Chronic urticaria (spontaneous / inducible)

Definition

Recurrent urticaria episodes lasting longer than 6 weeks.

Epidemiology

Prevalence: approx. 1% of the population
Women: Men = 2: 1

Etiopathogenesis

Chronic urticaria: differentiation according to aetiology.

Chronic spontaneous urticaria (CSU):
Chronic inducible urticaria:
- Physical urticaria (pressure, vibration)
- Cold urticaria
- Heat urticaria
- Light urticaria
- Cholinergic urticaria
- Autoimmune urticaria
- Aquagenic urticaria
- Exertional urticaria
- Contact urticaria
  - Allergic
  - Non-allergic

Clinical features

S. Urticaria.

Diagnosis

Stage 1 Medical history	Personal and family history for atopy, medication history (especially: ASA, NSAIDS, β-blockers, ACE inhibitors, histamine ligators). Frequency Duration Dependent on time of day? Localisation? Infections? FA: Atopy? Urticaria? Nicotine or alcohol abuse? Is there angioedema? Incompatibilities? Physical stimuli? Occupation? Hobbies? New implants? Insect bites? Association with menstrual cycle? Previous therapies?
Status	Quaddling?, petechiae, hyperpigmentation? Dermographism?, Darier? In isolated urticaria factitia: no further investigations
Laboratory	Blood count diff, CRP,TSH, fT4 Thyroid autoantibodies (anti-TPO, anti-TG, TRAK), ANA Tryptase, IgE total, ev. Fx5
Skin testing	Atopiescreening
Stage 2: according to history Angioedema without urticaria	C1 inhibitor concentration, function, C4
Vd. a. Food allergy (rare)	allergological clarification: skin testing, CAP, oral provocation testing (OPT)
Increase in intake of histamine-rich food	low-histamine diet with nutritional counselling, complaints diary
Anamnestically unclear connection with food intake	Ev. Rice-potato diet (ev inpatient) If improvement, try low additive diet
V.a. physical urticaria: Cold urticaria Heat urticaria Pressure urticaria Cholinergic urticaria Light urticaria Aquagenic urticaria	Cold test Heat test Pressure test Bicycle ergometer UV threshold Water test

V.a. autoreactive urticaria	autologous serum test
V.a. Hepatitis	Hepatitis serology, ev cryoglobulinaemia
Reflux, stomach pain	H. pylori breath test
Systemic symptoms (fever, arthral-gia, etc) V.a. Schnitzler's syndrome (rare) Cryopyrin-associated periodic syndromes (rare)	Biopsy (neutrophilic urticaria?) Immunelectrophoresis, immunofixation Ev. NLRP3 gene mutation search, measure IL-6 in relapse
Quaddles >24h/ hyperpigmentation/petechiae, resistance to therapy	Biopsy, ev. DIF, C3,C4
Darier's sign positive	Biopsy (mast cell stain)
ANA increased	≤1:80 no further work-up 1:160 Follow-up ≥ 1:320 ANA specificities (depending on clinic and binding pattern)
Depending on sexual history	HIV-Test
CRP↑ or leucocytosis	Focus search according to history
Eosinophilia or IgE↑ or tropical stay	Stool examination + serology
V.a. Early stage bullous pemphigoid	Biopsy with DIF, IIF in serum

Recording of suffering pressure by means of PRISM and quality of life questionnaire (CU-QoL).
Recording of urticaria activity by means of UAS-7 diagnostics.
According to guidelines, exclusion of malignant diseases is obsolete.

Dermatopathology

S. Urticaria.

Therapy

First line: Non-sedating antihistamine (nsAH) of the 2nd generation (levocetirizine (Xyzal®) p.o. 5 mg 1x tgl, desloratadine (Aerius®) p.o. 5 mg 1x tgl, fexofenadine (Telfast®) p.o. 180 mg 1x tgl)

Second line if symptom persistence > 2-4 weeks: Dose increase of nsAH up to 4 times the dose

Third line in case of symptom resistance > 2-4 weeks under second line therapy: Omalizumab (Xolair®) s.c. 300mg 1x monthly.

Approved for the therapy of chronic spontaneous urticaria from 12 years of age. For all other forms of urticaria, obtain off-label use à (cost approval).
If there is a response, attempt to reduce the dose to 150mg/month or extend the injection interval.

