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Abstract Background Morphine is widely used to treat moderate-to-severe cancer pain. However, it causes various adverse effects, with morphine-induced fever being an extremely rare and poorly understood symptom. Case presentation We report the case of a 58-year-old Chinese woman with advanced lung cancer. Due to the ineffectiveness of tramadol for pain relief, her treatment regimen was switched to morphine. Following the change, she developed nausea, vomiting, dizziness, and elevated body temperature. A similar episode occurred subsequently. After a drug review, the pharmacist speculated that morphine was the most likely causative agent. Upon discontinuation of morphine, her body temperature returned to baseline levels. Conclusions This case highlights the need for healthcare providers to consider morphine as a potential cause of unexplained fever in patients. The fever may be caused by a hypersensitive response, as there was a significant increase in eosinophils during the fever episodes.

Abstract Brucellosis, a zoonotic ailment induced by the Brucella and some patients may present with joint involvement. This report describes a pediatric patient diagnosed with Brucella arthritis, presenting with swelling and pain in the right knee. The patient had a reoccurrence of fever due to sulfamethoxazole-trimethoprim allergy during treatment. Symptoms improved after adjusting the antimicrobial regimen to ceftriaxone and rifampicin. This case emphasizes the importance of the need for brucellosis as a differential diagnosis for arthralgia and fever in brucellosis- endemic areas. Furthermore, it emphasizes the importance of timely recognition that recurrent fever after effective anti-infective therapy must be considered as a possibility of drug fever.

Background: Morphine is widely used to treat moderate-to-severe cancer pain. However, it causes various adverse effects, with morphine-induced fever being an extremely rare and poorly understood symptom. Case presentation: We report the case of a 58-year-old Chinese woman with advanced lung cancer. Due to the ineffectiveness of tramadol for pain relief, her treatment regimen was switched to morphine. Following the change, she developed nausea, vomiting, dizziness, and elevated body temperature. A similar episode occurred subsequently. After a drug review, the pharmacist speculated that morphine was the most likely causative agent. Upon discontinuation of morphine, her body temperature returned to baseline levels. Conclusions: This case highlights the need for healthcare providers to consider morphine as a potential cause of unexplained fever in patients. The fever may be caused by a hypersensitive response, as there was a significant increase in eosinophils during the fever episodes. [ABSTRACT FROM AUTHOR]

Brucellosis, a zoonotic ailment induced by the Brucella and some patients may present with joint involvement. This report describes a pediatric patient diagnosed with Brucella arthritis, presenting with swelling and pain in the right knee. The patient had a reoccurrence of fever due to sulfamethoxazole-trimethoprim allergy during treatment. Symptoms improved after adjusting the antimicrobial regimen to ceftriaxone and rifampicin. This case emphasizes the importance of the need for brucellosis as a differential diagnosis for arthralgia and fever in brucellosis- endemic areas. Furthermore, it emphasizes the importance of timely recognition that recurrent fever after effective anti-infective therapy must be considered as a possibility of drug fever. [ABSTRACT FROM AUTHOR]

Nitrofurantoin (NIT) is a commonly utilized antibiotic for the treatment of UTIs. Although well tolerated, NIT is not without potential adverse reactions. This case report details the observation of probable NIT-induced drug fever in a patient receiving clozapine. A 61-year-old female with treatment-refractory schizoaffective disorder was admitted to a psychiatric unit with paranoia and auditory hallucinations, prompting clozapine initiation during day 1 of hospitalization. Due to worsening hallucinations and anxiety, antibiotic therapy with NIT for a presumed UTI was initiated 8 days after admission. Febrile episodes were observed beginning on hospital day (HD) 9, leading to concern for possible neuroleptic malignant syndrome (NMS), which led to clozapine discontinuation. The patient received a total of 3 doses of NIT with continued fever until discontinuation on HD 10. No further complications were encountered, and clozapine was safely resumed on HD 13. Although sparsely described in the medical literature, occurrences of drug fever attributable to NIT are previously reported. A review of the medical literature identified only 5 previously published articles specific to NIT-induced drug fever, none of which specified interruptions of psychotropic therapy for a patient with acute psychiatric decompensation. This case highlights the differential diagnosis of fever related to NIT in a patient receiving clozapine when NMS was initially suspected.

