RESUMEN
This review summarizes new research developments and clinical practice recommendations for the diagnosis and management of anaphylaxis presented in the Joint Task Force on Practice Parameters 2023 Anaphylaxis practice parameter Update. It is intended to serve as a high-level summary of the 2023 practice parameter, which makes clinically impactful recommendations based on evidence that has emerged since the 2015 practice parameter. We invite clinicians to explore the full 2023 practice parameter to understand the research methods and underlying evidence that have informed the recommendations summarized here. There are new and evolving diagnostic criteria for anaphylaxis, rules for defining elevated tryptase levels, and recognition of signs and symptoms particular to infants and toddlers. The administration of epinephrine should not be used as a surrogate to diagnose anaphylaxis. Risk factors for anaphylaxis should be assessed on a case-by-case basis. Patient counseling and shared decision-making are essential to support patients' treatment decisions and capacity to manage the risk of anaphylaxis at home and in other community settings. Activation of emergency medical services after home epinephrine administration may not be required in all cases, and patients should be engaged in shared decision-making to determine when home management may be appropriate.
Asunto(s)
Anafilaxia , Epinefrina , Anafilaxia/diagnóstico , Humanos , Epinefrina/uso terapéutico , Factores de Riesgo , Guías de Práctica Clínica como Asunto , Triptasas/sangreRESUMEN
Mastocytosis is a disease of the mast cells caused by an increase in the number of mast cells due to abnormal proliferation. The disease is associated with a mutation in the c-kit gene, which is a key factor in the development of mast cells. Mastocytosis is classified into two main groups, namely, cutaneous and systemic mastocytosis, based on the site of mast cell accumulation. In cutaneous mastocytosis, the cells purely gather in the skin. In contrast, systemic mastocytosis must affect an internal organ, including the bone marrow, lymph nodes, liver, spleen, and/or the gastrointestinal tract with or without skin involvement. Cutaneous mastocytosis has four distinct presentations, including urticaria pigmentosa, cutaneous mastocytoma, diffuse cutaneous mastocytosis, and telangiectasia macularis eruptive perstans listed from most to least common. This case report presents a rare bullous variant of diffuse cutaneous mastocytosis.
RESUMEN
BACKGROUND: Systemic mastocytosis (SM) is a clonal disorder of mast cells (MCs) frequently associated with vertebral osteoporosis (OP) and subsequent vertebral fractures (VFs). The natural history of this OP remains unclear. Importantly, we do not know whether OP represents an early event triggered alongside MC abnormalities, and whether MC clonality is sufficient to trigger osteoporosis. OBJECTIVE: To describe OP in patients with medullar clonality in cutaneous mastocytosis (CM) and monoclonal mast cell activation syndrome (MMAS) and to compare their osteoporosis characteristics with those of nonadvanced SM patients (bone marrow mastocytosis and indolent systemic mastocytosis). METHODS: We retrospectively analyzed clinical, biological, and densitometric data of 27 CM, 13 MMAS, and 135 SM patients from the Mastocytosis Expert Center (CEREMAST) in Toulouse, France. RESULTS: The OP (respectively 3.7, 30.8, and 34.1%) and VFs (0.0%, 15.4%, and 20%) were less frequent in CM than in MMAS and SM, despite the presence of clonal MCs in the bone marrow. Most patients with OP and VFs in the non-SM groups had the usual risk factors for OP. Interestingly, the only non-SM patient with a typical SM-like OP had high bone marrow tryptase, developed bone marrow KIT mutation during follow-up, and had a family history of SM. Our data show that OP is not a common clinical finding in CM but is frequent in MMAS. When OP and VFs occur in CM and MMAS patients, they differ from the usual phenotype of SM bone fragility. CONCLUSIONS: Our findings suggest that, in most CM patients, the meaning and management of OP differs from that of OP in MMAS and nonadvanced SM. Prospective longitudinal studies and the validation of predictors are needed to identify CM and MMAS patients developing SM-related OP.