Alternatives: ciclosporin A, others.

Self-recording of urticaria activity: UAS-7

The patient records daily wheals (score 0-3) and itching (score 0-3) in a complaint diary. The daily maximum score is 6 points. The UAS-7 records the weekly score. The daily maximum score is added over a period of 7 days (maximum weekly score 42 points)

A clinically meaningful improvement in urticarial activity is reflected by a 10-point reduction in the UAS-7. Score	Quad count	Pruritus
0	none	none
1	mild (<20/24h)	mild (no subjective impairment)
2	moderate (20-50/24h)	vacuous (but no interference with daily activity or sleep)
3	pronounced (>50/24h) or large confluent areas of wheals	Expressed (interference with daily activity or sleep)

References

Zuberbier T, Henz BM. Acute and Chronic Urticaria. Urticaria: Springer Science + Business Media; 1998:39-44.
Heymann WR. Chronic urticaria and angioedema associated with thyroid autoimmunity: Review and therapeutic implications. Journal of the American Academy of Dermatology 1999;40:229-32.
Sabroe RA, Poon E, Orchard GE, et al. Cutaneous inflammatory cell infiltrate in chronic idiopathic urticaria: Comparison of patients with and without anti-FcϵRI or anti-IgE autoantibodies. Journal of Allergy and Clinical Immunology 1999;103:484-93.
Ring J. Desloratadine in the treatment of chronic idiopathic urticaria. Allergy 2001;56:28-32.
Grattan CEH, Sabroe RA, Greaves MW. Chronic urticaria. Journal of the American Academy of Dermatology 2002;46:645-60.
Kaplan AP. Chronic Urticaria and Angioedema. New England Journal of Medicine 2002;346:175-9.
Yosipovitch G, Ansari N, Goon A, Chan YH, Goh CL. Clinical characteristics of pruritus in chronic idiopathic urticaria. Br J Dermatol 2002;147:32-6.
Doeglas HMG. Reactions to aspirin and food additives in patients with chronic urticaria, including the physical urticarias*. British Journal of Dermatology 2006;93:135-44.
Asero R, Tedeschi A, Coppola R, et al. Activation of the tissue factor pathway of blood coagulation in patients with chronic urticaria. Journal of Allergy and Clinical Immunology 2007;119:705-10.
Powell RJ, Du Toit GL, Siddique N, et al. BSACI guidelines for the management of chronic urticaria and angio-oedema. Clinical & Experimental Allergy 2007;37:631-50.
Engin B, Özdemir M. Prospective randomized non-blinded clinical trial on the use of dapsone plus antihistamine vs. antihistamine in patients with chronic idiopathic urticaria. Journal of the European Academy of Dermatology and Venereology 2008;22:481-6.
Kaplan AP, Joseph K, Maykut RJ, Geba GP, Zeldin RK. Treatment of chronic autoimmune urticaria with omalizumab. Journal of Allergy and Clinical Immunology 2008;122:569-73.
Bunselmeyer B, Laubach HJ, Schiller M, Stanke M, Luger TA, Brehler R. Incremental build-up food challenge - a new diagnostic approach to evaluate pseudoallergic reactions in chronic urticaria: a pilot study. Clinical & Experimental Allergy 2009;39:116-26.
Godse K. Omalizumab in treatment-resistant chronic spontaneous urticaria. Indian Journal of Dermatology 2011;56:444.
Maurer M, Altrichter S, Bieber T, et al. Efficacy and safety of omalizumab in patients with chronic urticaria who exhibit IgE against thyroperoxidase. Journal of Allergy and Clinical Immunology 2011;128:202-9.e5.
Zuberbier, T. (2016). Klassifikation und Diagnostik der Urtikaria- deutschsprachige Version der internationalen S3-Leitlinie. Awmf.org. Retrieved 30 May 2016, from http://www.awmf.org/leitlinien/detail/ll/013-028.html
Saini, S. (2016). Chronic urticaria: Clinical manifestations, diagnosis, pathogenesis, and natural history. Uptodate.com. Retrieved 30 May 2016, from http://www.uptodate.com/contents/chronic-urticaria-clinical-manifestations-diagnosis-pathogenesis-and-natural-history?source=search_result&search=chronic+urticaria&selectedTitle=1~55