Oral Ulcers Research Articles

A retrospective analysis of syphilis cases with a focus on otolaryngology at a university hospital

ObjectivesIn recent years, there has been a notable increase in syphilis cases in Japan and Western countries. Syphilis, a classic sexually transmitted disease caused by treponemas, presents diagnostic challenges due to its diverse clinical manifestations. This study explores the diagnosis of syphilis in patients treated at our hospital. MethodsWe retrospectively reviewed patients who visited our hospital between April 2015 and March 2024. The review focused on the patients' clinical backgrounds, onset times, symptoms, diagnostic processes, and clinical courses. ResultsOur hospital had 45 cases of syphilis. Forty-five cases of syphilis were diagnosed as syphilis in our hospital (13 cases were diagnosed in the Otolaryngology: ENT department). The median age was 40 years, with a significant male predominance (male-to-female ratio of 34:11). The median duration from the onset of subjective symptoms to syphilis diagnosis was 54 days. The timeframe from the initial clinic visit to diagnosis ranged from 1 to 57 days, with a median of nine days. Notably, 47.5% of the patients reported a history of employment or patronage in the sex industry. 73.3% of patients presented to local clinics with any kind of subjective symptoms, but syphilis was often missed in the differential diagnosis. Patients visiting the ENT department were referred to our hospital with a diagnosis of persistent oral ulcer, oropharyngeal carcinoma and neck lymphadenopathy. Histological and cytological evaluation was performed in 33% of patients, but the diagnosis was often difficult to make. Additionally, some patients initially denied using sex services at their first visit but later disclosed this during subsequent visits to the Department of Infectious Diseases, highlighting the critical role of thorough medical history assessments. ConclusionDiagnosing syphilis can be challenging unless the physician specifically suspects it. It is crucial to consider syphilis in cases of pharyngeal mucosal inflammation and neck lymphadenopathy. This study highlights the need for heightened awareness and education regarding the signs and symptoms of syphilis, particularly oropharyngeal and skin findings, to ensure timely diagnosis and treatment.

Association of oral manifestations with severity of the disease in ulcerative colitis patients

ObjectiveInflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), are chronic conditions primarily affecting the intestines. This study aims to identify the nature and frequency of oral symptoms and signs in patients with ulcerative colitis and to explore the connection between these complications and the activity of the disease.MethodsThis descriptive-analytical study involved ulcerative colitis patients who visited the gastroenterology clinic at Shahid Sayad Shirazi Hospital in Gorgan, along with an equal number of healthy companions as a control group in 2019. A gastroenterology internist assessed the disease severity through clinical examination and a simple clinical disease activity index for colitis patients. The collected data were then analyzed statistically using SPSS version 19.ResultsThe average age of patients in the case group was 41.84 ± 11.66 years, while in the control group it was 40.43 ± 12.67 years. There was a significant correlation between difficulty swallowing, burning sensation in the mouth, vomiting, acidic taste, the presence of oral ulcers, and a coated tongue with the severity of disease activity (p < 0.05). However, no significant relationship was found between other variables and the severity of disease activity (p > 0.05).ConclusionThe results of this study confirm that as the severity of ulcerative colitis increases, the occurrence of oral lesions also rises, particularly during severe disease activity. Among oral symptoms, dry mouth had the highest incidence, followed by bad breath and changes in taste. The most common oral lesions observed were a coated tongue, grooved tongue, and oral ulcers, respectively.

Oral complications during the two waves of COVID-19 pandemic in China: a prospective cross-section analysis of 510 cases using questionnaire

BackgroundOral complications such as parageusia, xerostomia, and oral ulcers are frequently observed in patients with COVID-19. The aim of this study was to understand the oral complications and their influencing factors during the two waves of the COVID-19 pandemic in China between December 2022 and May 2023.MethodsA total of 347 patients during the COVID-19 pandemic from December 2022 and January 2023 and 163 patients during the second COVID-19 pandemic were recruited through the Disease Prevention and Control Reporting System. Data on oral complications were collected via researcher-made questionnaires.ResultsDuring both pandemic periods, more than 50% of the subjects developed oral complications. Specifically, the incidence of parageusia, pathological tongue coating, and xerostomia all exceeded 20%, while the incidence of oral ulcers surpassed 7%. Patients with allotriosmia and xerostomia had a significantly higher likelihood of developing other oral complications. Hospitalized patients requiring supplemental oxygen had a significantly higher incidence of oral complications.ConclusionsThe results of our study underline that oral complications during the COVID-19 pandemic are prevalent, and their incidence has not decreased during the subsequent pandemic. In the context of the ongoing global spread of COVID-19, this study lays the foundation for physicians in recognizing and managing oral complications, which will improve the oral health of communities globally.

Infliximab versus interferon-alpha in the treatment of Behçet's Syndrome: Clinical data from the BIO-BEH&Ccedil;ET'S randomised controlled trial.

