Chronic Inducible Urticaria (CIndU)/Physical Urticaria
Pathophysiology - Table
Subtypes, Clinical Presentation and Relevant Provocation Testing:
Type | Trigger | Clinical Presentation, Prognosis | Testing [9] |
Dermographism (aka dermatographism, urticaria factitial, dermographic urticaria) | Shearing forces (scratching, stroking, rubbing of skin) | - Wheals within 10 minutes of exposure, resolving within 30 minutes; shape reflects triggering stimulus - Simple dermographism: more common; urticaria without pruritis - Symptomatic: pruritis present - Red: follicular predominant lesions [10] - Angioedema not typically observed - Variable duration, some report approximately 6.5 years [9] | A smooth, blunt object (ex. tongue depressor, closed ball pen), or calibrated dermographometer (pressure < 36 g/mm2) held perpendicular to skin of forearm or upper back and light stroking pressure applied – • Positive test: pruritic papule ≥ 3 mm within 10 minutes - Trigger threshold: dermographometer or FricTest® (plastic comb with 4 tips 3-4.5 mm – stroke once across volar forearm for 60 mm) - Positive test is development of pruritic, palpable wheal by 10 minutes |
Cold urticaria | Exposure to cold
| - Wheals following contact cooling and subsequent re warming, lasting about 1 hour [9] - Angioedema less frequent than wheals, though oropharyngeal edema can develop after cold food or beverage consumption - Typical reactions are localized, though can have generalized reactions as well - Anaphylaxis can occur with significant and/or systemic cold exposure (ex. swimming, cold IVF)
- Onset during childhood or young adulthood in many
- May be associated with infection (Mycoplasma, hepatitis B or C, HIV) or malignancy [4] - Consider cryofibrinogens, cryoglobulins, cold agglutinins, paroxysmal cold hemoglobinuria, especially if signs of vasculitis, kidney or other end-organ disease - Can have familial, delayed, food-dependent and localized presentations - Duration 2-8 years [4, 9] - Differentiate from: • cold-dependent dermographism • cold-induced cholinergic urticaria (symptoms only when exercising in cold) • familial cold auto inflammatory syndrome (FCAS; autosomal dominant; fever, rash, arthralgias and fatigue also present) • PLCˠ-2-associated antibody deficiency and immune dysregulation (PLAID) • FXII-associated cold auto-inflammatory syndrome (FACAS) | Cold simulation: Melting ice cube in thin plastic bag (avoid cold damage, prevent direct water contact to mitigate confounding aquagenic urticaria), cool pack applied to skin of volar forearm for 5 minutes, • Assess 10 minutes after cold stimulus removed • Shorter or longer provocation times may be used (30 seconds – 20 minutes) • Positive test: wheals and/or swelling • If ice cube test negative, can try immersing arm in cold (5-10°C) for 10 minutes - Caution with cold water bath, as this may induce systemic reaction - If negative testing but compelling history, consider testing at previously affected site, need for co-factors (food, exercise) - TempTest®: device which provides a continuous temperature gradient along its length (4°C to 44°C) is placed in contact with the skin of the anterior forearm for 5 min, read 10 minutes after removal - Threshold testing: ice cube or TempTest®: time needed to elicit a positive test; ≤ 3 minutes associated with increased disease activity |
Heat urticaria | Exposure to heat: exercise, hot showers, hot weather, warm objects | - Wheals typically localized to area of exposure, though affected area can extend beyond heat-exposed skin - Can have mucosal involvement | Heat simulation: metal/glass cylinder filled with hot water (up to 44° C) to anterior forearm, hot water baths or TempTest® for 5 minutes • Positive test: erythematous wheal and flare by 10 minutes |
Delayed pressure urticaria/ angioedema | Pressure on skin (tight clothing, belts, bra, blood pressure monitor) | - Variable symptoms: itching, burning, pain - Symptoms occur 30 mins to 12 (usually 2-6) hours after provocation and resolve over 24-48 hours [4, 9] - Comorbid with CSU in ≤ 40% [3, 4] -Duration 6-9 years [9] | - Many maneuvers not standardized (use of different rod diameters, weights) Pressure simulation: application of 7 kg weights attached to 3 cm straps on shoulders; rod supported in frame lowered vertically onto back, thigh or forearm, (1.5 – 5.5 cm diameter, 2.5- 3.5 kg for 15-20 minutes) or using dermographometer (apply perpendicularly at 100 g/mm2for 70 seconds on upper back) • Testing should be assessed after 6 hours • Positive test: development of deep red palpable swelling; may be pruritic, burning and/or painful |
Solar urticaria | Exposure to sunlight (can be several different wavelengths of light, both visible and UV range) | - Transient pruritic erythema or wheals on uncovered skin (may occur through transparent clothing, glass) within minutes of sunlight exposure - A “hardening” phenomenon has been demonstrated whereby frequently exposed areas are less sensitive [11]
