Exploring the immunological basis of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome: immunohistochemical staining features of palatine tonsils.

OBJECTIVES: Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is the most common periodic fever syndrome during early childhood period with regular febrile attacks of sterile upper airway inflammation. The cessation of attacks following tonsillectomy points to fundamental role of tonsil tissue on etiopathogenesis of disease, which is not clarified satisfactorily. The aim of this study is to explore the immunological basis of PFAPA by evaluating the cellular properties of tonsils, and microbial exposition such as Helicobacter pylori on tonsillectomy materials. METHODS: The paraffinized tonsil samples of 26 PFAPA and 29 control patients with obstructive upper airway disorder were compared in terms of immunohistochemical staining features including CD4, CD8, CD123, CD1a, CD20, and H. pylori. RESULTS: The median number of CD8+ cells was 1485 (1218-1287) in PFAPA while it was 1003 (852-1261.5) in control group and the difference was statistically significant (p=0.001). Similarly, CD4+ cell counts were statistically higher in PFAPA group than control (833.5 vs 622). The ratio of CD4/CD8 did not differ between two groups; also, there was no statistically difference in terms of the other immunohistochemical staining results, such as CD20, CD1a, CD123 and H. pylori. CONCLUSION: This is the largest number of pediatric tonsillar tissue study of PFAPA patients in current literature and we emphasized the triggering effects of CD8+ and CD4+ T-cells on PFAPA tonsils. KEY POINTS: • The cessation of attacks following tonsillectomy points to fundamental role of tonsil tissue on etiopathogenesis of disease, which is not clarified satisfactorily. • In current study, 92.3% of our patients did not experience any attacks following operation similarly with literature. • We observed the increased number of CD4+ and CD8+ T cell counts on PFAPA tonsils compared to control group and emphasized the active role of both CD4+ and CD8+ cells localized on PFAPA tonsils in immune dysregulation. • Some other cell types evaluated in this study such as CD19+ (B cells), CD1a (dendritic cells), and CD123 (IL-3 receptors, for pluripotent stem cells) and H. pylori did not differ in PFAPA patients compared to the control group.

Heterotopic Gastric Mucosa in the Proximal Esophagus: Prospective Study and Systematic Review on Relationships with Endoscopic Findings and Clinical Data.

Cervical inlet patches (CIP) are common endoscopic findings with uncertain pathogenesis and clinical significance. We aimed to perform a systematic review and prospective study of clinical data and endoscopic findings related to CIP. It was a prospective single-center study conducted between 10/01/2017 and 9/01/2018. Forty patients with histopathologically confirmed CIP were compared with 222 individuals in the reference group. The systematic review was executed in accordance with the PRISMA guideline. Alcohol consumption tended to be higher among patients with CIP (3.0 ± 4.6 vs. 1.9 ± 5.0 standard drinks/week CIP patients and reference group, respectively; p < 0.001). Dysphagia was more frequent among patients with CIP (25% vs. 1.4%, CIP patients and reference group, respectively; p < 0.001), and sore throat and hoarseness were less frequent in patients with CIP (17.5% vs. 26.6% CIP patients and reference group, respectively; p < 0.01). In the multivariate regression analysis, the only risk factor of CIP occurrence was dysphagia (OR 21.9, 95%CI 4.9-98.6; p < 0.001). Sore throat and hoarseness were a reverse-risk factor of CIP diagnosis (OR 0.3, 95%CI 0.1-0.93; p = 0.04). Clinical data and coexisting endoscopic findings were not related to CIP. In the presented study, dysphagia was related to CIP occurrence, and sore throat and hoarseness tended to be less frequent among patients with CIP.

Potential active constituents responsible for treating acute pharyngitis in the flowers of Hosta plantaginea (Lam.) Aschers and their pharmacokinetics.

