Urticaria Flashcards
Aeitologies of urticaria
idiopathic
immunological (autoimmune, immune complex, allergic, complement)
Non immunological: direct mast cell releases, ACEI, aspirin, nsaids etc
Associations with urticaria
Thyroiditis, SLE, ?coeliac, H Pylori
Aggravating factors
URTIs, drugs e.g. salicylates, nsaids, ACEI, penicillin.
Pressure, overheating, premenstrual
Alcohol, stress, unrelated viral infections
tartrizine, azo dyes
T/F C1 esterase inhibitor deficiency and ACEI induced angioedema are due to mast cells
F - acei : kinins
T/F mast cells are responsible for autoinflamamtory syndromes
F - IL1 and 18 activated by caspase 1
H2 is responsible for itch, wheal, flare and erythema
F H2 for erythema and wheal only
What medication class may help in aspirin sensitive people?
leukotriene antagonists.
How are mast cells activated via immunological means?
linkage of 2 adjacent alpha subunits of IgE receptors of a mast cell
What type of hypersensitivy reaction is urticarial vasculitis
type III
How long does an IgE mediated urticaria last?
max 60 min
What are pseudoallergans
sensitization of the immune system is not involved, but clinically the same symptoms appear. e.g. aspirin, food additives, natural salicylate, contrast dye, muscle relaxants, plasma expanders
Non allergic causes of acute urticaria
histamine liberators (eg codeine, vancomycin)
Pseudoallergans eg aspirin, food additives
Alcohol
foods with vasoactivate amines: cheese, fish, tomatos, pineapple, avocados
Histamine from strawberries, scombroid fish
Tests for Chronic urticaria
FBC, ESR/CRP (increased in inflammatory syndromes, UV), thyroid abs and TFTs, ANA
Bx on wheal 12 hours old ?vasculitis
stool OCP
Consider: H pylori, strongyloides
consider pseudo allergen free diet for 2-3 weeks
?Anti-FceR(autoab to Fc receptor of IgE)
consider serum EPP, urine Bence jones - if fever, bony pain, raised CRP, neutrophils in bx.
Tests in acute
often none
maybe specific IgE, skin prick
URTI/bacterial screen
Q to ask re chronic urticaria
Can you induce the symptoms? Fever?Joint pain/malaise? Family hx? wheals last longer than 24 hours? Angioedema alone? Medications eg NSAID, ACEI
Treatment ladder for chronic urticaria
1st line = 2nd generation antihistamines. If persist > 2 weeks:
2nd line:Increase dose up to 4 x max
If persists after 1-4 weeks:
3rd line: omalizumab or cyclosporin A or montelukast
Can use short courses of CS if required.
Consider Doxepin or promethazine nocte
General measures: avoid overheating, stress, alcohol, drugs with potential to worsen e.g. codeine, aspirin, ACEI
1% menthol in aqueous
Other possibilitys: IVIg, plasmapheresis
Thyroxine in euthyroid with thyroid autoimmunity
nbUVB
Colchicine and dapsone if inflammatory infiltrate is neutrophil predominant
Tx of urticarial vasculitis
Dapsone, prednisone
How to use CsA in chronic urticaria
4mg/kg once daily 16 weeks.
helpful in about 2/3
How to use omalizumab
150-300mg sub cut every 4 weeks for 6/12
add on to antihistamines
keep in hospital to observe for 2-4 hours - risk of anaphylaxis
baseline platelets - risk of thrombocytopenia
Investigations if you suspect urticarial vasculitis
Bx DIF: vascular C3, fibrin and immunoglobulins
C3, C4, C1q, ANA, ENA, dsDNA, ANCAs
Hep B,C, HIV, EBV
serum EPP - schnitzlers if fever, bone pain, lymphadenopathy
due to risk of systemic involvement: ESR, Urinalysis
chest X-ray if symptomatic, RFTs
elfts
Important points on hx if you suspect UV
sx: burning, pain, how long they last, resolve with bruising? angioedema? fevers, malaise, bony pain abdo pain, nausea, vomiting Drugs e.g. cimetidine, diltiazem
In what % of patients does chronic urticaria last >5 years?
15%
% causes of acute urticaria
20% allergic e.g. drugs/food
30% infections
50% unknown
% causes of chronic urticaria
20% physical
80% unknown
Types of physical urticarias
Mechanical: delayed pressure, symptomatic dermatographism, vibratory
Thermal: cholinergic, cold contact, localised heat, systemic cold urticaria
Other: aquagenic, solar, exercise induced anaphylaxis
What treatment is recommended in delayed pressure urticaria
poorly responsive to antihistamines, but some help with 10mg tads cortisone as it also inhibits eosinophil migration, dapsone, colchicine, sulfasalzine, montelucast, nsaids (but may aggravate ordinary urticaria), topical steroids under occlusion
How to test for aquagenic urticaria
water in bath for 15min or water soaked towels at body temp for 30min
How to test for solar urticaria
Check porphyrins
Uusally fade in 2 hours cf to PMLE which appears hours later and lasts days
exposure to sunlight or solar stimulator - takes a few min, lasts less than 1 hour.
How to test for cholinergic urticaria
warm in hot bath 42 degrees for 15 min - raises core temp 0.7-1degree, or exercise until sweating.
How to test for delayed pressure urticaria
weight of 7kg hanging by broad strap, wheal at site 4-6 hours later, or 4.5kg weight rods with a 1.5cm diameter applied for 15 min.
How to test for systemic cold
ice cube test negative
cold room at 4 degrees for 30 min in lightweight clothes.
How to test for cold contact urticaria
consider cryoglobulins, cold agglutinins, cryofibrinogens, hep B, C, FBC, ANA
ice cube in a thin plastic bag for up to 20min to skin. Whealing occurs within 15 min usually during rewarming.
