Cutaneous reactions rashes

Cutaneous reactions such as rash or Stevens-Johnson syndrome are also consist with initiation through protein haptenation, although in this case dendritic cell activation/ migration and T-cell propagation are involved [31]. Other immune mediators such as cytokines, nitric oxide and reactive oxygen species which may be linked to the formation of reactive metabolites may also be implicated, as may specific processes occurring at the level of the keratinocyte. 

Skin and subcutaneous tissue disorders Reversible cutaneous reactions have been observed and are generally mild to moderate. Reactions are characterised by a rash including localised eruptions mainly on the feet and hands (including severe hand and foot syndrome), but also on the arms, face or thorax, and frequently associated with pruritus. Eruptions generally occur within one week after the docetaxel infusion. Severe nail disorders are characterised by hypo- or hyperpigmentation and sometimes pain and onycholysis. 

Adverse effects of phenytoin, many of which can be very slow to develop, include impairment of cognitive function, which has led many physicians to prefer carbamazepine and valproate. Other nervous system effects range from sedation to delirium to acute cerebellar disorder to convulsions. Peripheral neuropathy also occurs. Cutaneous reactions include rashes (dose related), coarsening of facial features and hirsutism. Gum hyperplasia (due to inhibition of collagen catabolism) may develop and is more marked in children and when there is poor gum hygiene. 

Cutaneous reactions, apart from purpura and ecchymoses in those who are excessively anticoagulated, include hypersensitivity, rash and alopecia. Skin necrosis due to a mixture of haemorrhage and thrombosis occurs rarely where induction of warfarin therapy is over-abrupt and/or the patient has a genetically determined or acquired deficiency of the anticoagulant protein C or its cofactor protein S it can be very serious. 

Rashes or other aUergic-tjrpe cutaneous reactions are usually noted during the azathioprine hypersensitivity syndrome. Isolated but convincing reports point to the occurrence of vasculitis with microscopic polyarteritis (SEDA-21, 381) and Sweet s syndrome, which recurred after subsequent azathioprine exposure (SEDA-22, 410). 

A 48-year-old woman with a long history of insulin-dependent diabetes meUitus developed a severe cutaneous reaction to icodextrin (3). This happened 10 days after changing over to 7.5% icodextrin in order to improve ultrafiltration. The rash was maculo-papular and it affected most parts of her body. It was associated with severe pruritus. By the 13th day after it first appeared the rash had become exfohative and erythrodermic. There was rapid improvement in the first few days after the icodextrin dialysate had been withdrawn and she reverted to conventional glucose peritoneal dialysate. 

A wide range of cutaneous reactions have been reported in patients receiving G-CSF. Most skin disorders were minor with a skin rash or itching in about 8% of patients (56). 

Allergic skin reactions occur in 1-2% of patients who take nitrofurantoin and comprise about 21% of all adverse reactions to nitrofurantoin (5,71). They often occur with other reactions, such as drug fever, lung, or hver reactions. The lesions can present as pruritus, as macular, maculopapular, or vesicular rashes, urticaria, angioedema, or erjdhema multiforme (72). The frequency of serious cutaneous reactions (erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis) after nitrofurantoin has been estimated to be 7 cases per 100 000 exposed individuals (71). 

Most of the cutaneous adverse reactions to sulfonamides are associated with increased in vitro reactivity to sulfonamide metabolites, such as unstable hydroxyl-amines (160,161). In some cases glutathione deficiency has been proposed as a major mechanism. This seems to be important in patients with AIDS, in whom glutathione deficiency is frequent, and in whom skin rashes are much more common than in other patients (160,162). A predominance of slow acetylator phenotype has also been observed among patients with sulfonamide hypersensitivity reactions, and an association with the phenotypes HLA-A29, B-12, and DR-7 in patients with bullous cutaneous reactions (161,163-165). 

