Mastocytosis and COVID19 infection and vaccination: A pediatric series

Introduction: Mastocytosis encompasses a heterogeneous group of diseases characterized by an accumulation of clonal mast cells (MC) in the skin and/or internal organs, and symptoms of MC activation. This MC activation can be elucidated by several factors, including infections or vaccination. Objective(s): We present our experience with COVID infection and vaccination in a series of 133 patients with pediatric mastocytosis. Method(s): Between January 1998 and December 2022, 133 pediatric patients have been referred to our hospital owing to clinically suspected MC disorder, mainly with mastocytosis in the skin. The final diagnoses of mastocytosis were established by the presence of typical skin lesions together with an increase of MC numbers in a biopsy from lesional skin or activating KIT mutations in lesional skin tissue. Serum baseline tryptase and total immunoglobulin E levels were measured, and patients underwent a comprehensive allergy workup to confirm atopic status and history of anaphylaxis. Regarding vaccination, REMA's (Spanish Network on Mastocytosis) protocol was followed. Result(s): 13 patients with COVID infection were identified, of which 25 (56,8%) were female and 0% had symptoms of MC activation. All of them had an asymptomatic or mild course of COVID infection. None of the patients experimented MC activation symptoms during viral illness. Regarding COVID vaccination, all patients received premedication with antihistamine 60 minutes prior vaccination. No one experimented immediate reactions and only one patient (0,75%) referred worsening of MC activation symptoms (baseline pruritus, urtication and brain fog) only after the first doses, recovering without changes in his treatment (oral cromoglycate and antihistamine) in two months. Discussion(s): Although MC have been implicated in the pathogenesis of cytokine storm in COVID19, there is no clinical evidence of SARSCoV- 2-induced MC activation, perhaps related to the fact that bone marrow MC lack angiotensin-converting enzyme 2 receptors.

Incidence of symptomatic Covid-19 infections in patients with mastocytosis and chronic myeloid leukemia: A comparison with the general Austrian population.

BACKGROUND: The SARS-COV-2 (Covid-19) pandemic has impacted the management of patients with hematologic disorders. In some entities, an increased risk for Covid-19 infections was reported, whereas others including chronic myeloid leukemia (CML) had a lower mortality. We have analyzed the prevalence of Covid-19 infections in patients with mastocytosis during the Covid-19 pandemic in comparison to data from CML patients and the general Austrian population. MATERIALS AND METHODS: The prevalence of infections and PCR-proven Covid-19 infections was analyzed in 92 patients with mastocytosis. As controls, we used 113 patients with CML and the expected prevalence of Covid-19 in the general Austrian population. RESULTS: In 25% of the patients with mastocytosis (23/92) signs and symptoms of infection, including fever (n = 11), dry cough (n = 10), sore throat (n = 12), pneumonia (n = 1), and dyspnea (n = 3) were recorded. Two (8.7%) of these symptomatic patients had a PCR-proven Covid-19 infection. Thus, the prevalence of Covid-19 infections in mastocytosis was 2.2%. The number of comorbidities, subtype of mastocytosis, regular exercise, smoking habits, age, or duration of disease at the time of interview did not differ significantly between patients with and without Covid-19 infections. In the CML cohort, 23.9% (27/113) of patients reported signs and symptoms of infection (fever, n = 8; dry cough, n = 17; sore throat, n = 11; dyspnea, n = 5). Six (22.2%) of the symptomatic patients had a PCR-proven Covid-19 infection. The prevalence of Covid-19 in all CML patients was 5.3%. The observed number of Covid-19 infections neither in mastocytosis nor in CML patients differed significantly from the expected number of Covid-19 infections in the Austrian population. CONCLUSIONS: Our data show no significant difference in the prevalence of Covid-19 infections among patients with mastocytosis, CML, and the general Austrian population and thus, in mastocytosis, the risk of a Covid-19 infection was not increased compared to the general population.

