Rapid, Near Point-of-Care Assay for HLA-B*57:01 Genotype Associated with Severe Hypersensitivity Reaction to Abacavir

Objective: The nucleoside reverse transcriptase inhibitor abacavir is commonly used to treat young children with HIV infection. Abacavir can trigger a severe hypersensitivity reaction in people who are homozygous or heterozygous for HLA-B*57:01. Testing for HLA-B*57:01 prior to abacavir initiation is standard-of-care in high-resource settings, but current tests are too costly for resource-limited settings. To address this gap, we developed an inexpensive, simple-to-use rapid assay to detect HLA-B*57:01. Methods: We designed and optimized a multiplexed PCR to amplify HLA-B*57 subtypes and the human beta-globin gene. Subsequently, probes annealed to the amplicon and were ligated when specific for the HLA-B*57:01 allele. Ligated products were detected by immunocapture in a lateral flow strip. Cell lines with known HLA genotypes were used to optimize the assay. The assay was then evaluated by comparing the genotype of clinical specimens (n=60) enriched for individuals with HLA-B*57:01 by the new assay to that from sequencing. Results: The optimized multiplex PCR for B*57 and beta-globin resulted in a 40-minute, 35-cycle amplification, followed by a 20-minute ligation reaction and 15-minute detection step. Evaluation of the HLA-B*57:01 oligonucleotide ligation assay using clinical specimens had a sensitivity of 100% (n=27/27 typed as B*57:01) and specificity of 100% (n=33/33 typed as non-B*57:01) by visual interpretation of lateral flow strips. Conclusions: This rapid and economical assay can accurately detect the presence of HLA-B*57:01 in clinical specimens. Use of this assay could expand access to HLA-B*57:01 genotyping and facilitate safe same-day initiation of abacavir-based treatment.

Differential response to biologics in a patient with severe asthma and ABPA: a role for dupilumab?

Background Allergic bronchopulmonary aspergillosis (ABPA) is a severe hypersensitivity reaction to aspergillus species colonizing the airways of patients with asthma or cystic fibrosis. Biologics including anti-IgE and anti-IL5 antibodies have strongly changed the treatment of severe asthmatics and have partly been reported to be effective in the treatment of ABPA. Recently, dupilumab, an anti-IL4-Rα antibody which inhibits signaling by the Th2-cytokines IL4 and IL13, has been approved for the treatment of severe asthma. Case presentation Here, we report the case of a 49-year-old woman with severe asthma and ABPA, who was uncontrolled despite maximum inhalative therapy, anti-IL5-Rα antibody and continuous oral steroid therapy. Moreover, trials of itraconazole as well as omalizumab showed insufficient efficacy. Lung function revealed peripheral obstruction. FeNO and IgE were increased, eosinophils were suppressed under treatment while marked increases had been documented previously. Switching to dupilumab led to a complete resolution of pulmonary symptoms, resolution of exacerbations and complete withdrawal of oral steroids. A drastic improvement in lung function was noted, with an increase in FEV1 of almost 1 l. FeNO was normalized and IgE strongly reduced. Conclusion Our case highlights that a patient may exhibit differential treatment responses to the currently available asthma biologics and suggests switching treatment if outcome is insufficient. A potential role for dupilumab in the treatment of ABPA warrants future studies.

Oxaliplatin induced laryngospasm: a case series

Oxaliplatin is a third-generation platinum derivative used as a first-line agent in the treatment of colorectal carcinoma, biliary tract cancer and gastric cancers and can be used as a neoadjuvant/adjuvant in these cancers. The dose limiting toxicity is peripheral neuropathy, others include hypersensitivity reactions, haematological toxicity and pulmonary fibrosis. Hypersensitivity reactions can extend from milder reactions like urticaria, rash to severe symptoms like hypotension and laryngospasm. The laryngospasm due to oxaliplatin is reported to be reversible with corticosteroids, antihistamines and oxygen. This case series suggest that oxaliplatin has a propensity to cause severe hypersensitivity reaction presenting as laryngospasm not with a single dose but with subsequent doses of oxaliplatin. Prompt symptomatic treatment with corticosteroids leads to reversal of symptoms and improvement in the condition of the patient.

Kerion of the pubis and vulva with bacterial superinfection: a rare occurrence

Kerion is a severe hypersensitivity reaction to fungal infection that is rarely seen in the groin. Frequent shaving of pubic hair and religious conservatism surrounding genital hygiene are common among Bedouin women in the Negev Desert, and may predispose to kerion. This case highlights the clinical course of a 20-year-old Bedouin woman who presented with severe kerion celsi of the pubis and vulva with secondary bacterial infection. The patient was successfully treated with intravenous antibiotics, oral antifungal medication and wet topical dressings. The case outlines the risk factors and treatment for severe kerion celsi of the groin, as well as possible preventive measures that may reduce its incidence.

Graded Dalbavancin Challenge in a Patient With Severe Vancomycin Hypersensitivity Reaction

Cross-reactivity should be considered when treating patients with a previous hypersensitivity reaction within the same class of antibiotics that share similar chemical structures. This case report describes a patient with severe hypersensitivity reaction to vancomycin who successfully tolerated a dalbavancin graded challenge.