Antibiotic allergy in cystic fibrosis.

Allergic reactions to antibiotics are more common in cystic fibrosis (CF) than in the general population. This in part is due to the improving survival in adults with CF and the increased use of high dose intravenous antibiotics. While some are immediate anaphylaxis type (IgE mediated) reactions, the majority are late onset and may have non-specific features such as rash and fever. Piperacillin has consistently been found to have the highest rate of reported reactions (30-50%). There is a low risk of cross reactions between penicillins and other non-beta-lactam classes of antibiotics in penicillin skin prick positive patients. Carbapenems should only be used with extreme caution in patients with positive skin prick tests to penicillin. However, aztreonam can be used safely in patients who are penicillin allergic with positive skin prick reactions. The aminoglycosides are a relatively uncommon cause of allergic reactions, but patients who react to one member of the family may cross react with other aminoglycosides. Desensitisation relies on the incremental introduction of small quantities of the allergen and has been used for penicillins, ceftazidime, tobramycin and ciprofloxacin and must be repeated before each course. Personalized cards should be regularly updated for patients who develop allergic reactions. Written instructions on the emergency treatment of allergic reactions should be provided to patients self-administering intravenous antibiotics at home. Further research is required to identify risk factors and predictors for antibiotic allergy.

Profound adrenal suppression secondary to treatment with low dose inhaled steroids and itraconazole in allergic bronchopulmonary aspergillosis in cystic fibrosis.

The case history is presented of a patient with cystic fibrosis in whom the treatment of allergic bronchopulmonary aspergillosis with itraconazole produced an initial response but was complicated by profound adrenal shutdown and impairment of inhaled steroid clearance resulting in paradoxical Cushing's syndrome. The authors conclude that, while it is laudable to attempt to reduce the steroid burden in any patient, it is imperative that due vigilance is exercised when using a combination of agents which interact. If such a combination therapy is embarked upon, regular assessment of the pituitary adrenal axis is advisable.

Alpha-1-antitrypsin deficiency, the serpinopathies and conformational disease.

Alpha-1-antitrypsin deficiency results from point mutations that distort the structure of the protein to allow a unique protein-protein interaction that we have termed loopsheet polymerisation. Polymers of Z alpha 1-antitrypsin accumulate within hepatocytes to form inclusion bodies that are associated with juvenile cirrhosis and hepatocellular carcinoma. The lack of circulating protein predisposes the Z alpha 1-antitrypsin homozygote to emphysema. This process also occurs in other members of the serine proteinase inhibitor (serpin) superfamily, antithrombin, C1-inhibitor and alpha 1-antichymotrypsin, in association with thrombosis, angioedema and chronic obstructive pulmonary disease, respectively, and we have recently shown that it underlies a novel inclusion body dementia. The interaction provides a useful paradigm for other 'conformational diseases' such as Huntington's disease, Creutzfeldt-Jakob disease and the amyloidoses.