Facial palsy after administration of immune checkpoint inhibitors: case report, literature review and clinical care management.

Neurological immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICI) are rare complications of immunotherapy, particularly dreadful for patients and clinical teams. Indeed, neurological irAEs are potentially severe and their diagnosis require prompt recognition and treatment. Additionally, the spectrum of neurological irAEs is broad, affecting either neuromuscular junction, peripheral or central nervous system. Here, we described the case of a 55-year man with metastatic melanoma, facing a brutal right peripheral cerebral palsy after his third ipilimumab/nivolumab infusion. After the case presentation, we reviewed the literature about this rare complication of immunotherapy, and described its diagnosis work-up and clinical management.

Parálisis facial, la importancia de realizar una buena historia clínica / Facial palsy, the importance of taking a good medical history

La parálisis facial plantea un diagnóstico diferencial amplio en Pediatría, sobre todo cuando se acompaña de sintomatología que orienta en contra de una parálisis de Bell, por lo que resulta imprescindible realizar una correcta anamnesis. La enfermedad de Lyme es una de las posibles causas de parálisis facial, habiendo sido poco descrita en niños en España. Presentamos el caso de un varón de 11 años con diagnóstico de parálisis facial asociada a infección por B. burgdorferi con evolución favorable tras tratamiento con doxiciclina. (AU)

Facial palsy poses a wide differential diagnosis in pediatrics, especially when it is accompanied by symptoms that make it doubtful whether Bell's palsy is present. It is essential to perform a correct anamnesis to rule out diagnoses that require early detection and treatment to improve the prognosis. Lyme disease (EL) is one of the possible causes of facial palsy, having been seldom described in children in Spain. We present the case of an 11-years-old male with diagnosis of facial palsy associated with B. burgdorferi infection with favorable evolution after treatment with doxycycline. (AU)

Ultrasound-Guided Injections for Treatment of Facial Paralysis Sequelae: A Randomized Study on Body Donors.

BACKGROUND: Botulinum toxin injection is the accepted standard treatment for synkinesis and gustatory hyperlacrimation in patients with facial paralysis. However, poor injection accuracy can result in inconsistent treatment outcomes, variable treatment durations, and complications. Ultrasound guidance should increase injection accuracy in the facial region; however, this has not been proven. METHODS: Twenty-six hemifaces of nonembalmed cadavers were studied in a randomized split-face manner. Ink was injected with ultrasound or landmark guidance into the lacrimal gland and three common synkinetic muscles: the orbicularis oculi, depressor anguli oris, and mentalis. Injection accuracy was evaluated using several measures. RESULTS: Using ultrasound guidance, most ink (>50%) was found inside the correct target in 88% of cases, compared with 50% using landmark guidance ( P < 0.001). This was most pronounced in the lacrimal gland (62% versus 8%), depressor anguli oris (100% versus 46%), and mentalis (100% versus 54%) ( P < 0.05). All ink was found inside the correct target (no ink outside) in 65% using ultrasound guidance versus 29% without ( P < 0.001). Injection accuracy (any ink in target) was 100% when using ultrasound guidance versus 83% without ( P < 0.01). Twenty-three percent of the landmark-guided depressor anguli oris injections stained the facial artery ( P = 0.22). CONCLUSIONS: Ultrasound guidance significantly increased injection accuracy and reduced the amount of ink lost in the surrounding tissue compared with landmark guidance. Clinical trials are needed to explore the effects of ultrasound guidance on treatment outcome, duration, and complications in patients with facial paralysis.

Comparison of oral versus intravenous steroid in the management of Bell's palsy: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Bell's palsy is a condition affecting cranial nerve VII that results in acute peripheral unilateral facial weakness or paralysis of unclear etiology. Corticosteroids are the primary therapy choice, because they improve outcomes. According to a recent study, prednisolone effectively treats Bell's palsy in the short and long term. This study aimed to assess the effectiveness and safety of Single-Dose Intravenous Methylprednisolone to Oral Prednisolone in treating Bell's palsy patients. METHODS: PRISMA statement guidelines were used to design and conduct this systemic review. MEDLINE, Cochrane Library, and EMBASE databases were used in our search. We conducted the database search in November 2022. RESULTS: Thirty-three publications were reviewed as a result of the literature review. Three studies were included in the meta-analysis after applying our criteria. 317 Bell's palsy patients were included in our study. Regarding complete recovery to grade 1 in 1 month, IV methylprednisolone was higher than oral prednisolone; (log OR = 0.52, 95% CI [0.08, 0.97], P = 0.022). However, at 3 months, the two groups had no significant difference. Patients with grade 4 Bell's palsy were more likely to fully recover to grade 1 in 1 month with IV methylprednisolone than with oral prednisolone (log OR = 0.73, 95% CI [0.19, 1.26], P = 0.008), but not for patients with grade 3 or grade 2 Bell's palsy. CONCLUSION: This study shows evidence that patients with Bell's palsy can fully recover to grade 1 in 1 month when IV methylprednisolone is used instead of oral prednisolone. At 3 months, however, there was no discernible difference between the two treatments. Within 3 days of the onset of symptoms, IV methylprednisolone treatment can be started, which may help patients recover fully to grade 1 in 1 month. However, administering IV methylprednisolone may not always have long-term advantages compared to oral prednisolone.