Asunto(s)
Mastocitosis Cutánea , Mastocitosis Sistémica , Osteoporosis , Humanos , Osteoporosis/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Prevalencia , Estudios Retrospectivos , Anciano , Mastocitosis Cutánea/epidemiología , Mastocitosis Sistémica/epidemiología , Mastocitos/inmunología , Francia/epidemiología , Médula Ósea/patología , Proteínas Proto-Oncogénicas c-kit/genética , Fracturas de la Columna Vertebral/epidemiologíaRESUMEN
Elevated basal serum tryptase (BST) levels are markers of both mast cell activation and overall mast cell burden. We present a family of four individuals with elevated tryptase levels greater than or equal to 20 mcg/L, all of whom exhibited signs and symptoms suggestive of mast cell activation. Differential diagnoses included hereditary alpha tryptasemia (HaT), systemic mastocytosis (SM), and mast cell activation syndrome (MCAS). In three individuals, SM was ruled out with normal morphology on bone marrow biopsy combined with negative genetic markers. Further workup would be required for the diagnosis of MCAS since serum tryptase levels were not obtained in our emergency department during acute episodes. Although genetic testing for HaT was not available upon initial workup, HaT remains the most likely explanation for this family's elevated BST.
RESUMEN
Mastocytosis is a rare neoplastic disorder of the mast cell lineage resulting in unregulated proliferation and activation of mast cells. Symptoms worsen in about one-third of pregnant patients. Treatment focuses on management of symptoms with antimediator therapy (H1 & H2 antihistamines, glucocorticoids, and epinephrine, if required). Medication selection requires care during labor and delivery. Although it is generally considered safe to use a medication patient tolerated before, some common medications may need to be avoided or used with caution (eg, codeine, morphine, nonsteroidal antiinflammatory drugs, vancomycin) if the patient does not have any history of exposure to them.
Asunto(s)
Mastocitosis , Femenino , Embarazo , Humanos , Mastocitosis/diagnóstico , Mastocitosis/terapia , Mastocitos , Antiinflamatorios no Esteroideos , Epinefrina , Glucocorticoides , Enfermedades RarasRESUMEN
BACKGROUND: Since 2010, patients and physicians have collaborated to understand unmet needs of patients with mast cell diseases, incorporating mastocytosis and mast cell activation disorders, which include mast cell activation syndromes. OBJECTIVE: This Open Innovation in Science project aims to expand understanding of the needs of patients affected by mast cell diseases, and encourage global communication among patient advocacy groups, physicians, researchers, industry, and government. A major aim is to support the scientific community's efforts to improve diagnosis, management, therapy, and patients' quality of life by addressing unmet needs. METHODS: In collaboration with mast cell disease specialists, 13 patient advocacy groups from 12 countries and regions developed lists of top patient needs. A core team of leaders from patient advocacy groups collected and analyzed the data and proposed possible actions to address patient needs. RESULTS: Findings identified similarities and differences among participating countries in unmet needs between patients with mastocytosis and those with mast cell activation syndromes. Issues emphasized struggles relating to the nature and rarity of mast cell diseases, their impact on quality of life, the diagnostic process, access to appropriate care, more effective treatment, and the need for research. CONCLUSIONS: Solutions vary across countries because situations differ, in particular regarding the existence of and access to centers of excellence and reference centers. Multifaceted mast cell activation syndrome barriers necessitate innovative approaches to improve access to appropriate care. The outcomes of this project should greatly support scientists and clinicians in their efforts to improve diagnosis, management, and treatment of patients with mastocytosis and mast cell activation disorders.
Asunto(s)
Trastornos de la Activación de los Mastocitos , Mastocitosis , Humanos , Mastocitos , Mastocitosis/diagnóstico , Mastocitosis/terapia , Calidad de VidaRESUMEN
Background: Uncertainties remain about the molecular mechanisms governing clonal mast cell disorders (CMCD) and anaphylaxis. Objective: This study aims at comparing the burden, phenotype and behavior of mast cells (MCs) and basophils in patients with CMCD with wasp venom anaphylaxis (CMCD/WVA+), CMCD patients without anaphylaxis (CMCD/ANA-), patients with an elevated baseline serum tryptase (EBST), patients with wasp venom anaphylaxis without CMCD (WVA+) and patients with a non-mast cell haematological pathology (NMHP). Methods: This study included 20 patients with CMCD/WVA+, 24 with CMCD/ANA-, 19 with WVA+, 6 with EBST and 5 with NMHP. We immunophenotyped MCs and basophils and compared baseline serum tryptase (bST) and both total and venom specific IgE in the different groups. For basophil studies, 13 healthy controls were also included. Results: Higher levels of bST were found in CMCD patients with wasp venom anaphylaxis, CMCD patients without anaphylaxis and EBST patients. Total IgE levels were highest in patients with wasp venom anaphylaxis with and without CMCD. Bone marrow MCs of patients with CMCD showed lower CD117 expression and higher expression of CD45, CD203c, CD63, CD300a and FcεRI. Within the CMCD population, patients with wasp venom anaphylaxis showed a higher expression of FcεRI as compared to patients without anaphylaxis. Expression of MRGPRX2 on MCs did not differ between the study populations. Basophils are phenotypically and functionally comparable between the different patient populations. Conclusion: Patients with CMCD show an elevated burden of aberrant activated MCs with a significant overexpression of FcεRI in patients with a wasp venom anaphylaxis.
