Urticaria and angioedema Flashcards
Key clinical components of urticaria?
Wheals lasts <24 hrs. They are pale to pink-red, edematous papules and plaques w/ central clearing that tend to be pruritic
What is the overlap b/w angioedema and wheals and urticaria?
Urticaria can have wheals, angioedema, or both
Clinical presentation of angioedema
ill-defined, deeper dermal and subQ +/- submucosal swelling. There is minimal to no overlying erythema. Lesions tend to be painful and pruritic and extracutaneous involvement can include the respiratory or GI systems
What is the pathogenesis of urticaria?
Pathogenesis mediated by the release of preformed and newly formed granules from mast cells -Preformed: histamine, heparin, chymase (tryptase) -Newly formed: PG, LT, PAF
What are some common mast-cell degranulating stimuli?
Immune-mediated: IgE against allergen (type I hypersensitivity) - Anti-IgE receptor and anti-FcεRI (chronic autoimmune urticaria) -Nonimmune-mediated: codeine, substance P, KIT ligand, C5a (anaphylatoxin) -Nettle stings -Medications: NSAIDs, ACEi
Definition of chronic urticaria?
Urticaria occurring for > 6 weeks
Describe acute urticaria?
M/c in children -Presents as large annular or polycyclic erythematous plaques (urticaria multiforme from dusky purple appearance) -Most common cause is idiopathic followed by URI
Describe chronic urticaria?
-M/c in adults (4th decade, W>M) -includes autoimmune form - a/w thyroid dz and celiac dz -Most common cause is idiopathic followed by inducible factors
Name and describe the 4 types of physical urticaria?
(i) mechanical stimuli: dermographism (affect 10% general population); delayed-pressure (wheals>24h; a/w arthralgias and malaise; sustained pressure to skin) (ii) temperature changes: cold (transition from cold->hot) >> heat-induced - use ice cube test (wheal on rewarming); idiopathic cause - <5% a/w cryoglobulins or cryofibrinogen (iii) physical exercise/sweating: cholinergic (body temp dependent)>adrenergic (blanched halo); exercise-induced anaphylaxis (not from increased body temp) (iv) solar (5-10 min exposure → UVA +/- visible light > UVB) and aquagenic (temp-independent)
Describe urticaria vasculitis?
The lesions tend to burn +/- painful, lasts >24h, purpura on resolution *commonly has extracutaneous sxs (arthralgias, abd pain, pulmonary dz, nephritis, uveitis)
Describe Schnitzler’s syndrome?
Associated with monoclonal gammopathy (IgM>>IgG) -Presents with fever, arthralgia, elevated ESR, LAN, leukocytosis
Describe Still’s disease?
Presents with fever (cyclic), pharyngitis, arthralgias, LAN, elevated ferritin
Serum-like sickness rxn?
Systemic drug reaction presents with fever, LAN, arthralgias, acral edema
Urticaria managment?
Do not get aggressive labs like allergy testing, other blood tests -eliminate modifiable causes -avoid NSAID’s, codeine products -trial of 2nd gen H1 antihistamines (cetirizine) can use up to 4x the standard dosing -Can consider using doxepin @ night, anticholinergic, do not use in glaucoma pts and those on MAOI -Can add H2 blocker -Omalizumab (anti-IgE mAb) for chronic autoimmune form
Desribe angioedema with no wheals?
*Pathogenesis - edema mediated by bradykinin NOT histamine (urticaria-angioedema) *Acquired vs hereditary* -Acquired: present later in life - a/w lymphoproliferative d/o (MGUS, lymphoma) - check C1q levels to differentiate from hereditary type I: a/w lymphoproliferative d/o type II: a/w autoimmune phenomenon → autoantibodies against C1-inh
Two types of angioedema w/ no wheals?
Type I: a/w lymphoproliferative d/o
Type II: a/w autoimmune phenomenon → autoantibodies against C1-inh
What are the 3 types of hereditary angioedema?
Type I: deficient C1 esterase inh (C1-inh), low C4 Type II: dysfunctional C1-inh, low C4 Type I and II both favor acral surfaces, GI system (acute abd), and larynx (laryngeal edema → airway compromise) *Type III: normal C4 levels; later-onset - affect face m/c and favor W>M
What medications are not effective in non urticarial angioedema?
Antihistamines, epinephrine, and steroids
What managment should be done for the non-urticarial angioedemas?