Variations in the treatment of acute peripheral facial paralysis. A nationwide survey.

BACKGROUND: Acute peripheral facial paralysis may be diagnosed and treated by different specialists. OBJECTIVE: The aim of this study was to explore the variability in the treatment of Bell's palsy (BP) and Ramsay Hunt Syndrome (RHS) among different medical specialties. METHODS: An anonymous nationwide online survey was distributed among the Spanish Societies of Otorhinolaryngology (ORL), Neurology (NRL) and Family and Community Medicine (GP). RESULTS: 1039 responses were obtained. 98% agreed on using corticosteroids, ORL using higher doses than NRL and GP. Among all, only 13% prescribed antivirals in BP routinely, while 31% prescribed them occasionally. The percentage of specialists not using antivirals for RHS was 5% of ORL, 11% of NRL, and 23% of GP (GP vs. NRL p = 0.001; GP vs. ORL p < 0.0001; NRL vs. ORL p = 0,002). 99% recommended eye care. Exercises as chewing gum or blowing balloons were prescribed by 45% of the participants with statistically significant differences among the three specialties (GP vs. NRL p = 0.021; GP vs. ORL p < 0.0001; NRL vs. ORL p = 0.002). CONCLUSION: There is general agreement in the use of corticosteroids and recommending eye care as part of the treatment of acute peripheral facial paralysis. Yet, there are discrepancies in corticosteroids dosage, use of antivirals and recommendation of facial exercises among specialties.

Predictive role of facial nerve palsy improvement in malignant external otitis.

PURPOSE: To evaluate the effects of different factors on facial nerve palsy improvement in patients with malignant external otitis (MEO) and the predictive role of improvement on MEO. METHODS: Data were collected from all MEO patients with facial paralysis who were hospitalized between 2012 and 2017 at a tertiary referral center. We contacted patients at least 6 months after their admission to evaluate their facial nerve function and survival rate. RESULTS: In a study of 19 samples with a mean age of 69.1 years, 9 patients (47.7%) had some or complete improvement, while 10 (52.6%) had no or very minimal improvement. In this study, there was no statistically significant difference between patients with and without facial nerve palsy improvement in terms of age, sex, usage of antifungal treatment alongside antibiotics, duration of hospital stays, HbA1c level, presentation of hearing loss and vertigo, the severity of facial palsy, comorbidity score, mean of fasting blood sugar, leukocytosis, first ESR and ESR drop, CRP and physiotherapy. We found a positive correlation between improving facial palsy and patients' survival rates. CONCLUSION: Considering the possible influence of facial paralysis improvement prognosis on MEO patients' survival, it could affect our approach to the disease.

Pain in children with Bell's palsy: secondary analysis of a randomised controlled trial.

OBJECTIVE: To describe the prevalence and severity of pain experienced by children with Bell's palsy over the first 6 months of illness and its association with the severity of facial paralysis. METHODS: This was a secondary analysis of data obtained in a phase III, triple-blinded, randomised, placebo-controlled trial of prednisolone for the treatment of Bell's palsy in children aged 6 months to <18 years conducted between 13 October 2015 and 23 August 2020 in Australia and New Zealand. Children were recruited within 72 hours of symptom onset and pain was assessed using a child-rated visual analogue scale (VAS), a child-rated Faces Pain Score-Revised (FPS-R) and/or a parent-rated VAS at baseline, and at 1, 3 and 6 months until recovered, and are reported combined across treatment groups. RESULTS: Data were available for 169 of the 187 children randomised from at least one study time point. Overall, 37% (62/169) of children reported any pain at least at one time point. The frequency of any pain reported using the child-rated VAS, child-rated FPS-R and parent-rated VAS was higher at the baseline assessment (30%, 23% and 27%, respectively) compared with 1-month (4%, 0% and 4%, respectively) and subsequent follow-up assessments. At all time points, the median pain score on all three scales was 0 (no pain). CONCLUSIONS: Pain in children with Bell's palsy was infrequent and primarily occurred early in the disease course and in more severe disease. The intensity of pain, if it occurs, is very low throughout the clinical course of disease. TRIAL REGISTRATION NUMBER: ACTRN12615000563561.

