Treating rosacea with botulism toxin: Protocol for a systematic review and meta-analysis.

BACKGROUND: Rosacea is a chronic inflammatory disease usually associated with persistent erythema and periodic flushing. This disease is difficult to treat, and the outcomes are often unsatisfactory and prone to recurrence. In recent years, botulinum toxin has been used as a new treatment for rosacea; however, its efficacy and safety remain under discussion. Although a systematic review of the effectiveness and safety of botulinum toxin has been previously conducted by other researchers, our systematic review and meta-analysis evaluate the efficacy of botulinum toxin from a more comprehensive and detailed perspective to provide evidence for clinicians. METHODS: Any study using botulinum toxin for the treatment of rosacea was considered for the analysis. RESULTS: A total of 22 studies were included, 9 of which were randomized controlled trials involving 720 subjects. After treatment, all studies showed varying degrees of improvement in patient signs and symptoms along with reduced Clinician's Erythema Assessment (CEA) scores. The improvement was maintained for several months, and the adverse effects were mild and self-limiting. CONCLUSION: Botulinum toxin may be an effective treatment for patients with rosacea; however, further clinical evidence is needed to confirm its long-term efficacy and side effects. The study was preregistered with Prospero (CRD42022358911).

Botulism after intragastric botulinum toxin injections for weight reduction.

Although-considering the risk-benefit ratio-botulinum neurotoxin A (BoNT/A) is unequivocally recommended to treat severe neurological diseases such as dystonia, this has not yet been determined for its endoscopic intragastric injection aimed at weight reduction in obesity. However, severe adverse effects of intragastric BoNT/A had not yet been reported, prompting some European countries to endorse its (off-label) use and treat patients transnationally. We here present three cases of botulism after intragastric BoNT/A injections for obesity treatment in a Turkish hospital. Patients presented with cranial nerve affection, bulbar symptoms, and descending paresis, and benefited from treatment with BoNT antitoxin and pyridostigmine. We assume that iatrogenic botulism was induced by overdosing in combination with toxin spread via the highly vascularized gastric tissue. Of note, within a few weeks, more than 80 cases of iatrogenic botulism were reported across Europe after identical intragastric BoNT/A injections. These cases demonstrate the risks of BoNT/A injections if they are not applied within the limits of evidence-based medicine. There is a need for international guidelines to define the indication and a safe dosing scheme, especially in the context of medical tourism.

Epidemiology and risk factors for notifiable Clostridium botulinum infections in Taiwan from 2003 to 2020.

Botulinum toxin is produced by Clostridium botulinum, a gram-positive anaerobic bacterium. This study aimed to examine the epidemiological characteristics, including sex, age, season in which infection occurred, place of residence, and epidemiological trends, of confirmed botulism cases in Taiwan from 2003 to 2020. This study examined the annual summary data on reported botulism in Taiwan' s Center for Disease Control from 2003 to 2020 available to the public on the internet. We found that there were 50 confirmed domestic cases of botulism. The incidence of botulism ranged from 0 to 0.48 per 1000,000 from 2003 to 2020 and peaked in 2008 and 2010. During the 18-year investigation period in which 6-year intervals were used, the study results showed a decreasing trend (2003-2008, 2009-14, and 2015-2020, had 22, 19, 9 cases each). In terms of patients' gender, age, and place of residence, most of the patients were females (56%), were aged ≥ 50 years (48%), and resided in Taipei and northern Taiwan (44%). The number of botulism cases in Taiwan from 2012 to 2020 compared with other years (from 2003 to 2011) found that there were significant differences among patients within an age group of <20 years (P = .003, odds ratio = 18.500, and 95% confidence interval = 3.287-104.111), and there were significant differences among patients whose place of residence was Taipei metropolitan area (P = .025, odds ratio = 5.667, and 95% confidence interval = 1.248-25.734). During 2003 to 2009, there was no case of botulism among those aged <20 years. Over the last 10 years, botulism in children showed an increasing trend. A total of 9 children were found to have botulism during 2010 to 2020; most of these children were male (66.7%) and were infected during spring and summer (66.7%). This study is the first to report the number of confirmed domestic cases with botulism from surveillance data from Taiwan's Center for Disease Control during 2003 to 2020. This study also found that the place of residence and age were associated with an increased risk of botulism in Taiwan. This information may be useful for policymakers and clinical experts to direct prevention- and control-based activities regarding botulism that result in the most severe illness and the greatest burden on Taiwanese.

[Iatrogenic botulism in therapeutic use of botulinum toxin].

