Drug-induced hypersensitivity reactions (DIHR) represent abroad spectrum of immune-mediated disorders that occur after exposure to medications and can affect various organ systems. The most important entities include drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN, Lyell's syndrome), serum sickness, drug-induced eosinophilic pneumonias, and hypersensitivity pneumonitis. Pulmonary manifestations are common and can have adecisive impact on the clinical course. This review article explains the immunological foundations, pathogenesis, and etiology of drug-induced hyperreactivity disorders, describes their clinical relevance, and presents the typical thoracic manifestations and imaging patterns in chest computed tomography (CT). The focus is on the importance of radiological diagnostics for the early detection and differentiation of these potentially life-threatening conditions.

Abstract Background QUASAR (NCT04033445) is a phase 2b/3 program evaluating guselkumab (GUS) in participants (pts) with moderately to severely active ulcerative colitis (UC).1,2 GUS is a selective dual-acting IL-23p19 subunit inhibitor that potently neutralises IL-23 and binds to CD64, a receptor on cells that produce IL-23.3 Here, we report ongoing QUASAR long-term extension (LTE) efficacy and safety results through week (W) 140. Methods GUS IV induction responders were randomised to receive SC maintenance treatment: GUS 100 mg q8w (GUS100); GUS 200 mg q4w (GUS200); or placebo (PBO). Pts could receive dose adjustment to GUS200 from W8-32. Pts completing the W44 visit could enter the LTE to continue their then-current treatment regimen. PBO pts discontinued after study unblinding. We evaluated efficacy among pts randomised to GUS who entered the LTE without receiving a dose adjustment. Data analysis methods were 1) “as observed” (AO) and 2) nonresponder imputation (NRI), accounting for pts with treatment failure or missing data. Safety was evaluated among all pts receiving LTE treatment. Results Overall, 87.0% of GUS-randomised pts entered the LTE, and 88.8% of those pts completed treatment through W140. At W140, among GUS100 and GUS200 pts, respectively, 80.1% and 81.5% achieved clinical remission and 86.5% and 87.5% of W0 clinical remitters maintained clinical remission at W140 (Fig; AO). Of 210 pts in clinical remission at W140, 205 (97.6%) were corticosteroid free for ≥8W before W140. Symptomatic remission was achieved in 92.1% and 92.3% of pts, endoscopic improvement in 84.6% and 84.0%, endoscopic remission in 55.9% and 51.2%, and histo-endoscopic mucosal improvement in 77.1% and 80.3% at W140 among GUS100 and GUS200 pts, respectively (Fig; AO). NRI results were numerically lower than AO results. Efficacy was consistent regardless of biologic and/or Janus kinase (JAK) inhibitor treatment history (Fig). The number of pts with ≥1 adverse event (AE) per 100 pt-years was similar in GUS groups (GUS100, 45.0; GUS200, 48.1) and numerically higher with PBO (67.1) (Table). One death (aortic dissection) and no active tuberculosis, opportunistic infection, anaphylaxis, serum sickness, or Hy’s Law were reported in GUS-treated pts. Serious infections were infrequent and generally similar across groups. Conclusion Both GUS maintenance dose regimens demonstrated sustained clinical, endoscopic, and histologic efficacy in pts with UC through W140. Efficacy was sustained regardless of biologic and/or JAK inhibitor treatment history. Although NRI results were numerically lower than AO results, the overall trends were consistent due to the high retention rate throughout the maintenance study and LTE. No new safety concerns were observed.