Drug fever is a febrile reaction that emerges temporarily with the administration of a drug or a variety of drugs and disappears after cessation of the targeting agent. There are a few previous reports about drug fever, but they pertain mainly to patients accompanied by no surgical intervention. Based on the literature reviewed, drug fever in patients after posterior cervical spine surgery has never been mentioned before; therefore, we present a 56-year-old man diagnosed with drug fever after posterior cervical spine surgery for traumatic cervical myelopathy. Fortunately, his body temperature rapidly came down in 2 days after discontinuing the antibiotics. He was discharged after two more days of observation, and the patient recovered well without any further complaints. Early diagnosis of drug fever may greatly reduce inappropriate and potentially detrimental diagnostic and therapeutic interventions. For patients with persistent fever, if it happened days after surgery, particularly when it is without any infectious evidence, then it is necessarily important to consider a possible reason of drug-induced fever.

A fever above 38°C is a common complication in the first few days after major surgery. Drug-induced fever is the most common cause of fever among the noninfectious causes of postoperative fever. Antimicrobial drugs and heparin, widely used for venous thromboembolism prophylaxis after major orthopedic surgery, are the drugs most commonly associated with postoperative fever. This case study, showing that enoxaparin may be the drug responsible for unexplained fever, may help significantly reduce patient morbidity and the additional costs of investigating the underlying causes of fever. At this stage, the approaches of the clinical pharmacist to provide counseling services to the patient and the healthcare professional in the treatment of medications, the detection of side effects of medications and the suggestion of a solution are important.

Periprosthetic joint infection (PJI) after total knee arthroplasty remains a challenging complication. The treatment options for PJI include different procedures; however, regardless of the strategy, antibiotics are required. The combination of different antibiotics increased the rates of PJI eradication. For almost 3 decades, rifampicin has been used as part of antibiotic therapy for PJI. Drug fever, a febrile response that coincides with the onset of drug administration and disappears after drug discontinuation in the absence of other underlying conditions that could cause fever, is frequently misdiagnosed. We present the case of a 72‐year‐old man with PJI 6 months after total knee arthroplasty. Two‐stage revision surgery was followed by culture‐directed antibiotic treatment (ciprofloxacin and rifampicin) against Staphylococcus aureus isolated from the periprosthetic tissue. On the fifth day of antibiotic treatment, the patient became febrile and, in the next 5 days, he had an intermittent fever of up to 40°C, although he showed clinical improvement. The patient was normotensive without a maculopapular rash, urticaria or clotting abnormalities. A drug fever was suspected, and rifampicin was discontinued. A re‐challenge test was performed, and the fever recurred. Antibiotic treatment with ciprofloxacin was continued and, after 12 months of follow‐up, the patient was doing well. Clinicians should be aware that fever could be a clinical presentation of drug fever. If it occurs during an infection, drug fever could necessitate additional diagnostic procedures for further evaluation, inadequate antibiotic therapy and prolonged hospitalisation. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have reported low incidence of carboplatin-related drug fever in early cancer treatment cycles. This study describes and analyzes relatively higher incidence rate of carboplatin-related drug fever associated with gynecologic cancer chemotherapy in order to allay anxiety in patients and avoid unnecessary interventions. Materials and methods: All gynecologic cancer cases treated with carboplatin in a women's hospital in 2017 and 2018 were retrospectively reviewed and analyzed. Data for patients who experienced carboplatin-induced drug fever and those who received the same treatment but did not experience drug fever were compared for statistical significance. Risk factors for drug fever were identified by logistic regression analysis. Results: In total, 318 females with a mean age of 52 years were included in the analysis. Drug fever was observed in 25 patients (7.86%) in 45 cycles of total 1605 carboplatin-containing infusions. Fever occurred at a median of the third (range: 1–7) cycle, starting at 10.62 h (range: 1.18–50.35 h) after carboplatin infusion, and was generally controlled within 3 days. After chemotherapy rechallenge, the mean frequency of drug fever was 2 times per patient (range: 1–4 times). There were 35/45 drug fever incidents (77.78%) that were classified as grade II; in 15/45 cases (33.33%), antibiotic treatment was immediately initiated to prevent infection. Younger age was found to be a risk factor for drug fever following carboplatin treatment (odds ratio = 0.126, 95% confidence interval: 0.025–0.628; p

