STUDY - Technical - New Dacian's Medicine
Drug-Induced
Skin Reactions (4)
Translation Draft
Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin (but not salicylates in general) and indomethacin, cause two broad categories of allergic-type symptoms in sensitive individuals: 1. about 1% of people have hives or angioedema and
2. about half of this number (0.5%) has rhinosinusitis and asthma (however, about 10% of adult asmatics and one third of individuals with nasal polyposis and sinusitis may have side effects with aspirin).
Urticaria/ angioedema may occur as early as 24 hours and may occur at any age. Rhinosinusitis-asthma syndrome generally occurs within the first hour of taking the drug. In young people, the reaction mode often begins as an aqueous rhinorrhea, which can be complicated by nasal and sinus infection, and polyposis, sanghinolent secretion and nasal eosinophilia. In many individuals with this syndrome, asthma eventually occurs, which can endanger life at any subsequent ingestion of NSAID, and symptoms may persist despite avoiding these drugs.
Proof of association of symptoms with NSAID use requires either an outright history of symptomatology following drug ingestion or oral testing. For the latter to be carried out in relative safety, 1. asthma must be well controlled, 2. the procedure must be performed in the hospital environment by experienced staff, able to recognise and treat acute respiratory reactions and 3. the challenge test should be started with very low doses of aspirin and increased every 1-2 hours by doubling the dose according to tolerance (up to 650 mg).
In a study of 50 successive patients with a positive history of aspirin-induced bronchospasm, 84% had pulmonary or naso-ocular symptoms of aspirin, but 16% did not react (moreover, when the subjects, who initially had positive tests on an exposure, were reexposed to aspirin, the clinical reaction model was identical at only 60%). While cross-reactivity between NSAIDs is common, it is non-immunological and patients who are sensitive to NSAID cannot be identified by evaluation of IgE antibodies to aspirin, lymphocytic sensitisation or in vitro immunological testing.
All cross-reacting drugs are cyclooxygenase inhibitors, although salicylates also inhibit cyclooxygenase, but (except aspirin) do not provide the answer. "Desensitization" to the adverse effects of NSAID can be performed through the challenge test outlined above, although repeated exposures with the initial dose of challenge may be required. Desensitization works through unknown mechanisms, makes the subject tolerant to all NSAIDs studied so far and persists for at least 24 to 96 hours and is likely universal, but does not have a positive effect on the underlying disorder.
We've reached the contrast substances for radiological exploration. More and more patients are subjected to radiocontrast agents and 5-10% of patients receiving them have a certain reaction: urticaria at 1%, dyspnea at 0.20% and exitus at 0.01%. Allergic reactions with urticaria and angioedema, asthma and hypotension, mimicking anaphylaxis, occur in less than 1% of radiological contrast procedures. About a third of those with mild reactions to previous exposures react again to reexposure. A mechanism for reactions to contrast media is not proven.
Increases in plasma histamine occur in those with and without reaction and may be due to the hypertonicity of these substances. In addition, the activation of the complement, both classical and alternative, occurs in reactive and normal individuals. In short, the mechanism of these reactions is not understood and no test identifies patients at risk of reaction to a radiological contrast environment. repeated reactions are common, performing a thorough anamnesis is the best technique available to identify those prone to an adverse reaction. Several regimens are recommended to decrease the reaction repetition rate to about 10%. A scheme consists of the administration of prednisone and diphenhydramin at least one hour before the procedure.
Phenytoin and other hydantoins cause morbiliform eruptions, polymorphic erythema and NET, as well as a hypersensitivity reaction (previously described) and pseudolymphomatous syndrome. In one study, 5% of children treated with phenytoin developed a mild, dose-dependent maculopapular rash lasting 3-5 days and occurring within the first 2 weeks after starting treatment.
Pseudolymphomatous syndrome, consisting of adenopathy and atypia on histological examination of the lymph nodes, is a chronic form of phenytoin hypersensitivity syndrome, and skin changes are less marked in this syndrome. The use of phenytoin is commonly associated with gingival hyperplasia and rarely with a syndrome similar to systemic lupus erythematosus, severe exfoliative dermatitis and node polyarteritis.
Since many side effects of hydantoin may be dose-related, drugs that interfere with its elimination (e.g. chloramphenicol) prolong those effects. Sulfasalazine, other sulfomanime and allopurinol cause reactions that cannot be distinguished from those of phenytoin hypersensitivity syndrome.