Whilst biologic therapy is used for Behçet's Syndrome of all subtypes refractory to first-line immunomodulation, there has been an absence of high-quality evidence-and no predictive biomarkers to optimally inform choice. BIO-BEH&Ccedil;ET'S was a randomised, controlled, head-to-head clinical trial comparing the two most frequently used biologics in active refractory Behçet's. Bayesian-designed, pragmatic, standard of care, two-arm, parallel head-to-head trial at four UK centres. Patients with active disease randomised to infliximab or interferon-α2a, and received follow-up with symptom-directed examination at Weeks 12 and 24. Primary outcome was Behçet's Disease Activity Index (BDAI) at 12 weeks. Secondary outcomes included BDAI at 24 weeks and significant improvement in individual organ systems, including ocular symptoms, oral and genital ulcers, arthritis pain, quality of life, disease activity, and steroid use. Biomarkers were also investigated but are reported elsewhere. 79 patients were recruited. Both treatments were equally effective, with a mean difference of 0.13 in BDAI (80% CI: -0.19, 0.46). No significant differences were observed for secondary outcomes, though there were clinically significant within-group reductions for each over time. A modest steroid-sparing effect was observed, with complete cessation of steroids in 20% and 44% of those randomised to infliximab and interferon-α2a, respectively. There was a trend for minor benefit in favour of infliximab in terms of tolerability and persistence. In this first reported, high-quality, head-to-head trial of two biologics in Behçet's, both infliximab and interferon-α2a showed comparable short-term clinical efficacy and safety in refractory active disease of all subtypes. EudraCT: 2014-005390-36; ISRCTN: ISRCTN49793874.

Anogenital Lesions in Children: A Critical Alert for Pediatricians.

A 7-y-old girl presented to the pediatric department with a two-week history of a skin lesion in the anogenital region. She appeared well-nourished, quiet, afebrile; vitals and her systemic examination was normal. Examination revealed a greyish white wart-like perianal lesion, unusual for her age. Further history revealed the child had become withdrawn, avoiding play recently, and had oral and vaginal ulcers a month earlier without treatment. These findings raised suspicion of sexual abuse. Investigations confirmed positive VDRL (1:64 titres), positive TPHA, and negative results for her parents' TPHA and HIV. A medicolegal case was registered, involving child welfare services and police. A psychiatrist diagnosed post-traumatic stress disorder and recommended counselling. Treatment with a single dose of intramuscular Benzathine penicillin led to improvement, with VDRL titres decreasing to 1:8 and complete resolution of the lesion after 3 months. Pediatricians are pivotal in identifying and managing child sexual abuse cases promptly.

Identification of a novel variant in the LAMB3 gene in a patient with a distinct junctional epidermolysis bullosa laryngo-onycho-cutaneous syndrome phenotype.

Junctional epidermolysis bullosa (JEB) represents a rare mechanobullous genodermatosis, characterized by fragility and blister formation of the skin and mucous membranes. Within the JEB spectrum, laryngo-onycho-cutaneous (LOC) syndrome is a rare subtype that manifests with excess granulation tissue of the eyes, nails, skin, and larynx. Thus far, the LOC subtype has been linked predominantly to mutations in LAMA3, disrupting the epidermal basement membrane zone. We present a unique case of a congenitally affected female with numerous cutaneous eroded plaques, oral ulcers, nail dystrophy, and laryngeal involvement phenotypically consistent with the rare JEB LOC subtype. Genetic testing revealed a previously unreported homozygous variant in the LAMB3 gene (p.C316Y) highlighting a novel variant in the LAMB3 gene and its association with the LOC phenotype of JEB.

Phase Ib study of anti-PD-L1 monoclonal antibody socazolimab in combination with nab-paclitaxel as first-line therapy for advanced urothelial carcinoma.

PD-1/PD-L1 immune checkpoint inhibitors (ICIs) have demonstrated activity in the post-platinum and platinum-ineligible settings for advanced urothelial carcinoma (aUC). As only around 50% of patients with aUC can tolerate platinum-containing treatment, treatments combining first-line ICIs with non-platinum drugs are urgently needed. Therefore, we assessed the safety and efficacy of the anti-PD-L1 monoclonal antibody Socazolimab in combination with nab-paclitaxel as first-line therapy in aUC (NCT04603846). This was a multi-center, single-arm, phase Ib study that enrolled patients with treatment-naive aUC. Patients received Socazolimab (5mg/kg) and nab-paclitaxel (260mg/m2) Q3w. The primary endpoint was safety and tolerability of the combination regimen. Second endpoints were the objective response rate (ORR) and progression-free survival. Between September, 2020 and September, 2021, 20 patients with urothelial carcinoma were enrolled, arising from renal pelvis (5), bladder (8), and ureter (7). After a median follow-up of 17 months, the median number of treatment cycles was 12. No patients had dose limiting toxicity. All patients had treatment-related adverse events (TRAEs), most of which were grade 1 or 2. The common TRAEs (≥20%) were peripheral neurotoxicity, alopecia, rash, increased ALT, weight loss, weakness, pruritus, increased AST, increased γGT, increased ALP, neutropenia, emesis, and anorexia. Nine patients (45%) developed grade 3 TRAEs including peripheral neurotoxicity (30.0%), increased ALT (10.0%), and increased γGT (5.0%). Two patients (10%) discontinued treatment because of grade 3 mouth ulcer (n = 1) and grade 2 lung fibrosis (n = 1). No grade 4-5 TRAEs were observed. Among the 17 patients who had received at least one tumor assessment, ORR was 58.8% (95% CI, 32.9%-81.6%) and the median progression-free survival was 8.3 months (95% CI, 5.2-19.5). The median duration of response was 13.3 months (95% CI, 2.0-20.1), and the overall survival was 19.5 months (95% CI, 11.2-not reached). Socazolimab combined with nab-paclitaxel has shown good safety and promising antitumor activity as first-line therapy in patients with advanced urothelial carcinoma.

