Naranjo Adverse Drug Reaction Probability Research Articles

Clinical Profile of Patients with Lichenoid Drug Eruption: A Observational Study

Background: Lichenoid drug eruption (LDE) is an uncommon cutaneous adverse drug reaction, where a variety of drugs used in day-to-day clinical practice have been implicated. Objective: To describe the clinico-demographic characteristics of patients with LDE and to identify the most likely drugs involved. Methods: In this prospective, observational study, consecutive patients with LDE presenting to the dermatology department of a tertiary teaching hospital were included. The clinico-demographic profile of patients with LDE and implicated drugs was noted. Treatment of drug reaction along with outcome was also documented. Naranjo adverse drug reaction probability scale was used for causality assessment of the drug reactions. A thorough literature review on LDE was also undertaken due to the paucity of existing literature. Results: A total of 15 patients (11 males and 4 females) with LDE were evaluated. Their age ranged from 37 to 61 years, with a mean of 51.53 ± 7.59 years. Anti-hypertensive medications (40%) were the most common culprit agent, followed by antitubercular drugs (33.4%), anti-diabetic agents (13.3%), and others (13.3%). The latent period (time from drug initiation to the appearance of a cutaneous eruption) varied from 15 days to 6 months (mean 2.2 months). Cutaneous involvement was generalized in 73.4% and photo-distributed lesions in 26.6%. Drug provocation test was done to identify the culprit drug. According to the Naranjo adverse drug reaction probability scale, one-third of LDEs were “definite,” whereas two-thirds were designated as “probable.” Conclusion: LDE is more common in the elderly population. The latent period is comparatively longer in LDE than in other common drug reactions. Prompt recognition and withdrawal of suspected drug are essential to minimize disease morbidity.

P839 Acute interstitial nephritis in patients with Inflammatory Bowel Disease treated with vedolizumab: a systematic review

Abstract Background Acute interstitial nephritis (AIN) is a complication of drugs that may cause permanent kidney injury. AIN has been reported in inflammatory bowel disease (IBD) patients treated with the anti-integrin inbibitor vedolizumab. However, systematically collected data on cases of AIN associated with vedolizumab treatment is lacking. We therefore, through systematic review of existing literature, aimed to identify and describe reported cases of AIN. Methods We searched Medline, Embase, Cochrane, and Web of Science Core Collection between January 1, 2009 and April 25, 2023. The search yielded 1473 publications after deduplication, for which titles and abstracts were screened by two independent reviewers. Of these, 75 publications were reviewed in full-text. Demographics and clinical characteristics of AIN cases were extracted. Case causality assessment was performed according to the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) system and the Naranjo Adverse Drug Reaction Probability Scale. Results were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A prespecified protocol was registered in the PROSPERO database. Results Eight publications met the inclusion criteria and were included in descriptive analysis of AIN in patients with IBD treated with vedolizumab. A total of nine biopsy-confirmed cases of AIN were reported in six patients with ulcerative colitis and three with Crohn’s disease. The mean age at AIN onset was 36 years (range: 19-58). The majority of patients were females (n=6/9). Time from vedolizumab treatment initiation to AIN onset spanned from hours to 12 months. Common symptoms were fever, malaise, and myalgia. Creatinine levels were elevated in all patients (mean: 219 µmol/L; range; 133-410). Rechallenge after pause and treatment with corticosteroids were reported in three cases, where one attempt was successful. Five patients sustained permanent kidney injury. According to the WHO-UMC scale, six of nine cases were assessed as “possible” or “probable”, and the remaining three cases as “unlikely” or “unclassifiable”. Three patients were treated with concomitant mesalazine or proton pump inhibitors, which both are associated with an increased risk of AIN. Conclusion In systematic review of existing literature, we identified nine cases of biopsy-confirmed AIN in patients with IBD treated with vedolizumab. Our findings suggest that vedolizumab, although rarely, could potentially cause AIN in patients with IBD. Awareness of laboratory findings and symptoms consistent with AIN, along monitoring of the kidney function, could be warranted in patients with IBD treated with vedolizumab.

