Drug hypersensitivity reactions, skin syndrome

Immune vasculitis can also be induced by drugs. The sulfonamides, penicillin, thiouracil, anticonvulsants, and iodides have all been implicated in the initiation of hypersensitivity angiitis. Erythema multiforme is a relatively mild vasculitic skin disorder that may be secondary to drug hypersensitivity. Stevens-Johnson syndrome is probably a more severe form of this hypersensitivity reaction and consists of erythema multiforme, arthritis, nephritis, central nervous system abnormalities, and myocarditis. It has frequently been associated with sulfonamide therapy. Administration of nonhuman monoclonal or polyclonal antibodies such as rattlesnake antivenin may cause serum sickness. 

Extrapyramidal reactions include parkinsonism, acute muscular dystonias, akathisia, tardive dyskinesia and malignant neuroleptic syndrome. They can also cause hypersensitivity reaction including cholestatic jaundice, skin rash, urticaria, photosensitivity and contact dermatitis. There is also blue pigmentation of skin, lenticular opacities on prolonged use of drug. 

Adverse reactions to cefuroxime have been generally mild and transient in nature. As with other cephalosporins there have been rare reports of erythema multiforme, Steven-Johnson syndrome, toxic epidermal necrolysis (exanthematic necrolysis) and hypersensitivity reactions including skin rashes, urticaria, pruritus, drug fever, serum sickness and very rarely anaphylaxis. 

The major adverse reactions to the penicillins are hypersensitivity responses. Manifestations of hypersensitivity inclnde nrticaria, angioedema, and anaphylaxis (type 1 reaction) hemolytic anemia (type 11 reaction) interstitial nephritis, vascnlitis, and serum sickness (type 111 reaction) and contact dermatitis or Stevens-Johnson syndrome (type IV reaction). A maculopapular rash occnrs late in the treatment course of 2% to 3% of patients receiving a penicillin drug. Once a patient has had a hypersensitivity response to a penicillin, it is probable, bnt not certain, that a reaction will occur with exposure to the same penicillin or to any other penicillin. Intradermal skin tests can predict whether a patient is at risk for developing a hypersensitivity reaction to the penicillins. If the resnlts are positive, penicillins should generally be avoided. 

A review of furosemide-induced skin reactions included a description of a unique case of an 88-year-old man who developed an eruption that clinically and histologically simulated Sweet s syndrome (acute febrile neutrophilic vasculitis) after 6 weeks (15). Atypical features and rapid resolution suggested a drug eruption rather than true Sweet s syndrome. However, a similar mechanism may have been implicated a hypersensitivity reaction involving immune complexes. 

Both paditaxel and docetaxel may result in anaphylactoid or severe hypersensitivity reactions manifested by dyspnea, bronchospasm, angioedema, hypotension (occasionally HTN), and urticarial skin reactions. The reaction may be due to the active drug itself or to the vehicle (Cremophor or polysorbate 80). Additionally, patients receiving docetaxel may experience serious or life-threatening fluid retention. This syndrome is characterized by poorly tolerated peripheral or generalized edema, pleural effusion, dyspnea, ascites, and cardiac tamponade. 

Adverse reactions to penicillins are rare diarrhoea can occur due to alteration in normal gastrointestinal bacteria. In fact, penicillins are probably the least toxic drugs known. Hypersensitivity reactions to penicillins occur in up to 10% of patients and vary from mild skin rashes to exfoliative dermatitis and Stevens-Johnson syndrome (immune vasculitis with arthritis, nephritis, central nervous system abnormalities and myocarditis) and from bronchoconstriction to life-threatening anaphylactic shock. 

