Flare Response Research Articles

Comparative evaluation of H1 receptor blocking activity and safety of newer H1antagonist mizolastine with loratadine and placebo: a randomized double blind three way crossover study

Background: Histamine is a naturally occurring body constituent synthesized from L-histidine by histidine decarboxylase enzyme that is expressed throughout the body including central nervous system neurons, gastric mucosa, mast cells and basophils. The objective of this study was to compare the pharmacological activity and safety of 10 mg mizolastine, 10 mg loratadine and placebo in healthy human volunteers. Methods: After randomly allocating the 3 drugs, a battery of psychometric tests was done. Histamine prick test for wheal and flare reaction, VAS for sedation and itch followed by salivary flow test were done. Vitals were recorded. The subjects were randomized to receive either of the treatment in a cross-over manner with washout period of 7 days. The wheal and flare areas were recorded before and after 1,2,4,8, and 24 hours. Results: Mean inhibition on histamine induced wheal and flare response with mizolastine was highly significant as compared to placebo from 1 hour onwards (p<0.001) with maximum inhibition of 98.1±1.8% at 4 hours and of 85.1±24.8percent at 8 hours, for wheal and flare, respectively. The mean inhibition on histamine induced response with loratadine was significant from 2 hours (p<0.05) for wheal area and 1 hour onwards up to 24 hours (P<0.01) for flare area with the maximum inhibition of 56.2±31.6 percent and 60.1±14.2percent at 8hours, respectively. Mean inhibition on histamine induced itch with mizolastine was also significant from 4 hours onwards and persisted up to 24 hours (p<0.05) with maximum inhibition of 58.6±54.2% at 8 hours for the itch response, unlike loratidine. There was no significant change in mean effect on sedation assessed on a VAS of 0-100 mm. There was no significant change in psychomotor functions, salivary flow or vital parameters. All were well tolerated. Conclusions: Mizolastine has good antihistaminic activity than loratadine. Neither drug causes any psychomotor impairment or has anti-cholinergic action.

Comparative Study of Positive Versus Negative Autologous Serum Skin Test in Chronic Spontaneous Urticaria and its Treatment Outcome.

Background:Chronic urticaria (CU) is defined as urticaria persisting daily or almost daily for more than 6 weeks and affecting 0.1% of the population. Mast cell degranulation and histamine release are of central importance in the pathogenesis of CU. About 40-50% of the patients with chronic idiopathic urticaria (CIU) or chronic spontaneous urticaria (CSU) demonstrates an immediate wheal and flare response to intradermal injected autologous serum. This led to the concept of autoimmune urticaria (AIU).Aims:To determine the occurrence, clinical features, associated clinical conditions, comorbidities of AIU, and to compare this with CSU. This study aimed to find the frequency of autologous serum skin test (ASST)-positive patients among patients with CSU and to identify the clinical and laboratory parameters associated with positive ASST and to compare the treatment outcome.Materials and Methods:A prospective correlation study in 110 patients with CSU was conducted, after screening 200 CU patients attending the outpatient Department of Dermatology during from January 2012 to May 2013. Patients were subjected to ASST, complete blood counts, urine routine examination, liver function tests, renal function tests, thyroid function tests (T3, T4, and TSH), and urine analysis.Results:Out of 200 CU patients screened, 90 patients had excludable causes based on detailed history and skin prick test, and the remaining 110 patients were considered to have CSU. These 110 patients were further subjected to ASST, serum immunoglobulin E (IgE), and peripheral blood eosinophilia. ASST was positive in 48 patients and negative in 62 patients. Frequency of urticarial attacks and associated diseases such as abnormal thyroid function tests in both ASST-positive and ASST-negative patients did not show any statistical significance. Only attacks of angioedema in ASST-positive individuals were higher and were statistically significant. In the ASST-positive group, 31 (81.25%) patients showed improvement with first-line antihistamines, along with oral prednisolone and injection Histaglobulin and 10 (10.41%) patients did not show any improvement. Thirty-three (43.54%) patients in the ASST-negative group showed improvement while 13 (30.62%) patients did not show improvement.Conclusion:ASST is considered a screening test for AIU, which decreases the rate of diagnosis of idiopathic form of CU. ASST-positive patients in addition to antihistamines, were treated with short course of oral steroids and weekly Histaglobulin injections for 5 weeks followed by the 3rd and 6th months.