Hydroxychloroquine-Induced Hypoglycemia in a Patient Without Diabetes.

Hydroxychloroquine is a disease-modifying antirheumatic drug commonly used in the treatment of autoimmune diseases. Although rare, hydroxychloroquine is associated with hypoglycemia in patients with or without diabetes due to its ability to alter insulin metabolism. There have been several cases described in the literature, but none of which, to our knowledge, detail follow-up and time to resolution of hypoglycemia. We describe a 55-year-old female who presents for episodes of hypoglycemia. She reported hypoglycemic symptoms and fasting blood glucoses in the 60-70s mg/dL regularly. Based on the Naranjo adverse drug reaction probability scale, hydroxychloroquine was the probable etiology of her hypoglycemic episodes due to the improvement at her 3-month follow up appointment after discontinuing the drug. Providers should be mindful of the hypoglycemia risk when using hydroxychloroquine and be aware that the effects may take an extended amount of time to resolve given the drug's long half-life.

A CASE POSSIBLE SEROTONIN SYNDROME CASE CAUSED BY COMBINED USE OF FLUOXETINE AND LOW DOSE TRAZODONE AND ASSESSED BY THE NARANJO ADVERSE DRUG REACTION PROBABILITY SCALE

Serotonin sendromu serotonerjik ajan kullanımı sonrasında
 oluşan serotonin reseptörlerinin aşırı uyarılması
 sonucu gelişen nadir görülen fakat mortal seyredebilen
 sendromdur. Klinik belirti ve bulgular kognitif,
 nöromüsküler ve otonomik alanda görülmektedir. Serotonerjik
 etkili bir veya daha fazla ajanın birlikte kullanılması
 bu sendroma neden olur. Klinik görünümü hafif
 şiddette olup gözden kaçabilen olgular olduğu gibi
 hayatı tehdit eden, yoğun bakım ve mekanik ventilasyon
 gerektiren şiddette de olabilmektedir. Bu yazıda
 fluoksetin tedavisine trazodon eklenmesi ve doz artırılması
 sonrasında 24 saat içerisinde gelişen serotonin
 sendromu düşündüren bir vaka sunulmuştur.

Ribociclib-induced pulmonary infiltrates in a patient with breast cancer.

Breast cancer is the most common cancer in women worldwide. One of the treatment choices used in hormone receptor positive and HER2 expression negative metastatic breast cancer is cyclin dependent kinase 4/6 (CDK) inhibitors. There are differences between the effects and adverse events of all CDK4/6 inhibitors. In this report, we describe a 48-year-old female patient with breast cancer who developed pulmonary infiltrates secondary to drug in the second year of follow-up with Ribociclib therapy. The patient who used ribociclib for metastatic breast cancer was admitted to hospital for routine controls. The patient, in the eighth month of ribociclib treatment, had no active complaints. In the patient's imaging, pulmonary infiltrates were detected in the lower lobe of the right lung. The drug was continued in the patient who was asymptomatic and had no infectious signs. Pneumonitis, interstitial lung disease, tuberculosis, COVID-19 and other viral agents were excluded in the patient. A minimal increase in pulmonary infiltrates was observed in the follow-up. However, the patient who does not have any complaints is currently continuing ribociclib at 600 mg/day. The pulmonary infiltrates that developed in the patient increased with continued use of ribociclib, suggesting that this was due to ribociclib. The Naranjo Adverse Drug Reaction Probability Scale also indicates probable relationship.

