Citations

Abstract Background Wide-spread mast cell (MC)-associated symptoms and MC activation syndrome (MCAS) are often reported in patients with hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD). The goal of this study was to develop a novel MC score based on 11 self-reported MC-related conditions with clinical and research utility to better understand MC symptoms in hEDS and HSD patients. Methods From November 1, 2019, to June 13, 2025, patients ( n =2,141) filled out an Intake Questionnaire at the Mayo Clinic Florida EDS Clinic that included 11 self-reported questions related to categories of MC-related conditions for a MC score ranging from 0/11 to 11/11. Based on the MC score distribution in hEDS and HSD patients, a MC score of 0-1 was considered a low MC score and ≥5 was considered a high MC score. Symptoms/comorbidities were compared between patients with high vs. low MC scores. Results From the 2,141 hEDS/HSD patients, 535 (25.0%) had a MC score ≥5 (Hi MC). MCAS-specific symptoms such as nausea and vomiting were reported more often in hEDS/HSD patients with a high vs. low MC score ( p <0.0001). Random clinical blood tryptase and urinary MC markers were not elevated in patients with high MC scores ( n =50/group), although high MC scores were found to significantly reduce urinary creatinine levels indicating that the protein used to normalize data was affected by MC activity. In contrast, random blood IgE, tryptase and major basic protein (MBP) by ELISA were increased in patients with high MC scores (e.g., IgE hEDS p =0.0004, HSD p =0.003). Of note, the percentage of patients reporting abuse or post-traumatic stress disorder was nearly doubled in patients with high vs. low MC scores (Abuse and PTSD: hEDS p < 0.0001; HSD p < 0.0001). Overall, 109/135 (80.7%) in hEDS and 129/135 (95.6%) in HSD reported more symptoms/comorbidities if they had a high MC score. Conclusions We found that hEDS/HSD patients with high MC scores self-reported more widespread symptoms/comorbidities and higher MC-related blood markers than patients with low MC scores indicating the utility of this tool to evaluate the level of widespread MC activity in hEDS, HSD and other patients.

Background: One in five Americans turn to TikTok before calling their own physician. Objective: With social media on the rise as a source of health-related information, we aimed to investigate and evaluate popular content about mast cell activation syndrome (MCAS) on TikTok. Methods: Between June 14 and 16, 2024, four different MCAS-relevant phrases were searched on TikTok, and the top 50 most watched videos were analyzed independently by three subinvestigators. The global quality score (GQS) (range from 1 to 5) was applied to assess the value of the educational videos. The profession of the content creator, use of MCAS Vienna diagnostic criteria, association with postural orthostatic syndrome (POTS)/Ehlers Danlos syndrome (EDS), and information trends were also analyzed. Results: The 50 most watched MCAS-related videos collectively had > 6.5 million views, and the average number of views per video was 131,500. Most videos were created by health-care professionals (58%), including physicians (26%) and other health-care professionals (32%), whereas the minority were created by non‐health-care professionals (42%). Only one video included the MCAS Vienna criteria (2%), and 12 videos associated MCAS with POTS and/or EDS (24%). The average GQS was 1.94 (SD 0.34). Common MCAS misinformation trends included the following: inaccuracy of symptoms, diagnostic criteria, triggers, and treatment options. Conclusion: Most MCAS videos on TikTok contained misinformation, did not include key diagnostic criteria, and had poor GQS. The most viewed videos were primarily created by health-care professionals. Patients and health-care providers need to be aware of the quality of health-care information on social media.

BACKGROUND Approximately 10% of patients report penicillin allergy. Based on historical guidelines, patients with a penicillin allergy should receive an alternative to cephalexin for prophylaxis in dermatologic surgery. OBJECTIVE To determine, based on evidence, if cephalexin should be used as a first-line prophylactic antibiotic in dermatologic surgery for patients with penicillin allergy. METHODS Systematic review of the literature was performed with defined search terms. RESULTS Less than 5% of those with penicillin allergy labels have a true penicillin allergy. For patients with true, persistent penicillin allergy, there is an overall low cross-reactivity with cephalosporins, especially with cephalosporins that do not share identical R1 side chain. The first-generation cephalosporins, including cephalexin, have a slightly higher risk of cross-reactivity in patients with reported allergy to amino-penicillins (amoxicillin, ampicillin) but not other penicillins. The risk of severe cross-reactivity of cephalosporins in patients with low-risk penicillin allergies is extremely low. Cephalexin has a superior side effect profile and efficacy compared to alternatives. CONCLUSION Cephalexin should be used as the first-line prophylactic antibiotic in dermatologic surgery for patients with documented penicillin allergy, including anaphylaxis. There may be a higher risk of cross-reactivity with cephalexin in patients with a confirmed amino-penicillin allergy.

