Patient on allergen immunotherapy developed systemic lupus erythematosus?– A clinico-pharmacological look out

Drug induced lupus is an autoimmune condition secondary to drug exposure which leads to development of systemic lupus erythematosus (SLE). However, labelling the culprit drug needs a prudent insight into the pharmacological plausibility of each of the offending drugs in suspicion. Here we present a report where allergen immunotherapy was suspected to cause SLE and a deeper clinico-pharmacological evaluation cleared the air.

Dipeptidyl-peptidase IV inhibitor (DPP4i) confers increased odds of bullous pemphigoid even years after drug initiation

The timing pattern in which dipeptidyl-peptidase IV inhibitors (DPP4i) confer the risk of bullous pemphigoid (BP) is unknown. To investigate the odds of BP following exposure to DPP4i and to perform a duration-response analysis evaluating the risk of BP in relation to the duration of exposure to the culprit drug. A population-based nested case–control study was performed comparing diabetic patients with BP (n = 1458) with age-, sex- and ethnicity-matched diabetic control subjects (n = 6051) with respect to the prevalence of exposure to DPP4i. Adjusted odds ratios (ORs) were estimated by logistic regression. Overall exposure to DPP4i was associated with an 80% increase in the odds of subsequent BP (OR, 1.81; 95% CI, 1.46–2.08; P < 0.001). In an intraclass analysis, the odds of BP were increased in association with vildagliptin (OR, 3.40; 95% CI, 2.69–4.29; P < 0.001) and sitagliptin (OR, 1.56; 95% CI, 1.33–1.84; P < 0.001). In a duration-response analysis, the highest likelihood of BP was found 1–2 years after commencing the drug (OR, 2.66; 95% CI, 1.97–3.59; P < 0.001). The odds of BP were increased across all time periods and retained its statistical significance even ≥ 6 years after the drug initiation (OR, 1.44; 95% CI, 1.09–1.91; P = 0.011). Relative to other diabetic patients with BP, patients with DPP4i-associated BP were more likely to be admitted to inpatient dermatologic wards (OR, 1.66; 95% CI, 1.30–2.13; P < 0.001) and had higher mean(SD) numbers of outpatient dermatologist visits (14.7[14.8] vs. 12.3[13.2], respectively; P = 0.006). DPP4i should be suspected as a predisposing factor for BP even numerous years after the drug initiation.

EBV Reactivation in A Case of DRESS Syndrome Associated with Lamotrigine – A Case Report

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) is a rare, T-cell mediated hypersensitivity reaction that develops secondary to a drug reaction. Several drugs have been associated with DRESS syndrome, most commonly carbamazepine. The mechanism is not clearly understood. It is a life-threatening condition that can present with skin rash, hematologic abnormalities, lymphadenopathy, and organ failure. Case Presentation: The authors report a case of 43-year-old gentleman who developed DRESS syndrome secondary to lamotrigine and was found to have EBV reactivation. Patient was managed with supportive care; topical steroids and the culprit drug were discontinued. He had full recovery almost 2 weeks following treatment. DRESS syndrome can occur 2 weeks following exposure to an offending drug in susceptible individuals. Conclusion: Lamotrigine and EBV reactivation are not frequently reported in patients with DRESS syndrome. Therefore, physicians should be vigilant about this rare drug related hypersensitivity reaction in order to prevent life threatening complications.

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.

Stevens-Johnson Syndrome Caused by Enzalutamide: A Case Report and Literature Review

ObjectiveEnzalutamide is the most frequently prescribed compound for treating metastatic castration-resistant prostate cancer (mCRPC). Common adverse drug events of enzalutamide are febrile neutropenia, hot flashes, hypertension, and fatigue.MethodsWe present a case of a patient with mCRPC who received enzalutamide and developed Stevens-Johnson syndrome (SJS). The culprit drug was confirmed using the Naranjo Adverse Drug Reaction Probability Scale. Clinical characteristics and management principles were analyzed in combination with literature reports.ResultsSJS occurred within two weeks of enzalutamide therapy. Supportive care such as steroid treatment led to a complete resolution of skin lesions and improved clinical symptoms after three weeks.ConclusionMost cutaneous adverse events occur early during enzalutamide therapy, and close observation should be given within two weeks of starting treatment.

Fixed Drug Eruptions Secondary to Fixed Drug Combination (ofloxacin/ornidazole): A Cross Sensitivity Case Report

Background: Fixed drug eruption (FDE) is an erythematous cutaneous patch caused by certain drugs through activation of immunologic reaction in the body. The onset of FDE is 30 minutes to 8 hours and is estimated to occur upto 16-21% of all cutaneous reactions. The irrational combination of fluoroquinolones and nitroimidazole is the most prescribed drug for diarrhea in India, and the drug is found to cause FDE either individually or in combination. Cross sensitivity is the major issue associated with Fluoroquinolones and nitroimidazole. Case repor: Our case is of a 45-year-old male who developed FDE due to a combination product of ofloxacin and ornidazole with past FDE history due to a combination product of norfloxacin and tinidazole. The patient presented with erythematous patches all over the body, swollen lips, mucosal erosion over the buccal cavity, and glans penis. Discussion: The patient was successively treated after the withdrawal of the culprit drug with oral Antihistamines, corticosteroids, and other topical creams and gels, which correlates with the standard management of FDE. Conclusion: Proper prescribing knowledge, documentation of drug allergies, and educating patient about allergic reaction play vital role to prevent future drug related problems.