Short term: IV C-1 inhibitor Long-term: androgen (oral danazol)
What are the most common triggers of drug-induced immunologic urticaria?
Penicillins, cephalosporins, latex gloves or medical devices
What common medication can worsen chronic urticaria in up to 30% of patients?
Aspirin
How is the timing of drug-induced acute urticaria different than other forms?
Can be more delayed (days after triggering event)
What are the most common causes of chronic urticaria?
60% = idiopathic and autoimmune-autoantibodies against FcepsilonR1 or Fc portion of IgE, infection-related and pseudo-allergic
35% = Physical
Vasculitis = 5%
How common is autoimmune urticaria?
Up to 50% of chronic urticaria
What conditions are associated with chronic urticaria?
Thyroid disease, vitiligo, IDDM, RA
How long does chronic urticaria usually last?
3-5 years
What is the most common physical urticaria?
Dermatographism
When does dermatographism-induced urticaria tend to be worst?
In the evening
What is the timing of pressure urticaria?
Tends to be quite delayed (up to 12 hrs after pressure event)
What is the clinical presentation of delayed pressure urticaria?
Occurs in areas of high friction or pressure (waistline after wearing tight clothes)
Painful, itchy and possibly long-lasting. Can even be associated with arthralgias, malaise, and flu-like symptoms
What warning about swimming must be discussed with patients with cold-induced urticaria?
They must never swim alone
The cold of the water can lead to a massive release of histamine leading to hypotension
What are some triggers of secondary cold urticaria?
Cryoglobulinemia, cryofibrinogenimia, hepatitis, lymphoproliferative dz, or mononucleosis
What is the clinical presentation of cholinergic urticaria?
Distinct lesions (multiple 2-3mm slightly papular wheels w/ pronounced flare of erythema
- Occur after sweating/increased body temp in young adults
- Can have systemic sx’s of faintness, wheezing, etc
In what disease is aquagenic urticaria more commonly seen in?
Cystic fibrosis
What is the treatment of Schnitzler’s syndrome?
Anakinra first line
What is the histology of urticaria?
Superficial dermal edema, vasodilation, scant perivascular and interstitial infiltrate that is predominantly made up of neutrophils (>eos and lymphs)
What labs should be pursued in chronic/recalcitrant urticaria?
CBC, ESR/CRP, thyroid antibodies, thyroid function tests, anti-FcepisilonR1/anti-IgE antibodies, immunoassays, functional assays (HRA) and autoreactivity (ASST)
What test must be performed/what must be ruled out in angioedema without urticaria?
C1 esterase inhibitor deficiency
What is the screening test of choice for acquired and inherited angioedema?
C4 (or CH50) [C4 will be low]
What is the inheritance pattern for all forms of inherited angioedema?
Autosomal dominant for all
What is the difference between type I and type II heritable angioedema?
Type I = decreased levels of C1 esterase inhibitor and Type 2 = decreased function but normal to elevated levels
What is the difference between type I and type II acquired angioedema?
Type I: Consumption of C1 esterase inhibitor
Type II: Antibodies against C1 esterase inhibitor
What is the cause of hereditary angioedema type III?
Activating mutation in Hageman factor (FXII)
What type of angioedema has low levels of C1q?
Only see in acquired angioedema
What is the timing of ACEi induced angioedema?
Occurs within the first 3 weeks most commonly, all occur within the first year
How do ACEi cause anigioedema?
Block kinase II –> Elevated bradykinin
What are the clinical features of angioedema?
Unlike urticaria it tends to be painful, non-erythematous, non-pitting, non-pruritic (but can burn)
Commonly lasts 2-5 days (worst in the first 36 hrs)
What are the most commonly affected areas in angioedema?
Face, lips, eyelids, throat, ears and nose
What are a couple of differences in the presentation of hereditary angioedema type III vs the other types?
Type III tends to have a later age of onset (teens), and has more facial edema
What labs should be checked if hereditary or acquired angioedema is suspected?
Check C4, C1 inhibitor (quantification and function) and C1q
What is the treatment of hereditary angioedema?
Type 1 (C1 inh deficiency): Oral danazol is the treatment of choice for prophylaxis and C1 inh concentrate is the treatment of choice for acute attacks
Icatibant is a synthetic bradykinin B2 receptor antagonist