Validation of Rash and Nonspecific Eruption Diagnoses Using ICD-9 and ICD-10 Codes

Despite being common cutaneous findings in the hospital setting, cutaneous drug eruptions have not been thoroughly validated for administrative claims data. The purpose of this study was to validate primary discharge diagnoses for the ICD code rash or other nonspecific eruptions by finding the positive predictive value (PPV) and to determine how often it was used to indicate an eruption that was eventually determined to be a drug eruption. Two dermatologists independently examined each of 39 hospital patient encounters to assess the validity of the ICD code used by stating whether the code used was appropriate or inappropriate, per table 1 criteria. Since in most patients, a drug eruption was suspected, the Naranjo Adverse Drug Reaction Probability Scale was utilized to externally validate our findings. Our results yielded a PPV for nonspecific rashes of 94.87% (83.11-98.58%) for appropriateness of use. The mean Naranjo score for appropriately versus inappropriately coded cases was 5.7 versus 2.5, respectively, with a mean difference of 3.17568 (0.18833-6.16302), (pooled P-value = 0.0378). Out of the cases analyzed, 29/39 or 74% were confirmed to be drug-related. Our high PPV supports the validity of non-specific eruptions found in national patient databases and the high Naranjo criteria suggest that often, these eruptions are drug related, yet not confirmed at the point of discharge.

Teclistamab-Associated Sclerouveitis with Hypopyon.

To report a case of presumed teclistamab-associated sclerouveitis with hypopyon. Case report. A 62-year-old female with relapsed refractory multiple myeloma presented with right eye pain and decreased vision one week after starting teclistamab, and was found to have sclerouveitis with hypopyon. She received intravitreal vancomycin and ceftazidime due to concern for infectious endophthalmitis, but cultures were negative. Systemic workup for infectious and inflammatory etiologies was unremarkable. Her signs and symptoms improved with topical steroids and a one-week pause in teclistamab. This case constituted a Naranjo Adverse Drug Reaction Probability Scale score of 5, representing a "probable" association. Teclistamab, a novel bispecific antibody recently approved for the treatment of relapsed or refractory multiple myeloma, may be associated with sclerouveitis with hypopyon.

Neuropsychiatric adverse reactions in patients treated with denosumab: two case reports and a review of data from the FDA Adverse Event Reporting System (FAERS).

Denosumab is a human monoclonal antibody indicated for patients with osteoporosis and a high risk of fractures. It targets RANKL, the receptor activator of NF-κB (RANK) ligand, blocking RANKL-RANK interaction and leading to rapid osteoclast-mediated bone resorption inhibition. But RANK is widely expressed in neurons, microglia, and astrocytes. RANKL/RANK/NF-κB system can play an important role in the neuroinflammatory response, depressive behavior, memory impairments, and neurotrophism. We present two well-documented case reports of recurrent neuropsychiatric manifestations in patients treated with denosumab and a descriptive review of similar cases reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) database between 2012 and 2022. Only those reported by healthcare professionals, coding denosumab as the only suspected drug, were retained. An 81-year-old woman with pre-existing mild cognitive impairment suffered two acute confusional episodes and another 81-year-old woman with depression in remission suffered two depressive recurrences with anxiety and psychomotor inhibition, in both cases following sequential administrations of denosumab without underlying calcium/phosphate imbalance. Scores on Naranjo Adverse Drug Reaction Probability Scale were 6 and 7, respectively, suggesting a probable causal relationship. Of the 91,151 cases with denosumab exposure reported to FAERS, 5.7% were related to psychiatric/neurological disorders and 23.8% of these corresponded to cognitive impairment, depressive/mood disturbances, or psychomotor retardation. Denosumab may cause transient but severe neuropsychiatric symptoms by several mechanisms involving RANKL blockade and subsequent immuno-inflammatory changes, at least in subjects with pre-existing neurobiological vulnerability. We recommend caution and careful monitoring of these patients following denosumab administrations.

Successful desensitization of a patient with hypersensitivity to pertuzumab: a case report

