Hoarseness as the presentation of immunoglobulin G4-related disease with vocal cord and mediastinal infiltration.

Immunoglobulin G4-related disease is a rare fibroinflammatory infiltrative condition with heterogeneous clinical manifestations. We present the case of a 64-year-old man that presented with hoarseness due to vocal cord involvement, a particularly rare manifestation. A large mediastinal mass compressing thoracic large vessels was also identified. The patient was initially treated with glucocorticoids but had relapses during glucocorticoid tapering. Rituximab was started after a careful pre-treatment evaluation of the infectious risk and treatment of comorbidities.

Vagus nerve stimulation for focal seizures.

BACKGROUND: This is an updated version of the Cochrane Review published in 2015. Epilepsy is a chronic neurological disorder, characterised by recurring, unprovoked seizures. Vagus nerve stimulation (VNS) is a neuromodulatory treatment that is used as an adjunctive therapy for treating people with drug-resistant epilepsy. VNS consists of chronic, intermittent electrical stimulation of the vagus nerve, delivered by a programmable pulse generator. OBJECTIVES: To evaluate the efficacy and tolerability of VNS when used as add-on treatment for people with drug-resistant focal epilepsy. SEARCH METHODS: For this update, we searched the Cochrane Register of Studies (CRS), and MEDLINE Ovid on 3 March 2022. We imposed no language restrictions. CRS Web includes randomised or quasi-randomised controlled trials from the Specialised Registers of Cochrane Review Groups, including Epilepsy, CENTRAL, PubMed, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. SELECTION CRITERIA: We considered parallel or cross-over, randomised, double-blind, controlled trials of VNS as add-on treatment, which compared high- and low-level stimulation (including three different stimulation paradigms: rapid, mild, and slow duty-cycle), and VNS stimulation versus no stimulation, or a different intervention. We considered adults or children with drug-resistant focal seizures who were either not eligible for surgery, or who had failed surgery. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods, assessing the following outcomes: 1. 50% or greater reduction in seizure frequency 2. Treatment withdrawal (any reason) 3. Adverse effects 4. Quality of life (QoL) 5. Cognition 6. Mood MAIN RESULTS: We did not identify any new studies for this update, therefore, the conclusions are unchanged. We included the five randomised controlled trials (RCT) from the last update, with a total of 439 participants. The baseline phase ranged from 4 to 12 weeks, and double-blind treatment phases from 12 to 20 weeks. We rated two studies at an overall low risk of bias, and three at an overall unclear risk of bias, due to lack of reported information about study design. Effective blinding of studies of VNS is difficult, due to the frequency of stimulation-related side effects, such as voice alteration. The risk ratio (RR) for 50% or greater reduction in seizure frequency was 1.73 (95% confidence interval (CI) 1.13 to 2.64; 4 RCTs, 373 participants; moderate-certainty evidence), showing that high frequency VNS was over one and a half times more effective than low frequency VNS. The RR for treatment withdrawal was 2.56 (95% CI 0.51 to 12.71; 4 RCTs, 375 participants; low-certainty evidence). Results for the top five reported adverse events were: hoarseness RR 2.17 (99% CI 1.49 to 3.17; 3 RCTs, 330 participants; moderate-certainty evidence); cough RR 1.09 (99% CI 0.74 to 1.62; 3 RCTs, 334 participants; moderate-certainty evidence); dyspnoea RR 2.45 (99% CI 1.07 to 5.60; 3 RCTs, 312 participants; low-certainty evidence); pain RR 1.01 (99% CI 0.60 to 1.68; 2 RCTs; 312 participants; moderate-certainty evidence); paraesthesia 0.78 (99% CI 0.39 to 1.53; 2 RCTs, 312 participants; moderate-certainty evidence). Results from two studies (312 participants) showed that a small number of favourable QOL effects were associated with VNS stimulation, but results were inconclusive between high- and low-level stimulation groups. One study (198 participants) found inconclusive results between high- and low-level stimulation for cognition on all measures used. One study (114 participants) found the majority of participants showed an improvement in mood on the Montgomery-Åsberg Depression Rating Scale compared to baseline, but results between high- and low-level stimulation were inconclusive. We found no important heterogeneity between studies for any of the outcomes. AUTHORS' CONCLUSIONS: VNS for focal seizures appears to be an effective and well-tolerated treatment. Results of the overall efficacy analysis show that high-level stimulation reduced the frequency of seizures better than low-level stimulation. There were very few withdrawals, which suggests that VNS is well tolerated. Adverse effects associated with implantation and stimulation were primarily hoarseness, cough, dyspnoea, pain, paraesthesia, nausea, and headache, with hoarseness and dyspnoea more likely to occur with high-level stimulation than low-level stimulation. However, the evidence for these outcomes is limited, and of moderate to low certainty. Further high-quality research is needed to fully evaluate the efficacy and tolerability of VNS for drug-resistant focal seizures.