Response of the Mars ionosphere to solar flares: Analysis of MGS radio occultation data

AbstractIncreased soft X‐ray irradiance during solar flares produces increased electron densities in the lower ionosphere of Mars, and the relative changes in electron density during a flare are greater for lower altitudes and larger flares. However, this relationship has not been quantified. This has impeded the validation of simulations of the ionospheric response to flares, which are necessary for developing accurate descriptions of the physical processes governing ionospheric behavior under extreme conditions. Here we develop a response function, a mathematical expression for the change in electron density during a solar flare as a function of the change in solar flux and an optical depth proxy. This function is based on analysis of 20 Mars Global Surveyor (MGS) radio occultation electron density profiles measured during solar flares. We find that characterizing the response as a function of optical depth, rather than altitude, provides the best description of ionospheric variability during a flare. A separate response function, determined from analysis of a numerical simulation of the response to a solar flare, was found to be grossly similar to the observationally based response function, though with a weaker dependence on optical depth. We identify 15 MGS profiles with an apparent solar flare response, but no coincident detected solar flare. We suggest that the observed response function can be used to detect flares not visible from Earth and to give an approximation of their strength. Additionally, it can estimate ionospheric electron densities during a flare; however, precision is limited by a small number of observations.

Nociceptors in the skin: fire-raisers to be kept at bay?

Nociceptors in the skin: fire-raisers to be kept at bay?

A randomized, double-blind, crossover study to evaluate the depth response relationship of intradermal capsaicin-induced pain and hyperalgesia in healthy adult volunteers.

The purpose of this study was to evaluate pain and hyperalgesia in response to different depths of intradermal (ID) capsaicin injections in healthy volunteers. Double-blind, cross-over study. Clinical Research Laboratory. Fifteen healthy male subjects received ID capsaicin injections into the volar aspect of each forearm at depths of 1 mm, 3 mm, 5 mm, and 7 mm. After injection, spontaneous pain, elicited pain, flare response, heat thresholds, and area of hyperalgesia were measured at various time points. Spontaneous pain, elicited pain (pinprick, stroking, and hot pain), hyperalgesia area, and allodynia area. No significant difference was found between any depths in spontaneous pain, elicited pain (pinprick, stroking, hot pain), hyperalgesia area, or allodynia area. A significant difference was found in the change in heat threshold between 5 mm and 1 mm, 7 mm and 1 mm, 5 mm and 3 mm, 7 mm and 3 mm depths. A significant difference was found in flare area between 5 mm and 3 mm depths. A significant difference was found in systolic blood pressure area under the curve (AUC) between 7 mm and 1 mm depths, and for both systolic and diastolic pressures for 5 mm and 1 mm depths, and 5 mm and 3 mm depths. A significant difference was found in pulse AUC between 5 mm and 1 mm depths and 5 mm and 3 mm depths. Injection of capsaicin at different depths in the skin had different effects on heart rate and blood pressure but no effect on pain. These results may have implications on the pharmacology and analgesic predictive value of the model of ID capsaicin.

(317) Increased neurogenic and inflammatory pain in healthy young adults with greater early life stress

Early life stress is a risk factor for chronic pain in adulthood, yet little is known about the underlying mechanisms. The purpose of this experiment was to evaluate whether healthy individuals reporting high levels of early life stress would show enhanced spontaneous pain and neurogenic flare responses to topical capsaicin. Capsaicin temporarily induces localized spontaneous pain and neurogenic inflammation by engaging mechanisms involved in neuropathic and inflammatory pain. A total of 2,625 participants were prescreened for their early life stressful events using the Early Trauma Inventory Self-report-short form (ETISR-SF).