The review summarises the current knowledge of the treatment of iatrogenic botulinum toxin overdose. The symptoms may be diffuse, and suspicion should be raised based on time of symptom appearance relative to the time of exposure. Iatrogenic botulism may appear if the maximum recommended total dose of botulinum toxin has been exceeded and if the drug is spread locally from the site of injection or is redistributed to the systemic circulation. The adverse drug reactions frequency is possibly underreported. Fast initiation of the available antidote may be needed. The guideline provided on treatment of iatrogenic botulism is developed from non-iatrogenic botulism.

Wound Botulism in Black Tar Heroin Injecting Users: A Case Series.

The incidence of wound botulism in injection drug users has increased since the introduction of black tar heroin. Many species of the Clostridium genus, most commonly Clostridium botulinum, Clostridium baratii, and Clostridium butyricum, have been associated with wound botulism. Patients often present with progressive bulbar weakness, including dysphagia, cranial nerve palsies, and loss of speech, in addition to symmetrical descending weakness of the upper extremities that may progress to the chest and lower extremities. In this article, we present 3 cases of wound botulism, in which the patients presented with bulbar weakness and were treated with botulism antitoxin heptavalent. The time to antitoxin administration and its effect on the patients' clinical courses is compared.

Use of Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)-(Equine) (BAT®) in Clinical Study Subjects and Patients: A 15-Year Systematic Safety Review.

Botulism is a rare, sometimes fatal paralytic illness caused by botulinum neurotoxins. BAT® (Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)-(Equine)) is an equine-derived heptavalent botulinum antitoxin indicated for the treatment of symptomatic botulism in adult and pediatric patients. This review assesses the cumulative safety profile for BAT product from 2006 to 2020, using data received from clinical studies, an expanded-access program, a post-licensure registry, spontaneous and literature reports. The adverse event (AE) incidence rate for BAT product was calculated conservatively using only BAT product exposures for individuals with a record (512) and was alternatively estimated using all BAT product exposure data, including post-licensure deployment information (1128). The most frequently reported BAT product-related AEs occurring in greater than 1% of the 512-1128 BAT product-exposed individuals were hypersensitivity, pyrexia, tachycardia, bradycardia, anaphylaxis, and blood pressure increase reported in 2.3-5.1%, 1.8-3.9%, 1.0-2.2%, 0.89-2.0%, 0.62-1.4%, and 0.62-1.4%, respectively. For patients properly managed in an intensive care setting, the advantages of BAT product appear to outweigh potential risks in patients due to morbidity and mortality of botulism. AEs of special interest, including bradycardia, hemodynamic instability, hypersensitivity, serum sickness, and febrile reactions in the registry, were specifically solicited.

Brain functional changes in patients with botulism after illegal cosmetic injections of botulinum toxin: A resting-state fMRI study.

BACKGROUND: Botulinum toxin type A (BoNT-A) is generally considered safe and is widely used to treat a variety of clinical conditions involving muscle hyperactivity and for cosmetic purposes. However, the effects of BoNT-A poisoning (botulism) on brain function are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Herein, we investigated brain functions in 9 patients who received illegal cosmetic injections of botulinum and 18 matched controls by combining the analysis methods of regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) based on resting-state fMRI. Compared with the controls, the patients with botulism exhibited significantly reduced ReHo values in the left posterior lobe of the cerebellum extending to the right anterior lobe of the cerebellum, as well as in the right anterior lobe of the cerebellum extending to the parahippocampal gyrus and right posterior lobe of the cerebellum. The patients with botulism also showed weakened ALFF values in the right anterior lobe of the cerebellum extending to the left anterior lobe of the cerebellum and right posterior lobe of the cerebellum, as well as in the right anterior lobe of the cerebellum. CONCLUSIONS/SIGNIFICANCE: The results indicate that BoNT-A may modulate cerebral activation in specific areas, which may play roles in both the adverse effects of botulism and the mechanism underlying clinical treatment with BoNT-A.

Clinical analysis of 86 botulism cases caused by cosmetic injection of botulinum toxin (BoNT).

This study was conducted to analyze the clinical characteristics of and treatment strategies for botulism among patients receiving cosmetic injection of botulinum toxin (BoNT).A total of 86 botulism patients caused by cosmetic injection of BoNT were enrolled in our study. All of the patients were diagnosed according to their history of cosmetic BoNT injection, clinical symptoms and signs, and other auxiliary examinations (including those on renal and liver functions, blood index detection, and chest X-ray). All of the patients received comprehensive treatments and botulinum antitoxin serum injection.The main symptoms of botulism patients included headache, dizziness, insomnia, fatigue, blurred vision, eye opening difficulty, slurred speech, dysphagia, bucking, constipation, and anxiety. These clinical symptoms occurred 0∼36 days after BoNT injection, especially from 2nd to 6th day after the operation. Furthermore, the usage dose of BoNT was negatively related to latent period. Finally, patients all discharged from our hospital 1∼20 days after treatments, and their symptoms relieved or disappeared.Botulism is a severe side effect for BoNT injection. Injecting botulinum antitoxin serum may be an effective approach to improve clinical outcomes of botulism cases.