The sulfonamides are associated with a number of skin and mucous membrane manifestations attributed to sensitization to sulfonamide, including various rashes, erythema nodosum, erythema multiforme of the Stevens-Johnson type, Behget s syndrome, exfoliative dermatitis, and photosensitivity. These hypersensitivity reactions usually occur after the first week of therapy but may appear earlier in previously sensitized individuals. Fever, malaise, and pruritus frequently are present simultaneously. The incidence of untoward dermal effects is -2% with sulfisoxazole, although a higher frequency is seen in patients with AIDS. A syndrome similar to serum sickness may appear after several days of sulfonamide therapy. Drug fever occurs in -3% of patients treated with sulfisoxazole. 

Type IVc. T cells themselves can also act as effector cells. They migrate to the tissue and can kill tissue cells such as hepatocytes or keratinocytes in a perforin/ granzymeB- and FasL-dependent manner (Schnyder et al. 1998 Nassif et al. 2002, 2004 Kuechler et al. 2004). Such reactions occur in most drug-induced delayed hypersensitivity reactions, mostly together with other type IV reactions (monocyte, eosinophil, or neutrophil recruitment and activation). Cytotoxic T cells thus play an important role in maculopapular or bullous skin diseases as well as in conditions characterized by neutrophilic inflammation (acute generalized exanthematous pustulosis, AGEP), and in contact dermatitis. Type IVc reactions appear to be dominant in bullous skin reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), where activated CD8-t T cells kill keratinocytes (Schnyder et al. 1998 Nassif et al. 2002, 2004). They may also be the dominant cell type in hepatitis or interstitial nephritis. 

Alanore L, Roujeau JC (2007) Clinic and pathogenesis of severe bullous skin reactions Stevens-Johnson syndrome, toxic epidermal necrolysis. In Pichler WJ (ed) Drug hypersensitivity. Karger, Basel, pp 267-277... 

The chemically similar teicoplanin, not approved in the USA, is not inferior to vancomycin with regard to efficiency of treating grampositive infections. It shows a lower rate of adverse reactions, particularly nephrotoxicity and, as already discussed, is used as a substitute for vancomycin in red man syndrome. When hypersensitivity reactions do occur with teicoplanin they are generally of the delayed type, but there are a few documented cases of apparent IgE antibody-mediated reactions implicated, for example, by an immediate wheal and flare skin reaction to the drug or by teicoplanin-induced histamine release from a patient s basophils. Despite the chemical and pharmacological... 

Many of the reactions to sulfonamides involve the skin and mucous membranes. The more severe reactions that occur include potentially lethal toxidermias and a delayed hypersensi-tivity-type syndrome characterized by fever, skin rash, and multi-organ toxicity, hnmediate type I reactions are the most well-defined sulfonamide-induced hypersensitivity reactions with the best defined allergenic drug structmes. Sulfonamides with one methyl substituent on a five- or six-membered aromatic heterocyclic ring on the carbon p to the sulfon-amido substituent are the structmes most complanentary to anti-sulfamethoxazole IgE antibody combining sites. 

Hypersensitivity or idiosyncrasy to quinidine or other cinchona derivatives manifested by thrombocytopenia, skin eruption or febrile reactions myasthenia gravis history of thrombocytopenic purpura associated with quinidine administration digitalis intoxication manifested by arrhythmias or AV conduction disorders complete heart block left bundle branch block or other severe intraventricular conduction defects exhibiting marked QRS widening or bizarre complexes complete AV block with an AV nodal or idioventricular pacemaker aberrant ectopic impulses and abnormal rhythms due to escape mechanisms history of drug-induced torsade de pointes history of long QT syndrome. 

SED-13, 513) (SEDA-18, 215) (SEDA-22, 216). Three cases of skin reactions (hypersensitivity syndrome reaction, pruritic exanthematous eruption, and acute generalized exanthematous pustulosis) possibly induced by diltiazem have been described and the literature on skin reactions associated with calcium antagonists has been reviewed. The number of diltiazem-induced cutaneous events was significantly greater than those induced by either nifedipine or verapamil. However, there was no difference in the proportion of serious cutaneous adverse events due to any of these three drugs (11). 

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