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Summary: Background: Human skin protects the body from external damage, pathogens and oxidative stress factors such as ultraviolet (UV) radiation. Excessive exposure to UV radiation can lead to increased production of free radicals and hence to skin damage such as inflammation, premature skin ageing and skin cancer. Besides UV, the visible and near infrared (NIR) regions are also a source of radical production. Half of all free radicals are induced by the visible + NIR region of the solar spectrum in people with skin types I–III, but data on the effects in people with skin types IV–VI are missing. Objectives: This in vivo pilot study addressed the distribution of radical production in skin types IV and V during irradiation in the UV, visible and NIR spectral regions, comparing the first results with those of skin type II. Methods: The measurements were performed in vivo using L‐band electron paramagnetic resonance spectroscopy and the spin probe PCA. Results: In skin types IV–V most radicals were induced in the visible + NIR region, followed by the NIR and UV regions of the sun spectrum. Significantly (P ≤ 0·05) more radicals were induced in skin types IV–V than in type II during NIR irradiation, whereas skin types IV–V exhibited significantly less UV‐induced radicals (P ≤ 0·01) than skin type II. Conclusions: All spectral regions (UV, visible and NIR) cause free radical formation in skin types II and IV–V. After 4 min of solar‐simulated exposure (UV‐NIR), the radical formation in skin types IV–V is 60% of that in skin type II. Therefore people with darker skin types also need solar protection. What's already known about this topic? Excessive exposure to ultraviolet (UV) radiation can lead to increased production of free radicals and hence to skin damage such as inflammation, premature skin ageing and tumour progression.The visible and near infrared (NIR) regions of the solar spectrum also induce radicals.Half of all free radicals in skin types I–III are due to visible + NIR exposure, but data about the effects in skin types IV–VI are missing. What does this study add? This in vivo pilot study addresses the distribution of radical production in skin types IV and V during irradiation in the UV, visible and NIR spectral regions, comparing the results with those of skin type II.The results provide the first ideas of possible long‐term effects of excessive exposure to visible and NIR radiation in skin types IV and V. What is the translational message? In people with skin types IV–V, significantly more radicals were formed during NIR irradiation compared with skin type II.As in skin types IV–V the NIR values reach or exceed those of the UV and visible, which could influence premature skin ageing and carcinogenesis.Individuals with skin types IV–VI might need a different type of sun protection from those with skin types I–III to avoid subsequent damage by solar radiation. Respond to this article Linked Comment:Young. Br J Dermatol 2019; 180:456–457. Plain language summary available online [ABSTRACT FROM AUTHOR]

Background Many physicians believe that the most effective way to treat chronic urticaria is to take a nonsedating second-generation H1-antihistamine in the morning and a sedating first-generation H1-antihistamine, usually hydroxyzine, at night to enhance sleep. But is this belief well founded? Objectives To test this belief by comparing the effectiveness and prevalence of unwanted sedative effects when treating patients with chronic spontaneous urticaria ( CSU) with levocetirizine 15 mg daily plus hydroxyzine 50 mg at night (levocetirizine plus hydroxyzine) vs. levocetirizine 20 mg daily (levocetirizine monotherapy). Methods In this randomized, double-blind, cross-over study, 24 patients with difficult-to-treat CSU took levocetirizine plus hydroxyzine or levocetirizine monotherapy for periods of 5 days each. At the end of each treatment period, assessments were made of quality of life (Chronic Urticaria Quality of Life Questionnaire, CU-Q2oL), severity of urticaria symptoms (Urticaria Activity Score, UAS), sleep disturbance during the night and daytime somnolence. Results Both treatments significantly decreased UAS, night-time sleep disturbances and CU-Q2oL scores ( P < 0·001) without significant differences between the two. Compared with baseline, daytime somnolence was significantly reduced by levocetirizine monotherapy ( P = 0·006) but not by levocetirizine plus hydroxyzine ( P = 0·218). Direct comparison of the two treatment modalities in terms of daytime somnolence favoured levocetirizine monotherapy ( P = 0·026). Conclusions The widespread belief that sleep is aided by the addition of a sedating first-generation H1-antihistamine, usually hydroxyzine, at night is not supported. These results are in line with the urticaria guidelines, which state that first-line treatment for urticaria should be new-generation, nonsedating H1-antihistamines only. [ABSTRACT FROM AUTHOR]

