Urticaria and Mastocytosis Dan Flashcards
T/F
Angioedema is itchy
False
painful not itchy
What is the definition of chronic urticaria?
more than 6 weeks duration
continuous urticaria occurring at least twice a week off treatment
What are the causes and mimics of acute urticaria?
Causes; Primary/Idiopathic 50% Secondary causes; Infection Drug eruption Contact urticaria Inhaled allergen urticaria Non immune drug/food urticaria Scombroid fish poisoning Serum sickness-like rcn
Mimics; AHOC SCLE EM, SJS onset of DH, Linear IgA, EBA PEP/PUPPP PMLE Sweets Neutrophilic eccrine hidradenitis Toxic erythemas
What are the causes and mimics of chronic urticaria?
Causes;
Primary = Chronic Spontaneous Urticaria
Secondary causes;
Chronic infection
AI disease
Drug reaction
Chronic inducible urticaria - MASTS
Cutaneous mastocytosis
Mimics;
Autoinflammatory syndromes
Schnitzler’s syndrome
Urticarial vasculitis
Urticarial dermatitis
Neutrophilic urticarial dermatitis
Pre-bullous BP
MF
Eosinophilic dermatosis of haematological malignancy/ exaggerated insect-bite reaction
Annular erythemas
Wells syndrome
What are the major types of Inducible (physical) urticarias?
MASTS (as in mast cells) Mechanical Aquagenic urticaria Solar Urticaria Thermal Stress
What are the types of mechanical urticarias?
Dermatographism • Immediate Simple dermatographism Symptomatic dermatographism • Delayed dermatographism Delayed pressure urticaria Vibratory angioedema • Inherited • Acquired
What are the types of thermal urticarias?
Heat contact urticaria
Cold contact urticaria
• Primary
• Secondary (cryoglobulins, cryofibringen)
• Reflex
(Familial - autoinflammatory syndrome not an inducable urticaria)
What are the types of stress-induced urticarias?
Cholinergic urticaria Adrenergic urticaria Exercise-induced urticaria • Exercise-induced anaphylaxis • Food- and exercise-induced anaphylaxis
What are the histo findings of urticaria?
An invisible dermatosis Epidermis normal Dermal oedema Sparse perivascular and interstitial inflammatory infiltrate of eosinophils, lymphocytes, neutrophils, and/or mast cells Neuts +/- eos in vessels
What questions are important for screening for autoinflammatory disorders?
Any; Fevers malaise Joint pains NB consider delayed pressure urticaria or urticarial vasculitis also
T/F
Angioedema occurs in 50% of cases of urticaria
True
esp face, lips, eyelids etc
May also get mucosal swellings of oral cavity but usually not larynx
T/F
cow’s milk allergy is commonest cause of urticaria in infants under 6 months old
True
What are the causes of acute and chronic urticarias in young children?
Acute
Common reaction to URTI or other infection inc glandular fever (EBV)
Other acute causes – AHOC, scarlet fever, serum-sickness-like rcn, drug rcn
Chronic
If chronic/recurrent think of Urticaria pigmentosa or food allergy - esp cow’s milk allergy
What are the major causes of acute urticarias and what proprtion of cases do they account for?
Does not include insect bites and stings responsible for many cases
Idiopathic 50%
Infection 40% esp URTI
Drugs 9% (several mechanisms)
Foods 1% (allergy or histamine releasers)
Others;
Inhaled allergens
- Grass pollens, mould spores, animal danders, house dust mites
Contact urticaria
- Food most common
- Latex
Which foods should be avoided if latex allergic due to cross-reactions?
Kiwi Chicks Like bananas and Avos Kiwi Chestnuts Lychees Bananas Avocado
Which foods cause most type 1 acute (contact) urticaria?
Fish, nuts, milk, crustaceans, spices, apples, peaches
Which foods cause direct histamine induced urticaria (non-allergic)?
histamine containing – cheese, fish, meat, tomatoes, pineapple, avocados
Esp fish with scombroid poisoning
histamine-releasing – strawberries, alcohol
What is Scombroid fish poisoning?
underprocessed tuna, mackeral where bacteria has generated histamine by histidine decarboxylase leading to acute uticaria, vomiting, diarrhoea
Which drugs cause urticaria?
Almost any drug can cause an urticarial eruption as a side effect (not type 1 allergy)
e.g.
Antibiotics, vaccines, radiocontrast media, antidepressants, antihypertensives, antihistamines (H1 and H2!), antifungals, antiplatelets, NSAIDS, OCP, HRT
Bleomycin, asparginase, cyclophosphamide, chlorambucil, daunorubicin
Imatinib, Nilotinib, Dasatinib
some cause true type 1 allergy and anaphylaxis
some cause anaphylactoid reactions via direct histamine release e.g.
