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General Mast Cell Disorders Discussion >> General Mast Cell Disorder Discussion >> ? MCA http://mastcelldisorders.wallack.us/yabb/YaBB.pl?num=1361596946 Message started by peter on 02/22/13 at 17:22:26 |
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Title: ? MCA Post by peter on 02/22/13 at 17:22:26 IF theses are the symptoms of mca ? is the ostoprosis coused by SM from the mast cells in the bone marrow or activation in the BM Symptom(s)a Diagnostic impact in the evaluation of severe MCA ( = suspected MCA syndrome = MCAS) a All these symptoms can be triggered by mast cell-derived compounds. Therefore, an isolated symptom is not a typical finding in MCAS patients. Rather, the likelihood of MCA, and thus MCAS, increases when two or more of these symptoms have been recorded and the symptoms improve in response to therapy with antimediator-type drugs or mast cell-stabilizing agents. Hypotension ± shock Pathognomonic key finding in MCAS (other underlying diseases that could explain hypotension need to be excluded) Tachycardia Tachycardia usually accompanies hypotension in MCAS Diarrhea Usually accompanied by systemic symptoms of MCAS; in the absence of these, the diagnosis remains uncertain Abdominal cramping Usually accompanied by systemic symptoms of MCAS; in the absence of these, the diagnosis remains uncertain Nausea Usually accompanied by systemic symptoms of MCAS; in the absence of these, the diagnosis remains uncertain Flushing Severe flushing may be an indicator of MCAS; in these cases; flushing is often accompanied by systemic symptoms Pruritus Severe pruritus may be an indicator of MCAS; in these cases; flushing is often accompanied by systemic symptoms Acute urticaria Severe acute urticaria may be an indicator of MCAS; in these cases, systemic symptoms are usually found Angioedema Severe angioedema may be an indicator of MCAS and then is usually accompanied by systemic symptoms Nasal congestion Diagnostic only in the context of other MCAS-related symptoms and the presence of other MCAS criteria Wheezing Diagnostic only in the context of other MCAS-related symptoms and the presence of other MCAS criteria Headache Diagnostic only in the context of other MCAS-related symptoms and the presence of other MCAS criteria Neurologic symptoms Diagnostic only in the context of other MCAS-related symptoms and the presence of other MCAS criteria Fatigue Diagnostic only in the context of other MCAS-related symptoms and the presence of other MCAS criteria |
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Title: Re: ? MCA Post by Lisa on 02/22/13 at 23:41:10 peter wrote on 02/22/13 at 17:22:26:
Hi Peter! I believe that BOTH conditions can create osteoporosis and this is because they have found that histamine and some of the other MC mediators are important modulators of bone and when they are too many or too few that this may be what is behind the osteoporosis. However, since osteoporosis is found more often in SM patients than appears to be in MCAS patients, FOR NOW, this would indicate that the proliferation of the MCs themselves is causing the bone modulation. HAVING SAID THIS AND TO BE FAIR, it must be openly stated that NOBODY HAS STUDIED THE MCAS PATIENT IN THIS AREA!! There are only two researchers who are doing studies on the MCAS patient and producing papers, Dr. Gerhard Molderings and Dr. Luis Escribano. Of the two, Dr. Molderings has made a connection of hepactic disorders in MCAS patients which correlates with what has been found in SM patients. Since nobody has begun to look at the bone involvement in MCAS patients it is only a presumption that the bone is also being affected by the MC mediators and that is based on other findings by other researchers who have seen and studied the effects of histamine and some of the other mediators upon bones and the medula ossea. So, in order for MCAS patients and their doctors to find understanding about any found osteoporosis, the doctors need to read the other research and make the connections for themselves - a complicated affair to say the least! I hope this makes sense. Lisa |
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Title: Re: ? MCA Post by peter on 02/23/13 at 09:23:35 hi lisa i thought thay would have some answers by now another ? the inflamation of the GL is not on the list but sodium stops it |
