S. Altrichter

Anti-Immunoglobulin E Treatment of Patients with Recalcitrant Physical Urticaria

In physical urticaria, exogenous physical factors such as thermal triggers, solar radiation and mechanic triggers including friction or pressure are responsible for the elicitation of symptoms in the skin of patients. Avoidance of the respective stimulus is usually difficult or impossible, and many patients are not sufficiently treated with standard antihistamines. We report that treatment with omalizumab (Xolair®) of 7 patients with physical urticarias [solar urticaria (n = 2), urticaria factitia/symptomatic dermographism (n = 2), cold urticaria, delayed pressure urticaria and localized heat urticaria] resulted in complete symptom control within days after the first injection in 5 patients. In 1 patient, symptoms improved after increasing the dose of omalizumab, and 1 patient with localized heat urticaria did not respond significantly to treatment. Before anti-immunoglobulin E treatment, all patients had suffered from their physical urticaria for years and had had numerous unsuccessful therapies. The overall excellent responses to omalizumab treatment reported here indicate that anti-immunoglobulin E is a safe and effective treatment for recalcitrant physical urticarias.

The definition, diagnostic testing, and management of chronic inducible urticarias - The EAACI/GA(2) LEN/EDF/UNEV consensus recommendations 2016 update and revision.

These recommendations for the definition, diagnosis and management of chronic inducible urticaria (CIndU) extend, revise and update our previous consensus report on physical urticarias and cholinergic urticaria (Allergy, 2009). The aim of these recommendations is to improve the diagnosis and management of patients with CIndU. Our recommendations acknowledge the latest changes in our understanding of CIndU, and the available therapeutic options, as well as the development of novel diagnostic tools.

Efficacy and safety of the interleukin-1 antagonist rilonacept in Schnitzler syndrome: an open-label study

Schnitzler syndrome (SchS) is a rare disease with suspected autoinflammatory background that shares several clinical symptoms, including urticarial rash, fever episodes, arthralgia, and bone and muscle pain with cryopyrin‐associated periodic syndromes (CAPS). Cryopyrin‐associated periodic syndromes respond to treatment with interleukin‐1 antagonists, and single case reports of Schnitzler syndrome have shown improvement following treatment with the interleukin‐1 blocker anakinra. This study evaluated the effects of the interleukin‐1 antagonist rilonacept on the clinical signs and symptoms of SchS.

Interleukin‐31 does not induce immediate itch in atopic dermatitis patients and healthy controls after skin challenge

The most intriguing function attributed to interleukin‐31 (IL‐31) is its ability to induce pruritus in pathologic conditions, such as atopic dermatitis (AD). As of today, this feature of IL‐31 was tested in vivo only in animal models.

