Mast cell disorders

Mast Cell Disorders By

Wat Mitthamsiri, MD.Allergy and Clinical Immunology FellowKing Chulalongkorn Memorial Hospital

Previous issues

• How long is the life span of mast cells in circulation (not in tissue)?

J Hallgren and MF Gurich, Mast Cell Biology: Contemporary and Emerging Topic, Springer Science+Business Media, 2011, p14-28.

Previous issues

• What is non-pathological, physiological role of mast cell?– One of the first responder in innate defense

against infections• Location• Arrays of innate sensors:

– PRRs: TLR1-7 and TLR9, NLRP3– Complement products receptors– CRP, LPS-binding proteins, pentraxins, collectins– Sensors for other peptide signals from other cells

CP Shellburne and SN Abraham, Mast Cell Biology: Contemporary and Emerging Topic, Springer Science+Business Media, 2011, p162-185.

Ligands that can activate MCs


Microbial sensors of MCs


Previous issues

• What is non-pathological, physiological role of mast cell?– One of the first responder in innate defense

against infections• Arrays of weapons:

– Mediators– Cytokines– Antimicrobial peptides: Beta-defensins, cathelicidin

• Powerful response: Neutrophil recruitment


Previous issues

• What is non-pathological, physiological role of mast cell?– Protection against toxic substances• MC’s carboxypeptidase is required to limit effect of:

– Endothelin-1 (ET-1) peptide from peritonitis– Pit viper venom– Honeybee (Apis mellifera) venom

• MC’s proteases limit toxic effect of neurotensin, IL-6


Previous issues

• What is non-pathological, physiological role of mast cell?– Enhance adaptive immune response• MC-deficient mice had impaired T-cell activation and

had reduced DC migration• MCs remotely enhance lymphocytes sequestration in

lymph nodes by using TNF-a• Using MC-activating compound as an adjuvant with

some Ag can elicit protective immunity to the corresponding pathogen only in host with normal MC• MC activating compound can increase IgA secretion in

mucosal challangeCP Shellburne and SN Abraham, Mast Cell Biology: Contemporary and Emerging Topic, Springer Science+Business Media, 2011, p162-185.

Summary of MC’s defense model


Mast Cell Disorders By

Wat Mitthamsiri, MD.Allergy and Clinical Immunology FellowKing Chulalongkorn Memorial Hospital

Outline

• Classification and epidemiology• Pathogenesis• Clinical features• Pathology• Approach for diagnosis• Treatment• Prognosis

Classificationand

Epidemiology

Diseases of mast cells

P Bradding, H Saito., Middleton’s Allergy 8th edition, 2013, 228-251.DD Metcalfe., Middleton’s Allergy 8th edition, 2013, 1224-1236.

Excessive mast cell no/Fn • Localized

mastocytosis• Systemic

mastocytosis

Mast cell deficiency• Never been found

Localized mastocytosis

• Cutaneous mastocytosis – Urticaria pigmentosa/maculopapular cutaneous

mastocytosis (UP/MPCM)– Diffuse cutaneous mastocytosis (DCM)– Solitary mastocytoma

• Extracutaneous mastocytoma

Horny H-P, et al. Mastocytosis. In: Swerdlow SH, et al, editors. WHO classification of tumors of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2008.DD Metcalfe., Middleton’s Allergy 8th edition, 2013, 1224-1236.

Systemic mastocytosis• Indolent Systemic Mastocytosis (ISM)• Systemic Mastocytosis with Associated Clonal,

Hematologic Non–Mast Cell Lineage Disease (SM-AHNMD)

• Aggressive Systemic Mastocytosis (ASM)• Mast Cell Leukemia (MCL)• Mast Cell Sarcoma (MCS)• Monoclonal mast cell activation syndrome

(MMAS)• Mast cell activation syndrome (MCAS)Horny H-P, et al. Mastocytosis. In: Swerdlow SH, et al, editors. WHO classification of tumors of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2008.

DD Metcalfe., Middleton’s Allergy 8th edition, 2013, 1224-1236.