Insights from a COVID-19 in-person vaccination program operated in an Allergy department over 13 months

Background: The Spanish COVID-19 vaccination program commenced in December 2020. Some patients were excluded due to background pathologies, ever changing vaccination protocols and the risk of the secondary effects. Some were allergy patients with previous non-vaccine- related anaphylactic episodes, mastocytosis, and food or drug allergies. There were concerns that patients with secondary effects after the first or second doses would be reluctant to have further doses. The Allergy department at the Hospital Universitario Central de Asturias created a COVID-19 pre-and post-vaccination in-person program in which allergy excipient testing and vaccination were carried out when necessary. As far as we are aware, this is the first ever allergy-led testing and vaccination centre protocol of this kind. Method(s): 110 consecutive patients received at least one vaccine dose under the program in the Allergy Department from January 2021 to February 2022. Result(s): Females were more likely to be referred to the Allergy Department (90% of the total). The mean patient age was 53 years and ranged from 18 to 92 years. 27% were existing patients referred internally by the Allergy department, with the remainder from elsewhere. Angioedema (9%), mastocytosis (4%) and anaphylaxis (17%) were some of the patients' preconditions. A third of patients had two or more doses administered in the department. 61% of patients who received one dose of vaccine in the Allergy department went on to complete the full vaccination course as per national Spanish protocol. Only 16% could not continue with immunizations due to a severe allergic reaction to their first or second doses. None of the patients in the Allergy department program required emergency care after vaccination. Conclusion(s): The majority of patients at high risk of secondary effects were able to complete their vaccination course after the Allergy department input. The Allergy department can work as a successful vaccination centre when required.

Pediatric COVID-19 vaccination -Lessons learned from the vaccination of the Portuguese children

Background: Following the use of COVID-19 vaccines worldwide, few cases of severe allergic reactions were reported. According to recent Portuguese guidelines, patients (pts) with suspected allergy to a COVID-19 vaccine component, history of anaphylaxis following vaccination, idiopathic anaphylaxis and mast cell disorders, should be referenced for Immunoallergology evaluation. Fear of a hypersensitivity reaction, especially among pts with allergic disease, is associated with lower vaccine adherence. This study aimed to evaluate BNT162b2 vaccination outcomes in pediatric pts with suspected severe allergic reactions prior to or after vaccination. Method(s): W e c onducted a p rospective s tudy i ncluding p ediatric pts with high risk of allergy to COVID-19 vaccine referred to Immunoallergology Department of a Tertiary Hospital. Demographic data, primary medical conditions and vaccination status were collected. After a detailed assessment by an allergologist, in selected cases, BNT162b2 vaccine administration in hospital facilities was performed, followed by a 1-hour observation period. Result(s): Twenty-two pts were included (18 males, 13.1+/-2.6years;min 7, max 17;13 atopic), referenced mainly from primary care (9) and other specialties (8). Most of the pts were referenced for the first dose of vaccine (18), due to mastocytosis/tryptasemia (5), previous allergic reaction to another vaccine (4), idiopathic anaphylaxis (3), complex comorbidities (2), drug anaphylaxis (1), parental reluctance (1), other (2). Four pts were evaluated for the second dose of COVID-19 vaccine, due to an acute urticaria after the first BNT162b2 vaccine dose. Three pts were eligible, after our evaluation, for primary care vaccination, that occurred without adverse reactions. Regarding the remaining 19 pts eligible for hospital vaccination, 13 were premedicated with oral antihistamines +/- montelukast. Eleven pts received BNT162b2 vaccine in hospital facilities [first dose (9);second dose (2)] with no reported adverse events. Vaccine administration was postponed in 3 pts due to SARS-CoV- 2 infection and 1 due to parental hesitancy. Conclusion(s): Our data support that allergic reactions to BNT162b2 vaccines are rare, even in the pediatric population with high risk of allergic reactions or with a history of previous severe allergic reactions. The favourable safety profile outcomes, along with the risk reduction of allergic reactions, increase vaccine confidence, broadening community protection.

SARS-CoV- 2 vaccines are well tolerated in patients with mastocytosis

Background: The overall risk for anaphylaxis in mastocytosis is increased compared to the general population and has been reported in up to 49% in some cohorts. Concerns about vaccine safety have necessitated updates to the recommendations, especially in terms of allergic diseases. Method(s): The hospital records of the 7 patients (57% female) who had been diagnosed of either cutaneous or systemic mastocytosis and being followed up in our tertiary center have been reviewed retrospectively. Result(s): Six patients had been vaccinated with Biontech and Sinovac vaccines. One (14%) patient had cutaneous, four (57%) had indolent systemic, and two (29%) had aggressive systemic mastocytosis. Two patients had been premedicated with antihistamine and corticosteroid. While one has had mild reactions after both doses of Sinovac, the other had no reaction after Biontech vaccine. A total of 15 vaccinations were administered to 6 patients, and one (43%) patient with cutaneous mastocytosis has experienced a non-life- threatening reaction after Sinovac vaccine. Conclusion(s): Our results point out that the COVID-19 vaccines in our patients with mastocytosis seem to be safe and they should be encouraged to get vaccinated, and the role of premedication in preventing vaccine reactions is unclear. (Figure Presented).

