Leukocytoclastic Vasculitis Following COVID-19 Vaccination: A Case Report

Background: Hypersensitivity or Leukocytoclastic vasculitis (LCV) following the COVID-19 vaccination has been reported rarely all over the world. LCV can be induced by certain factors such as infections, autoimmune disorders, malignancy, or some classes of drugs. Case presentation: A 32-year-old man, who was a known case of seizure disorder from his childhood presented to the department of dermatology with itchy red lesions on extremities and abdomen for the past 1 month. He explains a history of COVID-19 vaccination 1-month back and experienced itching on his lower limbs on the same day at night. A gradual worsening of the condition was observed day by day. He was hospitalized and diagnosed as LCV through clinical and laboratory findings. Conclusion: This case highlights a temporal association with the event of vaccination. The causality assessment showed an indeterminate causal association to LCV with COVID-19 Vaccination.

Adverse Drug Reaction Monitoring of Antidepressant Drugs in a Mental Health Institute in Odisha

Introduction: Antidepressants are used primarily in the management of depressive and anxiety disorders. The occurrence of adverse drug reactions (ADRs) to antidepressants is a major challenge as it influences patient compliance. Aim: The aim of this study was to find out the ADR profile of antidepressant drugs in a mental health institute in Odisha. Materials and Methods: This is a cross sectional observational study conducted in Department of Pharmacology in collaboration with Mental Health Institute (Centre of Excellence) S.C.B Medical College and Hospital, Cuttack from September 2017 to September 2019. Patients who received at least one antidepressant drug were included in the study irrespective of age and sex. Data were collected by interviewing the patients or attendants and on detection of ADR, it was recorded on suspected ADR reporting form designed by PvPI. Causality, severity and preventability of ADRs were assessed by, WHO-UMC causality assessment, modified Hartwig-Siegel Scale and modified Schumock-Thornton criteria respectively. Results: Out of 180 patients taking antidepressants, ADRs were reported in 24% of patients, with either possible or probable causality. None were labelled as certain. ADRs were observed in 50% of patients who received TCAs and among 34.5% who received polytherapy. Insomnia (27%), fatigue (17%) and agitation (13%) were most common ADRs. Most of the ADRs were of mild severity (91%) and not preventable (84%). Conclusion: Insomnia, fatigue and agitation were among most common ADRs. There was increased chance of ADRs with polytherapy and use of TCAs. Most ADRs were mild and not preventable.

Causality Evaluation of Drug-Induced Liver Injury in Newborns and Children in the Intensive Care Unit Using the Updated Roussel Uclaf Causality Assessment Method

Purpose: Drug-induced liver injury (DILI) is a common adverse reaction in the clinic; however, there are relatively few reports of DILI in critically ill newborns and children. Making use of the Pediatric Intensive Care database (PIC), this study identifies which drugs are related to DILI in neonates and children in China.Methods: Using the PIC, we screened for patients whose liver was suspected of being injured by drugs during hospitalization. The medicine they used was then assessed by the Roussel Uclaf Causality Assessment Method (RUCAM). At the same time, we also collated drug combinations that may affect CYP (Cytochrome P) enzyme metabolism, which may cause DILI.Results: A total of 13,449 patients were assessed, of whom 77 newborns and 261 children were finally included. The main type of liver injury in neonates was mixed (83.1%), while the hepatic injury types of children were mostly distributed between hepatocellular (59.4%) and cholestatic (28.4%). In terms of the RUCAM assessment, the drugs that were most considered to cause or be associated with hepatic injury in newborns were medium and long chain fat emulsions (17%), sodium glycerophosphate (12%), and meropenem (9%); while omeprazole (11%), methylprednisolone sodium succinate (10%), and meropenem (8%) were the primary culprits of DILI in children. Drug combinations frequently seen in neonates that may affect CYP enzyme metabolism are omeprazole + budesonide (16.9%), dexamethasone + midazolam (10.4%), and midazolam + sildenafil (10.4%). In children, the commonly used drug combinations are fentanyl + midazolam (20.7%), ibuprofen + furosemide (18.4%), and diazepam + omeprazole (15.3%).Conclusions: In this study, medium and long chain fat emulsions and sodium glycerophosphate have been strongly associated with DILI in newborns, while omeprazole and methylprednisolone sodium succinate play an important role in the DILI of children. Also, attention should be paid to the effect on CYP enzymes when using multiple drugs at the same time. In future DILI cases, it is advisable to use the latest RUCAM for prospective study design so that complete case data and high RUCAM scores can be collected.