Abstract Pegfilgrastim is a sustained-duration form of the granulocyte colony-stimulating factor filgrastim to which a polyethylene glycol molecule is covalently bound to the N-terminal methionine residue. Although rare, anaphylaxis to pegfilgrastim has been reported. Desensitization is a safe management option for drug hypersensitivity. To date, no desensitization protocols to pegfilgrastim have been reported. We present the case of a 36-year-old female diagnosed with breast cancer who was treated with paclitaxel and carboplatin every two weeks plus pegfilgrastim, to which she developed anaphylaxis. The lack of alternative treatment options led to the decision to proceed with desensitization, which was carried out successfully with a novel 12-step, 1-bag protocol, allowing the safe resumption of the medication. Although the mechanisms underlying hypersensitivity to pegfilgrastim remain unknown, clinicians must be aware of the possibility of anaphylaxis to this medication and of the available treatment options, such as desensitization. To our knowledge, this is the first report of a desensitization protocol to pegfilgrastim.

Abstract Patients with newly diagnosed Graves disease often elect for treatment with the drug methimazole (MMI) over alternative therapies. However, MMI can commonly result in skin allergy that in severe cases can lead to discontinuation of therapy. We present a case of Graves thyrotoxicosis with a delayed hypersensitivity reaction while on MMI. The patient was successfully treated with a novel, individualized, 27-day desensitization protocol that resulted in tolerance of MMI with subsequent improvement in thyroid indices. Previous literature has offered various rapid desensitization protocols to MMI for immediate type hypersensitivity reactions. However, in nonimmediate, delayed hypersensitivity reactions, a slower desensitization protocol can be considered. As demonstrated in this case, desensitization to MMI is a reasonable alternative in patients who wish to avoid definitive therapy who develop an initial adverse reaction to MMI, as this can occur in up to 13% of treated cases.

Purpose of review Perioperative anaphylaxis has historically been attributed to IgE/FcεRI-mediated reactions; there is now recognition of allergic and nonallergic triggers encompassing various reactions beyond IgE-mediated responses. This review aims to present recent advancements in knowledge regarding the mechanisms and pathophysiology of perioperative anaphylaxis. Recent findings Emerging evidence highlights the role of the mast-cell related G-coupled protein receptor X2 pathway in direct mast cell degranulation, shedding light on previously unknown mechanisms. This pathway, alongside traditional IgE/FcεRI-mediated reactions, contributes to the complex nature of anaphylactic reactions. Investigations into the microbiota-anaphylaxis connection are ongoing, with potential implications for future treatment strategies. While serum tryptase levels serve as mast cell activation indicators, identifying triggers remains challenging. A range of mediators have been associated with anaphylaxis, including vasoactive peptides, proteases, lipid molecules, cytokines, chemokines, interleukins, complement components, and coagulation factors. Summary Further understanding of clinical endotypes and the microenvironment where anaphylactic reactions unfold is essential for standardizing mediator testing and characterization in perioperative anaphylaxis. Ongoing research aims to elucidate the mechanisms, pathways, and mediators involved across multiple organ systems, including the cardiovascular, respiratory, and integumentary systems, which will be crucial for improving patient outcomes.