In Asia, the flower of Hosta plantaginea (Lam.) Aschers (hosta flower) is both an edible food and medicine. The hosta flower is often used as a material for cooking porridge and scented tea and in combination with other plants for alleviating pharyngitis. To clarify the anti-pharyngitis effect of the hosta flower and evaluate its potential active ingredients, an ethanol extract of the hosta flower was prepared and partially purified via chromatography on a column packed with D101 macroporous resin, which was eluted with different concentrations of ethanol. The anti-pharyngitis effect of the crude extract and the various partially purified fractions was examined in an ammonia-induced acute pharyngitis rat model. The 30% ethanol-eluted fraction significantly alleviated the severity of pharyngitis in the rat, as evaluated by changes in the levels of cytokines (IL-1ß, IL-6, and TNF-α) and histological changes in the pharynx tissues. Subsequent HPLC-QTOF/MS (high-performance liquid chromatography coupled with quadrupole-time of flight tandem mass spectrometry) analysis of this fraction revealed kaempferol and its glycosides as the main components. Three of the main components were isolated and identified by 1D NMR. Their pharmacokinetics were studied for the first time by UHPLC-QQQ/MS (ultrahigh-performance liquid chromatography coupled with mass spectrometry). The findings suggested that the 30% ethanol-eluted fraction of the hosta flower extract may be a potential functional food for treating pharyngitis.

Reactive arthritis: images.

Reactive arthritis is an extremely rare spondyloarthritis that affects the peripheral joints and spine, resulting in common symptoms such as arthritis, urethritis, conjunctivitis, and mucocutaneous lesions. On rare occasions, oral lesions such as circinate erosions on the hard and soft palate, gums, tongue, and cheeks may occur. Reactive arthritis may develop during or after genitourinary or gastrointestinal bacterial infections such as Shigella, Salmonella, Yersinia, and Chlamydia. A 36-year-old man presented with circinate balanitis, urethral discharge, oligoarthralgia, conjunctivitis, lymphadenopathy, pharyngitis, and erythematous lesions on the palate. Culture examination showed presence of Neisseria gonorrhoeae and antibiotic treatment resulted in improvement of conjunctivitis and the lesions on the penis. However, severe oligoarthralgia, palatal erosions that increased in severity and size, and depilated areas on the tongue were observed. The definitive diagnosis was reactive arthritis. The prevalence of sexually transmitted infections is increasing, highlighting the need to increase awareness of associated risks such as reactive arthritis. Moreover, consideration of non-specific oral manifestations in a systemic context may aid in effective diagnosis and treatment, suggesting the need for multidisciplinary teams.

Comparison of the efficacy of supraglottic airway devices in low-risk adult patients: a network meta-analysis and systematic review.

Numerous supraglottic airway device (SADs) have been designed for adults; however, their relative efficacy, indicated by parameters such as adequacy of sealing, ease of application, and postinsertion complications, remains unclear. We conducted a systematic review and network meta-analysis to evaluate the efficacy of various SADs. We searched electronic databases for randomized controlled trials comparing at least two types of SADs published before December 2019. The primary outcomes were oropharyngeal leak pressure (OLP), risk of first-attempt insertion failure, and postoperative sore throat rate (POST). We included 108 studies (n = 10,645) comparing 17 types of SAD. The Proseal laryngeal mask airway (LMA), the I-gel supraglottic airway, the Supreme LMA, the Streamlined Liner of the Pharynx Airway, the SoftSeal, the Cobra Perilaryngeal Airway, the Air-Q, the Laryngeal Tube, the Laryngeal Tube Suction II, the Laryngeal Tube Suction Disposable, AuraGain, and Protector had significantly higher OLP (mean difference ranging from 3.98 to 9.18 cmH2O) compared with that of a classic LMA (C-LMA). The Protector exhibited the highest OLP and was ranked first. All SADs had a similar likelihood of first-attempt insertion failure and POST compared with the C-LMA. Our findings indicate that the Protector may be the best SAD because it has the highest OLP.Systematic review registration PROSPERO: CRD42017065273.

High or low temperature extraction, which is more conducive to Triphala against chronic pharyngitis?