Oral health and chronic kidney disease: Findings from a descriptive survey in Lagos, Nigeria.

Background: Chronic kidney disease (CKD) is a global public health problem, characterized by a progressive and irreversible decline in renal functions, and affecting up to 22.3% of Nigerians. Oral diseases are increasingly recognized to have a bidirectional relationship with CKD, contributing to systemic inflammation, infections, protein-energy wasting, and atherosclerotic complications. Given this interconnectedness, we aimed to explore the relationship between CKD and oral conditions among LASUTH patients to better understand and address these co-occurring health issues. Methods: This descriptive observational study was conducted in the nephrology unit of LASUTH. Patients aged &gt;20 years with a diagnosis of CKD were enlisted and a validated questionnaire with the modified WHO oral health status proforma was utilized to record clinical data: Estimated Glomerular Filtration Rate (EGFR), End-Stage Renal Disease (ESRD), Creatinine and Urinalysis from medical records and oral examination findings, Oral Hygiene Index-Simplified (OHI-S), Gingival Index (GI), Community Periodontal Index of Treatment needs (CPITN), oral malodour, and Oral lesions. Multivariate logistic regression analysis was conducted with adjustments for covariates like age, alcohol use, and BMI to determine the association between oral diseases and CKD. The significance level (p) was set at 0.05, with a confidence interval (CI) of 95%. Results: A total of 200 patients at different stages of CKD were included. The age range was 22–83 years. The majority were aged 31-60 years (mean age 55.22 ± 14.35 years); 69% were males; 7% were current smokers while 12% currently drank alcohol; 27% had eGFR&lt; 15 mL/min/1.73m2 (ESRD); 27% had Creatinine values &gt;1.3mg/dl; prevalence of Gingivitis was 72%; periodontitis was 14% (CPI score ≥3: Pocket depth of ≥4 mm); and poor OHI was 22%. The commonest oral lesions were white lesions 2%, candidiasis 4.5%, hyperpigmentation 22%, oral ulcers 5%, hemorrhagic lesions 12.5%, and Oral malodor 74.5%. Multiple logistic regression analysis revealed significantly increased odds of ESRD among uneducated respondents (OR 1.194; CI: 0.832-1.713); those &gt;60years (OR: 1.129; CI:0.436-2.923); current alcohol drinkers (OR:1.125; CI: 0.281-4.409); and smokers (OR:2.328; CI: 0.27-20.289). The odds of low stimulated saliva flow rate (OR: 1.181; CI:0.768-4.512), oral malodor (OR:1.093; CI: 0.763-1.565), and periodontal disease (OR: 1.242; CI: 0.698-2.209) were also significantly higher among those with ESRD. Conclusion: Individuals with CKD and ESRD may have a higher prevalence of oral diseases and conditions. There were significantly increased odds of ESRD among uneducated respondents, those over 60, current alcohol consumers, and smokers. Additionally, the odds of low stimulated saliva flow rate, oral malodor, and periodontal disease was also significantly higher among those with ESRD. This relationship may also be bidirectional, highlighting the need for appropriate oral self-care and regular dental-care utilization in patients with renal disease. The findings underscore the need for integrated healthcare approaches that consider both oral and renal health, providing a foundation for further research and targeted interventions.

Epstein Barr Virus Positive Mucocutaneous Ulcer versus Classic Hodgkin Lymphoma: Challenges in Diagnosis

