STUDY - Technical - New Dacian's Medicine
Drug-Induced
Skin Reactions (5)
Translation Draft
We've come to the diagnosis of drug reactions. Possible causes of an adverse reaction can be assessed as certain, probable, possible or unlikely on the basis of six variables: 1. previous experience with the drug in the general population, 2. alternative etiological candidates, 3. chronology of events, 4. level of the drug or signs of overdose, 5. patient reaction to discontinuation of administration and 6. patient's reaction to re-exposure.
As for previous experience, tables of relative reaction rates are available and are useful to assess the likelihood that a particular medicine is responsible for a particular skin reaction.
The specific morphological type of a medicinal reaction may, however, alter these reaction indices by increasing or decreasing the likelihood that a particular medicinal product is responsible for a particular reaction. For example, because fixed drug rashes are more common in barbiturates than in penicillin, a drug-like fixed erythema in a patient receiving both types of drugs is more likely due to barbiturates, even if penicillin has a higher overall index of drug reactions.
For alternative etiological candidates, a rash may be due to exacerbation of a pre-existing disease or the occurrence of a drug-free disease. For example, a patient with psoriasis may experience an exacerbation of the disease coincidentaltose to taking penicillin for a streptococcal infection, in which case the infection is a more likely cause of the disease than the reaction to the medicine.
In the case of the chronology of events, since most skin drug reactions occur within the first 2 weeks after the start of therapy, reactions that begin after 2 weeks are less likely due to medication. In the case of the concentration of medicinal products, some skin reactions are dependent on dosage or cumulative toxicity.
For example, lichenoid dermatosis due to gold administration occurs more frequently in patients taking high doses. In case of discontinuation of exposure, most skin side effects are resolved to discontinuation of the suspected agent. A drug-related reaction is unlikely to be related if the improvement occurs when the medicine is still administered or if the patient's condition does not improve after discontinuation of the medicine and appropriate therapy.
The challenge test provides the most categorical information on skin adverse reactions to medicines, because if the reaction does not occur after the challenge test with a drug it is unlikely that the drug will be involved. The challenge test is often not practicable because patient safety and comfort are more important than obtaining certainty information through the challenge test.
Of particular importance is the rapid recognition of reactions that can become serious or fatal. In this case it is indicated to follow up the clinical and laboratory signs associated with the more serious clinical skin manifestations induced by drugs represented by: 1. skin (confluence disjointed erythema, facial edema or central facial damage, skin pain, palpable purpura, skin necrosis, bubbles or epidermal detachment, Nikolsky positive sign, mucous erosions, hives, swelling of the tongue), 2. (high fever greater than 40 degrees C, enlargement of lymph nodes, arthralgia or arthritis, dyspnoea, wheezing, hypotension), 3. laboratory results (eosinophilia greater than 1,000/ microL, lymphocytosis with atypical lymphocytes and abnormal liver function samples).
In this respect are helpful and the clinical characteristics of certain serious skin reactions frequently induced by drugs "attracted" by the following diagnoses: 1. Stevens-Johnson syndrome (with mucous lesions represented by erosions usually in at least 2 regions, with typical skin lesions represented by small blisters on brown purple macles or lesions "in the target", and rarely appear areas of confluence including take-off on less than 10% of the body surface , with common signs and symptoms represented by 10-30% of cases with fever, respiratory and gastrointestinal tract lesions, having alternative causes not related to drugs represented by postinfectious major polymorphic erythema, especially in the case of herpes simplex or mycoplasma infection), 2. Toxic epidermal necrolysis (with mucous lesions represented by erosions in at least 2 regions, with specific skin lesions represented by individual lesions such as those of Stevens-Johnson syndrome, the outer layer of the epidermis easily separating from the basal one at lateral pressure, with extensive necrotic epidermis beaches and total cleavage of more than 30% of the body surface , with signs and symptoms represented in almost all cases of fever, "acute skin failure", leukopenia, lesions of the airways and gastrointestinal tract), 3. hypersensitivity syndrome (with rare mucous lesions, with typical skin lesions represented by severe exantematous rashes, which may become purple and exfoliative dermatitis, with common signs and symptoms represented by 30-50% of cases of fever, lymphadenopathy, hepatitis, carditis, eosinophilia and atypical lymphocytes, having alternative causes not related to drugs represented by skin lymphoma), 4. vasculitis of small vessels (with rare mucous lesions, with typical skin lesions represented by palpable purpura, most often on the lower limbs, nodules, ulcerations and hives, with common signs and symptoms represented by 30-50% of cases affected gastrointestinal, including neuritis, fever and glomerulonephritis, having alternative causes not related to drugs represented by infections, rheumatic diseases and lymphomas), 5. serum disease or serum disease-like reactions (without mucous lesions, with typical skin lesions represented by morbiliform lesions, sometimes with hives, with common signs and symptoms represented by fever and arthralgia, having alternative causes not related to drugs represented by infections), 6. anticoagulant-induced necrosis (with rare mucous lesions, typical skin lesions represented by erythema, then purpura and necrosis, especially of regions with adipose layer, with common signs and symptoms represented by pain in the affected regions, having alternative causes not related to drugs represented by disseminated intravascular coagulation and septicaemia) and 7. angioedema (with frequently affected mucous membranes, with typical skin lesions represented by hives or swelling of the central part of the face, with common signs and symptoms represented by respiratory distress and cardiovascular collapse, having alternative causes not related to drugs represented by insect bites and food).