Outcome Measures for Gout Clinical Trials: a Summary of Progress

Gout is the most common form of inflammatory arthritis. With the development of new agents for the treatment of gout in the last decade, the lack of validated outcome measures for clinical trials in gout has become apparent. Gout has been a topic of discussion at Outcomes in Rheumatology Clinical Trials (OMERACT) meetings since 2002. This work has included identification of core domains for outcome measures for both acute and chronic gout studies. More recently, OMERACT have endorsed a number of these domains and measurement instruments for these domains. The domains appear to be largely relevant to patients with gout but additional issues have been identified, including the absence of an endorsed disease-specific measure of health-related quality of life. Concurrently, a preliminary definition of flare has been developed and leading from this, early versions of composite measures of disease activity and response criteria. With the ability for excellent serum urate control, remission should be possible and preliminary remission criteria have been proposed. Flare definition, response criteria and remission criteria require further validation. The role of serum urate as a biomarker for chronic gout studies is promising, but further work is required to show that serum urate is a biomarker of relevant clinical outcomes.

Inhibitory Effect of Phlai Capsule on the Histamine and Allergen-Induced Wheal and Flare Response on Skin Test Response Among Allergic Rhinitis Patients

Inhibitory Effect of Phlai Capsule on the Histamine and Allergen-Induced Wheal and Flare Response on Skin Test Response Among Allergic Rhinitis Patients

The reservoir effect of topical steroids in vitiliginous skin: A cross-sectional study.

Prolonged and frequent use of topical steroids may lead to decrease in efficacy as well as many local adverse effects. Stratum corneum has a unique property of reservoir effect. To study the reservoir effect of topical steroids in a steroid-responsive condition which may enable a decrease in the dosing frequency of topical steroids. A cross-sectional study design was used. Patients with at least three vitiliginous patches of more than 2 cm 2 present over the trunk or limbs were included. Exclusion criteria were topical or systemic corticosteroid use within the previous 4 weeks, antihistamine use within the previous 7 days, history of any allergy in the past and immunosuppression. Clobetasol propionate cream was applied on the first vitiliginous area (site A) and fluticasone propionate ointment was applied on the second vitiliginous area (site B). The third vitiliginous area, site C (control site) was left without applying any medication. Histamine-induced wheal suppression test was performed on each site, at the same time of the day, on every consecutive day following steroid application, until the values obtained at sites A and B approached those obtained at site C. SPSS software for Windows, version 16.0 was used for statistical analysis. The mean and standard deviation of the various studied parameters were calculated for various treatment groups and compared using analysis of variance (ANOVA) test. Forty patients were included in the study. The average wheal volumes and average erythema sizes at sites A and B were significantly smaller than the corresponding values at site C for up to 5 days after applying medication (P < 0.001). The presence of a cutaneous reservoir of topical steroid was confirmed based on its suppressive effect on the wheal and flare response to histamine. It is not certain that the concentration that suppresses histamine-induced wheal and flare is sufficient for therapeutic efficacy in vitiligo. The reservoir effect of topical clobetasol propionate and fluticasone propionate persisted for 5 days in vitiliginous skin. Hence, it may be possible to reduce the frequency of topical steroid application in vitiligo.

Measurement of cooling detection thresholds for identification of diabetic sensorimotor polyneuropathy in type 1 diabetes.