ABSTRACT Snakebite envenomation affects between 1.8 and 5.5 million people annually, many of whom suffer permanent disabilities or even death. Current antivenoms are composed of plasma‐derived antibodies, which, although effective when administered promptly, may cause anaphylaxis within an hour of treatment or serum sickness between 5‐ to 14‐days post‐treatment. Traditional antivenoms are the only approved therapeutic countermeasures to snake envenomation, and although crucial, they need to be updated. Research has explored recombinant monoclonal‐based antivenoms, small‐molecule inhibitors, and naturally derived treatments as viable alternatives; however, there remains an underexplored opportunity to utilize polymeric‐based nanoparticles. Herein, polymeric‐based nanoparticles are discussed as potential antivenoms for sequestering key toxins, as alternatives to traditional adjuvants, and as vital components in low‐cost diagnostic devices.

To report a rare, life-threatening mixed hypersensitivity reaction (Types I and III) induced by snake antivenom and describe a precision management strategy. A 55-year-old woman with a history of plant allergy received antivenom treatment(6 vials total) for a Trimeresurus stejnegeri bite, with initial symptom resolution. On post-serum day 7, she developed syncope, fever, generalized pruritus, and urticaria, followed by recurrent rash, pruritus, nausea, vomiting, abdominal pain, myalgia, arthralgia, and hypotension on day 8. Laboratory findings included leukocytosis, neutrophilia, elevated D-dimer, IgE (155.0 IU/mL), and serum creatinine (123 μmol/L). Multidisciplinary consultation diagnosed a mixed hypersensitivity reaction (anaphylaxis + serum sickness). Management employed a "Shock control-Inflammation suppression-Volume optimization" strategy: epinephrine (intramuscular/intravenous) for shock, dexamethasone and antihistamines for inflammation, and aggressive crystalloid resuscitation. Hemodynamic stability and symptom resolution were achieved. This represents the first documented case of severe mixed hypersensitivity (co-occurring Type I anaphylaxis and Type III serum sickness) triggered by antivenom. It highlights the diagnostic challenge posed by overlapping biphasic features and multi-system involvement occurring within the typical serum sickness window. Precision management addressing both pathogenic pathways simultaneously, specifically via combined hemodynamic stabilization, anti-inflammatory therapy, and volume support, was critical for successful recovery. Enhanced vigilance for this synergistic reaction pattern is warranted.

Snakebite envenomation is a significant public health issue in Iran, and it is crucial to have effective and easily accessible antivenom treatments. This study aimed to evaluate the non-inferiority of the SnaFab and the Razi antivenoms for treating snakebite envenomation. The study was a randomized, double-blind, multicenter, active-controlled, non-inferiority trial involving 98 snakebite victims. The patients received either the SnaFab or the Razi antivenoms, with the primary endpoint being the recovery rate within 48 hours after antivenom infusion. The secondary endpoints included adverse events over a 14-day monitoring period and total antivenom consumption. The non-inferiority margin (NIM) was set at 20 percent. The study was commenced on April 17th, 2020, and concluded on May 15th, 2021. The recovery rate was 100 percent in the SnaFab group, which was non-inferior to the Razi antivenom group (98%). The mean number of antivenom units administered was 8.95 ± 4.40 units in the SnaFab group, compared to 9.04 ± 4.49 units in the Razi group (P value: 0.92). Adverse events were reported by 10.2% of individuals in the SnaFab group and 20.4% in the Razi group (p value = 0.27). Muscle weakness was the most commonly reported adverse event in the Razi group (8%), while vertigo was most frequent in the SnaFab group (4%). Moreover, there were no reports of anaphylactic shock or serum sickness. In summary, this study found that SnaFab antivenom is non-inferior to Razi antivenom for treating snakebite envenomation in Iran. Overall, the incidence of adverse events was comparable between groups, with no statistically significant differences observed.

