Allergy, Asthma & Clinical Immunology

The present review addresses the literature regarding the sensitivity and specificity of the various diagnostic methods for evaluating non-immediate (ie, occurring more than 1 hour after drug administration) hypersensitivity reactions associated with β-lactams and other antibiotics, anticonvulsants, heparins, iodinated contrast media, etc. Such reactions include several clinical entities, which range from mild reactions, such as maculopapular rash and delayed-appearing urticaria, to severe ones, such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome, and toxic epidermal necrolysis (TEN). Clinical and laboratory studies indicate that a cell-mediated pathogenic mechanism is often involved in maculopapular rashes. However, this mechanism has also been demonstrated in other non-immediate reactions, such as urticarial and/or angioedematous manifestations, TEN, bullous exanthems, and AGEP. Patch tests, together with delayed-reading intradermal tests, lymphocyte transformation tests, and challenges, are useful tools for evaluating non-immediate drug eruptions. Patch tests can be performed with any form of commercial drugs and are safer than intradermal tests. However, patch tests are less sensitive than intradermal tests, and their sensitivity may vary, depending on the vehicle used.

Chronic spontaneous urticaria (CSU) is often associated with organ specific autoimmunity but is rarely caused by food allergy. Colourings and preservatives in pre-packaged foods, so called pseudoallergens, have also been implicated. Factors that promote inflammation or reduce anti-inflammatory mechanisms may however, predispose susceptible individuals to CSU. Chronic underlying infection and mental and emotional stress can sometimes precede the onset of CSU and once established can exacerbate the symptoms. There is early evidence of dysbiosis within the gastrointestinal tract in people with CSU and reduced levels of vitamin D are also evident. The latter may be related to the importance of vitamin D3 in increasing T regulatory function which can control a tendency to autoimmunity. It is quite possible that a state of on-going chronic inflammation with reduced anti-oxidant mechanisms may underlie the not infrequent association between CSU and metabolic syndrome. Effective treatment of CSU should involve the use of anti-histamines, intermittent steroids and anti-IgE therapy. For recalcitrant disease immune modulatory therapy has a place. However, talking therapies that reduce stress and anxiety, vitamin D3 supplementation, correction of intestinal dysbiosis and treatment of any chronic infection should also be considered.