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Title: Re: ? MCA Post by peter on 02/23/13 at 09:44:33 [Mast cell activation syndrome]. [Article in German] Brockow K. Source Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein, Klinikums rechts der Isar der Technischen Universität München, Biedersteiner Str. 29, 80802, München, Deutschland, knut.brockow@lrz.tu-muenchen.de. Abstract BACKGROUND: The description of a monoclonal mast cell activation syndrome in patients with anaphylaxis, who fulfill one or two minor-criteria of mastocytosis, has led to a search for new unrecognized mast cell activation syndromes. OBJECTIVE: New classification of mast cell diseases including well-known diseases is provided in order to be able to better recognize and describe new entities. METHODS: The term mast cell activation has been defined by verifiable scientific objective and subjective criteria, and known and idiopathic mast cell activation syndromes have been classified. RESULTS: Mast cell activation cannot be defined by symptoms alone, as different diseases and conditions, including those with contribution of different cell types and somatization disorders may lead to similar symptoms. For this reason the preclinical checkpoint mast cell activation was defined to require typical symptoms in combination with demonstration of mast cell mediator release in (an acute) episode(s) as well as with a good response to mast cell mediator-directed therapy. Mast cell activation syndromes were classified in primary (e.g. mastocytosis), secondary (e.g. IgE-mediated allergy) and idiopathic forms. CONCLUSION: Only through a deeper understanding of mast cell diseases, can new previously unrecognized idiopathic mast cell activation syndrome entities be described and analyzed. where are we now |
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Title: Re: ? MCA Post by Lisa on 02/24/13 at 01:41:12 Hi Peter! Dr. Brockow is a known researcher in mastocytosis and this is a good article, however I think that if you want a clearer picture of where mast cell research is going then I HIGHLY recommend you read Dr. Molderings´ work on this. I think if you can get through the technical greek then you can see where mast cell research is heading from here. Dr. Molderings is the most forward looking researcher we have in MCAS right now. Unfortunately you have the old school which still tends to insist that SM is the only true form and so they are don´t want to accept that MCAS is indeed masto. This is not a serious problem when you consider that we still need research on SM to understand why it´s the way it is, for it is through this research that you gain insight as to the many other forms which they are now finding. However, the problem is when you stick with going over the same old ground, you miss the bigger picture and the larger disease entity that MCAS is. Molderings is looking at the bigger picture and his work is beginning to reflect on SM itself as well as MCAS. So, I recommend you take a look at this article too. You will find his report here: http://link.springer.com/article/10.1007%2Fs00251-010-0474-8 Immunogenetics December 2010, Volume 62, Issue 11-12, pp 721-727 Comparative analysis of mutation of tyrosine kinase kit in mast cells from patients with systemic mast cell activation syndrome and healthy subjects Gerhard J. Molderings, Kirsten Meis, Ulrich W. Kolck, Jürgen Homann, Thomas Frieling Look Inside Get Access Abstract Systemic mast cell activation syndrome is a mast cell disorder characterized by an unregulated increased activation of mast cells leading to a pathologically enhanced release of mediators. Mutations in tyrosine kinase kit which crucially determines mast cell activity have been suggested as a necessary condition for the development of a clinically symptomatic mast cell disease. At the level of mRNA in mast cell progenitor cells of 20 patients with systemic mast cell activation syndrome and of 20 gender- and age-matched healthy volunteers, the tyrosine kinase kit was investigated for genetic alterations by means of RT-PCR and direct sequencing of the amplificates. In mast cells of 13 out of these 20 patients, multiple predominantly novel potential functionally activating point mutations or complex alterations of the mRNA sequence encoding the tyrosine kinase kit were detected. In contrast, in 19 of the 20 healthy subjects, no functionally relevant alterations of c-kit transcripts were detected. The present findings support the idea that the systemic mast cell activation syndrome is a clonal disease most commonly associated with variable activating mutations in the tyrosine kinase kit. This reports shows that there is more than one defect upon C-Kit and that this may explain why there are so many versions of the same disease and that those patients who show lesser degrees or quantities of defect may not show MCAS at all but MCAD - or in other words, those who have more defect may show MCAS, and those with lesser defect may only show some symptoms thus Mast Cell Activation Disorder, but never get to the point of showing the syndrome and Mast Cell Activation Syndrome. If you can´t get a copy of this, just send to me a PM with your email and tell me what article you want and I´ll be happy to send it to you. Hugs! Lisa |