Asunto(s)
Anafilaxia , Mastocitosis , Anafilaxia/metabolismo , Médula Ósea , Humanos , Inmunoglobulina E/metabolismo , Mastocitos/metabolismo , Mastocitosis/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores de IgE/metabolismo , Receptores de Neuropéptido/metabolismo , Triptasas/metabolismo , Venenos de Avispas/metabolismoRESUMEN
BACKGROUND: Anaphylaxis is frequent in patients suffering from primary mast cell disorders (PMCDs). In patients without mastocytosis in the skin (MIS) and a baseline serum tryptase (bST) less than 30 ng/mL, the diagnosis of PMCD is challenging. In these patients, detection of the KIT D816V mutation in peripheral blood (PB) has been suggested as screening tool for a PMCD. OBJECTIVE: In this study, we investigated whether KIT D816V in PB can contribute to the decision to perform a bone marrow (BM) biopsy in patients with anaphylaxis without MIS and a bST less than 30 ng/mL. METHODS: We selected 74 patients with severe anaphylaxis without MIS and a bST less than 30 ng/mL. All underwent a BM biopsy. KIT D816V mutation was quantified in both PB and BM using digital droplet polymerase chain reaction (ddPCR). RESULTS: Diagnosis of a PMCD was established in 40 patients (54%). Median bST for patients with and without PMCD was, respectively, 9.5 ng/mL (range 4.2-27 ng/mL) and 4.9 ng/mL (range 2.2-20.3 ng/mL) (P <.001). KIT D816V in PB was detected in 16 out of 40 (40%) patients with PMCD. KIT D816V in BM was detected in 22 out of 40 (55%) patients with PMCD. CONCLUSIONS: In patients without MIS and a bST less than < 30 ng/mL who experience anaphylaxis, determination of KIT D816V mutation in PB is of limited help in deciding when to proceed to a BM biopsy. Therefore, KIT D816V in PB mutation analysis should be interpreted together with scoring tools to make a better assessment in identifying patients who should undergo BM biopsy.
Asunto(s)
Anafilaxia , Mastocitosis Sistémica , Mastocitosis , Anafilaxia/diagnóstico , Humanos , Mastocitos , Mastocitosis Sistémica/diagnóstico , Mastocitosis Sistémica/genética , Mutación , Proteínas Proto-Oncogénicas c-kit/genéticaAsunto(s)
Mastocitosis , Urticaria , Humanos , Mastocitos , Mastocitosis/diagnóstico , Triptasas , Urticaria/diagnóstico , Urticaria/etiologíaRESUMEN
Mast cell activation syndrome (MCAS) is a heterogeneous and rare disorder with episodic and severe activation of mast cells. Because symptoms of mast cell activation are nonspecific, it is important to base the diagnosis on best available clinical and scientific evidence, and not make it one of exclusion. MCAS, much like the mast cell itself, as a whole is greater than the sum of its proposed diagnostic criteria. When each component is considered in isolation, criteria can seem nonspecific, and thus, a broad constellation of symptoms can be attributed to MCAS when they may be due to other disease processes.
Asunto(s)
Mastocitosis/diagnóstico , Evaluación de Síntomas , Diagnóstico Diferencial , HumanosRESUMEN
In recent years, an association between hypermobile Ehlers-Danlos syndrome (hEDS), mast cell activation syndrome (MCAS), and postural orthostatic tachycardia syndrome (POTS) has garnered attention and patients are increasingly presenting with this triad. However, a real relationship between these entities is unclear due to a lack of scientific validity. We conducted an extensive review of the literature using two different search strategies. A narrower strategy included 88 searches of various combinations of terms for each of the three conditions, yielding 19 unique papers. A broader search included 136 searches of various combinations of terms but included all forms of EDS and yielded 40 unique papers. Of these, only four and nine papers from the narrower and broader search strategies were original research articles. None of these papers resulted from a combination of the search terms for the three conditions. All three clinical entities are controversial in either existence or pathogenesis. MCAS is a poorly defined clinical entity, and many studies do not adhere to the proposed criteria when establishing the diagnosis. Patients previously diagnosed with EDS hypermobility type may not meet the new, stricter criteria for hEDS but may for a less severe hypermobility spectrum disorder (HSD). The pathophysiology of POTS is still unclear. An evidence-based, common pathophysiologic mechanism between any of the two, much less all three conditions, has yet to be described. Our review of the literature shows that current evidence is lacking on the existence of MCAS or hEDS as separate or significant clinical entities. Studies proposing a relationship between the three clinical entities are either biased or based on outdated criteria. The reason behind the purported association of these entities stems from an overlapping pool of vague, subjective symptoms, which is inadequate evidence to conclude that any such relationship exists.