Opiates (morphine, codeine)
Antibiotics (vancomycin ‘red man syndrome’)
Iodine based radiocontrast dyes
Aspirin and NSAIDs
Also alcohol
T/F
Antihistamines can cause urticarial drug eruptions
True
T/F
NSAIDs can cause urticarial drug eruptions either by an allergic side effect mechanism or direct histamine release effects
True
T/F
NSAIDs can trigger mast cell degranulation in mastocytosis but can also be used to treat mastocytosis
True
can reduce flushing due to anti-prostaglandin effects
Introduce catiously along with antihistamine esp if Hx of intolerance
What are the major causes of chronic urticarias and what proprtion of cases do they account for?
60% Primary chronic urticaria - Autoimmune - Pseudoallergic - food, drug - Infection-related - Idiopathic = chronic spontaneous urticaria 35% Inducible urticaria 5% Urticarial vasculitis
T/F, Regarding chronic spontaneous urticaria;
30%-50% due to activating IgG autoantibodies to alpha subunit of FcεRI (high affinity mast cell surface receptor), or less frequently against receptor-bound IgE
True
Cause of the remainder unknown but some may be unidentified Autoimmune, Pseudoallergic or Infection cases
T/F
Regarding Primary chronic urticaria;
Up to 60% are due to intolerance to dietary or drug pseudoallergens
False
Up to 30%
e.g. colouring agents, preservatives, antioxidants, flavour enhancers, aspirin
What factors can aggravate chronic urticarias?
Drugs esp Aspirin and other NSAIDs Histamine containing/releasing foods and drugs Dietary psudoallergens Infection e.g. URTIs Pressure Overheating Premenstrual periods Alcohol Stress Exercise Implants and nickel allergy
What must be excluded to make the diagnosis of chronic spontaneous urticaria?
Drug cause
Pseudoallergen cause - food, drugs
- colouring agents, preservatives, antioxidants, flavour enhancers, aspirin
Autoimmune disease
o Thyroid autoantibodies
o Coeliac disease (in children and adolescents)
o Pernicious anaemia
o Vitiligo
o SLE
Occult infection
o Dental abscess
o Helicbacter pylori gastritis
o Gastrointestinal candidiasis
o strongyloides
inducible urticaria (MASTS) - history and testing
Alternative diagnoses/mimics; esp;
Autoinflammatory syndromes
Schnitzler’s syndrome
Urticarial vasculitis
Urticarial dermatitis
Neutrophilic urticarial dermatitis
Pre-bullous BPT/F
chronic spontaneous urticaria is a diagnosis of exclusion
True
T/F
An extensive malignancy screen is prudent in chronic urticaria
False
No strong association
What is Episodic ordinary urticaria?
Urticaria occurring less frequently than twice per week over a long period; more likely to have an identifiable environmental trigger than chronic
What are the most common inducible urticarias?
o 9% dermographism
o 4% cholinergic urticaria
account for 13 of the 19% of all urticarias which are inducible
T/F
5% of normal people get dermographism
True
usually asymptomatic
Symptomatic dermographism is the most common physical urticaria
T/F
Symptomatic dermographism is worse at night and occurs in bouts
True
T/F
Symptomatic dermographism of the vulva occuring during sex can present as vulvodynia/vestibulodynia or dyspareunia
True
T/F
Symptomatic dermographism tends to improve over months
False
improves over years
What is Delayed dermatographism?
dermatographism which appears at least 30 mins after stroking stimulus
What is red dermatographism?
Response to repeated rubbing not stroking the skin
What is white dermatographism?
Feature of atopic dermatitis
What is cholinergic dermatographism?
Seen in some patients with cholinergic urticaria, whose dermographic response consists of an erythematous line studded with punctate weals characteristic of cholinergic weals
What is the delay in delayed pressure urticaria?
30mins-12 hrs after stimulus
Occurs under tight clothing (waistline, sockline of ankles, feet in tight shoes), palms after manual labour, buttocks/lower back after sitting, feet after walking or climbing ladders
Systemic features may occur (malaise, ‘flu-like’, arthralgias) which may be mistaken for urticarial vasculitis
T/F
delayed pressure urticaria persists lifelong
False
may resolve in 6-9 yrs
What are the features of Vibratory angioedema?
Type of inducible urticaria not true angioedema
Vary rare form of urticaria
Vibratory stimulus induces localised swelling and erythema within minutes, lasting 30 mins
Jogging, vigorous towelling, using lawnmowers
May be acquired or Inherited - AD
What are the features of heat contact urticaria?
One of the rarest forms
Within mins of contact with heat from any source, pruritus and whealing occur at the site of contact lasting up to 1 hr
Must be distinguished from cholinergic urticaria and solar uricaria
E.g contact with hot water (e.g. washing dishes), radiant heat or warm sunlight
What are the types of cold urticaria?
