Neurosarcoidosis-Induced Winging Scapula: Efficacy of Infliximab Treatment in Addressing Multifaceted Challenges.

Sarcoidosis, a systemic granulomatous disease primarily affecting the respiratory and lymphatic systems, can rarely manifest as neurosarcoidosis either in isolation or alongside other systemic symptoms. Here, we describe the case of a 45-year-old male with a history of recurrent sinusitis refractory to antibiotics, who presented to the emergency department with sinus congestion and dysphagia. Clinical examination revealed left lower motor neuron facial palsy and enlarged submandibular salivary glands. Despite obtaining negative results from various antibody panels, the patient exhibited elevated Angiotensin Converting Enzyme levels of 83 nmol/kg/min. Additionally, computed tomography chest scans revealed bilateral hilar and mediastinal lymph node enlargement, findings consistent with sarcoidosis. Otorhinolaryngology evaluation for dysphagia confirmed left vocal cord palsy. Following a negative infectious disease workup, submandibular salivary gland biopsy confirmed sarcoidosis. Treatment with mycophenolate mofetil and oral steroids led to gradual improvement in salivary gland swelling, dysphagia, and facial palsy. However, worsening left shoulder pain prompted further investigation, revealing winging of the left scapula on repeat examination. Magnetic resonance imaging (MRI) of the cervical spine revealed a six mm hyperintensity in the left dorsal cord at the C5 level, suggesting possible neurosarcoidosis vs. demyelinating disease. Subsequently, the patient was prescribed anti-tumor necrosis factor alpha inhibitor infliximab. Subsequent MRI of the cervical spine, conducted six months after initiating Infliximab therapy, indicated resolution of the lesions. This positive outcome was supported by the patient's report of symptom improvement, notably reduced shoulder pain and improvement in left scapular winging. This case underscores the unusual co-occurrence of Bell's palsy and vocal cord palsy in the same patient, along with the potential contribution of neurosarcoidosis to the winged scapula. Additionally, it sheds light on the positive response of neurosarcoidosis to Infliximab therapy.

Saline Breast Implant Associated With Inflammatory Arthritis and Positive Antinuclear Antibodies (ANA): A Case Report.

Breast implants, whether silicone or saline-filled, have a silicone shell and have been used for decades. Studies have shown an association between silicon with systemic lupus erythematosus, rheumatoid arthritis, progressive systemic sclerosis, and vasculitis. However, controversy and inconsistency have been pervasive in the literature with respect to the role of breast implants in the development of autoimmune diseases. A 39-year-old female with a past medical history of breast cancer and a family history of Sjogren's syndrome was referred to rheumatology for positive antinuclear antibodies (ANA) and polyarthralgia. She received textured saline breast implants for post-mastectomy reconstruction and subsequently developed fatigue, bilateral joint pain in her hands, wrists, and feet, and swelling in her fingers with prolonged morning stiffness, unintentional weight loss, and dry eyes. Physical examination revealed mild swelling of the bilateral metacarpophalangeal (MCP), proximal interphalangeal joint (PIP,) and distal interphalangeal (DIP) joints, and difficulty making a fist. Laboratory workup revealed a normal complete blood count (CBC) and comprehensive metabolic panel (CMP) with slight elevations in inflammatory markers. Autoimmune workup revealed positive ANA 1:640 (nucleolar) and 1:160 (speckled), positive U1RNP, and RNA polymerase III with negative SSA/SSB/dsDNA and Scl-70 Ab. Following elective implant removal after nationwide recall for heightened cancer risk, many of her symptoms spontaneously resolved. The clinical case of inflammatory arthritis with positive ANA antibodies following saline breast implants highlights the importance of considering the possible health implications of silicone from a rheumatologic perspective. This case demonstrates that it may be reasonable that an association exists, and further research on a large scale would be valuable.

Live Patient Encounters: A Perspective From Second-Year Medical Students.

