 99.97% | Chinese |
Carbamazepine | anticonvulsant | HLA-A*31:01 | SJS, TEN, SJS/TEN | ? | ? | Northern European, Japanese, Korean |
Carbamazepine | anticonvulsant | HLA-B*15:02 | SJS, TEN, SJS/TEN | 3% | 100% | Chinese, Tai, Malaysian, Koreans, Indian |
Carbamazepine | anticonvulsant | HLA-A*31:01 | MPE | 34/9% | 96.7% | Han Chinese |
Oxcarbazepine | anticonvulsant | HLA-B*15:01 | SJS, TEN, SJS/TEN | ? | ? | Han Chinese, Taiwanese |
Phenytoin | anticonvulsant | HLA-B*13:01 or HLA-B51:01 | DRESS syndrome, MPE | ? | ? | Han Chinese |
Phenytoin | anticonvulsant | HLA-B*15:02, HLA-Cw*08:01, or HLA-DRB1*16:02 | DRESS syndrome | ? | ? | Han Chinese |
Lamotrigine | anticonvulsant | HLA-B*15:02 or HLA-B*38 | SJS, TEN, SJS/TEN | ? | ? | Han Chinese |
Lamotrigine | anticonvulsant | HLA-B*38, HLA-B*58:01, or HLA:68:01 | SJS, TEN, SJS/TEN | ? | ? | European |
Lamotrigine | anticonvulsant | HLA-Cw*07, HLA-DQB*06:09, or HLA-DRB1*13:01 | SJS, TEN, SJS/TEN | ? | ? | European |
Oxicam | anti-inflammatory | HLA-B*73, HLA-A*2, or HLA-B*12 | SJS, TEN, SJS/TEN | ? | ? | European |
various sulfa drugs | antibiotic | HLA-Cw*4 | SJS, TEN, SJS/TEN | ? | ? | Han Chinese |
various sulfa drugs | antibiotic | HLA-B*38 | SJS, TEN, SJS/TEN | ? | ? | European |
Methazolamide | lowers intraocular pressure | HLA-B*59:01 or HLA-CW*01:02 | SJS, TEN, SJS/TEN | ? | ? | Korean, Japanese |
Dapsone | antibiotic, anti-inflammatory | HLA-B*13:01 | DRESS syndrome | 7.8% | 99.8% | Han Chinese |
Allopurinol | anti-gout drug | HLA-B*58:01 | DRESS syndrome, SJS, TEN, SJS/TEN | 3% | 100% in Han Chinese | Han Chinese, Korean, Thai, European |
Nevirapine | anti-retroviral | HLA-DRB1*01:01 or HLA-DRB1*01:012 | DRESS syndrome | 18% | 96% | Australian, European, South African |
Nevirapine | anti-retroviral | HLA-Cw*8 or HLA-Cw*8:-B*14 | DRESS syndrome | 18% | 96% | Italian, Japanese |
Nevirapine | anti-retroviral | HLA-B*35, HLA-B*35:01, or HLA-B*35:05 | SJS, TEN, SJS/TEN | ? | ? | Asian |
Nevirapine | anti-retroviral | HLA-C*04:01 | SJS, TEN, SJS/TEN | ? | ? | Malawian |
Abacavir | anti-retroviral | HLA-B*57:01 | DRESS syndrome | 55% | 100% | European, African |
Due to gene editing. the number of diverse T-cell receptors expressed is estimated to be as high as 10 trillion. This has made it difficult to identify specific T-cell receptor types that are uniquely associated with the development of SCARs. One study, however, identified the preferential presence of the TCR-V-b and complementarity-determining region 3 in T-cell receptors found on the T cells in the blisters of patients with allopurinol-induced SCARs. This finding is compatible with the notion that specific types of T-cell receptors are involved in the development of specific drug-induced SCARs. [15]
Certain variations in ADME (i.e. absorption, distribution, metabolism, and excretion of a drug) are associated with the development of SCARs. These variations influence the levels and duration of a drug or drug metabolite in tissues and thereby impact the drug's or drug metabolite's ability to evoke SCARs. [1] A prominent example of an ADME-based genetic predisposition to SCARs involves the CYP2CP*3 allele of the CYP2C9 gene. CYP2C9, a cytochrome P450 enzyme, metabolizes various substances including phenytoin. The CYP2CP*3 variant of CYP29C has reduced catalytic activity. Individuals studied in Japan or Malaysia, and the Han Chinese in Taiwan that express this variant have an increased chance of developing the DRESS syndrome, SJS, SJS/TEN, or TEN when taking phenytoin while Africans in Mozambique expressing this variant taking phenytoin have an increase risk of developing SJS, SJS/TEN, or TEN. These reactions appear due to increases in the drug's blood and tissue levels. [16] In a second example of a genetically based ADME defect causing SCARs, Japanese individuals bearing slow acetylating variants of the N-acetyltransferase 2 gene, (NAT2), viz., NAT2*6A and NAT2*7B, acetylate sulfasalazine more slowly than individuals homozygous for the wild type gene. Individuals expressing the NAT2*6A and NAT2*7 variants have an increased risk for developing a particularly severe form of the DRESS syndrome-like reactions to this anti-inflammatory drug. [10] None-genetic ADME factors are also associated with increased risks of developing SCARs. For example, allopurinol is metabolized to oxipurinol, a product with a far slower renal excretion rate than its parent compound. Renal impairment is associated with abnormally high blood levels of oxipurinol and an increased risk of developing the DRESS syndrome, particularly the more severe forms of this disorder. Dysfunction of the kidney and liver are also suggested to promote SCARs responses to other drugs due to the accumulation of SCARs-inducing drugs or metabolites in blood and tissues. [1] [6] Currently, it is suspected that the expression of particular HLA proteins and T-cell receptors interact with ADME factors to promote SCARs particularly in their more serious forms. [1] [16]
