Letter to the Editor

Omalizumab for the treatment of unprovoked anaphylaxis in patients with systemic mastocytosis

This practice parameter update focuses on 7 areas in which there are new evidence and new recommendations. Diagnostic criteria for anaphylaxis have been revised, and patterns of anaphylaxis are defined. Measurement of serum tryptase is important for diagnosis of anaphylaxis and to identify underlying mast cell disorders. In infants and toddlers, age-specific symptoms may differ from older children and adults, patient age is not correlated with reaction severity, and anaphylaxis is unlikely to be the initial reaction to an allergen on first exposure. Different community settings for anaphylaxis require specific measures for prevention and treatment of anaphylaxis. Optimal prescribing and use of epinephrine autoinjector devices require specific counseling and training of patients and caregivers, including when and how to administer the epinephrine autoinjector and whether and when to call 911. If epinephrine is used promptly, immediate activation of emergency medical services may not be required if the patient experiences a prompt, complete, and durable response. For most medical indications, the risk of stopping or changing beta-blocker or angiotensin-converting enzyme inhibitor medication may exceed the risk of more severe anaphylaxis if the medication is continued, especially in patients with insect sting anaphylaxis. Evaluation for mastocytosis, including a bone marrow biopsy, should be considered for adult patients with severe insect sting anaphylaxis or recurrent idiopathic anaphylaxis. After perioperative anaphylaxis, repeat anesthesia may proceed in the context of shared decision-making and based on the history and results of diagnostic evaluation with skin tests or in vitro tests when available, and supervised challenge when necessary.

Les mastocytes peuvent être activés dans de nombreuses conditions physiologiques et pathologiques. Les troubles d’activation mastocytaire sont classés comme primaires – associés à une population monoclonale mastocytaire –, ou secondaires (avec un nombre normal de mastocytes dits hyperréactifs), ou encore idiopathiques. Le syndrome d’activation mastocytaire (MCAS, Mast Cell Activation Syndrome) est caractérisé par une libération inappropriée et excessive par les mastocytes de médiateurs engendrant divers symptômes pouvant concerner plusieurs apparats, voire provoquer des réactions à type d’anaphylaxie à répétition. Nous avons voulu apporter des réponses claires aux questions suivantes pour aider la prise en charge globale des patients atteints de MACS : quelles sont la définition et la classification actuelles du MCAS ? Quels sont les critères diagnostiques, cliniques et biologiques à utiliser ? Quelles sont les stratégies thérapeutiques à mettre en œuvre ? Le but de ce travail est de présenter les connaissances actuelles concernant les MCAS, pour apporter une aide au processus diagnostique et thérapeutique de ces pathologies.

Mast cells may be activated secondary to different physiological and pathological conditions. Mast cell activation disorders are classified as primary – associated with a monoclonal mast cell population – or secondary (with a normal number of so-called hyperreactive mast cells), or even idiopathic. Mast Cell Activation Syndrome (MCAS) is characterized by an inappropriate and excessive release of mast cells mediators, leading to clinical symptoms that may affect several body systems, or even cause repeated anaphylaxis. We wanted to provide clear answers to the following questions to help the overall management of patients presenting with MACS: what is the current definition and classification of MCAS? Which diagnostic, clinical and laboratory criteria should be used? What are the most comment therapeutic strategies? The aim of the present work is to present current knowledge on MCAS, to aid clinicians in the diagnostic and therapeutic process of these conditions.

In recent years, knowledge about mechanisms underlying mast cell activation (MCA) and accumulation in various pathologic conditions increased substantially. In addition, criteria and a classification of MCA syndromes (MCASs) have been set forth. MCAS is defined by typical clinical symptoms, a substantial increase in serum tryptase level during an attack over the patient's baseline tryptase, and a response of the symptoms to drugs targeting mast cells, mediator production, and/or mediator effects. Alternative diagnostic criteria of MCAS have also been suggested, but these alternative criteria often lack specificity and validation. In this report, we critically review the contemporary literature relating to MCAS and compare the specificity, sensitivity, and strength of MCAS-related parameters within proposals to diagnose and classify MCAS and its variants. Furthermore, we highlight the need to apply specific consensus criteria in the evaluation and classification of MCAS in individual patients. This is an urgent and important medical necessity because as an increasing number of patients are being given a misdiagnosis of MCAS based on nonspecific criteria, which contributes to confusion and frustration by patients and caregivers and sometimes may delay recognition and treatment of correct medical conditions that often turn out to be unrelated to MCA.

Systemic mastocytosis (SM) is a myeloproliferative disorder characterized by symptoms of mast cell (MC) activation and/or organ dysfunction related to MC tissue accumulation. Treatment of this condition is evolving as our understanding of the pathophysiology of the disease advances. This article aims to highlight novel and experimental therapies for SM.

PubMed literature search and ClinicalTrials.gov.

Peer-reviewed studies involving therapies for SM were included. There was a particular focus on preclinical and clinical trial studies.

SM presents with a wide range of symptoms including symptoms of MC activation such as anaphylaxis, urticaria, diarrhea, and organ failure secondary to aggressive tissue infiltration. The treatment of the disease is dependent on the variant; patients with aggressive disease warrant advanced therapies and higher tolerance of adverse effects. As our understanding of the disease has advanced, several novel therapeutic options have emerged. These include tyrosine kinase inhibitors directed at the KIT protein and targeted monoclonal antibodies, which decrease MC activation or reduce mast cell burden. There are a variety of new medications under development that will revolutionize the treatment for patients with SM.

Current treatment options for SM have inherent limitations and, in many cases, unacceptable adverse effects. As our molecular understanding of the disease advances, novel, and experimental therapies are changing treatment paradigms of the disease.

Anaphylaxis is a rapidly evolving, acute, life-threatening reaction that occurs rapidly on contact with a trigger. Anaphylaxis is classically defined as an allergen-driven process that induces specific IgE and the activation of mast cells and basophils through the cross-linking of IgE receptors. However, it is clear that non–IgE-mediated pathways can induce symptoms indistinguishable from those of classic anaphylaxis, and their activation could explain the severity of IgE-mediated anaphylaxis. Indeed, mast cells and basophils can be activated by antibodies against IgE or their receptors, by molecules such as anaphylatoxins, or through G-coupled receptors. Some other allergens can induce antibodies of class IgG that can activate neutrophils to produce a molecule similar to histamine to induce anaphylaxis. Finally, some inflammatory mediators such as bradykinin or prostaglandin can also modulate mast cell and basophil activation as well as directly cause vasodilation and bronchoconstriction, resulting in anaphylaxis-like reactions.