Epidemiology• Unknown prevalence– Estimated 20,000-30,000 in the USA

• Male/female ratio of 1 : 1 to 1 : 3• Found in all ethnic backgrounds– More frequently reported in Caucasians

• May occur at any age• Familial occurrence is unusual


Pathogenesis

Pathogenesis

KIT-dependent

Apoptosis inhibition

Other modifying mutation


KIT-dependent

AM Gilfillan and C Tkaczyk, Nature Reviews Immunology, 2006, 6:218-230

KIT-dependent

J Lennartsson and L Rönnstrand, Physiological ReviewsPublished 1 October 2012Vol. 92no. 4,1619-1649.AM Gilfillan and C Tkaczyk, Nature Reviews Immunology, 2006, 6:218-230

Other names:• Mast/stem cell growth

factor receptor (SCFR)• Proto-oncogene c-Kit• Tyrosine-protein kinase

Kit• CD117

KIT-dependent

J Lennartsson and L Rönnstrand, Physiological ReviewsPublished 1 October 2012Vol. 92no. 4,1619-1649.Chromosome image: http://ghr.nlm.nih.gov/gene/KIT

Chromosome4Position 12

(4q12)

KIT-dependent

DD Metcalfe., Middleton’s Allergy 8th edition, 2013, 1224-1236.Chromosome image: http://ghr.nlm.nih.gov/gene/KIT

• Most common mutation = ASP 816 VAL (D816V)• Inheriable to next generation? No

evidence• Other mutations:• V560G (MCL cell line)• D816Y, D816F, D816H, E839K (pediatric

mastocytosis)• F522C• R815K, D820G, V533D, V559A, del419,

K509I, and A533D (Exceedingly rare <1%)

Apoptosis inhibition

FIP1L1-PDGFRA fusion

PRKG2-PDGFRB fusion

Anti-apoptotic proteins


FIP1L1-PDGFRA

Oncogene in pluripotential hematopoietic progenitor cells

Results from ~800-kb interstitial deletion of chromosome 4q12

Patients:• ↑ Mast cells• Peripheral eosinophilia• ↑ Serum tryptase levels


PRKG2-PDGFRB

Systemic mastocytosis

Chronic basophilic leukemia

Rare


Anti-apoptotic proteins

AB Gustafsson and RA Gottlieb, American Journal of Physiology - Cell Physiology,1 January 2007Vol. 292no. 1, C45-C51

http://ajpcell.physiology.org/content/292/1/C45







Clinical features

Clinical features

Systemic symptoms

Dermatologic symtoms

GI symtoms

Musculoskeletal symptoms

Hepatosplenic symptoms

Neuropsychiatric sypmtomsDD Metcalfe., Middleton’s Allergy 8th edition, 2013, 1224-1236.

Systemic symptoms


• Caused by mast cell’s mediators

Systemic symptoms


• Flushing and episodic hypotension• Hypotension may be provoked by– Alcohol– Aspirin– Insect stings– Infection– Exposure to iodinated contrast materials

• No increased risk in bacterial, fungal, or viral infections

Dermatologic symptoms


• Urticaria pigmentosa (UP)/maculopapular cutaneous mastocytosis (MPCM)– Most common pattern of skin involvement in both

adults and children– Found in >90% of ISM patients– Found in ~50% of SM-AHNMD or ASM patients

Urticaria pigmentosa


• Tend to spare palms, soles, face, and scalp• Rubbing the lesions => urtication and erythema

over and around the macules (Darier sign)• May be associated with pruritus exacerbated by:– Changes in temperature– Local frictionIngestion of hot beverages or spicy foods– Ethanol– Drugs

• Petechiae, ecchymoses, or telangiectasias may be present in or adjacent to UP lesions

Darier sign

http://www.allergikos.gr/%CE%BC%CE%B1%CF%83%CF%84%CE%BF%CE%BA%CF%85%CF%84%CF%84%CE%AC%CF%81%CF%89%CF%83%CE%B7/

Diffuse cutaneous mastocytosis


Both UP and DCM


• May have bullous eruptions with hemorrhage

• Blisters may erupt spontaneously or in association with infection or immunization

Solitary mastocytomas


• Fairly common cutaneous variant• May be present at birth but usually before age

3 months• Usually spontaneously involute during

childhood• Solitary extracutaneous mastocytomas of the

lung have been reported in adults

Solitary mastocytomas

(http://dermaamin.com/site/images/clinical-pic/m/mastocytoma-solitary_mastocytoma/mastocytoma-solitary_mastocytoma1.jpg

)

