Non-steroidal anti-inflammatory drug-induced anaphylaxis infrequent in 388 patients with mastocytosis: A two-center retrospective cohort study.

Background: Anaphylaxis is a well-known feature of mastocytosis, particularly in relation to hymenoptera venom stings. It is therefore hypothesized that mastocytosis patients may also be predisposed to severe hypersensitivity reactions to certain medications including non-steroidal anti-inflammatory drugs (NSAIDs). For this reason, these patients are usually discouraged from using these drugs. The current study aimed to determine the prevalence and evaluate the severity of NSAID-related hypersensitivity reactions among patients with mastocytosis. Methods: A retrospective study was conducted among a total of 388 (≥18 years old) consecutive patients from two independent European mastocytosis centers, in Sweden and Italy. Patients underwent a thorough allergy work-up where self-reported NSAID-hypersensitivity reactions were re-evaluated by an allergist in the first cohort (202 patients) and results were validated in the second cohort (186 patients). Results: Overall frequency of NSAID-hypersensitivity was 11.3% in the total study cohort. Most patients reacted with cutaneous symptoms (89%), whereas severe hypersensitivity reactions were infrequent with only 11 patients (2.8%) experiencing anaphylaxis. All NSAID-related hypersensitivity reactions had occurred before mastocytosis was diagnosed. There was no difference between the groups regarding gender, baseline tryptase levels or presence of atopy, asthma/rhinitis. Conclusion: Our study indicates an approximate 4-fold increased prevalence of NSAID hypersensitivity among mastocytosis patients compared to the general population. However, most NSAID reactions were limited to the skin as the prevalence of overall anaphylaxis was infrequent. Our results support that mastocytosis patients with a known tolerance to NSAIDs can continue using these medications without special precautions, whereas those with a prior reaction to NSAIDs should undergo thorough allergy work-up, including drug challenges.

Sustainable local development and agri-food system in the post Covid crisis: The case of Rome.

This paper focuses on the research pathway related to the drafting of a strategic Agri-Food Plan of Rome. The paper highlights the theoretical background and investigates the strategic vision and actions, as well as the role played by the Covid-19 Pandemic by changing priorities. The merging between two strands of study is identified: urban food strategies and sustainability in the debate on post Covid-19 food planning studies and the analysis of local agri-food systems for economic development. This work shows that in the case of urban and metropolitan areas around the Mediterranean, agriculture, the cultural dimension of food, logistics, research and innovation, and tourism marketing can be included within a single planning and policy tool. In the case of Rome, the place-based approach allowed us to consider the specificities of social and spatial contexts with interactions of market drivers with public institutions. This approach may constitute a promising path of research for the future of sustainable planning, particularly in Mediterranean cities. The results have interesting policy implications that should be more explicitly considered in addressing urban agendas, and in particular, the role of food to promote local development by integrating economic, social, and environmental and spatial values at a regional scale.

Hereditary alpha-tryptasemia.

PURPOSE OF REVIEW: To discuss our evolving knowledge about the genetic variations in human tryptase and recent advances in associated clinical phenotypes. RECENT FINDINGS: Hereditary alpha-tryptasemia (HAT) is an autosomal dominant genetic trait and a common cause of elevated basal serum tryptase (BST) in Western populations. It is a risk factor for severe anaphylaxis and an established modifier of mast cell mediator-associated symptoms among patients with systemic mastocytosis (SM). SUMMARY: The unique properties of naturally occurring alpha/beta-tryptase heterotetramers may explain certain elements of phenotypes associated with HAT. Understanding the physiology of tryptases and how this may relate to the clinical features associated with HAT is the first step in identifying optimal medical management and targets for novel therapeutics.

A Multidisciplinary Diagnostic Approach Reveals a Higher Prevalence of Indolent Systemic Mastocytosis: 15-Years' Experience of the GISM Network.

Systemic mastocytosis (SM) and other adult clonal mast cell disorders (CMD) are often underestimated, and their epidemiology data are scarce. We aimed at evaluating the impact of the activity of the Interdisciplinary Group for Study of Mastocytosis (GISM) of Verona on the prevalence and incidence of CMD. We examined the data of 502 adult patients diagnosed with CMD and residing in the Veneto Region, consecutively referred to GISM between 2006 and 2020. SM was diagnosed in 431 cases, while 71 patients had cutaneous mastocytosis or other CMD. Indolent SM represented the most frequent SM variant (91.0%), mainly with the characteristics of bone marrow mastocytosis (54.8%). The prevalence of SM in the adult population of the Veneto region and of the Verona province was 10.2 and 17.2/100,000 inhabitants, respectively. The mean incidence of new SM cases in Verona was 1.09/100,000 inhabitants/year. Hymenoptera venom allergy was the main reason (50%) leading to the CMD diagnosis. Osteoporosis, often complicated by fragility fractures, was present in 35% of cases, even in young patients, especially males. Our data show a higher prevalence and incidence of SM than previously reported, confirming that reference centers with multidisciplinary approach are essential for the recognition and early diagnosis of CMD.