Fever is considered a protective response having multitude of benefits in terms of enhancing resistance to infection, recruiting cytokines to the injured tissue, and promoting healing. In terms of an injured brain, this becomes a double-edged sword triggering an inflammatory cascade resulting in secondary brain injury. It is important to identify the etiology so that corrective measures can be taken. Here we report a case of persistent fever in a patient with Guillain-Barré syndrome, which was probably due to heparin. This is the first report of heparin-induced fever in a neurocritical care setting and third report overall.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, life-threatening conditions with a high mortality rate. SJS and TEN denote a group of disorders closely related to each other, characterized by extensive epidermal necrolysis and usually induced by drugs. Keratinocyte apoptosis is the main reason for widespread epidermal detachment. Its etiology usually depends on drugs. Drugs or their metabolites can act as a hapten after binding to the keratinocyte surface and initiate a cytotoxic immunological attack. In this article, a 16-year-old male patient diagnosed with SJS and turned into SJS/TEN overlap with the characteristics of skin lesions during the follow-up, whose complaints improved with treatment and later developed drug-related fever, is presented. Early diagnosis and withdrawal of suspected drugs are some of the most important steps in the treatment. SJS/TEN should be excluded from other diseases similar to SJS/TEN. Although various topical and systemic treatments have recently been used, supportive care is still the most important and effective therapeutic approach. This paper aimed to review clinical findings, with advances in etiopathogenesis and treatment of SJS/TEN and drug fever in light of current literature. [ABSTRACT FROM AUTHOR]

Piperacillin/tazobactam is a widely used anti-infective agent. However, prolonged use can lead to adverse drug reactions, primarily presenting as fever and various abnormal laboratory test results. Certain abnormal test outcomes may mislead clinical assessments. We present a case of a 50-year-old Chinese woman who developed a fever and abnormal blood tests after receiving piperacillin/tazobactam for more than 2 weeks. These tests showed elevated levels of C-reactive protein, procalcitonin, transaminases, myocardial enzymes, and a significant increase in D-dimer. After stopping piperacillin/tazobactam, all relevant test results returned to normal within 10 days. It is imperative for clinicians to be vigilant of this adverse effect in patients undergoing extended piperacillin/tazobactam treatment, as early recognition can prevent unnecessary diagnostic tests and therapeutic interventions., Competing Interests: The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

As of October 2020, there is still no specific drug to treat COVID-19 as it rages worldwide. Favipiravir, indicated for the treatment of new and re-emerging influenza infections, has been suggested to be effective against SARS-CoV-2, although this is not yet fully validated. We administered favipiravir to a 64-year-old female patient with COVID-19. Her symptoms resolved quickly after the start of treatment, with reduction of SARS-CoV-2 viral load, but she developed a fever again on day 12. Since the fever was relieved by discontinuation of favipiravir, and based on positive results with a drug-induced lymphocyte stimulation test, we diagnosed her with favipiravir-induced drug fever. A decrease in the serum concentration of favipiravir was observed along with resolution of the fever. The present case suggests that drug fever should be considered in the differential diagnosis of relapsing fever episodes in COVID-19 patients receiving favipiravir.

Favipiravir, an antiviral agent, is undergoing clinical trials for treating novel coronavirus disease 2019 (COVID-19). Here, we report two cases of COVID-19 with favipiravir-induced fever. In both cases, pyrexia was observed following the administration of favipiravir despite improvements in symptoms of COVID-19. No other cause for fever was evident after careful physical examination and laboratory investigation. The fever subsided in both patients after the discontinuation of favipiravir. To the best of our knowledge, this is the first report of favipiravir-induced fever in COVID-19 patients.

