Urticaria chronic spontaneous L50.8

Urticaria lasting longer than 6 weeks (in many cases the clinical picture persists for > 5 years). A distinction is made according to the clinical course:

• chronic-continuous spontaneous urticaria with daily attacks
• chronic-relapsing spontaneous urticaria with an intermittent course (with wheal attacks alternating with symptom-free intervals)

The term spontaneous or idiopathic urticaria refers to the unknown aetiology and is in contrast to chronic inducible urticaria (causes known or easily ascertainable, e.g. physical urticaria, see urticaria below).

see below Urticaria

Prevalence data varies between 0.1 % and 0.6 %. Cumulative prevalences (number of people who have experienced urticaria at least once in their lives) are between 9% and 25%.

• Up to 70% of the diseases are idiopathic.
• About 1/4 of patients have a positive history of atopy; total IgE is elevated in > 50% of cases.
• The model of molecular mimicry of epitopes is repeatedly discussed as a possible trigger of chronic urticaria. The model is based, for example, on the temporary presence of various antibodies (e.g. thyroid autoantibodies TAK/TPO) as well as on a temporary or permanent susceptibility to non-immunological hypersensitivity reactions (e.g. intolerance reactions characterized by non-IgE-mediated histamine release ).
• Depending on the type of urticaria, very different triggers are possible:
  • Drugs or foods (non-IgE-mediated; see also intolerance reaction; biogenic amines)
  • Food additives: colorants, benzoates, salicylates, sulphites, glutamates (non-IgE-mediated); the data on this is contradictory; causative in < 5 % of patients)
  • Acetylsalicylic acid: no association with salicylate-containing foods (non-IgE-mediated)
  • Food (IgE-mediated allergic reactions) or contamination (e.g. residues of antibiotics in meat): Such reactions are rather rare (< 1% in children and adults).
  • Bacterial infections (Helicobacter pylori [there is the highest level of evidence for this mode of infection], streptococci, staphylococci, Yersinia); for infections in the dental and ENT area, there are no confirmed correlations between therapy and the course of urticaria, although such correlations have been postulated in individual cases.
  • Viral infections (there are reports of hepatitis virus infections and norovirus infections [no convincing evidence to date])
  • Parasites (lamblia, entamoebae, worm infections; trichomonads, trichinella, toxocara canis)
  • Autoimmune processes (autologous serum test, thyroid autoantibodies - see autoreactive urticaria)
  • Rare: tumors, hepatitis

Women are affected about twice as often as men. The peak incidence is between the third and fourth decade of life.

Repeated or constantly occurring, raised, sharply defined, palpable, solitary or confluent, whitish to red, itchy, flat, transient skin lesions (wheals) of varying size (0.2-10.0 cm). In 52% of cases, the course of the disease is chronically recurrent. There is evidence of an increased rate (between 35% and 50% of the total collective, depending on the literature) of psychiatric comorbidities, such as: anxiety disorders, depression and somatoform disorders.

see below Urticaria

Step-by-step program for the diagnosis of chronic urticaria (according to Ring/Przybilla). The diagnosis of urticaria requires patience and the consistent execution of a clearly defined diagnostic program (discussed with the patient in advance) (see Table 1). Targeted provocation tests can be started when the patient is free of symptoms. The following provocation diets can be recommended according to the patient's medical history and previous test results:

• • build-up diet
  • additive-rich diet
  • Diet rich in salicylates
  • Biogenic amines
  • Oral provocation test for idiosyncrasy (OPTI)
• Pseudoallergic/intolerance reaction: About 20 - 50 % of cases of chronic urticaria are caused by non-immunological, i.e. pseudoallergic reactions (mainly acetylsalicylic acid). An antigen-antibody reaction does not take place in these reactions. IgE cannot be detected in increased amounts. RAST determinations in this sense are therefore not possible. Pseudoallergic reactions can be triggered by various pathomechanisms, e.g. direct complement activation, direct mediator release, enzyme defects, Jarisch-Herxheimer reaction, neuro-psychogenic. The CAST (cellular antigen stimulation test) is available as a laboratory test for suspected pseudoallergic reactions. Provocation diets with biogenic amines can confirm the suspicion.
• Salicycylates: Acetylsalicylic acid is the most common substance that can trigger an intolerance reaction. The pathomechanism has not yet been clearly clarified. An inhibition of cyclooxygenase is being discussed, which leads to a lack of protective prostaglandins and to increased formation of lipoxygenase metabolites or may cause direct mediator release, direct complement activation and altered platelet reactivity. There are pronounced cross-reactions with pharmacologically similar agents, e.g. other NSAs, but also with other chemicals such as food colorings (tartrazine) and preservatives. If an intolerance reaction to ASA is known, coxibs (e.g. celecoxib) can be given if necessary.

