Le manifestazioni allergologiche
particolari:
Orticaria / Angioedema
Diego Peroni
U.O.S. Allergologia
Pediatrica
Azienda Ospedaliera
Universitaria
Integrata Verona
[email protected]
La
definizione
Orticaria cronica- Angioedema
Orticaria associata o meno a angioedema che dura per più di 6-8
settimane con sintomatologia quotidiana.
Orticaria
Angioedema
Pomfo: lesione cutanea
evanescente, con centro
edematoso, pallido e margini
iperemici. Interessa gli strati
superficiali del derma.
Edema per stravaso
capillare dai vasi del derma
profondo o del sottocute
Istamina
LT
C5a
Orticaria cronica- Angioedema
Orticaria associata o meno a angioedema che dura per più di 6-8
settimane con sintomatologia quotidiana.
Orticaria
Pomfo: lesione cutanea
evanescente, con centro
edematoso, pallido e margini
iperemici. Interessa gli strati
superficiali del derma.
80% dei casi di
orticaria cronica
presenta lesioni
da orticaria
associate a
angioedema.
Istamina
LT
C5a
Angioedema
Edema per stravaso
capillare dai vasi del derma
profondo o del sottocute
Le manifestazioni allergologiche
particolari:
Orticaria / Angioedema
La
definizione
L’orticaria
[email protected]
acuta
• Almeno un episodio di orticaria acuta
nella vita con prevalenza del 15-20%
nella popolazione generale
• Una causa evidenziata in meno del 50%
dei casi:
• 40% postinfettiva
• 10% FANS
• 1% alimenti
• Un alimento è sospettato nel 63% dei
casi, ma viene dimostrato solo nell’1%
November 2012
Terapia orticaria
EAACI/GA2LEN/EDF/WAO guideline: management of urticaria.
T. Zuberbier, R. Asero et al. Allergy 2009: 64: 1417–1426
Le manifestazioni allergologiche
particolari:
Orticaria / Angioedema
La
definizione
L’orticaria
acuta
L’orticaria
La
cronica
diagnosi
[email protected]
Orticaria cronica
Orticaria associata a angioedema che dura da più di 6-8
settimane ….
Orticaria
Angioedema
Pomfo: lesione cutanea
evanescente, con centro
edematoso, pallido e margini
iperemici. Interessa gli strati
superficiali del derma.
Edema per stravaso
capillare dai vasi del derma
profondo o del sottocute
Istamina
LT
C5a
Orticaria Cronica:
Diagnosi Eziologica
1° valutazione:
•
Anamnesi
•
Esame obiettivo (se presenti valutare le lesioni cutanee)
•
Somministrare questionario e consegnare diario giornaliero
•
Test per dermografismo
•
Emocromo, VES, PCR.
•
Prescrivere antistaminici
•
Informare genitori del carattere benigno della malattia
•
Informare i genitori che nella maggior parte dei casi la causa rimane
ignota
Laboratory tests and identified diagnoses in patients with physical and chronic
urticaria and angioedema: A systematic review
Martina M. et al. J Am Acad Dermatol 2003
DIARIO - ORTICARIA
Giorno
Terapia in corso
Assunzione di cibi
Assunzione di farmaci
Prurito
Dolore
Altri sintomi
(febbre, g.e, artralgia)
Estensione
Durata
Luogo e situazione
(sport, doccia ..)
Data e ora
Nome del paziente ……………………...
Settimana dal…………. al ……………..
BSACI guidelines for the management of chronic urticaria and
angio-oedema.
R. J. Powell. CEA, 2007; 37, 631–650.
Orticaria cronica
Diagnosi eziologica
2° valutazione:
•
Valutazione andamento clinico (visione diario)
•
Esame obiettivo
•
Esecuzione esami diagnostici di 2° livello in base ai dati raccolti.
•
Eventuale sospensione di farmaci considerati triggers.
•
Prescrivere antistaminici (eventuale progressione negli step
terapeutici).