Snakebite envenomation is a significant public health issue in Iran, and it is crucial to have effective and easily accessible antivenom treatments. This study aimed to evaluate the non-inferiority of the SnaFab and the Razi antivenoms for treating snakebite envenomation. The study was a randomized, double-blind, multicenter, active-controlled, non-inferiority trial involving 98 snakebite victims. The patients received either the SnaFab or the Razi antivenoms, with the primary endpoint being the recovery rate within 48 hours after antivenom infusion. The secondary endpoints included adverse events over a 14-day monitoring period and total antivenom consumption. The non-inferiority margin (NIM) was set at 20 percent. The study was commenced on April 17th, 2020, and concluded on May 15th, 2021. The recovery rate was 100 percent in the SnaFab group, which was non-inferior to the Razi antivenom group (98%). The mean number of antivenom units administered was 8.95 ± 4.40 units in the SnaFab group, compared to 9.04 ± 4.49 units in the Razi group (P value: 0.92). Adverse events were reported by 10.2% of individuals in the SnaFab group and 20.4% in the Razi group (p value = 0.27). Muscle weakness was the most commonly reported adverse event in the Razi group (8%), while vertigo was most frequent in the SnaFab group (4%). Moreover, there were no reports of anaphylactic shock or serum sickness. In summary, this study found that SnaFab antivenom is non-inferior to Razi antivenom for treating snakebite envenomation in Iran. Overall, the incidence of adverse events was comparable between groups, with no statistically significant differences observed.

B-cell-depleting agents like rituximab (RTX) are central to treating severe steroid-dependent idiopathic nephrotic syndrome (SDNS) and frequent relapses. However, RTX can induce anti-RTX antibodies (ARA) that compromise efficacy. Obinutuzumab, a fully humanized anti-CD20 antibody, may overcome RTX resistance. We evaluate obinutuzumab's safety and efficacy in pediatric SDNS patients who developed ARA after RTX. We conducted a retrospective study in two pediatric nephrology centers in Paris, France, including SDNS patients treated with RTX who developed ARA and subsequently received obinutuzumab. Thirty-two patients (median age 4.1years) were included, previously treated with a median of 2 RTX infusions (IQR 1-2). ARA were detected at 3.2months (range 0-17), following a median depletion of 2.9months (IQR 2.1-5.8); 13/32 had titers ≥ 100ng/mL. Obinutuzumab was given for short/failed RTX depletion (n = 19) or early relapse (n = 13). Six infusion reactions occurred but no serum sickness. B-cell depletion after obinutuzumab lasted 6.5months (IQR 5.6-8.1). Among 28 patients with baseline ARA at obinutuzumab infusion, 50% had titers ≥ 100ng/mL, with no difference in B-cell depletion (median 5.3 vs. 6.8months; p = 0.40), or relapse-free survival at 24months (75% vs. 46%; p = 0.10). Longitudinal ARA monitoring showed sustained positivity in 76.5% at 6months, and one patient > 100ng/mL at 24months. Obinutuzumab is an effective and well-tolerated option in the context of ARA, providing prolonged B-cell depletion. Further studies with ARA monitoring are needed to optimize anti-CD20 therapy.

Background: In Europe, Vipera ammodytes ammodytes (Vaa, nose-horned viper) is considered the most venomous of the European vipers. The antivenom Viperfav®, composed of polyvalent equine F(ab′)2 fragments, is effective against Vipera aspis, Vipera berus and Vaa. Objectives: This study aimed to evaluate the clinical efficacy and pharmacokinetics of Viperfav in Vaa envenomations. Methods: Patients presenting with Vaa snakebite and treated with intravenous Viperfav were included. Clinical manifestations and laboratory findings were assessed on admission to the Emergency Department, prior to antivenom therapy, and monitored throughout hospitalization. Blood samples were collected on arrival and at defined intervals after Viperfav administration. Venom and antivenom concentrations in serum were determined by ELISA and subjected to pharmacokinetic analysis. Results: Twenty-one patients bitten by Vaa and classified with a severity score of 2b on the modified Audebert clinical severity scale received a single intravenous dose of Viperfav within 4 h of the bite. Viperfav attenuated the progression of local symptoms and prevented the development of new systemic manifestations. The serum concentrations of F(ab′)2 fragments reached 196 µg/mL, far exceeding the venom concentration at admission (35 ng/mL). The prolonged elimination half-life of Viperfav (49 h) corresponded with the absence of recurrent symptoms after a single dose. Bradycardia or hypotension occurred in 10% of patients; no cases of anaphylaxis or serum sickness were observed. Conclusions: A single intravenous dose of Viperfav demonstrated clinical efficacy and a favourable pharmacokinetic profile in Vaa envenomed patients when administered within hours of the bite.

