The Dysfunction of the Cerebellum and Its Cerebellum-Reward-Sensorimotor Loops in Chronic Spontaneous Urticaria.

Chronic spontaneous urticaria (CSU) is a common itchy skin disease. Despite its prevalence, the neuropathology of CSU is uncertain. In this study, we explored resting state functional connectivity (rs-FC) changes in CSU, as well as how the symptom changes following intervention can modulate rs-FC. Forty patients and 40 healthy controls (HCs) were recruited. Following an intervention, 32 patients participated in a second scan approximately 6 weeks after the first scan. Compared with healthy controls, CSU subjects exhibited higher regional homogeneity (ReHo) values in the cerebellum, which were positively associated with urticaria activity scores over 7 days (UAS7) at baseline. After an intervention accompanied with clinical improvement, we found that ReHo values decreased at the cerebellum and increased at the bilateral primary somatosensory cortex (SI)/primary motor cortex (MI)/supplementary motor area (SMA). Using the cerebellum as a seed, CSU subjects exhibited increased rs-FC with reward regions when compared with HCs and exhibited decreased rs-FC at the right orbitofrontal cortex and right sensorimotor region following the intervention. The improvement rate values were positively associated with reduced rs-FC values in the two regions. Using the cluster of SI/MI/SMA as a seed, CSU patients exhibited decreased rs-FC with the left putamen, caudate, accumbens, and thalamus following the intervention. These results demonstrate the altered cerebellar activity and cerebellum-reward-sensorimotor loops in CSU.

The Effectiveness and Safety of Acupuncture for Patients with Chronic Urticaria: A Systematic Review.

Background. Acupuncture might have effectiveness in relieving the symptoms of chronic urticaria. There are currently no systematic reviews of acupuncture for chronic urticaria published in English. Objective. We conducted a systematic review to assess the effectiveness and safety of acupuncture for chronic urticaria. Methods. A systematic review and meta-analysis of randomized, controlled trials were performed. The primary outcome was global symptom improvement. Results. We included 6 studies with 406 participants. Three trials showed significant difference between acupuncture and drugs in global symptom improvement (relative risk 1.37; 95% CI 1.11-1.70; P = 0.003). As an adjuvant to medication, acupuncture was also beneficial for global symptom improvement (relative risk 1.77; 95% CI 1.41-2.22; P < 0.01). There were no severe adverse events related to acupuncture. Limitations. Some methodological limitations were observed. The overall risk of bias in the 6 included trials was high and all included RCTs were conducted in China and published in Chinese. Besides, the lack of proper control groups and the use of different rating methods and cut-offs in the included trials also made the evidence of this review limited. Conclusions. Acupuncture might be effective and safe for chronic urticaria in relieving symptoms, based on a low level of evidence. To draw a reliable conclusion, more high quality trials are needed in the future. This trial is registered with PROSPERO CRD42015015702.

Are chronic urticaria, analgesic intolerance and seasonal rhinitis markers of different severities and phenotypes of the asthma they accompany?

BACKGROUND: Asthma is a heterogeneous disease that presents with different clinical phenotypes. We aimed to compare the patients with asthma diagnosis alone with the patients, who, in addition to their asthma had accompanying analgesic intolerance (AI), chronic urticaria (CU) or seasonal rhinitis (SR) if there are any distinctions and specific characteristics of these defined patient groups. METHODS: Eighty-four asthma patients diagnosed with SR, 46 with CU, 75 with AI and 71 patients with asthma alone were enrolled to the study retrospectively. The reference group for the comparisons was the group with asthma diagnosis alone. RESULTS: The mean age of all patients was 37.2±13 (15-80) and 70.7% of them were females. Asthma patients with SR had a significantly earlier onset of asthma (age: 27.4±10.8 and 34.5±15.9; respectively, p<0.01), significantly better pulmonary function tests and were significantly more atopic (92.9% and 28.8%; p<0.001). Moderate-to-severe asthma significantly correlated with older age at the time of diagnosis, older age of asthma onset, higher body mass index, less atopy and fewer pollen sensitivity. Asthma severity of patients with SR was significantly milder than the reference group (OR: 0.6, 95% CI 0.5-0.8). Asthma with AI tended to be more severe although the relation was insignificant (OR:1.6 95% CI:0.8-3.5). CONCLUSIONS: Asthma patients with SR have significantly milder and earlier onset of asthma, better pulmonary function tests and are significantly more atopic while asthma with AI tends to be more severe. Asthma with CU does not show a specific phenotypic characteristic.