Asunto(s)
Síndrome de Ehlers-Danlos/fisiopatología , Inestabilidad de la Articulación/fisiopatología , Mastocitosis/fisiopatología , Síndrome de Taquicardia Postural Ortostática/fisiopatología , Animales , Síndrome de Ehlers-Danlos/diagnóstico , Medicina Basada en la Evidencia , Humanos , Inestabilidad de la Articulación/diagnóstico , Mastocitosis/diagnóstico , Síndrome de Taquicardia Postural Ortostática/diagnósticoRESUMEN
OBJECTIVES: Idiopathic mast cell disorders, a recently defined and recognised syndrome in clinical practice, are similar to the previously termed non-clonal mast cell disorder. Patients with idiopathic mast cell activation syndrome (MCAS) suffer all the classical signs of mast cell activation but do not have evidence of mast cell clonality. Furthermore, treatment of these patients can be limited and burdensome in those with refractory symptoms. METHODS: Here, we describe treatment of a patient with idiopathic MCAS utilising a single monthly subcutaneous injection of omalizumab and review the current classification and therapeutic options for clonal and non-clonal MCAS. RESULTS: Low-dose omalizumab treatment has successfully led to a 5-year, sustained clinical response, controlled debilitating symptoms of mast cell activation and allowed for reintroduction and long-term maintenance of bee venom subcutaneous immunotherapy. CONCLUSION: Low-dose omalizumab of 150 mg monthly should be considered for maintenance management of patients with idiopathic MCAS for its cost and quality-of-life benefits.
RESUMEN
Understanding experiences, perceptions, and perspectives of patients with a mast cell disorder (MCD), including cutaneous mastocytosis, systemic mastocytosis, mast cell activation syndromes, and hereditary α-tryptasemia, is an important aspect of successful care, treatment, and informed development of novel therapies. This article reviews existing studies and presents new data on MCD patient perceptions regarding medical care, symptoms, allergies/sensitivities, triggers, future health/disease progression, treatment, impact on daily living, quality of life, support needs, and concerns regarding possible familial disease. Discussion includes aspects affecting the MCD community that require further consideration and development.
Asunto(s)
Mastocitos/fisiología , Mastocitosis/epidemiología , Prioridad del Paciente , Medición de Resultados Informados por el Paciente , Percepción , Emociones , Regulación Gubernamental , Humanos , Mastocitosis/psicología , Relaciones Médico-Paciente , Calidad de Vida , Estados Unidos , United States Food and Drug AdministrationRESUMEN
BACKGROUND: Rituximab (Rituxan) hypersensitivity (RITS) can be severe and limits the ability to further administer the treatment. Understanding its pattern and desensitization may permit administration in difficult cases. OBJECTIVE: Analyze RITS patient characteristics, hypersensitivity pattern, and desensitization outcomes to optimize management. METHODS: Twenty-five patients with RITS were referred to the Allergy/Immunology Unit at Massachusetts General Hospital over 5 1/2 years. Their clinical reaction patterns were analyzed. Drug desensitizations were performed using 3 related continuous intravenous protocols that were chosen on the basis of clinical history, skin test reactivity, and the patient's previous desensitization outcomes. RESULTS: Of the 25 referred patients, 23 had lymphoma of various types. The 25 patients underwent 170 continuous intravenous desensitizations based on 3 related protocols, with most based on the intermediate protocol. All but 2 desensitizations were completed successfully. Overall 24% of the desensitizations were complicated by hypersensitivity reactions. Two patients with serum sickness and a patient with mast cell disorder were also successfully managed. The average hypersensitivity reaction grade was 3.0 (2-4) before desensitization and 0.41 with desensitization. Skin tests were performed in 18 patients, with 5 patients positive initially and 2 more converted from negative to positive. Skin test status was not helpful for risk stratification for hypersensitivity reactions. Tryptase level was elevated during 21% of desensitizations with reactions but rare among asymptomatic desensitizations. CONCLUSIONS: Nearly all patients with severe sensitivity to rituximab can be successfully desensitized. IgE-mediated mechanism and mast cell degranulation, in addition to cytokine release syndrome and tumor lysis syndrome, may contribute to a significant portion of hypersensitivity reactions among patients with RITS.