Abstract Description The complement cascade is a key component of the innate immune system. Dysfunction of the complement regulator, factor H (FH) is linked to kidney disease, often accompanied by macrophage infiltration. Hepatic FH regulates serum complement activation, while intrinsic FH in cells such as macrophages regulates complement activation and maintains local homeostasis. Macrophages are heterogeneous and influenced by their microenvironment, prompting us to investigate the role of macrophage-derived FH in kidney pathology and fibrosis. We generated FloxFH (FHfl/fl) mice and crossed them with CMVcre, CX3CR1cre, and Csfr1cre mice to produce conditional FH knockout (cKO) mice with no FH (FHfl/flCMVcre) and with FH absent in the macrophages (FHfl/flCX3CR1cre and FHfl/flCsfr1cre). The mice were treated with horse spleen apoferritin to induce chronic serum sickness. FHfl/flCMVcre mice exhibited a significant increase in immune complexes in the glomeruli compared to FHfl/fl controls. FHfl/flCX3CR1cre and FHfl/flCsfr1cre mice showed kidney dysfunction and immune deposits, with FHfl/flCX3CR1cre deposits resembling those seen in global FH knockouts. Additionally, TGF-β and laminin expression were significantly elevated in the kidneys of the cKO mice. Our results for the first time, highlight the critical role of macrophage-derived FH in limiting inflammation, preventing kidney pathology, as well as its involvement in the development of fibrosis in immune complex-mediated kidney disease. Funding Sources N/A Topic Categories Immune Mechanisms of Human Disease (HUM)

Serum sickness: a mimic of septic shock.

Minimum effective low dose of antithymocyte globulin in people aged 5-25 years with recent-onset stage 3 type 1 diabetes (MELD-ATG): a phase 2, multicentre, double-blind, randomised, placebo-controlled, adaptive dose-ranging trial.

This reports a case of a 68-year-old woman with a history of snake bite from Porthidium ophryomegas (commonly known as Tamagás Negro), treated with polyvalent snake antivenom. The patient presents to the internal medicine service eight days after the snake bite, with generalized urticaria and palpable non-thrombocytopenic purpura. Based on her clinical history, she was diagnosed with serum sickness secondary to the snake antivenom, a potential complication of its administration. Serum sickness is caused by a type III hypersensitivity reaction, characterized by urticaria, fever, malaise, polyarthralgia, or polyarthritis, and less frequently, purpura secondary to allergic cutaneous vasculitis. There is no consensus regarding the diagnosis, which is clinical, based on medical history and suggestive symptomatology. This case was treated with corticosteroids, antihistamines, and topical antipruritic agents, resulting in the resolution of signs and symptoms without further complications. Although purpura is an uncommon manifestation of serum sickness, its occurrence following antivenom administration for snakebite should prompt consideration of this diagnosis. KEY WORDS: Purpura; antivenom serum; snake bite; hypersensitivity; vasculitis.

