Learned cautions regarding antibody testing in mast cell activation syndrome.

Objectives: To describe patterns observed in antibody titer trendlines in patients with mast cell activation syndrome (MCAS, a prevalent but underrecognized chronic multisystem inflammatory disorder of great clinical heterogeneity) and offer clinical lessons learned from such pattern recognition.

Methods: The available records of 104 MCAS patients drawn from the authors' practices were reviewed, including all antibody tests therein.

Results: All patients had positive/elevated antibodies of various sorts at various points, but for most of the antibodies which were found to be positive at least some points, the diseases classically associated with those antibodies were not present, marking such antibodies as clinically insignificant mimickers (likely consequent to inflammatory effects of MCAS on the immune system itself driving spurious/random antibody production) rather than "on-target" and pathogenic antibodies reflecting true disease warranting treatment.

A survey of the currently known mast cell mediators with potential relevance for therapy of mast cell-induced symptoms.

Mast cells (MCs) occupy a central role in immunological as well as non-immunological processes as reflected in the variety of the mediators by which MCs influence other cells. Published lists of MC mediators have all shown only subsets-usually quite small-of the full repertoire. The full repertoire of MC mediators released by exocytosis is comprehensively compiled here for the first time.

Cluster-Analytic Identification of Clinically Meaningful Subtypes in MCAS: The Relevance of Heat and Cold.

Background: Mast cell activation syndrome (MCAS) is a clinically heterogeneous disease with allergy-like symptoms and abdominal complaints. Its etiology is only partially understood and it is often overlooked.

Aims: The aim of this study was to identify subgroups of MCAS patients to facilitate diagnosis and allow a personalized therapy.

Efficacy and toxicity of hydroxyurea in mast cell activation syndrome patients refractory to standard medical therapy: retrospective case series.

Determine efficacy and adverse events (AEs) of hydroxyurea (HU) in mast cell activation syndrome (MCAS) patients who were refractory to standard medical therapy. An electronic chart review was performed to find MCAS patients who received HU in a MCAS medical practice. Diagnosis of MCAS was established on the basis of mast cell (MC) activation symptoms in ≥ 5 systems plus ≥ 1 abnormal MC mediators and/or ≥ 20 MC/high power field on duodenal biopsies.

Evaluation of a tryptase depletion index for better pathologic identification of mast cell activation syndrome.

Background: Laboratory evidence supporting diagnosis of the prevalent condition of mast cell activation syndrome (MCAS) currently includes elevated levels in blood or urine of mediators relatively specific to mast cells (MCs) and/or increased numbers of MCs in luminal gastrointestinal (GI) tract tissues. However, identification of elevated mediators is technically challenging and expensive, and controversy persists regarding the normal ranges of numbers/counts of MCs in various GI tract segments, let alone challenges in determining how many of the visualized MCs are activated. To aid diagnosis of MCAS, we developed a potential new approach for the pathologist to identify the extent of GI tract MC activation easily and inexpensively.

[Cystic diseases in urology : Recommendations for patients with systemic mast cell disease].

The systemic mast cell disease (MCAD; prevalence 17%) may occur frequently in urological patients. MCAD-induced changes include cysts in all organs, also in the urogenital system. In the presence of MCAD, the surgical removal of such cysts must consider specific features of the MCAD in order to reduce surgical and complication risks.

Restless legs syndrome is associated with long-COVID in women.

Study Objectives: Sleep disturbance is common in long-COVID (LC). Restless legs syndrome (RLS) is characterized by sleep disturbance and has been reported after viral infections. Therefore, we evaluated RLS symptoms cross-sectionally in individuals with LC at both current and pre-coronavirus disease 2019 (pre-COVID-19) time points.

Mast cell activation symptoms are prevalent in Long-COVID.

Objectives: Hyper-inflammation caused by COVID-19 may be mediated by mast cell activation (MCA) which has also been hypothesized to cause Long-COVID (LC) symptoms. We determined prevalence/severity of MCA symptoms in LC.

Methods: Adults in LC-focused Facebook support groups were recruited for online assessment of symptoms before and after COVID-19.

Effects of Primary Mast Cell Disease on Hemostasis and Erythropoiesis.

Mast cell disease is an epigenetically and genetically determined disease entity with very diverse clinical manifestations in potentially every system and tissue due to inap pro priate release of variable subsets of mast cell mediators together with accumulation of either morphologically normal or altered mast cells. Easy bruising, excessive bleeding, and aberrancies of erythropoiesis can frequently be observed in patients with mast cell disease. A thorough history, including a family history, will guide the appropriate work-up, and laboratory evaluations may provide clues to diagnosis.

Serotonin and beyond-a tribute to Manfred Göthert (1939-2019).

Manfred Göthert, who had served Naunyn-Schmiedeberg's Arch Pharmacol as Managing Editor from 1998 to 2005, deceased in June 2019. His scientific oeuvre encompasses more than 20 types of presynaptic receptors, mostly on serotoninergic and noradrenergic neurones. He was the first to identify presynaptic receptors for somatostatin and ACTH and described many presynaptic receptors, known from animal preparations, also in human tissue.