Primary
Secondary
Reflex
Familial (FCAS)
In primary cold urticaria, wheals occur when ice is applied to skin
False
Whealing occurs within minutes of rewarming after cold exposure
Test by application of an ice cube in a thin plastic bag for up to 20mins onto the skin and wealing occurs within 15 mins during rewarming
What are the features of primary cold urticaria?
common type of inducible urticaria
Dermographism and cholinergic urticaria are frequently associated
Whealing occurs within 15 minutes of rewarming after cold exposure
should warn against cold-water bathing due to risk of anaphylaxis and drowning
What is secondary cold urticaria?
Rare type of inducible urticaria
Due to serum abnormalities such as cryoglobulinemia or cryofibrinogenemia
associated with other manifestations such as Raynaud’s phenomenon or purpura
Exclude underlying causes such as Hep B/C, lymphoproliferative disease, or EBV
What is Reflex cold urticaria?
Widespread wealing occurs in response to cooling of core body temperature, but a local ice-cube test is negative
Dont test by cooling pt in freezer as risk of fatal anaphylaxis
What is Familial cold urticaria?
Now called Familial cold autoinflammatory syndrome (FCAS)
Rare type of cryopyrin-associated periodic syndrome
Patient has mutation in gene which encodes protein cryopyrin
AD, NLRP3 gene
symptoms onset at birth or shortly afterwards
Episodes triggered by cold but not locaised i.e. ice cube test negative; last about 24 hrs
several symptoms during episodes but figurate/urticarial rash present every time
Fever
Muscle pain (myalgia)
Joint pain (arthralgia) – 96%, stiffness and swelling of the hands and feet
Headache
Nausea
DrowsinessExtreme thirst
Eye – frequent conjunctivitis (84%), blurred vision, pain
What is Cholinergic urticaria?
common type of inducible urticaria
Occur within 15 mins of sweat-inducing stimuli (e.g. physical exertion, hot baths, sudden emotional stress, gustatory stimuli (spicy food), moving from cold room to a hot room, drinking alcohol)
Multiple small wheals on erythematous base
Cause of exercise-induced urticaria and sometiems anaphylaxis
Intradermal injection of nicotine, Ach or methacholine triggers the rash and is diagnostic
T/F
Cold urticaria, symptomatic dermographism, or aquagenic urticaria may be of cholinergic urticaria clinical type
True
small wheals
What is Adrenergic urticaria?
Rare type of inducible urticaria
Halo hives are characteristic - blanched vasoconstricted skin surrounding individual small pink wheals (‘halo hives’)
Due to Mast cell degranulation triggered by noradrenaline
Induced by sudden stress, trauma, emotional upset, chocolate, coffee, ginger
Can be wheeze, palpitations, SOB, paraesthesiae, malaise
IgE and serum catecholamines rise during episodes but histamine and serotonin are normal
Intradermal injection of adrenalin or NA (5-10ng each)triggers the rash and is diagnostic
Treat by avoiding triggers +/- oral propanolol up to 40mg TDS
(selective beta blockers are ineffective) complete response to propanolol in the correct clinical setting is probably sufficient to make the diagnosis
T/F
Propanolol is the only effective Rx for adrenergic urticaria
True
T/F
Serum histamine, IgE and serum catecholamines rise during episodes of adrenergic urticaria
False
IgE and serum catecholamines rise during episodes but histamine and serotonin are normal
T/F
Solar urticaria may be triggered by all types of UV light
True
T/F
Symptoms of solar urticaria appear after several hours of sun exposure
False
within minutes
T/F
Symptoms of solar urticaria fade after several hours out of sun exposure
True
usually 2 hrs
T/F
A quarter of cases of solar urticaria resolve in 10 years
True
15% at 5 yrs and 25% at 10 yrs
T/F
The eruption of aquagenic urticaria resembles that of cholinergic urticaria
True
T/F
Contact urticaria is always immunologically mediated
False Allergic (type 1, IgE mediated) and non-imminological types
What are the common causes allergic of conatct urticaria?
Latex Foods - Fish, nuts, milk, crustaceans, spices, apples, peaches Foods which cross react with latex - Kiwi Chicks Like bananas and Avos Kiwi Chestnuts Lychees Bananas Avocado
What are the common causes non-allergic of conatct urticaria?
Direct injection of vasoactive chemicals by plants (e.g. nettles) or animals (e.g. caterpillars, jellyfish)
Exposure to cosmetics (e.g. cinnamic aldehyde, balsam of Peru)
Food additive (e.g. sorbic acid or benzoic acid)
T/F
Episodes of anioedema usually settle within 24hrs
False
often do but can persist for hours or occasionally 2-3 days
Which drugs cause angioedema?