Prevalence of allergic reactions after Pfizer-BioNTech COVID-19 vaccination

Background: Allergic reactions to COVID-19 vaccines have raised concerns, particularly as repeated doses are required. Skin tests with vaccines excipient were found to be of low value whereas the utility of skin tests with the whole vaccine is yet to be determined. Objective(s): we set to evaluate a panel of skin tests and outcomes of subsequent doses of immunization among subjects that suffered an immediate allergic reaction to the Pfizer-BioNTech (BNT162b2) COVID-19 vaccine. Method(s): In a prospective cohort study during December 27th-2020 to February 22nd-2021 Individuals with allergies who applied to the COVID 19 vaccine referral center at the Sheba Medical Center in israel, underwent risk assessment using an algorithm that included a detailed questionnaire department. Patients were considered to be at high risk for allergic reactions if thery either had: (1) prior anaphylactic reaction to any drug or vaccine, (2) multiple drug allergies, (3) multiplemallergies, or (4) mast cell disorders, as were patients who were deferred by their GP or local allergist or the immunization team from vaccination in the regular setting because of concerns about allergic. reactions. This high-risk group was referred to be immunized with 2 hours of observation by a dedicated allergy team. Result(s): Of the 429/8102 individuals who applied to the COVID-19 referral center and were defined as "highly allergic", 304 (70.8%) were female, mean age was 52 +/- 16 years. This "highly allergic" group was referred to immunization under medical supervision. Following the 1st dose of the BNT162b2, 420/429 (98%) had no immediate allergic event, 6/429 (1.4%) developed minor responses and 3/429 (0.7%) had anaphylactic reactions. During the study period, 218/429 "highly allergic" patients received the 2nd dose, of which 214/218 (98.1%) had no allergic reactions while 4 patients had minor allergic reactions. Other immediate and late reactions were comparable to the general population except for delayed itch and rash that were more common among allergic patients. Conclusion(s): The rate of allergic reactions to BNT162b2 vaccine, is higher among allergic patients, particularly in a sub-group with high-risk history. In this study we showed that the vast majority of patients with a history of allergic diseases and particularly "highly allergic" patients can be safely immunized. Utilizing an algorithm that can be implemented in different medical facilities and include a referral center, a risk assessment questionnaire and a setting for immunization under medical supervision of "highly allergic" patients. Further studies are required to define more specific risk factors for allergic reactions to BNT162b2 vaccine.

Collaboration strategies for COVID-19 vaccination: Experience of an Allergy and Clinical Immunology Department from a tertiary hospital

Background: Vaccination plays an essential role in controlling SARS-CoV- 2 pandemics. Due to initial concerns about hypersensitivity reactions (HR) to these new vaccines, our department, in articulation with Primary Healthcare Services (PHS) has developed several strategies to support COVID-19 vaccination. This work aims to describe those strategies and report the results. Method(s): The strategies developed for COVID-19 vaccination, from March to December 2021, included: 1) telephone support for health professionals (TS for HP) from the Vaccination Centres (VC), 2) priority appointments (PA) of patients classified as a higher risk for HR, 3) hospital vaccination of high-risk patients as defined by the national health authority. A retrospective and descriptive analysis of the support activity developed and from the data of patients vaccinated at the hospital in the same period were performed. Result(s): During the considered period, our department screened 1618 patients: 420 (26%) through telephone support for HP (TS for HP) from VC and 1198 (74%) at priority appointments (PA). After TS for HP, community vaccination (CV) was recommended in 87% (n = 364) of cases and a PA was advised in 13% (n = 56). Of the patients evaluated in PA, 80% were recommended CV, with restriction of the vaccine to administer in 28% of them. We always found an option to vaccine all. At the hospital were vaccinated 178 patients, 83% (n = 147) women, median age (P25-75) 61 (46-76) years. Hospital vaccination criteria were: past history of multiple drug HR (n = 93;52%), HR to vaccines (n = 46;26%), HR to the 1st dose of anti-SARS- CoV- 2 vaccine (n = 30;17%), idiopathic anaphylaxis (n = 10;6%) and systemic mastocytosis (n = 2;1%). 15% of patients (n = 26) performed skin tests with vaccines, which were negative in 25 and inconclusive in 1 case. 145 (82%) were first shots, 32 (18%) second shots, and one booster shot. Only one patient had a mild immediate reaction (2nd booster vaccination), promptly treated with antihistamine and corticosteroid. Conclusion(s): The collaboration strategies adopted by our department allowed the vaccination of 1618 patients and avoided vaccination delays in most of the VC contacts. In our sample, hospital vaccination of patients at higher risk for HR was safe.