Summary Women with skin conditions may need topical corticosteroids during pregnancy. However, little is known about the effects of topical corticosteroids on the fetus. A guideline subcommittee of the European Dermatology Forum was organized to develop an evidence-based guideline on the use of topical corticosteroids in pregnancy (). The evidence from a Cochrane Review suggested that the major possible adverse effects on the fetus of topical corticosteroids were orofacial clefts when used preconceptionally and in the first trimester of pregnancy, and fetal growth restriction when very potent topical corticosteroids were used during pregnancy. To obtain robust evidence, a large population-based cohort study (on 84 133 pregnant women from the U.K. General Practice Research Database) was performed, which found a significant association of fetal growth restriction with maternal exposure to potent/very potent topical corticosteroids, but not with mild/moderate topical corticosteroids. No associations of maternal exposure to topical corticosteroids of any potency with orofacial cleft, preterm delivery and fetal death were found. Moreover, another recent Danish cohort study did not support a causal association between topical corticosteroid and orofacial cleft. The current best evidence suggests that mild/moderate topical corticosteroids are preferred to potent/very potent ones in pregnancy, because of the associated risk of fetal growth restriction with the latter. [ABSTRACT FROM AUTHOR]

To investigate the prevalence of urticaria with a focus on chronic urticaria (CU) in a general German population. A questionnaire survey was sent to a representative cross-sectional sample of 13 300 inhabitants of Berlin, Germany, of whom 4093 responded. All respondents who stated ever having had weals or angio-oedema ( n = 767) were interviewed by telephone. Any interviewees with recent symptoms (within the previous 3 years) were invited for personal investigation including allergy tests; double-blind, placebo-controlled food challenge tests; and quality of life (QOL) assessment. Reported prevalence rates were weighted with regard to age, gender and education so that they were representative of the total population of Berlin. Lifetime prevalence rate of urticaria was 8.8% (95% CI 7.9-9.7%) for all types of urticaria. Lifetime prevalence for CU was 1.8% (95% CI 1.4-2.3%), and prevalence for the 12 months before assessment was 0.8% (95% CI 0.6-1.1%), and 70.3% were female. QOL was markedly reduced for people with CU. Unlike other allergic diseases, there was no increased risk associated with higher education or social status. Prick tests found sensitization of ≥ 1 for type 1 allergens in 39.1% of patients. These were related to comorbidities such as allergic rhinitis or oral allergy syndrome, but were never the underlying cause of CU, as proven by double-blind, placebo-controlled provocation tests. Urticaria is a common disease with marked effects on QOL. The lifetime prevalence of 8.8% for urticaria must be regarded as a lower limit as it is based on conservative prevalence rate calculations, and under-reporting of previous disease can be expected in a questionnaire-based study. [ABSTRACT FROM AUTHOR]

Background Chronic urticaria (CU) is a common skin disorder characterized by spontaneous outbreaks of itchy weals and/or angio-oedema over a period of 6 weeks or longer. Very little is known about the health behaviour, symptom patterns or unmet treatment needs of patients with CU. Objectives To determine how patients with CU manage their condition, when and where their symptom outbreaks occur and what their greatest unmet treatment needs are. Methods An internet survey was conducted with 321 randomly selected, representative adults in Germany and France diagnosed with CU. The survey covered patient health behaviour, when and where symptoms occur and which effects of CU remain unaddressed. Results The survey found that 78% of the respondents were taking prescription or over-the-counter medication, yet only 33% of those taking medication did so preventively always or often. For 58% of respondents, CU outbreaks lasted 6–10 weeks, while 12% of patients had CU continuously for 52 weeks year−1. The body parts most frequently reported as most affected by CU were the arms (55% of women and 57% of men; not significant) and the legs (42% of women and 32% of men; P = 0·043). More respondents were bothered by symptoms in the evening (34%) than during the night (23%), morning (23%) or afternoon (20%), and the mode of the frequency for sleep being affected was three nights per week. Itching and physical discomfort remained inadequately addressed for 68% of the respondents, and sleep disturbances from CU remained inadequately addressed for 48% of respondents. Conclusions A better understanding of health behaviour, symptom pattern and unmet needs of patients with CU will enable physicians and patients to manage this disabling condition more effectively. [ABSTRACT FROM AUTHOR]

Acquired cold urticaria (ACU) is a frequent subtype of physical urticaria that is caused by the release of proinflammatory mast cell mediators after cold exposure. Although the underlying causes of ACU still remain to be clarified in detail, a wide range of diseases has been reported to be associated with ACU. This review gives an overview of the clinical picture, the differential diagnoses, diagnostic tests and the aetiology of ACU, and summarizes current and novel therapeutic options based on the current literature. [ABSTRACT FROM AUTHOR]