Let's move on to the drug allergy diagnosis now. IgE response tests include in vivo and in vitro methods, but these tests can only be done with a limited number of medicines, including penicillins and cephalosporins, some peptides and protein-structured medicines (insulin and xenogenic serums) and some substances used for general anesthesia.
In vivo testing is performed by prick (scarification) and/ or intradermal tests. An erythema-papula response greater than 2x2 mm than that observed in a physiological serum control sample occurring within 20 minutes is considered representative of the mediated IgE degranulation of mastocytes, provided that: 1. the patient does not have dermographism, 2. the drug does not degranulate nonspecific granulocytes, 3. the concentration of the drug is not high enough to be irritating and 4. solvent used does not produce erythema-papul response.
Skin tests with major and minor determinants of penicillins and cephalosporins have been shown to be useful for identifying patients at risk of developing anaphylactic reactions to these medicines. However, skin tests themselves have a small risk of anaphylaxis. Negative skin tests do not exclude IgE-mediated reactivity and the risk of anaphylaxis in response to penicillin in patients with negative skin tests is about 1% (approximately two thirds of patients with a positive skin test and a history of penicillin adverse reactions have an allergic risk of reexposure).
Skin tests may be negative in patients receiving antihistamines or in those in whom the allergy is in determinants not present in the test reagent. Although less well studied, similar techniques can identify patients who are sensitive to protein drugs and agents such as galamine and succinylcholine. Most other drugs are small molecules and skin testing on them is not enlightening.
In vitro testing for IgE can be done by assessing the serum's ability to bind to the antigen and then binding radio-marked antibodies to IgE (RAST test) or by assessing the drug's ability to cause histamine release from basophilics from drug-sensitive individuals. The RAST test is sensitive and specific, but is not available for most medicines, even in the case of penicillin, being available only for major determinants.
Also, the release of histamine from basophils is a research technique that is not generally available. There are no safe and widely available tests for NSAID sensitivity testing, agents that directly derange mastocytes or drugs that cause manifestations by activating the immune complex-mediated complement. Although it is possible to investigate for the absence of IgA antibodies, the usefulness of this maneuver in preventing anaphylaxis associated with transfusions in individuals deficient in IgA has not been revealed.
I'm done! From tomorrow we move on to the skin manifestations of internal diseases.
All good!
We've come to the diagnosis of drug reactions. Possible causes of an adverse reaction can be assessed as certain, probable, possible or unlikely on the basis of six variables: 1. previous experience with the drug in the general population, 2. alternative etiological candidates, 3. chronology of events, 4. level of the drug or signs of overdose, 5. patient reaction to discontinuation of administration and 6. patient's reaction to re-exposure.
As for previous experience, tables of relative reaction rates are available and are useful to assess the likelihood that a particular medicine is responsible for a particular skin reaction.
The specific morphological type of a medicinal reaction may, however, alter these reaction indices by increasing or decreasing the likelihood that a particular medicinal product is responsible for a particular reaction. For example, because fixed drug rashes are more common in barbiturates than in penicillin, a drug-like fixed erythema in a patient receiving both types of drugs is more likely due to barbiturates, even if penicillin has a higher overall index of drug reactions.
For alternative etiological candidates, a rash may be due to exacerbation of a pre-existing disease or the occurrence of a drug-free disease. For example, a patient with psoriasis may experience an exacerbation of the disease coincidentaltose to taking penicillin for a streptococcal infection, in which case the infection is a more likely cause of the disease than the reaction to the medicine.
In the case of the chronology of events, since most skin drug reactions occur within the first 2 weeks after the start of therapy, reactions that begin after 2 weeks are less likely due to medication. In the case of the concentration of medicinal products, some skin reactions are dependent on dosage or cumulative toxicity.
For example, lichenoid dermatosis due to gold administration occurs more frequently in patients taking high doses. In case of discontinuation of exposure, most skin side effects are resolved to discontinuation of the suspected agent. A drug-related reaction is unlikely to be related if the improvement occurs when the medicine is still administered or if the patient's condition does not improve after discontinuation of the medicine and appropriate therapy.
The challenge test provides the most categorical information on skin adverse reactions to medicines, because if the reaction does not occur after the challenge test with a drug it is unlikely that the drug will be involved. The challenge test is often not practicable because patient safety and comfort are more important than obtaining certainty information through the challenge test.
Of particular importance is the rapid recognition of reactions that can become serious or fatal. In this case it is indicated to follow up the clinical and laboratory signs associated with the more serious clinical skin manifestations induced by drugs represented by: 1. skin (confluence disjointed erythema, facial edema or central facial damage, skin pain, palpable purpura, skin necrosis, bubbles or epidermal detachment, Nikolsky positive sign, mucous erosions, hives, swelling of the tongue), 2. (high fever greater than 40 degrees C, enlargement of lymph nodes, arthralgia or arthritis, dyspnoea, wheezing, hypotension), 3. laboratory results (eosinophilia greater than 1,000/ microL, lymphocytosis with atypical lymphocytes and abnormal liver function samples).