Introduction Epidural steroid injections and epidural blood patches commonly involve the injection of a small amount of radiocontrast media under fluoroscopy to properly identify the target tissue or anatomic space and prevent off-target or intravascular delivery of therapeutic or diagnostic drugs. Iodinated low osmolar non-ionic contrast media is the standard preparation used as it is considered safe and cost-effective, but gadolinium-based preparations have been used as an alternative for patients with an ‘iodine’-related or radiocontrast media allergy label to prevent hypersensitivity reactions. The risk of neurotoxic events when gadolinium is inadvertently injected into the intrathecal space has been reported in recent years, raising concerns when gadolinium-based contrast media is used in lieu of iodinated low osmolar non-ionic contrast media. Methods A retrospective review was conducted of patients who received gadolinium-based contrast media for procedures with risk of inadvertent intrathecal access from January 1, 2019 to May 1, 2022. Information on patient demographics, allergy label information, and procedure description was documented for all patients who received gadolinium-based contrast media for axial spine procedures (including epidural steroid injections, epidural blood patch procedures, and selective nerve root blocks), and all side effects reported within 1 month of the procedure were recorded. Saved fluoroscopy images of all procedures for which there was concern for possible gadolinium-based contrast media-related side effect were reviewed for evidence of inadvertent intrathecal gadolinium-based contrast media administration. Descriptive statistical analysis was performed using REDCap and IBM SPSS Statistics V.28. Results We identified 508 patients who received gadolinium-based contrast media during a fluoroscopically guided axial spine procedure. These patients underwent 697 epidural procedures and 23 patients were identified as experiencing an adverse event that could be consistent with possible, probable, or clear signs of exposure to intrathecal gadolinium. Our calculated adverse event rate was 3.3%. Ten patients required additional medical evaluation or treatment. Discussion Almost all patients in our cohort had an allergy label on their chart that guided the provider to switch to gadolinium-based contrast media, but most were incomplete, ill-defined, or related to allergy to iodine but not iodinated contrast media. Such practice is not recommended based on current guidelines. The current study raises concern regarding the use of gadolinium-based contrast media in axial spine procedures, with the risk of potential severe adverse events, without evidence-based need for avoiding iodinated contrast media.

Abstract Disclosure: J. Arguinchona: None. A. Mahajan: None. A. Gonzalez-Estrada: None. E. De Filippis: None. Introduction: Patients with newly diagnosed Graves’ disease often choose treatment with methimazole (MMI) over traditional ablation therapies. However, MMI can result in adverse reactions including skin rash, pruritus, and urticaria. We present a case of Graves’ thyrotoxicosis with a type IV hypersensitivity reaction while on MMI. The patient was successfully treated with a novel, individualized, 27-day desensitization protocol which resulted in tolerance of MMI with subsequent improvement in thyroid indices. Clinical Case: A 42-year-old female presented for abnormal thyroid studies with associated insomnia, heat intolerance, palpitations, resting tremor, and weight loss. Lab work revealed a thyroid-stimulating hormone &lt;0.005 (0.450-4.500 μIU/mL), free thyroxine 3.28 (0.82-1.77 ng/dL), triiodothyronine 310 (71-180 ng/dL), thyroid peroxidase antibody (Ab) 62 (0-34 IU/mL), thyroid-stimulating immunoglobulin 0.67 (0.00 -0.55 IU/L), and thyrotropin receptor Ab of 6.00 (0.00-1.75 IU/L). She was started on MMI, 10 mg daily for Graves’ disease. Three weeks later, T3 and T4 remained elevated prompting an increase in MMI dose to 10 mg twice daily. Two weeks later, she developed a diffuse, pruritic maculopapular exanthema over her trunk, neck, and extremities. Methimazole was discontinued while prednisone was initiated that subsided her rash. Unfortunately, the patient’s symptoms recurred upon repeat MMI exposure. The patient declined propylthiouracil due to concerns of hepatotoxicity and elected to avoid ablation therapy with iodine or surgery. With the assistance of an allergist, a novel, 10-step, 27-day desensitization protocol was developed specifically for her reaction to MMI with plans to taper prednisone once desensitization was completed. The patient underwent desensitization with development of mild lower extremity exanthema that was successfully treated with high dose antihistamines. Three months later, she was tolerating MMI at 15 mg daily without further adverse reactions and tapered off prednisone. While on MMI, her immune titers normalized with euthyroid clinical and biochemical restoration. Conclusion: Many patients and clinicians initially prefer medical management over definitive ablation therapies in the treatment of Graves’ disease. This case demonstrates with the assistance of an allergist, desensitization to MMI is a viable option in the setting of a known hypersensitivity reaction when it is the first line treatment and no equally efficacious alternatives exist. In addition, patient’s preferences should also be considered during medical decision making. Previous literature has offered various rapid desensitization protocols for MMI for immediate type hypersensitivity reactions. However, in non-immediate, type IV hypersensitivity reactions, a slower desensitization protocol can be considered, as demonstrated in this case. Presentation: Thursday, June 15, 2023