Abstract Introduction/Objective Epstein- Barr virus positive mucocutaneous ulcer (EBVMCU) is a clinicopathologic entity first identified in 2010. It occurs in patients with immunosuppression and presents as a well circumscribed ulceration on the oropharyngeal mucosa, skin or gastrointestinal tract. Infiltrates of atypical lymphoid cells that may have appearances similar to Diffuse Large B-cell Lymphoma (DLBCL) or Classic Hodgkin Lymphoma (CHL) are seen. Methods/Case Report A 41 year old male patient with history of HIV infection presented with hematochezia and rectal pain, underwent sigmoidoscopy and a large ulcerated mass was present at the anal verge. Polymorphic infiltrates of small lymphoid cells, eosinophils, granulocytes, plasma cells, histiocytes and scattered large atypical lymphoid cells, morphologically mimicking Reed-Sternberg cells were identified. The large atypical lymphoid cells were positive for CD30, MUM-1, BCL-6, EBER (EBV) and negative for CD3, CD15, CD20, CD45, CD79a, SOX-10. Based on lack of B-symptoms, no lymphadenopathy, superficial lesions, reduced CD4/CD8 ratio and specific location, EBVMCU was favored. Eight months later, he presented with night sweats, decreased appetite and inguinal lymphadenopathy. Lymph node excision displayed infiltrates of predominantly small lymphocytes, histiocytes, plasma cells and eosinophils. Foci of scattered large atypical cells morphologically compatible with Hodgkin/Reed Sternberg cells with focal necrosis were noted. The atypical cells were positive for CD30, PAX5 (weak), CD20 (subset), CD15 (focal), MUM-1 and EBV-EBER. CHL, Mixed Cellularity Subtype was diagnosed. Results (if a Case Study enter NA) NA Conclusion As a newer entity, we don’t know if EBVMCU can co-exist with or progress to CHL/DLBCL. Therefore, EBVMCU patients should undergo vigilant screening.

Evaluation of effective strategies in the prevention of chemotherapy induced mucositis among Children

Abstract Background Oral mucositis is a frequent side effect of anticancer treatments. It impairs the patient’s quality of life, aggravate clinical condition, increase the risk of infection and can delay anticancer treatment. Health care workers at the NIBD and BMT Karachi, Pakistan emphasize on oral hygiene to prevent such complications for the patients. Proper oral hygiene protocol can reduce the risk of oral ulcers. In this study we have done the evaluation of oral hygiene. At NIBD and BMT among pediatric population are advice to brush their teeth twice a day, use pyodine/ Chlorhexidine 0.2% mouth wash thrice a day followed by application of anti-fungal jell. Methods A cross-sectional survey was conducted from date 8/5/2020 to 11/5/2020 at children hospital. 73 admitted patients were the study using convenient sampling, team approached eligible patients and informed consent was obtained from parents. A standardized questionnaire was then administered in Urdu (Pakistan’s national language). Results 11% of patients reported that they frequently or always suffered from oral ulcer and use mouth washes for gargles; however 79.5% reported that they rarely or never suffered from oral ulcer and use mouth washes. In contrast, 9.6% patients reported that they rarely or never suffered from oral ulcer and do not use mouth washes, whereas none of the patients who reported that they do not use mouth washes for gargles had suffered from oral ulcer frequently or all the time. 2.7% of the patients experienced oral ulcer frequently or always and brush once in a day, 6.8% experienced oral ulcer frequently or always and brush twice or more in a day and 1.4% don’t brush and suffered from oral ulcer frequently or always. Conversely, 27.4% never or rarely had oral ulcer and brush once in a day, 54.8% never or rarely had oral ulcer and brush twice or more in a day and 6.8% don’t brush and had never or rarely experienced oral ulcer Conclusion The use of proper oral hygiene protocol can decrease the risk of chemotherapy induced mucositis. Majority of the patients at NIBD 02 + 103 understand the importance of oral hygiene after their doctor’s Furthermore oral hygiene can decrease levels of oral mucositis and eventually decrease inpatient admissions, delays in treatments and improving the quality of life.

Ferric Iron/Shikonin Nanoparticle-Embedded Hydrogels with Robust Adhesion and Healing Functions for Treating Oral Ulcers in Diabetes.

Oral ulcers can be addressed using various biomaterials designed to deliver medications or cytokines. Nevertheless, the effectiveness of these substances is frequently limited in many patients due to poor adherence, short retention time in the mouth, and less-than-optimal drug efficacy. In this study, a new hydrogel patch (FSH3) made of a silk fibroin/hyaluronic acid matrix with light-sensitive adhesive qualities infused with ferric iron/shikonin nanoparticles to enhance healing effects is presented. Initially, this hydrogel forms an adhesive barrier over mucosal lesions through a straightforward local injection, solidifying when exposed to UV light. Subsequently, FSH3 demonstrates superior reactive oxygen species elimination and near-infrared photothermal bactericidal activity. These characteristics support bacterial elimination and regulate oxidative levels, promoting a wound's progression from inflammation to tissue regeneration. In a diabetic rat model mimicking oral ulcers, FSH3 significantly speeds up healing by adjusting the inflammatory environment of the injured tissue, maintaining balance in oral microbiota, and promoting faster re-epithelialization. Overall, the light-sensitive FSH3 hydrogel shows potential for rapid wound recovery and may transform therapeutic methods for managing oral ulcers in diabetes.