Jiawen Zhang,1,* Hequn Huang,2,* XiXi Xiong,1 Yan Lu,1 Lorna Martin Kasyanju Carrero,1 Bingrong Zhou,1 Yang Xu1 1Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province 210029, People’s Republic of China; 2Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Hefei, Anhui Province 230032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yang XuDepartment of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province 210029, People’s Republic of ChinaTel +86-13851856794Email yangxu@njmu.edu.cnAbstract: Acitretin, an active metabolite of etretinate, is the most widely used systemic retinoid in the treatment of psoriasis. Several side effects of acitretin have been reported such as teratogenicity, cheilitis, xerosis, dyslipidemia, and photosensitivity. Here, we reported a case of acitretin-induced intermittent asymptomatic fever in a 79-year-old male psoriasis patient. To the best of our knowledge, only one such case has been reported in the literature so far. We report our case to draw clinical attention that acitretin may cause drug fever, which might not be a rare phenomenon.Keywords: acitretin, drug fever, psoriasis

Abstract A 69‐year‐old man started taking the dipeptidyl peptidase‐4 inhibitor, vildagliptin. One week later, C‐reactive protein and plasma immunoglobulin E levels were markedly elevated, and the vildagliptin was stopped. After the patient's laboratory findings were normalized, we decided to restart vildagliptin with the patient's agreement. The next day, he had a high fever, and C‐reactive protein and procalcitonin levels were elevated. Although we failed to find a focus of infection, we started antibiotics therapy. Two days later, the high fever had improved, and the C‐reactive protein level had decreased. A drug lymphocyte stimulation test showed a positive result for vildagliptin. We examined various kinds of cytokine and infection markers just before and after the treatment with vildagliptin. Finally, we diagnosed the patient with vildagliptin‐induced drug fever, probably based on the increase of various inflammatory cytokine levels and the response to this. Taken together, we should be aware of the possibility of vildagliptin inducing drug fever and/or acute inflammation.

Drugs can cause fever of unknown origin. Drug fever is a diagnosis of exclusion and can lead to unnecessary investigations and prolonged hospitalization. Any drug can be responsible. Here, we describe the case of a woman admitted because of acute hepatitis. Pantoprazole was started for stress ulcer prophylaxis when she was admitted to the ICU. Fever developed a few days later and an extensive diagnostic work-up was negative. Fever remitted after pantoprazole discontinuation and the diagnosis of drug fever was established.

We present an atypical case of risedronate-induced chronic fever in an 85-year-old woman with Parkinson's disease, with a dosage regimen of 17.5 mg/week. Our patient had been administered an analgesic/antipyretic drug, acetaminophen, at a rate of 600 mg/day for treatment of a vertebral fracture that occurred relatively frequently, which might have masked the fever caused by risedronate. We noted two clinically significant indications. Firstly, blood test results do not necessarily show the cause of risedronate-induced fever, as white blood cell counts and C-reactive protein levels vary. A simple way to diagnose risedronate-induced fever is to suspend risedronate for a certain period and observe if the patient's fever lowers. Secondly, in general, cases receiving polypharmacy tend to include an analgesic antipyretic agent, which may mask the drug-induced fever. Even in patients with Parkinson's disease whose body temperature is generally unstable due to autonomic nerve system disorder, if they are administered risedronate and experience chronic fever of unknown cause, the possibility of drug fever may be considered. This study concludes that risedronate-induced chronic fever, as observed in our case, represents a rare phenomenon, and it may be necessary to reconsider treatment methods for osteoporosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Higaki et al.)