Laboratory tests and identified diagnoses in patients with physical and chronic
urticaria and angioedema: A systematic review
Martina M. J Am Acad Dermatol 2003
Esami diagnostici di 2° livello – BSACI guidelines. CEA 2007
Eziologia
Che esami
Idiopatica (40-50%)
Indagini negative
Autoimmune
ANA, ab antitiroide, ASST
Da stimolo fisico
Challenge con lo stimolo
appropriato
Da farmaci
Sospensione (beneficio
settimane-mesi)
Infezioni
Sierologie in base alla
storia clinica
Allergia
SPTs, ImmunoCAP
Deficit C1 esterasi-inibitore
C4, C1 inibitore (Ag., Funz.)
Vasculite
ANCA, ANA, C3, Ig,
sierologie epatite,
funzionalita’ epatica e
renale, biopsia cutanea
Pat. linfoproliferativa
Paraproteine
Additivi alimentari
Esclusione e reintroduzione
..ma non dimentichiamo
altre cause di Orticaria….
• Pseudoallergeni (conservanti, coloranti,
additivi).
• Infezione da Helicobacter Pylori.
• Infezioni parassitarie.
• Infezioni delle vie urinarie.
L’ OC rappresenta
spesso il sintomo
di esordio.
• Celiachia.
• Manifestazione iniziale di malattie
reumatologiche sistemiche (JRA, SLE).
BSACI guidelines for the management of chronic urticaria and angio-oedema
R. J. Powell. CEA 2007; 37, 631–650.
Patogenesi di asma e CU esacerbati da FANS
FANS e COX 1
inibitori
Asma
Urticaria
angioedema
Cutaneous Reactions to Aspirin and Nonsteroidal Antiinflammatory Drugs
Mario Sánchez-Borges, Clinical Reviews in Allergy & Immunology Volume 24, 2003
Le manifestazioni allergologiche
particolari:
Orticaria / Angioedema
La
definizione
L’orticaria
acuta
L’orticaria
cronica
La
diagnosi
Le
nuove evidenze
[email protected]
Activation of blood coagulation in chronic urticaria:
pathophysiological and clinical implications
Cugno Intern Emerg Med; 2010, 5:97
Activation of blood coagulation in chronic urticaria:
pathophysiological and clinical implications
Cugno Intern Emerg Med; 2010, 5:97
Mechanisms of eosinophil and mast cell activation in chronic urticaria (CU).
Activation of blood coagulation in chronic urticaria:
pathophysiological and clinical implications
Cugno Intern Emerg Med; 2010, 5:97
Mechanisms of eosinophil and mast cell activation in chronic urticaria (CU).
Mast cells release
histamine and other
inflammatory
mediators after stimulation
by autoantibodies directed
against the high-affinity
IgE receptor (FceRI) and
IgE, complement
anaphylatoxin C5a,
eosinophil-derived major
basic protein (MBP) and
possibly other molecules
Activation of blood coagulation in chronic urticaria:
pathophysiological and clinical implications
Cugno Intern Emerg Med; 2010, 5:97
Mechanisms of eosinophil and mast cell activation in chronic urticaria (CU).
Eosinophils are activated by
autoantibodies directed
against the low-affinity IgE
receptor (FceRII) and
potentially by other factors,
release MBP and express
tissue factor which in turn
activates the coagulation
cascade (factors VII, X, V
and prothrombin)
leading to thrombin
generation.
Activation of blood coagulation in chronic urticaria:
pathophysiological
and
clinical implications
Thrombin
generation
is
Cugno Intern Emerg Med; 2010, 5:97
demonstrated
in CU patients by
Mechanisms
eosinophil and
mast levels
cell activation
in chronic urticaria (CU).
theofincreased
plasma
of
the fragment F1+2 released from
prothrombin after its activation.
Finally, fibrin degradation is
documented by elevated plasma
levels of the fibrin fragment
Eosinophils
are activated
D-dimer
in by
CU patients with
autoantibodies directed
active disease
against the low-affinity IgE
receptor (FceRII) and
potentially
by other factors, release MBP
and express tissue factor
which in turn activates the
coagulation cascade (factors
VII, X, V and prothrombin)
leading to thrombin
generation.
