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

[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

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 FcgammaRI 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