Muckle–Wells syndrome is a rare familial disease with autosomal dominant inheritance, characterized by cold sensitivity and polyarthralgias since childhood, with possible later development of nerve deafness and renal amyloidosis. The nature of the skin manifestations is, however, not well characterized. To clarify the nature of cutaneous cold sensitivity in patients with Muckle–Wells syndrome by studying clinical aspects and histological features. Eighteen members of a family with Muckle–Wells syndrome and the recently identified mutation of the CIAS1 gene at locus 260 of chromosome 1q44 were available for study. Examination included a thorough history, physical examination and a battery of laboratory tests. In two brothers, standard cold contact and cold air provocation tests were performed, as were biopsies from normal and lesional skin. All affected family members reported an increased sensitivity to cold, dampness or changes in temperature, and most had arthritis and conjunctivitis. Eight had developed hearing loss, four renal involvement, and amyloid deposits were found in three of five patients in whom rectal biopsies were performed. Laboratory tests showed leucocytosis and elevated C-reactive protein, but no serum cold agglutinins and cryoglobulins. Skin eruptions, with weals of 0·2–3 cm, lasted from 5 to 24 h and were associated with local itching or pain as well as fever, malaise and chills. On cold provocation of two patients, lesions could be reproduced by cold air, but not by contact with an ice cube or cold water. On histology, there was increased vasodilatation, marked infiltration with neutrophils and monocytes/macrophages, and increased expression of β2 integrins in lesional vs. normal skin. Numbers of mast cells as well as expression of interleukin-3 and tumour necrosis factor-α were unchanged. Cold-induced skin lesions in Muckle–Wells syndrome represent typical generalized cold air/wind inflammatory reactions, as also observed in familial cold urticaria. Microscopic features are similar to those observed in other types of urticaria. [ABSTRACT FROM AUTHOR]

Summary Background Mast cells, the main effector cells in urticaria, have been reported to be increased in number in lesional and nonlesional skin of urticaria patients, but the underlying mechanisms have so far not been studied. Serum NGF has however, been reported to be increased in urticaria. Objectives We have therefore explored the potential involvement of known mast cell growth modulating factors in urticaria. Methods Tissue sections from patients with different types of urticaria and healthy controls were studied for the immunohistochemical expression of known mast cell growth factors (stem cell factor, SCF; nerve growth factor, NGF), of the inhibitory granulocyte-macrophage colony-stimulating factor (GM-CSF), and of the corresponding receptors, using the alkaline phosphatase–antialkaline phosphatase technique. Results Compared to skin of normal controls, staining for SCF, but not for NGF and GM-CSF, was significantly decreased in epidermis, endothelium and perivascular cells in lesional and nonlesional skin of all urticarias. On separate analysis of urticaria subtypes, decreased expression reached significance only in delayed pressure urticaria. Expression of the p75NGF receptor (p75NGFR) was also significantly decreased on endothelium and on perivascular cells of lesional and nonlesional skin in all urticarias. On evaluation of serial sections, p75NGFR expression was also decreased on c-Kit positive dermal mast cells. In contrast, expression of the NGF receptor tyrosine kinase and of the SCF and GM-CSF receptors was unchanged. Conclusions These findings show that SCF and p75NGFR are selectively and systemically down-regulated in the skin of urticaria patients and may represent a negative feedback to increased mast cell reactivity and proliferation. [ABSTRACT FROM AUTHOR]

We report the in vitro and in vivo effects of granulocyte macrophage colony stimulating factor (GM-CSF), a known inhibitor of in vitro mast cell differentiation, in a patient with benign, adult-onset systemic mastocytosis. In vitro effects of GM-CSF on bone marrow cultures before the start of treatment showed a marked inhibition of mast cell marker expression [tryptase, Kit, and high-affinity IgE receptor (FcεRIα)] at both protein and mRNA levels. Therefore, the patient was treated with daily injections of GM-CSF for 10 weeks. After an initial improvement, increasing worsening of clinical symptoms was noted, and the patient refused further treatment. Lesional skin biopsies showed an increase of toluidine blue-positive mast cells, compared with uninvolved skin, with further significant increase after treatment. Similar results were obtained on staining for mast cell-specific tryptase and Kit, as well as for CD1a and FcεRIα. These findings show that GM-CSF inhibits human bone marrow mast cell differentiation in vitro , and also in mastocytosis. However, GM-CSF apparently enhances recruitment of mast cell as well as dendritic cell precursors into the tissue during systemic treatment. These findings and the observed adverse clinical effects in the present patient make it unlikely that GM-CSF monotherapy will be beneficial for the treatment of mastocytosis. [ABSTRACT FROM AUTHOR]

Discusses abstracts of research articles on urticaria angioedema and related disorders, published as of April 1999. History of urticaria and angioedema; Quality of life of patients with urticaria; Contact urticaria; Urticaria without rash; Solar urticaria; Exercise-induced urticaria and anaphylaxis; Histamine-releasing fators in chronic urticaria.