Improvement of chronic idiopathic urticaria with L-thyroxine: a new TSH role in immune response?

BACKGROUND: The association between chronic idiopathic urticaria (CIU) and autoimmune thyroiditis (AT) is known, as well as major prevalence of antithyroid antibodies in the allergical subjects and other autoimmune diseases. We have evaluated the effects of l-thyroxine on clinical symptoms of CIU in AT patients suggesting the hypothesis of a new thyroid-stimulating hormone (TSH) role in immune system. METHODS: In 20 female patients with CIU + AT, both hypothyroid and euthyroid, we have investigated the therapeutic effects of l-thyroxine dosed to suppress the TSH. Free-T3, Free-T4, TSH, antithyroperoxidase and antithyroglobulin antibodies, total immunoglobulin (Ig)E, Rheuma test and eritro-sedimentation rate were monitored during treatment. RESULTS: In 16 patients a strong decrease of urticaria symptoms has happened after 12 weeks. The TPO Ab and HTG Ab clearly decreased in 14 patients. Furthermore, in two patients with rheumatoid arthritis and in two patients with pollen allergy a strong decrease of rheuma test titer and total IgE has happened. CONCLUSION: The reason of AT is associated to CIU and others allergical and autoimmune diseases is poorly known. The exclusive hormonal therapy reduces the symptoms of CIU and inflammatory response in many chronic diseases associated to AT. We suggest a stimulatory effect of TSH able to produce considerable changes of the immune response and immune tolerance in patients with AT causing target organs damage. The causal mechanism involves immune, nervous and endocrine system, sharing a common set of hormones, cytokines and receptors, in a unique totally integrated loop (the neuro-immuno-endocrine axis).

Urticaria solar. Estudio de 20 casos / Solar urticaria. Study of 20 cases

Introducción. La urticaria solar es una enfermedad poco frecuente, pero probablemente infradiagnosticada. Se caracteriza por la aparición de forma súbita de habones en zonas habitualmente no fotoexpuestas tras irradiación solar o con otras fuentes artificiales de luz visible o ultravioleta. Los casos publicados en la literatura médica son pocos, por lo que la información que tenemos acerca de la enfermedad y su evolución natural es limitada. Material y métodos. Se han recopilado los datos de los 20 pacientes que han sido diagnosticados de urticaria solar en nuestro servicio en los últimos 12 años (1990-2002), para intentar obtener información acerca de las características de esta enfermedad. Resultados. Como características más relevantes de nuestra serie cabe destacar que el 60 % de los pacientes eran mujeres; la duración media de la enfermedad antes de acudir a un dermatólogo era de alrededor de 3 años. En el 55 % de los pacientes se respetaban zonas habitualmente fotoexpuestas como cara y manos (fenómeno de habituación o hardening). Los espectros responsables de la urticaria solar eran luz visible, UVA y UVB, por ese orden. Respecto a los tratamientos, con antihistamínicos y fotoprotectores se obtuvo una respuesta parcial y buenos resultados mediante desensibilizaciones progresivas con UVA/sol. Conclusión. La urticaria solar es probablemente una enfermedad infradiagnosticada en nuestro medio. Hay pocas series publicadas que nos permitan conocer las características más importantes de la enfermedad. Se han recopilado los datos más interesantes de nuestros pacientes y se han comparado con el resto de las series publicadas en el intento de conocer mejor esta fotodermatosis

Introduction. Solar urticaria is an infrequent disorder, but is probably underdiagnosed. It is characterized by the sudden appearance of weals in areas that are not usually photoexposed after exposure to the sun or to artificial sources of visible or ultraviolet light. Few cases have been published in literature, so the information available about this disorder and its natural evolution is limited. Material and methods. We have compiled data from 20 patients diagnosed with solar urticaria in our department in the last 12 years (1990-2002) in order to try to obtain information about the characteristics of this condition. Results. As the most relevant characteristics of our series, we can mention the fact that 60 % of the patients were women, and the average duration of the condition before consulting a dermatologist was 3 years. In 55 % of the patients, areas that are usually photoexposed, such as the face and hands, were less severely affected (due to acclimatization or hardening). The spectra responsible for the SU were visible light, UVA and UVB, in that order. With regard to treatment, we obtained a partial response with antihistamines and photoprotectors, and good results using progressive desensitization with UVA/sunlight. Conclusion. Solar urticaria is probably an underdiagnosed condition in our milieu. There are few series in literature that provide any information about the most significant characteristics of this disorder. We have compiled the most relevant data from our patients and we have compared it with the other published series in an attempt to learn more about this photodermatosis