Comparison of the efficiency of two different proton pump inhibitor formula in treatment of patients with atypical gastroesophageal reflux disease: a prospective randomized study.

BACKGROUND AND AIM: The prospective, open-label, randomized study aims to compare the efficacy of lansoprazole, a fast orally disintegrating proton pump inhibitor (PPI), and dexlansoprazole, a dual delayed release PPI, in patients with atypical symptoms of gastroesophageal reflux disease (GERD). METHODS: Patients with atypical GERD symptoms with a total reflux symptom index score > 10 were eligible for enrollment. From February 2018 to December 2019, 232 subjects were randomly assigned (1:1 ratio) to receive oral lansoprazole, Takepron OD 30 mg, once daily before breakfast or oral dexlansoprazole, Dexilant 60 mg, once daily before breakfast for 8 weeks. The primary end-point is to compare the symptoms response rate after an 8-week PPI therapy between the two groups. RESULTS: There were 232 study subjects enrolling in this study. After the 8-week PPI therapy, dexlansoprazole-treated group had a significantly higher response rate than lansoprazole-treated group in cough (76.5% vs 38.0%) and globus (69.7% vs 30.8%) (P all < 0.05 by intention-to-treat). Multivariate logistic regression analysis showed that the use of dexlansoprazole, presence of dyslipidemia, and typical GERD symptoms (acid reflux and heartburn) were predictors for symptom response for cough; the use of dexlansoprazole and presence of erosive esophagitis were predictors for symptom response for globus (P all < 0.05). No predictor for therapy response to hoarseness was noted. CONCLUSIONS: There is a higher response rate for cough and globus symptoms in patients with atypical GERD after the 8-week PPI therapy with dexlansoprazole rather than lansoprazole.

Clinical and Acoustical Voice Quality Evolutions Throughout Empirical Treatment for Laryngopharyngeal Reflux Disease According to Gender: A Preliminary Study.

OBJECTIVE: To compare symptoms, signs, and acoustical voice quality changes throughout the 6-month course of empirical treatment between laryngopharyngeal reflux (LPR) males and females. MATERIALS AND METHODS: Forty clinically diagnosed LPR females and 40 males with a reflux finding score (RFS) >7 and a reflux symptom index (RSI) >13 were treated with pantoprazole and diet recommendations during 3 or 6 months according to their evolution. RSI, RFS, and acoustic parameters were assessed at baseline and 3 and 6 months posttreatment. A correlation analysis between videolaryngostroboscopic findings and acoustic measurements was performed. RESULTS: RSI, RFS, and many acoustic measurements (i.e., percent jitter, percent shimmer, phonatory fundamental frequency range, fundamental frequency variation, and peak-to-peak amplitude variation) significantly improved from baseline to 3 months posttreatment in male group. In female group, RSI and RFS total score significantly improved along the 3 first months of treatment. However, some clinical outcomes (i.e., RSI total score, hoarseness, cough, and globus) continued to improve from 3 to 6 months of treatment. We did not identify significant improvement of acoustic measurements in female group. The correlation study did not reveal significant correlation between videolaryngostroboscopic findings and acoustic measurements. CONCLUSION: This preliminary study suggests the occurrence of gender-related differences in the LPR therapeutic response. Further studies need to clarify whether females require a longer course of therapy than males.

Ectoine lozenges in the treatment of acute viral pharyngitis: a prospective, active-controlled clinical study.