Case Report on Mild Anemia and Gastritis due to Zidovudine, Lamivudine and Nevirapine (ZLN) Regimen

AIDS is a deadly syndrome in which Highly Active Anti-retroviral therapy is used to reduce the viral load. However these anti-retroviral drugs are supposed to cause several adverse drug reaction. There are several studies that report anemia with Zidovudine and gastrointestinal symptoms with Lamivudine. In this report, We present a case of a 38 year old female patient suffering from HIV infection who is suspected to drug induced anemia and gastritis due to Zidovudine, Lamivudine and Nevirapine combination (ZLN) regimen. The relationship between the administered drug regimen and the suspected ADR’s was found using causality assessment. Severity, predictability and probability was also found for the suspected ADR’s. We need to monitor the HIV patients who are under ZLN regimen for their blood haemoglobin and gastrointestinal symptoms.

Methods for Identifying Culprit Drugs in Cutaneous Drug Eruptions: A Scoping Review

Background Cutaneous drug eruptions are a significant source of morbidity, mortality, and cost to the healthcare system. Identifying the culprit drug is essential; however, despite numerous methods being published, there are no consensus guidelines. Objectives Conduct a scoping review to identify all published methods of culprit drug identification for cutaneous drug eruptions, compare the methods, and generate hypotheses for future causality assessment studies. Eligibility criteria Peer-reviewed publications involving culprit drug identification methods. Sources of evidence Medline, Embase, and Cochrane Central Register of Controlled Trials. Charting methods Registered PRISMA-ScR format protocol on Open Science Forum. Results In total, 109 studies and 26 reviews were included comprising 656,635 adverse drug events, most of which were cutaneous. There were 54 methods of culprit drug identification published, categorized as algorithms, probabilistic approaches, and expert judgment. Algorithms had higher sensitivity and positive predictive value, but lower specificity and negative predictive value. Probabilistic approaches had lower sensitivity and positive predictive value, but higher specificity and negative predictive value. Expert judgment was subjective, less reproducible, but the most frequently used to validate other methods. Studies suggest that greater accuracy may be achieved by specifically assessing cutaneous drug eruptions and using combinations of causality assessment categories. Conclusions Culprit drug identification for adverse drug reactions remains a challenge. Many methods have been published, but there are no consensus guidelines. Using causality assessment methods specifically for cutaneous drug eruptions and combining aspects of the different causality assessment categories may improve efficacy. Further studies are needed to validate this hypothesis.

Safety Profile of Recommended Vaccinations in Adolescents: Data from Surveillance of Adverse Events Following Immunization in Puglia (Italy), 2016–2020

Adolescence is a critical period for immunization, in which the adhesion rate to recommended vaccinations is often lower than desired. Since the safety of new vaccines is one of the most important factors determining vaccination hesitancy, post-marketing surveillance of adverse events following immunization (AEFIs) is recommended by the World Health Organization (WHO) to better understand the safety of these drugs. This report describes AEFIs notified in Puglia (Italy) after recommended vaccinations in adolescents aged 12 to 18 years in 2016–2020 to determine the safety profile of these products in a real-life scenario. This is a retrospective observational study. Data were gathered from the list of AEFIs notified in subjects between 12 and 18 years of age following administration of recommended vaccines in Puglia in 2016–2020. AEFIs were classified according to the WHO’s decisional algorithm, and causality assessment was carried out for serious AEFIs. From 2016 to 2020, 323,627 doses of vaccine were administered to adolescents in Puglia and 50 AEFIs were reported (reporting rate: 15.4 × 100,000 doses). Of these, 17 (34.0%) were classified as serious, and causality assessment identified 13 of them (76.5%) as vaccine related. The most common symptoms were local reactions, fever and neurological symptoms. No deaths were notified. The benefits of immunization in adolescents appear to be greater than the risk of AEFIs for all studied vaccines; in fact, AEFIs occur in less than 0.1‰ of patients and are generally mild and self-limiting.

IgA Vasculitis and COVID-19 in Children: A Systematic Review

Background: Immunoglobulin A vasculitis is the most common form of vasculitis in children. The diagnosis is made clinically and patients will present with a rash, together with gastrointestinal, musculoskeletal, and renal system involvement. Progress in the classification of the systemic vasculitides has facilitated better understanding of the pathogenesis underlying these inflammatory conditions. Over the past year, several cases of IgA vasculitis have been reported in both children and adults in association with SARS-CoV2 infection, raising the question of whether there is any causal or even a synergistic association.Methods: This systematic review was performed following the guidelines of Meta-analysis of Observational Studies in Epidemiology. A literature search was conducted using MEDLINE, SciELO and Google Scholar using the search terms “COVID-19” or “SARS-CoV-2" in combination with “IgA vasculitis”, or “Henoch-Schonlein Purpura”. We considered articles to be eligible for inclusion if they reported a case report or series of cases of IgA vasculitis associated with proven COVID-19 infection. We excluded cases from further review if the case reported was a patient older than 18 years. WHO causality assessment categories were used to standardize case causality. Results: After reviewing the complete article and applying our exclusion criteria, 12 articles describing 12 cases of COVID-19 associated IgA vasculitis in children were included. In 83% of the cases the diagnosis of COVID-19 was made on presentation of IgA symptoms or on presentation to seek medical care. In 17% of cases the SARS Cov-2 test was positive before IgA vasculitis symptoms presentation. The mean age of the patients was 7.3 years of age (SD ±4.8). Male to female ratio was 3:1. Lower extremity purpura was present in all 12 patients. Gastrointestinal manifestations were present in 7 patients. Oligoarthritis was present in 7 patients. Three patients presented renal involvement with hematuria/proteinuria. Conclusions: During the pandemic, several autoimmune phenomena have been described to co-occur with or following COVID-19. The exact role of COVID-19 in the development of these IgA-related diseases is still being explored. Our review of case series and case reports with standardized causality assessment identified 12 cases of IgA vasculitis associated with COVID-19 infection in children.