Background Interactive patient cases have been shown to be a valuable resource in medical education. Previous studies have demonstrated that using patients as teachers can help students improve clinical reasoning and have educational benefits; however, there is limited research on student feedback on patients as teachers. The objective of this study is to evaluate second-year medical students' (MS2s) perceptions of patient encounters during the teaching of the Skin and Musculoskeletal System Course (BMS 6635). Methods A retrospective descriptive study on prospectively maintained survey data was performed. Following course completion, MS2s were surveyed on their experience from four to five live patient encounters at the University of Central Florida College of Medicine from 2016-2022. The interactive cases involved patients with dermatologic, autoimmune, and musculoskeletal diseases. All MS2s enrolled in BMS 6635 were included. Statistical analysis was performed on survey responses to students' perceptions of live patient encounters. Results Seven hundred surveys were completed following the interactive patient encounters. Ninety percent of participants answered that they enjoyed the cases, 92% agreed the cases were an appropriate learning experience for their education, and 76% agreed the cases helped with material retention. From 2016 to 2022, there was a slight decrease in enjoyment in the cases over time (97%, 88%, 93%, 94%, 86%, 81%, p<.001, respectively), and student agreement that patient cases were an appropriate learning experience in their education (98%, 92%, 94%, 95%, 93%, 84%, p=.001, respectively), but overall remained greater than 80% satisfaction. Conclusions Patient cases are perceived to be a valuable educational resource by second-year medical students and therefore should be integrated in medical curricula. Students enjoyed patient cases, believed they had an educational benefit, and perceived they aided in material retention.

Diet as a Risk Factor for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease that involves primarily synovial tissues and typically affects women more than men. An exact cause has yet to be identified, but the disease is thought to manifest due to both genetic and environmental factors. The predominant theory is that RA is an autoimmune disease with environmental triggers. Recently, diet as a risk factor for RA has become of interest. The objective of this narrative review is to determine which dietary factors have an influence on developing RA by examining existing literature on this topic. A PubMed search was built using the MeSH terms: "rheumatoid arthritis," "risk factors," "diet," "nutritional status," "nutrition therapy," "nutrition assessment," "nutrition disorders," "diet, food, and nutrition," and "nutritional requirements." Articles containing a sample size of >10, published in the last 30 years, and written in English were included. Current literature has examined dietary items, such as alcohol, fruit, red meat, and caffeinated beverages, as risk factors for RA. However, the effect of each dietary item has often been variable across studies. The variation in results may be attributed to the variable categorization of each dietary item across studies, variations in the phrasing of dietary items, differing methods of data collection, and the cohort chosen. This narrative review of the literature showed that moderate alcohol consumption and increased ß-cryptoxanthin are protective against developing RA. Overall, specific dietary elements and their influence on RA risk is a promising topic, and significant findings may be helpful in preventing the development of RA.

Achenbach Syndrome: A Case Series.

Achenbach syndrome, also known as "paroxysmal finger haematoma", is a rare, benign, self-limiting condition with unknown etiology that results in an acute onset swelling and pain, and subsequently blue discoloration of the fingers and sometimes the feet. The pathophysiology of this syndrome is not entirely clear, but intermittent spontaneous hematoma formation is reported as its characteristic symptom. Achenbach syndrome is more predominant in the female population. There are no known risk factors such as trauma, drug use, bleeding disorders, or rheumatologic diseases associated with the etiology of this syndrome. Although the symptoms are alarming to patients, the condition itself is not accompanied by any significant complications. Herein we present our case series of four patients experiencing symptoms compatible with the diagnosis of Achenbach syndrome. The aim of this study is to increase awareness of this condition and its benign nature to avoid unnecessary referrals or invasive procedures and investigations as well as alleviate the anxiety of patients.

Anti-TNF-α agents Modulate SARS-CoV-2 Receptors and Increase the Risk of Infection Through Notch-1 Signaling.