Anaphylaxis caused by mosquito allergy in systemic mastocytosis

In the summer of 1996, a 56-year-old man was bitten on his arm by a mosquito in his garden in Bavaria, Germany. About 15 min later he had diarrhoea, felt nauseous, and lost consciousness. He was bitten again by a mosquito in May, 2001, and August, 2001. Following the bite in August, 2001, the reaction developed rapidly, and he immediately lost consciousness and went into cardiac arrest before the ambulance arrived. Because of delayed resuscitation, he had hypoxic brain damage to the basal ganglia, resulting in spastic tetraplegia. Red-brown maculo papular skin lesions were seen on his upper legs and a skin biopsy showed increased mast cell numbers. In 2006, he was bitten a fourth time by a mosquito. Despite immediate adminis tration of rescue medi cation consisting of epinephrine, H1-antihistamine, and corticosteroid, he again had a severe reaction and cardiac arrest. In 2012, the patient was referred to the depart ment of dermatology and allergy, Charite—Universitatsmedizin Berlin, Germany, for further investigation. On the basis of the history of maculopopular skin lesions and increased mast cell numbers on skin biopsy, we suspected systemic mastocytosis. WHO diagnostic criteria for systemic mastocytosis were confi rmed. Despite having only slightly raised serum tryptase of 11·5 μg/L (normal range <11·4 μg/L), bone marrow exam ination showed spindle shaped mast cells expressing CD25, and the typical Kit-mutation (D816V) was detected by PCR of peripheral blood leucocytes. From the pat ient’s description of the appearance of the mosquitoes that bit him, and knowledge of the geographic region where the incidents occurred, Culex pipiens was identifi ed by an expert from the Bernhard Nocht Institute, Hamburg, Germany, as the most likely of the 100 known mosquito species in central Europe to be responsible for inducing such reactions. As an alternative possibility, the patient’s skin prick test reaction and basophil release in response to Aedes communis, another common European species, was also tested. Total serum IgE of 48·4 kU/L was within normal range (<100 kU/L). ImmunoCAP (ThermoFisher, Uppsala, Sweden) failed to detect mosquito-specifi c IgE. Measurement of serum Culex pipiens-specifi c IgE by indirect ELISA showed no diff erence between the patient and four healthy controls (patient 0·067 optical density; controls 0·049, 0·05, 0·106 and 0·082; blank 0·062). To test for functional reactivity to mosquito allergens, skin prick testing was done on the patient and in healthy controls. Additionally, the patient showed a very strong basophil activation response to Culex pipiens and a weaker response to Aedes communis (appendix). Previous studies have shown that desensitisation treatment of individuals with strong local immediate or delayed reactions to mosquito bites are eff ective and safe. However we did not consider immunotherapy as a therapeutic option in this patient because of his un predictable and severe reactions to mosquito bites. Instead he is taking desloratadine 5 mg daily prophylactically and is meticulously avoiding mosquitoes. He is also equipped with emergency medication including epinephrine, H1-antihistamine, and cortico steroid. The patient was instructed to carry two epinephrine autoinjectors at all times. We have also off ered him prophylactic treatment with omalizumab during the mosquito season (usually April–October). Omalizumab had a protective eff ect against severe anaphylactic reactions in a masto cytosis patient who had had several near-fatal anaphylactic reactions to bee stings. Anaphylaxis to mosquito bite has been previously reported but at present remains unexplained. The unique nature of this case of a grade IV allergic reaction to mosquito bites is that a clonal mast cell disorder was identifi ed as concomitant disease without remark able increase in serum tryptase. Unidentifi ed mosquito allergy could be an underestimated cause of anaphylaxis, especially in combination with occult systemic mastocytosis.

[Chronic urticaria. Prevalence, course, prognostic factors and impact].

Chronic urticaria (CU) is one of the most frequent diseases in the field of dermatology. Recent studies have shown a point prevalence between 0.5 and 1% in the total population with a predominance of females. In general, all age groups and all classes of the population can be affected. An incidence peak has been found in the third and fourth decades. According to the current guidelines, CU is characterized by the spontaneous occurrence of wheals and/or angioedema for more than 6 weeks. However, epidemiological studies have revealed that the majority of patients suffer for several months, or frequently years. Disease duration is likely to be longer in case of angioedema, a combination with physical urticaria, positivity in the autologous serum skin test (autoreactivity) and a high disease severity. Studies on the impairment of quality of life have been shown that many CU patients suffer as strong from their disease as patients with coronary artery disease. Apart from pure physical symptoms, patients experience restrictions in daily life activities and social life. In addition, sleep disturbances are common and CU patients frequently exhibit psychiatric comorbidities. To avoid frustration in care, it is important to perceive all different dimensions of CU that impact the patients life and to take the patients and their disease seriously. The aim of therapy should be to obtain total symptom control.

H1-antihistamine up-dosing in chronic spontaneous urticaria: patients' perspective of effectiveness and side effects--a retrospective survey study.