In this respect are helpful and the clinical characteristics of certain serious skin reactions frequently induced by drugs "attracted" by the following diagnoses: 1. Stevens-Johnson syndrome (with mucous lesions represented by erosions usually in at least 2 regions, with typical skin lesions represented by small blisters on brown purple macles or lesions "in the target", and rarely appear areas of confluence including take-off on less than 10% of the body surface , with common signs and symptoms represented by 10-30% of cases with fever, respiratory and gastrointestinal tract lesions, having alternative causes not related to drugs represented by postinfectious major polymorphic erythema, especially in the case of herpes simplex or mycoplasma infection), 2. Toxic epidermal necrolysis (with mucous lesions represented by erosions in at least 2 regions, with specific skin lesions represented by individual lesions such as those of Stevens-Johnson syndrome, the outer layer of the epidermis easily separating from the basal one at lateral pressure, with extensive necrotic epidermis beaches and total cleavage of more than 30% of the body surface , with signs and symptoms represented in almost all cases of fever, "acute skin failure", leukopenia, lesions of the airways and gastrointestinal tract), 3. hypersensitivity syndrome (with rare mucous lesions, with typical skin lesions represented by severe exantematous rashes, which may become purple and exfoliative dermatitis, with common signs and symptoms represented by 30-50% of cases of fever, lymphadenopathy, hepatitis, carditis, eosinophilia and atypical lymphocytes, having alternative causes not related to drugs represented by skin lymphoma), 4. vasculitis of small vessels (with rare mucous lesions, with typical skin lesions represented by palpable purpura, most often on the lower limbs, nodules, ulcerations and hives, with common signs and symptoms represented by 30-50% of cases affected gastrointestinal, including neuritis, fever and glomerulonephritis, having alternative causes not related to drugs represented by infections, rheumatic diseases and lymphomas), 5. serum disease or serum disease-like reactions (without mucous lesions, with typical skin lesions represented by morbiliform lesions, sometimes with hives, with common signs and symptoms represented by fever and arthralgia, having alternative causes not related to drugs represented by infections), 6. anticoagulant-induced necrosis (with rare mucous lesions, typical skin lesions represented by erythema, then purpura and necrosis, especially of regions with adipose layer, with common signs and symptoms represented by pain in the affected regions, having alternative causes not related to drugs represented by disseminated intravascular coagulation and septicaemia) and 7. angioedema (with frequently affected mucous membranes, with typical skin lesions represented by hives or swelling of the central part of the face, with common signs and symptoms represented by respiratory distress and cardiovascular collapse, having alternative causes not related to drugs represented by insect bites and food).
Let's move on to the drug allergy diagnosis now. IgE response tests include in vivo and in vitro methods, but these tests can only be done with a limited number of medicines, including penicillins and cephalosporins, some peptides and protein-structured medicines (insulin and xenogenic serums) and some substances used for general anesthesia.
In vivo testing is performed by prick (scarification) and/ or intradermal tests. An erythema-papula response greater than 2x2 mm than that observed in a physiological serum control sample occurring within 20 minutes is considered representative of the mediated IgE degranulation of mastocytes, provided that: 1. the patient does not have dermographism, 2. the drug does not degranulate nonspecific granulocytes, 3. the concentration of the drug is not high enough to be irritating and 4. solvent used does not produce erythema-papul response.
Skin tests with major and minor determinants of penicillins and cephalosporins have been shown to be useful for identifying patients at risk of developing anaphylactic reactions to these medicines. However, skin tests themselves have a small risk of anaphylaxis. Negative skin tests do not exclude IgE-mediated reactivity and the risk of anaphylaxis in response to penicillin in patients with negative skin tests is about 1% (approximately two thirds of patients with a positive skin test and a history of penicillin adverse reactions have an allergic risk of reexposure).
Skin tests may be negative in patients receiving antihistamines or in those in whom the allergy is in determinants not present in the test reagent. Although less well studied, similar techniques can identify patients who are sensitive to protein drugs and agents such as galamine and succinylcholine. Most other drugs are small molecules and skin testing on them is not enlightening.
In vitro testing for IgE can be done by assessing the serum's ability to bind to the antigen and then binding radio-marked antibodies to IgE (RAST test) or by assessing the drug's ability to cause histamine release from basophilics from drug-sensitive individuals. The RAST test is sensitive and specific, but is not available for most medicines, even in the case of penicillin, being available only for major determinants.
Also, the release of histamine from basophils is a research technique that is not generally available. There are no safe and widely available tests for NSAID sensitivity testing, agents that directly derange mastocytes or drugs that cause manifestations by activating the immune complex-mediated complement. Although it is possible to investigate for the absence of IgA antibodies, the usefulness of this maneuver in preventing anaphylaxis associated with transfusions in individuals deficient in IgA has not been revealed.
I'm done! From tomorrow we move on to the skin manifestations of internal diseases.
All good!
Dorin, Merticaru