ObjectiveCompared to recently-studied novel morphological measures, conventional small nerve fiber functional tests have not been systematically studied for identification of diabetic sensorimotor polyneuropathy (DSP). We aimed to determine and compare the diagnostic performance of cooling detection thresholds (CDT) in a cross-sectional type 1 diabetes cohort.Research Design and Methods136 subjects with type 1 diabetes and 52 healthy volunteers underwent clinical and electrophysiological examination for DSP classification concomitantly with the Toronto Clinical Neuropathy Score (TCNS) and three small fiber function tests: CDT, heart rate variability (HRV), and laser doppler imaging of axon-mediated neurogenic flare responses to cutaneous heating (LDIFLARE). Area under the curve (AUC) and optimal thresholds were determined by receiver operating characteristic (ROC) curves in the type 1 diabetes cohort.ResultsType 1 diabetes subjects were 42±17 years of age with mean HbA1c 7.9±1.7%. Fifty-nine (45%) met the case definition for DSP. CDT values were lowest in cases with DSP (18.3±8.4°C) compared to controls without DSP (28.4±3.5°C) and to healthy volunteers (29.6±1.8°C; p-value for both comparisons<0.0001). AUCCDT was 0.863 which was similar to AUCTCNS (0.858, p = 0.24) and AUCHRV (0.788, p = 0.05), but exceeded AUCLDIFLARE (0.750, p = 0.001). The threshold of <25.1°C was equivalent to the lower bound of the healthy volunteer 95% distribution [25.1, 30.8°C] and performed with 83% sensitivity and 82% specificity.ConclusionsAkin to novel small fiber morphological measures, CDT is a functional test that identifies DSP with very good diagnostic performance. These findings support further research that revisits the role of CDT in early DSP detection.

Effects of neonatal treatment with the TRPV1 agonist, capsaicin, on adult rat brain and behaviour

Treatment of neonatal rats with the transient receptor potential vanilloid 1 (TRPV1) channel agonist, capsaicin, produces life-long loss of sensory neurons expressing TRPV1 channels. Previously it was shown that rats treated on day 2 of life with capsaicin had behavioural hyperactivity in a novel environment at 5–7 weeks of age and brain changes reminiscent of those found in subjects with schizophrenia. The objective of the present study was to investigate brain and behavioural responses of adult rats treated as neonates with capsaicin. It was found that the brain changes found at 5–7 weeks in rats treated as neonates with capsaicin persisted into adulthood (12 weeks) but were less in older rats (16–18 weeks). Increased prepulse inhibition (PPI) of acoustic startle was found in these rats at 8 and 12 weeks of age rather than the deficit commonly found in animal models of schizophrenia. Subjects with schizophrenia also have reduced flare responses to niacin and methylnicotinate proposed to be mediated by prostaglandin D2 (PGD2). Flare responses are accompanied by cutaneous plasma extravasation. It was found that the cutaneous plasma extravasation responses to methylnicotinate and PGD2 were reduced in capsaicin-treated rats. In conclusion, several neuroanatomical changes observed in capsaicin-treated rats, as well as the reduced cutaneous plasma extravasation responses, indicate that the role of TRPV1 channels in schizophrenia is worthy of investigation.

Bilateral Hypersensitivity to Capsaicin, Thermal, and Mechanical Stimuli in Unilateral Complex Regional Pain Syndrome

Complex regional pain syndrome is multifactorial. Exaggerated inflammatory responses to limb injury may be involved. The authors hypothesized that capsaicin-induced pain and neurogenic inflammation (skin perfusion and flare area) are increased in patients with complex regional pain syndrome compared with that in controls. Twenty patients with unilateral upper-limb complex regional pain syndrome and 20 age-, sex-, and body mass index-matched controls participated. Topical capsaicin 5% was applied to the back of both hands for 30 min, and pain intensity was assessed on a visual analogue scale. A laser Doppler perfusion imager scanner estimated capsaicin-induced skin perfusion and flare area. Autonomic and small-fiber function was assessed by sensory testing, quantitative sudomotor axon reflex test, and vasoconstrictor responses. The authors found bilateral hypersensitivity to capsaicin (P ≤ 0.02), skin fold (P = 0.001), joint pressure (P < 0.0001), cold (P ≤ 0.01), and heat pain (P ≤ 0.04) in patients compared with that in controls and thermal and mechanical hyperalgesia in the complex regional pain syndrome-affected hand compared with that in the unaffected hand (P ≤ 0.001). The patients had normal capsaicin-induced flare areas, thermal detection thresholds, quantitative sudomotor axon reflex test, and vasoconstrictor responses. The main finding is bilaterally increased capsaicin-induced pain in patients compared with controls. The flare response to capsaicin was normal, suggesting that the increased pain response was not due to increased neurogenic inflammation. The bilateral hypersensitivity to painful chemical, thermal, and mechanical stimuli not confined to the innervation area of a peripheral nerve or root cannot be explained by a regional change and may partly be due to central sensitization.

