BackgroundIn Cushing’s syndrome (CS), when surgery is unsuccessful or contraindicated, ketoconazole is the drug most frequently used to treat hypercortisolism.In July 2013, European Medicines Agency announced their negative risk-benefit assessment of oral ketoconazole as treatment of fungal infections, because it can cause liver damage and drug interactions due to cytochrome P450 inhibition. Ketoconazole was suspended as an antifungal in the European Union, but compassionate use is authorised for CS.PurposeTo analyse the hormonal effects and tolerance of ketoconazole in CS over the last year.Material and methodsNine patients [32–83 years old] were treated in hospital. All patients were retrospectively studied with a follow-up of 26 months; their treatment had lasted from 12 days–25 years. One patient had ectopic ACTH production, two had pituitary adenoma, and six had adrenal neoplasia. Four patients had previously had surgery, but it was not effective in two cases. The dose of ketoconazole was between 200–1,200 mg/day.Liver tests checked: transaminases, total bilirubin and alkaline phosphatase. Hormonal control was observed with Nugent’s test and 24 h urinary free cortisol. The patient’s current treatment was noted to check for drug interactions.ResultsAll patients were checked. No adrenal insufficiency was observed. Liver function tests were normal. Five patients stopped ketoconazole: two for surgery; two died of metastatic cancer; and one because of a potential drug interaction with calcium antagonism. 77.8% of the patients had some possible drug interactions, but only one stopped ketoconazole. Other interactions were with drugs metabolised by CYP450; or with proton pump inhibitors which reduce the pH-dependent absorption of ketoconazole. These problems were solved by changing the dose of the drugs concerned.ConclusionKetoconazole seems to be a safe and efficacious treatment in CS. However, it is necessary to perform a bigger study to get significant conclusions.ReferenceFeelders RA, Hofland LJ, de Herder WW. Medical treatment of Cushing’s syndrome: adrenal-blocking drugs and ketoconazole. Neuroendocrinology 2010;92(Suppl 1):111–15No conflict of interest.

BackgroundPleural aspergillosis (PA) was first described in 1842 but remains a relatively rare entity when compared with other Aspergillus infections.PurposeTo describe the pharmacological management of a patient diagnosed with PA and the efficacy of intracavitary instillation of amphotericin B (ICAB) treatment.Material and methodsA 32-year-old woman with multiple drug allergy syndrome (NSAIDs, pyrazolones, quinolones, lincosamides, SSRIs, ondansetron) was admitted to our hospital because of postoperative Pseudomonas pneumonia complicated with empyema and bronchopleural fistula. The patient underwent thoracostomy. Pleural biopsy showed septate fungal hyphae and pleural fluid culture grew Aspergillus fumigatus while serum galactomannan antigen was negative. Systemic antifungal therapy, with oral voriconazole at first and then with posaconazole, was started. Concurrently, amphotericin B deoxycholate, diluted in 75 ml of 5% glucose solution, was infused directly into the pleural cavity, at 5 mg on the first day, rising to 10 mg and 25 mg on the second and third day, respectively, and then 50 mg, after washing of the pleural cavity with 5% glucose solution. Daily dressing with amphotericin B-impregnated gauze was introduced in the cavity. Local treatment was continued for about two weeks.ResultsThe treatment was well tolerated with no adverse drug reactions. The symptoms and the physical signs improved greatly during hospitalisation and the patient left the hospital 3 days after the end of treatment. Repeat pleural fluid culture was negative 2 weeks after the end of treatment.ConclusionICAB may improve the efficacy of systemic antifungal therapy and it should be considered as an additional treatment option. Moreover, the use of this method avoids repeated needling of the cavity and may allow extended treatment on a domiciliary basis.ReferenceKravitz JN, Berry MW, Schabel SI, et al. A modern series of percutaneous intracavitary instillation of amphotericin B for the treatment of severe hemoptysis from pulmonary aspergilloma. Chest 2013;143(5):1414–21No conflict of interest.

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Background Brentuximab is a monoclonal antibody targeting CD30 receptors, authorised in 2011 by FDA for the treatment of Hodgkin’s lymphoma and other lymphomas refractory to conventional treatment. Although there are limited references in the literature to related infusion reactions, they are an adverse effect described in the data sheet and can compromise treatment. Purpose To describe a case of hypersensitivity reaction to brentuximab and evaluate the utility of a desensitisation protocol. Materials and methods Male, 29 years old, diagnosed with Hodgkin’s lymphoma in progression to different lines of chemotherapy. Brentuximab was prescribed every 21 days at a dose of 180 mg over 30 min and premedicated with intravenous methylprednisolone, dexchlorpheniramine and paracetamol. During the first cycle he didn’t present any reaction. Twenty minutes after starting the second cycle, the patient presented a feeling of numbness in the extremities, itchy skin lesions, heat and nausea, so the infusion was stopped. He was treated with intravenous paracetamol and dexchlorpheniramine. The infusion was restarted but the signs reappeared, so was stopped. The severity of the reaction was considered grade 2. During the third cycle skin lesions reappeared and although the cycle was completed, it was suspended. The need to continue with the treatment led to a desensitisation protocol for brentuximab being prescribed, which consisted of 13 steps with a final dose equal to the therapeutic dose over 3 h and 10 min. At each step the dose was gradually increased until the full dose was reached. The initial dose was 0.01 mg and generally at each step twice the previous dose was given. The protocol was administered by the Allergy Service. Results Since brentuximab protocol desensitisation was prescribed, the patient has received 3 cycles, during which he hasn’t experienced any reaction, allowing continued treatment. Conclusions The use of a brentuximab desensitisation protocol allows patients with allergic reactions to the drug to be treated when it is the only available option. No conflict of interest.