ACE inhibitors - most common
NSAIDs
Penicillins
T/F
Hereditary angioedema accounts for less than 5% of cases of angioedema without weals
True
T/F
Hereditary angioedema usually presents in childhood
True
75% present before puberty but some not until adult life
T/F
In Hereditary angioedema abdominal symptoms may occur in absence of skin changes sometimes presenting as an acute abdomen
True
also nausea, vomiting, colic and urinary symptoms
What are triggers for attacks in Hereditary angioedema?
trauma (emotional or physical) esp intubation, dental extraction etc
Oestrogens (OCP)
T/F
C3 is a good initial screening test for C1 esterase inhibitor deficiency (inherited and acquired)
False
C4 good test - investigate if LOW
Low in Types 1 and 2 HAE and in acquired angioedema
(but normal in rare type 3 HAE)
C2 and CH50 are also low during attacks and sometimes between attacks
T/F
Hereditary angioedemas are autosomal recessive
False
AD usually family history
25% new mutations
T/F
Pts with type 3 Hereditary angioedema have a later age of onset and higher frequency of facial angioedema compared to types 1 and 2
True
T/F
Type 1 Hereditary angioedema is due to reduced amount of C1 esterase inhibitor
True
80% of caes of HAE
T/F
Type 2 Hereditary angioedema is due to reduced function of C1 esterase inhibitor
True
Levels are normal
What are the triggers of acquired C1 esterase inhibitor deficiency angioedema?
B-cell lymphoma
SLE
Auto-Antibody against the inhibitor without an identifiable cause
T/F
In acquired C1 esterase inhibitor deficiency angioedema pts have low C4, Low C1 (C1q) and low C1 esterase levels
True
can request C1 esterase inhibitor antibody serology
T/F
Anabolic steroids are useful for acute attacks of HAE
False
Danazol or stanozolol used for prevention
Acute attacks treated with FFP or or purified C1 inhibitor
T/F
autoinflammatory syndromes are the same as autoimmune diseases
False
caused by defects in the innate immune system as opposed to autoimmune diseases caused by defects in the adaptive immune system
What are the types of autoinflammatory syndromes?
Cryopyrin-associated periodic fever syndromes;
• Muckle-Wells syndrome
• Familial cold autoinflammatory syndrome (FCAS)(familial cold urticaria)
• Neonatal-onset multisystem inflammatory disease AKA Chronic Infantile Neurological Cutaneous Articular syndrome (MOMID/CINCA)
Familial Mediterranean fever
Schnitzler syndrome
Episodic angioedema with eosinophilia
Systemic capillary leak syndrome (Clarkson’s syndrome)
Wat are the features of Muckle-Wells syndrome?
Episodic rash (urticarial or ‘inflammatory’)
Fever
Arthralgias
Late onset sensorineural deafness
get systemic (renal) amyloidosis (AA protein) →renal failure
How does Familial cold autoinflammatory syndrome (FCAS) differ from Muckle-Wells?
Very similar
In FCAS the rash is triggered by cold (not localised cold so ice cube test negative)
Less risk of deafness but get conjunctivitis and eye pain
Which autoinflammatory syndromes are Herditary periodic fever syndromes?
Cryopyrin-associated periodic fever syndromes;
• Muckle-Wells syndrome
• Familial cold autoinflammatory syndrome (FCAS)(familial cold urticaria)
• Neonatal-onset multisystem inflammatory disease AKA Chronic Infantile Neurological Cutaneous Articular syndrome (NOMID/CINCA)
Familial Mediterranean fever
What are teh features of NOMID/CINCA?
Rash – migratory, urticaria starts from birth
Arthralgia/arthropathy – severe progressive
CNS features – chronic meningitis, hearing loss
+ frontal bossing, broad nasal root, short stature
T/F
Cryopyrin-associated periodic syndromes are AR due to muattions in NLPR3 (CIAS1) gene
False
AD
NLPR3 (CIAS1) gene
The 3 subtypes are allelic variants
T/F
Type IIII HAE is caused by a mutation in the gene for C1
False
mutation in gene that encodes factor XII (Hageman factor)
AD
Almost always women
Attacks triggered by oestrogen – pill, pregnancy
Normal C4
T/F
Familial Mediterranean fever is common in Ashkenazi jews
False
arabs and sephardic jews and armenians
T/F
Familial Mediterranean fever is due to an AR mutation that encodes gene for Pyrin – MEVR1
True
What are the clinical features of Familial Mediterranean fever?
Fever and Mediterranean SEA
Recurrent fevers
Serositis - episodes of peritonitis, pleurisy and synovitis
Erysipelas-like lesions on lower leg, but urticarial and vasculitic lesions may occur rarely
Amyloidosis - 25% of patients develop renal amyloidosis (AA protein)
T/F
Familial Mediterranean fever is the most common genetic autoinflammatory disease
True
What is the gene for Schnitzler syndrome?
No clear genetic cause identified
What are the features of Schnitzler syndrome?