Although millions of patients with underlining conditions are treated primarily with anti-TNF-α agents, little is known about the safety of this standard therapy during the coronavirus disease-2019 (COVID-19) pandemic. In this study, we investigated the effect of anti-TNF-α monoclonal antibodies on the cellular entry mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and increasing the risk of COVID-19 development. We focused on the expression of angiotensin-converting enzyme II (ACE2), type II transmembrane serine proteases (TMPRSS2)/TNF-α converting enzyme (TACE) ratio. We also investigated the involvement of Notch-1 signaling and its downstream influence on IL-6, myeloid cell leukemia sequence-1(MCL-1) in the anti-TNF-α mode of action and increased the susceptibility to Mycobacterium avium subspecies paratuberculosis (MAP) infection. Surprisingly, anti-TNF-α downregulated ACE2 expression by 0.46-fold and increased TMPRSS2/TACE ratio by 44% in THP-1 macrophages. Treatment of macrophages with rIL-6 also downregulated ACE2 and increased TMPRSS2/TACE ratio by 54%. Interestingly, anti-TNF-α treatment upregulated Notch-1, IL-6, and MCL-1 by 1.3, 1.2, and 1.9-fold, respectively, and increased viability and burden of MAP infection in macrophages. Blocking Notch signaling doubled ACE2 expression, decreased TMPRSS2/TACE ratio by 38%, and reduced MAP viability by 56%. In a small group of patients, ACE2 level was significantly lower in the plasma from rheumatoid arthritis (RA) patients on anti-TNF-α treatment compared to healthy control. The data in this critical study demonstrated that through Notch-1/IL-6 signaling, anti-TNF-α agents decreased ACE2 expression and shedding through TMPRSS2/TACE modulation and increased the susceptibility to infection. Overall, this study warns against anti-TNF-α therapy in some patients with underlining inflammatory conditions during the COVID-19 pandemic. The findings should impact current guidelines regarding treatment decisions of patients on anti-TNF-α during the COVID-19 pandemic.

Prevalence of Anxiety, Depression, Sleep Disturbance, Fibromyalgia, Obesity, and Gastroesophageal Disease in Patients with Rheumatic Diseases.

BACKGROUND: Patients with rheumatologic disorders often have comorbidities that complicate their psychological well-being. In this study, we looked at 216 patients with rheumatoid arthritis (RA), systemic lupus erythematous (SLE), psoriatic arthritis (PsA), and Sjogren's syndrome (SS) to determine the prevalence of anxiety, depression, sleep disturbance, fibromyalgia (FM), obesity (BMI greater than 23), and gastroesophageal disease (GERD) and the correlation between FM, BMI, disease activity measure, known as Routine Assessment of Patient Index Data 3 (RAPID3). METHODS: Study participants were 216 rheumatology patients seen at the UCF Pegasus Health Clinic from November 2011 to May 2014 with one or more of the following diseases: RA, SS, SLE, or PsA. 116 had rheumatoid arthritis, 27 with systemic lupus erythematous, 22 with psoriatic arthritis, 20 with Sjogren's syndrome, and 31 with more than one diagnosis. Variables that were collected from patients' charts included RAPID3 scores, patient demographics (age, sex), BMI, presence of GERD, and presence of FM. Each patient was randomly assigned, unique and had an unidentifiable study number. RESULTS: Anxiety, depression, sleep disturbance and obesity were found to be more prevalent in patients with Sjogren's syndrome, and fibromyalgia was noted to be more prevalent in patients with more than 1 diagnosis. The presence of fibromyalgia was significantly correlated with higher RAPID3 scores in all patients except those with PsA. Significant correlation among higher BMI and greater RAPID3 scores was found for patients with rheumatoid arthritis and for patients with Sjogren's syndrome. CONCLUSION: Our study showed an increased prevalence of anxiety in patients with Sjogren's syndrome. Fibromyalgia was found to be related to higher disease activity scores. In RA and SS patients, BMI was significantly correlated with higher RAPID3 scores. These results provide a basis for future studies to evaluate these correlations in more detail.

Polymorphisms in TNF Receptor Superfamily 1B (TNFRSF1B:rs3397) are Linked to Mycobacterium avium paratuberculosis Infection and Osteoporosis in Rheumatoid Arthritis.