Comparison of treatment modalities for non-tuberculous mycobacterial cervicofacial lymphadenitis in children.

PURPOSE: We aim to compare the different treatment modalities of non-tuberculous cervicofacial lymphadenitis in children, by means of a retrospective study conducted in the University Hospitals of Leuven of patients treated between 2012 and 2022. METHODS: For this retrospective cohort study, data were collected and pseudonimised from 52 patients with non-tuberculous cervicofacial lymphadenitis, who were treated in our hospital between January 2012 and December 2022, either conservatively, antibiotically, surgically, or with a combination of these options. We only included patients who were considered immunocompetent. All of the included patients were below 10 years at time of treatment. We collected data regarding time to resolution and adverse effects, i.e., skin discoloration, excessive scar formation, fistula formation, persistence of adenopathies after treatment, need for additional treatment, facial nerve paresis/paralysis, or systemic side-effects due to antibiotic treatment. RESULTS: The mean time to resolution (in days) when looking at primary treatments, was shortest in partial excisions (16), followed by complete excisions (19), antibiotic therapy (129), incision and drainage (153), curettage (240), and finally conservative management (280). Taking into account isolated treatments (i.e., both primary and adjuvant), we also observed consistently faster time to resolution in surgical and antibiotic treatments when compared to conservative treatment. Antibiotic therapy (p = 0.003), incision and drainage (p = 0,004) were associated with a significantly higher need for adjuvant treatment. Curettage was associated with a higher incidence of fistula formation (p = 0,006) and higher number of adjuvant treatments (p = 0,002). CONCLUSIONS: This study shows a faster resolution of nontuberculous mycobacterial cervicofacial lymphadenitis in children when treated surgically, more specifically when treated with partial or complete lymph node excision. Antibiotic treatment also leads to faster resolution than conservative management. There was a low rate of complications, and no permanent facial nerve damage was reported.

Bell Palsy: Facts and Current Research Perspectives.

Bell palsy is a non-progressive neurological condition characterized by the acute onset of ipsilateral seventh cranial nerve paralysis. People who suffer from this type of facial paralysis develop a droop on one side of their face, or sometimes both. This condition is distinguished by a sudden onset of facial paralysis accompanied by clinical features such as mild fever, postauricular pain, dysgeusia, hyperacusis, facial changes, and drooling or dry eyes. Epidemiological evidence suggests that 15 to 23 people per 100,000 are affected each year, with a recurrence rate of 12%. It could be caused by ischaemic compression of the seventh cranial nerve, which could be caused by viral inflammation. Pregnant women, people with diabetes, and people with respiratory infections are more likely to have facial paralysis than the general population. Immune, viral, and ischemic pathways are all thought to play a role in the development of Bell paralysis, but the exact cause is unknown. However, there is evidence that Bell's hereditary proclivity to cause paralysis is a public health issue that has a greater impact on patients and their families. Delay or untreated Bell paralysis may contribute to an increased risk of facial impairment, as well as a negative impact on the patient's quality of life. For management, antiviral agents such as acyclovir and valacyclovir, and steroid treatment are recommended. Thus, early diagnosis accompanied by treatment of the uncertain etiology of the disorder is crucial. This paper reviews mechanistic approaches, and emerging medical perspectives on recent developments that encounter Bell palsy disorder.

Improvement in Epiphora Using TEARS Grading Following Surgical Treatment of Meibomian Gland Inversion in Patients With Facial Nerve Palsy.