U eat Vegetarian Schnitzel Made of Mycoprotein
Urticarial
Vasculitis
Monoclonal gammopathy
IgM
Chronic recurrent urticaria resembling urticarial vasculitis
Malaise, fever, lymphadenopathy, arthralgia/arthritis may occur
Monoclonal gammopathy – usually IgM
Overall prognosis is usually but not always benign
Patients respond very well to Anakinra
Histo may show UV and often is neutrophilic
T/F
Episodic angioedema with eosinophilia is characterised by Episodic angioedema with hypereosinophilia, weight gain, and fever
True
What are the features of Systemic capillary leak syndrome (Clarkson’s syndrome)?
Rare acquired disorder
Episodic massive plasma exudation from blood vessels, leading to potentially life-threatening hypotension, analogous to anaphylaxis
Angioedema may be a feature
Associated with IgG paraproteineia
Which forms of angioedema without weals have normal versus low C4?
Low in - HAE type 1 and 2 - Acquired C1 esterase inhibitor deficiency angioedema Normal in - HAE type 3 - Idiopathic angioedema - Drug-induced non-allergic angioedema - Episodic angioedema with eosinophilia - Capillary leak syndrome
what are the diagnostic criteria for Hypocomplementaemic urticarial vasculitis syndrome (HUVS)?
need both major + at least 2 minor; Major - Urticaria lasting >6 months - Hypocomplementaemia Minor (GRAVEL) 1. Glomerulonephritis 2. Recurrent abdo pain 3. Arhralgia or arthritis 4. Vasculitis on skin biopsy 5. Episcleritis or Uveitis (can also get iritis or conjunctivitis) 6. Low C1q level and +ve C1q precipitin test
T/F
there is no rash in pts with HAE
False
can get reticulate erythematous rash prior to attacks of angioedema
what are the associations of urticarial vasculitis?
Autoimmune CTD (esp. Sjogren’s + SLE)
Cryoglobulinemia
Infections (Hep B/C, EBV, Lyme disease(Borrelia))
Medications (cimetidine, diltiazem, biologics, fluoxetine, MTX, NSAIDs)
Hematological malignancies (leukemia, lymphoma, plasma cell dyscrasias, castleman’s disease)
IgM/IgA gammopathies
Solid organ malignancy – rare (colon, renal)
Serum sickness
what is a basic screening investigations in chronic urticaria?
History very important - screen for associations, infections and triggers of inducible urticarias
FBC, ESR, and TFT/thyroid autoantibodies
What tests may be considered in chronic urticaria?
FBC, ESR, ELFT as baseline
TFT, thyroid autoantibodies, B12, folate, IF
EBV, CMV, HIV, Hep B and C
ANA if any lupus/AI-CTD symptoms
C3, C4, CH50 +/- C1 esterase reasonable if any angio-oedema component
stool OCP
H. pylori serology
Strongyloides test important in Aus
And add coeliac antibodies TTG in children
EPP if schnitzler suspected
Cryoglobulins, cryofibrinogen, EBV and Hepatitis screen if cold urticaria
Refer to dentist if not seen recently (dental abscess can trigger recurrent urticaria)
what tests should be done for angioedema without weals?
Hereditary; C3, C4 if low C1 esterase inhibitor level If level normal check C1 esterase inhibitor function For acquired; C3, C4 ANA serology for anti-C1 esterase inhibitor antibodies EPP Bone marrow /LN biopsy (lymphoma)
What histamine releasing/containing drugs and foods should be avoided by people with chronic urticaria?
Opiates (morphine, codeine)
Antibiotics (vancomycin ‘red man syndrome’)
Iodine based radiocontrast dyes
Aspirin and NSAIDs
Alcohol (including cough mixtures/medicines)
Foods
- histamine containing – cheese, fish, meat, tomatoes, pineapple, avocados
- histamine-releasing – strawberries
What is treatment ladder for chronic spontaneous urticaria?
2nd gen antihistamine standard or increased dose cetirizine or loratine (both 10mg) best later try Fexofenadine 180mg, levocetirizine, desloratidine Ranitidine 150mg BD Phenergan or polaramine noce Doxepin 10-25mg nocte Monteleukast 10-20mg daily Omalizumab 300mg every 4 wks Pred for flares if necessary CsA MTX, MMF IVIg some evidence for UVB, PUVA, UVA1 Epipen if anaphylaxis
What are the histo features of dermal hypersensitivity?
Mild spongiosis
Papillary-mid dermal perivascular infiltrate of lymphocytes with variable number of eos
What are the clinical features of urticarial dermatitis?
Pts have typical urticarial weals (small like cholinergic or large/typical type) and also an eczematous dermatitis which is usually symmetrical
Urticated lesions last >24 hrs
Most common in middle aged-elderly
What are DDs for urticarial dermatitis?
As per chronic urticaria Also; drug eruption protein contact dermatitis Autoimmune progesterone urticarial dermatitis Dermatitis herpetiformis Pre-bullous BP
What is treatment for urticarial dermatitis?