OBJECTIVE: Explore the effects of high-temperature reflux extraction and low-temperature decompressing inner ebullition on Triphala's chemical composition and anti-chronic pharyngitis activity. METHODS: The network pharmacology was used to analyze the material basis, targets and pathways of Triphala for chronic pharyngitis. HPLC were used to compare the fingerprint profile and content of components between the two extracts. The antioxidant and anti-chronic pharyngitis activities of the two extracts were compared by DPPH assay and ammonia induced chronic pharyngitis model in rats. RESULTS: The network pharmacology results showed that the active ingredients of Triphala for chronic pharyngitis are epigallocatechin-3-gallate, (+)-catechin, epicatechin, epicatechin gallate, (+)-gallocatechin, quercetin, luteolin, leucodelphinidin and other flavonoids; phenolic acids such as gallic acid and ellagic acid; alkaloids such as ellipticine, cheilanthifoline; hydrolyzed tannins such as corilagin and chebulic acid. The high-temperature reflux extract and the low-temperature decompressing inner ebullition extract have extremely significant differences in the fingerprint profile. Among them, the content of gallic acid, ellagic acid, chebulic acid, catechin, epicatechin, corilagin, quercetin, and epicatechin gallate in the reflux extract is 1.1-5.3 times as much as decompressing inner ebullition extract. The free radical scavenging ability of reflux extract is significantly stronger than that of decompression extract (p < 0.01), and it has a repairing effect on pharyngeal mucosal damage (reducing keratinization or hyperplasia of mucosal epithelium, reducing inflammatory cell infiltration and bleeding), and reducing IL-1ß (P＜0.05), IL-6 (p＜0.05), TNF-α overexpression ability is stronger than the decompressing inner ebullition extract. CONCLUSIONS: gallic acid, ellagic acid, chebulic acid, catechin, epicatechin, corilagin and epicatechin gallate are the basic aglycones or oligomers of tannin. High temperature reflux extraction can significantly promote the occurrence of the hydrolysis of tannins and significantly increases the content of these components.Therefore, its anti-chronic pharyngitis activity is enhanced. It is suggested that high temperature reflux extraction should be used in the treatment of chronic pharyngitis.

Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome: Relapse and Tonsillar Regrowth After Childhood Tonsillectomy.

OBJECTIVES/HYPOTHESIS: Tonsillectomy is an effective treatment for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, but the role of adenoidectomy, as well as later tonsillar regrowth, is unclear. To find out if the volume of lymphoid tissue is pivotal to the efficacy, we analyzed the association between the relapse of the symptoms of PFAPA syndrome and regrowth of tonsillar tissue after tonsillectomy or adenotonsillectomy. STUDY DESIGN: Prospective cohort study of operated PFAPA pateints. METHODS: We invited all patients that had undergone tonsillectomy or adenotonsillectomy due to PFAPA syndrome at the Oulu University Hospital, Oulu, Finland, between the years 1990 and 2007, at the age of ≤12 years, to a follow-up visit, after an average period of 9.8 years after their diagnoses. Out of the 132 invited, 94 (71%) participated in the follow-up study. RESULTS: At the follow-up study visit, 5 (5%) of the 94 PFAPA syndrome cases experienced recurrent fevers. The regrowth of palatine tonsillar tissue was seen in four of them (80%) as compared to 19/89 (21%) of symptom-free patients (P = .006). Two of the patients with clear PFAPA relapse at the time of the study visit were reoperated with clear effect on the symptoms. At the time of the study visit, 59/63 (94%) of the patients who had undergone adenotonsillectomy and 30/31 of the patients (97%) who had undergone tonsillectomy earlier were free of fever flares (P = .99). CONCLUSION: Palatine tonsil regrowth was associated with PFAPA syndrome relapse after tonsillectomy. Reoperation might be a treatment option in these patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2149-E2152, 2021.

Outcome of an outpatient specialty clinic for chronic epipharyngitis.