Coronavirus-disease-2019-associated Stevens–Johnsons syndrome in a 15-year-old boy: a case report and review of the literature

BackgroundStevens–Johnson syndrome (SJS) is a life-threatening condition characterized by high fever and severe mucocutaneous lesions, often triggered by drugs or infection. During the coronavirus disease 2019 pandemic, there was a marked increase in Stevens–Johnson syndrome cases, but relatively few cases were reported in children. The present article reports a pediatric case of Stevens–Johnson syndrome due to coronavirus disease 2019 infection and provides a review of the most relevant literature.Case presentationA previously healthy 15-year-old Han Chinese boy from China presented to the hospital with oral ulcers, conjunctival hyperemia, and widespread maculopapular rash. He had a history of fever 9 days prior and tested positive for coronavirus disease 2019 infection. Upon admission, his rash and mucosal lesions worsened, with the development of blisters on the fingertips of both hands, ocular pain, photophobia, and erosive lesions on the genital mucosa with exudation. He was diagnosed with Stevens–Johnson syndrome and received treatment with methylprednisolone, intravenous immunoglobulin, and dermatological and mucosal care. The patient’s condition was managed, and the dosage of high-dose intravenous methylprednisolone was tapered down, followed by a transition to oral prednisolone. He was discharged without sequelae.ConclusionWe should be aware that coronavirus disease 2019 infection is associated with the development of Stevens–Johnson syndrome in children and may lead to a wide spectrum of dermatologic presentations. Although Stevens–Johnson syndrome is a relatively rare condition, given its potentially serious consequences, it is crucial to identify it as early as possible and to take appropriate preventive and therapeutic measures to reduce complications and improve the quality of life for patients.

Genetically Supported Drug Targets and Dental Traits: A Mendelian Randomization Study

Current interventions for oral/dental diseases heavily rely on operative/surgical procedures, while the discovery of novel drug targets may enable access to noninvasive pharmacotherapy. Therefore, this study aims to leverage large-scale data and Mendelian randomization (MR) techniques, utilizing genetic variants as instruments, to identify potential therapeutic targets for oral and dental diseases supported by genetic evidence. By intersecting 4,302 druggable genes with expression quantitative trait loci from 31,684 blood samples, we identified 2,580 druggable targets as exposures. Single nucleotide polymorphisms associated with dental disease/symptom traits were collected from FinnGen R9, the Gene–Lifestyle Interactions in Dental Endpoints consortium, and the UK Biobank to serve as outcomes for both discovery and replication purposes. Through MR analysis, we identified 43 druggable targets for various dental disease/symptom traits. To evaluate the viability of these targets, we replicated the analysis using circulating protein quantitative trait loci as exposures. Additionally, we conducted sensitivity, colocalization, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes annotation, protein–protein interaction analyses, and validated dental trait–associated druggable gene expression in animal models. Among these targets, IL12RB1 (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.01–1.01) and TNF (OR, 0.98; 95% CI, 0.97–0.99) exhibited therapeutic promise for oral ulcers, whereas CXCL10 (OR, 0.84; 95% CI, 0.76–0.91) was for periodontitis. Through a rigorous quality control and validation pipeline, our study yields compelling evidence for these druggable targets, which may enhance the clinical prognosis by developing novel drugs or repurposing existing ones.

12533 A Rare Case of a Growth Hormone Releasing Hormone-Secreting Pulmonary Carcinoid Tumor: Clinical Presentation and Management

Abstract Disclosure: I. Yaseen: None. C. Woods: None. D.B. O'Shea: None. R.K. Crowley: None. D. O'Toole: None. H. Almeamar: None. We present a rare case of an ectopic Growth Hormone Releasing Hormone (GHRH)-secreting pulmonary neoplasm manifesting with acromegaly. A 62-year-old woman presented with Bell’s palsy. An incidental lung mass proved to be a 17.5cm carcinoid tumor, DOTATOC-avid, with bony and liver metastases, Ki67 1% on lung and bone biopsy. After pulmonary service referral to endocrinology, she was noted to have acromegalic features, the most troubling of which was macroglossia associated with mouth ulceration. IGF1 was 549ug/L (57-186), random growth hormone was 225. GHRH in serum was 1937ng/ml (reference &amp;lt; 60). MR Pituitary revealed hyperplasia.The multidisciplinary team discussion was that the lung lesion was unresectable, therefore she was commenced on somatuline autogel 120mg every 28 days and an opinion requested re suitability for Peptide Receptor Radionuclide Therapy. After 6 months of therapy IGF1 normalised to 90ug /L. GHRH reduced to 1056ng/L.Imaging at 8 months showed stability of lung primary and bone / liver metastases, with no benefit likely from PRRT at this time. This case highlights the importance of considering endocrine syndromes in the setting of a lung mass. The prevalence of acromegaly in Ireland is 69 per million people; this is the second Irish case known of GHRH-associated GH excess. Ectopic GH-secreting pulmonary tumors are a rare but important differential in patients presenting with acromegalic features. Complete surgical resection can be curative, underlining the significance of a multidisciplinary approach in management, encompassing endocrinology, thoracic surgery, and pathology. This case of successful medical management adds to the limited literature on such tumors and underscores the potential for non-pituitary neoplasms to cause systemic endocrinopathies. Presentation: 6/1/2024