Avoid precipitants if identified antihistamines + TCS nbUVB MTX MMF AZA, CsA
What is treatment for autoimmune progesterone dermatitis?
Can try oestrogen to inhibit ovulation
Tamoxifen
Danazol
Bilateral oophorectomy
What are the causes of a positive Darier’s sign?
Mastocytoma
JXG
ALL in neonates
What diagnostic tests can be used to confirm spontaneous urticaria?
Autologous serum skin test
Histamine release assay
How is the Autologous serum skin test performed?
inject intradermally a small vol of the pts own serum along with saline as negative control and histamine 0.1mg/ml as positive control
Look for weal and flare after 15 mins
For +ve test the weal induced by the serum should be twice the size of any weal from the negative control
What are the types of mastocytosis?
Solitary mastocytoma - kids
Urticaria pigmentosa - kids and adults
Diffuse cutaneous mastocytosis - kids and adults
Telangiectasia macularis eruptiva perstans (TMEP) - adults
T/F
90% of mastocytosis cases are cutaneous only
True
T/F
systemic symptoms in mastocytosis usually indicate systemic disease
False
Can have flushing, headache, diarrhoea, heat/cold intolerance or wheeze with cutaneous disease only
T/F
>50% of adults with Urticaria Pigmentosa (maculopapular urticaria) have BM involvement but very few children
True
T/F
Nearly all cases of mastocytosis with bone marrow disease have cutaneous involvement
True
T/F
A solitary skin mastocytoma never has systemic involvement
True
T/F
Childhood UP and diffuse cutaneous mastocytosis have high risk systemic involvement
False
low risk
T/F
All types of skin mastocytosis in adults have a significant risk of systemic mastocytosis
True
difuse more than TMEP more than UP
T/F
In cutaneous mastocytosis there is mast cell hypertrophy
False
hyperplasia
Which organs may be affected by mastocytosis?
skin alone or can affect BM, liver, spleen, LNs or rarely other organs
T/F
cutaneous mastocytosis may be familial
True
but most cases sporadic
T/F
Most but not all mastocytosis patients have activating mutations of c-kit protooncogene
True
T/F
C-kit gene codes for KIT RTK expressed on mastocytes, melanocytes, germ cells and primitive haematopoetic stem cells
True
T/F
histamine release is responsible for all the symptoms of cutaneous mastocytosis
False
Mast cells secrete a range of cytokines and peptides when they degranulate – these are responsible for the symptoms
eg) histamine, heparin, eicosanoids, tryptase, chymase, neut and eo chemotactic factors, PAF, PGs, leukotrienes, interleukins, TNFalpha, GM-CSF
T/F
wheeze is a common systemic symptom in pts with significant mastocytosis
False
wheeze and SOB can occur but v rare
T/F
In pts with cutaneous mastocytosis some systemic symptoms at the time of significant degranulation is expected and does not always indicate systemic disease
True
Flushing, bullae, pruritis, urticaria affect the skin
Can be can be headache, diarrhoea, heat/cold intolerance or wheeze when degranulates
What are symptoms which should prompt investigation for systemic mastocytosis?
General – malaise, night sweats, fever, wt loss (B symptoms)Cognitive – fatigue, confusion
GIT - Abdo pain/cramps, diarrhoea, N+V
CVS – chest pain, palpitations, SOB, dizziness, hypotension & syncope
Bone – bone pain (osteoporosis, osteosclerosis, osteopetrosis, spontaneous fractures)
T/F
55% of mastocytosis cases start before age 2
True
T/F
mastocytosis affects males more than females
False
M=F
What are triggers of mast cell degranulation in mastocytosis?
Exercise, stress, anxiety, pain
Heat/cold
Local trauma/rubbing/irritation of skin lesions (towel drying etc)
Insect and snake venom
Radiocontrast media (esp if iodine)
Allergens – IgE mediated (must ask if allergic reactions)
Some foods in some people (eggs, nuts, cheese, shellfish and variety of other foods)
Drugs
- Alcohol
- NSAIDS/salicylates (inc dipyridiamole)
- Opiates
- Beta blockers
- Quinine
- Amphotericin
- Scopolamine
- General anaesthetic agents;
• anticholinergics and sympathomimetics
• non-depolarising muscle relaxants – d-tubocurarium, gallamine
• depolarising muscle relaxants – Suxamethonium, Decamethonium
- plasma expanders
- IgE
- polymixin B
What are key points in history of Mastocytosis?