Asunto(s)
Desensibilización Inmunológica/métodos , Hipersensibilidad a las Drogas/epidemiología , Linfoma/epidemiología , Mastocitos/inmunología , Rituximab/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Degranulación de la Célula/inmunología , Citocinas/metabolismo , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/terapia , Femenino , Humanos , Inmunoglobulina E/metabolismo , Linfoma/diagnóstico , Linfoma/terapia , Masculino , Persona de Mediana Edad , Rituximab/efectos adversos , Enfermedad del Suero/etiología , Triptasas/metabolismo , Síndrome de Lisis Tumoral/etiología , Adulto JovenRESUMEN
OBJECTIVES: Systemic mastocytosis (SM) is a disorder characterized by the excessive accumulation of clonally derived mast cells in various tissues. When triggered, mast cells release large amounts of histamine, prostaglandins and leukotrienes. Leukotriene E4 (LTE4) is the primary stable metabolite of total cysteinyl leukotrienes. We hypothesized that secretion of LTE4 would be increased in SM and could be used alone or in combination with current urinary biomarkers to optimize screening for SM. DESIGN AND METHODS: LTE4 was measured by liquid chromatography followed by tandem mass spectrometry (LC-MS/MS). Analytical assay validation was performed using residual urine specimens. LTE4 results were normalized to urine creatinine for clinical use. Reference interval was established using a healthy volunteer cohort. Clinical sensitivity and specificity for SM detection were determined by measuring urinary biomarkers (LTE4, N-methyl histamine [NMH] and 11ß-prostaglandin F2α [BPG]) in a cohort of 409 patients referred to allergy specialists, 66 (16%) of which were diagnosed with SM. RESULTS: Urinary LTE4 measurement was accurate, precise and linear across a range of 31-3020pg/mL. The 95th percentile of the reference interval population was <104pg/mg creatinine. Median urine LTE4 concentrations were significantly higher among patients with SM (97pg/mg cr. vs. 50pg/mg cr.; p<0.01). Elevated urinary LTE4 was 48% sensitive and 84% specific for SM. Clinical sensitivity was 53% for BPG (>1000ng/mL) and 71% for NMH (>200ng/mL). Incorporating all three urinary metabolites improved the SM diagnostic sensitivity to 97%, with minimal change in specificity. CONCLUSIONS: We have developed a sensitive and precise LC-MS/MS assay for quantitation of LTE4 in urine. Incorporating LTE4 into a panel including BPG and NMH provides a much-needed screening tool for a complicated disease with non-specific symptoms and invasive confirmatory testing.
Asunto(s)
Biomarcadores/orina , Cromatografía Liquida/métodos , Leucotrieno E4/orina , Mastocitosis/orina , Espectrometría de Masas en Tándem/métodos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Mast cell diseases include mastocytosis and mast cell activation syndromes, some of which have been shown to involve clonal defects in mast cells that result in abnormal cellular proliferation or activation. Numerous clinical studies of mastocytosis have been published, but no population-based comprehensive surveys of patients in the United States have been identified. Few mast cell disease specialty centers exist in the United States, and awareness of these mast cell disorders is limited among nonspecialists. Accordingly, information concerning the experiences of the overall estimated population of these patients has been lacking. OBJECTIVE: To identify the experiences and perceptions of patients with mastocytosis, mast cell activation syndromes, and related disorders, The Mastocytosis Society (TMS), a US based patient advocacy, research, and education organization, conducted a survey of its members and other people known or suspected to be part of this patient population. METHODS: A Web-based survey was publicized through clinics that treat these patients and through TMS's newsletter, Web site, and online blogs. Both online and paper copies of the questionnaire were provided, together with required statements of consent. RESULTS: The first results are presented for 420 patients. These results include demographics, diagnoses, symptoms, allergies, provoking factors of mast cell symptoms, and disease impact. CONCLUSION: Patients with mastocytosis and mast cell activation syndromes have provided clinical specialists, collaborators, and other patients with information to enable them to explore and deepen their understanding of the experiences and perceptions of people coping with these disorders.