Elimination or avoidance of the triggering factors after careful anamnesis and diagnosis.

• Focus search: Rehabilitation of a chronic focus or treatment of the underlying disease (e.g. antibiotic or surgical treatment of dental and ENT foci [no confirmed evidence]; eradication of Helicobacter pylori [high level of evidence], treatment of candida infections [no confirmed evidence]; see also candidiasis, enteric, etc.).
• In case of parasitic cause: adequate therapy
• Medication: discontinuation or conversion of possibly causative medication (e.g. analgesics, antibiotics such as penicillin, acetylsalicylic acid, insulin, vaccinations)
• If food or additives are possible triggers and other trigger factors have been ruled out, a standardized pseudoallergen-free basic diet (see Table 4) should be followed for 4-6 months. 70 % of patients experience significant improvement, even freedom from symptoms(placebo effect?). During the diet, a dietary log / symptoms log should be kept and the severity of urticaria should be assessed. About 50 % of patients tolerate a full diet again after six months.

Blande, antipruritic local therapy e.g. Optiderm lotion, Tannolact lotion, Lotio alba, Lotio Cordes, zinc oxide emulsion LAW, if necessary with addition of 2-5% polidocanol (e.g. Thesit, rp. 200 rp. 196 ) or 1% menthol rp. 160. 160. if necessary, topical glucocorticoids as lotion (e.g. Triamgalen lotion, rp. 123) or cream (e.g. Triamgalen cream, rp. 121 rp. 120). Alternatively, gels containing antihistamines (e.g. Fenistil, Tavegil, Soventol).

The use of UVA irradiation can lead to clinical improvement in individual cases. UVB therapy is more reserved for cholinergic urticaria and urticaria factitia.

For evidence-based therapy, see below Urticaria (the therapy options listed here are partly based on smaller study results or personal experience).