Any systemic symptoms - from major degranulation or from systemic disease
Any triggers identified for degranulation
Any episodes of anaphylaxis
Can ask about family Hx but doesnt affect management
T/F
Solitary mastocytoma accounts for about a third of childhood cutaneous mastocytosis
True
10-35%
T/F
Solitary mastocytoma presents in middle childhood
False
Infancy or early childhood but can be at birth
T/F
Solitary mastocytoma never occurs in adults
False
but very rare
T/F
Solitary mastocytomas may blister if rubbed
True
not that uncommon esp in nappy area
UP lesions and diffuse cutaneous masto can also blister
50% of pts have blistering lesions, mainly kids
T/F Urticaria Pigmentosa (maculopapular urticaria) is the most common presentation of cutaneous mastocytosis
True
T/F
Urticaria Pigmentosa accounts for 65% of childhood cutaneous mastocytosis
True
T/F
55% of Urticaria Pigmentosa starts in first year of life
False
>80%
T/F
In adults, Urticaria Pigmentosa presents at age 20-40
True
T/F
Urticaria Pigmentosa spares the head, palms and soles
True
T/F
Telangiectasia are a feature of TMEP and not other forms of cutaneous mastocytosis
False
not uncommon in UP lesions
Which lesions show +ve Dariers sign?
JAM
JXG
ALL of neonates
Mastocytomas
T/F
Half of kids with UP get flushing
True
T/F
60% of kids with UP get some symptoms
True
e.g. headache, diarrhoea, heat/cold intolerance or wheeze (rare)
T/F
Indolent systemic mastocytosis has a worse prognosis that cutaneous mastocytosis
False
does not change prognosis from pure skin disease
T/F
>50% of adults with UP have BM involvement
True
T/F
Diffuse cutaneous mastocytosis is very itchy
True
T/F
Diffuse cutaneous mastocytosis usually presents in adulthood
False
usually neonates but can be any age
T/F
In Diffuse cutaneous mastocytosis children have doughy skin and adults have leathery skin
False
infants leathery skin
adults doughy skin
T/F
Diffuse cutaneous mastocytosis can cause blistering after minor trauma
True
superficial blisters
DD for BCIE
T/F
thickened skin folds and distorted facial features can occur in Diffuse cutaneous mastocytosis
True
late features
what are xanthelasmoidal mastocytosis?
thick yellow plaques in Diffuse cutaneous mastocytosis
T/F
Diffuse cutaneous mastocytosis is high risk for systemic disease
True
In adults but still low risk in kids
also often have systemic features of mast cell degranulation e.g. diarrhoea, anaphylaxis
T/F
Telangiectasia Macularis Eruptiva Perstans occurs in adults but is very rare in children
True
T/F
Telangiectasia Macularis Eruptiva Perstans is characterised by widepsread Red telangiectatic macules esp on trunk
True
T/F
Telangiectasia Macularis Eruptiva Perstans has a vigorous Darier sign
Fase
Darier neg
dont urticate
T/F
Telangiectasia Macularis Eruptiva Perstans can co-exist with UP
True
T/F
Telangiectasia Macularis Eruptiva Perstans can co-exist with solitary mastocytoma
False
T/F
Telangiectasia Macularis Eruptiva Perstans runs a chronic resistant course
True
esp in adults
tends to resolve in kids
T/F
systemic mastocytosis always implys bone marrow invovlement
False
usually is BM involvement except for the very rare Mast cell sarcoma and extracutaneous mastocytoma
Which types of systemic mastocytosis are most likely to have skin mastocytosis?
Indolent systemic types
• Smouldering systemic mastocytosis
• Well differentiated systemic mastocytosis
T/F
systemic mastocytosis may co-exist with Non-Mast cell haematological disease with or without skin mastocytosis
True = Systemic mastocytosis with AHNMD (Associated clonal Haemtological Non-Mast cell Disease) • Myeloproliferative disease • Myelodysplastic disease • CMML • AML • Non-Hodgkins lymphoma • Hypereosinophilic syndrome Rarely cutaneous lesions
T/F
Bone lesions are a marker of aggressive systemic mastocytosis
True
Bone pain, cysts, fractures, other bone disease are very concerning
Skull, spine and pelvis most common
T/F
It is likely that pts with severe systemic mastocytosis will be diagnosed by dermatology
False
Most cases seen in derm will be adults with clinically UP/maculopapular masto with BM involvement and therefore indolent systemic mastocytosis with very low risk for progression to other forms
They may have mast cell infiltrates in LNs and organs but usually no organ dysfunction and mild or absent symptoms
Pts with aggressive systemic types develop many symptoms and will present elsewhere with these
T/F
The WHO criteria to diagnose systemic mastocytosis deliberately does not include skin features
True
Which pts ned investigation for systemic mastocytosis?
