Type 1 Ig-E mediated allergy to human insulin, insulin analogues and\nbeta-lactam antibiotics
We present the case of a 69-year-old male with type 2 diabetes mellitus\ndiagnosed at the age of 63, that due to insufficient glycemic control on oral\ntherapy alone and intolerance to some oral antidiabetics, was treated with premixed\ninsulin analogues lispro and lispro protamine (Humalog Mix 25TM) during the\nprevious two years. The onset of pruriginous urticariform abdominal plaques with\nperipheral pale halos was observed, arising within minutes at the sites of subcutaneous\ninsulin administration and occasionally at distant sites, recurring at nearly every\ninsulin injection in the past year ().\nLesions regressed spontaneously in the space of a few minutes or hours. Glycemic control\nwas acceptable (serum glycated hemoglobin A1c levels were 53mmol/mol - 7.0% -\nat presentation) and apparently unaffected by the cutaneous reaction.\nThe patient presented class I obesity (body mass index 31), dyslipidemia and arterial\nhypertension and was regularly treated with oral atorvastatin 20mg o.d., telmisartan\n80mg o.d., hydrochlorothyazide 12.5mg o.d. and triflusal 300mg o.d.. No known allergies\nwere reported, apart from a generalized erythematous cutaneous eruption of unclear\nnature following intramuscular penicillin injection in his childhood, which justified\nthe avoidance of beta-lactam antibiotics ever since.\nThe diagnosis of immediate hypersensitivity to insulin analogue lispro was therefore\nsuspected. Rechallenging administration of 2U of the regularly used insulin induced, in\nfew minutes, a new pruriginous urticariform lesion at the site of the injection ().\nPrick tests using several different types of human insulin and insulin analogues were\nperformed and all of them triggered positive reactions (papule diameters >3mm\nafter 20minutes and >5mm after 60 minutes) (). Papules 5 and 7mm in diameter were observed 20 and 60 minutes after\nprick test with Merck histamine 10mg/ml solution\n(positive control), while no reaction was induced by isotonic sodium chloride solution\n(negative control).\nTotal serum IgE was three times above the normal limit (312UI/ml), with class 3\nradioallergosorbent tests (RAST) for human, bovine and porcine insulins (13.2KU/L,\n16.0KU/L and 14.3KU/L respectively). Interestingly, RAST for beta-lactam antibiotics\nwere reported as Class 2 (1.0KU/L for penicillin G, 0.94KU/L for penicillin V, 0.87KU/L\nfor ampicillin and 0.72KU/L for amoxycillin), and Class 0 for cefaclor (0.08KU/L).\nThese results allowed the confirmation of type 1 IgE-mediated hypersensitivity to human\ninsulin and insulin analogues lispro, glargine and detemir. In addition, despite being\ninsufficient for clear identification of hypersensitivity to beta-lactams, results\nconcerning these antibiotics were considered relevant, based on the previous cutaneous\neruption following penicillin treatment and the age of the patient, which in association\nwith the lack of re-exposure to beta-lactams during several decades might explain the\nlow serum concentration of specific IgE. Even so, it is interesting to notice the\nabsence of cross-reactivity with cephalosporin.\nAfter evaluation by an endocrinologist, insulin therapy was suspended and the patient\nbegan the intake of an oral anti-diabetic drug association. Cutaneous lesions did not\nrecur and reasonable glycemic control was achieved after three months (fasting blood\nglucose levels ranging between 5,511.0mmol/L; serum glycated hemoglobin 55mmol/mol -\n7.2%). As a high risk diabetic patient with several associated vascular and metabolic\ncomorbidities, oral therapy has been considered insufficient and the patient has been\nproposed for insulin desensitization.