Background Sodium cromoglicate (SCG) has long been used in the management of allergic diseases, including as an ointment for atopic dermatitis. Although mast cell stabilization was initially considered as its mechanism of action, anti-inflammatory actions and modulation of sensory nerve function have also been suggested. Objectives To investigate the mechanism(s) by which SCG relieves allergen- and histamine-induced dermal inflammation by assessing its effects on pruritus, flare, skin temperature and weal volume. Methods Aqueous cream containing 0·2%, 1% or 4% SCG or no SCG (placebo) was applied in a randomized single-blind manner to four areas on each forearm (two sites per arm) and covered with an occlusive dressing. One hour later, skin-prick tests were performed in 20 allergic subjects with allergens to which they had previously shown sensitization, and in 40 nonallergic subjects with codeine (9 mg mL−1, 20 subjects) and histamine (10 mg mL−1, 20 subjects). Weal volume, skin temperature increase, erythema area and pruritus intensity were assessed at 0, 5, 10 and 15 min. Results SCG significantly ( P < 0·05 to P < 0·001) reduced pruritus induced by all stimuli, with 4% SCG being most effective. Significant ( P < 0·05 to P < 0·01) reductions of erythema area were also seen but there was no inhibition of weal volume or temperature increase. Conclusions SCG is effective in reducing pruritus but has no effect on weals, supporting the proposition that, in the skin, SCG inhibits sensory C-fibre nerve activation rather than preventing mast cell degranulation. We suggest that topical SCG treatment, delivered in an appropriate vehicle, may be beneficial for symptomatic relief of pruritus in patients with cutaneous mastocytosis and other pruritic dermatoses. [ABSTRACT FROM AUTHOR]

Background Acquired cold urticaria (ACU) is a physical urticaria characterized by local skin reactions after cold exposure. Objective markers of disease severity and activity would be helpful. Unfortunately, such markers are not yet available, even though stimulation time and temperature thresholds are promising candidates. Objectives We assessed and correlated critical temperature thresholds (CTTs) with disease severity and activity in patients with ACU. Methods CTTs were determined in 45 patients with ACU by Temp Test®-based cold contact stimulation tests (Emo Systems GmbH, Berlin, Germany), and ACU severity and activity were assessed using Likert scales. Results Patients with ACU exhibited mean ± SEM CTTs of 17 ± 6 °C (range 4–27 °C). These thresholds and their changes correlated with the severity ( r = 0·53, P < 0·05) and activity of disease ( r = 0·64, P < 0·05), respectively. Conclusions These findings indicate that temperature threshold measurements may be used for assessing disease severity and activity as well as the efficacy of therapeutic measures including novel treatment approaches for cold urticaria. [ABSTRACT FROM AUTHOR]

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Summary: Excessive solar (sun) exposure, especially ultraviolet radiation, can lead to sunburn and increased damage to cells, called oxidative stress. This can cause skin damage such as inflammation, premature skin aging and tumour development. Statistics from the U.S. National Cancer Institute show that the number of new cases of melanoma and non‐melanoma skin cancer are rising every year. Therefore, it is important to understand the negative effects of solar radiation in skin. Beside the ultraviolet light, the visible and near infrared regions of the solar spectrum induce oxidative stress in fair skin types but data about the effects in darker skin types are missing. A German study addressed the distribution of oxidative stress in dark skin during solar irradiation and compared the results to those of fair skin types. Free radicals are a marker for (i.e. sign of) oxidative stress. The scientists measured the formation of free radicals on volunteers during solar irradiation, using technology called electron paramagnetic resonance spectroscopy. The authors found that darker skin was better protected against ultraviolet radiation than fair skin. However, darker skin types showed significantly more oxidative stress during near infrared irradiation compared to fair skin types. The oxidative stress in the near infrared is at least as high as in ultraviolet and visible spectral regions and could cause skin damage in darker skin. The results show that individuals of darker skin might need a different type of sun protection than those of paler skin to avoid long term damage by solar radiation. Linked Article: Albrecht et al. Br J Dermatol 2019; 180:597–603 [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which reports the advancement of aetiology and pathogenesis of urticaria, including its classification and nomenclature that recommends the changing of the outdated term, chronic idiopathic urticaria (CIU).

In dermographic urticaria (DU), shearing forces on the skin result in weals and itching. Second-generation antihistamines are recommended as the first-line treatment, but to date only a few have ever been tested for this condition. The objective of this pilot study was to assess the safety and efficacy of ebastine in preventing symptoms of DU. Seven adult patients with DU participated in a double-blind cross-over trial of ebastine 20 mg. Safety was assessed using a sensitive psychometric battery, testing cognitive performance and mood. Efficacy was assessed by rating weals, erythema, pruritus and burning after challenge. Ebastine had no negative effective on cognitive performance or mood. Weals, pruritus and burning were greatly reduced for most subjects. This pilot study suggests that ebastine is safe and effective in preventing the symptoms of DU and should be tested on a larger scale. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor in response to an article addressing the benefits of an additive-free diet in chronic urticaria published in the "British Journal of Dermatology."