Effetto della trombina
Vasodilatazione
Produzione di
mediatori
infiammatori
Trombina
Attivazione diretta
degranulazione
mastocitaria
Attivazione
diretta di C5a
bypassando C3
Pathogenesis of chronic urticaria
A. P. Kaplan Clin Exp All, 2009, 39, 777
ASST - Autologous Serum Skin Test •
Circa il 50% dei pazienti con
Orticaria cronica idiopatica presenta
ASST + ma:
•
In circa il 50% non c’ è
corrispondenza tra test in vivo e in
vitro;
•
Decomplementazione e deplezione di
IgG dal siero non riducono la capacità
di indurre reazione in vivo;
•
Il 50% delle orticarie idiopatiche
rimane comunque inspiegato.
Pathogenesis of chronic urticaria
A. P. Kaplan Clin Exp All, 2009, 39, 777
ASST - Autologous Serum Skin Test •
Circa il 50% dei pazienti con
Orticaria cronica idiopatica presente
•
•
Altri fattori
ASST + ma:
istaminoliberatori
In circa il 50% non c’ è
potrebbero essere
corrispondenza tra test in vivo e in
implicati nella
vitro;
patogenesi della
Decomplementazione e deplezione di
malattia.
IgG dal siero non riducono la capacità
di indurre reazione in vivo;
•
Il 50% delle orticarie idiopatiche
rimane comunque inspiegato.
Orticaria cronica, ASST, APST e HRA
• Orticaria cronica
•APST positivo nel 75-85%
dei casi
•ASST positivo nel 50-60%
dei casi
• HRA positivo nel 25-30%
dei casi
Le manifestazioni allergologiche
particolari:
Orticaria / Angioedema
La
definizione
L’orticaria
acuta
L’orticaria
cronica
La
diagnosi
Le
nuove evidenze
La
terapia
Terapia orticaria cronica
EAACI/GA2LEN/EDF/WAO guideline: management of urticaria. T.
Zuberbier, R. Asero et al. Allergy 2009: 64: 1417–1426
EAACI taskforce position paper: evidence for
autoimmune urticaria and proposal for defining
diagnostic criteria. Konstantinou GN Allergy 2013
Circumstantial evidence for CU being an autoimmune
disease comes from
an observed association with other autoimmune
diseases,

a strong association between serum functionality and
HLA-DR4 haplotype and
the good response of CU patients to immunotherapies
Chronic urticaria and autoimmunity:
Associations found in a large population study
Confino-Cohen, JACI 2012;129:1307
In patients with CU OR for
 12,778 patients
with CU during 17
years in a large
health
maintenance
organization.
 A control group
of 10,714 patients
who had no CU.
30 –
28.8
25 –
20 –
15 –
17.3
13.2
10 –
05 –
0
Hypothyroidism
6%
Hyperthyroidism
Rheumatoid
arthritis
Chronic urticaria and autoimmunity:
Associations found in a large population study
Confino-Cohen, JACI 2012;129:1307
In patients with CU OR for
 12,778 patients
with CU during 17
years in a large
health
maintenance
organization.
 A control group
of 10,714 patients
who had no CU.
30 –
26.9
25 –
20 –
15 –
15.2
10 –
05 –
0
7.7
Type I
diabetes
mellitus
Sjögren
syndrome
14.6
6%
Celiac
disease
Systemic
LE
EAACI taskforce position paper: evidence for autoimmune
urticaria and proposal for defining diagnostic criteria
Konstantinou G. N, Allergy 2013;68:27-36
 Chronic urticaria (CU).
 Approximately 25% of CU patients have a
positive basophil histamine release assay and
show autoreactivity (a positive autologous serum skin test),
whereas 50% are negative regarding both.
 Basophil activation by CU sera is predominantly restricted to
IgG1 and IgG3 subclasses.
 Circumstantial evidence for CU being an autoimmune disease
comes from an observed association with other autoimmune
diseases, a strong association between serum functionality and
HLA-DR4 haplotype and the good response of CU patients to
immunotherapies.
