peter
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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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