PURPOSE: To assess epiphora outcomes using the TEARS grading score in patients with concomitant meibomian gland inversion (MGI) and facial nerve palsy (FNP) undergoing correction of MGI. METHODS: Retrospective, 5-year, noncomparative, single-center study of patients with MGI and FNP, treated with MGI correction, under the supervision of a single surgeon. A validated "TEAR" score was used to assess changes in epiphora. RESULTS: Ten patients with FNP, MGI, and epiphora were analyzed from a group of 160 patients with FNP who underwent MGI surgery between 2017 and 2022. The mean age at surgery was 50 years (range, 13-76 years). T, E, and A scores significantly improved (p < 0.05). Eighty percent of patients saw a reduction in tearing frequency (T), with 60% gaining ≥ 2-grade improvement. Improvements in clinical effects (E) and activity limitation (A) were seen in 80% of patients, with 40% and 50% gaining ≥ 2-grade improvement, respectively. R scores (related to reflex tearing) improved by 60%, with 40% seeing ≥ 2-grade improvement. Nine patients (90%) improved symptomatically with an average improvement "S" score of 65% over a mean follow-up period of 30 months. All patients demonstrated restoration of the normal anatomical position of the meibomian glands. CONCLUSIONS: MGI can cause epiphora in patients with FNP and may explain cases where symptoms persist despite standard surgical intervention. This study provides proof of concept that MGI correction can improve epiphora and that identifying MGI may be considered a critical step in the treatment algorithm for epiphora in patients with FNP.

Botulinum toxin treatment of the buccinator muscle facial synkinesis: A systematic review.

BACKGROUND: The purpose of this review is to provide an overview of the available literature assessing the treatment of botulinum toxin injections for the treatment of synkinesis of the buccinator muscle in patients with peripheral facial palsy (PFP). MATERIALS AND METHODS: A multi database search was performed, including the following databases: Pubmed, Medline, Embase, and the Cochrane Library. Each database was searched from its earliest date until 8 June 2023. The following outcome measures were extracted from the articles when available: subjective, somatic, and psychological effects on the patients and objective outcomes such as the House-Brackmann, Sunnybrook and Sydney scores. The methodological quality of the included studies was rated using the Newcastle-Ottawa scale for nonrandomised trials. RESULTS: The primary literature search generated 37 articles. After removing duplicates, 25 articles remained for abstract appraisal, of which 20 underwent full-text appraisal, resulting in 3 studies for analysis. All of these studies showed (significant) improvement in synkinesis either measured using the Synkinesis Assessment Questionnaire or subjectively measured by asking treated patients. CONCLUSION: The available literature supports the finding that botulinum toxin treatment of the buccinator muscle could be a welcome addition to facial synkinesis treatment and could significantly improve patient outcomes. In future studies, the efficacy of EMG-guided buccinator injections, optimal dose, and a validated measuring method could be beneficial in optimising treatment for patients with a PFP and synkinesis.

Neuromuscular retraining therapy combined with preceding botulinum toxin A injection for chronic facial paralysis.

BACKGROUND: Neuromuscular retraining therapy (NMRT) is the central treatment for synkinesis. The efficacy of botulinum toxin type A (BTX-A) may be enhanced with the addition of physical therapy. OBJECTIVES: To investigate the effects of NMRT combined with preceding BTX-A injection (NMRT-B) on facial synkinesis and asymmetry in chronic facial paralysis. MATERIALS AND METHODS: We recruited 99 patients with unilateral facial paralysis and no recovery for > 6 months who underwent NMRT-B for > 1 year. The patients were scheduled to receive NMRT after 1-2 weeks of BTX-A injection. We used a computer-based numerical scoring system to evaluate the facial functions. Primary, secondary, and final facial movement scores were evaluated before and after 1 year of treatment. RESULTS: Patients with chronic facial paralysis who underwent NMRT-B exhibited improved facial movement after 1 year of treatment. NMRT-B provided satisfactory control of synkinesis and improved the primary movements. The mean primary and final facial movement scores were significantly increased after treatment, while the mean secondary facial movement scores were significantly decreased. CONCLUSIONS AND SIGNIFICANCE: NMRT-B improved the final facial movement in patients with chronic facial paralysis and synkinesis, regardless of the degrees of facial synkinesis and asymmetry before treatment.

Botulinum Toxin in Facial Reanimation: Map of the Facial Musculature and Dosage.

Recovery from flaccid facial paralysis can lead to the development of postfacial paralysis synkinesis. Chemodenervation, or treatment with botulinum toxin (BT), is a common treatment for individuals with synkinesis. Patients should be assessed in a multidisciplinary setting to create a specific, individualized, and targeted chemodenervation regimen. This article highlights relevant facial musculature, anatomy, suggested injection patterns, and BT dosages for treating synkinesis patients. These patients require postinjection follow-up, and they should be evaluated by a specially trained facial physical therapist for facial retraining.

