prostaglandin-d2 and Syndrome

Mast cell activation syndrome (MCAS) is a condition with signs and symptoms involving the skin, gastrointestinal, cardiovascular, respiratory, and neurologic systems. It can be classified into primary, secondary, and idiopathic. Earlier proposed criteria for the diagnosis of MCAS included episodic symptoms consistent with mast cell mediator release affecting two or more organ systems with urticaria, angioedema, flushing, nausea, vomiting, diarrhea, abdominal cramping, hypotensive syncope or near syncope, tachycardia, wheezing, conjunctival injection, pruritus, and nasal stuffiness. Other criteria included a decrease in the frequency, severity, or resolution of symptoms with anti-mediator therapy including H(1) and H(2)histamine receptor antagonists, anti-leukotrienes, or mast cell stabilizers. Laboratory data that support the diagnosis include an increase of a validated urinary or serum marker of mast cell activation (MCA), namely the documentation of an increase of the marker above the patient's baseline value during symptomatic periods on more than two occasions, or baseline serum tryptase levels that are persistently above 15 ng/ml, or documentation of an increase of the tryptase level above baseline value on one occasion. Less specific assays are 24-h urine histamine metabolites, PGD(2) (Prostaglandin D(2)) or its metabolite, 11-β-prostaglandin F(2) alpha. A recent global definition, criteria, and classification include typical clinical symptoms, a substantial transient increase in serum total tryptase level or an increase in other mast cell derived mediators, such as histamine or PGD2 or their urinary metabolites, and a response of clinical symptoms to agents that attenuate the production or activities of mast cell mediators.

Topics: Animals; Histamine; Humans; Leukotrienes; Mast Cells; Mastocytosis; Prostaglandin D2; Syndrome

Mast cell activation syndrome (MCAS), a recently recognized nonneoplastic mast cell disease driving chronic multisystem inflammation and allergy, appears prevalent and thus important. We report the first systematic characterization of a large MCAS population.. Demographics, comorbidities, symptoms, family histories, physical examination and laboratory findings were reviewed in 298 retrospective and 115 prospective patients with MCAS. Blood samples from prospective subjects were examined by flow cytometry for clonal mast cell disease and tested for cytokines potentially driving the monocytosis frequent in MCAS.. Demographically, white females dominated. Median ages at symptom onset and diagnosis were 9 and 49 years, respectively (range: 0-88 and 16-92, respectively) and median time from symptom onset to diagnosis was 30 years (range: 1-85). Median numbers of comorbidities, symptoms, and family medical issues were 11, 20, and 4, respectively (range: 1-66, 2-84, and 0-33, respectively). Gastroesophageal reflux, fatigue and dermatographism were the most common comorbidity, symptom and examination finding. Abnormalities in routine laboratories were common and diverse but typically modest. The most useful diagnostic markers were heparin, prostaglandin D. Our study highlights MCAS׳s morbidity burden and challenging heterogeneity. Recognition is important given good survival and treatment prospects.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Child; Child, Preschool; Chromogranin A; Female; Heparin; Histamine; Humans; Infant; Infant, Newborn; Male; Mastocytosis; Middle Aged; Prospective Studies; Prostaglandin D2; Retrospective Studies; Syndrome; Young Adult

Some sickle cell anemia (SCA) patients suffer significantly worse phenotypes than others. Causes of such disparities are incompletely understood. Comorbid chronic inflammation likely is a factor. Recently, mast cell (MC) activation (creating an inflammatory state) was found to be a significant factor in sickle pathobiology and pain in a murine SCA model. Also, a new realm of relatively noncytoproliferative MC disease termed MC activation syndrome (MCAS) has been identified recently. MCAS has not previously been described in SCA. Some SCA patients experience pain patterns and other morbidities more congruent with MCAS than traditional SCA pathobiology (eg, vasoocclusion). Presented here are 32 poor-phenotype SCA patients who met MCAS diagnostic criteria; all improved with MCAS-targeted therapy. As hydroxyurea benefits some MCAS patients (particularly SCA-like pain), its benefit in SCA may be partly attributable to treatment of unrecognized MCAS. Further study will better characterize MCAS in SCA and identify optimal therapy.

Topics: Adult; Anemia, Sickle Cell; Antisickling Agents; Caseins; Chromogranin A; Cohort Studies; Female; Heparin; Histamine; Humans; Hydroxyurea; Inflammation; Male; Mastocytosis; Methylhistamines; Middle Aged; Phenotype; Prostaglandin D2; Protein Hydrolysates; Syndrome; Young Adult

The term mast cell activation syndrome (MCAS) is finding increasing use as a diagnosis for subjects who present with signs and symptoms involving the dermis, gastrointestinal track, and cardiovascular system frequently accompanied by neurologic complaints. Such patients often have undergone multiple extensive medical evaluations by different physicians in varied disciplines without a definitive medical diagnosis until the diagnosis of MCAS is applied. However, MCAS as a distinct clinical entity has not been generally accepted, nor do there exist definitive criteria for diagnosis. Based on current understanding of this disease "syndrome" and on what we do know about mast cell activation and resulting pathology, we will explore and propose criteria for its diagnosis. The proposed criteria will be discussed in the context of other disorders involving mast cells or with similar presentations and as a basis for further scientific study and validation.

Topics: Abnormalities, Multiple; Cell Degranulation; Cytokines; Diagnosis, Differential; Humans; Leukotriene C4; Mast Cells; Practice Guidelines as Topic; Prostaglandin D2; Syndrome

Topics: Adult; Aspirin; Erythema; Humans; Hypotension; Male; Prostaglandin D2; Prostaglandins; Prostaglandins D; Shock; Syndrome; Urticaria Pigmentosa