During the progression of the DRESS syndrome certain viruses which previously infected an individual and then became latent are reactivated and proliferate. Viruses known to do so include certain members of the Herpesviridae family of Herpes viruses viz., Epstein–Barr virus, human herpesvirus 6, human herpesvirus 7, and cytomegalovirus. Individuals suffering the DRESS syndrome may exhibit sequential reactivation of these four virus, typically in the order just given. Reactivation of these viruses is associated with sequential flare-ups in symptoms, a prolonged course, and increased disease severity which includes significant organ involvement and the development of certain autoimmune diseases viz., systemic lupus erythematosus, autoimmune thyroiditis, and type 1 diabetes mellitus. While these viral reactivations, particularly of human herpes virus 6, have been suggested to be an important factor in the pathogenesis of the DRESS syndrome, studies to date have not clearly determined if they are a cause or merely a consequence of T cell-mediated tissue injury. Rare case reports have associated the SJS/TEN spectrum of SCARs with reactivation of human herpesvirus 6; reactivation of cytomegalovirus has also been proposed to be associated with AGEP although a large study failed to observe the latter association. In all cases, the relationships of viral reactivation to the development and severity of any SCARs disorder is uncertain and requires further study. [1] [4]
Although more than 90% of AGEP are associated with the intake of a presumptively offending drug, reports have associated infection with Parvovirus B19, mycoplasma, cytomegalovirus, coxsackie B4 virus, Chlamydophila pneumoniae , E. coli , and Echinococcus with the drug-independent development of this disorder. The pathophysiology for the development of these drug-independent cases of AGEP is unclear. [11] Viral infections have also been observed to be associated with the development of SJS, SJS/TEN, and TEN in the absence of a causative drug. [6]
Individuals suffering autoimmune disorders such as systemic lupus erythematosus may have an increased incidence of developing SCARs. While the cause for this possible predilection has not been determined, the altered immune system and the excessive production of cytokines occurring in these disorders could be contributing factors. [2] [6]
The tissue injury in SCARs is initiated principally by CD8+ or CD4+ T cells. Once drug-activated, these lymphocytes elicit immune responses to self tissues that can result in SCARs drug reactions by mechanisms which vary with the type of disorder that develops. Salient elements mediating tissue injury for each type of disorder include: [2] [13]
Future studies may find that drugs which neutralize one or more of these effectors to be useful for treating SCARs disorders.
Screening individuals for the expression of certain variant alleles of HLA genes before initiating treatment with particular SCARs-inducing drugs is recommended. These recommendations typically apply only to specific populations that have a significant chance of expressing the indicated variant since screening of populations with extremely low incidences of expressing the variant allele is considered cost-ineffective. [17] Individuals expressing the HLA allele associated with sensitivity to an indicated drug should not be treated with the drug. These recommendations include: [1] [18]
Current trials are underway to evaluate the cost-effectiveness of genetic screening for HLA-B*13:01 to prevent dapsone-induced SCARs in China and Indonesia. Similar trials are underway in Taiwan to prevent phenytoin-induced SCARs in individuals expressing the CYP2C9*3 allele of CYP2C9 or a series of HLA alleles. [18]
In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.
Stevens–Johnson syndrome (SJS) is a type of severe skin reaction. Together with toxic epidermal necrolysis (TEN) and Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN) overlap, they are considered febrile mucocutaneous drug reactions and probably part of the same spectrum of disease, with SJS being less severe. Erythema multiforme (EM) is generally considered a separate condition. Early symptoms of SJS include fever and flu-like symptoms. A few days later, the skin begins to blister and peel, forming painful raw areas. Mucous membranes, such as the mouth, are also typically involved. Complications include dehydration, sepsis, pneumonia and multiple organ failure.
In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". Prominent examples include celiac disease, diabetes mellitus type 1, Henoch–Schönlein purpura, systemic lupus erythematosus, Sjögren syndrome, eosinophilic granulomatosis with polyangiitis, Hashimoto's thyroiditis, Graves' disease, idiopathic thrombocytopenic purpura, Addison's disease, rheumatoid arthritis, ankylosing spondylitis, polymyositis, dermatomyositis, and multiple sclerosis. Autoimmune diseases are very often treated with steroids.
The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are called MHC molecules.