DM Thappa,B. Jeevankumar, Indian Pediatrics 2005; 42:390

http://dermaamin.com/site/images/clinical-pic/m/mastocytoma-solitary_mastocytoma/mastocytoma-solitary_mastocytoma1.jpg

http://dermaamin.com/site/images/clinical-pic/m/mastocytoma-solitary_mastocytoma/mastocytoma-solitary_mastocytoma1.jpg

Mast cell sarcomas


• Exceedingly rare• Characterized by a tumor consisting of highly

atypical immature mast cells• Distant spread is possible• Leukemia phase may occur

Telangiectasia macularis eruptiva perstans (TMEP)


• Found <1% of mastocytosis patients• Reported only in adults• Characteristic skin lesion– Telangiectatic, red macule on a tan-brown

background– 2-6 mm in diameter– No sharply defined borders

• Pruritus, purpura, blister -> Uncommon• May become edematous when rubbed• Occasionally coexist with UP

Telangiectasia macularis eruptiva perstans (TMEP)

Ahmet Altiner MD, Julia Tzu MD, Rishi Patel MD, Shane Meehan MD, Miguel Sanchez, et al., Dermatology Online Journal 17 (10): 7

GI symptoms


• 80% of patients had significant GI symptoms• Abdominal pain = Most common GI symptom– Followed by diarrhea and N/V– 70% of patients with dyspeptic pain had evidence

of gastric acid hypersecretion– PU occured in 4-44% of all patients– Plasma concentration of histamine correlated with

basal acid output• GI bleeding -> Uncommon

GI symptoms


• Diarrhea, from:– Altered intestinal secretion– Structural disease of the small intestinal mucosa– Hypermotility or transit disorder

• Malabsorption– Found in 31% of patients– Usually not severe– Primarily occurred as mild steatorrhea with

impaired absorption of d-xylose or vitamin B12– Diffuse, small intestinal mucosal dysfunction has

been proposed as the cause

Musculoskeletal symptoms


• Uncertain etiology– Unless associated with osteopenia or osteoporosis

• Osteoporosis leading to pathologic fractures– Back pain from osteoporosis– Vertebral compression fractures– May be the initial manifestation of mastocytosis

Hepatosplenic symptoms


• ~60% of patients had evidence of liver disease– 24% -> Hepatomegaly – 54% -> Elevated ALP and GGT• ALP levels correlated with GGT levels, hepatomegaly,

splenomegaly, and liver mast cell infiltration and fibrosis

• In SM-AHNMD or ASM patients– Elevated ALP -> More frequently– Reported 5 cases of ascites or portal hypertension

• Severe liver disease is uncommon– Except in patients with aggressive disease

Neuropsychiatric symptoms


• In adults– Decreased attention span– Memory impairment– Irritability– May caused by therapeutic medicines as well as

circulating mediators• In children– No clear excess pathology– No specific behavioral pattern implicating

histamine overproduction was identified

Pathology

Pathology

Dermatologic pathology

Bone marrow pathology

Radiologic pathology

Liver pathology

Spleen pathology

Lymph nodes pathologyDD Metcalfe., Middleton’s Allergy 8th edition, 2013, 1224-1236.



• Increased mast cells (>/= 10x of normal) within the papillary dermis

• With variable extension throughout reticular dermis and into the subcutaneous fat

• Absence of other pathology• Gross skin examination must be correlated

with the number of mast cells in the skin


http://www.skinpathology.org/wp-content/uploads/Urticaria-Pigmentosa-Histopathology-1024x768.jpg


http://www.skinpathology.org/wp-content/uploads/Urticaria-Pigmentosa-Histology-1024x768.jpg

Diffuse cutaneous mastocytosis


TMEP

Ahmet Altiner MD, Julia Tzu MD, Rishi Patel MD, Shane Meehan MD, Miguel Sanchez, et al., Dermatology Online Journal 17 (10): 7



• Most common site of pathologic mast cell infiltrates in mastocytosis

• Most useful Bx site for pathologic diagnosis

• Majority of infiltrates are focal (may be diffuse in some cases)



• Often situated paratrabecularly

• Consist of nodular aggregates of spindle-shaped mast cells, which may be accompanied by lymphocytes and eosinophils



