A Review of Intra-Articular Corticosteroid Injection Safety and Clinical Effectiveness during Covid-19

Background/Aims Intraarticular corticosteroid injections (CSI) are used as a short-term treatment for inflammatory arthritis and osteoarthritis. At the outset of the COVID-19 pandemic there was concern regarding the immunosuppressive effect of steroids and the potential risk of COVID-19 infection in patients treated with CSI. There is no universal evidencebased consensus on the optimum dosing of CSI. Nationally there was a mixed response to CSI use during the COVID- 19 pandemic. Early during the pandemic, our Trust advised using only the lowest BNF indicated steroid dose to minimize any potential side effects. Large joints (knees and shoulders) were injected with 40mg of Kenalog compared to 80mg pre pandemic. No previous survey has reported the incidence of covid infection post CSI. The primary aim of this project was to address this gap. A secondary aim was to review the clinical effectiveness of a 'larger' versus 'smaller' steroid dose in CSI. Methods Retrospective data collection was carried out for 107 patients who received CSI during the pandemic. All patients who received CSI within the Trust rheumatology department were followed up with a sixweek phone call. During this consultation the effectiveness of the CSI was considered by asking them to score the effectiveness of the CSI out of 10 (10 being maximum improvement). The incidence of COVID- 19 infection was also recorded. This data was compared to the same data from a group of patients injected with a larger dose of CSI pre-pandemic (n=114). Results The patient reported incidence of COVID-19 infection within 6 weeks of CSI was 1.87%. Patient reported outcomes showed a mean improvement in joint symptoms of 6.97 using 80mg of kenalog, versus 5.02 improvement using the smaller 40mg dose at six week follow up. Interestingly 56% of people injected with a larger dose reported a minimum 8/10 improvement compared to 22% of patients injected with a smaller dose. Conclusion The low incidence of COVID-19 infections following CSI indicates that there is no significant correlation with increased in risk of contracting COVID-19. This study did not collect any data on outcomes of infection but at the time of the phone calls no patients had been hospitalized or died. The incidence of COVID-19 infection was below the national average. Some of the Rheumatology patients injected may have been advised to shield which may have contributed to the lower-than-expected figure. The significantly increased benefit consistently reported by patients supports the use of a higher dose steroid (Kenalog 80mg) versus lower dose (40mg) when injecting large joints in patients with arthritis. It is important to weight up the risks and benefits of CSI but this suggests that we should use the higher dose in clinical practice.

Polyethylenglycol and polysorbate evaluation for COVID vaccines in two patients with multiple drug allergies

Background: Covid 19 is a global epidemic. One of the most important steps in the fight against this epidemic is vaccination. mRNA vaccines are used in vaccination in our country. Among the additives in the vaccine, the substance with the highest allergenic risk is polyethylene glucose (PEG). There are different molecular weights of PEG. Another additive that has a high risk of cross-reaction with PEG as an additive is POLISORBAT 80. Skin tests with drugs containing PEG and POLISORBAT 80 and, if available, tests with vaccines are instructive. Among the drugs containing PEG: Moxifloxacin tablet, ciprofloxacin tablet, Amoxicillin clavulanic acid tablet;Medicines containing polysorbate include: Omalizumab vaccine, Mepolizumab vaccine. The results of the skin test with PEG-containing methylprednisolone (DEPO-MEDROL) and POLYSORBAT-containing triamcinolone (KENACORT-A) in order to be evaluated in terms of vaccine in our 2 patients who had multiple drug sensitivities before were shared. Method(s): Case 1: 33 y, F *There are diagnoses of urticaria and angioedema. Urticaria 30 minutes after taking aspirin, levofloxacin, cefdinir tablet;5 minutes after taking ciprofloxacin tablets, he has anaphylaxis. *Applies before Biontec vaccine. *The patient had a history of anaphylaxis with PEG-containing ciprofloxacin. In the skin tests performed with DEPO-MEDROL and KENACORT-A, 1/100 intradermal test was positive. *The patient for whom Biontec vaccine was not recommended received Synovac vaccine without any problems. Case 2: 52 years, F * He has a diagnosis of urticaria. 5 minutes after general anesthesia and local anesthesia;The patient who had cardiac arrest 3 times was evaluated. The patient, who had Synovac for 2 times without any problems, wanted to have the 3rd dose of Biontec vaccine. *Tested with general -local anesthetic agents. *Ciprofloxacin skin tests are negative;Urticaria plaques developed after 30 minutes of 1/4 tb in oral provocation. In the skin tests performed with DEPO-MEDROL and KENACORT-A, 1/100 intradermal test was positive. *Biontec vaccine is not recommended. Result(s): A safer vaccination is ensured by testing with additives in Covid 19 vaccines. Conclusion(s): Drug additives should also be kept in mind in patients with multiple drug allergies.