5175 A Rare Case of Type B Insulin Resistance Syndrome

Abstract Disclosure: S. Fatima: None. A. Champion: None. S. Ward: None. Q. Aziz: None. K.E. Izuora: None. Introduction: Severe insulin resistance may be defined as a severely diminished response to insulin’s biological effects and is characterized by substantial hyperinsulinemia and impaired glucose response to endogenous and exogenous insulin. We hereby present a rare case of Type B Insulin Resistance Syndrome (TBIRS). Case:40-years old female with history of systemic lupus erythematosus (SLE), diabetes mellitus was admitted with multiple rheumatologic complaints, including arthralgias, oral ulcers, skin rash, and hair loss secondary to SLE flare. Endocrinology was consulted for diabetes management. Her HbA1c had increased from 7.3% to 11.6% in 3 months despite taking Glargine 45 units daily, Lispro 15 units pre-meals and metformin. She noticed 80 lbs weight loss for past 6 months. Her BMI was 26 and exam showed acanthosis of neck, armpits, groin, hair loss on scalp, multiple genital ulcers, and facial rash. She was noted to have refractory hyperglycemia despite high insulin doses. By 14th day of hospitalization, she was on 287 units of insulin (3.4units/kg) daily. We suspected TBIRS in the setting of SLE. Metformin and pioglitazone were started. Further testing showed insulin level 152mIU/ml (2.6-14.9mIU/ml), C-peptide 1.7 ng/ml (1.1-4.4 ng/ml), islet-cell antibody negative, GAD-65 antibody &amp;lt;5 u/ml, insulin antibody 6.5 uU/ml, IGF-1 14 (79-259 ng/ml), adiponectin 13.3 (2.4-17.9 ug/ml), testosterone 7 (8-60 ng/dl), free testosterone &amp;lt;0.2 (0-4.2 pg/ml), total cholesterol 200 mg/dl (&amp;lt;200 mg/dl), triglycerides 85 mg/dl (&amp;lt;150 mg/dl), LDL 154 mg/dl (&amp;lt;100 mg/dl), HDL 29 mg/dl (&amp;gt;60 mg/dl). She was transferred to National Institute of Health for further care. She was confirmed to have TBIRS by insulin receptor antibody testing, started on regular insulin U500 initially, and then switched to IV insulin drip requiring up to 1700 units of insulin per hour. She received methylprednisolone, cyclophosphamide (2 doses), rituximab (2 doses), hydroxychloroquine and IV immunoglobulin. Her stay was complicated by hemophagocytic lymphohistiocytosis. She was discharged on U-500 Regular insulin, 1000 units with breakfast and 500 units with lunch, Prednisone 60 mg daily and Hydroxychloroquine. Two months later she was found unresponsive at home secondary to hypoglycemic seizures. She required dextrose drip and was discharged on Glargine 16 units and Lispro 6 units with meals. Conclusion: TBIRS is caused by a highly specific polyclonal autoantibody against the cell surface insulin receptor that decreases the cellular insulin response and causes refractory hyperglycemia. About 100 cases have been reported in literature. 60% of the cases are associated with SLE. The goal of therapy is to reverse the hypercatabolic state with high doses of insulin and to eliminate the autoantibodies with immunosuppressive therapy. The most common cause of mortality is hypoglycemia. Presentation: 6/3/2024

7876 Complex Complications of Thionamide Therapy in One Patient: Methimazole-Induced Agranulocytosis and PTU-Induced ANCA-Vasculitis

Abstract Disclosure: E. Zweibach: None. A. Chang: None. Introduction: Thionamides, including methimazole and propylthiouracil (PTU), are essential for treating Graves' disease but can cause serious side effects such as agranulocytosis and ANCA-vasculitis. Although agranulocytosis itself is quite uncommon, the incidence of ANCA vasculitis is even more infrequent, making combination of conditions particularly exceptional. We present a unique case of a Graves' disease patient who suffered both complications: agranulocytosis due to methimazole and ANCA vasculitis from PTU, with successful resolution of both the clinical signs and laboratory findings following drug discontinuation. Case: 61-year-old female with a history of Graves' disease previously managed with methimazole but discontinued due to agranulocytosis, presented with lower extremity swelling, atrial fibrillation with RVR, and high output cardiac failure. Laboratory tests showed hyperthyroidism (TSH 0.008, Free T4 3.07), leading to a diagnosis of thyroid storm. Patient was started on PTU inpatient and discharged with this medication to home. Eight months later, the patient developed alarming signs including gross hematuria, oral ulcers, widespread muscle pain, found to have AKI with Cr of 2.79 and hospitalized for further eval. While hospitalized, the patient was found to have a range of complications including leukopenia with normal granulocyte count, anemia, AKI, proteinuria, and microscopic hematuria. Rheumatological evaluation showed +ANA and a high ANCA titer &amp;gt;1:1280, along with elevated levels of MPO and PR-3, and reduced complement levels. These symptoms and laboratory findings led to a diagnosis of ANCA vasculitis induced by PTU, resulting in the cessation of this medication. Following the discontinuation of PTU there was a notable improvement with normalization of serum Cr and resolution of proteinuria within 1.5 months. Concurrently, MPO and PR-3 levels began to decrease, and her hematological abnormalities resolved. During this period, her Free T4 levels gradually increased, leading to the administration of radioactive iodine for the treatment of her Graves' disease. Discussion: This case underscores the complexities in treating a patient with Graves' disease highlighting the unpredictable and severe side effects of antithyroid drugs like agranulocytosis and ANCA vasculitis. We report the first documented case of sequential thionamide-induced complications: agranulocytosis with methimazole, followed by ANCA vasculitis with propylthiouracil. Although both can arise from immune responses to these medications, they are distinct in their pathophysiology and are not associated with one another. The unpredictable nature of these side effects complicates prevention. Educating patients to promptly report any unusual symptoms and immediate medical intervention with drug discontinuation are key to managing these adverse reactions effectively. Presentation: 6/1/2024