All adults need biopsy and serum tryptase and FBC and ELFT at presentation (or when cut mast confirmed) – additional tests guided by symptoms etc
Young children with solitary or few mastocytomas and nil else concerning don’t need to Ix also can monitor asymptomatic (but clinically typical) UP in very young children
Investigate;
Children with diagnostic uncertainty – biopsy +/- proceed
Children with UP + systemic symptoms – FBC, ELFT, serum tryptase +/- skin Bx +/- refer
Anyone with enlarged LNs (haem refer) or hepatosplenomegally clinically (USS +/- refer)
Anyone with bone symptoms or evidence of fractures or bone disease – DEXA and Xrays +/- refer haem
Anyone with severe symptoms esp those whose occur without a stimulus for cutaneous mast cell degranulation (haem refer)
Anyone with severe allergies (allergist/immunologist refer)
Anyone with B symptoms – indicates likely at least Smouldering SM (haem refer)
Anyone with signif GI symptoms ?peptic ulcer -OGD +/- haem refer
Anyone with anaemia, raised WCC or eosinophilia or other derangement (haem refer)
Anyone with total serum tryptase >75 or >20 on 2 occasions
What are the biopsy features of mastocytosis?
Increased number of mast cells in dermis, often spindle-shaped
In UP and solitary and DCM they are filling the papillary dermis in aband
sparser and with superficial capillaries and dilated venules in TMEP
Often eos
What special stains are used for mastocytosis?
IHC use CD117 (C-kit) or tryptase
Mast cell granules stain with toluidine blue or Giemsa or chloroacetate esterase stains
How is biopsy taken in suspected mastocytosis?
ring block
no adrenaline
gentle tissue handling
What investigations hould you consider in mastocytosis?
Whata re the findings you may see?
Serum tryptase – marker for BM disease but not conclusive
FBC – deranged in BM disease
ELFTs – deranged in severe form of systemic disease
24 hr Urine for Histamine and histamine metabolites
BM biopsy
Biopsy of LN or other non-skin tissue may be req to reach diagnostic criteria
USS or CT if hepatosplenomegally
DEXA - osteoporosis
Xrays/skeletal survey/bone scan - bone cysts, fractures
OGD - peptic ulcer disease
What are indications for bone marrow biopsy in mastocytosis?
Hepatosplenomegally (USS/CT) Bone disease (X-ray or bone scan) Abnormal FBC or LFTs Significant systemic symptoms B symptoms
Whats the prognosis of childhood urticaria pigmentosa?
50% of children clear by puberty, many by age 5
Children who do not resolve have same prognosis as adult onset indolent disease
Whats the prognosis of adult urticaria pigmentosa?
10% of adults clear in over 10 years
Progressing to significant haematological disease is rare even with BM involvement
T/F
Indolent systemic mastocytosis has same life expectancy as age matched controls
True
What are the important general measures in the management of cutaneous mastocytosis?
- Careful explanation - info sheet/websites
- Avoid triggers – provide written info
- Symptomatic relief – see below
- Test for and monitor for systemic disease/progression if indicated
- Plan for emergencies
- Medicalert bracelet
- Pt/parent to know what to do in emergency
- May need epipen (PBS prescription must be from allergist/immunologist/paediatrician/ED) – if IgE mediated allergy or history of anaphylaxis
Need careful planning prior to any surgery in discussion with surgeon and anaesthetist
- Prednisone and antihistamine prior to surgery is usual
- 24 hrs postop monitoring in case delayed anaphylaxis after surgery
What investgations should be done in adults with mastocytosis?
Biopsy to confirm diagnosis
FBC, ELFT, serum tryptase
Other as guided by Hx, exam and results of above
What local/topical Rx can be used for mastocytosis?
Short term topical steroids are important
- Can use potent or very potent, can use occlusion but side effects are a risk esp atrophy and systemic effects if applied over wide area (can just use on exposed areas to improve appearance)
ILCS also useful for selected lesions
Topical or IL steroid can clear a lesion of mast cells for >1 year
Can use calcineurin inhibitors
2% cromoglycate cream
emollients
What systemic/physical Rx can be used for mastocytosis?
H1 antihistamines sedating H1 antihistamines H2 blockers Doxepin Sodium cromoglycate montelukast NSAIDs Imatinib (Glivec) IFNalpha 2B for systemic disease CsA Thalidomide High dose oral steroids can be used temporarily in aggressive systemic mastocytosis or for recurrent anaphylaxis nbUVB PUVA, UVA1 XRT for bone pain
T/F
NSAIDs are used for itch in mastocytosis
False
For flushing
Aspirin and other NSAIDs can reduce flushing due to anti-prostaglandin effects
Introduce catiously along with antihistamine esp if Hx of intolerance
T/F
Imatinib is a mAb against c-kit
False
TKI which acts on c-kit
What resources are useful for pts/families with mastocytosis?
Support group http://mastocytosisaustralasia.com/
Child support group http://www.mastokids.org/
T/F
Phototherapy can reduce number of dermal mast cells in mastocytosis
True
can also help itch, wealing and appearance in UP but benefit is temporary – use up to 4 times per week
T/F
sodium cromoglycate orally can help all symptoms of mastocytosis
False
minimal oral absorption
mainly helps GI symptoms
T/F
seminal fluid usually causes type I rather than type IV hypersensitivity
T
latex and semen are major causes of type 1 contact hypersensitivty in vulva - can cause anaphylaxis