Real-World Data of Tigecycline-Associated Drug-Induced Liver Injury Among Patients in China: A 3-year Retrospective Study as Assessed by the Updated RUCAM

Background: Tigecycline, a glycylcycline antibiotic, is increasingly used clinically for the treatment of severe infections caused by multidrug-resistant bacteria, but it is also associated with hepatotoxicity. However, the incidence and risk factors of tigecycline-associated drug-induced liver injury (DILI) are unclear. We conducted this study to investigate the incidence, characteristics and risk factors of tigecycline-associated DILI in the real-world clinic setting.Patients and Methods: A retrospective analysis was conducted in inpatients who received tigecycline treatment from January 2018 to January 2020. Based on the biochemical criteria of DILI and the causality assessment by Roussel Uclaf Causality Assessment Method (RUCAM) using cases with a probable or highly probable causality grading, two clinical pharmacists and one clinician worked together to screen patients for tigecycline-associated DILI. Then patients with DILI were randomly matched by gender in a ratio of 1:2 to the remaining patients in the tigecycline cohort without biochemical abnormalities to identify risk factors.Results: A total of 973 patients from 1,250 initial participants were included. The incidence of tigecycline-associated DILI was 5.7% (55/973). Among 55 DILI patients, 10 cases presented with the hepatocellular pattern, 4 cases belonged to the mixed pattern, and 41 presented with the cholestatic pattern. Most cases reached the severity of grade 1 and 2. The rate of recovery in hepatocellular pattern, mixed pattern, and cholestatic pattern was 70.0, 50.0, and 41.5%, respectively. The proportion of the DILI cases treated with high dose (100 mg) and prolonged duration (>14 days) was significantly higher than standard dose and routine duration (100.0% vs. 18.1%, p < 0.05). Logistic regression analysis showed that high maintenance dose (OR = 1.028, p = 0.002), prolonged duration (OR = 1.208, p = 0.000), and number of hepatotoxic drugs (OR = 2.232, p = 0.000) were independent factors of tigecycline-associated DILI.Conclusion: Tigecycline was associated with liver injury, with a slightly higher incidence (5.7%) than the frequency of “frequent” (5%) defined by the Medical Dictionary for Regulatory Activities. Patients with a high maintenance dose and prolonged tigecycline regimen, as well as concomitant use of multiple hepatotoxic drugs should be paid more attention.

Clinical Pattern and Causality Assessment of Drug-induced Cutaneous Reactions in a Tertiary Care hospital in India – A Prospective Study

Background: Cutaneous Adverse Drug Reactions (ADRs) are very common and is an important challenge to the physician especially in situations of multiple comorbidities of the patient, polypharmacy and self-administration of over-the-counter medications. Objective: To analyze the clinical pattern and incidence of cutaneous ADRs and perform causality assessment using the WHO-UMC scale and Naranjo’s scale and severity of the reactions were determined by Hartwig scale. Method: This was conducted as a prospective observational study in patients admitted in SRM Medical College, Kattankulathur, Tamil Nadu, India, between November 2016 to August 2018 after obtaining Institutional Ethics Committee clearance, of all adverse drug reactions reported at the hospital. Results: Of the 158 ADRs reported during the time period, 101 were cutaneous ADRs, of which the most common presentation was maculopapular rash (n=42; 41.58%). The most common drug which produced cutaneous adverse reaction were antimicrobials (n=58; 57.42%) followed by NSAIDs (n=35; 34.6%). The causality assessment as per the Naranjo scale yielded 3.96% (4) cases as definite, 81.18 % (82) as probable and 14.85 % (15) as possible whereas the WHO scale yielded 9 (89.10%) certain, 64 (63.36%) probable and 28 (27.72%) possible cases. The severity of the cases determined as per the Hartwig scale yielded 82.17% cases as mild and 17.82 % as moderate. Conclusion: It is important to recognise the ADRs at the right time and exert caution in future use. This can minimise harm to the patient both physically and financially and improve outcome of the treatment.