Background Immune checkpoint inhibitor (ICI) use in clinical practice has unravelled a spectrum of immune-related adverse events (irAEs) due to immune system hyper-activation. ICI-related haemophagocytic lymphohistiocytosis (HLH) has been recently outlined in single case reports, raising a concern about the need of increasing our knowledge on this rare yet life threatening ICI haematological toxicity. Methods To determine ICI-related HLH clinical, haematological, and coagulation features, its timing and outcome, concurrent irAEs and concomitant infections, we performed a retrospective observational cross-sectional study and queried VigiBase, the WHO global database of suspected adverse drug reactions (ADRs), on September 30th, 2018. We retrieved the individual case safety reports reporting HLH in association with ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab or durvalumab, gathered in the database starting from the ICIs’ approval dates by the US Food and Drug Administration. The main outcome measures were co-suspected drugs, concurrent irAEs, HLH clinical, haematological and coagulation features, concomitant infections, HLH median time to onset and outcome. Results Among 49′883 ICI-related ADRs collated in VigiBase as of September 30th, 2018, HLH was reported in 38 cases of which 34 (90%) mentioned ICIs as the solely suspected drugs. ICI-related HLH showed clinical, haematological and coagulation features similar to those of HLH with different etiology. Concurrent irAEs occurred in 5 (13%) patients and 6 (16%) reported concomitant viral infections. 31 (82%) cases defined ICI-related HLH outcome, which resolved in 19 (61%) cases. HLH developed a median of 6.7 weeks after initiation of ICI treatment (IQR 2.9–15.4, n = 18, 47%). Conclusions By evaluating the largest cohort of ICI-related HLH cases, we observed that ICI-related HLH arises with a delayed timing with respect to initiation of ICI treatment, and usually presents without other irAEs and concomitant infections. Keeping in mind these findings, clinicians should consider ICIs’ involvement in the onset of HLH whenever they diagnose a disease of this group of syndromes in cancer patients treated with ICIs.

A computerised drug-drug interaction program (detection) together with clinical pharmacological experience (interpretation/evaluation) can be useful for decreasing the number of potentially harmful drug combinations. This approach may lead to an improvement in the quality of prescription, reducing possible risks and thus contributing to patient safety.

Since marketing authorization, cases of neuralgic amyotrophy (NA), facial paralysis/Bell’s palsy (FP/BP), and Guillain-Barré syndrome (GBS) were reported with COVID-19 vaccines of different technologies. This study aimed to assess whether NA, FP/BP, and GBS were more frequently reported in VigiBase with COVID-19 vaccines (of any technologies) than with other viral vaccines, over the full database and across potential risk groups by sex and age. The reporting odds ratio (ROR) with 95% confidence interval (95% CI) was used as the measure of disproportionality and subgroup disproportionality analyses were performed by sex and age. Out of 808,906 safety reports with COVID-19 vaccines, 57 (0.01%) reported NA, 3320 (0.4%) FP/BP, and 632 (0.1%) GBS. There were not signals of disproportionate reporting for NA and GBS with COVID-19 vaccines against other viral vaccines. FP/BP was disproportionately more frequently reported with COVID-19 vaccines than with other viral vaccines over the full database (ROR 1.12, 95%CI 1.07–1.17), in males (ROR 1.65, 95%CI 1.54–1.78) and in age subgroups 65–74 years (ROR 1.21, 95%CI 1.05–1.39) and ≥75 years (ROR 1.84, 95%CI 1.52–2.22). Albeit not proving causation, these findings might support clinicians in decision-making for patients potentially at risk for developing an acute inflammatory neuropathy with COVID-19 vaccines.

Background: The spectrum of inflammatory marker response in DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome has not been systematically characterized. Methods: An epidemiological biomarker study of C-reactive protein (CRP) and procalcitonin (PCT) values in patients with DRESS syndrome reported at 2 regional pharmacovigilance centers in Switzerland or published in the medical literature 2008–2016 was performed. Results: Ninety-four DRESS cases were studied. All cases showed a CRP value > 10 mg/L (the upper limit of normal). The mean CRP value was 109.2 ± 79.4 mg/L. CRP values were significantly higher in 22 cases where a cause of inflammation besides DRESS could not be excluded (mean 162.1 vs. 92.9 mg/L; p = 0.003). Receiver operator characteristics curve analysis showed a moderate performance with a CRP cut-off value of 99.4 mg/L (AUC 0.717) to distinguish between patients with and without a possible additional cause of inflammation. The mean and median PCT values were 2.44 ± 5.94 and 0.69 ng/mL, respectively (n = 25 patients). Patients in whom an additional cause of inflammation besides DRESS could not be excluded showed a median PCT of 1.37 ng/mL (n = 9) versus 0.67 ng/mL (n = 16) in patients with DRESS only. PCT values were above the normal cut-off of 0.1 ng/mL, suggestive of bacterial infection in all but 1 case. Furthermore, there was a correlation between PCT values and hepatic enzyme measurements. Conclusions: Evaluating CRP and PCT values might be of use in helping physicians to distinguish between cases of DRESS syndrome with and without concurrent infection or other causes of inflammation. Further prospective investigation is required to define the use of these inflammatory markers in the management of DRESS.

When prescribing Sirdalud, the possible pharmacological side effects and interactions should be taken into careful account.

No abstract

According to the Human Research Act (810.30, of September 30th, 2011-status as of January 1st, 2014), from the Federal Assembly of the Swiss Confederation, ethical approval was not required (Art.2: "It does not apply to research which involves anonymously collected or anonymised health-related data").

A 45-year-old previously healthy caucasian man was admitted for pruritus, scleral icterus and dark urine. The patient was reported to have taken a spoon of a preparation containing camu-camu (myrciaria dubia) a day. He took no other drugs and did not drink alcohol or use illicit substance. Laboratory studies reveiled an elevated aspartate transaminase of 403 U/L, and alanine transaminase of 1185 U/L, alkalinephosphatase of 335 U/L, gamma glutamyl transpeptidase of 300 U/L, and elevated total bilirubin of 142 μmol/L. His complete blood count was normal. Tests for viral, metabolic or autoimmune causes of liver injury were negative. Liver biopsy demonstrated centrilobular hepatocellular damage was compatible with drug toxicity which was not of very recent origin. Clinical and laboratory signs of liver injury gradually improved and the patient was discharged. Myrciaria dubia is used as a dietary supplement with antioxidant properties. To our knowledge, this is the first report of liver injury probably related to use of camu-camu. Exclusion of other causes and the histological diagnosis were compatible with drug toxicity render camu-camu which was most likely as the cause of acute heaptitis most likely. It is important to increase the awareness of both clinicians and patients about the potential dangers of herbal remedies in absence of reliable studies of clinical efficacy and benefit-risk assessment.