OBJECTIVE: In Japan, chronic epipharyngitis became a subject of interest in the 1960s and is currently garnering renewed attention. Previous studies have focused only on the similarities between the immunological characteristics of the tonsil and epipharynx and reported the efficacy of epipharyngeal abrasive therapy (EAT) in patients with IgA nephropathy. However, endoscopic findings of chronic epipharyngitis have not yet been fully evaluated, and. this study aimed to elucidate those findings. METHODS: The study period was from November 2016 to October 2017. Two hundred and twelve new patients visited the specialty outpatient clinic for EAT. Age distribution and mean age of patients, sex, chief complaint, diagnosis at other departments and outcomes were retrospectively reviewed based on medical records. Band-limited light endoscopy was performed, and the findings were videotaped in 102 of the 212 new patients, who underwent endoscopic EAT for the first time. RESULTS: The study included 32 men and 70 women with a mean age of 46.0 years (range, 22-83 years). The most common complaint was postnasal drip (42 patients), followed by pharyngeal pain (12 patients), and throat discomfort (11 patients). The outcomes of 74 patients who continued treatment until the last session were; complete cure in 48.6% of cases, marked improvement in 21.6%, improvement in 16.2%, and no change in 13.5%. Band-limited light endoscopic findings included black spots (73%), granular changes (76%), vessel truncations (92%), crust/mucus adhesion (54%), adenoidal hypertrophy (31%) and tonsil cysts (7%). With regard to the appearance of the mucous membranes, 48% patients had an ivory-like-colored mucous membrane, 72% had a green vascular network, and 89% had a dark red to reddish-brown appearance. Six to nine months' EAT remarkably improved their symptoms with resolution of the endoscopic findings in 86% of the patients. CONCLUSION: Nasal endoscopy using band-limited light is useful for diagnosis and management of chronic epipharyngitis. We believe that this study not only provides information to help the diagnosis of chronic epipharyngitis but also contributes to treat sick patients suffering from chronic epipharyngitis.

The efficacy of a compounded micronutrient supplement on the incidence, duration, and severity of the common cold: A pilot randomized, double-blinded, placebo-controlled trial.

PURPOSE: Viral upper respiratory infections are associated with significant health and economic impact. This study sought to determine the efficacy of routine immune system micronutrient supplementation on the incidence, duration and severity of common cold symptoms. METHODS: This pilot study was a randomized, double-blinded, placebo-controlled trial of N = 259 with asymptomatic participants aged 18 to 65 in two cold seasons of 2016 and 2017. The treatment group received an immune system targeted micronutrient caplet, while the placebo group received a micronized cellulose caplet externally identical to the treatment caplet. Weekly surveys were sent electronically to participants to document common cold incidence, duration and severity. Primary statistical results were obtained using mixed-effects logistic regressions to account for longitudinal measurements for participants. RESULTS: The odds of acquiring an upper respiratory infection, adjusted for potential confounders, was estimated to be 0.74 times lower in the treatment group (p = 0.14). The odds of reporting specific symptoms were statistically lower in the treatment arm compared to the placebo arm for runny nose (OR = 0.53, p = 0.01) and cough (OR = 0.51, p = 0.04). Shorter durations of runny nose and cough were also observed in the treatment arm compared to placebo (both p < 0.05). There was no significant difference in severity of symptoms in either group. The observed proportion of reported cold symptoms in the treatment group was lower compared to the placebo group between late January and February in two consecutive cold seasons. Given the physical, workplace and economic impact of upper respiratory infections, this low cost and low risk intervention should be further studied with more robust investigation and meticulous experimental design.

Streptococcus pyogenes genes that promote pharyngitis in primates.

Streptococcus pyogenes (group A streptococcus; GAS) causes 600 million cases of pharyngitis annually worldwide. There is no licensed human GAS vaccine despite a century of research. Although the human oropharynx is the primary site of GAS infection, the pathogenic genes and molecular processes used to colonize, cause disease, and persist in the upper respiratory tract are poorly understood. Using dense transposon mutant libraries made with serotype M1 and M28 GAS strains and transposon-directed insertion sequencing, we performed genome-wide screens in the nonhuman primate (NHP) oropharynx. We identified many potentially novel GAS fitness genes, including a common set of 115 genes that contribute to fitness in both genetically distinct GAS strains during experimental NHP pharyngitis. Targeted deletion of 4 identified fitness genes/operons confirmed that our newly identified targets are critical for GAS virulence during experimental pharyngitis. Our screens discovered many surface-exposed or secreted proteins - substrates for vaccine research - that potentially contribute to GAS pharyngitis, including lipoprotein HitA. Pooled human immune globulin reacted with purified HitA, suggesting that humans produce antibodies against this lipoprotein. Our findings provide new information about GAS fitness in the upper respiratory tract that may assist in translational research, including developing novel vaccines.