Safety of Covid-19 vaccination in patients with mastocytosis

Background: Mastocytosis is a disorder characterized by an accumulation of mast cells in one or more organ systems and increased risk for severe anaphylaxis. Coronavirus disease 2019 (COVID-19) is associated with a relatively high rate of severe lung disease and mortality. During 2020, vaccines against COVID-19 were developed. The reported frequency of severe side effects appears to be low even in patients with severe allergies and mastocytosis. The aim of this study was to evaluate the safety of vaccines against COVID-19 in patients with mastocytosis. Method(s): Retrospective analysis of patients with a diagnosis of mastocytosis who have been vaccinated against COVID-19 in our department, from January to December 2021. Demographic data, history of anaphylactic reactions, COVID-19 vaccines used, premedication with antihistamines and hypersensitivity reactions were reviewed. Result(s): This study included 14 patients (64% (n = 9) were female, median age 51 +/- 18 years). Twelve (86%) patients had indolent systemic mastocytosis and two (14%) had cutaneous mastocytosis. Four (29%) patients had a history of idiopathic anaphylaxis, three (21%) reported anaphylaxis to hymenoptera venoms and one (7%) anaphylaxis to NSAID. The median basal serum tryptase level was 38.9 ng/ml, with a range from 12.7 to 91 ng/ml. Thirteen (93%) patients received an mRNA vaccine, and one adenoviral vector vaccine (7%), 2 doses each (28 administrations in total). None of the patients received premedication with antihistamines before the vaccination. None of the patients presented hypersensitivity reactions after the vaccine against COVID-19. Conclusion(s): As reported in recent studies, vaccination against COVID-19 in adult patients with mastocytosis is safe. Some authors recommend premedication in patients with mastocytosis at high risk for anaphylaxis. In our study, none of the patients received premedication and no hypersensitivity reactions were observed. More studies are needed, but in our sample, as observed for other vaccines, the vaccine against COVID-19 in patients with mastocytosis was safe.

COVID-19 vaccination in primary Mast Cell Disorders: Real-life data from a single centre

Background: Mast cell disorders (MCDs) are characterized by the proliferation and accumulation of mast cells in different tissues and their inappropriate release of mediators. Primary MCDs include systemic and cutaneous mastocytosis and monoclonal MC activation syndrome. They manifest with symptoms ranging from rash to anaphylaxis, idiopathic or elicited by heterogeneous factors, including vaccines. Vaccines are useful to prevent severe lung disease and mortality in COVID-19. Early reports of allergic reactions to COVID-19 vaccines emerged;however, their frequency is low. There are limited data on the safety of COVID-19 vaccine for immediate allergic reactions in high-risk patients like those with MCDs. To date, data concerning both the type of premedication and its need in these patients undergoing COVID-19 vaccines are limited. The objective of this study is to evaluate the safety of COVID-19 vaccine in patients with MCDs. Method(s): We included retrospectively patients with primary MCDs, according to WHO criteria, attending the Clinical Immunology and Allergy Unit at AO Mauriziano from June 2000 to December 2021, who underwent COVID-19 vaccination. We reported demographic and clinical data and noted -by phone call -vaccine type, premedication scheme, and contingent reactions. Result(s): We enrolled 44 patients (22 female, 50%), with a median age at diagnosis of 43.4 yrs. 25 patients had ISM, 8 CM, and 11 MMCAS. Median tryptase level was 44.3 ng/ml. 17 patients had history of anaphylaxis, none after vaccination. 37 patients (84.1%) underwent COVID-19 vaccination, 7 refused it. 32 completed the vaccination course, and 5 received two doses only. 25 patients were fully vaccinated with mRNA vaccine. The PEG-allergic one underwent Ad26.COV2.S vaccine, another one had first ChAdOx1, then mRNA-1273. All patients were vaccinated in hospital setting and observed for one hour. Most patients continued the daily antihistamine;9 started it few days before the injection;4 patients underwent vaccination without premedication. None showed anaphylaxis. One patient had immediate flushing;another had a delayed asthma exacerbation. A non-premedicated patient had immediate urticaria at first dose, while he tolerated others with AH The small cohort and the retrospective design limit this study. Nonetheless, the absence of severe hypersensitivity reactions to COVID-19 vaccines in our patients with MCDs, is an important finding. Conclusion(s): Our results confirm that patients with MCDs may be safely vaccinated to COVID-19.

