Infant hemangioma (IH) is the most common tumor in infants, which affects 5-10% of white children. It is a tumor of vascular origin that appears in the first months of life. The indication for the treatment of the IH is not approved in the datasheet of the product, however it has been used in the infant hemangioma by topical administration as an alternative to oral propranolol, avoiding the main problems of the oral route (bradycardia and hypotension). The objective of this work is to study the physical and chemical (HPLC stability indicating method) stability of a 0.5% timolol gel for topical application during 60 days (considering the stability limit as 90% of initial concentration of timolol maleate). The gel was prepared with a polyacrylic acid derivative and the physical stability of the system was studied by visual control, rheological and mechanical characterization. The studied formulation guarantees the correct dose administering and stability after 60 days stored at 25 ± 2 °C and light protected (tube of aluminum). We have developed an easy topical gel for the treatment of infant hemangioma with physical and chemical stability higher than those provided by the majority of hospitals.
We describe a successful desensitization to alemtuzumab in one patient diagnosed with T-cell prolymphocytic leukaemia. Alemtuzumab treatment was initiated during infusion number 18, the patient showed cutaneous eruption with a miliary pattern, despite premedication with corticosteroids and antihistamines. The eruption returned with successive alemtuzumab infusions (infusions 19, 20 and 21), remained present for longer and was more severe with each infusion. The patient was referred to our Allergy Unit as it was necessary to maintain alemtuzumab treatment. Total immunoglobulin E level was 3 UI/ml and specific immunoglobulin E against more common pneumo-allergens, food, latex and hamster were inferior to 0.35 UI/ml. Prick test using the undiluted drug (30 mg/ml) and intradermal tests using serial dilutions (1/10, 1/100) were performed. The result of alemtuzumab skin prick test was 4 mm. The intradermal skin test result was positive at 1/100 dilution (papule: 8 mm; erythema: 12 mm). The basophil activation test with alemtuzumab was performed concluding that 10% of the basophils were activated by alemtuzumab. The patient underwent alemtuzumab desensitization according to a 12-step protocol that resolved to be safe and efficacious. Our experience may be helpful for similar clinical cases where the therapeutic options are very limited and a life-threatening condition such T-cell prolymphocytic leukaemia is present. In addition, a careful risk/benefit ratio should be considered and accurate informed consent is mandatory.
Denosumab is a human monoclonal antibody indicated for the treatment of osteoporosis in postmenopausal women with a high risk of fractures. To our knowledge, no cases of desensitization to this drug have been described in the literature. We report the first case of generalized urticarial reaction and facial angioedema after therapy with denosumab. A subcutaneous desensitization protocol was successfully completed in this patient. Rapid desensitization is a promising method for the delivery of denosumab after a hypersensitivity reaction, and should be considered in osteoporosis treatment when no acceptable therapeutic alternatives are available.
References 1. Pommier Y. Drugging topoisomerases: lessons and challenges. ACS Chem Biol. 2013;8(1):82-95. 2. Cernadas JR, Brockow K, Romano A, Aberer W, Torres MJ, Bircher A, Campi P, Sanz ML, Castells M, Demoly P, Pichler WJ; European Network of Drug Allergy and The EAACI interest group on drug hypersensitivity. General considerations on rapid desensitization for drug hypersensitivity -a consensus statement. Allergy. 2010;65(11):1357-66. 3. Alvarez-Cuesta E, Madrigal-Burgaleta R, Angel-Pereira D, Ureña-Tavera A, Zamora-Verduga M, Lopez-Gonzalez P, Berges-Gimeno MP. Delving into cornerstones of hypersensitivity to antineoplastic and biological agents: value of diagnostic tools prior to desensitization. Allergy. 2015;70(7):784-94. 4. Castells MC, Tennant NM, Sloane DE, Hsu FI, Barrett NA, Hong DI, Laidlaw TM, Legere HJ, Nallamshetty SN, Palis RI, Rao JJ, Berlin ST, Campos SM, Matulonis UA. Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413 cases. J Allergy ClinImmunol. 2008;122(3):574-80. 5. Abu-Amna M, Hassoun G, Hadad S, Haim N, Bar-Sela G. Successful Desensitization Protocol for Hypersensitivity Reaction Caused by Irinotecan in a Patient With Metastatic Colorectal Cancer. Clin Colorectal Cancer. 2015;14(4):e49-51. 6. Castells Guitart MC. Rapid drug desensitization for hypersensitivity reactions to chemotherapy and monoclonal antibodies in the 21st century. J Investig Allergol Clin Immunol. 2014;24(2):72-9. 7. Breslow RG, Caiado J, Castells MC. Acetylsalicylic acid and montelukast block mast cell mediator-related symptoms during rapid desensitization. Ann Allergy Asthma Immunol. 2009;102(2):155-60.immunoblotting assay. In addition, after the allergic reaction, all patients tolerated poultry meat, indicating that a-livetin (quail albumin) was not involved in any of these cases.The difficulty in obtaining a QE yolk sample without QE white contamination, as reported elsewhere [7], could explain the positive results for QE yolk in the SPPT and immunoblotting assay.Although allergy to QE-with or without HE sensitivityhas been reported [2,3,8,9], ours is the first case series in which the causative proteins were identified.We found only 1 case of non-IgE-mediated food hypersensitivity reaction to QE [10].In conclusion, in the 5 patients we report, the main QE allergen is ovalbumin. Although proteins from HE and QE showed cross-reactivity, patients commonly tolerate HE consumption even when they have QE allergy. Since patients with QE allergy can show different HE skin test results (positive SPT and/or SSPT and/or specific IgE to HE proteins, with good tolerance to HE), these results should not be used to predict intolerance to HE.and Longo et al [7]. Finally, based on the results obtained in this study and other studies [8][9][10], it could be concluded that oral immunotherapy leads to tolerance and may accelerate induction of tolerance in patients with cow's milk allergy.
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