Delayed onset peripheral facial nerve palsy after dental extraction: a case report and literature review.

Peripheral facial nerve palsy (PFP) is a rare occurrence after dental extraction. Early onset PFP after the procedure can be caused by trauma and/or local anesthesia, whereas delayed onset PFP has more speculative etiologies. The latter has a certain affiliation to Bell's palsy and is therefore primarily treated with corticosteroids, and long-term follow-up is often warranted. This article reports a unique case of a 30-year-old woman developing a delayed onset right-sided PFP after local intraoral anesthetic injection for molar extraction. Facial nerve injury was identified with signs of denervation and neuritis and the patient was treated with nonsteroidal anti-inflammatory drug, corticosteroids, vitamin B supplements, and mime therapy. After 9 months, the patient showed an improvement of the facial muscle activity and went from a grade IV to a grade III on the House-Brackmann grading scale.

Comparing the Use of High-Dose to Standard-Dose Corticosteroids for the Treatment of Bell's Palsy in Adults-A Systematic Review and Meta-analysis.

OBJECTIVE: Bell's palsy is typically treated with oral corticosteroids (40-60 mg daily). Concomitant antivirals are currently not recommended. The objective of this systematic review and meta-analysis was to examine the effect of high-dose versus standard-dose corticosteroids, without antivirals, in the management of Bell's palsy. DATABASES REVIEWED: Embase, MEDLINE, PubMed, CINAHL, Cochrane Library. METHODS: A systematic review and meta-analysis was performed according to PRISMA guidelines. Studies comparing high-dose (≥80 mg) or standard-dose (40-60 mg) corticosteroid therapy for Bell's palsy were included. Exclusion criteria were coexisting antiviral treatment, nonoral drug delivery, and facial palsy due to other causes. Risk of bias was assessed using ROBINS-I. A weighted estimate of treatment effects across trials as odds ratios (OR) using a Mantel-Haenzel random-effects model was calculated. RESULTS: Three articles were included in the analysis, representing 485 patients. There was a significant decrease in nonrecovery with high-dose, compared with standard-dose, corticosteroids at 6 months follow-up (OR = 0.17, 95% confidence interval = 0.05-0.56, p = 0.004). Overall adverse events were 5.8% (n = 28), all reported in one study in the high-dose group (transient elevated liver enzymes and fecal occult blood). CONCLUSIONS: Our analysis shows a favorable effect of high-dose corticosteroid in the treatment of Bell's palsy. It is the first to evaluate this effect without the use of antivirals in keeping with current treatment recommendations. As all included studies had a serious risk of bias, future research should focus on larger trials with more robust methodology. This will allow for more up-to-date and large-scale analyses where more valid conclusions can be drawn that may potentially influence treatment protocols.

Two cases of Ramsay-Hunt syndrome following varicella zoster viral meningitis in young immunocompetent men: case reports.

BACKGROUND: Ramsay-Hunt syndrome (RHS) due to varicella zoster virus (VZV) infection is commonly reported in individuals aged at least 50 years or immunocompromised individuals. VZV infection may invade the central nervous system (CNS) and cause meningitis or encephalitis, which are more likely to occur in patients with chronic diseases such as diabetes and chronic renal failure. However, cases with VZV-induced concurrent RHS and CNS infections are rare. CASE PRESENTATION: Two young male patients, aged 32 and 43 years, with no underlying disease developed VZV meningitis, followed by RHS involving cranial nerves VII and VIII. Both patients presented with symptoms of peripheral facial palsy, and dizziness accompanied by tinnitus and hearing loss, which appeared several days after the onset of fever and headache. These symptoms were documented as facial neuropathy and sensorineural hearing loss in the electrophysiologic studies. Lymphocyte-dominant pleocytosis and VZV positivity were confirmed from cerebrospinal fluid examination and polymerase chain reaction, respectively. The patients were treated with intravenous acyclovir and oral steroids simultaneously. Following the treatment completion, both patients were relieved of their headaches and fever; however, facial palsy, dizziness, and tinnitus persisted. They were followed up at the outpatient clinic. CONCLUSION: These cases confirmed that RHS and CNS infections can co-exist even in young adults with normal immune function and more importantly, that CNS infection can precede RHS. Since early detection and treatment of RHS improve the prognosis, it is critical to closely monitor patients with VZV meningitis or encephalitis considering the possible superimposition of RHS.

Facial Nerve Paralysis and COVID-19: A Systematic Review.