Abstract Introduction: Pertuzumab is a humanized monoclonal antibody used in the treatment of human epidermal growth factor receptor 2–positive early breast cancer. Its use can lead to a type-I hypersensitivity, which can be the result of an IgE-related reaction. This case describes a successful desensitization to pertuzumab in a patient diagnosed with a breast cancer. Method: A patient without a personal history of hypersensitivity and diagnosed with a human epidermal growth factor receptor 2–positive breast cancer was started on chemotherapy with association of trastuzumab, pertuzumab, and paclitaxel. While receiving the fourth cycle of pertuzumab, the patient developed a grade 2 hypersensitivity reaction resolved by the intravenous injection of dexchlorpheniramine and methylprednisolone. A premedication protocol has been setting up with a short desensitization protocol. Results: No adverse event occurred during the desensitization, which permits to continue pertuzumab at normal dose with a low occurrence of adverse events (spontaneous and favorable resolution). On analyzing the suspected adverse drug reaction, the event scored 10 and can found to be considered definite using the Naranjo Adverse Drug Reaction Probability Scale. This successful protocol of desensitization has helped to inhibit a hypersensitivity reaction. The monitoring showed the well-tolerance of the patient. Conclusion: This desensitization avoided a too early changing line treatment, which could have been deleterious. Very few cases of pertuzumab hypersensitivity occurred in France, and none benefited from a desensitization. This case illustrated the fact that rapid drug desensitization is possible, important and a simple opportunity to pursuit effective treatments.

Progressive erythrocytosis under lenvatinib treatment in patients with advanced hepatocellular carcinoma

PurposeThis manuscript reports on the occurrence of early and frequent erythrocytosis in advanced hepatocellular carcinoma (HCC) patients treated with lenvatinib.MethodsA cohort of 23 patients with advanced HCC, treated with this antiangiogenic drug for at least one month, was retrospectively analyzed.ResultsThese patients (82.7% men, median age 58.3, cirrhosis in 60.8%) were treated between October 2019 and September 2020 with lenvatinib, as first-line systemic therapy for 82.6% of them. For 20 patients (87%), an early and significant increase in hemoglobin (Hb) level, up to 1.41 g/dL (p < 0.001) was reported and remained elevated. Ten patients (43.5%), all men, reached erythrocytosis (Hb > 16.5 g/dL), 7 were treated with low-dose aspirin for primary thromboprophylaxis and 2 needed phlebotomy. None underwent thromboembolic complications. A significant Hb decrease was observed after treatment discontinuation (p < 0.05). Erythropoietin (EPO) serum levels also increased, which was attributed to HCC after immunostaining for EPO in liver biopsies. The Naranjo adverse drug reaction probability scale documented the relationship between erythrocytosis and lenvatinib and regression at treatment discontinuation. Erythrocytosis was hypothesized to be a class effect of anti-VEGF therapies, the magnitude of which might depend on the IC50 value of each molecule.ConclusionThis report documents the frequent occurrence of erythrocytosis during lenvatinib treatment for advanced HCC, likely secondary to EPO secretion by tumor cells through the antiangiogenic activity levatinib. An early and close monitoring of hematologic parameters is, thus, recommended, together with thromboprophylaxis by low-dose aspirin and phlebotomy in case of symptomatic erythrocytosis.

Infliximab induced severe depression and suicidal thoughts in patient with bipolar disorder

IntroductionInfliximab is a tumor necrosis factor-alpha (TNF-α) inhibitor commonly used in the treatment of autoimmune disorders such as rheumatoid arthritis and ankylosing spondylitis. An increased risk of opportunistic infections, malignancy, and neurodegenerative diseases have been widely documented as adverse effects of IFX therapy. Few reports exist serving the notice of new-onset psychiatric symptoms linked to IFX treatment, such as suicidal behaviors in adults and elderly patients, as well as psychosis in an adolescent. Psychiatric side effects while under IFX treatment are reported to be rare.ObjectivesHere, we present a case of a female with bipolar disorder who developed a long-standing depressive episode with suicidal thoughts after her fourth infusion of infliximab for her ankylosing spondylitisMethodsRetrospective life chart was created, including infliximab infusion.Montgomery Asberg Depression Scale was applied at time of hospitalisation and discharge.The Naranjo Adverse Drug Reaction Probability Scale was applied.ResultsA 55 year old female with ankylosing spondylitis and bipolar disorder was treated with IFX for 8 months. During this period, a total of 4 infusions were administered and AS symptoms were well responding to the treatment. Patient describes the onset of depressive symptoms such as anhedonia and insomnia after the infusion of third IFX infusion, gradually progressing to loss of function and suicidal thoughts and hospitalization in a psychiatry clinic.The patient had a history of bipolar disorder for 10 years with recurrent manic and depressive episodes, 4 hospitalisations and 1 cure of ECT. Patient was on sertraline, maprotiline and diazepam at the time of hospitalization. We started treatment with aripiprazole, quetiapine and valproate, followed for 4 weeks as an inpatient, consulted with rheumatology treatment options and neurology for demyelinating disorders, no pathology was discovered. Rheumatology suggested the continuation of IFX infusion under psychiatric control. Fifth dose of IFX infusion was administered and patient was discharged after euthymic mood was established and insomnia and suicidal thoughts were deteriorated. Upon follow up, depressive symptoms recurred and lamotrigine was added for augmentation.Image:ConclusionsAlthough there is very scarce evidence that IFX causes psychiatric symptoms, there are few clinical trials too, showing evidence that TNF-alpha inhibitors may improve depressive symptoms. While we need more information and evidence to support the ideas of TNF alpha inhibitors effects on human neuropsychology, it is of great importance for especially patients with psychiatric history to be closely watched while administering the product, at least to minimize unintended adverse events.Disclosure of InterestNone Declared