Urticaria multiforme is a morphological subtype of acute urticaria, often mistaken for erythema multiforme, serum sickness, or cutaneous vasculitis. Synonyms include acute annular urticaria, acute urticarial hypersensitivity syndrome, echymotic urticaria, and urticaria hemorrhagica. Diagnostic criteria are typical annular and polycyclic urticaria, echymotic changes, pruritus, acral edema, and absence of target lesions, necrosis, or bullous changes. Echymotic changes last 24-48 hours, with rapid response to antihistamines and corticosteroids. It typically affects children aged 4 months to 4 years. We describe two pediatric cases with typical clinical and laboratory features of urticaria multiforme. A 3-year-old boy was admitted with migratory, erythematous, pruritic wheals that appeared on the fourth day of fever, following antipyretic treatment. No prior medical history or recent vaccinations. By day 2, peripheral edema and diffuse erythema developed. Between days 3-5, polycyclic, ecchymotic wheals appeared along with new itchy lesions. An otherwise healthy 11-month-old girl was hospitalized with erythematous, pruritic wheals and annular, urticaroid, erythema multiforme-like lesions. Symptoms began on day 2 after a 7-day course of antibiotics for an upper respiratory infection. No prior medical history, allergies, or recent vaccinations. After corticosteroid and antihistamine treatment, the lesions resolved completely by over the course of one week in both cases.

Chronic spontaneous urticaria significantly impairs quality of life in children, with limited treatment options beyond antihistamines. Omalizumab, an anti-IgE antibody, has shown promise in adults but data on its use in children, especially those under 12, are scarce. This systematic review and meta-analysis aim to evaluate the efficacy and safety of omalizumab in pediatric chronic spontaneous urticaria, providing insights to inform clinical practice and future guidelines. PubMed, Scopus, Embase, Cochrane, and Web of Science databases have been searched for relevant studies. The "R" software has been utilized to analyze the response and relapse rates, changes in urticaria scores, and adverse event rates. Subgroup analyses were also done based on response rate. The assessment of heterogeneity utilized the I2 and chi-squared tests, applying the random effect model. This systematic review included 36 studies met the inclusion criteria. The pooled response rate for omalizumab was 88.0% (95% CI: 80.7%-95.2%; I2 = 61.0%; p = .001), with a complete response rate of 51.0% (95% CI: 32.7%-69.2%; I2 = 90.0%; p < .001). Good or well-controlled response rates were 50.5% (95% CI: 33.9%-67.1%; I2 = 54.2%; p = .068), while poor or partial responses were 20.1% (95% CI: 14.3%-27.3%; I2 = 0.0%; p = .787). Relapse rate were 24.3% (95% CI: 8.1%-40.6%; I2 = 66.6%; p = .006). The Urticaria Activity Score showed a significant mean reduction in symptoms (SMD = -3.08; 95% CI: -5.45 to -0.71; I2 = 89.1%; p < .001). Adverse events occurred in 3.4% of patients, with specific events including urticaria, angioedema, headaches, fatigue, flu-like symptoms, and mild joint pain. In pediatric patients under 12 years, 18 out of 21 achieved complete response, with a median age of 8 years and follow-up durations between 4 and 18 months. Adverse events in this group included serum sickness in one patient. Omalizumab appears to be an effective treatment option for chronic spontaneous urticaria, demonstrating effectiveness in improving symptoms and providing significant relief. The treatment is generally well-tolerated, with adverse events being rare and manageable. Overall, omalizumab contributing to better disease management and quality of life.

