Exploring the Methodological Benefits and Challenges of Utilising a Photovoice Methodology With Individuals in Recovery From Problem Substance Use.

Photovoice is a type of visual research method which supports participants to reflect upon their experiences by capturing digital images. It is a methodology that is routinely used with groups that could be considered vulnerable, as a way of allowing participants to tell their stories for themselves. This article details the process of conducting a Photovoice study with individuals in recovery from problem substance use and reflects on the methodological benefits and challenges of utilising a visual research methodology with this population. Researchers wishing to conduct a Photovoice study with individuals in recovery should be mindful of striking a delicate balance between respecting an individual's autonomy and ensuring their wellbeing. Although ethically complex, Photovoice is an ideal method for research with this population as it allows participants to convey meaning and introduce narratives for themselves in an engaging way.

The Normal Range of Baseline Tryptase Should Be 1 to 15 ng/mL and Covers Healthy Individuals With HαT.

Physiological levels of basal serum tryptase vary among healthy individuals, depending on the numbers of mast cells, basal secretion rate, copy numbers of the TPSAB1 gene encoding alpha tryptase, and renal function. Recently, there has been a growing debate about the normal range of tryptase because individuals with the hereditary alpha tryptasemia (HαT) trait may or may not be symptomatic, and if symptomatic, uncertainty exists as to whether this trait directly causes clinical phenotypes or aggravates certain conditions. In fact, most HαT-positive cases are regarded as asymptomatic concerning mast cell activation. To address this point, experts of the European Competence Network on Mastocytosis (ECNM) and the American Initiative in Mast Cell Diseases met at the 2022 Annual ECNM meeting and discussed the physiological tryptase range. Based on this discussion, our faculty concluded that the normal serum tryptase range should be defined in asymptomatic controls, inclusive of individuals with HαT, and based on 2 SDs covering the 95% confidence interval. By applying this definition in a literature screen, the normal basal tryptase in asymptomatic controls (HαT-positive persons included) ranges between 1 and 15 ng/mL. This definition should avoid overinterpretation, unnecessary referrals, and unnecessary anxiety or anticipatory fear of illness in healthy individuals.

Extrinsic and Intrinsic Modulators of Anaphylaxis.

The severity of anaphylaxis is determined by many factors. The allergenic source as well as the age of the affected individual and the route of allergen exposure encompass the major contributors of the clinical outcome. Moreover, the severity can be modulated further by intrinsic and extrinsic factors. Among these, the genetic predisposition, certain comorbidities such as uncontrolled asthma, and hormonal fluctuations have been proposed as intrinsic and antihypertensive medications or physical activity as extrinsic factors. Recent advances have highlighted immunologic pathways that may exacerbate the response to allergens through receptors on mast cells, basophils, platelets, and other granulocytes. Atopy, platelet-activating factor acetylhydrolase deficiency, hereditary alpha tryptasemia, and clonal mast cell disorders are examples associated with genetic alterations that may predispose to severe anaphylaxis. Identifying risk factors that lower the threshold of reactivity or increase the severity of multisystem reactions is important in the management of this patient population.

Assessment of low immunoglobulin levels and clinical manifestations in patients with mastocytosis.

Background: Patients with a low IgG level alone or with low IgA or IgM levels have been reported to be susceptible to respiratory tract infections and recurrent sinusitis. Patients diagnosed with CVID have a higher prevalence of autoimmune diseases and lymphoid malignancies. Mastocytosis is a myeloproliferative disease, not typically associated with autoimmune disease or frequent infections. Objective: We sought to determine the distribution of immunoglobulins in children and adults with mastocytosis. Evaluate the impact of low immunoglobulins on the clinical management of patients with mastocytosis. Methods: We performed a 10-year retrospective analysis on 320 adult and pediatric patients with mastocytosis for immunoglobulins using an electronic medical query. We identified 25 adults and 9 children with one or more low immunoglobulins. Patient records were examined for a history of infections and autoimmune disorders. Results: Serum immunoglobulins in children and adults with mastocytosis fell within a normal range. Among patients with low IgG levels alone or with low IgM and /or IgA, 20% had a history of infections and 20% of adults had autoimmune disorders. The most common infection was recurrent otitis media (OM). Conclusion: Patients with mastocytosis typically have normal immunoglobulins. With few exceptions, those with low immunoglobulins did not have frequent infections or autoimmune diseases. This data supports the conclusion that routine determination of immunoglobulins in patients with mastocytosis is not required and reserved for patients with clinical conditions, which might be related to an immunoglobulin deficiency.

sCD14 and Intestinal Fatty Acid Binding Protein Are Elevated in the Serum of Patients With Idiopathic Anaphylaxis.