- Rare, estimated to account for 0.08-0.4% of all urticarias [12] - Duration 3-6 years [9] | Solar simulators with filters (UV-A/-B) or monochromator (UV-A/-B and visible light) for provocation; apply to buttocks separately (UV-A 6 J/cm2), broad-band UV-B (60 mJ/cm2) and visible light) for up to 10 minutes • Can test visible light with slide projector at 10 cm • Avoid sunscreen, photoactive medications prior to testing • Positive test: wheal and flare within 10 minutes |
Vibratory urticaria/ angioedema | Vibration or friction on the skin (from tools or machinery, running/walking, massages) | - Itching, swelling and/or urticaria onset within minutes after exposure and lasting up to 24 hours [9]
- Some symptoms can be delayed onset, with peak symptoms 4-6 hours after exposure [13]
- Familial: autosomal dominant, gain-of-function ADGRE2 (aka EMR2), a cell surface receptor on mast cells | Forearm held on flat plate laid on vortex mixer running 780-1380 rpm for 5 minutes • Positive test: urticaria and/or swelling within 10 minutes; may measure arm circumference (wrist, mid-forearm and elbow) pre- and post-challenge |
Cholinergic urticaria | Increase in body temperature: may be active (sweating, exertion, emotional stress) or passive (hot weather, hot bath) warming | - Wheals tend to be smaller (1-3 mm) with surrounding flares that may coalesce, beginning on trunk and neck and spreading distally; symptoms usually subside within 1 hour [4, 9] - Uncommonly, may have systemic symptoms (hypotension, angioedema, bronchospasm) [4, 14] - Tingling, itching or burning may precede appearance of hives
- Onset usually during adolescence to young adulthood [4] - Atopic comorbidity in 34- 50% [4, 5, 14] - Often improves with age, duration 4-7.5 years, although some cases can persist [4, 9] - Cholinergic vs exercise induced urticaria/anaphylaxis; both may have systemic symptoms, although systemic symptoms are more common in exercise-induced anaphylaxis. Cholinergic urticaria has pathognomonic appearance and is triggered by elevation in body temperature; exercise induced anaphylaxis may have urticaria as an early symptom, and the wheals are typically larger in size than wheals seen in cholinergic urticaria. Additionally, exercise is the only trigger for anaphylaxis in this condition. | Two step combination challenge to differentiate cholinergic from exercise induced urticaria: exercise challenge first; if positive, perform passive heat challenge ≥ 24H later (cholinergic diagnosed if both are positive) • Exercise: to the point of sweating and up to 15 minutes thereafter or onset of symptoms (warm room and/or clothing may facilitate positive test) • Passive warming (if exercise test positive): 42 °C full bath for up to 15 minutes; body temperature should increase by ≥ 1°C • Pulse-controlled ergometry: bicycle ergometry pedaling rate to achieve increase in pulse of 15 bpm every 5 minutes (max increase 90/min above starting at 30 minutes) - Time to urticaria inversely correlates with disease severity |
Aquagenic urticaria | Exposure to water, independent of temperature, pH | - Rare - Typically present with characteristic 1–3 mm sometimes folliculocentric wheals with surrounding 1–3 cm erythematous flares within 5–30 minutes following skin contact with water and fade in 30-60 minutes [3, 9, 15] • Similar in appearance to cholinergic urticaria • Topical solvents (including alcohol) or epilation, may facilitate reactivity, possibly by altering skin permeability [15] - Rarely, systemic symptoms can occur [9, 15] - There may be a multi-hour long refractory period [15] - Salinity may be important (rain, tap water, snow vs sea water vs body fluids)[15] - Differentiate from aquagenic pruritis (itching without wheals), other forms of urticaria (spontaneous, cholinergic, cold, heat), polymorphous light eruption, erythropoietic protoporphyria, drug induced phototoxicity, photoallergic reactions, cutaneous lupus erythematosus, brachioradial pruritis | Water simulation: apply a compress or towel soaked with 35-37°C water or physiological saline to trunk for 40 minutes (or earlier, if pruritis and/or wheals develop) • Water of any temperature can provoke aquagenic urticaria; using room temperature helps minimize confusion with cold or local heat urticaria |
Postural urticaria | Going from supine or seated to standing position | - Rare, only 2 case reports - Urticaria on lower extremities after standing [16, 17] | Standing for 10-20 minutes (16) |
Contact urticaria | Exposure to exogenous substance | - Urticaria within 30 minutes [9] - May have systemic involvement - Immunologic contact urticaria (ICU): IgE mediated, may spread beyond areas of direct contact - Non-immunologic (NICU): confined within initial areas of contact - Indeterminate: unclear mechanism | Open controlled application, skin prick, closed patch test (20 minutes) - Testing often not necessary if trigger is obvious (stinging nettles, jellyfish) - ssIgE testing for ICU if available |