PURPOSE: Acute pharyngitis is an uncomfortable disorder mostly caused by viruses and for which antibiotics are unwarranted. This study compared lozenges containing ectoine, a natural extremolyte, with hyaluronic acid lozenges and hypertonic saline gargle for symptomatic treatment of acute viral pharyngitis. METHODS: This prospective, controlled clinical study, recruited 90 patients with moderate-to-severe pharyngitis symptoms who chose to use either ectoine (n = 35), hyaluronic acid (n = 35), or saline gargle (n = 20). Patients applied their 7-day treatment from the inclusion visit (V1) until the end-of-study visit (V2). Patients' pharyngitis symptoms, general health, general treatment effectiveness and tolerability, and patient compliance were assessed by investigators and patients. RESULTS: The sum score for three primary symptoms (pain on swallowing, urge to cough, and hoarseness) decreased by 79.5% (ectoine), 72.2% (hyaluronic acid), and 44.8% (saline gargle). Both lozenges were significantly superior to saline gargle (P < 0.05). Regarding general health improvement, ectoine was significantly superior to saline gargle (72.5% vs. 45.2%, P < 0.05), but hyaluronic acid (63.3%) was not. At V2, 65.7% of patients receiving ectoine reported "very good" general health vs. 48.6% of those receiving hyaluronic acid and 20.0% using saline gargle. Ectoine was significantly superior (P < 0.05) to both hyaluronic acid and saline gargle in terms of tolerability and patient compliance. No patients taking ectoine reported unpleasant sensations while applying their treatment, whereas almost half of patients using hyaluronic acid lozenges and saline gargle did. CONCLUSION: Treatment with ectoine lozenges significantly relieves moderate-to-severe symptoms of acute viral pharyngitis and is more effective and tolerable than treatments with hyaluronic acid lozenges and hypertonic saline gargle.

Bamboo Nodes of Vocal Folds: A Description of 10 Cases and Review of the Literature.

OBJECTIVE: Bamboo nodes are vocal fold lesions, mostly associated with autoimmune diseases. PATIENTS AND METHODS: This is a retrospective clinical study including 10 patients with bamboo nodes. Data were collected regarding associated autoimmune disorder and type of treatment. A systematic review of the literature was conducted. RESULTS: All patients were women, with hoarseness as the most frequent symptom. There was in most cases an associated autoimmune disease: 3 patients with systemic lupus erythematosus; 3 with rheumatoid arthritis; 1 with Sjögren syndrome; 1 with Hashimoto disease; and 1 with mixed connective tissue disease. Four patients were treated with speech therapy, 3 with oral steroids, 1 with speech therapy and oral steroids combined, 1 with oral steroids and laryngeal steroid injections, and 1 had oral steroids, surgery, and speech therapy. Speech therapy was the first-line treatment. CONCLUSION: Bamboo nodes should be looked for in every patient with a diagnosis of autoimmune disease complaining of dysphonia.

The Effect of Betamethasone Gel and Lidocaine Jelly Applied Over Tracheal Tube Cuff on Postoperative Sore Throat, Cough, and Hoarseness.

PURPOSE: The purpose of the study was to investigate the effect of betamethasone gel and lidocaine jelly (over tracheal tube cuff) compared with distilled water on the postextubation syndrome incidence (sore throat, cough, and hoarseness). DESIGN: Double-blind randomized clinical trial study was used. METHODS: Ninety-nine patients of either sex undergoing elective surgery, under general anesthesia with endotracheal intubation, were recruited. Patients were randomized into three group, betamethasone gel, lidocaine jelly, or distilled water applied on the external surface of the tracheal tube. Patients were assessed for postoperative sore throat, cough, and hoarseness at 1, 6, and 24 hours after surgery. FINDINGS: In the first hour after surgery, the patients who received lidocaine or betamethasone had a significantly greater incidence of sore throat than the patients who received distilled water (RR = 2.9). In the sixth hour after surgery, there was a better effect of distilled water on reducing the incidence of sore throat, but no significant differences between the three groups were seen 24 hours after surgery. The incidence of cough was significantly lower in the distilled water group (P < .02) except at the first and 24 hours postoperative when the incidence of cough was similar. The incidence of hoarseness was similar between the three groups at 1, 6, and 24 hours after surgery. CONCLUSION: In this study, the use of lidocaine gel and betamethasone does not reduce the incidence of sore throat or cough after intubation as much as distilled water.

Gastroesophageal reflux disease with laryngopharyngeal manifestation in Korea.