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Title: Re: ? MCA Post by peter on 02/24/13 at 09:44:55 2001 Mastocytosis Cem Akin, MD, PhD Harvard Medical School Brigham and Women’s Hospital Department of Medicine Division of Rheumatology, Immunology and Allergy Boston, MA e-mail: cakin@partners.org WHO Mastocytosis Consensus Classification • Cutaneous mastocytosis • Indolent systemic mastocytosis (without AHD) – Smoldering systemic mastocytosis – Isolated bone marrow mastocytosis • Systemic mastocytosis with an AHNMD – MDS, MPD, AML, NHL • Aggressive systemic mastocytosis • Mast cell leukemia • Mast cell sarcoma • Extracutaneous mastocytoma Leukemia Research, 25(7):603-625, 2001 WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues, p:293-302, 2001 Diagnostic Criteria for Systemic Mastocytosis (need the major + 1 minor or 3 minor criteria for diagnosis) • Major: – Characteristic multifocal dense infiltrates of mast cells in bone marrow biopsy • Minor: – Morphology of mast cells: Spindle shaped – Detection of a codon 816 c-kit mutation – Flow cytometric co-expression of CD117, CD2 and CD25 by the bone marrow mast cell population – Serum tryptase >20 ng/ml Signs and symptoms of mastocytosis Skin: Episodic flushing, itching, hyperpigmented maculopapular lesions (UP) Cardiovascular: Episodic tachycardia, hypotension, lightheadedness Gastrointestinal: Abdominal cramping, diarrhea, heartburn, nausea, vomiting, peptic ulcer, hepatomegaly, ascites Musculoskeletal: Osteoporosis, osteosclerosis, diffuse soft-tissue pain Hematologic: Splenomegaly, lymphadenopathy, signs and symptoms of the associated hematologic disorder, if present Constitutional: Fatigue, headache When to suspect systemic mastocytosis 1. Adult patient with urticaria pigmentosa 2. Child with late onset of skin lesions (>2 years of age) and hepatosplenomegaly, unexplained CBC abnormality or unexplained pathologic lymphadenopathy 3. Patients with recurrent unexplained anaphylaxis: Syncopal or pre-syncopal episodes associated with other signs of mast cell mediator release 4. Patients with premature osteoporosis, or pathologic fractures When to consider referral 1. Patients with aggressive variants who are candidates for investigational or cytoreductive therapies 2. Patients with anaphylaxis and low tryptase levels (expected to have low mast cell burden and thus need more sensitive diagnostic evaluation such as flow cytometry) 3. Any time you need an expert opinion and the patient is willing and stable enough to travel Treatment of mastocytosis Symptomatic H1 antihistamines: e.g. Fexofenadine, Cetirizine, Hydroxyzine, Diphenhydramine H2 antihistamines: e.g. Ranitidine, Famotidine Antileukotrienes: e.g. Montelukast, Zileuton Mast cell stabilizer: Gastrocrom Epinephrine (Epi-Pen) as needed for anaphylactoid attacks Glucocorticoids: e.g. Prednisone PUVA Cytoreductive Consider in aggressive categories associated with decreased life expectancy Consider a second opinion from a referral center Refer to a Hematology/Oncology specialist IFN-α (SQ injection) 2-CDA (Cladribine) (IV) Imatinib in selected cases (D816V c-kit mutation negative; most patients are not candidates) Investigational therapy (new kinase inhibitors: PKC412) Associated hematologic disorder (myeloproliferative, MDS, leukemias, lymphomas): Treat accordingly Mast cell activators of clinical relevance • IgE-dependent – Allergen • IgE-independent – IgG via FcgammaRI and III – Bacterial components • Peptidoglycan: TLR2/6 • LPS: TLR4 • fMLP – C3a, C5a – Cysteinyl leukotrienes – Cytokines/chemokines • SCF, NGF – Neuropeptides – Drugs • Opioids, muscle relaxants, radiocontrast material, adenosine – Physical stimuli • Heat, cold, pressure, exercise – Hormones • Estrogen, progesterone, CRH, alpha-MSH Mast cell activation disorders 1. Primary a. Anaphylaxis with an associated clonal mast cell disorder (systemic mastocytosis) b. Monoclonal mast cell activation syndrome 2. Secondary a. Allergic diseases b. Mast cell activation associated with chronic inflammatory or neoplastic disorders c. Physical urticarias d. Chronic autoimmune urticaria 3. Idiopathic a. anaphylaxis b. angioedema c. urticaria d. mast cell activation disorder yes lisa YoU are right the only truble is thay put Us [ige sm] in with mcas you see i have both . but it is what demege that gives it a name |
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Title: Re: ? MCA Post by peter on 02/25/13 at 10:53:25 computer security problem third party changing security settings compromised email possible articles may have been CHANGED Edited from original peter |
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