Hypersensitivity mechanisms

A 75-year-old man developed triamcinolone-induced anaphylaxis and dose-related positive prick skin tests to triamcinolone, suggesting that an IgE-mediated hypersensitivity mechanism may have played a part... 

The different types of immune-mediated injury are not mutually exclusive. More than one hypersensitivity mechanism may be involved in the response to a particular antigen. Also the resulting pathology, particularly that caused by type III and IV, reactions may appear very similar, although the mechanisms leading to the effect are different. 

Aminophenazone (amidopjrine) is the most toxic and most dangerous anti-inflammatory analgesic. Blood dyscrasias have been documented beyond any doubt, perhaps due to a hypersensitivity mechanism. The Committee on the Safety of Drugs of the Japanese Pharmaceutical Affairs Bureau has ordered its withdrawal because of its serious adverse effects (SEDA-12, 82) and it has been withdrawn in most developed countries. However, aminophenazone is still used in some developing countries (1). 

A 53-year-old woman with Rajmaud s phenomenon developed an urticarial rash, pruritus, and hjrpotension 10 minutes after the parenteral administration of buflomedil. She received corticosteroids and recovered within 6 hours. When she later underwent skin tests with buflomedil, there was an immediate positive reaction, suggesting a type I hypersensitivity mechanism. 

Melphalan can cause an acute interstitial pneumonia with hypoxemia (3). This is probably due to a hypersensitivity mechanism and should be distinguished from fibrosing pneumonitis, which melphalan can also cause (4). 

The primary toxicity following captafol exposure probably occurs through a hypersensitivity mechanism. 

Other foods have been known to be linked to delayed hypersensitivities. Symptoms associated with delayed hypersensitivity reactions may not begin to appear until 24 h after ingestion of the offending food. The symptoms of delayed hypersensitivity reactions do not reach the severity involved in immediate hypersensitivity. However, thresholds triggering reactions, or the level of tolerance for the offending food, is equally low for delayed as well as immediate hypersensitivities. Mechanisms involved in delayed hypersensitivities remain poorly defined, except perhaps for celiac disease (Taylor, 2000 Kagnoff, 2007 Braini et al., 2008). 

It is perhaps difficult to challenge the evidence supporting a methyldopa-in-duced effect for both types of hepatoxicity, but there is not sufficient data, either clinical or experimental, to indicate that the syndromes are the result of hypersensitivity mechanisms. 

Egido J, Sanchez Crespo M, Lahoz C, Garcia R, Lopez-Trascasa M, Hernando L. Evidence of an immediate hypersensitivity mechanism in systemic lupus erythematosus. Ann Rheum Dis 1980 39(4) 312-317. 

In addition to the proteins discussed above, a large number of reactive chemicals used in industry can cause asthma and rhinitis. Hypersensitivity pneumonias have also been described. Isocyanates and acid anhydrides are industrial chemicals that cause occupational asthma. Acid anhydrides, such as phthalic anhydride, seem to cause mainly type I reactions, whereas the IgE-mediated mechanism explains only a part of the sensitizations to isocyanates. Several mechanisms have been suggested, but despite intensive research no models have been generally accepted. The situation is even more obscure for other sensitizing chemicals therefore, the term specific chemical hypersensitivity is often used for chemical allergies. This term should not be confused with multiple chemical sensitivity (MCS) syndrome, which is a controversial term referring to hypersusceptibility to very low levels of environmental chemicals. ... 

In type III or immunocomplex-mediated allergy, IgG antibodies form complexes with antigen. At low exposures, the body is able to remove diese complexes, but if there is a severe exposure, immunocomplexes release a variety of proinflammatory cytokines. The involvement of this mechanism is clearest in serum sickness. This mechanism is also considered to be most important in the development of extrinsic allergic alveolitis (hypersensitivity pneumonitis, especially... 

The exact mechanism of action of thiabendazole (Mintezol) is unknown. This drug appears to suppress egg or larval production and tiierefore may interrupt die life cycle of the helminth. Thiabendazole is used to treat threadworm. Thiabendazole may cause hypersensitivity reactions, drowsiness, and dizziness. 

These drugp are contraindicated in patients with known hypersensitivity to die drugs, asthma, peptic ulcer disease, coronary artery disease, and hyperthyroidism. Bethanecol is contraindicated in those with mechanical obstruction of die gastrointestinal or genitourinary tracts. Fhtients with secondary glaucoma, iritis, corneal abrasion, or any acute inflammatory disease of the eye should not use die ophtiialmic cholinergic preparations. 

Radiocontrast media (RCM) are highly concentrated solutions of triiodinated benzene derivatives used for performing diagnosis and treatment of vascular disease and enhancement of radiographic contrast [1,2]. However, adverse reactions after RCM administration are common [3]. The frequency and mechanisms of hypersensitivity reactions differ between monomeric and dimeric as well as between ionic and non-ionic types of RCM. Mild immediate reactions have been reported to occur in 3.8-12.7% of patients receiving ionic monomeric RCM and in 0.7-3.1% of patients receiving non-ionic RCM [4-6]. Severe immediate adverse reactions to ionic RCM have been reported in 0.1-0.4% of intravenous procedures, while reactions to nonionic iodinated RCM are less frequent (0.02-0.04%) [4-7]. Fatal hypersensitivity... 

The evidence that immediate hypersensitivity reactions may indeed be caused by an IgE-mediated allergic mechanism is also mainly indirect. However, some data support the concept that a subgroup of reactions may be IgE-mediated ... 

The authors thank Cathrine Christiansen and Werner Pichler for stimulating discussions and support on the way of clarifying the imderlying mechanism s of RCM hypersensitivity. 

A non-allergic mechanism imderlying precipitation of asthmatic attacks by aspirin in hypersensitive patients was proposed over 30 years ago [4]. It was founded on pharmacological inhibition of COX of arachidonic acid and explained a cross-reactivity between different NSAIDs varying in chemical structure. This COX theory was confirmed by several studies [11] and was further refined following discovery of the second COX isoenzyme - COX-2. At least two COX isoenzymes, COX-1 and COX-2, are coded by separate genes. Their role in inflammation, asthma and anaphylaxis has been reviewed previously [12]. 

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