Case report: desensitization of hypersensitivity against the antisense oligonucleotide volanesorsen

Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive metabolic disorder that causes extremely elevated plasma triglyceride levels, with limited therapeutic options. Volanesorsen is an antisense oligonucleotide approved for its treatment. A 24-year-old woman with genetically diagnosed FCS secondary to a pathogenic variant in APOA5 and a history of recurrent hypertriglyceridemia-induced pancreatitis episodes was being treated with volanesorsen, 285 mg every 2 weeks. Treatment with volanesorsen achieved normalization of triglycerides to <200 mg/dl. However, after the fifth dose of the medication, the patient developed urticaria and volanesorsen was discontinued. In the absence of alternative pharmacological treatments, the patient received a novel desensitization protocol for volanesorsen that allowed continuation of therapy, without evidence of hypersensitivity reactions after subsequent administrations. FCS requires aggressive multimodal therapy and close follow-up. Volanesorsen has shown great efficacy, but a significant rate of discontinuation due to side effects has been observed. Here, the patient presented an immediate hypersensitivity reaction to volanesorsen, but the provision of a desensitization protocol was effective, facilitating continued treatment and impacting the survival and quality of life of the patient

Case report: desensitization of hypersensitivity against the antisense oligonucleotide volanesorsen

Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive metabolic disorder that causes extremely elevated plasma triglyceride levels, with limited therapeutic options. Volanesorsen is an antisense oligonucleotide approved for its treatment. A 24-year-old woman with genetically diagnosed FCS secondary to a pathogenic variant in APOA5 and a history of recurrent hypertriglyceridemia-induced pancreatitis episodes was being treated with volanesorsen, 285 mg every 2 weeks. Treatment with volanesorsen achieved normalization of triglycerides to <200 mg/dl. However, after the fifth dose of the medication, the patient developed urticaria and volanesorsen was discontinued. In the absence of alternative pharmacological treatments, the patient received a novel desensitization protocol for volanesorsen that allowed continuation of therapy, without evidence of hypersensitivity reactions after subsequent administrations. FCS requires aggressive multimodal therapy and close follow-up. Volanesorsen has shown great efficacy, but a significant rate of discontinuation due to side effects has been observed. Here, the patient presented an immediate hypersensitivity reaction to volanesorsen, but the provision of a desensitization protocol was effective, facilitating continued treatment and impacting the survival and quality of life of the patient

A 17-year-old male with a Small Bowel Neuroendocrine Tumor: flushing differential diagnosis

Abstract Background Neuroendocrine tumors (NETs) are heterogeneous neoplasms that originate from cells with a secretory function. Small bowel NETs (SB-NETs) are related to serotonin hypersecretion which causes: flushing, diarrhea, abdominal pain, bronchoconstriction and heart involvement, also known as carcinoid syndrome (CS). CS can be confused with an allergic reaction and thus should be considered as a differential diagnosis in the allergy consult. We present the case of a pediatric patient initially referred under the suspicion of food allergies. Case presentation We present the case of a 17-year-old male with evanescent non-pruriginous erythematous lesions- flushing that appeared with food consumption, associated with conjunctival injection, warmth and diaphoresis after the lesions disappeared. He denied abdominal pain, diarrhea, cough or wheezing. The 24-h urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion was elevated. The CT scan showed thickening of the distal ileum and multiple lesions on both hepatic lobules and the colonoscopy revealed a tumor in the ileocecal valve. Hepatic and intestinal biopsies reported a well-differentiated NET of the ileocecal valve with hepatic metastasis. He was started on octreotide and underwent a wide hepatectomy and right hemicolectomy with improvement of symptoms. Conclusions NETs can present as carcinoid syndrome (flushing, diarrhea, abdominal pain, wheezing), which constitutes vague symptomatology and represents a challenging diagnosis for physicians. They can be confused with an allergic reaction and the allergist should consider it as a differential diagnosis. Accurate diagnostic tests will help to diagnose NETs earlier and potentially prevent carcinoid heart disease, bowel obstruction, and improve quality of life and mortality in these patients

Fig 1 -

3D structure of the human HSP60 (A), alpha enolase (B) and gamma enolase (C). Cartoon and surface models are showed to represent the position of the epitope predicted in the human antigens. All the epitopes are indicated in color on surface models: blue, red, green, yellow, cyan, magenta, orange. LE. Lineal epitope. DE: discontinuous epitope.</p

Overlay of the 3-D models between type 1 gNET antigens and <i>H</i>. <i>pylori</i> proteins.

Samples: human HSP60 (gold) vs H. pylori chaperonin Groel (Magenta) are shown as the complete unit (A) and a subunit (B). (C) Human Alpha enolase (orange) vs H. pylori phosphopyruvate (cyan). (D) Gamma enolase (gray) vs phosphopyruvate (yellow). RMSD: Root-mean-square deviation are showed in Armstrong (Å).</p

Pairwise alignment between human HSP 60 vs chaperonin Gro EL.

Unconserved sequence are shown with blue color and high conserved sequence with red color. Moderately conserve sequence is showed with green and orange color. (TIFF)</p

Pairwise alignment between human H/K ATPase vs cooper translocate ATPase.

Unconserved sequence are shown with blue color and high conserved sequence with red color. Moderately conserve sequence is showed with green and orange color. (TIFF)</p

Pairwise alignment between human FUT 2 and 1,2 fucosyltransferase.

Unconserved sequence are shown with blue color and high conserved sequence with red color. Moderately conserve sequence is showed with green and orange color. (TIFF)</p

Pairwise alignment between human Alpha enolase vs phosphopyruvate.

Unconserved sequence are shown with blue color and high conserved sequence with red color. Moderately conserve sequence is showed with green and orange color. (TIFF)</p

Tumoral neuroendocrine antigens and proteins associated with urticaria used to compare with the <i>H</i>. <i>pylori</i> proteome.

Tumoral neuroendocrine antigens and proteins associated with urticaria used to compare with the H. pylori proteome.</p