Patients with a history of a reaction to penicillin are advised not to receive cephalosporins if they can be avoided. Patients who have negative penicillin skin tests or experienced only mild cutaneous reactions, such as macu-lopapular rashes, have a low risk of serious reactions to cephalosporins. 

Cutaneous adverse reactions were reported to occur in 2.7% of hospitalized patients. Serious dermatologic drug reactions are estimated to occur in 1.9 cases per 1 million people per year and can have a mortality rate as high as 40%. Table 86-2 lists drugs and agents associated most commonly with cutaneous reactions. Antimicrobials are implicated most frequently with reaction rates ranging from 1 % to 8%. In a report of almost 6000 children, about 12% developed rashes with cefaclor compared with 7.4% with penicillins and 8.5% with sulfonamides. " ... 

Adverse hypersensitivity may start 1 to 8 weeks after start of drug use and clinically display as anaphylaxis, fever, rash and various cutaneous reactions (exanthema s, bullous responses, etc.), blood dyscrasias and involve multiple internal organs, including liver, kidney and lungs (Sullivan and Shear, 2001 Gomes and Demoly, 2005). Occasionally drug hypersensitivity results in very serious and life-threatening conditions, such as Steven Johnsons Syndrome (SJS) and toxic epidermal necrolysis (TEN). 

Allopurinol may cause a cutaneous reaction (3%) that is predominantly pruritic and maculopapular in nature, is accompanied by fever, malaise, or muscle ache, and the incidence increases with renal impairment. Because the onset of skin rash may be followed by severe hypersensitivity reactions, allopurinol should be discontinued by patients who develop such rashes. Patients with impaired renal function require less drug and careful observation. 

The cutaneous reaction caused by allopurinol is predominantly a pruritic, erythematous, or maculopapular eruption, but occasionally the lesion is urticarial or purpuric. Rarely, toxic epidermal necrolysis or Stevens-Johnson syndrome occurs, which can be fatal. The risk for Stevens-Johnson syndrome is limited primarily to the first 2 months of treatment. Because the rash may precede severe hypersensitivity reactions, patients who develop a rash should discontinue allopurinol. If indicated, desensitization to allopurinol can be carried out starting at 10—25 fjbg/day, with the drug diluted in oral suspension and doubled every 3—14 days until the desired dose is reached. This is successjul in approjdmately half of patients. Oxypurinol is available for compassionate use in the U.S. for patients intolerant of allopurinol. The safety of oxypurinol in patients with severe allopurinol hypersensitivity is unknown it is not recommended in this setting. 

The most frequent manifestations of drug allergies are delayed appearing cutaneous reactions, so-called rashes . They comprise a broad spectrum of clinical and distinct histopathological features which appear from 6 h to 10 days after drug... 

A fully robust animal model of NVP-induced hepatotoxicity has yet to be developed (Walubo et al. 2006), but Uetrecht and colleagues have characterized extensively a dose-dependent, NVP-induced, skin rash in female Brown Norway rats that resembles the idiosyncratic cutaneous reaction seen in humans and appears to be immune-mediated (Popovic et al. 2006 Shenton et al. 2007). An association between 12-hydroxy NVP metabolism and skin toxicity has been shown in a recent study (Chen et al. 2008), when it was found that 12-OH-NVP caused a rash at a lower dose than required for NVP. The authors proposed that the rash produced in rats may be due to quinonemethide formed in the skin via sulfation of 12-hydroxy NVP metabolite followed by loss of inorganic sulfate. 

The occurrence of anaphylactic shock (Lochmann et al. 1977), acute urticaria, and angioedema (Walker 1969) have been reported and postulated to be hypersensitivity reactions. In addition, other cutaneous reactions such as rashes (Geddes et al. 1970 Maulide and Villar 1974), and the Stevens-Johnson syndrome (Fulghum and Catalano 1973 Maulide and Villar 1974) have been described, but their etiology has not been defined. However, allergic contact dermatitis due to clindamycin therapy has been observed in two patients (Coskey 1978 Herstoff 1978). 