Preparations of exploration of immediate hypersensitivity to antineoplastic agents: An oncology pharmacy perspective

Background Cancer patients are being exposed to antineoplastic drugs more frequently and for longer periods, resulting in a higher risk of hypersensitivity reactions. The aim of this study was to assess the pharmaceutical time and direct cost of drug allergy explorations following immediate hypersensitivity reactions to antineoplastic agents. Methods A micro-costing method was used to collect data on consumption of human and material resources for allergy exploration preparations. The monetisation was carried out on the basis of prices and hourly wage costs applied in 2018. The number and type of allergy explorations prepared by the pharmacy as well as nature of antineoplastic drugs tested, and the number of culprit drugs reintroductions were collected. Results Almost 1.5 h is required to realise allergy tests for one patient including pharmacist time for prescription analysis and pharmacy technician's time for tests preparation. The mean manufacturing cost of these tests is estimated at €62.87 (€57.82–65.49) per culprit drug for one patient. Programming patients according to culprit drugs tested allows rationalising healthcare provider time and increasing efficiency. From January 2010 to December 2018, 277 patients were tested and 490 allergy explorations were performed, corresponding to more than 5000 preparations. Mostly, the culprit drug could be reintroduced ( n = 383, 78.2%) allowing patients to receive the best possible treatment. Conclusion Management of hypersensitivity reactions is constantly progressing, as it contributes to improving patient care in oncology. This activity is time-consuming for the pharmacy team but allows patients with previous hypersensitivity reaction to continue effective treatment.

The Role of Skin Tests and Premedication in Radiocontrast Media Hypersensitivity: A Clinical Dilemma

ABSTRACT Objective: Controversies continue over the diagnostic approach, prediction, and premedication in radiocontrast media (RCM) hypersensitivity. One of the most important problems encountered in daily clinical practice is that patients do not recall which contrast agent has been used in previous exposures. Also, in most cases, the details of the reaction have not been recorded. Therefore, difficulties are experienced in decision-making about skin testing and premedication in patients who are suspected of RCM hypersensitivity. To assess the clinical value of skin tests and premedication in RCM hypersensitivity. Materials and Methods: A retrospective evaluation was made of the medical records of patients between October 2014 and December 2019. The skin tests were performed with the culprit agent if it was known, otherwise, with iohexol, one of the most commonly used RCM in Turkey. As premedication, oral methylprednisolone 40 mg 13-7-1 hours before the procedure and oral pheniramine 22.7 mg 1 hour before the procedure were prescribed. Results: A total of 41 patients were evaluated (32 females and 9 males). Of the reactions, 35 (85.4%) were immediate and 6 (14.6%) were non-immediate. Three (7.3%) had a positive intradermal test result. It was determined that 20 patients (17 immediate, 3 non- immediate), required imaging with RCM again. Of these, 18 received premedication and two did not, although it was recommended. Of the patients who received premedication, one (5.5%) had an urticarial reaction of the same grade, while both patients (100%) who did not receive premedication developed an immediate allergic reaction that was of a similar grade to that of the previous reaction. Conclusion: Skin test positivity for RCM was observed at low rates. In cases with negative skin tests and when the culprit drug cannot be identified, re-exposure to alternative RCM under premedication may reduce the risk of the reaction. Keywords: Allergy, iodinated contrast media, iobitridol, iohexol, premedication

Acute Facial Edema in a Patient with Systemic Lupus Erythematosus

Allergies have been found to be associated with systemic lupus erythematosus (SLE). However, few reports have described angioedema occurring in elderly men with systemic lupus erythematosus. Herein, we report the case of an 85-year-old man who presented with angioedema with eosinophilia. The patient was initially thought to have a drug-induced allergy. The differentiation between allergic reactions caused by drugs and those caused by eosinophilia with SLE can be challenging. The effect of the withdrawal of the suspected culprit drug and allergic dermal findings can be key to differentiating the two conditions. SLE is prevalent among younger generations; hence, active immunity can induce various symptoms, including eosinophilia, which causes angioedema. Even older people with SLE can have a strong immune reaction, resulting in angioedema with eosinophilia. In cases of localized facial edema in elderly patients with SLE, it is critical to consider angioedema caused by eosinophilia as a differential diagnosis.

Evaluation of Hypersensitivity Reactions in Pediatric Patients Using Biological Drugs

<b><i>Introduction:</i></b> Biological drugs are currently used for the treatment of chronic inflammatory, autoimmune, and neoplastic diseases. With their expanding indication spectrum and increasing use, hypersensitivity reactions to these drugs are also becoming more frequent. The present study aimed to report the incidence and the features of such reactions in pediatric patients using biologicals for the treatment of various diseases. <b><i>Methods:</i></b> The medical records of pediatric patients treated with biological agents between October 1, 2011 and August 31, 2019 were reviewed and adverse reactions were evaluated retrospectively. <b><i>Results:</i></b> During the study period, 211 patients (116 boys, 55%) used 21 different biological drugs for the treatment of various diseases. Their median age at the time of the first treatment was 139.9 (IQR: 92.2–187.8) months. Hematologic-oncologic diseases were the most common indication for biological therapy (97/211; 46.0%), followed by rheumatologic diseases (82/211; 38.9%). Of the 211 patients, 14 (6.64%) experienced reactions to biological drugs. The most common culprit agent was rituximab (57.1%). Most of the patients (85.7%) had a history of reactions either during the infusion or within 1 h after taking the drug. Five patients underwent desensitization to the culprit drug, while 7 other patients continued treatment with a reduced dose/infusion rate or premedication. Also 1 patient continued to take the drug without any additional treatment. <b><i>Conclusion:</i></b> It was reported that 6.64% of the patients who received biologic drug therapy for various reasons in our hospital had hypersensitivity. The most common culprit agent was rituximab, and most of the reactions were immediate reactions.