Chronic spontaneous urticaria L50.8

Autoimmuneurticaria lasting longer than 6 weeks (in many cases, the condition persists for more than 5 years). A distinction is made based on the clinical course:

• chronic-continuous spontaneous urticaria with daily flare-ups
• chronic-recurrent spontaneous urticaria with a relapsing course (in which episodes of hives alternate with symptom-free intervals)

The term “spontaneous” or “idiopathic” urticaria refers to its unknown etiology and contrasts withchronic inducible urticaria ( causes are known or easily identified, 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 cases are idiopathic.
• About one-quarter of patients havea history of atopy; totalIgE is elevated in more than 50% of cases.
• The model of molecular mimicry of epitopes as a possible trigger of chronic urticaria is a recurring topic of discussion. This model is based, for example, on the transient presence of various antibodies (e.g., thyroid autoantibodies TAK/TPO) as well as on a transient or persistent susceptibility to non-immunological hypersensitivity reactions (e.g.,intolerance reactions characterized by non-IgE-mediatedhistamine release ).
• Depending on the type of urticaria, a wide variety of triggers may be involved:
  • medications or foods (non-IgE-mediated; see alsointolerance reaction; biogenic amines)
  • Food additives: colorants, benzoates, salicylates, sulfites, glutamates (non-IgE-mediated); the evidence on this is contradictory; causative in < 5% of patients)
  • Acetylsalicylic acid: no association with foods containing salicylates (non-IgE-mediated)
  • Foods (IgE-mediated Type I inflammation) or contaminants (e.g., antibiotic residues in meat): Such reactions are relatively rare (< 1% in children and adults).  
  • Bacterial infections (Helicobacter pylori [the strongest evidence exists for this mode of infection], streptococci, staphylococci, Yersinia); For infections in the dental and ENT areas, there are no established links between treatment and the course of urticaria, although such links have been postulated in individual cases.
  • Viral infections (reports of hepatitis virus infections and norovirus infections exist [no convincing evidence to date])
  • Parasites (Giardia, Entamoeba,helminth infections; Trichomonas, Trichinella, Toxocara canis)
  • Autoimmune processes (autologous serum test, thyroid autoantibodies—seeautoreactive 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.

Recurrent or persistent, raised, sharply defined, palpable, solitary or confluent, whitish to red, itchy, flat, transient skin elevations (wheals) of varying sizes (0.2–10.0 cm), often combined with angioedema.

In 52% of cases, the disease course is chronic and recurrent, with symptoms that can be highly distressing and unpredictable. These symptoms can severely impair patients’ quality of life. In this context, an increased rate (ranging from 35% to 50% of the total population, depending on the literature) of psychiatric comorbidities—such as anxiety disorders, depression, and somatoform disorders—can be explained. 

Determination of RAST classes, possibly ANA, rheumatoid factors, thyroid gland antibodies (according to medical history).

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.

Urticarial vasculitis; urticarial or maculo-papular drug exanthema

Elimination or avoidance of triggering factors following a thorough medical history and diagnostic evaluation.

• Identification of the source: Treatment of a chronic source or management of the underlying disease (e.g., antibiotic or surgical treatment of dental and ENT sources [no established evidence]; eradication of Helicobacter pylori [high level of evidence], treatment of Candida infections [no conclusive evidence]; see alsocandidiasis, enteric, etc.)
• If caused by a parasite: appropriate therapy
• Medications: Discontinuation or substitution of potentially causative medications (e.g.,analgesics,antibiotics such aspenicillin,acetylsalicylic acid, insulin, vaccinations)
• If foods or additives are suspected as triggers and other triggering factors have been ruled out, a standardized, pseudoallergen-free basic diet (see Table 4) for 4–6 months is recommended. 70% of patients experience significant improvement, up to and including complete remission (placebo effect?). During the diet, a food diary and symptom log should be maintained, and the severity of the urticaria should be assessed. Approximately 50% of patients can tolerate a normal diet again after six months on the diet.

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 treatment, see“Urticaria” below (the treatment options listed here are based in part on the results of small studies or personal experience).

Conventional systemic therapies:

• Antihistamines: Oral administration of second-generation non-sedating antihistamines (H1 blockers) such asloratadine10 mg (e.g., Lisino), 1 tablet once daily by mouth; desloratadine5 mg (e.g., Aerius) 1 tablet orally once daily,cetirizine10 mg (e.g., Zyrtec) 1 tablet once daily by mouth, orlevocetirizine5 mg (Xusal) 1 tablet once daily by mouth. If treatment fails (after 14 days), switch to high-dose antihistamine therapy:
• High-dose antihistamine therapy: If the response is inadequate, individually tailored dose increases (e.g., desloratadine in escalating doses up to four times the standard dose) may be used.
• Sedating antihistamines (this treatment approach is considered outdated by many authors). Particularly for inpatients, sedating antihistamines such ashydroxyzine (e.g.,^Atarax®), 1–3 tablets per day, may be considered at night.