Comparison of antibiotic prescriptions in adults and children with upper respiratory tract infections in Bangka Tengah primary health care centers.

Background Inappropriate antibiotic therapy is accelerating the development of antimicrobial resistance (AMR). Upper respiratory tract infections (URTIs) are predominantly caused by viruses, resulting in the prescription of antibiotics to a few selected patients. Previous studies in primary health care centers (PHCCs) in Indonesia have shown a high percentage of antibiotic therapy for URTIs. This study tries to analyze the difference in profiles of antibiotic prescription in the treatment of children and adults with URTI in Bangka Tengah, Indonesia. Methods Random prescriptions from patients diagnosed with URTIs (sinusitis, bronchitis, common cold, and pharyngitis) from all PHCCs in Bangka Tengah were collected from January to February 2018. Prescriptions from patients with overlapping diagnoses, such as URTI with diarrhea or typhoid, were excluded. Results During the two months of data collection, 1348 prescriptions for adults and children with URTIs were studied. Children were 1.30 (95% CI, 1.03-1.58) times more likely to be treated with antibiotics compared to adults. Amoxicillin was the most commonly prescribed antibiotic both in children (92.3%) and adults (78.6%). Ciprofloxacin was commonly prescribed in adults (14.6%) but not in children (0.3%). Conclusions This study confirms the major antibiotic overuse in patients with URTI, especially in children. Owing to the fact that children are more likely to get URTI of viral origin, they receive high percentage of antibiotic therapy. These findings support the need for collaborated intervention to decrease unnecessary prescription of antibiotics in Bangka Tengah.

Surgical outcomes and unique histological features of tonsils after tonsillectomy in adults with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome.

OBJECTIVES: Data on the adult-onset periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome are scarce. European studies reported that unlike pediatric-onset PFAPA, tonsillectomy is ineffective for adult-onset PFAPA. The aims of this study were (1) to assess the response to tonsillectomy in a cohort of Japanese adult-onset PFAPA patients and (2) to evaluate the histologic appearance of tonsils in adult-onset PFAPA patients and to compare them with those of tonsils from age- and sex-matched controls with chronic tonsillitis. METHODS: In this retrospective cohort study, 5 adults with PFAPA and 15 controls who had undergone tonsillectomy were recruited. The size of the tonsil germinal centers was measured by hematoxylin and eosin staining, and the number and density of B and T lymphocytes in germinal centers were measured by immunohistochemistry, using CD3, CD4 and CD8 as T cell markers and CD20 as B cell marker. RESULTS: All patients had complete remission of the symptoms after surgery. PFAPA patients had significantly smaller germinal center areas than controls. The number and density of CD8+ cells in germinal centers were significantly lower in tonsils from PFAPA compared with controls. No differences were found between the two groups in CD3+, CD4+, and CD20+ cells. These results are compatible with the tonsillar features of pediatric-onset PFAPA. CONCLUSION: Our report demonstrates that tonsillectomy might be effective for adult-onset PFAPA and that tonsils of adult- and pediatric-onset PFAPA share the same histological features. These results suggest that the pathogenic mechanisms of adult- and pediatric-onset PFAPA are identical.

Sore throat turned to be a bronchogenic carcinoma with superior vena cava syndrome.