Allopurinol is a medication used to decrease high blood uric acid levels. It is specifically used to prevent gout, prevent specific types of kidney stones and for the high uric acid levels that can occur with chemotherapy. It is taken orally or intravenously.
The human leukocyte antigen (HLA) system or complex of genes on chromosome 6 in humans which encode cell-surface proteins responsible for regulation of the immune system. The HLA system is also known as the human version of the major histocompatibility complex (MHC) found in many animals.
Toxic epidermal necrolysis (TEN) is a type of severe skin reaction. Together with Stevens–Johnson syndrome (SJS) it forms a spectrum of disease, with TEN being more severe. Early symptoms include fever and flu-like symptoms. A few days later the skin begins to blister and peel forming painful raw areas. Mucous membranes, such as the mouth, are also typically involved. Complications include dehydration, sepsis, pneumonia, and multiple organ failure.
HLA-B is a human gene that provides instructions for making a protein that plays a critical role in the immune system. HLA-B is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders such as viruses and bacteria.
Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted:
HLA-DQ (DQ) is a cell surface receptor protein found on antigen-presenting cells. It is an αβ heterodimer of type MHC class II. The α and β chains are encoded by two loci, HLA-DQA1 and HLA-DQB1, that are adjacent to each other on chromosome band 6p21.3. Both α-chain and β-chain vary greatly. A person often produces two α-chain and two β-chain variants and thus 4 isoforms of DQ. The DQ loci are in close genetic linkage to HLA-DR, and less closely linked to HLA-DP, HLA-A, HLA-B and HLA-C.
HLA-A is a group of human leukocyte antigens (HLA) that are encoded by the HLA-A locus, which is located at human chromosome 6p21.3. HLA is a major histocompatibility complex (MHC) antigen specific to humans. HLA-A is one of three major types of human MHC class I transmembrane proteins. The others are HLA-B and HLA-C. The protein is a heterodimer, and is composed of a heavy α chain and smaller β chain. The α chain is encoded by a variant HLA-A gene, and the β chain (β2-microglobulin) is an invariant β2 microglobulin molecule. The β2 microglobulin protein is encoded by the B2M gene, which is located at chromosome 15q21.1 in humans.
Drug rash with eosinophilia and systemic symptoms or drug reaction with eosinophilia and systemic symptoms (DRESS), also termed drug-induced hypersensitivity syndrome (DIHS), is a rare reaction to certain medications. It involves primarily a widespread skin rash, fever, swollen lymph nodes, and characteristic blood abnormalities such as an abnormally high level of eosinophils, low number of platelets, and increased number of atypical white blood cells (lymphocytes). However, DRESS is often complicated by potentially life-threatening inflammation of internal organs and the syndrome has about a 10% mortality rate. Treatment consists of stopping the offending medication and providing supportive care. Systemic corticosteroids are commonly used as well but no controlled clinical trials have assessed the efficacy of this treatment.
HLA-B58 (B58) is an HLA-B serotype. B58 is a split antigen from the B17 broad antigen, the sister serotype B57. The serotype identifies the more common HLA-B*58 gene products. B*5801 is associated with allopurinol induced inflammatory necrotic skin disease.
HLA-B57 (B57) is an HLA-B serotype. B57 is a split antigen from the B17 broad antigen, the sister serotype being B58. The serotype identifies the more common HLA-B*57 gene products. Like B58, B57 is involved in drug-induced inflammatory skin disorders.
The following outline is provided as an overview of and topical guide to immunology:
In medicine, a drug eruption is an adverse drug reaction of the skin. Most drug-induced cutaneous reactions are mild and disappear when the offending drug is withdrawn. These are called "simple" drug eruptions. However, more serious drug eruptions may be associated with organ injury such as liver or kidney damage and are categorized as "complex". Drugs can also cause hair and nail changes, affect the mucous membranes, or cause itching without outward skin changes.
Allopurinol hypersensitivity syndrome(AHS) typically occurs in persons with preexisting kidney failure. Weeks to months after allopurinol is begun, the patient develops a morbilliform eruption or, less commonly, develops one of the far more serious and potentially lethal severe cutaneous adverse reactions viz., the DRESS syndrome, Stevens Johnson syndrome, or toxic epidermal necrolysis. About 1 in 1000 patients receiving allopurinol are affected, and mortality rates have been reported to be between 20% and 25%.
Acute generalized exanthematous pustulosis (AGEP) is a rare skin reaction that in 90% of cases is related to medication.
Peptide-based synthetic vaccines are subunit vaccines made from peptides. The peptides mimic the epitopes of the antigen that triggers direct or potent immune responses. Peptide vaccines can not only induce protection against infectious pathogens and non-infectious diseases but also be utilized as therapeutic cancer vaccines, where peptides from tumor-associated antigens are used to induce an effective anti-tumor T-cell response.
The p-i concept refers to the pharmacological interaction of drugs with immune receptors. It explains a form of drug hypersensitivity, namely T cell stimulation, which can lead to various acute inflammatory manifestations such as exanthems, eosinophilia and systemic symptoms, Stevens–Johnson syndrome, toxic epidermal nercrolysis, and complications upon withdrawing the drug.