Prevalence of Pol d 1 Sensitization in Polistes dominula Allergy and Its Diagnostic Role in Vespid Double-Positivity.

BACKGROUND: Stings by Polistes species frequently cause allergic reactions. However, standard allergy diagnostics are often unable to differentiate between primary sensitization and cross-reactivity in case of Vespula/Polistes double-sensitization because antigen 5 is the only Polistes venom molecule currently available in diagnostics (Pol d 5). OBJECTIVE: To evaluate the frequency of phospholipase A1 in Polistes venom allergy (Pol d 1) and its diagnostic role in vespid allergy. METHODS: We performed component-resolved diagnostics in patients with vespid allergic reactions who were positive to Polistes venom. A prevalence analysis was performed and the diagnostic accuracy of Pol d 1 was evaluated to detect primary Polistes sensitization in double-sensitized patients. RESULTS: Blood samples were collected from 132 patients. Pol d 1 was present in 97% to 100% of 128 Polistes-positive patients. It was frequently involved in case of positivity to a single Polistes molecule (48% in double- and 80% in mono-sensitized patients). Furthermore, Pol d 1 was positive in 95% of Pol d 5-negative subjects. The diagnostic accuracy of Pol d 1 was good (folded type: area under the curve = 87%; 82% sensitivity and 77% specificity at the best cutoff of 5.773), and even better when used combined with the whole extract ratio (area under the curve = 99%; 91% sensitivity and 100% specificity). CONCLUSIONS: The study shows that Pol d 1 is the most frequent Polistes allergen in Italian patients. It can distinguish Polistes primary sensitizations with good diagnostic accuracy, which supports its use in clinical practice.

Proposed global prognostic score for systemic mastocytosis: a retrospective prognostic modelling study.

BACKGROUND: Several risk stratification models have been proposed in recent years for systemic mastocytosis but have not been directly compared. Here we designed and validated a risk stratification model for progression-free survival (PFS) and overall survival (OS) in systemic mastocytosis on the basis of all currently available prognostic factors, and compared its predictive capacity for patient outcome with that of other risk scores. METHODS: We did a retrospective prognostic modelling study based on patients diagnosed with systemic mastocytosis between March 1, 1983, and Oct 11, 2019. In a discovery cohort of 422 patients from centres of the Spanish Network on Mastocytosis (REMA), we evaluated previously identified, independent prognostic features for prognostic effect on PFS and OS by multivariable analysis, and designed a global prognostic score for mastocytosis (GPSM) aimed at predicting PFS (GPSM-PFS) and OS (GPSM-OS) by including only those variables that showed independent prognostic value (p<0·05). The GPSM scores were validated in an independent cohort of 853 patients from centres in Europe and the USA, and compared with pre-existing risk models in the total patient series (n=1275), with use of Harrells' concordance index (C-index) as a readout of the ability of each model to risk-stratify patients according to survival outcomes. FINDINGS: Our GPSM-PFS and GPSM-OS models were based on unique combinations of independent prognostic factors for PFS (platelet count ≤100 × 109 cells per L, serum ß2-microglobulin ≥2·5 µg/mL, and serum baseline tryptase ≥125 µg/L) and OS (haemoglobin ≤110 g/L, serum alkaline phosphatase ≥140 IU/L, and at least one mutation in SRSF2, ASXL1, RUNX1, or DNMT3A). The models showed clear discrimination between low-risk and high-risk patients in terms of worse PFS and OS prognoses in the discovery and validation cohorts, and further discrimination of intermediate-risk patients. The GPSM-PFS score was an accurate predictor of PFS in systemic mastocytosis (C-index 0·90 [95% CI 0·87-0·93], vs values ranging from 0·85 to 0·88 for pre-existing models), particularly in non-advanced systemic mastocytosis (C-index 0·85 [0·76-0·92], within the range for pre-existing models of 0·80 to 0·93). Additionally, the GPSM-OS score was able to accurately predict OS in the entire cohort (C-index 0·92 [0·89-0·94], vs 0·67 to 0·90 for pre-existing models), and showed some capacity to predict OS in advanced systemic mastocytosis (C-index 0·72 [0·66-0·78], vs 0·64 to 0·73 for pre-existing models). INTERPRETATION: All evaluated risk classifications predicted survival outcomes in systemic mastocytosis. The REMA-PFS and GPSM-PFS models for PFS, and the International Prognostic Scoring System for advanced systemic mastocytosis and GPSM-OS model for OS emerged as the most accurate models, indicating that robust prognostication might be prospectively achieved on the basis of biomarkers that are accessible in diagnostic laboratories worldwide. FUNDING: Carlos III Health Institute, European Regional Development Fund, Spanish Association of Mastocytosis and Related Diseases, Rare Diseases Strategy of the Spanish National Health System, Junta of Castile and León, Charles and Ann Johnson Foundation, Stanford Cancer Institute Innovation Fund, Austrian Science Fund.