Clinical management of urticaria using omalizumab: the first licensed biological therapy available for chronic spontaneous urticaria.

This supplement reports proceedings of the second international Global Urticaria Forum, which was held in Berlin, Germany in November 2015. Omalizumab is approved for the treatment of chronic spontaneous urticaria (CSU) in adult and adolescent (12 years and above) patients with inadequate response to/who remain symptomatic despite H1 -antihistamine treatment, and has demonstrated good efficacy and safety in the clinical trial setting. Real-life clinical experience with omalizumab can be explored to address important practical questions relating to its use in CSU patients. Some experts have proposed that a consensus algorithm, covering various aspects to consider when using omalizumab in real-life clinical practice for the management of CSU, could answer many of these questions.

Questions and answers in chronic urticaria: where do we stand and where do we go?

This supplement reports proceedings of the second international Global Urticaria Forum, which was held in Berlin, Germany in November 2015. In 2011, a report of the GA(2) LEN task force on urticaria outlined important and unanswered questions in chronic urticaria (CU). These included, but were not limited to, questions on the epidemiology and course of chronic spontaneous urticaria (CSU) [also called chronic idiopathic urticaria (CIU)], the resources allocated for the diagnosis and treatment of CSU, whether patients with angioedema as an isolated symptom can be regarded as a subgroup of CSU, and the efficacy and long-term safety of therapies. Many of these questions have been addressed by recent studies. Some of the answers obtained raise new questions. Here, we summarize some of the key insights on CU obtained over recent years, and we discuss old and new unmet needs and how to address them with future studies. We need to analyze the influence of recent advances in understanding of the burden of CU on patients and society, disease management and the CU patient journey. Our increased understanding of urticarial pathophysiology and consideration of the patient as a whole will need to be translated to better treatment algorithms and protocols. Actions to address these challenges include the 5th International Consensus Meeting on Urticaria, which will take place later this year. The formation of a global network of Urticaria Centers of Reference and Excellence over the next few years has also been proposed, with the aim of providing consistent excellence in urticaria management and a clear referral route, furthering knowledge of urticaria through additional research and educating/promoting awareness of urticaria.

Class action of oral coumarins in the treatment of a patient with chronic spontaneous urticaria and delayed-pressure urticaria.

Chronic spontaneous urticaria is a common condition, with a lifetime prevalence of 0.5-1.0%. It has a significant effect on quality of life, comparable to having triple-vessel coronary artery disease. Warfarin and nicoumalone are synthetic derivatives of the plant toxin coumarin. We report the first case of successful response to both warfarin and nicoumalone in the same patient, thereby demonstrating a class action of synthetic coumarins in the disease. Complete response with both coumarins occurred once an INR above 2.0 was achieved, and was maintained during a 12-month follow-up. The mechanism of action of coumarins on urticaria is not known, but may be related to decrease in thrombin production or to interference of activation of other inflammatory proteins produced during the coagulation process. Side-effects of anticoagulation can be catastrophic, and coumarin treatment currently remains reserved for restricted severe recalcitrant cases only.

Interventions for chronic palmoplantar pustulosis.

BACKGROUND: Chronic palmoplantar pustulosis (PPP) is a chronic inflammatory skin condition characterised by crops of sterile pustules (yellow pus spots) on the palms and soles which erupt repeatedly over months or years. The affected areas tend to become red and scaly; cracks may form and these are often painful. Many different treatments have been used for palmoplantar pustulosis but none is generally accepted as being reliably effective. OBJECTIVES: To assess the effects of treatments for palmoplantar pustulosis, both in reducing disease severity and in maintaining remission once achieved. SEARCH STRATEGY: We searched the Cochrane Skin Group Specialised Register (January 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2003), MEDLINE (1966 to February 2003), EMBASE (1988 to February 2003). We also cross-checked with the Salford Database of Psoriasis Trials and reference lists of articles. We also contacted authors included trials, members of the Cochrane Skin Group and dermatologists interested in psoriasis. SELECTION CRITERIA: Any randomised controlled trial in which patients with chronic palmoplantar pustulosis were randomised to receive one or more interventions. DATA COLLECTION AND ANALYSIS: At least two reviewers independently assessed trial eligibility and quality. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: Twenty-three trials involving 724 people were included. There is evidence supporting the use of systemic retinoids (improvement rate difference 44%, 95 CI 28 to 59%), oral PUVA (improvement rate difference 44%, 95 CI 26 to 62%). However, a combination of PUVA and retinoids is better than the individual treatments. The use of topical steroid under hydrocolloid occlusion is beneficial. It would also appear that low dose ciclosporin, tetracycline antibiotics and Grenz Ray Therapy may be useful in treating PPP. Colchicine has a lot of side effects and it is unclear if it is effective and neither was topical PUVA (rate difference of 0.00, 95% CI -0.04 to +0.04). There is no evidence to suggest that short-term treatment with hydroxycarbamide (hydroxyurea) is effective. AUTHORS' CONCLUSIONS: Many different interventions were reported to produce "improvement" in PPP. There is, however, no standardised method for assessing response to treatment, and reductions in pustule counts or other empirical semi-quantitative scoring systems may be of little relevance to the patient. This review has shown that the ideal treatment for PPP remains elusive and that the standards of study design and reporting need to be improved to inform patients and those treating them of the relative merits of the many treatments available to them.