BACKGROUND/AIMS: Globus pharyngeus and hoarseness are common extraesophageal manifestations inpatients with gastroesophageal reflux disease. The aim of this study was to evaluate the clinical characteristics, laryngoscopic findings, endoscopic findings, and response to proton pump inhibitors in patients presenting laryngeal symptoms suspected to be caused by GERD. METHODOLOGY: We retrospectively reviewed the medical records of 160 patients that presented with globus and/or hoarseness and underwent acid suppression therapy under the impression of GERDfrom May 2003 to April 2009. RESULTS: Sixty patients(37.5%) reported classical GERD symptoms such as heartburn and/or acid regurgitation. Sixty nine percent(69%) of patients (95/138) showed abnormal laryngoscopic findings such as laryngeal edema/hyperemia, vocal cord swelling/hyperemia, arytenoids swelling/hyperemia, vocal cord nodule, vocal cord polyp, post-glottic swelling/hyperemia, etc. Endoscopically, 41.9%(39/93) showed normal endoscopic findings and 49.5% (46/93) showed minimal changes. 8.6% (8/93)of patients showed erosive reflux disease. Therapeutic response was not significantly different among patients treated with standard dose PPIs (44/58, 75.9%),half dose PPIs (17/22, 77.3%), or revaprazan (18/21,85.7%). CONCLUSIONS: Among patients with globus pharyngeus and/or hoarseness and suspected GERD, only 37.5% reported classical symptoms of GERD such as heartburn and/or acid regurgitation, 69% showed ab-normal laryngoscopic findings, 58.1% showed abnormal endoscopic findings, and 80% showed therapeutic response to acid suppression therapy.

Endoscopic treatment of anterior glottic webs according to Lichtenberger technique and results on 18 patients.

Anterior glottic webs are most frequently acquired and result in a major vocal handicap. Many treatment modalities have been reported in the literature. None of them achieves perfect morphological or functional results. We present our series treated by an endoscopic technique based on CO(2) laser section of the web, mitomycin application and placement of a temporary silastic stent. We retrospectively reviewed the charts of 18 consecutive patients with anterior webs treated at our university hospital between 2003 and 2010. The endoscopic technique consisted of the section of the web with the CO(2) Acublade system, immediate application of mitomycin C and placement of a silastic stent. No tracheostomy was required. The stent was removed 3 weeks later. Patients had a vocal evaluation pre and postoperatively. It consisted of a video-stroboscopic examination, the global score of the Voice Handicap Index, the global and roughness scores of the perceptive voice evaluation according to Hirano, acoustic and aerodynamic parameters. Eighteen patients were included in the study with a mean age of 46 years (min. = 5, max. = 76). Twenty-two percent were women. All patients had postoperative speech therapy. The mean follow-up is 48.4 months (3-87 months). At the last follow-up, none of the patients had recurrence of the laryngeal web. The grade G of dysphonia significantly decreased from 2 to 1 (p = 0.035). CO(2) laser resection of anterior webs with mitomycin C application and placement of a silastic stent for 3 weeks induces a good morphological result with absence of web reformation but without substantial voice improvement observed in our series.

A case of vocal polyps improved with herbal medicine: A case report.

Vocal polyps are benign vocal cord lesions, which mainly manifest as a hoarse voice. Laryngeal microsurgery is the most common treatment. However, because of anxiety regarding invasive treatment, it is necessary to have a non-invasive treatment option. A 43 year old female patient who is a teacher visited a Korean medical hospital for persistent hoarseness with a vocal polyp. After taking herbal medicine for hoarseness (Kyung-Hee-cheong-um-whan) and pharyngitis (cheong-in-li-gyok-tang and cheong-in-ryu-que-whan) for almost 10 weeks, the vocal polyp was reduced and symptoms improved. Herbal prescription for pharyngitis and hoarseness can be applied to vocal polyps as non-invasive treatment.

Intracordal Injection of Basic Fibroblast Growth Factor in 100 Cases of Vocal Fold Atrophy and Scar.

