Comparison and interpretability of the available urticaria activity scores.

The urticaria activity score (UAS) is the gold standard for assessing disease activity in patients with chronic spontaneous urticaria (CSU). Two different versions, the UAS7 and UAS7TD , are currently used in clinical trials and routine care. To compare both versions and to obtain data on their interpretability, 130 CSU patients applied both versions and globally rated their disease activity as none, mild, moderate, or severe. UAS7 and UAS7TD values correlated strongly (r = .90, P < .001). Interquartile ranges for UAS7 and UAS7TD values for mild, moderate, and severe CSU were 11-20 and 10-24, 16-30 and 16-32, and 27-37 and 28-40. UAS7 values were slightly, but significantly lower as compared to UAS7TD values (mean difference: 1.6 ± 4.6, P < .001). This difference was driven by lower wheal subscores (2.1 ± 3.5, P < .001) and was most pronounced in patients with severe CSU (2.5 ± 5.6, P < .01). The UAS7/UAS7TD ratio was 0.96 ± 0.21 and did not differ significantly between mild, moderate, and severe CSU. Since the results of both UAS versions are comparable, we recommend the use of the UAS7, which is less burdensome in administration and scoring.

Increased angiogenesis and VEGF expression correlates with disease severity in prurigo patients.

BACKGROUND: Vascular endothelial growth factor-A (VEGF-A) is known as the major skin angiogenesis factor and can be produced by various resident skin cells including keratinocytes. OBJECTIVES: To identify and characterize the role of VEGF-A in the pathogenesis of prurigo. METHODS: Expression of VEGF, VEGFR2, CD-31, and D2-40 was analyzed in the skin of eleven prurigo patients and seven healthy controls by immunohistochemistry. RESULTS: VEGF immunoreactivity (IR) was markedly increased in the epidermis, dermis and subcutis of prurigo patients, whereas expression of the main receptor for VEGF-A in the skin, VEGFR2, was comparable to that of healthy controls. The increased VEGF expression in the skin was associated with a marked increase in the number (12.8 ± 2.1 vs 5.6 ± 0.5, P < 0.05) but not in the size of blood vessels, as assessed by staining of the endothelial cell marker CD31. This increase in small blood vessels correlated closely with increases in the epidermal thickness in prurigo lesions. The number of lymphatic vessels as assessed by D2-40 staining was found to be similar in prurigo patients and healthy controls. CONCLUSIONS: Based on these findings, we speculate that the observed profound vascular remodelling in prurigo might contribute to the pathogenesis of prurigo and the corresponding clinical symptoms and that targeting of VEGF may present a novel therapeutic strategy in the treatment of prurigo patients.

Validation of a simplified provocation instrument for diagnosis and threshold testing of symptomatic dermographism.

BACKGROUND: Symptomatic dermographism is a common urticarial condition, which requires determination of provocation thresholds to confirm diagnosis and allow physicians to individualize management and therapy for optimal control of symptoms. To determine provocation thresholds, we have developed a provocation test device, the FricTest(®) 4.0. This simple and inexpensive device, which is stroked across the skin to produce a response, consists of a flat plastic comb with four round-ended plastic pins, 3 mm in diameter, and of differing lengths. AIM: To validate the FricTest(®) 4.0 by comparison with FricTest 3.0 in determining provocation thresholds in symptomatic dermographism, METHODS: Dermal provocation with the FricTest 4.0 and FricTest 3.0 was performed in parallel on the volar forearm of 30 patients with symptomatic dermographism and 30 healthy controls. The widths of the resulting weals were measured, and weals with a width of ≥ 3 mm were considered positive. Accompanying pruritus was assessed using a 10-point verbal rating scale. RESULTS: All 30 patients with symptomatic dermographism, but none of the healthy volunteers, showed positive responses to provocation with the strongest trigger strength, showing that FricTest(®) 4.0 has 100% sensitivity and specificity for diagnosing symptomatic dermographism. Quantitatively, both devices were similar in the number of patients who responded positively to different pin lengths. Results for pruritus were also similar with both instruments. CONCLUSIONS: The FricTest 4.0 is a simple and inexpensive instrument for determining provocation thresholds in patients with symptomatic dermographism. It should find a place in both routine clinical investigation and in therapeutic trials.

Symptomatic dermographism: an inadequately described disease.