Therapeutic Plasma Exchange in a rare case myasthenic crisis after Botox injection.

BACKGROUND AND AIMS: Botulinum toxin (Botox) injections are used as a cosmetic treatment to decrease wrinkles in face and chin. Being a neurotoxic agent it minimizes muscle activity, while side effects are usually rare. This article subsequently presents one case of these rare effects. CASE: A 30-year-old woman presenting with ptosis, diplopia, dysarthria, dysphagia and muscle weakness was admitted to our hospital. She had no history of disease. For cosmetic reasons, she had three Botox injections during the preceding months. On physical examination, muscle weakness 4/5 (cervical extensor, ocular and pharynx) was detected and a diagnosis of myasthenia gravis was made. Protective artificial ventilation was necessary. As a consequence, eight sessions of 2.5 L volume Therapeutic Plasma Exchange (TPE) were applied using normal saline/albumin as substitute. Due to TPE, her muscle force and clinical condition improved. Artificial ventilation could be stopped. CONCLUSIONS: Clinical symptoms of myasthenia gravis and systemic Botox effects are very similar. This should be taken into consideration during medical history taking. The injection of high doses of Botox (more than 200 units in every injection) or boostering within less than one month is dangerous. (Botox BCC2024). Systemic side effects can be treated using TPE to lower the circulating dose of Botox.

Neurotoxins from Clostridium botulinum (serotype A) isolated from the soil of Mendoza (Argentina) differ from the A-Hall archetype and from that causing infant botulism.

The type A of neurotoxin produced by Clostridium botulinum is the prevalent serotype in strains of Mendoza. The soil is the main reservoir for C.botulinum and is possibly one of the infection sources in infant botulism. In this study, we characterized and compared autochthonous C. botulinum strains and their neurotoxins. Bacterial samples were obtained from the soil and from fecal samples collected from children with infant botulism. We first observed differences in the appearance of the colonies between strains from each source and with the A Hall control strain. In addition, purified neurotoxins of both strains were found to be enriched in a band of 300 kDa, whereas the A-Hall strain was mainly made up of a band of ∼600 kDa. This finding is in line with the lack of hemagglutinating activity of the neurotoxins under study. Moreover, the proteolytic activity of C. botulinum neurotoxins was evaluated against SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) proteins from rat brain. It was observed that both, SNAP 25 (synaptosomal-associated protein 25) and VAMP 2 (vesicle-associated membrane protein) were cleaved by the neurotoxins isolated from the soil strains, whereas the neurotoxins from infant botulism strains only induced a partial cleavage of VAMP 2. On the other hand, the neurotoxin from the A-Hall strain was able to cleave both proteins, though at a lesser extent. Our data indicate that the C.botulinum strain isolated from the soil, and its BoNT, exhibit different properties compared to the strain obtained from infant botulism patients, and from the A-Hall archetype.

Substrate-based inhibitors exhibiting excellent protective and therapeutic effects against Botulinum Neurotoxin A intoxication.

Potent inhibitors to reverse Botulinum neurotoxins (BoNTs) activity in neuronal cells are currently not available. A better understanding of the substrate recognition mechanism of BoNTs enabled us to design a novel class of peptide inhibitors which were derivatives of the BoNT/A substrate, SNAP25. Through a combination of in vitro, cellular based, and in vivo mouse assays, several potent inhibitors of approximately one nanomolar inhibitory strength both in vitro and in vivo have been identified. These compounds represent the first set of inhibitors that exhibited full protection against BoNT/A intoxication in mice model with undetectable toxicity. Our findings validated the hypothesis that a peptide inhibitor targeting the two BoNT structural regions which were responsible for substrate recognition and cleavage respectively could exhibit excellent inhibitory effect, thereby providing insight on future development of more potent inhibitors against BoNTs.

[Intoxication of botulinum toxin]. / Toksyny Clostridium perfringens jako zagrozenie naturalne i bioterrorystyczne.

Botulinum toxin is an egzotoxin produced by Gram positive bacteria Clostridium botulinum. It is among the most potent toxins known. The 3 main clinical presentations of botulism are as follows: foodborne botulism, infant botulism and wound botulism. The main symptom of intoxication is flat muscles paralysis. The treatment is supportive care and administration of antitoxin. In prevention the correct preparing of canned food is most important. Botulinum toxin is accepted as a biological weapon.

Botulinum Neurotoxins Can Enter Cultured Neurons Independent of Synaptic Vesicle Recycling.