Recurrent Hyponatremia: Levetiracetam - An Uncommon Cause.

Dear Editor, Hyponatremia can be an adverse drug reaction with the use of some of the anti-seizure medications (ASM). Carbamazepine and oxcarbazepine are the most common ASMs which induce hyponatremia. Rarely sodium valproate, eslicarbazepine, lamotrigine, levetiracetam, and gabapentin have also been reported to cause hyponatremia.[1] We report a case of Levetiracetam induced hyponatremia and review the English literature of similar cases. A 50-year-old male had traumatic brain injury in November 2015 and neuroimaging was normal. He was started on prophylactic levetiracetam at another facility. Since then, he had three admissions for hyponatremia: First admission was for acute symptomatic seizures due to hyponatremia, serum sodium of 118 mmol/L; second admission in February 2016 for dizziness, serum sodium 131 mmol/L; and third admission during April 2016 for drowsiness, serum sodium 108 mmol/L [Table 1]. During the latter two admissions, the work-up for hyponatremia was suggestive of syndrome of inappropriate antidiuretic hormone secretion (SIADH). During the first admission, patient was on levetiracetam 500 mg q12h and the dose was escalated to 1000 mg q12h at discharge. Patient was started on tolvaptan 15 mg q24h at discharge in the first admission (25.12.2015). During his subsequent admissions, workup for other causes of hyponatremia was negative. He was continued with tolvaptan intermittently. Review of the case records and drug chart suggested possible relation between hyponatremia and levetiracetam, a diagnosis of levetiracetam induced hyponatremia was considered and levetiracetam was discontinued. Since then, he had no further episode of hyponatremia. Patient was not started on any ASM as it is not our practice to use ASMs for primary prophylaxis in traumatic brain injury.Table 1: Admission profile of the patientIn this patient, diagnostic workup suggested that SIADH was the possible mechanism for hyponatremia. He had a mild closed traumatic brain injury and normal brain imaging. This clinical scenario is very unlikely to cause SIADH. Workup for other causes of hyponatremia was negative. When levetiracetam was discontinued patient had no further episodes of hyponatremia. On Naranjo Adverse Drug Reaction Probability Scale[2] this patient had a score of 7 suggesting levetiracetam being the “probable” culprit responsible for hyponatremia. Review of English literature revealed report of four patients with levetiracetam induced hyponatremia [Table 2]. In four patients, including the present case SIADH was the mechanism of hyponatremia. There are no specific clinical characteristics which are common among these 5 cases. In all the patients, hyponatremia was corrected after withdrawing levetiracetam. In patient “3” in addition to levetiracetam, hydrochlorothiazide would have added to the misery of hyponatremia.Table 2: Characteristics of the patientsIn conclusion this case illustrates that chronic hyponatremia in a patient with epilepsy on ASMs, one should check the ASM list to exclude the possible drug that can be associated with hyponatremia. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Risperidone-induced respiratory depression in a neonate through breast milk.