EAACI taskforce position paper: evidence for autoimmune
urticaria and proposal for defining diagnostic criteria
Konstantinou G. N, Allergy 2013;68:27-36
How not to miss autoinflammatory diseases
masquerading as urticaria
Krause K, Allergy 2012;67:1465-1474
Le manifestazioni allergologiche
particolari:
Orticaria / Angioedema
La
definizione
L’orticaria
acuta
L’orticaria
cronica
La
diagnosi
Le
nuove evidenze
Il
caso clinico
APR:
P.P 5 aa e 6 mesi
- Otiti ricorrenti;
Persistenza del quadro:
10/02/2012: PS VR.
MT dx iperemica e bombata:
20/12/2011
Deltacortene 2.5 mg/die
Otite  Amoxicillina 
comparsa di rash orticarioide 
Cetirizina 0.25 mg/kg + Bentelan
4 mg/die
Aerius + Fenistil
Peggioramento orticaria  PS a
BZ: Deltacortene 15 mg/die
Singulair
Orelox (OM persistente).
Peggioramento  PS BZ:
Augmentin Zinnat;
Visita allergologica BZ:
Zirtec  Aerius + Fenistil la sera
Controllo esami ematici: TAS
329IU/ml, resto normale.
Ancora deltacortene 2.5 mg
Profilassi ambientale.
- Autismo.
DH allergologia
20/02/2012
Totale:
• 2 mesi di sintomi
continui.
• 2 mesi di CSO;
Allergia agli acari.
Scalo deltacortene a 5 mg 
2.5 mg/die + Augmentin (MT
iperemiche + TAS elevato).
- Bronchiti asmatiformi
ricorrenti;
2 visite dermatologiche BZ 
dieta bianca senza nessun
beneficio
• 8 visite
specialistiche;
• 4 Abt diverse.
DH allergologia 20/02/2012
APST +
• Immunoglobuline: nella norma;
• Sierologie HBV, HCV, EBV,
Parvovirus B19: nella norma;
• Ricerca parassiti fecali: neg;
• Ab antigliadina anti TG: neg;
• Ricerca HP Pylori nelle feci: neg.
• D-dimero: 1.2 mg/l .
[email protected]
Le manifestazioni allergologiche
particolari:
Orticaria / Angioedema
La
definizione
L’angioedema
I
meccanismi
[email protected]
BSACI guidelines for the management of chronic urticaria and
angio-oedema.
R. J. Powell. CEA, 2007; 37, 631–650.
Hereditary angio-oedema. Longhurst H. Lancet 2012; 379:474
Angio-oedema of hand
Capsule endoscopy
during abdominal attack
Erythema marginatum on anterior
chest wall
C1-inhibitor deficiency and angioedema: molecular mechanisms and
clinical progress. Cugno M, Trends in Molecular Medicine, 2009; 15: 69
Simplified representation of the kinin system. Bradykinin is generated
through the cleavage of high molecular weight kininogen (HK) by plasma
kallikrein during contact-system activation
C1-inhibitor deficiency and angioedema: molecular mechanisms and
clinical progress. Cugno M, Trends in Molecular Medicine, 2009; 15: 69
The most important inhibitor
of the contact system is C1INH, which inactivates
kallikrein and FXIIa.
Bradykinin is degraded by
peptidases, such as human
kininase I, also called
carboxypeptidase N, and
kininase II, also called
angiotensinconverting enzyme
(ACE).
C1-inhibitor deficiency and angioedema: molecular mechanisms and
clinical progress. Cugno M, Trends in Molecular Medicine, 2009; 15: 69
Representation of the pathogenesis of
angioedema due to C1-INH deficiency
In HAE, the deficiency of C1-INH is due to a mutation in the C1-INH gene, which
impairs C1-INH synthesis or function. In AAE, C1-INH deficiency is due to the
cleavage of C1-INH by autoantibodies or to its consumption by neoplastic, mainly
lymphoproliferative, tissue.
C1-inhibitor deficiency and angioedema: molecular mechanisms and
clinical progress. Cugno M, Trends in Molecular Medicine, 2009; 15: 69
Representation of the pathogenesis of
angioedema due to C1-INH deficiency
Reduced C1-INH plasma levels
result in hyperactivation of the
classical complement pathway
with increased consumption of
C1-INH and further
reduction of its plasma level.