Objective Drug fever is defined as a fever that temporally coincides with the start of a culprit drug and disappears after discontinuation of the drug. It is a common cause of nosocomial fever, which refers to a fever that develops beyond the first 48 h after hospital admission. However, the exact prevalence of drug fever among cases of nosocomial fever is unclear, as is the variation in prevalence depending on the clinical setting and most common causative drugs. Methods PubMed MEDLINE, Dialog EMBASE, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov were systematically searched. Studies that reported the prevalence of drug fever in patients with nosocomial fever were included. Two of the four reviewers conducted independent assessments of the inclusion, data extraction, and quality. Pooled adjusted odds ratios were generated using a random-effects model and presented with 95% confidence intervals (CIs). Results Fifteen meta-analysis from 15 studies were included. Ten studies did not report the definition of drug fever or excluded febrile patients who were admitted to the hospital within 24-48 h. The pooled prevalence of drug fever among cases of nosocomial fever was 3.0% (95% CI, 0.6-6.8%), which was largely consistent across the settings, except for at oriental medicine hospital. Only four studies reported the causative agents, and antibiotics were the most frequently reported. Conclusions The prevalence of drug fever is low in patients with nosocomial fever. Clinicians should recognize that drug fever is a diagnosis of exclusion, even in cases of nosocomial fever.

Fever is considered a protective response having multitude of benefits in terms of enhancing resistance to infection, recruiting cytokines to the injured tissue, and promoting healing. In terms of an injured brain, this becomes a double-edged sword triggering an inflammatory cascade resulting in secondary brain injury. It is important to identify the etiology so that corrective measures can be taken. Here we report a case of persistent fever in a patient with Guillain-Barré syndrome, which was probably due to heparin. This is the first report of heparin-induced fever in a neurocritical care setting and third report overall. [ABSTRACT FROM AUTHOR]

Patients infected with COVID-19 can develop coinfections or acute respiratory disorder that result in ventilation. Dexmedetomidine is a common medication used to sedate ventilated patients in the intensive care unit and for nonintubated patients prior to a surgical procedure. As a highly selective alpha-2 agonist, dexmedetomidine provides sedation while reducing the need for anxiolytics or opioids. However, previous case reports suggest dexmedetomidine can induce fever in a variety of conditions. The purpose of this case report is to describe a patient who acquired a fever of 42.6°C in the setting of COVID-19 after administration of dexmedetomidine., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A 69‐year‐old man started taking the dipeptidyl peptidase‐4 inhibitor, vildagliptin. One week later, C‐reactive protein and plasma immunoglobulin E levels were markedly elevated, and the vildagliptin was stopped. After the patient's laboratory findings were normalized, we decided to restart vildagliptin with the patient's agreement. The next day, he had a high fever, and C‐reactive protein and procalcitonin levels were elevated. Although we failed to find a focus of infection, we started antibiotics therapy. Two days later, the high fever had improved, and the C‐reactive protein level had decreased. A drug lymphocyte stimulation test showed a positive result for vildagliptin. We examined various kinds of cytokine and infection markers just before and after the treatment with vildagliptin. Finally, we diagnosed the patient with vildagliptin‐induced drug fever, probably based on the increase of various inflammatory cytokine levels and the response to this. Taken together, we should be aware of the possibility of vildagliptin inducing drug fever and/or acute inflammation. We experienced the patient with vildagliptin‐induced drug allergy probably based on the increase of IL‐18 level and the stimulation of Th2‐mediated immune response. We should keep in mind the possibility that vildagliptin induces drug allergy and/or acute infection when we examine one of the uncertain causes of high fever and/or elevated CRP levels during the treatment with vildagliptin in subjects with type 2 diabetes. [ABSTRACT FROM AUTHOR]

• We report a case of COVID-19 diagnosed with favipiravir-induced drug fever. • Drug-induced lymphocyte stimulation test (DLST) was positive for favipiravir. • A decrease in serum favipiravir concentration was observed along with fever resolution. • Differential diagnosis of fever in COVID-19 on favipiravir should include drug fever. As of October 2020, there is still no specific drug to treat COVID-19 as it rages worldwide. Favipiravir, indicated for the treatment of new and re-emerging influenza infections, has been suggested to be effective against SARS-CoV-2, although this is not yet fully validated. We administered favipiravir to a 64-year-old female patient with COVID-19. Her symptoms resolved quickly after the start of treatment, with reduction of SARS-CoV-2 viral load, but she developed a fever again on day 12. Since the fever was relieved by discontinuation of favipiravir, and based on positive results with a drug-induced lymphocyte stimulation test, we diagnosed her with favipiravir-induced drug fever. A decrease in the serum concentration of favipiravir was observed along with resolution of the fever. The present case suggests that drug fever should be considered in the differential diagnosis of relapsing fever episodes in COVID-19 patients receiving favipiravir. [ABSTRACT FROM AUTHOR]