Let's move on to thiazides and sulfonamides! Thiazides are among the most common causes of drug-induced urticaria and morphoform rash (they also produce polymorphic erythema, drug-induced skin vasculitis and lichenoid and photosensitivity rashes). Because they are substituted sulfonamides, antibodies to these diuretics can cross-react with sulfonamide antibiotics and hypoglycaemic agents of the sulfonamide class.
The combination of sulfamethoxazole and trimetoprim causes two distinct skin reactions: 1. a urticaria rash starting from the first few days of treatment and 2. a morbiliform rash often occurring more than a week after the start of therapy. Morbiliform reaction is common in AIDS patients and is associated with pancytopenia in some patients. The rash may have an intense purple character, independent of the presence of vasculitis. One patient had NET and pancytopenia after administration of trimetoprim-sulfamethoxazole.
The "time" has come to approach the agents used in cancer therapy. Because many agents used in cancer chemotherapy inhibit cell division, the rapidly proliferative structures of the skin, including hair, mucous membranes and appendages, are sensitive to their effects (as a result, stomatitis and alopecia are among the most common dose-dependent side effects of chemotherapy).
Onicodystrophy (angle dystrophic changes) is found in bleomycin, hydroxyurea (hydroxycarbamide) and 5-fluorouracil. Sterile cellulitis, phlebitis and ulceration of pressure zones occur in many of these agents. Urticaria, angioedema, exfoliative dermatitis and palmar and plantar erythema have also been encountered, as have local and diffuse hyperpigmentation. The diagnosis and treatment of these reactions are particularly difficult, due to the underlying malignant disease.
Another topic to address is that of tetracyclines. While urticaria and morbiliform rashes sometimes cause other skin side effects, including a photosensitivity reaction (as a result of drug-induced phototoxicity) and onicolize (sometimes without apparent skin photosensitivity). These reactions occur in demecloclycline, doxycycline, minocycline, tetracycline and oxytetracycline. Tetracyclines also cause lichenoid eruptions, as well as fixed drug rashes.
A gram-negative, gram-negative acneiform folliculitis after long-term use of tetracycline is due to the proliferation of resistant bacteria. Several pigmentation abnormalities have been noted. If used during pregnancy or in young children, tetracycline stains the teeth, sometimes permanently. Minocycline has been associated with a flu-like syndrome (accompanied by headache, malaise and eosinophilia), which recurs upon reexposure.
Glucocorticoids, both systemic and topical, cause various skin changes, including acneiform rashes, atrophy, striae and other stigmas of Cushing syndrome, and in high enough doses can delay wound healing. Patients using glucocorticoids have a higher risk for bacterial, mycotic and levuri skin infections that may be misinterpreted as drug rashes, but are actually adverse drug effects.
Antimalarials (antimalarial agents) are used in the treatment of several skin diseases, including skin manifestations of lupus and polymorphic rash, but can also induce skin reactions. In patients with asymptomatic tartaria cutanea, chlorochin increases porphyrin levels and may exacerbate the disease.
Pigmentation disorders, including black pigmentation of the face, mucous membranes and pretibial and sub-angle regions, occur in antimalarials, and quinacrine (mepacrin) causes a generalized change in skin color to yellow. Antimalarial agents may exacerbate psoriasis and have been reported as adverse reactions exfoliative dermatitis, drug fixed erythema, lichenoid dermatitis and centrifugal annular erythema during their use.
Gold, "present" in chrysotherapy, has been associated with various dose-dependent dermatological reactions (including maculopapular rashes), which can develop up to 2 years after initiation of therapy and require months to heal. As side effects, nodos erythema, psoriatic dermatitis, vaginal pruritus, rashes similar to pitiriazis rosea, hyperpigmentation and lichenoid rashes similar to those found in antimalarial agents have been reported. After a skin reaction, it is sometimes possible to restore gold therapy at lower doses without recurrence of dermatitis.
Ready for today! Tomorrow I will address the diagnosis of drug reactions (including drug allergy).
Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin (but not salicylates in general) and indomethacin, cause two broad categories of allergic-type symptoms in sensitive individuals: 1. about 1% of people have hives or angioedema and
2. about half of this number (0.5%) has rhinosinusitis and asthma (however, about 10% of adult asmatics and one third of individuals with nasal polyposis and sinusitis may have side effects with aspirin).