Superior vena cava (SVC) syndrome is a group of symptoms caused by complete or partial obstruction of the flow of blood through the SVC. The obstruction is, in most cases, caused by the formation of thrombus or infiltration of a tumour through the vessel wall. The result is venous congestion that creates a clinical situation relating to increase in the venous pressure in the upper part of the body. Symptoms commonly associated with vena cava syndrome include cough, dyspnoea, swelling of the neck, face and the upper extremities and dilation of the chest vein collaterals. In this paper, we examine the case of a 50-year-old man who presented to the emergency department with 'sore throat' which can be easily misdiagnosed as a case of uncomplicated acute pharyngitis. It was a real challenge to diagnose our patient as SVC syndrome caused by bronchogenic carcinoma.

A case report of Talaromyces marneffei Oro-pharyngo-laryngitis: a rare manifestation of Talaromycosis.

BACKGROUND: The incidence of Taralomyces marneffei infection in HIV-infected individuals has been decreasing, whereas its rate is rising among non-HIV immunodeficient persons, particularly patients with anti-interferon-gamma autoantibodies. T. marneffei usually causes invasive and disseminated infections, including fungemia. T. marneffei oro-pharyngo-laryngitis is an unusual manifestation of talaromycosis. CASE PRESENTATION: A 52-year-old Thai woman had been diagnosed anti-IFNÉ£ autoantibodies for 4 years. She had a sore throat, odynophagia, and hoarseness for 3 weeks. She also had febrile symptoms and lost 5 kg in weight. Physical examination revealed marked swelling and hyperemia of both sides of the tonsils, the uvula and palatal arches including a swelling of the epiglottis, and arytenoid. The right tonsillar biopsy exhibited a few intracellular oval and elongated yeast-like organisms with some central transverse septum seen, which subsequently grew a few colonies of T. marneffei on fungal cultures. The patient received amphotericin B deoxycholate 45 mg/dayfor 1 weeks, followed by oral itraconazole 400 mg/day for several months. Her symptoms completely resolved without complication. CONCLUSION: In patients with anti-IFN-É£ autoantibodies, T. marneffei can rarely cause a local infection involving oropharynx and larynx. Fungal culture and pathological examination are warranted for diagnosis T. marneffei oro-pharyngo-laryngitis. This condition requires a long term antifungal therapy.

The epipharynx-kidney axis triggers glomerular vasculitis in immunoglobulin A nephropathy.

Macroscopic hematuria concomitant with acute pharyngitis is a characteristic feature of immunoglobulin A nephropathy (IgAN). Although the underlying mechanism of worsening hematuria has not been fully elucidated, activation of the innate immune system of nasopharynx-associated lymphoid tissue is thought to play an important role. The epipharynx is an immunologically activated site even under normal conditions, and enhanced activation of innate immunity is likely to occur in response to airborne infection. As latent but significant epipharyngitis presents in most IgAN patients, it is plausible that acute pharyngitis due to airway infection may contribute as a trigger of the epipharyngeal innate immune system, which is already upregulated in the chronically inflamed environment. The aim of this review was to discuss the mechanism of epipharynx-kidney axis involvement in glomerular vasculitis responsible for the worsening of hematuria in IgAN.

Pharyngeal Immunity in Early Vertebrates Provides Functional and Evolutionary Insight into Mucosal Homeostasis.

The pharyngeal organ is located at the crossroad of the respiratory and digestive tracts in vertebrate, and it is continuously challenged by varying Ags during breathing and feeding. In mammals, the pharyngeal mucosa (PM) is a critical first line of defense. However, the evolutionary origins and ancient roles of immune defense and microbiota homeostasis of PM are still unknown. In this study, to our knowledge, we are the first to find that diffuse MALT is present in PM of rainbow trout, an early vertebrate. Importantly, following parasitic infection, we detect that strong parasite-specific mucosal IgT and dominant proliferation of IgT+ B cell immune responses occurs in trout PM, providing, to our knowledge, the first demonstration of local mucosal Ig responses against pathogens in pharyngeal organ of a nonmammal species. Moreover, we show that the trout PM microbiota is prevalently coated with secretory IgT and, to a much lesser degree, by IgM and IgD, suggesting the key role of mucosal Igs in the immune exclusion of teleost pharyngeal bacteria. Overall, to our knowledge, our findings provide the first evidence that pharyngeal mucosal immunity appear earlier than tetrapods.