Background The guidelines recommend that first line treatment of chronic spontaneous urticaria should be second generation non-sedating H1-antihistamines with a positive recommendation against the use of old sedating first generation antihistamines. If standard dosing is not effective, increasing the dosage up to four-fold is recommended. The objective of this study was to obtain the chronic spontaneous urticaria-patient perspective on the effectiveness and unwanted effects of H1-antihistamines in standard and higher doses. Methodology/Principal Findings This was a questionnaire based survey, initially completed by 368 individuals. 319 (248 female, 71 male, median age 42 years) had a physician-confirmed diagnosis of chronic spontaneous urticaria and were included in the results. Participants believed standard doses (manufacturers recommended dose) of second generation antihistamines to be significantly (P<0.005) more effective than first generation drugs. Furthermore, they believed that second generation drugs caused significantly (P<0.001) fewer unwanted effects and caused significantly (P<0.001) less sedation than first generation antihistamines. Three-quarters of the patients stated that they had up-dosed with antihistamines with 40%, 42% and 54% reporting significant added benefit from taking 2, 3 or 4 tablets daily respectively. The number of reports of unwanted effects and sedation following up-dosing were not significantly different from those reported for standard doses. Conclusions This survey supports the urticaria guidelines recommendations that the first line treatment for chronic spontaneous urticaria should be second generation rather than first generation H1-antihistamines and that, if standard dosing is not effective, the dosage should be increased up to four-fold.

Matrix metalloproteinase‐9: a novel biomarker for monitoring disease activity in patients with chronic urticaria patients?

Background:  Matrix metalloproteinase (MMP)‐9, an enzyme that contributes to inflammatory responses and subsequent tissue remodelling, has recently been suggested to be a good biomarker for monitoring disease activity in patients with chronic urticaria (CU). Here, we assessed whether total MMP‐9 and/or active MMP‐9 plasma levels are increased and correlated to disease activity in patients with CU.

Comorbidity of chronic spontaneous urticaria and autoimmune thyroid diseases: A systematic review

Patients with chronic spontaneous urticaria (CSU) are widely held to often have other autoimmune disorders, including autoimmune thyroid disease. Here, we systematically evaluated the literature on the prevalence of thyroid autoimmunity in CSU and vice versa. There is a strong link between CSU and elevated levels of IgG antithyroid autoantibodies (AAbs), with most of a large number of studies reporting rates of ≥10%. Levels of IgG against thyroid peroxidase (TPO) are more often elevated in CSU than those of other IgG antithyroid AAbs (strong evidence). Levels of IgG antithyroid AAbs are more often elevated in adult patients with CSU than in children (strong evidence). Patients with CSU exhibit significantly higher levels of IgG antithyroid AAbs (strong evidence) and IgE‐anti‐TPO (weak evidence) than controls. Elevated IgG antithyroid AAbs in CSU are linked to the use of glucocorticoids (weak evidence) but not to disease duration or severity/activity, gender, age, or ASST response (inconsistent evidence). Thyroid dysfunction rates are increased in patients with CSU (strong evidence). Hypothyroidism and Hashimotos thyroiditis are more common than hyperthyroidism and Graves’ disease (strong evidence). Thyroid dysfunction is more common in adult patients with CSU than in children (strong evidence) and in female than in male patients with CSU (weak evidence). Urticaria including CSU is more prevalent in patients with thyroid autoimmunity than in controls (weak evidence). CSU can improve in response to treatment with levothyroxine or other thyroid drugs (strong evidence). Pathogenic mechanisms in CSU patients with thyroid autoimmunity may include IgE against autoantigens, immune complexes, and complement.

An improved Peltier effect‐based instrument for critical temperature threshold measurement in cold‐ and heat‐induced urticaria

Cold‐ and heat‐induced urticaria are chronic physical urticaria conditions in which wheals, angioedema or both are evoked by skin exposure to cold and heat respectively. The diagnostic work up of both conditions should include skin provocation tests and accurate determination of critical temperature thresholds (CTT) for producing symptoms in order to be able to predict the potential risk that each individual patient faces and how this may be ameliorated by therapy.