A COVID-19 Risk Reduction Strategy for the Treatment of Acute Vogt-Koyanagi-Harada Disease Utilizing the Antiviral Potential of Cyclosporine.

PURPOSE: To report on the successful treatment of patients with acute Vogt-Koyanagi-Harada (VKH) disease utilizing the antiviral potential of cyclosporine during the COVID-19 pandemic. STUDY DESIGN: Case series. METHODS: Clinical records were retrospectively reviewed of 4 patients presenting with new-onset acute VKH disease who elected to receive initial treatment consisting of bilateral sub-Tenon injection of triamcinolone acetonide combined with immediately starting oral cyclosporine without the use of systemic corticosteroids. RESULTS: The mean follow-up was 17.0 months. Choroidal thickness decreased to normal with recovery of bilateral best-corrected visual acuity (BCVA) of 1.2 in 3 patients. One elderly patient had decreased BCVA (OD 0.5, OS 0.8) due to cataract progression and mild epiretinal membrane. No recurrences of intraocular were observed in any patients. Mild renal dysfunction developed in 2 elderly patients, but importantly no patients developed COVID-19 disease. CONCLUSIONS: Oral cyclosporine as the initial systemic treatment of acute VKH disease, in combination with sub-Tenon injection of triamcinolone acetonide, lead to favorable clinical outcomes. Due to the known antiviral properties of cyclosporine, we suggest that this may represent a good treatment strategy for patients during the COVID-19 pandemic.

Delayed-Onset Urticaria Following Vaccination for COVID-19

Background: As COVID-19 vaccines continue to be administered worldwide, there are an increasing number of studies documenting cutaneous reactions following vaccination. Systemic reactions, such as urticarial diseases, occur. Purpose(s): The main objective of this study was to investigate the association between urticaria and recent vaccination for COVID-19. Method(s): A retrospective chart review examining the association of urticaria and COVID vaccination was conducted. Result(s): We report 17 patients who developed an urticarial reaction following vaccination against COVID and one patient who developed an urticarial reaction following a COVID infection. The vast majority of the patients were women with a mean age of 42.8 years. Conclusion(s): Cutaneous manifestations often follow COVID vaccination and infection. It may be helpful to inquire about recent infections and vaccinations in patients presenting with urticarial diseases. Copyright © 2022 Journal of Dermatology and Dermatologic Surgery.

Postauricular Incision Keloid: An Unintended Consequence of COVID-19 Mask Precautions

Introduction: Keloids of the head and neck can result in significant disfigurement and psychological stress. Here we report a novel case of keloid formation at a well-healed postauricular incision presenting after a year of daily ear loop mask use and discuss unique considerations for management. Method(s): This is a retrospective case review of a 35-year-old African American man with Klinefelter syndrome, type 2 diabetes mellitus, and a history of hypertrophic scar formation who presented to otology clinic in 2015 with chronic left otitis media and cholesteatoma. He underwent left tympanoplasty and mastoidectomy in 2016 through a postauricular incision 1 cm posterior to retroauricular sulcus in a standard fashion. In 2018, the patient was noted to have a hypertrophic scar without extension beyond the borders of the incision that was stable until 2021. Result(s): In 2021, the patient was noted to develop a 12A 7-cm postauricular keloid in the setting of mechanical irritation from his mask worn throughout the COVID-19 pandemic. Given the disfiguring cosmesis and resulting challenges securing an ear loop mask, he elected to undergo complete excision of the postauricular keloid with tension-free primary closure of the wound, intralesional corticosteroid injection (triamcinolone acetonide 40 mg/mL), and pressure dressing. The patient was counseled on options for mask wearing to avoid contact with the postauricular incision. Conclusion(s): When designing postauricular incisions in patients prone to hypertrophic scar or keloid formation, the point of postauricular contact of ear loop masks is a novel consideration to minimize risk of future pressure-related injury. Counseling on alternative face masks that tie behind the head or anchoring ear loops to buttons sewn onto a hat or headband are other preventative pressures.