OBJECTIVE: Several cases of facial nerve paralysis (FNP) post-COVID-19 infection have been reported with varying presentations and management. This study aims to identify FNP clinical characteristics and recovery outcomes among patients acutely infected with COVID-19. We hypothesize that FNP is a potentially unique sequalae associated with COVID-19 infections. METHODS: A systematic review of PubMed-Medline, OVID Embase, and Web of Science databases from inception to November 2021 was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: This search identified 630 studies with 53 meeting inclusion criteria. This resulted in 72 patients, of which 30 (42%) were diagnosed with Guillain-Barré Syndrome (GBS). Non-GBS patients were on average younger (36 vs. 53 years) and more likely to present with unilateral FNP (88%) compared to GBS patients who presented predominantly with bilateral FNP (74%). Among non-GBS patients, majority (70%) of FNP presented a median of 8 [IQR 10] days after the onset of initial COVID-19 symptom(s). Treatment for non-GBS patients consisted of steroids (60%), antivirals (29%), antibiotics (21%), and no treatment (21%). Complete FNP recovery in non-GBS patients was achieved in 67% patients within a median of 11 [IQR 24] days. CONCLUSION: FNP is a possible presentation post COVID-19 infections, associated with both GBS and non-GBS patients. Although no causation can be assumed, the clinical course of isolated FNP associated with COVID-19 raises the possibility of a unique presentation differing from Bell's palsy, seen with higher proportion of patients developing bilateral FNP and a shorter duration to complete recovery. Laryngoscope, 133:1007-1013, 2023.

Blastomyces Induced Otomastoiditis With Local Soft Tissue Invasion: A Case Report.

The aim of this report is to document a very rare case of Blastomycosis dermatitidis mastoiditis with extension into the retromastoid soft tissue and surrounding muscle. Blastomycosis dermatitidis is a dimorphic fungus of endemic areas which classically infiltrates the lungs; however, dissemination presenting as otomastoiditis is exceedingly rare. The patient was an immunocompetent 27-year-old male with no significant preexisting health conditions. He had significant work exposure to dust and soil and was referred to our department for evaluation of otalgia with headaches, hearing loss, and intermittent facial paralysis. Initially, the extent of the infection was unknown. Based on extensive disease on magnetic resonance imaging, the patient was scheduled for urgent tympanoplasty and mastoidectomy. Postoperative treatment with itraconazole resolved any further manifestations and halted further soft tissue invasion. It is important to consider uncommon fungal infections in the workup of persistent otalgia, especially when presenting with facial paralysis and a history of environmental exposure to soil and dust. This type of infection should be considered regardless of immunodeficiency status. Early detection may prevent hearing loss and local invasion into surrounding structures.

Vaccines and Bell's palsy: A narrative review.

The association between vaccines and peripheral facial palsy (PFP), an issue that has been the subject of debate for many years, has been raised again following results of clinical trials assessing mRNA based COVID-19 vaccines. To review the available literature on this topic, PubMed was searched from inception until February 25, 2022. Inclusion criteria were case reports with documented rechallenge and comparative epidemiological studies. Cases of COVID-19 vaccine-induced PFP with available data on vaccine rechallenge were also identified from Vigibase until December 31, 2021. Of the 347 articles retrieved, 32 comparative epidemiological studies, 1 meta-analysis and 4 case reports met our criteria, of which 13 involved COVID-19 vaccines. Eight studies found an association between at least one vaccine and the occurrence of PFP, whereas 24 did not. Positive studies involved seasonal or pandemic H1N1 influenza vaccines administered parenterally (4 studies) or intranasally (1 study with a toxin-adjuvanted vaccine), BNT162b2, a mRNA COVID-19 vaccine (1 disproportionality analysis and 1 observed-to-expected analysis) and an inactivated virus COVID-19 vaccine (CoronaVac®) (1 study combining a case-control and an observed-to-expected approach). Strong evidence was found only for the intranasal influenza vaccine while other positive studies detected only a marginal association between PFP and vaccination. Of the four case reports with documented rechallenge, only two were positive and involved an influenza vaccine and tozinameran in one case each. In Vigibase, rechallenge was documented in 49 reports with 29 (59.2%) cases being negative and 20 (40.8%) positive. The available data did not confirm an excess risk of PFP after vaccination in most studies. Moreover, of the eight epidemiological studies suggesting a possible excess risk of PFP after any vaccine, three were disproportionality analyses and two observed-to excepted analyses, suggesting great caution should be taken when interpreting these results.