OBJECTIVES/HYPOTHESIS: Vocal fold atrophy, scar, and sulcus reduce the vibratory function of the vocal fold mucosa, which causes severe refractory dysphonia. We have reported encouraging preliminary results using an intracordal injection of basic fibroblast growth factor (bFGF) and showed improvement in phonatory parameters and voice. The present study summarizes our experience with 100 cases of stiffened vocal folds that were treated with bFGF injections. STUDY DESIGN: Retrospective chart review with Interstitial Review Board (IRB) approval. METHODS: Local injection of bFGF was performed in 100 cases of vocal fold pathology, which included 43 cases of vocal fold atrophy, 41 cases with scar, and 16 cases with sulcus. Ten micrograms of bFGF were injected into the vocal folds under topical anesthesia 4 times in each patient. Therapeutic outcomes were examined with maximum phonation time (MPT), voice handicap index-10 (VHI-10), and GRBAS scale. RESULTS: MPT, VHI-10, and GRBAS scores significantly improved in all pathology groups. An improvement on the VHI-10 greater than five points was observed in 82% of atrophy cases, 78% of scar cases, and 67% of sulcus cases. Improvement on the VHI-10 was significantly better in the atrophy group than the scar or sulcus groups. The mild/moderate cases of scar and sulcus showed better improvement than severe cases. CONCLUSIONS: The current large case series indicates positive effects of intracordal injection of bFGF for improvement of voice with no severe adverse events. The effects appeared best for cases of atrophy, while the treatment of severe scar and sulcus requires further improvement. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2059-2064, 2021.

Inhaled fluticasone propionate reduces postoperative sore throat, cough, and hoarseness.

BACKGROUND: Sore throat is a common complication after surgery. Postoperative cough and hoarseness can also be distressing to patients. We sought to determine the effect of an inhaler steroid on sore throat, cough, and hoarseness during the first 24 hours of the postoperative period. METHODS: We enrolled 120 women with ASA physical status I or II and term singleton pregnancy who were scheduled for elective cesarean delivery under general anesthesia. Patients were randomized into 2 groups: in the sitting position, group F patients received 500 µg inhaled fluticasone propionate via a spacer device during 2 deep inspirations, after arrival in the operating room, and group C had no treatment. The patients were interviewed by a blinded investigator for postoperative sore throat, cough, and hoarseness at 1 and 24 hours after surgery. RESULTS: There were no significant differences in age, height, weight, body mass index, duration of surgery, intubation, and grade of laryngeal exposure between the 2 groups. The incidence of sore throat, cough, and hoarseness was significantly lower in group F (3.33%, 3.33%, and 3.33%) compared with the control group (36.67%, 18.33%, and 35%) (P < 0.05 for all comparisons), not only in the first postoperative hour but also 24 hours after surgery (13.33%, 13.33%, and 25% in group F vs 40%, 41.67%, and 50% in the control group). The incidence of moderate and severe hoarseness in group F at the first hour was significantly less than the control group (P < 0.05). CONCLUSIONS: Inhaled fluticasone propionate decreases the incidence and severity of postoperative sore throat, cough, and hoarseness in patients undergoing cesarean delivery under general anesthesia.

Oral flurbiprofen spray for postoperative sore throat and hoarseness: a prospective, randomized, double-blind, placebo-controlled study.

BACKGROUND: Sore throat and hoarseness are common complications after surgery. Flurbiprofen spray has been successfully used for treatment of oral inflammations, but its effects on postoperative sore throat and hoarseness are unknown. We conducted this study to evaluate the effectiveness of flurbiprofen spray on postoperative sore throat and hoarseness, by comparing it with benzydamine hydrochloride spray and placebo. METHODS: One hundred fifty patients who were scheduled to undergo elective ear surgery were enrolled. Patients were randomized to three groups of 50 patients each; flurbiprofen oral spray, benzydamine hydrochloride oral spray and placebo spray groups. Patients received sprays just before intubation, and the incidence and severity of postoperative sore throat and hoarseness were evaluated by a blinded investigator at 0, 1, 6 and 24-hour post extubation. Patients were also questioned for possible side effects at all time points. RESULTS: The sore throat severity scores were significantly lower in treatment groups when compared to placebo group at all time points (P=0.003/108). Similarly, the incidence of sore throat was significantly lower in both of the treatment groups (P=0.007/104). The incidence of hoarseness and hoarseness scores were significantly lower in treatment groups when compared to placebo group (P=0.006/105 and P=0.005/104, respectively). While none of the patients complained of any adverse effects in flurbiprofen group, only two patients in benzydamine hydrochloride group experienced numbness. CONCLUSIONS: Both oral flurbiprofen and benzydamine hydrochloride sprays were found to be more effective than placebo in decreasing the incidence and severity of postoperative sore throat and hoarseness, with no adverse effects.