Urticaria/ angioedema may occur as early as 24 hours and may occur at any age. Rhinosinusitis-asthma syndrome generally occurs within the first hour of taking the drug. In young people, the reaction mode often begins as an aqueous rhinorrhea, which can be complicated by nasal and sinus infection, and polyposis, sanghinolent secretion and nasal eosinophilia. In many individuals with this syndrome, asthma eventually occurs, which can endanger life at any subsequent ingestion of NSAID, and symptoms may persist despite avoiding these drugs.
Proof of association of symptoms with NSAID use requires either an outright history of symptomatology following drug ingestion or oral testing. For the latter to be carried out in relative safety, 1. asthma must be well controlled, 2. the procedure must be performed in the hospital environment by experienced staff, able to recognise and treat acute respiratory reactions and 3. the challenge test should be started with very low doses of aspirin and increased every 1-2 hours by doubling the dose according to tolerance (up to 650 mg).
In a study of 50 successive patients with a positive history of aspirin-induced bronchospasm, 84% had pulmonary or naso-ocular symptoms of aspirin, but 16% did not react (moreover, when the subjects, who initially had positive tests on an exposure, were reexposed to aspirin, the clinical reaction model was identical at only 60%). While cross-reactivity between NSAIDs is common, it is non-immunological and patients who are sensitive to NSAID cannot be identified by evaluation of IgE antibodies to aspirin, lymphocytic sensitisation or in vitro immunological testing.
All cross-reacting drugs are cyclooxygenase inhibitors, although salicylates also inhibit cyclooxygenase, but (except aspirin) do not provide the answer. "Desensitization" to the adverse effects of NSAID can be performed through the challenge test outlined above, although repeated exposures with the initial dose of challenge may be required. Desensitization works through unknown mechanisms, makes the subject tolerant to all NSAIDs studied so far and persists for at least 24 to 96 hours and is likely universal, but does not have a positive effect on the underlying disorder.
We've reached the contrast substances for radiological exploration. More and more patients are subjected to radiocontrast agents and 5-10% of patients receiving them have a certain reaction: urticaria at 1%, dyspnea at 0.20% and exitus at 0.01%. Allergic reactions with urticaria and angioedema, asthma and hypotension, mimicking anaphylaxis, occur in less than 1% of radiological contrast procedures. About a third of those with mild reactions to previous exposures react again to reexposure. A mechanism for reactions to contrast media is not proven.
Increases in plasma histamine occur in those with and without reaction and may be due to the hypertonicity of these substances. In addition, the activation of the complement, both classical and alternative, occurs in reactive and normal individuals. In short, the mechanism of these reactions is not understood and no test identifies patients at risk of reaction to a radiological contrast environment. repeated reactions are common, performing a thorough anamnesis is the best technique available to identify those prone to an adverse reaction. Several regimens are recommended to decrease the reaction repetition rate to about 10%. A scheme consists of the administration of prednisone and diphenhydramin at least one hour before the procedure.
Phenytoin and other hydantoins cause morbiliform eruptions, polymorphic erythema and NET, as well as a hypersensitivity reaction (previously described) and pseudolymphomatous syndrome. In one study, 5% of children treated with phenytoin developed a mild, dose-dependent maculopapular rash lasting 3-5 days and occurring within the first 2 weeks after starting treatment.
Pseudolymphomatous syndrome, consisting of adenopathy and atypia on histological examination of the lymph nodes, is a chronic form of phenytoin hypersensitivity syndrome, and skin changes are less marked in this syndrome. The use of phenytoin is commonly associated with gingival hyperplasia and rarely with a syndrome similar to systemic lupus erythematosus, severe exfoliative dermatitis and node polyarteritis.
Since many side effects of hydantoin may be dose-related, drugs that interfere with its elimination (e.g. chloramphenicol) prolong those effects. Sulfasalazine, other sulfomanime and allopurinol cause reactions that cannot be distinguished from those of phenytoin hypersensitivity syndrome.
Let's move on to thiazides and sulfonamides! Thiazides are among the most common causes of drug-induced urticaria and morphoform rash (they also produce polymorphic erythema, drug-induced skin vasculitis and lichenoid and photosensitivity rashes). Because they are substituted sulfonamides, antibodies to these diuretics can cross-react with sulfonamide antibiotics and hypoglycaemic agents of the sulfonamide class.
The combination of sulfamethoxazole and trimetoprim causes two distinct skin reactions: 1. a urticaria rash starting from the first few days of treatment and 2. a morbiliform rash often occurring more than a week after the start of therapy. Morbiliform reaction is common in AIDS patients and is associated with pancytopenia in some patients. The rash may have an intense purple character, independent of the presence of vasculitis. One patient had NET and pancytopenia after administration of trimetoprim-sulfamethoxazole.