Mechanisms of phototherapy and photochemotherapy for photodermatoses.

Most photodermatoses represent indications for preventive ultraviolet (UV) phototherapy and/or psoralen plus ultraviolet A (PUVA) photochemotherapy. The aim of treatment is to prevent the outbreak of disease by increasing the patient's tolerance to sunlight. The mechanisms by which ultraviolet B (UVB) and PUVA induce such tolerance are not completely understood. Pigmentation and skin thickening may be important factors in the protective effect, but they cannot sufficiently explain the degree of protection induced. Other mechanisms that may be of critical importance for the therapeutic efficacy encompass a variety of immunomodulatory effects on human skin known to be induced by UVA, UVB, and PUVA. Obviously the mechanisms of prophylactic phototherapy are strongly intertwined with the pathogenesis of the photodermatoses. The possible mechanisms of photoprevention are discussed for polymorphic light eruption (PMLE), actinic prurigo, chronic actinic dermatitis, and solar urticaria.

Dual effects of CGRP-antagonist on allergic contact dermatitis in human skin.

There is increasing evidence of an interaction between the nervous and the immune systems. The aim of this study was to investigate the rôle of calcitonin gene-related peptide (CGRP) in the modulation of the elicitation of immediate and delayed, immunological and non-immunological reactions in human skin. CGRP (13 pmol and 39 pmol), and the CGRP-antagonist, CGRP/8-37/, (50 pmol and 500 pmol) were injected intracutaneously prior to provocation tests. Patients with allergy to nickel were provoked with nickel sulfate epicutaneously, and the reactions were evaluated by a clinical scoring system (guidelines of the International Contact Dermatitis Research Group). Patients with allergy to birch pollen were provoked by a prick test with the allergen, and the volume of the weals was measured. The patients were also provoked with tuberculin (delayed immunologic reaction), benzalkonium chloride (irritant contact dermatitis), UV-light and benzoic acid (non-immunologic contact urticaria). The test reactions were estimated by planimetry. CGRP/8-37/ exerted dual effects on allergic contact dermatitis, causing potentiation at a dose of 500 pmol (p= 0.004) and inhibition at a dose of 50 pmol (p=0.012). Other reactions were not significantly affected by the pretreatments. The results suggest that CGRP participates in delayed inflammatory reactions, but is not involved in immediate immunologic reactions.

Solar urticaria: mechanism and treatment.

A patient with solar urticaria induced by wavelengths 290-420 nm is reported. Wheals appeared after a few seconds of exposure to the sun; longer exposure caused general malaise and syncope. Intradermal injection of in vitro irradiated plasma caused a local whealing which was not seen with plasma kept dark. The wheals induced by irradiation could be inhibited by local injection of an antihistamine. Local injection of lidocaine and hydrocortisone was ineffective. Depletion of substance P in the skin by topical application of capsaicin did not change the sensitivity to irradiation with 313 nm and a single PUVA treatment did not change the minimal urticarial dose (MUD). Sunscreens were in practice of limited value with the exception of a protective plastic helmet. Repeated daily irradiation with UVA in increasing doses normalized his response to sunlight.

Ultraviolet light therapy in chronic urticaria.

Fifteen patients with chronic urticaria were treated with ultraviolet light B (UVB) for 1-3 months during the spring 1984 and a follow-up study was performed in November 1984-January 1985. Patients with cold urticaria, cholinergic urticaria and dermographism became clearly better or got rid of their symptoms more often than those with "non-specific" chronic urticaria. The good results achieved during the phototherapy held during the summer but in the autumn urticaria became worse in one third of the cases. The result suggests that UV-therapy might be worth trying in many patients with chronic urticaria.