• Hypercellular marrow, as a prognostic factor– With ↓percentage of fat cells = Significant predictor

of poor prognosis– 1/3 of patients had associated hematologic disorders

• Dysmyelopoietic syndromes• Myeloproliferative disorders• Acute leukemia• Malignant lymphoma• Chronic neutropenia• Had significantly reduced 5-year survival rates• In most patients, hematologic disorder is detected after

mastocytosis is diagnosed



• In mast cell leukemia– Diffuse infiltration by atypical, immature mast cells– Mast cells account >/= 10% of the peripheral WBC

• In aggressive mastocytosis with a terminal leukemic phase– Circulating mast cells appear late in the disease

course– Percentage of circulating mast cells is relatively

low



• BM Mast cell hyperplasia in non-mast cell diseases– Uremia– Osteoporosis– Hematologic conditions (lymphomas,

preleukemias, leukemias)

Radiologic pathology


• Radiographically detectable BM infiltration are up to 70% of patients– Proximal long bones = Most often affected– Followed by the pelvis, ribs, and skull

• Skeletal scintigraphy– More sensitive than radiographic surveys in

detecting and locating active lesions– May aid in evaluating the extent of disease and

disease progression

Liver pathology• Mast cell infiltration in liver– More severe in patients with SM-AHNMD or ASM– Correlates with hepatomegaly, splenomegaly, ALP

levels, and GGT levels• Portal fibrosis correlates with mast cell

infiltration and portal inflammation• Nodular regenerative hyperplasia, portal

venopathy, and venoocclusive disease may contribute to portal hypertension


Spleen pathology• Most common finding = Trabecular fibrotic

thickening• Splenic mast cell lesions have been found in– Paratrabecular– Parafollicular– Follicular– Diffuse red pulp


Spleen pathology

http://www.webpathology.com/image.asp?case=385&n=2

LN pathology• Most common location of infiltration =

Paracortical region• Less frequent– Parafollicular and follicular replacement– Medullary cord– Sinus infiltration

• May resemble follicular and T cell lymphomas, monocytoid B cell hyperplasia and lymphoma, Kaposi sarcoma, hairy cell leukemia, and histiocytosis X


LN pathology

John Lazarchick, http://imagebank.hematology.org/Content/740/3803/3803_full.JPG

LN pathology

John Lazarchick, http://imagebank.hematology.org/AssetDetail.aspx?AssetID=3804

Approach for diagnosis

Proposed algorithm

P. Valent, et al., Int Arch Allergy Immunol 2012;157:215–225.

Proposed algorithm


= WHO’s criteria

Classification of MCAS


Classification of MC disorders


Diagnosis(WHO’s criteria for Dx)

Cutaneous mastocytosis• Typical clinical findings of:– Urticaria pigmentosa/maculopapular cutaneous

mastocytosis (UP/MPCM)– Diffuse cutaneous mastocytosis (DCM)– Or solitary mastocytoma

• With typical infiltrates of mast cells in a multifocal or diffuse pattern on skin biopsy


Systemic mastocytosis• 1 major+1 minor, or 3 minor criteria are

required

– Major Criterion • ≥15 foci of mast cells infiltrates in sections of bone

marrow and/or another extracutaneous organ• (Confirmed by tryptase immunohistochemistry or

other special stains)


Systemic mastocytosis• 1 major+1 minor, or 3 minor criteria are

required– Minor Criteria• >25% of mast cells are abnormal:

– Spindle shape or atypical morphology (in Bx of BM/other extracutaneous organs)

– Immature or atypical morphology (in BMA specimens)

• Detection of activating point mutation at codon 816 of KIT in BM, blood, or another extracutaneous organ• Mast cells in BM, blood, or another extracutaneous

organ express CD117 with CD2 and/or CD25• Serum total tryptase persistently >20 ng/mL (without

associated clonal myeloid disorder)Horny H-P, et al. Mastocytosis. In: Swerdlow SH, et al, editors. WHO classification of tumors of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2008.DD Metcalfe., Middleton’s Allergy 8th edition, 2013, 1224-1236.

Varients of mastocytosis• “B” findings – >30% infiltration by mast cells (focal, dense

aggregates) in BMBx and/or serum total tryptase >200 ng/mL

– Signs of dysplasia or myeloproliferation in non–mast cell lineages (but insufficient for Dx of a hematopoietic

neoplasm) + normal/slightly abnormal blood counts– Hepatomegaly without impairment of LFT, and/or

palpable splenomegaly without hypersplenism, and/or lymphadenopathy.