PV267 / #708Poster Topic:AS24 - SLE-TreatmentBackground/PurposeIn rheumatoid arthritis (RA), we previously showed that nonmedical switch from rituximab originator (RTX-O) to rituximab biosimilar (RTX-B) was largely effective with comparable 18-month retention rates between those who switched vs remained on RTX-O, 76% and 82% respectively.[1] However, the uptake of nonmedical switch in SLE and other connective tissue diseases and vasculitis (CTD-VAS) has been slow due to a concern with cross-reactivity of antibodies. Our study objectives were to evaluate the effectiveness of nonmedical switch from RTX-O to RTX-B or between RTX-Bs in CTD-VAS.MethodsWe conducted a retrospective observational cohort study of rheumatic and musculoskeletal diseases (RMD) patients in a single center between October 2017 (Index date) and November 2024. During this period, all patients were encouraged to switch to RTX-B (Truxima®) unless declined by the patient or specified by the treating clinician. Furthermore, between 2021-2023, patients on Truxima®were switched to Rixathon®and then reverted to Truxima®in 2024 due to contractual agreement. Due to differences in disease activity tools, clinical responses were graded into full response; partial; and nonresponse. Other measures of effectiveness include the depth of CD20+ cells depletion by highly sensitive flow cytometry and 5-year rituximab retention rate between those who underwent nonmedical switch (Group 1) vs remained on RTX-O (Group 2).ResultsAt Index date, of 829 RMD patients treated with rituximab, 306 (37%) were given for CTD-VAS, while the remaining for RA. Of these, 84/306 (27%) underwent nonmedical switch, Group 1 [RTX-O to RTX-B=58 (69%); between RTX-Bs=26 (31%)]. They had mean (SD) age 51 (15) years, 61 (72%) were female, 61 (72%) had European ancestry, and diagnoses were SLE (54%), AAV (31%), Sjögren (5%), Myopathies (2%) and other CTD (8%). 16/306 (5%) patients remained on RTX-O (Group 2), while 206/306 (67%) initiated treatment with RTX-B. At the last follow-up, of 84 patients in Group 1, 72 (86%) remained on RTX-B [64/72 (89%) switched from RTX-O to RTX-B; 6/72 (8%) switched between RTX-Bs; and 2/72 (3%) reverted to previous RTX-B brand]. 5/84 (6%) of patients on RTX-B reverted to RTX-O and regained response. Reasons were infusion reaction=1, serum sickness=1; neutropenic sepsis 5 days post-rituximab switch=1; skin lesion=1; incomplete depletion and inferior response=1. Of 82/84 and 74/84 patients in Group 1 with paired clinical response and B cells data respectively, there was no difference in response rate (partial or full) and CD20+ cell complete depletion in the rituximab cycle before and after switch, p=0.289 and p=0.815 respectively (McNemara’s test). Patients in Group 2 had more comorbidities, number of rituximab cycles, and number of previous immunosuppressants than those in Group 1. At 5 years, 8/84 (9.5%) patients discontinued rituximab in Group 1 (inefficacy=7 including 2 who reverted to RTX-O); death due to pneumonia=1), while all 16 patients in Group 2 continued therapy. Unadjusted Kaplan-Meier analysis showed no difference in 5-year rituximab retention between Group 1 and Group 2; p=0.152 (Figure 1).Figure 1:Kaplan-Meier plot of rituximab retention survival from Index dateConclusionsOur findings support the nonmedical switch either from RTX-O to RTX-B or between RTX-Bs in CTD-VAS with no difference in clinical response and depth of B cell depletion before and after switch. 5-year rituximab retention rate was very good regardless of nonmedical switch and appeared higher than in RA. Analysis of outcomes of patients who initiated RTX-B is in progress and will help estimate number needed to harm with nonmedical rituximab switch.

Serum Sickness--Like Reactions in Children—Is Lifelong Avoidance Indicated?

Serum sickness-like reactions (SSLRs) consist of urticaria or urticarial-like rashes with joint pain and variable features of fever, angioedema, and gastrointestinal distress. Allergists typically evaluate patients in the clinic for an implicated medication, such as an antibiotic or vaccine. Although SSLR may be mistaken for classical serum sickness or anaphylaxis owing to overlapping clinical features, there is minimal evidence for type I or type III hypersensitivity reactions. Despite recent studies showing antibiotic allergy is rarely verified, patients rarely undergo allergy evaluation. A difficulty is that there is no agreement about challenge procedures- multiple-day dosing protocols lead to a risk for hives and joint pain that does not occur with single-day challenges. In addition, tolerance of either challenge protocol does not fully prevent rashes and repeat episodes of SSLR in all nonallergic children who used the culprit or an unrelated antibiotic again. Owing to the distressing symptoms, lack of abortive therapies, and uncertainty with challenge, many health care professionals and families may prefer to bypass allergy evaluation and continue lifelong avoidance. However, medication allergy labels may be associated with poor health outcomes. Well-designed prospective studies are needed to provide better insight into the diagnosis, effective treatments, and true recurrence rates.