The major psoriasis susceptibility locus PSORS1 is not a risk factor for late-onset psoriasis.

PSORS1 is the major susceptibility locus for psoriasis vulgaris (PV) and lies within an approximately 200 kb segment of the major histocompatibility complex on chromosome 6p21.3. Alleles of candidate genes in this region including human leukocyte antigen (HLA)-C, alpha-helical coiled coil rod (HCR), and corneodesmosin (CDSN) show association with early-onset PV. Late-onset psoriasis (LOP) is defined as a disease with onset after 40 y of age and is typically sporadic. We assessed the role of PSORS1 in genetic susceptibility to LOP. Genotyping for HLA-C alleles and seven single nucleotide polymorphisms (SNP) within the genes HCR and CDSN was performed in LOP (n=145) and normal controls (n=309). Statistical analysis of allelic frequencies included calculation of odds ratio and chi2 comparisons. LOP demonstrated only a weak association to PSORS1 alleles HLA-Cw*6 (p=0.037), CDSN*5 (p=0.041), HCR*WC (p=0.013), and HCR SNP +325 (p=0.038). Patients with age of onset for psoriasis of 50 y or above provided no evidence of association with any of these alleles. These data suggest that the study cohort may include a number of subjects who harbor PSORS1 predisposition to early-onset psoriasis and yet do not present with disease by the age of 40 y. Thus this study demonstrates that PSORS1 is not a major inherited risk factor in the pathogenesis of LOP. These data suggest that the exclusion of LOP subjects from case-control studies will aid further delineation of the PSORS1 locus. Future genome-wide studies will be required to identify loci conferring risk for late-onset disease.

Treatments for chronic palmoplantar pustular psoriasis.

Chronic palmoplantar pustular psoriasis (PPP) is a disabling condition characterized by recurrent crops of sterile pustules on a background of erythema, fissuring and scaling. Genetic and environmental factors have been implicated in its etiology. Topical treatments are frequently ineffective although corticosteroids under hydrocolloid occlusion have been demonstrated to be useful. There is evidence supporting the use of systemic retinoids, PUVA and a combination of both. Oral tetracycline antibiotics may be helpful, but rarely clear PPP. Cyclosporine has been shown to be of some benefit at low doses. The choice of systemic treatments for an individual patient is influenced as much by their potential side effects as by differences in efficacy.

Effects of calcineurin inhibitors on an in vitro assay for chronic urticaria.

BACKGROUND: Chronic urticaria is a common skin disorder, which causes considerable morbidity. In approximately 40% of cases, patients have an autoimmune disorder in which functional antibodies cause degranulation of mast cells and basophils, and C5a complement augments this in varying amounts from patient to patient. Since the calcineurin inhibitor ciclosporin has been used in chronic autoimmune urticaria, we examined the effect of ciclosporin and other drugs on the release of histamine from basophils when stimulated by sera from patients with chronic autoimmune urticaria. METHODS: Leucocytes from healthy donors were isolated and incubated in varying concentrations of ciclosporin, ascomycin, methotrexate, diphenhydramine or hydroxyzine for 30 min prior to stimulation with serum from urticaria patients known to have functional immunoglobulin (Ig)G antibodies directed against the alpha subunit of the IgE receptor. Histamine release was then measured. RESULTS: Pre-incubating cells with ciclosporin and ascomycin produced dose-dependent inhibition of histamine release when cells were stimulated by sera of urticaria patients, by purified IgG from these sera, but not by C5a. Inhibition was not prevented by C5a receptor blocking antibodies. No inhibition was seen with methotrexate, diphenhydramine or hydroxyzine. CONCLUSIONS: This is the first demonstration of inhibition of histamine release by calcineurin inhibitors employing sera of patients with chronic autoimmune urticaria. These drugs may work by interfering with intracellular signalling in cells following cross-linking of the IgE receptor, but not following stimulation of the C5a receptor.

Successful treatment of severe recalcitrant psoriasis with combination infliximab and methotrexate.

Plaques of psoriasis contain increased levels of cytokines, including tumour necrosis factor-alpha (TNF-alpha), which are thought to be essential to the maintenance of the psoriatic process. We report the successful treatment of severe, recalcitrant psoriasis when infliximab (a monoclonal antibody to TNF-alpha) was used in combination with methotrexate.