Varients of mastocytosis• “C” findings :– BM dysfunction: >/= 1 of

• ANC <1.0 x109/L• Hb <10 g/dL• Platelets <100 × 109/L)• And no obvious non–mast cell hematopoietic malignancy

– Palpable hepatomegaly + impaired LFT, ascites, and/or portal hypertension

– Skeletal involvement + large osteolytic lesions and/or pathologic fractures

– Palpable splenomegaly + hypersplenism– Malabsorption + Wt loss (from GI mast cell infiltrates)Horny H-P, et al. Mastocytosis. In: Swerdlow SH, et al, editors. WHO classification of tumors of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2008.


Varients of mastocytosis• Indolent Systemic Mastocytosis (ISM) – Meets criteria for systemic mastocytosis– No “C” findings– No evidence of an associated clonal, hematologic

non–mast cell lineage disease (AHNMD) – In this variant the mast cell burden is low, and skin

lesions are usually present • BM mastocytosis – ISM + BM involvement, but no skin lesions

• Smoldering systemic mastocytosis – ISM, with >/=2 “B” findings and no “C” findings Horny H-P, et al. Mastocytosis. In: Swerdlow SH, et al, editors. WHO classification of tumors of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2008.


Varients of mastocytosis• Systemic Mastocytosis with Associated Clonal,

Hematologic Non–Mast Cell Lineage Disease (SM-AHNMD) – Meets criteria for SM– And criteria for AHNMD• (MDS, MPN, AML, lymphoma, or other hematologic

neoplasm that meets criteria for distinct entity in WHO classification)


Varients of mastocytosis• Aggressive Systemic Mastocytosis (ASM) – Meets criteria for SM with one or more “C” findings– No evidence of mast cell leukemia.– Usually without skin lesions– Lymphadenopathic mastocytosis with eosinophilia– Progressive lymphadenopathy

• With peripheral blood eosinophilia• Often with extensive bone involvement, and

hepatosplenomegaly• Usually without skin lesions

– Cases with rearrangement of PDGFRA are excluded Horny H-P, et al. Mastocytosis. In: Swerdlow SH, et al, editors. WHO classification of tumors of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2008.


Varients of mastocytosis• Mast Cell Leukemia (MCL) – Meets criteria for SM– BMBx: Diffuse infiltration by atypical, immature

mast cells– BMA smears: >/= 20% mast cells + mast cells >/=

10% peripheral WBC• Variant:– Leukemic mast cell leukemia as above– <10% of WBC are mast cells– Usually without skin lesions


Varients of mastocytosis• Mast Cell Sarcoma (MCS) – Unifocal mast cell tumor– No evidence of SM– Destructive growth pattern; high-grade cytology

• Extracutaneous Mastocytoma – Unifocal mast cell tumor– No evidence of SM. – No skin lesions; nondestructive growth pattern;

low-grade cytology


Varients of mastocytosis• Proposed additional criteria – Monoclonal mast cell activation syndrome (MMAS)• BM examination to have met 1-2 minor diagnostic criteria

for mastocytosis• But lack the full diagnostic criteria for systemic

mastocytosis

– Mast cell activation syndrome (MCAS)• Episodic allergy-like signs and symptoms (e.g., flushing,

urticaria, diarrhea, wheezing) involving >/=2 organ systems• Without identifiable etiology


Other surrogate markers• Serum histamine and 24-hr urinary histamine

metabolites (N-methylhistamine, and methylimidazoleacetic acid)

– Less often used– Disadvantages• Variability among healthy individuals and patients• Difficulty in assay standardization• False-positive• Easily altered result• Nonspecific


Other surrogate markers• Metabolites of arachidonic acid– Urinary PGD-M or 9α,11β- dihydroxy-15-oxo-

2,2,18,19-tetranorprost-5-ene-1,20-dioxic acid– Plasma thromboxane B2 and its metabolites– Limitations• Source is not exclusively limited to mast cells ->

insufficient specificity for diagnostic purposes

• 24-hr urinary 5-hydroxyindoleacetic acid and urinary metanephrines– For R/O carcinoid tumor/pheochromocytoma


Other W/U• Other tissue Bx• Bone scans or skeletal surveys• Abdominal U/S or CT scan• Upper GI series• Small bowel radiography• Endoscopy (to R/O PU or GERD)