Alternative combinations: 

• The response to the various H1 blockers varies greatly from person to person; therefore, the success of their combinations must be evaluated on a case-by-case basis. Different H1 blockers can be combined in dual combinations (e.g., levocetirizine and fexofenadine) or in triple combinations (levocetirizine and fexofenadine, as well as levocetirizine at double the standard dose). Combinations with H2 receptor blockers such ascimetidine (e.g., Tagamet) 400–800 mg/day orranitidine (e.g., Sostril) 300 mg once daily or 150 mg twice daily by mouth

• Combinations of H1 blockers with a leukotriene antagonist (e.g.,montelukast), particularly in patients with concomitant angioedema

• Combination of an H1-AH (e.g., desloratadine 10 mg/day) withdapsone (50–150 mg/day)

Alternative systemic therapies:  

• Omalizumab(^Xolair®): Approved since 2014 for the treatment of (treatment-resistant) chronic spontaneous urticaria. Dosage: 300 mg subcutaneously every 28 days. Clinical efficacy has been demonstrated in several studies (Staubach P et al. 2016). 
• Dupilumab (^Dupixent®): Approved for CsU in patients aged 2 years and older. May be used if symptoms cannot be adequately controlled with conventional H1 antihistamines and no prior anti-IgE therapies (such as omalizumab) have been administered. Initial dose for adults: 600 mg subcutaneously (s.c.), followed by 300 mg every 2 weeks (q2w).
• Remibrutinib (^Rhapsido®): BTK inhibitor (Bruton’s tyrosine kinase inhibitor) approved for patients 18 years of age and older; dose: 25 mg twice daily. Increased risk of bleeding during therapy.
• Barzolovimab: blocks the KIT receptor tyrosine kinase, which is essential for the function and survival of mast cells.
• Rupatadine (antiallergic agent with antihistamine and PAF-blocking effects):Rupatadine (e.g.,^Rupafin®) 10 mg/day orally.
• Cyclosporine (strong evidence) (2.5 mg/kg body weight orally in 2 divided doses). However, cyclosporine should only be used in cases of severe, completely treatment-resistant chronic urticaria, possibly in combination with an H1 antihistamine. 
• Case reports:Dapsone (limited evidence): 50–100 mg/day orally for 3–6 months (no longer mentioned in the latest guidelines)  
• Mast cell stabilizers (limited evidence): In cases of additional intestinal intolerance reactions, success has been reported withdisodium cromoglicic acid (200 mg 4 times daily or 400 mg 15–30 minutes before exposure).
• Case reports (limited evidence): Success has been reported with high-dose intravenous immunoglobulin therapy (IVIG).
• Case reports:Plasmapheresis/ immunoadsorption (low evidence). Not least, chronic urticaria in its severe form—especially after failure of other therapeutic approaches—constitutes an indication for plasmapheresis or immunoadsorption. The method appears to be particularly successful in patients in whom autoantibodies against the high-affinity portion of IgE (α-chain) have been detected. These autoantibodies cause degranulation and histamine release by binding to the IgE receptor, e.g., on the surface of basophils or mast cells. Furthermore, this finding offers the possibility of a cost-saving reduction in the need for extensive diagnostic testing in some patients. At the same time, it is important to note the high cost of the procedure!
• Not recommended for long-term therapy:Glucocorticoids (are no longer listed in the guidelines or are considered outdated): In cases of pronounced findings and severe, treatment-resistant symptoms (pruritus), glucocorticoids in moderate doses are usually very effective. Glucocorticoids are indicated for intermittent flare-ups. Prednisolone (e.g., Solu Decortin H): initial dose 40–60 mg/day IV, followed by gradual dose reduction to the lowest possible maintenance dose and switch to oral administration. Caution!The maintenance dose should remain below the Cushing’s threshold. Gastric protection is required when administered orally.
• Treatment during pregnancy: There are no known reports of fetal harm associated with H1-AH. If treatment is necessary in pregnant or breastfeeding women, loratadine or cetirizine should be used at the usual dosage; the best evidence is available for loratadine. No safety data are available for high-dose H1-AH therapy.    

The course of chronic urticaria varies. If the clinical signs are only mild, the disease usually heals within 24 months. In moderate to severe cases, healing occurs in only 50% of cases. 30% of these patients suffer > 60 months from relapses of the disease.

Biological Urticaria 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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