Risperidone is commonly used in postnatal mothers for depression and psychotic symptoms in spite of little data on its safety profile in neonates. It is reported previously that 6 mg/day can be used in mothers without having any untoward in breastfed neonates. Excretion of risperidone is dependent on the enzyme CYP2D6 whose activity varies as per individual phenotype. Maximum therapeutic levels are achieved at 2 h of administration of the drug. We are reporting a case of preterm breastfed neonate who presented with respiratory depression twice due to risperidone usage in its mother. This is the first reported case where 1 mg/day dosage of risperidone in nursing mother was associated with acute adverse effects such as respiratory depression in her neonate. The Naranjo Adverse Drug Reaction Probability Assessment Scale scored to 8 which suggests probable relation between the drug and its reaction in neonates. It underscores cautious use in mothers and close monitoring of neonates when risperidone is prescribed irrespective of dosage.

A naturalistic study on side effects of selective serotonin reuptake inhibitors in psychiatric out-patient department

Introduction: &gt;Antidepressants are one of the most commonly prescribed psychotropic drugs. Six SSRIs are approved for various disorders. SSRIs have fewer side effects owing to its selective blocking the serotonin transporter. Nonetheless SSRI has several troublesome side effects, including nausea, diarrhoea, headache, dizziness, sexual side effects, tachycardia, or weight gain. Methodology: This cross-sectional comprised of 200 patients who were divided into two groups. Group 1 had participants who had received SSRI for less than 6 weeks duration and group 2 had patients who had taken SSRI for more than 6 months. Side effects of medications were recorded using UKU side effect rating scale and causality was ascertained using Naranjo adverse drug reaction probability scale. Results: Among the early side effect group consisting of 100 patients, 40% of patients reported at least one side effect. Tension/inner unrest, nausea and vomiting and orgastic dysfunction was the most common side effect reported. 30% of patients in late side effect group had at least one side effect. Orgastic dysfunction, decreased sexual desire and weight gain were the main side effects reported. All the reported side effects were probably associated due to the prescribed SSRI, as inferred from Naranjo causality scoring system.  Conclusion: Escitalopram was the most commonly prescribed SSRI among all the SSRIs. Paroxetine and fluvoxamine were the least prescribed SSRIs. Sertraline was found to cause maximum side effects in the early group and fluoxetine caused the most side effects in the late group. Tension/Inner unrest was the most commonly reported side effects followed by sexual side effects.

Relationship between piperacillin concentrations, clinical factors and piperacillin/tazobactam-associated acute kidney injury.

Piperacillin/tazobactam, a commonly used antibiotic, is associated with acute kidney injury (AKI). The relationship between piperacillin concentrations and AKI remains unknown. Estimate piperacillin exposures in critically ill children and young adults administered piperacillin/tazobactam to identify concentrations and clinical factors associated with piperacillin-associated AKI. We assessed piperacillin pharmacokinetics in 107 patients admitted to the paediatric ICU who received at least one dose of piperacillin/tazobactam. Piperacillin AUC, highest peak (Cmax) and highest trough (Cmin) in the first 24 hours of therapy were estimated. Piperacillin-associated AKI was defined as Kidney Disease: Improving Global Outcomes (KDIGO) Stage 2/3 AKI present >24 hours after initial piperacillin/tazobactam dose. Likelihood of piperacillin-associated AKI was rated using the Naranjo Adverse Drug Reaction Probability Scale. Multivariable logistic regression was performed to identify patient and clinical predictors of piperacillin-associated AKI. Out of 107 patients, 16 (15%) were rated as possibly or probably having piperacillin-associated AKI. Estimated AUC and highest Cmin in the first 24 hours were higher in patients with piperacillin-associated AKI (2042 versus 1445 mg*h/L, P = 0.03; 50.1 versus 10.7 mg/L, P < 0.001). Logistic regression showed predictors of piperacillin-associated AKI included higher Cmin (OR: 5.4, 95% CI: 1.7-23) and age (OR: 1.13, 95% CI: 1.05-1.25). We show a relationship between estimated piperacillin AUC and highest Cmin in the first 24 hours of piperacillin/tazobactam therapy and piperacillin-associated AKI, suggesting total piperacillin exposure early in the course is associated with AKI development. These data could serve as the foundation for implementation of model-informed precision dosing to reduce AKI incidence in patients given piperacillin/tazobactam.

