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Dx Mastocystosis Treatment: Read more...


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Observation:
Mastocytosis

Medscape
states:
"Systemic mastocytosis, often termed systemic mast cell disease (SMCD), is a myeloproliferative neoplasm characterized by infiltration of clonally derived mast cells in different tissues, including bone marrow, skin, the gastrointestinal tract, the liver, and the spleen. Median survival ranges from 198 months in patients with indolent systemic mastocytosis to 41 months in aggressive systemic mastocytosis and 2 months in mast cell leukemia.

Essential update:
Better understanding of bone involvement in systemic mastocytosis
Indolent systemic mastocytosis with or without cutaneous manifestations is characterized by decreased trabecular bone mass and an increased number of osteoclasts and osteoblasts. In a retrospective study of 300 patients with histologically proven indolent systemic mastocytosis, bone cell numbers in patients with mast cell granulomas were significantly higher than in those with diffuse mast cell distribution. Severity of bone disease in these patients may be dependent on the amount of mast cells and their distribution within bone marrow rather than the presence or absence of cutaneous involvement.

Signs and symptoms:
Manifestations of systemic mastocytosis may include the following: Systemic mastocytosis, often termed systemic mast cell disease (SMCD), is a myeloproliferative neoplasm characterized by infiltration of clonally derived mast cells in different tissues, including bone marrow, skin, the gastrointestinal tract, the liver, and the spleen.[1, 2, 3, 4, 5] Median survival ranges from 198 months in patients with indolent systemic mastocytosis to 41 months in aggressive systemic mastocytosis and 2 months in mast cell leukemia. Essential update: Better understanding of bone involvement in systemic mastocytosis Indolent systemic mastocytosis with or without cutaneous manifestations is characterized by decreased trabecular bone mass and an increased number of osteoclasts and osteoblasts. In a retrospective study of 300 patients with histologically proven indolent systemic mastocytosis, bone cell numbers in patients with mast cell granulomas were significantly higher than in those with diffuse mast cell distribution. Severity of bone disease in these patients may be dependent on the amount of mast cells and their distribution within bone marrow rather than the presence or absence of cutaneous involvement.

Signs and symptoms:
Manifestations of systemic mastocytosis may include the following:
*Anemia and coagulopathy
*Abdominal pain is the most common GI symptom, followed, by diarrhea, nausea, and vomiting
*Symptoms and signs of gastroesophageal reflux disease (GERD)
*Pruritus and flushing
*Anaphylactoid reaction (eg, to Hymenoptera stings, general anesthetics, intravenous contrast media, other drugs, foods)

Findings on physical examination may include the following:
*Signs of anemia (eg, pallor)
*Hepatomegaly (27%)
*Splenomegaly (37%)
*Lymphadenopathy (21%)
*Urticaria (41%)
*Osteolysis and pathological fractures (rare)

Diagnosis:
Findings on blood studies may include the following:
*Anemia (45% of patients)
*Thrombocytopenia
*Leukocytosis
*Some patients have eosinophilia, basophilia, thrombocytosis, and monocytosis
*The combination of anemia, thrombocytopenia, hypoalbuminemia, and excess bone marrow blasts (>5%) portends a poor prognosis.

Measurement of serum tryptase may reveal the following:
*Total serum tryptase levels of 20 ng/mL or higher in a baseline serum sample with a total–to–beta-tryptase ratio greater than 20:1
*Serum tryptase levels of 11.5 ng/mL or higher (the cut-off value used in more recent studies) are found in more than 50% of patients The following imaging studies may be necessary to identify the extent and stage of the disease:
*GI radiography, ultrasonography, and liver-spleen computed tomography scanning in patients with abdominal pain Skeletal surveys and bone CT scanning in patients with suspected bone involvement
Diagnostic procedures are as follows:

*Bone marrow aspiration and biopsy are essential
*GI procedures (eg, barium studies, endoscopy) are indicated for patients with GI symptoms
*Liver biopsy can show mast cell infiltration in patients with hepatomegaly
*Skin biopsy may be warranted in patients with cutaneous manifestations

The major diagnostic criterion for systemic mastocytosis is the presence of dense infiltrates of mast cells in bone marrow or other extracutaneous tissues. Mast cells should be seen in aggregates of 15 or more.

Major criteria may be absent in early disease. In this situation, the minor criteria are used to make the pathologic diagnosis. Three of the following 4 minor criteria are required to make the diagnosis:
*Atypical mast cell morphology in 25% or more of the mast cells
*Expression of CD2 and/or CD25 in addition to normal mast cell markers
*Serum/plasma tryptase levels greater than 20 ng/mL
*A codon-816 c-kit mutation in peripheral blood, bone marrow, or involved tissue

Types of mastocytosis (World Health Organization criteria) are as follows:
*Cutaneous mastocytosis
*Indolent systemic mastocytosis (systemic mast cell disease)
*Systemic mastocytosis with associated clonal hematologic non–mast cell lineage disease

Aggressive systemic mastocytosis
*Mast cell leukemia
*Mast cell sarcoma

Extracutaneous mastocytoma

Management:
Therapy for systemic mastocytosis is primarily symptomatic; no therapy is curative. Treatment modalities include the management of the following:
*Anaphylaxis and related symptoms
*Pruritus and flushing
*Intestinal malabsorption

Agents for symptomatic relief include the following:
*Epinephrine is used in acute anaphylaxis
*H1 and H2 receptor blockers are used to control anaphylactic symptoms
*Corticosteroids have been used to control malabsorption, ascites, and bone pain and to prevent anaphylaxis
*Cromolyn is helpful for decreasing bone pain and headaches and for improving skin symptoms
* Patients with osteopenia that does not respond to therapy may receive a trial of interferon alfa-2b
*First-generation histamine H1 antagonists (eg, diphenhydramine, hydroxyzine) have been used to treat pruritus and flushing
*Histamine H2 antagonists and proton pump inhibitors have been used to treat gastric hypersecretion and peptic ulcer disease
*Aspirin can be used when H1 and H2 receptor blockers do not prevent vascular collapse
*Mast cell stabilizers (eg, ketotifen) have been used to treat pruritus and whealing
*Leukotriene antagonists (eg, zafirlukast, montelukast) have been used Cromolyn is helpful for decreasing bone pain and headaches and for improving skin symptoms
*Psoralen ultraviolet A therapy may provide transient relief of pruritus and may cause fading of skin lesions
*Anticholinergics have been used in the treatment of diarrhea
*Disodium cromolyn has been used in the treatment of abdominal cramping and diarrhea

Chemotherapy has not been particularly successful in the management of systemic mastocytosis, but the following regimens have been tried:
*Interferon-alfa may be beneficial, especially in patients with aggressive systemic mastocytosis
*2-Chlorodeoxyadenosine (Cladribine)
*Thalidomide in advanced disease
*Imatinib mesylate (Gleevec) in patients who do not have mutations of the codon 816 on the c-kit gene and carry the wild-type kit, or who carry the FIP1L1-PDGFRA rearrangement.

Medications Used in Treatment:
1. Mast Cell Stabilizers: Gastrocrom®/cromolyn
2. Kinase Inhibitors: Gleevec®/imatinib

Suggested Links:
*The Merck Manual Home Edition
*N.H.S. Choices

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