Covid-19 hyperinflammation and post-Covid-19 illness may be rooted in mast cell activation syndrome.

Objectives: One-fifth of Covid-19 patients suffer a severe course of Covid-19 infection; however, the specific causes remain unclear. Mast cells (MCs) are activated by SARS-CoV-2. Although only recently recognized, MC activation syndrome (MCAS), usually due to acquired MC clonality, is a chronic multisystem disorder with inflammatory and allergic themes, and an estimated prevalence of 17%.

Adrenal insufficiency is a contraindication for omalizumab therapy in mast cell activation disease: risk for serum sickness.

Omalizumab is an effective therapeutic humanized murine IgE antibody in many cases of primary systemic mast cell activation disease (MCAD). The present study should enable the clinician to recognize when treatment of MCAD with omalizumab is contraindicated because of the potential risk of severe serum sickness and to report our successful therapeutic strategy for such adverse event (AE). Our clinical observations, a review of the literature including the event reports in the FDA AE Reporting System, the European Medicines Agency Eudra-Vigilance databases (preferred search terms: omalizumab, Xolair®, and serum sickness) and information from the manufacturer's Novartis database were used.

Mast Cell Activation Syndrome: A Primer for the Gastroenterologist.

Mast cell activation syndrome is thought to be a common, yet under-recognized, chronic multi-system disorder caused by inappropriate mast cell activation. Gastrointestinal symptoms are frequently reported by these patients and are often mistaken by physicians as functional gastrointestinal disorders. This syndrome can be diagnosed by the medical history and measurable biomarkers.

Diagnosis of mast cell activation syndrome: a global "consensus-2".

The concept that disease rooted principally in chronic aberrant constitutive and reactive activation of mast cells (MCs), without the gross MC neoplasia in mastocytosis, first emerged in the 1980s, but only in the last decade has recognition of "mast cell activation syndrome" (MCAS) grown significantly. Two principal proposals for diagnostic criteria have emerged. One, originally published in 2012, is labeled by its authors as a "consensus" (re-termed here as "consensus-1").

Restless legs syndrome is associated with mast cell activation syndrome.

Study Objectives: Mast cell activation syndrome (MCAS) is an inflammatory and allergic disorder. We determined the prevalence of restless legs syndrome (RLS) in MCAS because each common syndrome may be inflammatory in nature and associated with dysautonomia.

Methods: Individuals with MCAS were evaluated for RLS by two standard questionnaires.

Case Report: Treatment of systemic mastocytosis with sunitinib.

Mast cell activation disease typically presents as chronic multisystem polymorbidity of generally inflammatory ± allergic theme.  Presently, treatment of the rare, cytoproliferative variant systemic mastocytosis employs empirically selected therapies to impede mast cell mediator production and action and, when necessary, inhibition of proliferation. Some tyrosine kinase inhibitors (TKIs) have been used successfully in uncommon cases of systemic mastocytosis not bearing that disease's usual imatinib-resistant KIT mutation.

Risk of solid cancer in patients with mast cell activation syndrome: Results from Germany and USA.

 It has been shown repeatedly that mast cells can promote or prevent cancer development and growth. If development and/or progression of a solid cancer is substantially influenced by mast cell activity, the frequencies of occurrence of solid cancers in patients with primary mast cells disorders would be expected to differ from the corresponding prevalence data in the general population. In fact, a recent study demonstrated that patients with systemic mastocytosis (i.

Lower prevalence of vitamin D insufficiency in German patients with systemic mast cell activation syndrome compared with the general population.

 The common mastocytosis variant systemic mast cell activation syndrome (MCAS) may underlie at least a subset of patients with irritable bowel syndrome (IBS). A critical role of vitamin D (VD) in the stabilization of mast cells (MCs) with deficiency of VD resulting in MC activation has been demonstrated. If so, supplementation of VD would be a potential therapeutic approach in the treatment of those IBS patients.

A Practical Guide for Treatment of Pain in Patients with Systemic Mast Cell Activation Disease.

Systemic mast cell activation disease (MCAD, a subclass of mastocytosis), which has a prevalence of around 17% (at least in the German population), is characterized by accumulation of genetically altered dysfunctional mast cells with abnormal release of these cells' mediators. Since mast cells affect functions in potentially every organ system, often without causing abnormalities in routine laboratory or radiologic testing, this disease has to be considered routinely in the differential diagnosis of patients with chronic multisystem polymorbidity of a generally inflammatory and allergic theme. Pain in its different manifestations is a common symptom in MCAD found in more than three-quarters of the MCAD patients.

Siglec-8 as mast cell selective target: developing paradigms amidst inconvenient truths.

Due to the limited efficacy of current drugs in treating systemic mast cell activation disease, there is an urgent need for more effective drugs selectively acting at mast cells. In the past, a large number of compounds have been claimed to be effective and mast cell selective on the basis of cell culture experiments and studies on blood leukocytes which could not be verified in organ and animal studies. Nevertheless, over time in review papers about potential mast cell targets mast cell selectivity of these targets has been no longer challenged.