7044 It Is Back, Three Decades Later! When To Stop Glucagonoma surveillance?

Abstract Disclosure: A.T. Wahba: None. J.S. Dillon: Advisory Board Member; Self; Crinetics Pharmaceuticals, CA. A 76-year-old woman presented to the Neuroendocrine Tumor (NET) Clinic for evaluation of sore mouth, perianal area and itchy ankles. She had a medical history notable for glucagonoma, status post distal pancreatectomy and splenectomy in 1988, 32 years prior to her current presentation. She recalled that she had CT imaging post operatively for a few years, but no more recent imaging. She was diagnosed with diabetes mellitus in approximately 2002, with highly variable glucose control. She developed a left leg DVT with pulmonary emboli one year prior to presentation. Shortly after her thromboembolic events, she noted her current presenting complaints. A CT abdomen scan with contrast was reported as normal. Three months later, an abdomen ultrasound for evaluation of right upper quadrant pain and intractable vomiting, showed a liver mass. MRI revealed a contrast enhancing 3.1x2.1x1.8 cm lesion in liver segment 6 and 7. Her plasma Glucagon concentration, which had been undetectable when last checked in 2007, was 382 (N: &amp;lt; 80 pg/ml). CT-guided needle biopsy of the liver lesion confirmed a well differentiated neuroendocrine tumor, immunohistochemically positive for somatostatin receptor 2 (SSTR2A), Islet-1 and PAX6, with low mitotic count and Ki-67 proliferation index of 0.45%. Gallium-68 DOTATATE-PET scan showed a single avid hepatic metastasis, with no other evidence of somatostatin receptor expressing tumor. She was initially started on a combination of short-acting Octreotide 100 mcg TID and monthly 20 mg Sandostatin LAR injections for symptomatic relief. Zinc copper 100 mg capsules were prescribed with significant improvement of skin rash and glossitis within 2-4 months. Repeat MRI abdomen at 3 months and 6 months showed a stable single liver lesion without evidence of additional metastasis. She has continued annual clinic visits and abdomen MRI follow up with stable imaging findings at 3 years. Percutaneous ablation, trans hepatic arterial embolization and surgical resection were discussed, but the patient preferred a more conservative approach of monthly octreotide LAR, which she tolerated well, and which resolved her symptoms. Glucagonoma syndrome presents classically with 5D’s: Dermatitis (Necrolytic Migratory Erythema), DVTs, Diabetes mellitus, Depression, Diarrhea. The National Comprehensive Cancer Network guidelines recommend monitoring glucagonoma patients post-resection for up to 10 years with clinical evaluation, glucagon levels every 6-12 months and imaging studies as clinically indicated. Our case illustrates that recurrence can occur after 30 years from initial resection and that longer surveillance should be considered. Presentation: 6/3/2024

Integrating network pharmacology and transcriptomics to study the potential mechanism of Jingzhi Niuhuang Jiedu tablet in rats with accumulation of heat in the lungs and stomach

Ethnopharmacological relevanceAccumulation of heat in the lungs and stomach (AHLS) is an important syndrome within the realm of traditional Chinese medicine (TCM). It is the fundamental reason behind numerous illnesses, including mouth ulcers, dermatological conditions, acne, and pharyngitis. Jingzhi Niuhuang Jiedu tablet (JN) serves as the representative prescription for treatment of AHLS clinically. However, the effective components and mechanism of JN's impact on AHLS remain unexplored. Aim of the studyThe objective of this research was to analyze the effective components of JN and investigate the therapeutic effect and potential mechanism of JN on AHLS. Materials and methodsThe effective compounds of JN extract were analyzed and identified using UHPLC-Q-Exactive/HRMS. Utilizing network pharmacology to investigate JN's multi-target, multi-pathway process in treating AHLS. Subsequently, anti-inflammatory activities of JN extract were evaluated in the RAW264.7 cells stimulated by lipopolysaccharide (LPS). In addition, a rat AHLS model induced by LPS and dried ginger was established. Pathological changes in rat lung and stomach tissues observed by HE staining and Masson's trichrome staining. Additionally, the expression of TNF-α, IL-6, and IL-1β in bronchoalveolar lavage fluid (BALF) was identified through the ELISA assay. For a deeper understanding of how JN might affect AHLS, transcriptomics was utilized to examine differential genes and their underlying mechanisms. Concurrently, techniques like quantitative polymerase chain reaction (q-PCR), immunofluorescence, and western blotting (WB) were employed to confirm various mRNA and protein expression, including Il17ra, Il17re, IL-17A, IL-1β, IL-6, PPARγ, PGC1-α and UCP1. ResultsWe identified 178 potential effective components in the JN extract. Network pharmacology analysis showed that the 144 components in JN act on 200 key targets for the treatment of AHLS by suppressing inflammation, regulating energy metabolism, and gastric function. In addition, JN suppressed the LPS-stimulated generation of NO, TNF-α, IL-1β, and IL-6 in RAW264.7 cells. And JN treatment effectively alleviated lung and stomach injury and reduced inflammation in rats. Analysis of RNA-seq from lung tissues revealed JN's substantial control over crucial genes in the IL-17 signaling pathway, including Il1b and Il17ra. Likewise, RNA sequencing of stomach tissues revealed that JN markedly decreased crucial genes in the Thermogenesis pathway, including Ppargc1a and Ppara. Additional experimental findings confirmed that treatment with JN significantly reduced the expression levels of mRNA (Il17ra, Il17re, Il1b, Ppargc1a and Ucp1), and the expression levels of protein (IL-17A, IL-1β, IL-6, PPARγ, PGC1-α and UCP1). ConclusionThis study not only analyzes the effective components of JN but also reveals that JN could effectively ameliorate AHLS by inhibiting IL-17 signaling pathway and Thermogenesis pathway, which provides evidence for subsequent clinical studies and drug development.

