The Profile of Type 1 Leprosy Reaction at Leprosy Division of Dermatology and Venerology Outpatient Clinic of Dr. Soetomo General Academic Hospital, Surabaya, Indonesia

Background: Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Type 1 leprosy reaction is a delayed hypersensitivity reaction caused by the increased response of cellular-mediated immunity to the Mycobacterium leprae antigen on the skin and nerves with a reversal result. The clinical manifestation includes inflammation which can cause skin and nerve lesions, swell, to permanent disabilities. Purpose: To describe the demographic and clinical profile of type 1 leprosy reaction at the Leprosy Division of the Dermatology and Venerology Outpatient Clinic of Dr. Soetomo General Academic Hospital in 2017–2019. Methods: This was a descriptive study. We used secondary data from the medical records of leprosy patients at the Leprosy Division of Dermatology and Venereology outpatient clinic, Dr. Soetomo General Academic Hospital Surabaya, from January 2017 to December 2019. Result: Out of 364 patients, 65 (17.9%) had type 1 reactions. They were mostly in productive age at 35–55 years old (56.9%). The patients were predominantly male (75.4%), with normal nutritional status (98.5%) and negative bacterial index (72.3%). The most common types of leprosy were BB (Borderline) with 61.6% and BL (Borderline Lepromatous) with 20.8%. All patients took WHO (World Health Organization) MDT (Multi Drug Therapy) MB (Multi-Bacillary). Conclusion: The profile of type 1 leprosy reaction at the Leprosy Division of Dermatology and Venerology Outpatient Clinic of Dr. Soetomo General Academic Hospital in 2017–2019 shows an average data as follows: age 35–55 years, male, normal nutritional status, negative bacterial index, leprosy type BB.

Severe delayed hypersensitivity reactions to IL-1 and IL-6 inhibitors link to common HLA-DRB1*15 alleles

ObjectivesDrug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, delayed hypersensitivity reaction (DHR). We observed DRESS to inhibitors of interleukin 1 (IL-1) or IL-6 in a small group of patients with Still’s disease with atypical lung disease. We sought to characterise features of patients with Still’s disease with DRESS compared with drug-tolerant Still’s controls. We analysed human leucocyte antigen (HLA) alleles for association to inhibitor-related DHR, including in a small Kawasaki disease (KD) cohort.MethodsIn a case/control study, we collected a multicentre series of patients with Still’s disease with features of inhibitor-related DRESS (n=66) and drug-tolerant Still’s controls (n=65). We retrospectively analysed clinical data from all Still’s subjects and typed 94/131 for HLA. European Still’s-DRESS cases were ancestry matched to International Childhood Arthritis Genetics Consortium paediatric Still’s cases (n=550) and compared for HLA allele frequencies. HLA association also was analysed using Still’s-DRESS cases (n=64) compared with drug-tolerant Still’s controls (n=30). KD subjects (n=19) were similarly studied.ResultsStill’s-DRESS features included eosinophilia (89%), AST-ALT elevation (75%) and non-evanescent rash (95%; 88% involving face). Macrophage activation syndrome during treatment was frequent in Still’s-DRESS (64%) versus drug-tolerant Still’s (3%; p=1.2×10−14). We found striking enrichment for HLA-DRB1*15 haplotypes in Still’s-DRESS cases versus INCHARGE Still’s controls (p=7.5×10-13) and versus self-identified, ancestry-matched Still’s controls (p=6.3×10−10). In the KD cohort, DRB1*15:01 was present only in those with suspected anakinra reactions.ConclusionsDRESS-type reactions occur among patients treated with IL-1/IL-6 inhibitors and strongly associate with common HLA-DRB1*15 haplotypes. Consideration of preprescription HLA typing and vigilance for serious reactions to these drugs are warranted.

Refractory in-stent stenosis after flow diverter stenting associated with delayed cobalt allergic reaction

In-stent stenosis (ISS) triggered by a metal-induced allergic reaction of Pipeline embolization device (PED) placement is extremely rare. The present report describes a patient who presented with delayed parent artery occlusion and refractory ISS after PED placement due to cobalt allergy. A patient in her 70s underwent PED placement for a right internal carotid artery (ICA) large aneurysm; 4 months later, the patient presented with left-sided hemiparesis, and MRI revealed right ICA occlusion even though antiplatelet therapy was optimal. She underwent mechanical thrombectomy, and successful recanalization was achieved. However, follow-up angiography 6 months after the thrombectomy revealed severe ISS, and the patch testing showed a positive reaction for cobalt. As a result of long-term administration of oral steroids and antihistamine, progression of ISS was suppressed. It was supposed that a delayed hypersensitivity reaction to cobalt might induce refractory ISS after PED placement.

