Fish oil/omega-3-fatty-acid/insulin suspension isophane
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Maculopapular exanthema secondary to cross reactivity: case report A 64-year-old woman developed maculopapular exanthema secondary to cross reactivity between protamine in insulin suspension isophane and a preparation containing fish oil and omega-3 fatty acid [routes, dosages and durations of treatments to reactions onsets not stated]. The woman had multiple morbidities, including type 2 diabetes mellitus, for which she had been on insulin therapy for 15 years. She had used insulin preparations included insulin suspension isophane [Insulatard NPH], insulin aspart [NovoRapid], insulin [human insulin], insulin glulisine [Apidra], insulin detemir [Levemir], insulin glargine [Lantus, Toujeo] and insulin degludec [Tresiba]. She presented to a clinic in August 2019 with new-onset skin symptoms. During this time, an upper respiratory tract infection was also diagnosed. She was prescribed an unspecified steroid and received antibiotic therapy for the infection, after which her symptoms subsided. Towards the end of September 2019, she developed red rashes on her lower limb at the site of insulin degludec [Tresiba] administration. Her symptoms developed several hours after the administration of insulin degludec. Similar changes were not observed at the site of administration of insulin glulisine [Apidra]. Physical examination showed maculopapular exanthema in the lower extremity. A review of her medications revealed that she had been using beclometasone/formoterol, an unspecified long-acting β2-agonist and had recently started using a preparation containing fish oil and omega-3 fatty acid before the onset of symptoms. As her symptoms appeared several hours after insulin administration, late-type hypersensitivity reaction was initially considered (differential diagnosis). Hence, the woman underwent in-vitro lymphocyte transformation tests (LLTs) using insulin glargine [Lantus, Toujeo], insulin degludec [Tresiba] and protamine as an alternative to the formulation containing omega-3 fatty acid and fish oil. The LLTs showed negative results for all tested preparations of insulin, but it was positive for protamine. Immunoserological tests revealed slightly elevated levels of total IgE. Of the thyroid contra auto-antibodies, thyroglobulin (TG) was found to be negative and auto-antibodies to thyroid peroxidase (TPO) were found positive; hence, a TSH assay was performed, which showed a normal value. Subsequent test results for autoantibody to insulin (IAA) were also found negative; hence, insulin hypersensitivity was ruled out. However, protamine-positive LTT indicated protamine sensitisation, which might have been due to prior use of the protamine sulfatecontaining insulin suspension isophane. Although she did not receive a protamine sulphate-containing insulin preparation in recent years and had no history of fish allergy, the possibility of a cross-reaction with a preparation containing omega-3 fatty acid and fish oil could not be ruled out, which was supported by the fact that following discontinuation of the product, her
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