BACKGROUND: Intestinal epithelial integrity compromise has been identified in gastrointestinal (GI), atopic, and autoimmune diseases. OBJECTIVE: Episodes of idiopathic anaphylaxis (IA) are often accompanied by GI manifestations. We, therefore, sought to determine whether surrogate markers of GI permeability were aberrant in this patient population. METHODS: Serum concentrations of zonulin, intestinal fatty acid binding protein (I-FABP), and soluble CD14 (sCD14) measured in 54 patients with IA were compared with concentrations in healthy controls (HCs); and correlated with clinical and laboratory parameters. RESULTS: The I-FABP was elevated in sera of patients with IA compared with HCs (median 1,378.0 pg/mL vs 479.0 pg/mL, respectively; P < .001). The sCD14 was also elevated compared with HCs (median 2,017.0 ng/mL and 1,189.0 ng/mL, respectively; P < .001), whereas zonulin was comparable between patients with IA and HCs (median 49.6 ng/mL vs 52.4 ng/mL, respectively; P = .40). The I-FABP was elevated in patients with IA who experienced vomiting and/or diarrhea compared with patients with IA who did not (P = .0091). CONCLUSIONS: The I-FABP and sCD14 are elevated in the serum of patients with IA. Elevations in these biomarkers of IA provides evidence that increased GI permeability, as is observed in other allergic conditions such as food allergy, is a common finding in those with IA and offers possible insight into the pathogenesis of this disease.

Diversity, Equity, and Inclusion: A Decade of Progress?

The concepts of diversity, equity, and inclusion are fundamental and more recently heavily discussed within medicine, research, and the larger society. There is increasing awareness that diversity of thoughts, perspectives, and backgrounds yields stronger teams and more effective results. There is also increasing awareness that stark inequities from systemic, institutional, and individual levels exist that limit the baseline opportunities for many populations. To close disparity gaps, broad aspects of diversity and promoting equity are required and efforts must be inclusive of those most marginalized. In this Clinical Commentary, we discuss, "How and If progress has been made in Diversity, Equity, Inclusion within the field of Allergy/Asthma/Immunology in the past decade?" We discuss the current state of clinical practice and what has been revealed over the past 10 years; describe our current workforce and what progress has or has not occurred there; and finally, review the state of scientific and medical research.

Investigating recovery from problem substance use using digital photovoice.

This study investigates the complex process of recovery from problem substance use using a visual research method known as 'Photovoice'. Seven service users from a harm reduction drug service were given digital cameras and asked to photograph 'people, places, and things' meaningful to them in their recovery. These photographs were then used as a catalyst for discussion during two in-depth interviews. This study demonstrates the nuanced experiences of recovery as some participants expressed feeling isolated while others reflected upon their access to various forms of social capital. These findings recognise the link between social capital and recovery outcomes, while also reflecting upon how services might imbed the need for relationship quality within artificial recovery networks. The use of photographs is a novel way of providing voice to the lived experience of service users and adds to the discussion and debate concerning how recovery services may develop.

Genetically defined individual reference ranges for tryptase limit unnecessary procedures and unmask myeloid neoplasms.

Serum tryptase is a biomarker used to aid in the identification of certain myeloid neoplasms, most notably systemic mastocytosis, where basal serum tryptase (BST) levels >20 ng/mL are a minor criterion for diagnosis. Although clonal myeloid neoplasms are rare, the common cause for elevated BST levels is the genetic trait hereditary α-tryptasemia (HαT) caused by increased germline TPSAB1 copy number. To date, the precise structural variation and mechanism(s) underlying elevated BST in HαT and the general clinical utility of tryptase genotyping, remain undefined. Through cloning, long-read sequencing, and assembling of the human tryptase locus from an individual with HαT, and validating our findings in vitro and in silico, we demonstrate that BST elevations arise from overexpression of replicated TPSAB1 loci encoding canonical α-tryptase protein owing to coinheritance of a linked overactive promoter element. Modeling BST levels based on TPSAB1 replication number, we generate new individualized clinical reference values for the upper limit of normal. Using this personalized laboratory medicine approach, we demonstrate the clinical utility of tryptase genotyping, finding that in the absence of HαT, BST levels >11.4 ng/mL frequently identify indolent clonal mast cell disease. Moreover, substantial BST elevations (eg, >100 ng/mL), which would ordinarily prompt bone marrow biopsy, can result from TPSAB1 replications alone and thus be within normal limits for certain individuals with HαT.

A widespread blistering eruption: diffuse cutaneous mastocytosis.