Safety of a mRNA COVID-19 vaccine in patients with indolent systemic mastocytosis

Background: The development of vaccines against coronavirus disease 2019 (COVID-19) and the report of associated allergic reactions has led to growing concern about their safety, especially in populations at risk for anaphylaxis such as patients with systemic mastocytosis. Method(s): We conducted a retrospective descriptive analysis of patients with systemic mastocytosis referred to our Allergy and Clinical Immunology Department, between June 2021 and February 2022, for COVID-19 vaccination. Patients were divided into two groups according to their risk of allergic reaction: low/moderate-risk (no history of severe allergic reaction, with or without a history of allergic disease) and high-risk (history of any severe allergic reaction). All patients were premedicated with 60 mg of oral prednisolone 24 hours and 1 hour prior inoculation, and with an oral antihistamine 1 hour before vaccine administration. Low/moderate-risk patients were monitored for 30 minutes after vaccine inoculation. High-risk patients got a peripheral venous access and remained under medical surveillance for 60 minutes. Result(s): A total of 45 patients were included in the analysis: 62.2% females, with a mean age of 48.8 years (range: 22-85). All patients had indolent systemic mastocytosis subtype, with a median tryptase level of 15.6 ng/mL (range: 4.3-185 ng/mL);11 (24.4%) were in the high-risk group (8 with history of anaphylaxis to hymenoptera venom and 3 with prior drug anaphylaxis). Low/moderate-risk and high-risk groups had similar median levels of serum tryptase (15.5 vs. 16.6 ng/ mL, p = 0.932). All patients received BNT162b2 mRNA COVID-19 vaccine and a total of 118 doses were administered (24.6% in the high risk group). No adverse events, including allergic reactions, after vaccine inoculation were recorded during the surveillance period. Conclusion(s): To our knowledge, this is the largest series reporting safety of a mRNA COVID-19 vaccine in patients with systemic mastocytosis. Our data reinforce the fact that even patients with increased risk for allergic reactions can be safely vaccinated against COVID-19, and that earlier concerns should be abandoned so a widespread immunization can be achieved.

Vaccination against COVID-19 in patients with allergic diseases

Background: In the context of the COVID-19 pandemic it is very important to achieve collective immunity. Allergic reactions to vaccines are rare -up to 30 per 100 000, but 4-8 may have anaphylaxis. The aim of this study was to develop safe COVID-19 vaccination algorithm for patients with allergic diseases (AD). Method(s): Patients with the history of AD were invited for vacination to the Regional Allergy Center in Dnipro (Ukraine). Before vaccination all patients underwent: serum tryptase, whole blood count (WBC), D-dimer, blood biochemistry, electrocardiogram (ECG) and spirometry (for patients with asthma (A) only). 126 patients with AD 19-85 (53.2+/-1.5) years old (50, 39.68% men) were included into the study. 25.39% of them had seasonal allergic rhinitis (SAR);15.07% -A;10.32% -A+ SAR;35.71% -urticaria;11.11% -drug allergy;2.38% -history of anaphylaxis. Result(s): There were not any clinically significant changes found in WBC, blood biochemistry and ECG. At the same time in 4 patients (3.2%) high tryptase level was detected. Mastocytosis was diagnosed by sternal puncture in 3 of them. During 12 weeks they were treated by monoclonal antibodies and after that vaccinated with two doses of mRNA vaccine without adverse reactions. For 1 patient with high tryptase level and a history of 3 anaphylaxis with hospitalization vacination was postponed. 1 patient had elevated D-dimer (PTA was diagnosed by CT) -vaccination was temporarily delayed. In 10 patients uncontrolled A with FEV1 below 70% (36-65%) was found. After the correction of basic therapy, within 2 weeks vaccination was carried out. All patients were given a 4-fold dose of desloratadine 30 minutes before vaccination. Conclusion(s): 1. AD are not a contraindication for vacciantion against COVID-19. 2. Before vacciantion all patients with a history of AD should be examined by an allergist. 3. For patients with severe AD level of serum tryptase should be detected before vacciantion. 4. Patients with AD should be vaccinated in an allergy center with premedication of H1-blocker in a 4-fold dose.