Angioedema without wheals - causes
Idiopathic
Drugs usually ACEI, Angiotensin II receptor blockers
Hereditary: C1 esterase inhibitor deficiency or impaired function or females with oestrogen dependant angioedema
Acquired C1 esterase inhibitor deficiency.
Causes of acquired C1 esterase inhibitor deficiency angioedema
1) lymphoproliferative: b cell lymphoma, nHL, multiple myeloma
2) SLE, autoimmune
3) Abs directed against inhibitor but no evidence of lymphoma
Different types of hereditary angioedema
1) Reduced amts of C1 esterase inhibitor
2) inactive form : 15% normal, or increased but dysfunctional
3) women with family hx but normal levels - oestrogen dependent
Treatment of hereditary angioedema
avoid oestrogen check for SLE, sjogrens Stanozolol 2mg alt days to 10mg daily Danazol 200mg mond to fri to 400mg daily Tranexamic acid 0.5-3mg daily C1 esterase inhibitor concentrate FFP Icatibant (bradykinin 2 receptor antagonist) 30mg SC
Ix of angioedema
check meds
C3, C4, C1q, CH50, C1 esterase inhibitor and function
ANA, ENA, dsDNA (associations with SLE, Sjogrens)
If C1q is LOW: consider acquired: serum EPP, hence ones, lymphoma,
What do you expect in results of complement studies in hereditary angioedema type 1
Low C1 INH
Low C4
normal C1q
CH50 may reduce during attacks
What do you expect in results of complement studies in hereditary angioedema type 2
Normal or elevated C1 INH but dysfunctional
low C4
normal C1q
What do you expect in results of complement studies in hereditary angioedema type 3
normal C1 INH, normal C4, normal C1q
mutation in factor XII gene
Diagnostic criteria for schnitzlers
Major criteria (must have these) and 2 minor criteria Major: chronic urticarial rash, monoclonal IgM or IgG Minor: recurrent fever, abnormal bone remodelling, neutrophilic dermal infiltrate, leucocytoisis and/or elevated CRP
What are Cryopryin associated periodic syndromes
NLRP3 gene mutation. Rare hereditary inflammatory disorder with 3 phenotypes. Due to a gain of function mutation affecting the cryopyrin protein
1) familial cold auto inflammatory syndrome AD
2) Muckle Wells - AD
3) Neonatal onset multisystem inflammatory disease/chronic infantile neurological cutaneous and articular syndrome
If you suspect a CAPS what do you do?
check FBC - neutrophilic CRP, ESR - elevated urinary protein to detect amyloid call renal Bx: perivascular and sometimes peregrine neutrophilic infiltrate of the reticular dermis without mast cells or vasculitis Tx is anakinra
What is familial mediterranean fever?
AR, MEVR1 gene
self limiting attacks of fever, peritonitis, pleurisy and synovitis. Erysipelas like lesions on the lower leg. 1/4 may develop renal amyloidosis.
Types of hereditary auto inflammatory syndromes
CAPS
familial mediterranean fever
hyperIgD syndrome
TRAPS
What are TRAPS
TNF receptor associated periodic syndrome
AD disorder.
Migratory erythema, febrile epidsodes, migratory muscle pain, amyloidosis
Clinical features of muckle wells
sensioneural hearing loss in 2/3, headaches, abdominal pain, mouth ulcers, amyloidosis in 25% leading to kidney failure and death, delayed puberty.
urticarial/angioedema like conditions associated with paraproteins
schnitzlers, acquired C1 esterase inhibitor deficiency angioedema, systemic papillary leak syndrome
People with auto inflammatory syndromes do not have angioedema as an associated symptom T/F
T
Diseases which may manifest urticarial lesions (according to the curriculum)
Arthropod bites - immediate, hypersensitivity reaction (papular urticaria)
contact dermatitis, exanthematous drug eruption
urticarial dermatitis
Polymorphic eruption of pregnancy
Mastocytosis in children
Autoimmune bullous diseases
Rare: autoimmune progesterone/oestrogen dermatitis, interstitial granulumatous dermatitis, eosinophilic cellulitis, neutrophilic eccrine hidradenitits, urticaria like follicular mucinosis.
Angioedema not associated with urticaria
hereditary angioedema
acquired C1 esterase inhibitor deficiency
idiopathic recurrent angiodema
Systemic diseases that can present with urticarial skin lesions (curriculum)
Vasculitides eg churg strauss, wegeners, PAN
urticarial vasculitis
SLE, Sjogrens, dermatomyositis
Mixed connective tissue disease
Juvenile RA
Haematologic disease
NHL (b cell), cryoglobulinaemia, hypereosinophilic syndromes, polycythaemia vera.
In angioedema without wheals, but normal C4 - consider what?
idiopathic, drug induced, episodic angiodema with eosinophilia, hereditary type III, capillary leak syndrome
What is urticarial dermatitis
Usually in elderly with both urticaria like and eczema like lesions. Often reported as dermal hypersensitivity reaction with minimal spongiosis, mixed inflammatory cells in the dermis. May be an early sign of BP, but could be related to drug, malignancy
Neutrophilic urticarial dermatoses
Urticaria with neutrophilic dermatoses histopathologically
Strongly associated with a systemic disease (schnitzler, adult onset stills, LE, hereditary auto inflammatory fever syndromes)
Clinical features of adult onset Still’s disease
High fevers often occur late afternoon, arthritis with carpal ankylosis, asymptomatic macular exanthema which accompanies the fevers (salmon pink in colour) and frequently koebnerises
F>M (usually presents 60)
Patients often have very elevated ferreting
Think of it in 3 weeks of fever, elevated CRP, ESR, platelets, arthritis