Diffuse cutaneous mastocytosis with bullous formation is a rare childhood disease. We report a 5-month-old male who presented with a 3-week history of cutaneous bullae and pruritus. On examination, he had erythema of the cheeks bilaterally and diffuse slightly hyperpigmented, indurated skin on his trunk and abdomen. There were tense vesicles, bullae, and erosions linearly arranged on his trunk and extremities. Both the laboratory and imaging workup were normal. Subsequently, a punch biopsy of a vesicle on the abdomen was obtained and findings confirmed a diagnosis of diffuse cutaneous mastocytosis. An EpiPen(r) was prescribed due to the slightly increased anaphylaxis risk compared to other forms of mastocytosis. There are many purported triggers of diffuse cutaneous mastocytosis and there is currently no known cure which makes management of this disease challenging. This case highlights a rare condition for which official treatment guidelines do not exist. A prompt dermatologic diagnosis is necessary to ensure proper workup and regulation is in place.

Proposed European Competence Network on Mastocytosis-American Initiative in Mast Cell Diseases (ECNM-AIM) Response Criteria in Advanced Systemic Mastocytosis.

Advanced systemic mastocytosis (AdvSM) is characterized by the presence of KIT D816V and other somatic mutations (eg, in SRSF2, ASXL1, and RUNX1) in 95% and 60% to 70% of patients, respectively. The biological and clinical consequences of AdvSM include multilineage involvement (eg, associated hematologic neoplasm) in 60% to 80% of patients, variable infiltration and damage (C-findings) of predominantly bone marrow and visceral organs through affected mast cell (MC) and non-MC lineages, and elevated levels of serum tryptase. Recently, the treatment landscape has substantially changed with the introduction of the multikinase/KIT inhibitor midostaurin and the selective KIT D816V inhibitor avapritinib. In this review, we discuss the evolution of AdvSM response criteria that have been developed to better capture clinical benefit (eg, improved responses and progression-free and overall survival). We propose refined response criteria from European Competence Network on Mastocytosis and American Initiative in Mast Cell Diseases investigators that use a tiered approach to segregate the effects of histopathologic (eg, bone marrow MC burden, tryptase), molecular (eg, KIT D816V variant allele frequency), clinical (eg, C-findings), and symptom response on long-term outcomes. These response criteria require evaluation in future prospective clinical trials of selective KIT inhibitors and other novel agents.

Standards of Pathology in the Diagnosis of Systemic Mastocytosis: Recommendations of the EU-US Cooperative Group.

Pathology plays a central role in the diagnosis of systemic mastocytosis (SM), its delineation from other neoplasms and reactive conditions, and in monitoring of SM under therapy. The morphologic hallmark of SM is the accumulation of spindle-shaped, hypogranulated mast cells (MCs) in bone marrow (BM) and other extracutaneous tissues. Four of the 5 World Health Organization-defined diagnostic criteria (ie, compact MC aggregates [=major criterion]; atypical MC morphology; activating KIT point mutations; aberrant expression of CD25 and/or CD2 and/or CD30 in MCs [=minor criteria]) can be addressed by the pathologist. The final classification of SM variants as either BM mastocytosis, indolent SM, smoldering SM, aggressive SM (ASM), SM with an associated hematologic neoplasm (SM-AHN), or MC leukemia (MCL) has important prognostic significance and requires the integration of certain morphological, clinical, radiological, and biochemical data, referred to as B- and C-findings. Substantial diagnostic challenges may be posed to the pathologist and clinician especially in the so-called advanced SM variants, that is, ASM, MCL, and SM-AHN. In this article, updated recommendations of the EU-US Cooperative Group regarding standards of pathology in the diagnosis of SM, presented during the year 2020 Working Conference held in September in Vienna, are reported.

Refined Treatment Response Criteria for Indolent Systemic Mastocytosis Proposed by the ECNM-AIM Consortium.

Indolent systemic mastocytosis (ISM) has a favorable prognosis and normal life expectancy. However, many patients suffer from mast cell (MC) mediator-related symptoms, which significantly affect quality of life (QoL). Cutaneous, gastrointestinal, and neurological complaints, musculoskeletal pain, and the presence of skin lesions, anaphylaxis, and osteoporosis are the main symptoms and signs in ISM and must be assessed in all patients before and during treatment. Validated mastocytosis-specific patient-reported outcome measures (PROMs) should be used for this purpose. Serum tryptase and KIT D816V allele burden are recommended as secondary outcome parameters, noting that they do not reflect the severity of signs, symptoms, and related QoL impairment, but indirectly express MC burden. Changes from baseline of 90%, 60%, and 30% indicate complete response >90%, major response 60% to 90%, partial response 30% to 60%, and no response <30% to treatment. To conclude, we recommend the use of PROMs as primary outcome parameters to define treatment response in patients with ISM in clinical trials and in everyday clinical practice.

Global Classification of Mast Cell Activation Disorders: An ICD-10-CM-Adjusted Proposal of the ECNM-AIM Consortium.