Serum-Like Sickness Syndrome (SLS) is a rare hypersensitivity reaction characterized by-immune-mediated systemic symptoms resembling serum sickness. Serum sickness-like reactions are generally less severe than classic serum sickness and can include arthralgias

Introduction Improper use of botulinum neurotoxin may result in poisoning. This study aimed to investigate the causes, characteristics, and risk factors of iatrogenic botulism incidents in China. Methods Patients diagnosed with iatrogenic botulism who presented to the emergency department of the Second Hospital of Hebei Medical University between June and July 2024 were included. We assessed baseline demographics, clinical symptoms, disease grade, and botulinum toxin type A-related variables. Multivariate regression analysis was used to identify independent risk factors influencing the 30-day prognosis. Results A total of 195 patients were included in the study, with a median age of 38 years (IQR: 33–47 years) and a male-to-female ratio of 1:38. Blurred vision was the most common early feature (82.1%), followed by dizziness and ptosis (75.9%), fatigue (65.1%), and dysarthria (63.1%). The most frequently observed complications were acute gastroenteritis (9.7%), followed by aspiration pneumonia (7.2%). Fifty-one patients experienced severe poisoning with early ocular, facial, limb muscle, and respiratory muscle involvement. Thirty-two patients (16.4%) required mechanical ventilation. The median latent period was 3 days (IQR: 2–4 days), with a median interval of 7 h (IQR: 4–10 h) observed between symptom onset and antitoxin administration. The median duration of hospitalization was 6 days (IQR: 4–8 days). Adverse reactions to the antitoxin included serum sickness in 11 patients and allergic reactions in 20 patients. Based on the presence or absence of clinical signs 30 days post-discharge, we categorized the cohort into good and poor prognostic groups; 87 patients (44.6%) had a poor prognosis. Independent risk factors for a poor prognosis included a latent period ≤3 days, increased time from onset of features to antitoxin treatment, longer hospital duration, disease severity, and need for mechanical ventilation. Discussion Iatrogenic botulism frequently leads to severe outcomes due to delayed diagnosis and intervention. We identified a disease severity grading system alongside additional risk factors to predict patient prognosis. Conclusion Our study underscores the critical importance of early recognition and timely treatment of iatrogenic botulism. Clinicians should implement prompt treatment to mitigate disease progression.

Drug fever is a febrile reaction that coincides in time with and is pathogenetically associated with the use of a drug. The review presents publications of epidemiological and clinical studies on various variants of fever development due to the use of pharmacological agents. Febrile reactions associated with both immune hypersensitivity and those with other mechanisms of development, as well as drug hypersensitivity syndromes, including fever as one of the syndromes (drug-induced hypersensitivity syndrome, serum sickness, drug-induced lupus), are considered. Most often, the term “drug fever” is used to define cases with isolated febrile increase in body temperature, not accompanied by other clinical symptoms (for example, rash or organ damage), and having an immune genesis. An association of drug fever with an extremely wide range of drugs has been established, but most often it is caused by beta-lactam antibiotics. There is a high probability of drug fever in intensive care unit patients who have a high risk of bacterial infection and receive long courses of antibiotics. Underdiagnosis of drug fever leads to unjustified continuation and intensification of antibacterial therapy, increased risk of iatrogenic complications and economic costs. The review also presents variants of drug hyperthermia: malignant neuroleptic syndrome, malignant hyperthermia, serotonin syndrome, propofol infusion syndrome and some others. Despite the long history of studying the issue, the pathogenesis of the pathology remains not entirely clear, there are no specific diagnostic markers and the diagnosis is still made by exclusion.