COVID-19 Vaccines Are Safely Tolerated in Adolescents with Cutaneous Mastocytosis.

INTRODUCTION: The management of the COVID-19 vaccine in children with mastocytosis is unclear due to a lack of data. In the current study, we aimed to evaluate the adverse reactions following COVID-19 vaccination in adolescents with cutaneous mastocytosis (CM). METHODS: This study included 27 paediatric patients who were diagnosed with CM and were followed up in the paediatric allergy department of a tertiary care children's hospital. RESULTS: The median (IQR) age of the patients at the time of COVID-19 vaccination was 180 (156-203) months. Forty-four per cent of patients were vaccinated with the COVID-19 vaccine. Among all participants, the vaccination rate was found to be higher in older children, those who had been diagnosed with MPCM, and those who had not been infected with COVID-19 (p = 0.019, p = 0.009, p = 0.002, respectively). A total of 23 doses of the COVID-19 vaccine, including two doses of Sinovac/CoronaVac and 21 doses of Pfizer/BioNTech, were administered to 12 paediatric patients with CM. One of the patients had a history of intense itch, erythematous urticarial plaques, and had an exacerbation of existing skin lesions within 24-48 h after both doses of Pfizer/BioNTech vaccination. CONCLUSION: The COVID-19 vaccination of patients with CM in this series seems to be safe, and the rate of adverse events was comparable to that in the general population. These results found in adolescents with CM are in line with the existing evidence that CM does not preclude vaccination in children.

Practice Notes from the AAAI

99441 – [Telephone evaluation and management service by a physician or other qualified healthcare professional who may report evaluation and management services provided to an established patient, parent, or guardian not originating from a related E/M service provided within the previous seven days nor leading to an E/M service or procedure within the next 24 hours or soonest available appointment;Five-10 minutes of medical discussion.] Cellular Partners of Mast Cells and Basophils in Homeostasis and Allergic Disease You can find a full list of 2020 Virtual Annual Meeting sessions, including pricing for special sessions, by visiting the AAAAI Continuing Education Center at education.aaaai.org.Earn CME Credit with Select AAAAI Podcast Episodes The AAAAI is excited to offer free CME credit for members who listen to select episodes of our podcast, Conversations from the World of Allergy. Episodes offering CME credit will be identified with a CME icon and CME language in the podcast description.Lay Organizations The AAAAI places a high value on its relationships with patient advocacy organizations in support of our mutual concern for the needs of people with allergy, asthma and immunologic disease and their families. Allergy & Asthma Network allergyasthmanetwork.org American Partnership for Eosinophilic Disorders (APFED) apfed.org Asthma & Allergy Foundation of America (AAFA) aafa.org Alaska Chapter: aafaalaska.com California Chapter: aafa-ca.com Greater Kansas City Chapter: aafakc.org Maryland/Washington DC Chapter: aafa-md.org Michigan Chapter: aafamich.org New England Chapter: asthmaandallergies.org Texas Chapter: aafatexas.org St. Louis Chapter: aafastl.org Campaign Urging Research for Eosinophilic Disease (CURED) curedfoundation.org Food Allergy and Anaphylaxis Connection Team (FAACT) foodallergyawareness.org Food Allergy Research & Education (FARE) foodallergy.org Immune Deficiency Foundation (IDF) primaryimmune.org International FPIES Association fpies.org The Mastocytosis Society (TMS) tmsforacure.org US Hereditary Angioedema Association (HAEA) haea.org You Can Now Use Our Internet Point-of-Care Activity to Earn MOC The COVID-19 pandemic has altered the way we see patients and conduct research.

