The cutoff time of 8 days between fast and slow responders was chosen because it corresponds with the peak plasma level of omalizumab after its initial injection.3 We hypothesized that a slow ...response to omalizumab occurs in patients with CSU in whom IgG antibodies to unoccupied IgE receptors (FcepsilonRI) activate mast cell mediator release to cause wheal and angioedema formation.4 This hypothesis is based on the knowledge that omalizumab first complexes soluble IgE then sequesters IgE released from mast cells, thus uncovering membrane FcepsilonRI, which subsequently decays slowly over several weeks.5 To test this, the basophil histamine release assay (BHRA) was used. Quantification of free serum IgE, IgE neutralization, and omalizumab concentrations A commercially available recoveryELISA kit was used for the quantification of free IgE, IgE neutralization rates, and omalizumab levels in patient serum (BioTeZ Berlin Buch GmbH, Berlin, Germany) as described previously.E4 Characteristic All complete responders (n = 56) Complete response within 8 d Complete response after 8 d P value Age (y) 48 (33-60) 49 (37-58) 42 (31-63) .544 Sex Female 40 (71.4%) 28 (71.8%) 12 (70.6%) .583 Male 16 (28.6%) 11 (28.2%) 5 (29.4%) BMI 27.3 ± 4.8 27.9 ± 4.9 26.1 ± 4.6 .192 UAS7low * 24.0 ± 9.7 23.0 ± 9.3 26.5 ± 4.6 .215 Disease durationlow * 36 (16-102) 40 (18-103) 24 (14-85) .240 ASST+low * 23 of 46 (50.0%) 12 of 33 (36.4%) 11 of 13 (84.6%) <.01 BHRA+low * 9 of 55 (16.4%) 1 of 38 (2.6%) 8 of 17 (47.1%) <.001 Anti-FcepsilonRI+low * 5 of 44 (11.4%) 4 of 30 (13.3%) 1 of 14 (7.1%) .485 Anti-IgE+low * 1 of 44 (2.3%) 1 of 30 (3.3%) 0 of 14 (0.0%) .682 Total IgElow * 205.4 ± 229.6 239.2 ± 250.6 130.0 ± 155.0 .104 Free IgE after omalizumabdagger 31.8 ± 47.7 31.2 ± 39.6 33.2 ± 64.7 .893 % IgE neutralizationdagger 94.7 ± 13.4 96.7 ± 2.2 90.0 ± 24.5 .106 Omalizumab (μg/mL)dagger 16.2 ± 7.8 16.6 ± 7.2 15.2 ± 9.2 .557 Table I CSU responders to omalizumab:
Chronic spontaneous urticaria (CSU) is a mast cell–driven skin disease characterized by the recurrence of transient wheals, angioedema, or both for more than 6 weeks. Autoimmunity is thought to be ...one of the most frequent causes of CSU. Type I and II autoimmunity (ie, IgE to autoallergens and IgG autoantibodies to IgE or its receptor, respectively) have been implicated in the etiology and pathogenesis of CSU. We analyzed the relevant literature and assessed the existing evidence in support of a role for type I and II autoimmunity in CSU with the help of Hill's criteria of causality. For each of these criteria (ie, strength of association, consistency, specificity, temporality, biological gradient, plausibility, coherence, experiment, and analogy), we categorized the strength of evidence as “insufficient,” “low,” “moderate,” or “high” and then assigned levels of causality for type I and II autoimmunity in patients with CSU from level 1 (causal relationship) to level 5 (causality not likely). Based on the evidence in support of Hill's criteria, type I autoimmunity in patients with CSU has level 3 causality (causal relationship suggested), and type II autoimmunity has level 2 causality (causal relationship likely). There are still many aspects of the pathologic mechanisms of CSU that need to be resolved, but it is becoming clear that there are at least 2 distinct pathways, type I and type II autoimmunity, that contribute to the pathogenesis of this complex disease.
Background Chronic urticaria is a frequent and debilitating skin disease. Its symptoms commonly fluctuate considerably from day to day. As of yet, the only reliable tool to assess disease activity is ...the Urticaria Activity Score, which prospectively documents the signs and symptoms of urticaria for several days. Objective We sought to develop and validate a novel patient-reported outcome instrument to retrospectively assess urticaria control, the Urticaria Control Test (UCT). Methods Potential UCT items were developed by using established methods (literature research and expert and patient involvement). Subsequently, item reduction was performed by using a combined approach, applying impact and regression analysis. The resulting UCT instrument was then tested for its validity, reliability, and screening accuracy. Results A 4-item UCT with a recall period of 4 weeks was developed based on 25 potential UCT items tested in 508 patients with chronic urticaria. A subsequent validation study with the 4-item UCT in 120 patients with chronic urticaria demonstrated that this new tool exhibits good convergent and known-groups validity, as well as excellent test-retest reliability. In addition, the screening accuracy to identify patients with urticaria with insufficiently controlled disease was found to be high. Conclusions The UCT is the first valid and reliable tool to assess disease control in patients with chronic urticaria (spontaneous and inducible). Its retrospective approach and simple scoring system make it an ideal instrument for the management of patients with chronic urticaria in clinical practice.