• Antihistamines: Oral administration of non-sedating antihistamines (H1-blockers) of the 2nd generation such as loratadine 10 mg (e.g. Lisino) 1 tbl. p.o. once a day, desloratadine 5 mg (e.g. Aerius) 1 tbl. p.o. once a day, Cetirizine 10 mg (e.g. Zyrtec) 1x daily 1 tbl. p.o. or levocetirizine 5 mg (Xusal) 1x daily 1 tbl. p.o. If therapy fails (after 14 days) switch to high-dose antihistamine therapy:
• Antihistaminic high-dose therapy: If the response is insufficient, individually adjusted dose increases (e.g. desloratadine in increasing doses up to 4 times the standard dose) can be used.
• Alternatively: combinations. The response to the various H1-blockers varies greatly from individual to individual, so the success of their combination must also be assessed differently. Different H1 blockers can be combined in double combinations (e.g. levocetiricin and fexofenadine) or also in triple combinations (levocetirizine and fexofenadine as well as levocetiricin [<- PLEASE CORRECT] in double the standard dose). Combinations with H2 receptor blockers such as cimetidine (e.g. Tagamet) 400-800 mg / day or ranitidine (e.g. Sostril) 1x daily 300 mg or 2x daily 150 mg p.o. have also been successfully described.
• Alternative: Omalizumab (Xolair): Approval for (therapy-resistant) chronic spontaneous urticaria has been available since 2014. Dosage: 300 mg / s.c. every 28 days. The clinical efficacy has been proven in several studies (Staubach P et al. 2016).
• Alternative: sedating antihistamines (therapeutic principle is considered outdated by many authors). Sedating antihistamines such as hydroxyzine (e.g. Atarax®) 1-3 tablets/day are particularly suitable for hospitalized patients at night.
• Alternatively: anti-allergic drugs with an antihistaminic and PAF-blocking effect such as rupatadine (e.g. Rupafin) 10 mg / day p.o.
• Alternative: Combination of H1-blockers with a leukotriene antagonist (e.g. montelukast), especially in patients with concomitant angioedema
• Alternative: Combination of an H1-AH (e.g. desloratadine 10 mg / day) with dapsone (50-150 mg / day)
• Alternative: Ciclosporin (good evidence) (2.5 mg / kg bw p.o. in 2 ED). However, ciclosporin should only be used in severe, absolutely therapy-resistant chronic urticaria, possibly in combination with an H1-AH.
• Casuistic: Dapsone (low evidence): 50-100 mg / day p.o. for 3 - 6 months (no longer mentioned in the latest guideline)
• Mast cell stabilizers (low evidence): In case of additional intestinal intolerance reactions, success with disodium cromoglicic acid (4 x daily 200 mg or 400 mg 15-30 min before exposure) has been described.
• Casuistic (low evidence): Successes have been described with high-dose intravenous immunoglobulin therapy(IVIG).
• Casuistic: Plasmapheresis / immunoadsorption (low evidence). Last but not least, chronic urticaria in its pronounced form, especially after failure of other therapeutic approaches, is an indication for plasmapheresis or immune adsorption. The method appears to be particularly successful in patients in whom autoantibodies against the high-affinity part of IgE (α chain) have been detected. By binding to the IgE receptor, these AK cause degranulation and histamine release, e.g. on the surface of basophils or mast cells. In addition, this finding offers the possibility of a cost-saving reduction in the time-consuming diagnostics for some patients. At the same time, the high costs of the procedure should be noted!
• Not recommended for long-term therapy: glucocorticoids (no longer listed in the guidelines or considered obsolete): Glucocorticoids in medium doses are usually very effective in the case of pronounced findings and pronounced, therapy-resistant symptoms(pruritus). Glucocorticoids are indicated for intermittent flare activity. Prednisolone (e.g. Solu Decortin H) initially 40 - 60 mg / day i.v., gradual dose reduction to the lowest possible maintenance dose and switch to oral administration. Caution! The maintenance dose should be below the Cushing's threshold. Gastric protection is required for oral administration.
• Therapy during pregnancy: Nothing is known about H1-AH-related fruit damage. If treatment is necessary in pregnant women or nursing mothers, loratadine or cetirizine should be used in the usual dosage; the best evidence is available for loratadine. No safety data are available for H1-AH high-dose therapy.

• Week 1:
• Nystatin Drg. 3 times/day 2 Drg.
• Ozovit powder: 2 times/day 2 measuring spoons.
• Week 2-4:
• Markalact powder: 2 times/day 3 teaspoons.
• Amara drops Pascoe: 2 times/day 10 trp.
• Hepar-Pasc 100: 2 times/day 2 tbl.
• week 5-12:
• Markalakt powder: 2 times/day 3 teaspoons.
• Hepar-Pasc 100: 2 times/day 2 tbl.
• Amara mixture: 2 times/day 30 trp. of the mixture of 25 ml Amara drops of Pascoe/20 ml Pascoepankreat Novo drops/20 ml Quassia Similiaplex drops.
• MDS: 2 times/day 30 trp.

Three-step programme of urticaria diagnostics

Urticaria diagnostics (proposal for an in-patient diagnostic programme)

Urticaria basic diet (tea-potato-rice diet)

Oligo-Allergenic Basic Diet

Build-up diet1

Provocation diet: Food rich in additives

Provocation diet - Salicylate-rich food: Without colouring, without seasoning

Provocation Day - Biogenic Amines

Oral provocation test for idiosyncrasy (OPTI)

Rules of thumb for differentiating between allergic and pseudoallergic reactions (according to Ring J, Applied Allergology, MMW)

Low salicylate diet (with proven ASS intolerance)

Low pseudoallergen diet

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6. Guidelines of the German Dermatological Society (DGG) (2006) AWMF Guidelines Register No. 013/013
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