Ciprofloxacin induced toxic epidermal necrolysis with cholestatic hepatitis: A case report with literature review and revisit to the Naranjo adverse drug reaction probability scale

Ciprofloxacin, among the many Fluoroquinolones, has been widely used as a broad-spectrum antibiotic due to its wide range of action and relatively safe adverse effect profile. However, among the cutaneous adverse drug reactions due to Ciprofloxacin, toxic epidermal necrolysis occurring along with cholestatic hepatitis is a rare one. Here, we present a case of a 22-year-old male patient who was diagnosed with toxic epidermal necrolysis with cholestatic hepatitis secondary to Ciprofloxacin. Naranjo adverse drug reaction probability scale was used for the causal association.

Anti-programmed death-1 inhibitor nivolumab-induced immune-related adverse events: hepatitis, renal insufficiency, myositis, vitiligo, and hypothyroidism: a case-based review.

Nivolumab (NIVO) is a monoclonal antibody used to treat renal cell cancer. It is an anti-programmed death-1 (anti-PD-1) inhibitor, enhancing the tumor-targeted immune response of T lymphocytes, resulting in immune-mediated adverse events (AEs). We present five immunologicalAEs in a single patient treated with NIVO. A 68-year-old male patient with metastatic renal cell carcinoma and right-sided nephrectomy received NIVO after pazopanib and sunitinib treatment. Two and a half months after starting NIVO, hepatocellular enzymes and creatinine were elevated. Concomitantly, the patient noticed hypopigmentation of the hand skin and a change in voice and speech. Due to hepatitis, he has been treated with dexamethasone 16mg daily for 22days, after which hypothyroidism and increased creatine kinase were found without muscle pain and functional impairment. Dexamethasone was continued, and a rapid decline in all parameters except thyroid-stimulating hormone (TSH) and vitiligo was observed. Myositis was initially considered a part of hypothyroidism and elevated renal parameters due to hypohydration. The rapid regression on glucocorticoid treatment and a longer time for creatinine normalization than expected with hydration were noticed. Nivolumab likely induced those side effects as assessed by Naranjo Adverse Drug Reaction Probability Scale. The literature review shows that theconsequences of PD-1 inhibition are not uniform. Side effects of checkpoint inhibitors should be monitored carefully in the early and later treatment schedules evaluating subclinical manifestations like myositis and worsening of kidney parameters. Early administered higher doses of glucocorticoids can stop drug toxicity and reverse-induced tissue damage.

Sodium Nitrite Intoxication and Death: Summarizing Evidence to Facilitate Diagnosis.

Over the years, forensic pathology has registered the spread of new methods of suicide, such as the ingestion of sodium nitrite. Sodium nitrite causes increased methemoglobin, resulting in systemic hypoxia, metabolic acidosis, and cyanosis. Since sodium nitrite is a preservative, the ingestion of foods containing an excessive amount of this substance can also cause acute intoxication up to death. The present review is aimed at guiding health professionals in the identification and management of sodium-nitrite-related intoxications and deaths. A systematic literature search was carried out on PubMed by following the PRISMA statement's criteria. A total of 35 studies with 132 cases were enrolled, and the data were cataloged in Microsoft Excel. To establish the causal correlation between sodium nitrite ingestion and death, the Naranjo Adverse Drug Reaction Probability Scale was used. In addition to the small number of cases that have currently been published, the study demonstrated that there was a general methodological discrepancy in the diagnostic process. However, some interesting results have emerged, especially in post-mortem diagnostics. Sodium-nitrite-related deaths represent a challenge for forensic pathologists; therefore, it is important to promptly recognize the essential features and perform the necessary and unrepeatable examinations for the correct diagnosis of the cause of death.