Mast cell activation (MCA) is common and occurs in a number of pathologic conditions, including IgE-dependent and independent allergic reactions, atopic disorders, autoimmune processes, and mastocytosis. In a subset of patients, no underlying disease and no known trigger of MCA are found. When the symptoms are severe, systemic, and recurrent, and accompanied by a diagnostic increase in the serum tryptase level or other mast cell mediators, an MCA syndrome (MCAS) may be diagnosed. In these patients, the symptoms typically respond to drugs suppressing MCA, mediator production in mast cells, or mediator effects. In each case, diagnostic consensus criteria must be fulfilled to diagnose MCAS. In other patients, MCA may be local, less severe, or less acute, or may be suspected but not confirmed, so that the diagnostic criteria of MCAS are not fulfilled. In these patients, it may be difficult to prove MCA, for example, by measuring multiple mast cell mediators or basophil activation, the latter as a surrogate of IgE-dependent hypersensitivity. However, validated diagnostic criteria for implicating suspected MCA behind such conditions are lacking, even if some of these conditions have recently been assigned to an International Classification of Diseases-10-Clinical Modification code (ICD-10-CM). In this article, we discuss diagnostic features and criteria and propose a ICD-10-CM-adjusted classification for disorders associated with MCA, herein referred to as MCA disorders (MCADs), with special emphasis on the delineation between confirmed MCAS, MCAD not fulfilling MCAS criteria, and suspected MCAD that is not present. In addition, we discuss the discrimination between overt MCAD and predisposing conditions, such as atopic states, mastocytosis, and hereditary alpha tryptasemia.

Personalized Management Strategies in Mast Cell Disorders: ECNM-AIM User's Guide for Daily Clinical Practice.

Mastocytosis is a myeloid neoplasm defined by expansion and focal accumulation of clonal mast cells (MCs) in one or more organs. The disease exhibits a complex pathology and may be complicated by MC activation, bone abnormalities, neurological problems, gastrointestinal symptoms, and/or hematologic progression. The World Health Organization divides mastocytosis into cutaneous forms, systemic mastocytosis (SM) and MC sarcoma. In most patients with SM, somatic mutations in KIT are detected. Patients with indolent SM have a normal to near-normal life expectancy, whereas patients with advanced SM, including aggressive SM and MC leukemia, have a poor prognosis. In those with advanced SM, multiple somatic mutations and an associated hematologic neoplasm may be detected. Mediator-related symptoms can occur in any type of mastocytosis. Symptoms may be mild, severe, or even life-threatening. In patients with severe acute symptoms, an MC activation syndrome may be diagnosed. In these patients, relevant comorbidities include IgE-dependent and IgE-independent allergies. Management of patients with SM is an emerging challenge in daily practice and requires in-depth knowledge and a multidisciplinary and personalized approach with selection of appropriate procedures and interventions. In this article, we review the current knowledge on SM and MC activation syndrome, with emphasis on multidisciplinary aspects in diagnosis and patient-specific management. In addition, we provide a user's guide for application of markers, algorithms, prognostic scores, and treatments for use in daily practice.

Standards of Genetic Testing in the Diagnosis and Prognostication of Systemic Mastocytosis in 2022: Recommendations of the EU-US Cooperative Group.

Mastocytosis comprises rare heterogeneous diseases characterized by an increased accumulation of abnormal mast cells in various organs/tissues. The pathogenesis of mastocytosis is strongly linked to the presence of KIT-activating mutations. In systemic mastocytosis (SM), the most frequent mutation encountered is KIT p.D816V, whose presence constitutes one of the minor diagnostic criteria. Different techniques are used to search and quantify the KIT p.D816V mutant; however, allele-specific quantitative PCR and droplet digital PCR are today the most sensitive. The analysis of the KIT p.D816V allele burden has undeniable interest for diagnostic, prognostic, and therapeutic monitoring. The analysis of non-mast cell hematological compartments in SM is similarly important because KIT p.D816V multilineage involvement is associated with a worse prognosis. In addition, in advanced forms of SM, mutations in genes other than KIT are frequently identified and affect negatively disease outcome and response to therapy. Thus, combined quantitative and sensitive analysis of KIT mutations and next-generation sequencing of other recurrently involved myeloid genes make it possible to better characterize the extent of the affected cellular compartments and additional molecular aberrations, providing a more detailed overview of the complex mutational landscape of SM, in relation with the clinical heterogeneity of the disease. In this article, we report the latest recommendations of the EU-US Cooperative Group presented in September 2020 in Vienna during an international working conference, on the techniques we consider standard to detect and quantify the KIT p.D816V mutant in SM and additional myeloid mutations found in SM subtypes.