Botulinum neurotoxins (BoNTs) are the causative agent of the severe and long-lasting disease botulism. At least seven different serotypes of BoNTs (denoted A-G) have been described. All BoNTs enter human or animal neuronal cells via receptor mediated endocytosis and cleave cytosolic SNARE proteins, resulting in a block of synaptic vesicle exocytosis, leading to the flaccid paralysis characteristic of botulism. Previous data have indicated that once a neuronal cell has been intoxicated by a BoNT, further entry of the same or other BoNTs is prevented due to disruption of synaptic vesicle recycling. However, it has also been shown that cultured neurons exposed to BoNT/A are still capable of taking up BoNT/E. In this report we show that in general BoNTs can enter cultured human or mouse neuronal cells that have previously been intoxicated with another BoNT serotype. Quantitative analysis of cell entry by assessing SNARE cleavage revealed none or only a minor difference in the efficiency of uptake of BoNTs into previously intoxicated neurons. Examination of the endocytic entry pathway by specific endocytosis inhibitors indicated that BoNTs are taken up by clathrin coated pits in both non pre-exposed and pre-exposed neurons. LDH release assays indicated that hiPSC derived neurons exposed consecutively to two different BoNT serotypes remained viable and healthy except in the case of BoNT/E or combinations of BoNT/E with BoNT/B, /D, or /F. Overall, our data indicate that previous intoxication of neuronal cells with BoNT does not inhibit further uptake of BoNTs.

Long lasting dysautonomia due to botulinum toxin B poisoning: clinical-laboratory follow up and difficulties in initial diagnosis.

BACKGROUND: Botulism is an acute form of poisoning caused by one of four types (A, B, E, F) toxins produced by Clostridium botulinum, ananaerobic, spore forming bacillus. Usually diagnosis of botulism is considered in patients with predominant motor symptoms: muscle weakness with intact sensation and preserved mental function. CASE PRESENTATION: We report a case of 56-year-old Caucasian female with a history of arterial hypertension, who presented with acute respiratory failure and bilateral ptosis misdiagnosed as brainstem ischemia. She had severe external and internal ophtalmoplegia, and autonomic dysfunction with neither motor nor sensory symptoms from upper and lower limbs. Diagnosis of botulinum toxin poisoning was made and confirmed by serum antibody testing in the mouse inoculation test. CONCLUSIONS: Ophtalmoplegia, autonomic dysfunction and respiratory failure can be caused by botulism. Early treatment and intensive care is essential for survival and recovery. The electrophysiological tests are crucial to correct and rapid diagnosis. Botulism (especially type B) should be considered in any case of acute or predominant isolated autonomic dysfunction.

Iatrogenic botulism after the therapeutic use of botulinum toxin-A: a case report and review of the literature.

Local injection of botulinum toxin-A is an accepted treatment for hyperhidrosis. We report 2 cases of primary hyperhidrosis who developed iatrogenic botulism after the therapeutic dose of onabotulinumtoxinA (Botox). This case report highlights the necessity of clinicians having sufficient information of potentially adverse effects, optimal dose, and correct preparation and injection of botulinum toxin-A.

Injectable neurotoxins and fillers: there is no free lunch.

Injection of neurotoxins and filling agents for the treatment of facial aesthetics has increased dramatically during the past few decades due to an increased interest in noninvasive aesthetic improvements. An aging but still youth-oriented population expects effective treatments with minimal recovery time and limited risk of complications. Injectable neurotoxins and soft tissue stimulators and fillers have filled this niche of "lunch-time" procedures. As demand for these procedures has increased, supply has followed with more noncore cosmetic specialty physicians, as well as unsupervised ancillary staff, becoming providers and advertising them as easy fixes. Despite an excellent record of safety and efficacy demonstrated in scores of published studies, injectable agents do carry risks of complications. These procedures require a physician with in-depth knowledge of facial anatomy and injection techniques to ensure patient safety and satisfaction. In general, adverse events are preventable and technique-dependent. Although most adverse events are minor and temporary, more serious complications can occur. The recognition, management, and treatment of poor outcomes are as important as obtaining the best aesthetic results. This review addresses important considerations regarding the complications of injectable neurotoxins and fillers used for "lunch-time" injectable procedures.

Iatrogenic botulism due to therapeutic botulinum toxin a injection in a pediatric patient.

Botulinum toxin A is commonly used to reduce spasticity and dystonia in children with cerebral palsy. We report a pediatric patient who developed systemic botulism as a result of a severe overdose of the injected toxin (40 U/kg). This case highlights the importance of physicians having adequate knowledge of primate and human literature on the lethal dose, 50% of botulinum toxin A before injecting children.