Pacemaker implantation-related infective endocarditis is an uncommon, but serious complication. The estimated incidence of infection after permanent endocardial pacemaker implantation varies from 0.2% to 3%. Infective endocarditis shows a mortality rate of 30% to 35%. Conservative medical treatment without removing the pacemaker is prone to failure, and reinfection rates of 51% to 77% have been noted in patients whose pacemaker systems become infected. Therefore, diagnosis of the primary infection is particularly important because surgical removal of the pacemaker system is usually required for its treatment. We describe here an 80-year-old woman who had drug fever that could have been misdiagnosed as infective endocarditis after pacemaker implantation.

• Favipiravir is undergoing clinical trials for treating COVID-19. • Drug fever is difficult to diagnose in patients with febrile illnesses. • We report 2 cases of favipiravir-induced drug fever in patients with COVID-19. Favipiravir, an antiviral agent, is undergoing clinical trials for treating novel coronavirus disease 2019 (COVID-19). Here, we report two cases of COVID-19 with favipiravir-induced fever. In both cases, pyrexia was observed following the administration of favipiravir despite improvements in symptoms of COVID-19. No other cause for fever was evident after careful physical examination and laboratory investigation. The fever subsided in both patients after the discontinuation of favipiravir. To the best of our knowledge, this is the first report of favipiravir-induced fever in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Dexmedetomidine use in the pediatric intensive care unit has increased in recent years. Reports of dexmedetomidine-associated drug fever have been described in adult patients; however, this has not been reported in the pediatric population. We report a case of persistent fever that resolved with the discontinuation of dexmedetomidine and successful transition to clonidine. This is the first report of dexmedetomidine drug fever in a pediatric patient. [ABSTRACT FROM AUTHOR]

Drug fever is an adverse drug reaction accompanied by a febrile response and is a common problem among clinicians, hence an updated knowledge of drug fever is important. A consensus regarding the definition of drug fever is lacking. Thus, descriptions of drug fever in previous literature are often inconsistent. In this narrative review, we summarized various features of drug fever, including its definition, epidemiology, risk factors, clinical presentation, diagnosis, treatment and prognosis, based on the earliest literature. Recent advances in information technology have encouraged researchers to use pharmacovigilance databases for clinical and pharmacological research. We outlined how a pharmacovigilance database, along with recently developed research methods, could be used to research drug fever., Competing Interests: The authors have nothing to declare., (© 2023 Society for Clinical Epidemiology.)

Purpose: The aim of this paper is to review the pathophysiology of thermoregulation mechanism, various causes of fever after maxillofacial surgery and the different treatment protocols advised in the literature. Discussion: Fever is one of the most common complaints after major surgery and is also considered to be an important clinical sign which indicates developing pathology that may go unnoticed by the clinician during post operative period. Several factors are responsible for fever after the maxillofacial surgery, inflammation and infection being the commonest. However, other rare causes such as drug allergy, dehydration, malignancy and endocrinological disorders, etc. should be ruled out prior to any definite diagnosis and initiate the treatment. Proper history and clinical examination is an essential tool to predict the causative factors for fever. Common cooling methods like tepid sponging are usually effective alone or in conjunction with analgesics to reduce the temperature. Conclusion: Fever is a common postoperative complaint and should not be underestimated as it may indicate a more serious underlying pathology. A specific guideline towards the management of such patients is necessary in every hospital setting to ensure optimal care towards the patients during post operative period. [ABSTRACT FROM AUTHOR]