Hereditary angio-oedema. Longhurst H. Lancet 2012; 379:474
Criteria for diagnosis of hereditary angio-oedema
Type III hereditary angioedema: defined, but not
understood. Kaplan, Ann Allergy Asthma Immunol
2012;109:153
1) Type III hereditary angioedema (HAE) is a familial form
of angioedema in which complement C4 and C1 inhibitor (C1
INH) protein and function are normal.
2) Most patients are women, although an occasional male is
identified, and a close association with estrogen as a
precipitant of attacks of angioedema is seen
(contraception, postmenopausal symptom control).
3) Like types I and II HAE, angioedema is recurrent,
it is not associated with urticaria, and it is unresponsive
to antihistamines or corticosteroids.
Type III hereditary angioedema: defined, but not
understood. Kaplan, Ann Allergy Asthma Immunol
2012;109:153
1) Type III hereditary angioedema (HAE) is a familial form
of angioedema in which complement C4 and C1 inhibitor (C1
INH) protein and function are normal.
2) Most patients are women, although an occasional male is
We
do association
not havewith
a test
identified, and
a close
estrogen as a
precipitant
of attacks
of used
angioedema
is seen the
that
can be
to make
(contraception, postmenopausal
symptom control).
diagnosis.
3) Like types I and II HAE, angioedema is recurrent,
it is not associated with urticaria, and it is unresponsive
to antihistamines or corticosteroids.
Type III hereditary angioedema: defined, but not
understood. Kaplan, Ann Allergy Asthma Immunol
2012;109:153
1) Type III hereditary angioedema (HAE) is a familial form
of angioedema in which complement C4 and C1 inhibitor (C1
INH) protein and function are normal.
2) Most patients
are women, although
an occasional male is
Overproduction
of bradykinin
identified, and a close association with estrogen as a
isofassumed,
precipitant of attacks
angioedema is seen
(contraception, postmenopausal
symptom control).
but not proven.
3) Like types I and II HAE, angioedema is recurrent,
it is not associated with urticaria, and it is unresponsive
to antihistamines or corticosteroids.
Type III hereditary angioedema: defined, but not
understood. Kaplan, Ann Allergy Asthma Immunol
2012;109:153
a) A mutation in factor XII, exon 9 consisting of either Thr 309 lys or
Thr 309 arg has been associated with type III HAE patients, and,
although specific for this disorder, it is found only in 25-30% of
patients whose swelling is unexplained but is clearly familial.
b) The mutation was reported to cause excessive conversion
of prekallikrein to kallikrein and was described
as a “gain of function” mutation.
Clinical, biochemical, and genetic characterization
of type III hereditary angioedema in 13
Northwest Spanish families.
Marcos, Ann Allergy Asthma Immunol 2012;109:195
1) 22 of these patients had the
estrogen-dependent phenotype.
 Population with
type III hereditary
angioedema.
 29 patients
(26 female, 3
male).
2) All had functional C1 inhibitor
activity within the normal range
in periods without high estrogen
levels, but during attacks
(in female patients) and
pregnancy, activity decreased to
below 50%.
3) The C4 and antigenic C1 inhibitor
levels were always normal.
Clinical, biochemical, and genetic characterization
of type III hereditary angioedema in 13
Northwest Spanish families.
Marcos, Ann Allergy Asthma Immunol 2012;109:195
1) 22 of these patients had the
estrogen-dependent phenotype.
 All
Population
studied patients
with
had
typethe
III hereditary
c.1032C>A,
Thr309Lys
angioedema.
mutation
factor XII gene.
 in29the
patients
(26 female, 3
male).
2) All had functional C1 inhibitor
activity within the normal range
in periods without high estrogen
levels, but during attacks
(in female patients) and
pregnancy, activity decreased to
below 50%.
3) The C4 and antigenic C1 inhibitor
levels were always normal.