Primary Laryngeal Tuberculosis: Our Experiences at a Tertiary Care Teaching Hospital in Eastern India.

INTRODUCTION: Primary laryngeal tuberculosis is a chronic bacterial infection of the larynx by Mycobacterium tuberculosis without affecting the lungs. It is a rare type of extrapulmonary tuberculosis seen in clinical practice. OBJECTIVES: This study aimed to evaluate the clinical presentation, diagnosis, and treatment of primary laryngeal tuberculosis at a tertiary care teaching hospital in eastern India. MATERIALS AND METHODS: This is a retrospective study of 11 cases of primary laryngeal tuberculosis managed between December 2013 and January 2018. The detailed clinical presentations, investigations, and treatment of primary laryngeal tuberculosis of the patients were studied. RESULTS: Primary laryngeal tuberculosis is common in men with mean age of 38.63 years. Hoarseness of the voice is the most common symptom, and the most common site for primary laryngeal tuberculosis is the vocal fold with ulcerative lesion. Endoscopic examinations of the larynx in laryngeal tuberculosis are nonspecific and are to be confused with laryngeal cancer. Histopathological and bacteriological examinations are confirmatory tests for the diagnosis. After confirmation of the diagnosis, all patients had taken antitubercular therapy for 6 months, which gave excellent outcome. CONCLUSIONS: Delayed diagnosis or untreatable laryngeal tuberculosis will lead to high morbidity and mortality of the patient. Although primary laryngeal tuberculosis has nonspecific clinical presentations, it is very important to have a high index of suspiciousness to rule out tubercular lesion in the larynx as this disease is curable.

[Efficacy of systemic glucocorticoids combined with inhaled steroid on children with acute laryngitis].

Objective: To evaluate the efficacy of systemic glucocorticoid (steroid) combined with high dose inhaled steroid in the treatment of children with acute laryngitis. Methods: A total of 78 children with acute laryngitis were randomly divided into study group(n=40) and control group(n=38) between November 2016 and April 2017. In addition to routine treatment of anti infection and symptomatic treatment, Dexamethasone injection(0.3-0.5 mg/kg, 1-3 d, according to the patient's condition) was provided to each group. In addition to the treatment mentioned above, the study group were assigned to receive 1.0 mg Budesonide suspension for inhalation, oxygen-driven atomizing inhalation, every/30 minutes, 2 times in a row, after that every 12 hours. The improvement of inspiratory dyspnea, hoarseness, barking cough and wheezing of both groups was evaluated at 30 min, 1 h, 2 h, 6 h, 12 h, 24 h and 72 h after treatment.Sigmaplot 11.5 software was used to analyze the data. Results: No significant difference was detected in terms of inspiratory dyspnea, hoarseness, barking cough or stridor score before treatment between the two groups(P>0.05). Compared with those before treatment, symptoms of inspiratory dyspnea, hoarseness, barking cough and stridor score of both groups improved markedly at 12 h and 24 h after treatment(P<0.05). While there was no significant difference regarding inspiratory dyspnea, hoarseness, barking cough or stridor score at each time point after treatment between the two groups(P>0.05). The effective rate was 92.50% and 92.11% in study group and control group, respectively, and no significant difference was noted (P>0.05). Conclusion: Compared with single systemic glucocorticoid, systemic glucocorticoids combined with inhaled steroid possessed similar efficacy in treating acute laryngitis and relieving laryngeal obstruction of children.

Painful rash with hoarseness: an atypical presentation of syphilis.

Syphilis is a sexually transmitted disease that can affect multiple organ systems, with central nervous system involvement at any stage. We present a 53-year-old woman with an unusual truncal rash with painful anogenital lesions, accompanied by patchy alopecia, oral lesions, photophobia and hoarseness. She was found to have positive serological tests for syphilis with cerebrospinal fluid findings suggestive of neurosyphilis. She underwent a 14-day course of intravenous penicillin G and exhibited successful resolution of painful anogenital lesions as well as marked improvement in dermatological, oropharyngeal, laryngeal, and neurological symptoms.