Cutaneous reactions are among the most prevalent adverse effects of therapeutic drugs. Ranging from relatively minor skin rashes to more serious toxic consequences such as SJS and TEN, these cutaneous effects can impose major limitations on clinical therapeutic use. Mechanisms of adverse cutaneous drug reactions may be immune mediated, photochemical, directly related to therapeutic activity, or idiosyncratic toxidties for which the mechanisms are poorly understood. 

Allergy a hypersensitivity of the immune apparatus s pathological immune reaction induced either by antibodies (immediate hypersensitivity) or by lymphoid cells (delayed type A.). Unlike the delayed type, immediate hypersensitivity can be passively transmitted in the serum. Symptoms of immediate hy-peisensitivity begin shortly after contact and decay rapidly, but delayed type symptoms do not attain a maximum for 24-48 hours then decline slowly over days or weeks Examples of immediate type A. are anaphylaxis the Arthus reaction and serum sickness. The best known A., anaphylaxia, can occur as a local (cutaneous) reaction (e.g. a rash with blisters) or as a systemic reaction (anaphylactic shock). Asthma, hay fever and nettle rashes are also examples of local anaphylactic reactions which are induced by reagins (see Immunoglobulins IgE). Only primates can be sensitized by injection with human reagins. An example of delayed type A. is the tuberculin reaction, which is based on a cellular immune response. 

Skin Cutaneous reactions that are associated with intravenous immunoglobulin include erythema at the injection site, rashes, urticaria [40 ], and eczema [43 ]. 

Skin Cutaneous reactions to fluorouracil include photosensitivity, erythema, maculo-pamlar rashes, and hyperpigmentation [8 ]. Alopecia is uncommon. Hand-foot syndrome affects about 50% of patients but it is usually mild. It occurs after a median of nine cycles of treatment and necessitates dosage reduction or delay in 15% of patients [90 ]. It is less frequent with bolus doses than infusions [83 ]. 

Another subdivision of type IV hypersensitivity reactions has categories distinguished by the effector cells and mediators involved together with the resulting associated cutaneous reactions. Four subdivisions are defined type IVa, mediated by monocytes with IFN-y as dominant cytokine type IVb, mediated by eosinophils with IL-5 and IL-4 involvement type IVc, mediated by T cells with perforin and granzyme B as important effector molecules and type IVd, mediated by neutrophils with IL-8 involvement. Representative skin reactions for the so-called types IVa, b, c, and d are, respectively, maculopapular rash, maculopapular rash with eosinophilia, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP). 

Delayed-type cutaneous reactions to clindamycin include pruritus, exanthematous rash, generalized maculopapular exanthema, erythroderma, generalized exanthematous pustulosis, and Stevens-Johnson syndrome. 

Systemic and cutaneous reactions have been reported following administration of infliximab. These include anaphylaxis, serum sickness, maculopapular rashes, urticaria, psoriasis, flare-up of atopic dermatitis, and leukocytoclastic vascuhtis. The overall incidence of infusion reactions in one study was 6.1 %. Mild, moderate, and severe reactions occurred in 3.1, 1.2, and 1 % of infliximab infusions, respectively. Patients with lymphocyte counts greater than 50 XIQP/L experienced a severe cytokine release syndrome shown by peaks in release of TNF and lL-6 90 min after infusion with rituximab. A number of post-infusion hypersensitivity or hypersensitivity-like reactions occur to rituximab. These reactions include serum sickness, vasculitis, various cutaneous manifestations, interstitial pneumonitis, and acute respiratory distress syndrome. 

Serious immune-mediated reactions to antithymocyte globulin include anaphylaxis, severe cytokine release syndrome, and severe acute infusion-associated reactions. Serum sickness with fever, rash, arthralgia, and myalgia may appear 5-15 days after the initiation of therapy. Cutaneous reactions seen include urticaria, morbilliform eruptions, and acral erythematous eruptions preceding rash. 

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