A bio-inspired Janus hydrogel patch facilitates oral ulcer repair by combining prolonged wet adhesion and lubrication

Oral ulcers, the most common type of mucosal lesion, are both highly prevalent and prone to recurrence. In the persistently moist environment of the oral cavity, current therapeutic patches face challenges such as short adhesion time, disruption by food particles and bacteria, and oral movements. To address these challenges, we develop a Janus patch, named ANSB, inspired by the multi-layered and asymmetric structure of natural mucosa, featuring a long-lasting adhesive layer and a lubricating layer. By eliminating the salivary barrier and leveraging covalent crosslinking between tissue surface amine groups and N-hydroxysuccinimide ester (NHS), the adhesive layer—composed of gelatin and acrylic acid—achieves rapid (≤ 30 s), strong (≥ 45 kPa), and durable (≥ 8 h) adhesion to wet buccal tissues. Furthermore, the efficient lubricating effect (COF = 0.02 ± 0.003) provided by zwitterions renders the lubricating layer of ANSB highly similar to natural mucosal tissue, effectively preventing bacterial invasion, secondary damage, and unintended adhesion. Additionally, the strong interlayer bonding and complementary mechanical properties are confirmed, resulting in a unified performance characterized by rapid wet adhesion, hydration lubrication, and enhanced mechanical strength. Importantly, ANSB treatment demonstrates a long-term protective barrier and superior therapeutic effects in rat oral ulcers, inhibiting pseudomembrane formation and accelerating tissue regeneration without causing secondary damage. Consequently, this distinctive Janus patch, characterized by prolonged adhesion, efficient lubrication, and simple preparation, holds significant potential for clinical oral ulcer treatment. Statement of SignificanceOral ulcers, with healing impeded by secondary injury and bacterial invasion due to the absence of protective barriers, are highly prevalent and recurrent. However, sustaining therapeutic materials and physical barriers in the highly dynamic and moist oral environment poses a considerable challenge. In this study, a Janus patch (ANSB) that integrated a soft wet adhesive layer and a tough lubricating layer was developed to reconstruct a new protective barrier thus preventing external stimuli such as secondary damage and bacterial infiltration. This innovative patch with high therapeutic potential for oral ulcers may offer a new way for ulcer treatment based on barrier protection.

Effective Treatment of Refractory Oral Ulcers Using a Compound Chinese Herbal Mouthwash: A Report of Two Cases

Oral ulcers are a prevalent oral mucosal disorder, characterized by benignancy and self-limiting progression. However, a subset of these ulcers exhibits resistance to conventional therapeutic interventions, necessitating alternative treatment strategies. In this study, we present two cases of refractory oral ulcers that demonstrated limited responsiveness to standard treatments but achieved significant therapeutic benefits following the application of a compound Chinese herbal mouthwash. Case 1 involved a 60-year-old female patient diagnosed with Behçet's syndrome. Initial treatment with glucocorticoids and immunosuppressants yielded limited improvement in her oral ulcers; however, combination therapy involving the Chinese herbal mouthwash resulted in significant improvement and complete healing after a 2-week period. Case 2 presented a 48-year-old female patient with chronic tongue ulceration pain persisting for one year without any detectable systemic etiology. Despite receiving oral vitamin supplementation and local analgesic jelly, her symptoms remained unalleviated. A 3-week treatment regimen involving the administration of the Chinese herbal mouthwash in conjunction with thalidomide led to the complete resolution of her oral ulcers. The findings from this study suggest that the compound Chinese herbal mouthwash may serve as an adjuvant therapeutic approach for managing chronic oral ulcers that are resistant to conventional treatment.