Treatment of Advanced Systemic Mastocytosis with Midostaurin: Practical Guidance for Optimal Therapy and Management.

Systemic mastocytosis (SM) is a rare disease with a range of clinical presentations, and the vast majority of patients have a KIT D816V mutation that results in a gain of function. The multikinase/KIT inhibitor midostaurin inhibits the D816V mutant and has a well-established role in treating advanced SM. Even if considered the standard of therapy, some open questions remain on optimizing midostaurin management in daily practice. The current review presents the opinions of a group of experts who met to discuss routine practice using midostaurin in patients with advanced SM. The efficacy and safety of midostaurin in Phase 2 trials are overviewed, followed by practical guidance for optimal therapy management and adverse events during therapy with midostaurin. Specific guidance is given for initiating therapy and evaluating response with midostaurin as general assessment and laboratory, instrumental, pathological, and molecular exams. Special consideration is given to dose interruption, reduction, and discontinuation of therapy, as well as adverse event management and supportive therapy. Patients should be informed about possible side effects and receive practical advice to avoid or limit them and antiemetic prophylaxis so that therapy with midostaurin can continue as long as clinical benefit is observed or until unacceptable toxicity occurs. Lastly, considerations on the use of midostaurin during the ongoing Covid-19 pandemic are made. The overall scope is to provide guidance that can be useful in daily practice for clinicians using midostaurin to treat patients with advanced SM.

The Role of Mast Cells in the Pathogenesis of Covid-19

Background: The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) was first reported in December 2019 in Wuhan. The problem of COVID-19 treatment is still relevant, and it is necessary to study in details the pathogenesis of COVID-19, including the role of mast cells (MCs). Aim: The aim of the review is to reveal the role of MCs, their receptors and mediators in the pathogenesis of the COVID-19. Results: This review demonstrates a possible role of MCs in the pathogenesis of COVID-19. Conclusion: MCs may be key elements of inflammation caused by COVID-19. MCs express various receptors on their surface that ensure the interaction of SARS-CoV-2 and MCs. Activated MCs release inflammatory cytokines, chemokines and proteases, which are involved in both the protective function and hyperinflammation in COVID-19.

Patient's Adherence and Compliance and Quality of Life During/After VIT.

Adherence and compliance, respectively considered as a more positive, proactive behavior, resulting in a patient's lifestyle change to follow a daily regimen, and, as a more enforced response to an external command, are a critical aspect of any medical therapy, since it is estimated that less than half of the patients who are prescribed a therapy perform it, respecting the doses and duration. As far as aeroallergen immunotherapy is concerned, current data show that adherence is respected in about 50% of subcutaneous immunotherapy and in percentages even lower than 20% in sublingual immunotherapy treatments. This review analyzes the adherence to venom immunotherapy (VIT), in which, given its purpose of preventing potentially fatal anaphylactic reactions to insect stings, this aspect plays a critical role. In fact, protection from stings already takes place when the maintenance dose is reached, but VIT interruption before the recommended duration of 5 years exposes patients to new sting reactions. The data on adherence to VIT are far less abundant than that for aeroallergen immunotherapy. One of the first studies reported poor adherence in Austria, but the model used, consisting in the estimate of the percentage of patients with systemic reactions who accepted or rejected VIT, does not meet the criteria that define adherence to treatment. As for appropriate adherence studies, rates higher than 70% were reported in the United States and European countries. Studies from Italy found that good adherence were observed also in patients receiving, after 4 years of VIT, 3 months extended maintenance dose, as well as in patients treated during the COVID-19 pandemic, <10% of whom stopped VIT. Instead, only 35% of the patients treated for allergy to imported fire ant remained adherent after 1 year of treatment. However, also concerning honeybees and vespids, although adherence is satisfactory, it is possible to further improve it by increasing information and support for patients. Health-related quality of life (HRQL) is an efficient measure to estimate the effectiveness and safety of medical treatment. Tools designed to make patients aware of its improvement through VIT and, in particular, of the complete prevention of the risk of fatal reactions have an important role in reinforcing adherence. However, aspects not yet evaluated, such as the possible relationship between the efficacy of VIT and HRQL or its particular features in patients with mastocytosis, deserve specific studies.