BACKGROUND: Symptomatic dermographism is the most common form of physical urticaria with a prevalence of 2-5%. However, its clinical picture has rarely been described. OBJECTIVE: To understand more of patients' views about the practical aspects of their condition, its cause and impact on quality of life. METHODS: Ninety-one of 150 patients with symptomatic dermographism from our specialist urticaria clinic completed a 38-question questionnaire sent them by mail. RESULTS: The mean duration of disease was 6» years. In most patients, the condition was continuous, but ~25% had prolonged symptom-free phases. Severity was evaluated as moderate in 45%, severe in 33% and very severe in 6% of respondents. Other responses included: symptoms worse in the evening in 81%; quality of life significantly impaired in 44%; normal life not possible 7%; stress induces acute episodes 44%; other urticarial forms coexist 21%; allergy coexist 48%. A family history was reported in 14%. Almost all patients were taking H1 -anti-histamines, 49% getting marked improvement and 23% becoming symptoms free. LIMITATIONS: It is a survey only of patient opinions. CONCLUSIONS: This questionnaire survey confirmed that symptomatic dermographism is a debilitating condition with profound effects on quality of life but its underlying cause and disease mechanisms remain obscure.

[Chronic spontaneous urticaria: An autoimmune disease?]. / Chronische spontane Urtikaria: Eine Autoimmunerkrankung?

The identification of the causes of chronic spontaneous urticaria (CSU) is difficult. The recognition of functional autoantibodies against FcεRI and/or against IgE in some patients with CSU led to the concept of autoimmune etiology of the disease. Clinical and laboratory features in a subpopulation of CSU patients also point to an autoimmune etiology of the disease. This review will present and discuss the relevance of functional autoantibodies in CSU pathogenesis and their implications for treatment and prognosis.

Selected urticaria patients benefit from a referral to tertiary care centres--results of an expert survey.

BACKGROUND: Urticaria is a frequent reason for consultations. Recently, it has been demonstrated that the management of chronic spontaneous urticaria (csU) in the practice setting does not fully comply with published guidelines. In addition, it was shown that one of four csU patients is referred to specialized centres. OBJECTIVE: To analyse the management of urticaria patients in tertiary referral centres. METHODS: During a standardized expert-to-expert interview, 41 specialists from German tertiary care centres were asked for different aspects of urticaria patient care with a special focus on csU. RESULTS: On average, the participating centres saw 25 csU patients per month. All ran programmes for the identification of underlying causes with an average success rate of 45 ± 3% which is considerably higher as has been found in the practice setting. In those patients where an identification succeeds, infections, drugs, intolerance and autoreactivity were reported to be causes in 41%, 20%, 17% and 16%. In their symptomatic treatment the majority of centres (71%) followed the guidelines by using regular dosed non-sedating H(1)-antihistamines as first line and higher doses (61%) as second line option. In contrast to the practice setting, meaningful experience also existed for alternative therapies in antihistamine-resistant patients, such as dapsone, cyclosporin and omalizumab. The expenditure of time, laboratory costs and frequency of follow-up visits was reported to be above average in case of csU. CONCLUSION: This study indicates that some urticaria patients, especially those with unknown causes or with an H(1)-antihistamine-resistant disease, may benefit from a referral to tertiary care centres.

Effects of topical treatment with the raft modulator miltefosine and clobetasol in cutaneous mastocytosis: a randomized, double-blind, placebo-controlled trial.

Background Mastocytosis is characterized by the accumulation and activation of mast cells in different organs, most commonly the skin. Miltefosine, a raft modulator, has recently been shown to inhibit the activation of mast cells and to reduce mast cell-driven skin inflammatory responses. Objectives To study the safety and efficacy of topical miltefosine treatment of skin lesions in patients with mastocytosis. Methods Thirty-nine adult patients with mastocytosis with skin involvement were treated in a double-blind, placebo-controlled, parallel trial with topical miltefosine and clobetasol for 2 weeks. Treatment areas were analysed for changes in skin lesions and symptoms following mechanical irritation using novel volumetric imaging techniques and quantitative histomorphometry. Results Miltefosine and clobetasol failed to reduce significantly weals and flare-type skin responses following mechanical provocation. Miltefosine showed a trend towards reducing the volume of weals. Clobetasol significantly decreased the volume of weals and the number of mast cells in the upper dermis. Treatment with miltefosine, but not with clobetasol, was often associated with eczematous skin irritation, which may, at least in part, be related to the formulation of miltefosine containing the potentially irritating alkanol propanediol as the vehicle. Conclusions Raft modulators such as miltefosine are promising candidates for novel therapeutic strategies in patients with cutaneous mastocytosis. Future studies should be performed with improved formulations using nonirritant vehicles.