Le manifestazioni allergologiche
particolari:
Orticaria / Angioedema
La
definizione
L’angioedema
I
meccanismi
La
terapia
[email protected]
C1-inhibitor deficiency and angioedema: molecular mechanisms and
clinical progress. Cugno M, Trends in Molecular Medicine, 2009; 15: 69
Current and potentially new treatments for angioedema due to
hereditary or acquired C1-INH deficiency
Terapia angioedema
Terapia attacco acuto
Terapia cronica profilattica
• Idratazione,
• Antidolorifici,
• Berinert (pdC1- INH
pastorizzato, liofilizzato
concentrato);
• Ecallantide (inibitore
della Kallikreina);
•
FPP (fresh frozen
plasma)
SDP (solvent detergenttreated plasma)
•
Androgeni blandi:
•
Danazolo
•
Stanazolo
•
Metiltestosterone
Antifibrinolitici
• Icatibant (antagonista
competitivo di BK2R);
• Rhucin (C1-INH
ricombinante umano)
Effetti collaterali
pdcC1 INH umano, indicato per gli attachi acuti di HAE con interessamento
addominale, facciale e laringeo negli adulti e negli adolescenti.
Le manifestazioni allergologiche
particolari:
Orticaria / Angioedema
La
definizione
L’angioedema
I
meccanismi
La
Il
terapia
caso clinico
[email protected]
Angioedema – Francesca 4 anni
Accesso al PS per comparsa di edema importante a livello dell’arto
sup di sin
Pregressa faringite trattata con Amox-Clavul
Familiarita’ per angioedema ereditario (madre)
E.O.
Edema a livello della mano e avambraccio di sin, cute calda, pallida.
Non dolore
Rx avambraccio e mano: non lesioni ossee a focolaio
Ecodoppler: pervio l’asse venoso succlavio-ascellare-omerale. Diffuso
infarcimento dei tessuti molli
Complemento C4 0.04 g/L (vn 0.10-0.40), C1 inibitore 0.06 g/L (vn
0.15-0.35)
Conclusioni: Angioedema ereditario
Si consiglia visita specialistica presso la Clinica Medica Milano
In caso di emergenza Berinert f. 500 UI
C1-inhibitor deficiency and angioedema: molecular
mechanisms and clinical progress.
Cugno M, Trends in Molecular Medicine, 2009; 15: 69
Le manifestazioni allergologiche particolari:
Le sindromi da attivazione mastocitaria
Diego Peroni
U.O.S. Allergologia
Pediatrica
Azienda Ospedaliera
Universitaria
Integrata Verona
[email protected]
Characteristics of human mast cell subsets
Selected mast cell activators of clinical relevance
Mast cell
activation
syndrome:
Proposed
diagnostic
criteria.
Akin C, JACI;
2010; 126:1099
Mast cell activation syndrome: Proposed diagnostic
criteria.
Akin C, JACI; 2010; 126:1099
Activation of mast cells results in
(1)
degranulation with resulting release of
preformed mediators stored in granules, including
histamine, heparin, proteases, and cytokines,
such as TNF-a;
(2) De novo synthesis of arachidonic acid
metabolites (most notably prostaglandin D2 and
leukotriene C4) from membrane lipids;
(3) synthesis and secretion of cytokines and
chemokines
Le manifestazioni allergologiche particolari:
Le sindromi da attivazione mastocitaria
The
mast cell
Mast
cell activation
syndrome
MCAS,
SM or MMCA
[email protected]
Mast cell activation syndrome: Proposed diagnostic
criteria.
Akin C, JACI; 2010; 126:1099
Disease states associated with evidence of mast cell activation
Mast cell activation syndrome: Proposed diagnostic
criteria.
Akin C, JACI; 2010; 126:1099
Classification of diseases associated with mast cell activation
Mast cell activation syndrome: Proposed diagnostic
criteria.
Akin C, JACI; 2010; 126:1099
Signs and symptoms suggested to potentially occur in MCAS or
mast cell activation disorder
These symptoms are
attributed to
mast cell degranulation
in mastocytosis, and
those with mast cell
activation disorder/
MCAS are said to have
many of the same
symptoms.