Background Schnitzler syndrome is an adult-onset autoinflammatory disease characterized by urticarial exanthema and monoclonal gammopathy accompanied by systemic symptoms such as fever, bone, and ...muscle pain. Up to now, approved treatment options are not available. Objective We assessed effects of the anti–IL-1β mAb canakinumab on the clinical signs and symptoms of Schnitzler syndrome. Methods In this phase II, randomized placebo-controlled multicenter study, 20 patients with active disease enrolled in 4 German study centers. Patients were randomly assigned to receive single subcutaneous canakinumab 150 mg or placebo injections for 7 days, followed by a 16-week open-label phase with canakinumab injections on confirmed relapse of symptoms. The primary end point was the proportion of patients with complete clinical response evaluated by physician global assessment at day 7. Key secondary end points included changes in patient-reported disease activity (Schnitzler activity score), inflammation markers (C-reactive protein and serum amyloid A), and quality-of-life assessments (Dermatology Life Quality Index and 36-item short form health survey). Results The proportion of patients with complete clinical response at day 7 was significantly higher ( P = .001) in the canakinumab-treated group (n = 5 of 7) than in the placebo group (n = 0 of 13). Levels of inflammation markers C-reactive protein and serum amyloid A and quality-of-life scores were significantly reduced in canakinumab-treated but not in placebo-treated individuals. Positive effects continued up to 16 weeks. Adverse events were manageable and included respiratory tract infections, gastrointestinal symptoms, and hypertension. Conclusions In this first placebo-controlled study, canakinumab was effective in patients with Schnitzler syndrome, and thus canakinumab may be further evaluated as a therapeutic option for this rare disease.
Short Summary This study demonstrates the responsiveness of the Urticaria Control Test (UCT). Changes of its score by 3 points or more reflect a clinically relevant change of disease control (minimal ...important difference).
Background Psoriasis vulgaris is characterized by disfiguring and stigmatizing skin lesions. The links among lesions distribution, severity, and stigmatization remain unclear. Objective We sought to ...investigate if the involvement of visible and sensitive areas is linked to stigmatization. Methods In all, 115 patients with psoriasis vulgaris were assessed for disease severity, skin lesions distribution, itch, and stigmatization using the Feelings of Stigmatization Questionnaire. Quality of life was assessed with the Dermatology Life Quality Index and the World Health Organization Quality of Life-BREF. Results The localization of psoriatic lesions on the back of hands was related to higher stigmatization levels ( P = .011, total score of the Feelings of Stigmatization Questionnaire), but not the involvement of nails, the palms, the face, or the genital area nor overall disease severity. All patients reported some level of stigmatization, regardless of the localization of lesions and type of psoriasis. Higher levels of stigmatization characterized patients who claimed not to be able to hide their lesions by clothing ( P = .025), women ( P = .001), and the unemployed ( P = .004). Stigmatization was the strongest predictor of quality of life impairment. Limitations Only hospitalized patients were included. Conclusions Psoriatic lesions on the back of hands are debilitating and warrant effective treatment. Special attention should be paid to female patients, who are more sensitive to stigmatization.
Secondary end points included changes in the physician and patient global assessment of disease activity (10-point visual analog scale VAS) and changes in inflammation markers C-reactive protein ...(CRP) and erythrocyte sedimentation rate (ESR) during the 16 weeks following canakinumab treatment as compared to baseline. Methods Eligibility criteria To be included in the study, patients had to fulfill the following diagnostic criteria of UV: (1) urticarial rash with individual lesions persisting for more than 24 hours and (2) UV confirmed by biopsy from lesional skin showing signs of leukocytoclasis (fragmentation of neutrophils with nuclear dust) and/or fibrinoid deposits in perivascular and interstitial locations.E1 Participation in the study required active UV and insufficient response to treatment with antihistamines, nonsteroidal anti-inflammatory drugs, and/or immunomodulating or immunosuppressive drugs.
Objective Left ventricular assist device (LVAD) implantation is an established option for treatment of patients with end-stage heart failure, but outcome may be worsened by right ventricular failure. ...The aim of this study was to evaluate the acute effect of LVAD on right ventricular geometry and function and the pulmonary circulation. The effect of inhaled nitric oxide (iNO) was assessed. Methods We evaluated pre- and postoperatively obtained transesophageal echocardiography images and hemodynamics of patients participating in a randomized trial on the effect of inhaled nitric oxide during LVAD implantation. Twenty-four patients were randomized to the iNO group and 23 to the placebo group. Results After LVAD implantation marked decreases in pulmonary capillary wedge pressure ( P < .01) and mean pulmonary artery pressure ( P < .01) were observed in both groups. Pulmonary vascular resistance decreased only in the iNO group (311 ± 35 to 225 ± 17, P < .01). Transesophageal echocardiography measurements show significant improvement of right ventricular geometry (right ventricular end-diastolic diameter: 50 ± 2 to 45 ± 2, P < .01 and 48 ± 2 to 44 ± 2 mm, P < .05 in iNO and placebo groups) and function (right ventricular fractional area change: 24% ± 2% to 31% ± 2%, P < .05 and 23% ± 2% to 29% ± 2%, P < .05 in iNO and placebo groups) without any difference between the iNO and placebo groups. The overall incidence of postoperative right ventricular failure was 4 of 47 (8.5%). Conclusions LVAD implantation markedly improved right ventricular geometry and function in most of the patients, probably by resolving left ventricular congestion and thus reducing right ventricular afterload. Beneficial effects of iNO may have been masked by more pronounced consequences of left ventricular unloading on right ventricular function.
Clinical Measures of Chronic Urticaria Weller, Karsten; Siebenhaar, Frank; Hawro, Tomasz ...
Immunology and allergy clinics of North America,
02/2017, Letnik:
37, Številka:
1
Journal Article
Recenzirano
The use of standardized, valid, and reliable clinical measures is an important element in modern patient management, particularly in diseases that are not objectively assessable and are associated ...with a high disease burden. Chronic urticaria is such a disorder for which several new and well-developed clinical measures became available. These measures comprise tools to assess disease activity, disease control, and health-related quality-of-life impairment. This review provides an overview of the currently available clinical measures for chronic urticaria. In addition, it provides information on their strengths and limitations and how to best use them and evaluate their results.
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