Failure of a single day metronidazole desensitization protocol, and success of a modified two-day protocol in an outpatient setting

Background True allergy to metronidazole, a common anti-infective in clinical practice, is rarely reported in the literature. In the case of Trichomonas, there are few alternatives to the nitrimidazole class of drugs, and the alternatives that do exist are associated with worse clinical outcomes. Accordingly, for the rare patients with Type 1 hypersensitivity reactions to metronidazole but compelling need, desensitization protocols have been adapted previously. Reactions during these protocols appear common. Patients in previous regimens have required higher level care for observation, which is costly and resource-intensive. Case presentation We report here on a successful outpatient two-day regimen for metronidazole desensitization. Our patient had compelling indication for metronidazole, but reacted after receiving the very first dose of a previously described desensitization protocol. Accordingly, the protocol was adapted further. Despite this, she went on to develop objective hives prior to reaching the full intended dose. With appropriate symptom management and pre-medication on the second day in clinic, she was successfully desensitized and able to complete a week of full-dose metronidazole. No acute care resources were needed. Conclusion We propose this two-day desensitization regimen for patients who react during the previously described desensitization protocols. This regimen was effective and safe, and did not necessitate the use of acute-care resources. Two-day desensitization protocols while relatively uncommon, can be successful.

Hypersensitivity Reactions to Platinum Agents and Taxanes

Hypersensitivity reactions (HSRs) to chemotherapy agents can present a serious challenge to treating patients with preferred or first-line therapies. Allergic reactions through an immunologic mechanism have been established for platinum and taxane agents, which are used to treat a wide variety of cancers including gynecologic cancers. Platin HSRs typically occur after multiple cycles of chemotherapy, reflecting the development of drug IgE sensitization, while taxane HSRs often occur on first or second exposure. Despite observed differences between platin and taxane HSRs, drug desensitization has been an effective method to reintroduce both chemotherapeutic agents safely. Skin testing is the primary diagnostic tool used to risk-stratify patients after initial HSRs, with more widespread use for platinum agents than taxanes. Different practices exist around the use of skin testing, drug challenge, and choice of desensitization protocol. Here, we review the epidemiology, mechanism, and clinical presentation of HSRs to platinum and taxane agents, as well as key controversies in their evaluation and management.

Immediate hypersensitivity reaction followed by successful oral desensitization to ursodiol

Background Immediate hypersensitivity reaction to ursodiol is rare and there is no previously published protocol on ursodiol desensitization. Case presentation A 59-year-old woman with primary biliary cholangitis (PBC) developed an immediate hypersensitivity reaction to ursodiol—the first-line treatment for PBC. When she switched to a second-line treatment, her PBC continued to progress. As such, she completed a novel 12-step desensitization protocol to oral ursodiol. She experienced recurrent pruritus after each dose following desensitization, which subsided after a month of being on daily ursodiol. Conclusion Immediate hypersensitivity reaction to ursodiol is uncommon. Our case demonstrated that this novel desensitization protocol to ursodiol could be safely implemented when alternative options are not available or have proven inferior in efficacy.

Successful Drug Desensitization to Ustekinumab in a Patient with Crohn’s Disease

Ustekinumab is a monoclonal antibody used as treatment for various inflammatory conditions. We present a pediatric patient with Crohn’s disease who did not tolerate infliximab and was then changed to ustekinumab. He developed anaphylaxis to the medication after the second dose. A drug desensitization protocol was created by the allergy team leading to successful administration of both intravenous and then subcutaneous ustekinumab. As monoclonal agents become mainstays of therapy for inflammatory conditions, there are increased reports of allergic reactions. Prior reports and protocols of ustekinumab desensitization have not been reported. This case report highlights successful desensitization to ustekinumab as well as the importance of a multidisciplinary approach to addressing treatment needs of patients who develop life-threatening reactions to such medications.

4-step, 2-h carboplatin desensitization in Japanese patients with ovarian cancer: a prospective study

Background Carboplatin is a key drug for ovarian cancer. However, it sometimes induces hypersensitivity reactions (HSRs) that result in the discontinuation of the treatment. Although various desensitization protocols have been reported in previous retrospective studies, a limited number of prospective studies have analyzed these protocols. Methods Patients with platinum-sensitive relapsed ovarian cancer who experienced carboplatin-induced HSRs were treated with diluted solutions of 1/1000, 1/100, 1/10 and an undiluted solution of carboplatin over a 1-h period. If no HSRs occurred within the first two cycles, a short protocol regimen over a 30-min period per solution was followed. The primary endpoint was treatment completion rate. Results Between May 2015 and September 2018, 21 patients were enrolled from two institutions. One patient experienced platinum-sensitive recurrence after the desensitization protocol; thus, 22 sessions were analyzed. Epinephrine use, treatment-related death, and intensive care unit (ICU) admissions did not occur. The median number of desensitization cycles was 6 (range 1–6). Two sessions were discontinued early because of grade 2 dysgeusia and grade 2 malaise. Treatment in two (9.1%) patients was discontinued because of HSR development. The treatment completion rate was 90.9%. Six (27.3%) sessions met the criteria for transition to the short protocol regimen. In 14 (63.6%) sessions, HSRs were observed during infusion of the undiluted solution. The median progression-free survival and overall survival were 14.8 and 23.8 months, respectively. Conclusion This 4-step, 2-h carboplatin desensitization protocol is safe and feasible. Patients require careful monitoring with a rapid response to HSRs, especially during the administration of undiluted solutions.

Persistent Neutropenia after ABOi Kidney Transplantation: A Case Report

Post-transplant neutropenia (PTN) is frequently reported in the first-year after transplantation. Although prevalence and clinical consequences are widely described, there are no guidelines to manage diagnosis and treatment. We report here a case of persistent PTN occurred in a patient undergoing a kidney transplant from an AB0-incompatible living donor. The desensitization protocol consisted of Rituximab administration and immunoadsorption while the pre-transplant protocol, which was initiated 14 days before the transplant, included Tacrolimus, Mofetil Mycophenolate (MMF), antimicrobial and antiviral prophylaxis. Induction therapy consisted of anti-thymocyte globulins and steroids, while maintenance after transplantation consisted of steroid, tacrolimus and MMF. When the first occurrence of leukopenia was observed six weeks after the transplant, firstly antimicrobial/antiviral prophylaxis was stopped and later also MMF treatment was interrupted but severe neutropenia relapsed after MMF resuming treatment. Immunological and virological causes were excluded. The patient was treated with Filgrastim. Bone marrow biopsy, which was performed to exclude a hematological cause of severe persistent neutropenia, revealed a bone marrow hypoplasia with neutrophils maturation interrupted at the early stages. This case highlights the need to establish diagnostic and therapeutic guidelines for PTN which take in consideration all the therapeutic steps including the pre-transplant phase in particular in the context of AB0i where immunosuppression is more consistent.