Mastocytosis-A Review of Disease Spectrum with Imaging Correlation.

Mastocytosis is a rare disorder due to the abnormal proliferation of clonal mast cells. Mast cells exist in most tissues, mature in situ from hematopoietic stem cells and develop unique characteristics of local effector cells. Mastocytosis develops by activation mutation of the KIT surface receptor which is involved in the proliferation of a number of cell lines such as mast cells, germ cells, melanocytes, and hematopoietic cells. It manifests as two main categories: cutaneous mastocytosis and systemic mastocytosis. Imaging can play an important role in detection and characterization of the disease manifestation, not only by radiography and bone scans, but also magnetic resonance imaging and computed tomography, which can be more sensitive in the assessment of distinctive disease patterns. Radiologists should be aware of various appearances of this disease to better facilitate diagnosis and patient management. Accordingly, this review will discuss the clinical presentation, pathophysiology, and role of imaging in detection and extent estimation of the systemic involvement of the disease, in addition to demonstration of appearance on varying imaging modalities. Familiarity with the potential imaging findings associated with mastocytosis can aid in early disease diagnosis and classification and accordingly can lead directing further work up and better management.

COVID-19 Vaccination Is Safe among Mast Cell Disorder Patients, under Adequate Premedication.

Reported cases of anaphylaxis following COVID-19 vaccination raised concerns about the safety of these vaccines, namely in patients suffering from clonal mast cell (MC) disorders-a heterogenous group of disorders in which patients may be prone to anaphylaxis caused by vaccination. This study aimed to assess the safety of COVID-19 vaccines in patients with clonal MC disorders. We performed an ambidirectional cohort study with 30 clonal MC disorder patients (n = 26 in the prospective arm and n = 4 in the retrospective arm), that were submitted to COVID-19 vaccination. Among these, 11 (37%) were males, and median age at vaccination date was 41 years (range: 5y to 76y). One patient had prior history of anaphylaxis following vaccination. Those in the prospective arm received a premedication protocol including H1- and H2-antihistamines and montelukast, while those in the retrospective arm did not premedicate. Overall, patients received a total of 81 doses, 73 under premedication and 8 without premedication. No MC activation symptoms were reported. COVID-19 vaccination seems to be safe in patients with clonal mast cell disorders, including those with prior anaphylaxis following vaccination. Robust premedication protocols may allow for vaccination in ambulatory settings.

A systematic review on mucocutaneous presentations after COVID-19 vaccination and expert recommendations about vaccination of important immune-mediated dermatologic disorders.

With dermatologic side effects being fairly prevalent following vaccination against COVID-19, and the multitude of studies aiming to report and analyze these adverse events, the need for an extensive investigation on previous studies seemed urgent, in order to provide a thorough body of information about these post-COVID-19 immunization mucocutaneous reactions. To achieve this goal, a comprehensive electronic search was performed through the international databases including Medline (PubMed), Scopus, Cochrane, Web of science, and Google scholar on July 12, 2021, and all articles regarding mucocutaneous manifestations and considerations after COVID-19 vaccine administration were retrieved using the following keywords: COVID-19 vaccine, dermatology considerations and mucocutaneous manifestations. A total of 917 records were retrieved and a final number of 180 articles were included in data extraction. Mild, moderate, severe and potentially life-threatening adverse events have been reported following immunization with COVID vaccines, through case reports, case series, observational studies, randomized clinical trials, and further recommendations and consensus position papers regarding vaccination. In this systematic review, we categorized these results in detail into five elaborate tables, making what we believe to be an extensively informative, unprecedented set of data on this topic. Based on our findings, in the viewpoint of the pros and cons of vaccination, mucocutaneous adverse events were mostly non-significant, self-limiting reactions, and for the more uncommon moderate to severe reactions, guidelines and consensus position papers could be of great importance to provide those at higher risks and those with specific worries of flare-ups or inefficient immunization, with sufficient recommendations to safely schedule their vaccine doses, or avoid vaccination if they have the discussed contra-indications.