The "time" has come to approach the agents used in cancer therapy. Because many agents used in cancer chemotherapy inhibit cell division, the rapidly proliferative structures of the skin, including hair, mucous membranes and appendages, are sensitive to their effects (as a result, stomatitis and alopecia are among the most common dose-dependent side effects of chemotherapy).
Onicodystrophy (angle dystrophic changes) is found in bleomycin, hydroxyurea (hydroxycarbamide) and 5-fluorouracil. Sterile cellulitis, phlebitis and ulceration of pressure zones occur in many of these agents. Urticaria, angioedema, exfoliative dermatitis and palmar and plantar erythema have also been encountered, as have local and diffuse hyperpigmentation. The diagnosis and treatment of these reactions are particularly difficult, due to the underlying malignant disease.
Another topic to address is that of tetracyclines. While urticaria and morbiliform rashes sometimes cause other skin side effects, including a photosensitivity reaction (as a result of drug-induced phototoxicity) and onicolize (sometimes without apparent skin photosensitivity). These reactions occur in demecloclycline, doxycycline, minocycline, tetracycline and oxytetracycline. Tetracyclines also cause lichenoid eruptions, as well as fixed drug rashes.
A gram-negative, gram-negative acneiform folliculitis after long-term use of tetracycline is due to the proliferation of resistant bacteria. Several pigmentation abnormalities have been noted. If used during pregnancy or in young children, tetracycline stains the teeth, sometimes permanently. Minocycline has been associated with a flu-like syndrome (accompanied by headache, malaise and eosinophilia), which recurs upon reexposure.
Glucocorticoids, both systemic and topical, cause various skin changes, including acneiform rashes, atrophy, striae and other stigmas of Cushing syndrome, and in high enough doses can delay wound healing. Patients using glucocorticoids have a higher risk for bacterial, mycotic and levuri skin infections that may be misinterpreted as drug rashes, but are actually adverse drug effects.
Antimalarials (antimalarial agents) are used in the treatment of several skin diseases, including skin manifestations of lupus and polymorphic rash, but can also induce skin reactions. In patients with asymptomatic tartaria cutanea, chlorochin increases porphyrin levels and may exacerbate the disease.
Pigmentation disorders, including black pigmentation of the face, mucous membranes and pretibial and sub-angle regions, occur in antimalarials, and quinacrine (mepacrin) causes a generalized change in skin color to yellow. Antimalarial agents may exacerbate psoriasis and have been reported as adverse reactions exfoliative dermatitis, drug fixed erythema, lichenoid dermatitis and centrifugal annular erythema during their use.
Gold, "present" in chrysotherapy, has been associated with various dose-dependent dermatological reactions (including maculopapular rashes), which can develop up to 2 years after initiation of therapy and require months to heal. As side effects, nodos erythema, psoriatic dermatitis, vaginal pruritus, rashes similar to pitiriazis rosea, hyperpigmentation and lichenoid rashes similar to those found in antimalarial agents have been reported. After a skin reaction, it is sometimes possible to restore gold therapy at lower doses without recurrence of dermatitis.
Ready for today! Tomorrow I will address the diagnosis of drug reactions (including drug allergy).
Note: From tomorrow the
posts will begin to "shrink" quantitatively (they will not have
at least 1,500 words), because the holidays come, I start the
project New Medicine on www.dorinm.ro, I start another project
that goes to my heart ("the card game" called by me "Around the
Worlds"/ "Around the Worlds")
and... What difference does it make?!? I will never give up this project and, while I am still around, I will always write by improving the data presented, making more testing software, etc. You'll see! Rarely when I have been given not to keep my word (regardless of the interpretations of those around me)... Remember, this blog (and its clone on facebook) are just the precursors of materials that will be implemented by me on www.dorinm.ro, where everything will be completely different, much better structured, accessible, where there will be images, tests, evaluation software and autotherapy, etc. etc. etc. etc.
and... What difference does it make?!? I will never give up this project and, while I am still around, I will always write by improving the data presented, making more testing software, etc. You'll see! Rarely when I have been given not to keep my word (regardless of the interpretations of those around me)... Remember, this blog (and its clone on facebook) are just the precursors of materials that will be implemented by me on www.dorinm.ro, where everything will be completely different, much better structured, accessible, where there will be images, tests, evaluation software and autotherapy, etc. etc. etc. etc.
Have a good day!
Dorin, Merticaru