Anatomy of a successful stewardship intervention: Improving perioperative prescribing in penicillin-allergic patients

Objective: To evaluate whether a series of quality improvement interventions to promote safe perioperative use of cephalosporins in penicillin-allergic patients improved use of first-line antibiotics and decreased costs. Design: Before-and-after trial following several educational interventions. Setting: Academic medical center. Patients: This study included patients undergoing a surgical procedure involving receipt of a perioperative antibiotic other than a penicillin or carbapenem between January 1, 2017, and August 31, 2019. Patients with and without a penicillin allergy label in their electronic medical record were compared with respect to the percentage who received a cephalosporin and average antibiotic cost per patient. Methods: A multidisciplinary team from infectious diseases, allergy, anesthesiology, surgery, and pharmacy surveyed anesthesiology providers about their use of perioperative cephalosporins in penicillin-allergic patients. Using findings from that survey, the team designed a decision-support algorithm for safe utilization and provided 2 educational forums to introduce this algorithm, emphasizing the safety of cefazolin or cefuroxime in penicillin-allergic patients without history of a severe delayed hypersensitivity reaction. Results: The percentage of penicillin-allergic patients receiving a perioperative cephalosporin improved from ∼34% to >80% following algorithm implementation and the associated educational interventions. This increase in cephalosporin use was associated with a ∼50% reduction in antibiotic cost per penicillin-allergic patient. No significant adverse reactions were reported. Conclusions: An educational antibiotic stewardship intervention produced a significant change in clinician behavior. A simple intervention can have a significant impact, although further study is needed regarding whether this response is sustained and whether an educational intervention is similarly effective in other healthcare systems.

DRESS induced by amoxicillin-clavulanate in two pediatric patients confirmed by lymphocyte toxicity assay

Background Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but serious delayed hypersensitivity reaction that can be caused by antibiotic exposure. The reaction typically develops in 2 to 6 weeks. The pathophysiology is thought to involve toxic drug metabolites acting as a hapten, triggering a systemic response. The diagnosis is made clinically but can be confirmed using assays such as the lymphocyte toxicity assay (LTA), which correlates cell death upon exposure to drug metabolites with susceptibility to hypersensitivity reactions. Case presentations Case 1 involves a previously healthy 11-month-old male with first exposure to amoxicillin-clavulanate, prescribed for seven days to treat a respiratory infection. The patient developed DRESS fourteen days after starting the drug and was successfully treated with corticosteroids. LTA testing confirmed patient susceptibility to hypersensitivity reactions with amoxicillin-clavulanate. Parental samples were also tested, showing both maternal and paternal susceptibility. Neither parent reported prior hypersensitivity reactions. Lifelong penicillin avoidance for the patient was advised along with the notation in medical records of penicillin allergy. The parents were advised to avoid penicillin class antibiotics and be monitored closely for DRESS if they are exposed. Case 2 involves an 11-year-old female with atopic dermatitis with first exposure to amoxicillin-clavulanate, prescribed for ten days to treat a secondary bacterial skin infection. She developed DRESS eleven days after starting antibiotics and was successfully treated with corticosteroids. LTA testing confirmed patient susceptibility to hypersensitivity reactions with amoxicillin-clavulanate. Maternal samples were also tested and showed sensitivity. The mother reported no prior hypersensitivity reactions. Lifelong penicillin avoidance for the patient was advised along with the notation in medical records of penicillin allergy. Conclusions Amoxicillin-clavulanate is a commonly used antibiotic and the cases we have described suggest that it should be recognized as a potential cause of DRESS in pediatric patients. Furthermore, these cases contribute to current literature supporting that there may be a shorter latent period in DRESS induced by antibiotics. We have also shown that the LTA can be a helpful tool to confirm DRESS reactions, and that testing may have potential implications for family members.

Drug Reaction with Eosinophilia and Systemic Symptoms: A Complex Interplay between Drug, T Cells, and Herpesviridae

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, also known as drug induced hypersensitivity (DiHS) syndrome is a severe delayed hypersensitivity reaction with potentially fatal consequences. Whilst recognised as T cell-mediated, our understanding of the immunopathogenesis of this syndrome remains incomplete. Here, we discuss models of DRESS, including the role of human leukocyte antigen (HLA) and how observations derived from new molecular techniques adopted in key studies have informed our mechanism-based understanding of the central role of Herpesviridae reactivation and heterologous immunity in these disorders.