Urticaria chronic spontaneous L50.8

Urticaria persisting for 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-recurrent spontaneous urticaria with an intermittent course, in which wheal attacks alternate 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 below. urticaria)

S.u. Urticaria

• Up to 70% of the disease is idiopathic.
• Positive atopy history exists in about 1/4 of patients. Total IgE is elevated in > 50% of cases.
• The model of molecular mimicry of epitopes as a possible trigger of chronic urticaria is discussed again and again. The model is based e.g. on the transient presence of various antibodies (e.g. thyroid autoantibodies TAK/TPO) as well as transient 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 come into question:
  • Drugs or foods (non-IgE-mediated; see also intolerance reaction; biogenic amines).
  • Food additives: dyes, benzoates, salicylates , sulfites, glutamates (non-IgE-mediated); data on this are 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 etc.): such reactions are rather rare (< 1% in children and adults)
  • Bacterial infections (Helicobacter pylori [for this mode of infection there is the highest evidence], streptococci, staphylococci, yersinia); for infections in the dental and ENT area, there are no confirmed correlations between therapy and urticaria course, although in individual cases these correlations are postulated.
  • Viral infections (reports on hepatitis virus infections and norovirus infections are available [no convincing evidence so far]).
  • parasites (lamblia, entamoeba, worm infections; trichomonads, trichinella, Toxocara canis)
  • Autoimmune processes (autologous serum test, thyroid autoantibodies - see autoreactive urticaria)
  • Rarely: tumors, hepatitis.

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

• • Advanced diet
  • Additiva rich diet
  • Salicylate-rich diet
  • 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. as pseudoallergic reactions (especially acetylsalicylic acid). An antigen-antibody reaction does not take place in these reactions. IgE cannot be detected in increased quantities. RAST determinations in this sense are therefore not possible. Pseudo-allergic 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 substantiate the suspicion.
• Salicycylate: Acetylsalicylic acid is the most common substance that can trigger an intolerance reaction. The pathomechanism has not yet been clearly clarified. Inhibition of cyclooxygenase is being discussed, which leads to a lack of protective prostaglandins and to increased formation of lipoxygenase metabolites or can cause direct mediator release, direct complement activation and altered platelet reactivity. There are pronounced cross-reactions with pharmacologically similar acting agents, e.g. other NSA, but also with other chemicals such as food dyes (tartrazine) and preservatives. If an intolerance reaction to ASA is known, Coxibe (e.g. Celecoxib) can be given if necessary.

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

• Focus search: Remediation of a chronic focus or treatment of the underlying disease (e.g. antibiotic or surgical treatment of dental and ENT foci [no firm evidence]; eradication of Helicobacter pylori [high level of evidence], treatment of candida infections [no firm evidence]; see also candidiasis, enteritis, etc.).
• In case of parasitic cause: adequate therapy.
• Medications: Discontinuation or conversion of possibly causative medications (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 the patients are clearly improved or free of symptoms(placebo effect?). During the diet, a food/complaint protocol including an assessment of urticaria severity should be performed. About 50% of the patients tolerate whole food again after 6 months of diet.

Blande, itch-killing local therapy e.g. Optiderm Lotion, Tannolact Lotio, 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 . If necessary topical glucocorticoids as lotio (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 also personal experience).

• Antihistamines: Oral administration of non-sedating antihistamines (H1 blockers) of the 2nd generation such as loratadine 10mg (e.g. Lisino) 1 tbl. p.o. 1 time/day, desloratadine 5mg (e.g. Aerius) 1 tbl. p.o. 1 time/day, Cetirizine 10mg (e.g. Zyrtec) 1 time/day 1 tbl. p.o. or Levocetirizine 5mg (Xusal) 1 time/day 1 tbl. p.o. In case of therapy failure (after 14 days) change to antihistaminic high-dose therapy:
• Antihistaminic high-dose therapy: If response is insufficient, individually adjusted dose increases (e.g., desloratadine in increasing doses up to 4 times the standard dose) may be used.
• Alternative: Combinations: The response to the different H1 blockers varies greatly from individual to individual, therefore the success of their combination is equally variable. Different H1 blockers can be combined in double combinations (e.g., levocetericin and fexofenadine) or in triple combinations (levocetericin and fexofenadine plus levocetericin at twice the standard dose. Combinations with H2 receptor blockers such as cimetidine (e.g. Tagamet) 400-800 mg/day or ranitidine (e.g. Sostril) 1 time/day 300 mg or 2 times/day 150 mg p.o. have also been successfully described.
• Alternative: omalizumab (Xolair): Approved in (refractory) chronic spontaneous urticaria since 2014. Dosage 300mg/s.c. every 28 days. Clinical efficacy has been demonstrated in several studies (Staubach P et al. 2016).
• Alternative: Sedating antihistamines (therapeutic principle is considered obsolete by many authors). Especially in hospitalized patients, sedating antihistamines such as hydroxyzine (e.g. Atarax®) 1-3 tbl./day may be considered at night.
• Alternative: Anti-allergic drugs with antihistaminic and PAF-blocking effect such as rupatadine (e.g. Rupafin) 10 mg/day p.o.
• Alternative: combinations 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 refractory chronic urticaria, gfls. 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): For additional intestinal intolerance reactions, success with disodium cromoglicic acid (4 times/day 200 mg or 400 mg 15-30 min before exposure) is described.
• Casuistic (low evidence): Successes with high-dose intravenous immunoglobulin therapy(IVIG) have been described.
• Casuistic: Plasmapheresis/immunadsorbtion(low evidence): Last but not least, chronic urticaria in its pronounced form, especially after failure of other therapeutic approaches, represents an indication for plasmapheresis or immunadsorbtion. The method seems to be particularly successful in patients in whom autoantibodies against the high affinity part of IgE (α-chain) have been detected. These AK cause degranulation and histamine release via binding to the IgE receptor, e.g. at the surface of basophils or mast cells. Furthermore, this finding offers the possibility of a cost-saving reduction of the complex diagnostics in a part of the patients. At the same time, the high costs of the procedure must be pointed out!
• 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 cases of pronounced findings and pronounced, therapy-resistant symptoms(pruritus). Glucocorticoids are indicated for intermittent relapsing activity. Prednisolone (e.g. Solu Decortin H) initially 40-60 mg/day i.v., gradual dose reduction to lowest possible maintenance dose and switch to oral administration. Caveat. Maintenance dose should be below Cushing's threshold. Gastric protection is required for oral use.
• Therapy in pregnancy: Nothing is known about H1-AH-induced fertility damage. If treatment of pregnant women or nursing mothers is necessary, loratadine or cetericine in usual dosage should be used. The best study results are 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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