We previously discovered that single nucleotide polymorphisms (SNPs) in PTPN2/22 (T-cell negative-regulators) occur in 78% of rheumatoid arthritis (RA), along with Mycobacterium avium paratuberculosis (MAP) infection in 33% of patients. In Crohn's disease, we reported that SNPs in TNFα and receptors (TNFRSF1A/TNFRSF1B) benefited intracellular MAP-survival, increased infection, and elevated inflammatory response mimicking the poor response to anti-TNFα treatment in some patients. Here, we studied the frequency and effects of SNPs in TNFα/TNFRSF1A/TNFRSF1B in RA including gene expression, MAP infection, and osteoporosis marker levels in blood (54 RA and 48 healthy controls). TNFα:rs1800629 (GA) was detected in 19/48 (40%) RA and 8/54 (15%) controls (p-value < 0.05, odds ratio (OR) = 3.6, 95% CI: 1.37-9.54). TNFRS1B:rs3397 (CT) was detected in 21/48 (44%) RA and 10/54 (19%) controls (p-value < 0.05, OR = 4.43, 95% CI: 1.73-11.33). In RA, rs3397 downregulated TNFRSF1B expression (CC > CT (0.34 ± 0.14) and CC > TT (0.27 ± 0.12)), compared to wildtype CC (0.51 ± 0.17), p-value < 0.05. MAP DNA was detected significantly in 17/48 (35.4%) RA compared to 11/54 (20.4%) controls (p-value < 0.05, OR = 2.14, 95% CI: 1.12-5.20). The average osteocalcin level was significantly lower (p-value < 0.05) in RA (2.70 ± 0.87 ng/mL), RA + MAP (0.60 ± 0.31 ng/mL), RA + TNFRSF1B:rs3397 (TT) (0.67 ± 0.35 ng/mL), compared to the healthy control (5.31 ± 1.39 ng/mL), and MAP-free RA (3.85 ± 1.31 ng/mL). Overall, rs3397 appears to downregulate TNFRSF1B, increase MAP infection, worsen inflammation, and cause osteocalcin deficiency and possibly osteoporosis in RA.

Polymorphisms in Protein Tyrosine Phosphatase Non-receptor Type 2 and 22 (PTPN2/22) Are Linked to Hyper-Proliferative T-Cells and Susceptibility to Mycobacteria in Rheumatoid Arthritis.

A shared genetic pre-disposition, chronic inflammation, and treatment with similar biologics between Rheumatoid arthritis (RA) and Crohn's disease (CD) have intrigued us to investigate whether the two disorders share trigger association or possible causation. We hypothesized earlier that Single Nucleotide Polymorphisms (SNPs) in the negative regulators Protein Tyrosine Phosphatase Non-receptor type 2 and 22 (PTPN2/22) lead to a dysregulated immune response, susceptibility to environmental triggers, and continued apoptosis as seen in chronic inflammation in RA and CD. To test the hypothesis, peripheral leukocytes samples from 132 consented subjects were genotyped for 9 SNPs in PTPN2/22 using TaqMan™ genotyping. The effect of the SNPs on PTPN2/22 and IFN-γ expression was determined using real time PCR. T-cell proliferation and response to phytohematoagglutonin (PHA) mitogen and mycobacterial antigens were determined by BrdU proliferation assay. Blood samples were also analyzed for the Mycobacterium avium subspecies paratuberculosis (MAP) IS900 gene by nPCR. Out of 9 SNPs examined, heterozygous (TC) or minor (CC) alleles of PTPN2:rs478582 occurred in 79% RA compared to 60% healthy controls (p-values ≤ 0.05; OR = 2.28). Similarly, heterozygous (GA) or minor (AA) alleles of PTPN22:rs2476601 occurred in 29% RA compared to 6% healthy controls (p-values ≤ 0.05; OR = 5.90). PTPN2/22 expression in RA was decreased by 1.2-fold compared to healthy controls. PTPN2:rs478582 upregulated IFN-γ in RA by 1.5-fold. Combined PTPN2:rs478582 and PTPN22:rs2476601 increased T-cell proliferation by 2.7-fold when treated with PHA. Surprisingly, MAP DNA was detected in 34% of RA samples compared to 8% healthy controls, (p-values ≤ 0.05, OR = 5.74). RA samples with PTPN2:rs478582 and/or PTPN22:rs2476601 were more positive for MAP than samples without polymorphisms. Combined occurrence of PTPN2:rs478582 and PTPN22:rs2476601 in association with the presence of MAP has significantly increased T-cell response and elevated IFN-γ expression in RA samples. The data suggest that genetic polymorphisms may play vital role in T-cell regulation, susceptibility to mycobacteria and ultimately response to treatment. This is the first study to report the detection of MAP DNA in the blood of RA patients; further studies are needed using larger number of samples.