Mast cell activation syndrome: Proposed diagnostic
criteria.
Akin C, JACI; 2010; 126:1099
MCAS as a distinct clinical entity has not
been generally accepted, nor do there exist
definitive criteria for diagnosis.
Based on current understanding of this
disease ‘‘syndrome’’ and on what we do know
about mast cell activation and resulting
pathology, we will explore and propose
criteria for its diagnosis.
WHO classification of tumours of haematopoietic and
lymphoid tissues. Horny HP, Lyon:IARC Press; 2008. p. 54-63.
The diagnostic standard for systemic mastocytosis
has been the demonstration of:
Major criterion
•multifocal mast cell clusters of atypical morphology
in a bone marrow biopsy specimen.
The minor diagnostic criteria
•a tryptase level of greater than 20 ng/mL,
•atypical (spindle-shaped and hypogranulated) mast
cell morphology,
•aberrant expression of CD2 and CD25 on mast cells,
•detection of a codon 816 mutation in c-Kit.
Mast cell activation syndrome: Proposed diagnostic
criteria.
Akin C, JACI; 2010; 126:1099
Proposed criteria for the diagnosis of MCAS
1.Episodic symptoms consistent with mast cell
mediator release affecting >2 organ systems
evidenced as follows:
a. Skin: urticaria, angioedema, flushing
b. Gastrointestinal: nausea, vomiting, diarrhea,
abdominal cramping
c. Cardiovascular: hypotensive syncope or near
syncope, tachycardia
d. Respiratory: wheezing
e. Naso-ocular: conjunctival injection, pruritus,
nasal stuffiness
Plus
Mast cell activation syndrome: Proposed diagnostic
criteria.
Akin C, JACI; 2010; 126:1099
Proposed criteria for the diagnosis of MCAS
2. A decrease in the frequency or severity or resolution of symptoms with
antimediator therapy: H1- and H2-histamine receptor agonists,
antileukotriene medications (cysteinyl leukotriene receptor blockers or 5lipoxygenase inhibitor), or mast cell stabilizers (cromolyn sodium)
3. Evidence of an increase in a validated urinary or serum marker of mast
cell activation: documentation of an increase of the marker to greater
than the patient’s baseline value during a symptomatic period on >2
occasions or, if baseline tryptase levels are persistently >15 ng,
documentation of an increase of the tryptase level above baseline value
on 1 occasion. Total serum tryptase level is recommended as the marker
of choice; less specific (also from basophils) are 24-hour urine
histamine metabolites or PGD2 or its metabolite 11-b-prostaglandin F2.
4. Rule out primary and secondary causes of mast cell activation and welldefined clinical idiopathic entities
Mast cell activation syndrome: Proposed diagnostic
criteria.
Akin C, JACI; 2010; 126:1099
Proposed criteria for the diagnosis of MCAS
2. A decrease in the frequency or severity or resolution of symptoms with
antimediator therapy:
H1-for
andnow
H2-histamine
agonists,
MCAS
remains receptor
an
antileukotriene medications
leukotriene
blockers or 5idiopathic(cysteinyl
disorder;
however,receptor
in
lipoxygenase inhibitor), or mast cell stabilizers (cromolyn sodium)
some cases it could be an early
reflection
of a monoclonal
3. Evidence of an increase
in a validated
urinary or serum marker of mast
population of
cells,ofinthe marker to greater
cell activation: documentation
of mast
an increase
than the patient’s
baseline
during
symptomatic
period on >2
which
casevalue
with
timea it
could
occasions or, if
baseline
persistently
>15 ng,
meet
thetryptase
criterialevels
for are
MMAS
as
documentation of an increase of the tryptase level above baseline value
1 or 2 minor criteria for
on 1 occasion. Total serum tryptase level is recommended as the marker
mastocytosis
fulfilled
of choice; less specific
(also fromare
basophils)
are 24-hour urine
histamine metabolites or PGD2 or its metabolite 11-b-prostaglandin F2.
4. Rule out primary and secondary causes of mast cell activation and welldefined clinical idiopathic entities