Bioactive components of different nasal spray solutions may defeat SARS-Cov2: repurposing and in silico studies.

The recent outbreak "Coronavirus Disease 2019 (COVID-19)" is caused by fast-spreading and highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). This virus enters into the human respiratory system by binding of the viral surface spike glycoprotein (S-protein) to an angiotensin-converting enzyme2 (ACE2) receptor that is found in the nasal passage and oral cavity of a human. Both spike protein and the ACE2 receptor have been identified as promising therapeutic targets to develop anti-SARS-CoV2 drugs. No therapeutic drugs have been developed as of today except for some vaccines. Therefore, potent therapeutic agents are urgently needed to combat the COVID-19 infections. This goal would be achieved only by applying drug repurposing and computational approaches. Thus, based on drug repurposing approach, we have investigated 16 bioactive components (1-16) from different nasal spray solutions to check their efficacies against human ACE2 and SARS-CoV2 spike proteins by performing molecular docking and molecular dynamic (MD) simulation studies. In this study, three bioactive components namely ciclesonide (8), levocabastine (13), and triamcinolone acetonide (16) have been found as promising inhibitory agents against SARS-CoV2 spike and human ACE2 receptor proteins with excellent binding affinities, comparing to reference drugs such as nafamostat, arbidol, losartan, and benazepril. Furthermore, MD simulations were performed (triplicate) for 100 ns to confirm the stability of 8, 13, and 16 with said protein targets and to compute MM-PBSA-based binding-free energy calculations. Thus, bioactive components 8, 13, and 16 open the door for researchers and scientist globally to investigate them against SARS-CoV2 through in vitro and in vivo analysis.

Systemic dendrimer nanotherapies for targeted suppression of choroidal inflammation and neovascularization in age-related macular degeneration.

Inflammation and neovascularization are key pathological events in human age-related macular degeneration (AMD). Activated microglia/macrophages (mi/ma) and retinal pigmented epithelium (RPE) play an active role in every stage of disease progression. Systemic therapies that can target these cells and address both inflammation and neovascularization will broaden the impact of existing therapies and potentially open new avenues for early AMD where there are no viable therapies. Utilizing a clinically relevant rat model of AMD that mirrors many aspects that of human AMD pathological events, we show that systemic hydroxyl-terminated polyamidoamine dendrimer-triamcinolone acetonide conjugate (D-TA) is selectively taken up by the injured mi/ma and RPE (without the need for targeting ligands). D-TA suppresses choroidal neovascularization significantly (by >80%, >50-fold better than free drug), attenuates inflammation in the choroid and retina, by limiting macrophage infiltration in the pathological area, significantly suppressing pro-inflammatory cytokines and pro-angiogenic factors, with minimal side effects to healthy ocular tissue and other organs. In ex vivo studies on human postmortem diabetic eyes, the dendrimer is also taken up into choroidal macrophages. These results suggest that the systemic hydroxyl dendrimer-drugs can offer new avenues for therapies in treating early/dry AMD and late/neovascular AMD alone, or in combination with current anti-VEGF therapies. This hydroxyl dendrimer platform but conjugated to a different drug is undergoing clinical trials for severe COVID-19, potentially paving the way for faster clinical translation of similar compounds for ocular and retinal disorders.