Role of PTPN2/22 polymorphisms in pathophysiology of Crohn's disease.

AIM: To establish the relationship of protein tyrosine phosphatase non-receptor type 2 and 22 (PTPN2/22) polymorphisms and mycobacterial infections in Crohn's disease (CD). METHODS: All 133 subjects' blood samples were genotyped for nine single nucleotide polymorphisms (SNPs) in PTPN2/22 using TaqMan™ genotyping, while the effect of the SNPs on PTPN2/22 and IFN-γ gene expression was determined using RT-PCR. Detection of Mycobacterium avium subspecies paratuberculosis (MAP) IS900 gene was done by nPCR after DNA extraction from the isolated leukocytes of each subjects' blood samples. T-cells isolated from the patient samples were tested for response to phytohematoagglutonin (PHA) mitogen or mycobacterial antigens by BrdU proliferation assays for T-cell activity. RESULTS: Out of the nine SNPs examined, subjects with either heterozygous (TC)/minor (CC) alleles in PTPN2:rs478582 occurred in 83% of CD subjects compared to 61% healthy controls (P-values < 0.05; OR = 3.03). Subjects with either heterozygous (GA)/minor (AA) alleles in PTPN22:rs2476601 occurred in 16% of CD compared to 6% healthy controls (OR = 2.7). Gene expression in PTPN2/22 in CD subjects was significantly decreased by 2 folds compared to healthy controls (P-values < 0.05). IFN-γ expression levels were found to be significantly increased by approxiately 2 folds in subjects when either heterozygous or minor alleles in PTPN2:rs478582 and/or PTPN22:rs2476601 were found (P-values < 0.05). MAP DNA was detected in 61% of CD compared to only 8% of healthy controls (P-values < 0.05, OR = 17.52), where subjects with either heterozygous or minor alleles in PTPN2:rs478582 and/or PTPN22:rs2476601 had more MAPbacteremia presence than subjects without SNPs did. The average T-cell proliferation in CD treated with PHA or mycobacteria antigens was, respectively, 1.3 folds and 1.5 folds higher than healthy controls without any significant SNP. CONCLUSION: The data suggests that SNPs in PTPN2/22 affect the negative regulation of the immune response in CD patients, thus leading to an increase in inflammation/apoptosis and susceptibility of mycobacteria.

Developing a Continuous Quality Improvement Assessment Using a Patient-Centered Approach in Optimizing Systemic Lupus Erythematosus Disease Control.

Systemic lupus erythematosus (SLE) is a multi-organ, autoimmune disease in which patients lose self-tolerance and develop immune complexes which deposit systemically causing multi-organ damage and inflammation. Patients often experience unpredictable flares of symptoms with poorly identified triggers. Literature suggests exogenous exposures may contribute to flares in symptoms. An online pilot survey was marketed globally through social media to self-reported SLE patients with the goal to identify specific subpopulations who are susceptible to disease state changes based on analyzed exogenous factors. The pilot survey was promoted for two weeks, 80 respondents fully completed the survey and were included in statistical analysis. Descriptive statistical analysis was performed on de-identified patient surveys and compared to previous literature studies reporting known or theorized triggers in the SLE disease state. The pilot survey identified similar exogenous triggers compared to previous literature, including antibiotics, increasing beef intake, and metal implants. The goal of the pilot survey is to utilize similar questions to develop a detailed internet-based patient interactive form that can be edited and time stamped as a method to promote continuous quality improvement assessments. The ultimate objective of the platform is to interact with SLE patients from across the globe longitudinally to optimize disease control and improve quality of care by allowing them to avoid harmful triggers.