• Dual-energy x-ray absorptiometry (DEXA) scan (to monitor osteoporosis)


Treatments

Treatments

MC-mediated symptoms

GI symptoms

Hematologic abnormality

Osteoporosis


MC-mediated symptoms• Epinephrine– Rx episodes of systemic hypotension– Patients should be taught to administer this

medication themselves– Intensive therapy as for anaphylaxis might be needed

• H1 & H2 receptor antagonist– Mainly reduce flushing– Anti-H1 first, if inadequate response, then use anti-

H2• LTRA– Add on to antihistamines to help flushing


MC-mediated symptoms• Disodium cromoglycate (cromolyn sodium) – Inhibits degranulation of mast cells– Relief of GI complaints– Not reduce plasma or urinary histamine levels

• 8-methoxypsoralen with PUVA (or even natural sunlight in some cases)– Relieve pruritus&whealing in adult after 1-2 mo of Rx– Associated with transient decrease dermal mast cells– Pruritus relapsed in 3-6 months after discontinuation– Used only in patients with extensive cutaneous

disease unresponsive to other therapyDD Metcalfe., Middleton’s Allergy 8th edition, 2013, 1224-1236.

MC-mediated symptoms• Topical steroids with plastic wrap occlusion

for 8 hr/day x 8-12 wks– Used to treat UP or DCM– Number of mast cells decreases as lesions resolve– Lesions recur after Rx discontinuation but may be

last for up to 1 year


GI symptoms• Gastric acid hypersecretion symptoms (peptic

symptoms and PU)– H2 RA and PPI

• Diarrhea– Anticholinergics -> partial relief

• Severe malabsorption– Oral steroids

• Ascites– Portacaval shunt


Osteoporosis• Calcium supplementation• Estrogen replacement (postmenopausal women)• Bisphosphonates• Narcotic analgesics– May potentiate mast cell degranulation

• Radiotherapy– Palliative role in decreasing bone pain in patients with

aggressive forms of disease• IFN-α2b– Relieve musculoskeletal pain– Improve bone mineralization


Hematologic abnormality• Managed as dictated by associated specific

hematologic abnormality• IFN-α2b and 2-chloro-2-deoxyadenosine

(cladribine, 2-CdA)– Potential first-line therapy for patients with

aggressive forms • BMT– Good for associated hematologic disorders– Poor effect on mast cell hyperplasia


Hematologic abnormality• Imatinib mesylate – Approved for Rx of aggressive forms of mastocytosis in

patient without D816V mutation– May be useful in unusual presentations of mastocytosis,

which are associated with novel mutations in c-kit– Patients with increased mast cells + peripheral

eosinophilia + FIP1L1-PDGFRA fusion oncogene also respond

– Mutational analysis of lesions are essential before Rx• Other tyrosine kinase inhibitors eg. midostaurin

(PKC412)– Able to inhibit KIT with the D816V mutation in vitro– Now in clinical study


Hematologic abnormality• Chemotherapy– Unable to produce remission– Unable to prolong survival in MCL– Has no place in the treatment of indolent

mastocytosis– But may be considered for advanced disease


Hematologic abnormality• Splenectomy– May improve survival times in mastocytotic

patients with with poor prognosis• Radiotherapy– Used in the management of refractory bone pain

in patients with aggressive disease• BMT– May be considered for extremely ill patients, – May yield a better prognosis if mast cell

suppression is attempted before BM


Prognosis

Prognosis• Patients with CM only = Best prognosis, followed by

those with ISM• >50% of children with isolated UP resolve by

adulthood• UP in adulthood may evolve into systemic disease• Occasionally, ISM converts to SM-AHNMD• Course depends largely on prognosis of specific

hematologic disorder and response to Rx• Mean survival of MCL pt: <12 months• Survival time ASM pt: 2-4 years (with aggressive

symptomatic management)DD Metcalfe., Middleton’s Allergy 8th edition, 2013, 1224-1236.

Take Home Message• Mast cell disorders vary greatly in clinical

presentations • Primary pathomechanism is the activating

mutation in KIT • Signs and symptoms are caused by:– Mast cell mediators– Increased mast cell burden– Associated hematologic disorder

• Treatments– Symptomatic Rx for mastocytosis– Specific Rx for associated hematologic disorders

Thank you

Mast cell disorders

Health & Medicine

Transcript of Mast cell disorders