Prevalence of iatrogenic CNS inflammation at a tertiary neuroimmunology clinic

BackgroundVarious vaccines, tumor-necrosis-factor-alpha inhibitors (TNFAIs), immune-checkpoint inhibitors (ICIs), and other immunomodulators have been linked to inflammatory CNS events. The prevalence of iatrogenic events in the neuroimmunology clinic is unknown. ObjectiveTo evaluate the prevalence and clinical characteristics of iatrogenic CNS inflammation in a tertiary neuroimmunology clinic. MethodsWe analyzed 422 consecutive patients seen over five years at a tertiary neuroimmunology clinic who were systematically screened for exposure to vaccines, TNFAIs, ICIs, or other immunomodulators. In patients with suspected iatrogenic events, the Naranjo Adverse Drug Reaction Probability Scale was used to score the probability of iatrogenicity. ResultsIn total, 27 potential iatrogenic events were observed, accounting for 6.4% of all new referrals. The average Naranjo score was 5.78 +/− 1.65 with 74% of the cases scored as probable and 26% scored as possible. The clinical phenotypes included MS relapses (37%); autoimmune encephalitis (30%); NMOSD attacks (15%); transverse myelitis (11%); optic neuritis (4%); and MOGAD attacks (4%). A monophasic course was observed in 44% of cases while 41% had a relapsing course. All patients stopped or interrupted treatment with the offending agent. In addition, 41% of the iatrogenic events were fully responsive to corticosteroids; 22% were partially responsive; and 15% resolved spontaneously. The most common potential triggers were vaccines (37%) followed by TNFAIs (33%) then ICIs (26%). A significantly higher number of probable iatrogenic events were observed among the ICI and vaccine groups compared to a higher number of possible events among the TNFAI group. The latter group also had a significantly longer interval since exposure. The ICI group was more likely to present with monophasic autoimmune encephalitis. ConclusionIatrogenic CNS inflammation is rare and typically involves steroid-responsive monophasic events. A subset of iatrogenic events can unmask or worsen relapsing disorders. The probability of iatrogenicity was higher in vaccine and ICI-related events compared to TNFAI-related events.

Characteristics and Management of Granulomatous Lobular Mastitis Associated with Antipsychotics-Induced Hyperprolactinemia.

Background: Granulomatous lobular mastitis (GM) is a rare inflammatory breast disease. Reports focusing on GM caused by antipsychotic-induced hyperprolactinemia (HPRL) are very rare. Aim: To report a study of GM associated with antipsychotic-induced HPRL and discuss the mechanism and management. Materials and Methods: A retrospective review of patients with GM and psychiatric disorders were carried out. The clinical characteristics, management and outcome were collected and analyzed. The relationship between antipsychotics and GM was evaluated using the Naranjo Adverse Drug Reaction Probability Scale (Naranjo scale). Results: Nineteen female GM patients with psychiatric diseases, aged 21-39 years, who had received antipsychotics for 0.5-10.2 years were included. Most patients took multiple antipsychotics, and 10 (52.6%) took risperidone-containing regimens. Increased prolactin (PRL) was detected in all patients (range 35.15-200 ng/mL). The scores of Naranjo scale were 7-8, indicated the antipsychotics probably induced GM. All patients received systemic therapy, and were prescribed bromocriptine. Seven patients (36.8%) decreased the dose of antipsychotics, six (31.6%) switched antipsychotics, three (15.8%) continued the primary antipsychotics, and three (15.8%) discontinued antipsychotics. In addition, 14 patients (73.7%) received corticosteroid, 4 (21.1%) received antimycobacterials. PRL decreased to normal in 1 month. Seven patients (36.8%) received excisional surgery. After 12 months' follow-up (range 9-56 months), only three patients (15.8%) had a recurrence. Conclusion: Long-term use of antipsychotics may increase PRL levels, and lead to GM. It is vital to assess PRL level and reduce PRL to normal in patients with GM.