Complex Generalized Instead of Complex Regional?

FOR more than 100 yr, the pain community has puzzled over what we now call complex regional pain syndrome (CRPS), and this contemplation seems to have been scientifically productive, given that a PubMed search using the CRPS keywords returns 4,862 results (as of January 21, 2014) with a steadily increasing number of publications over the last 20 yr. One result of this research is a lively scientific discussion whether the main pathophysiology of CRPS has to be looked for in the peripheral or the central nervous system.In this issue of Anesthesiology, Terkelsen et al.1 have added another chapter to this story: Generalized central sensitization as indicated by bilateral hyperalgesia to various painful stimuli in patients with CRPS. To investigate the function of the peripheral nervous system, the authors tested thermal sensation, sympathetic reflexes, and capsaicin-evoked flare responses and did not observe any differences between patients and controls. On the basis of their results, the authors concluded that CRPS is not regional, rather it is a generalized central pain syndrome, and peripheral changes might be of minor importance. However, in the first months after onset clinical observation of patients with CRPS very often reveals all signs of inflammation as defined by early Galen: reddening (rubor), pain/hyperalgesia (dolor), edema (tumor), temperature increase (calor), and loss of function (functio laesa). In addition, there is localized proliferation of fibroblasts, bone cells, and hairs.First of all, we would like to commend the authors for their comprehensive study and the clear presentation of their results—from a group of mainly chronic patients with CRPS. However, as indicated above, we doubt that these results are generalizable to all patients with CRPS. This raises two questions: “What is CRPS?” and “What is central sensitization in CRPS?” We believe that one could be as diverse as the other and that many central findings in CRPS follow the peripheral changes.We would like to discuss these points:There are a number of ways peripheral changes can develop into something that we call centralized in CRPS, but in fact may not involve changes within the central nervous system as a driving force. Bilateral central nociceptive sensitization (as defined by quantitative sensory testing hyperalgesia) has been described in various pain diseases, for example, in whiplash patients, in radicular and nonradicular lower back pain,9 and in fibromyalgia. In particular, fibromyalgia is a very good example that these ostensibly central findings are not necessarily specific to central nervous system mechanisms. A significant proportion of these patients had peripheral small-fiber pathology.10 The inflammatory mediators and neuropeptides in localized CRPS (shown also for migraine) spill over from the local release site into the circulation, which might cause spinal sensitization such as mechanical hyperalgesia.11 From focal brain damage, we know that the exposure of neuronal tissue to the circulation could lead to autoimmune encephalopathies. In posttraumatic CRPS (local damage to the peripheral nervous system), we found autoantibodies to sympathetic structures in the serum,12 which may have systemic effects. In all of these cases, it is the periphery that drives the central symptoms.We have written this controversial comment to encourage all CRPS researchers, ourselves included, to move a step forward. We should leave behind categorizations that lump together too many pathophysiologies and bring too much variation into scientific studies—we must be more specific. Headache researchers and the headache classification (which is to some extend arbitrary but very useful for research) should be paragons. In clinical practice, however, complexity is the rule. Terkelsen et al. must be thanked for adding another piece to this complex puzzle—a generalized central piece.The authors thank Darragh O’Neill, Ph.D. (Department of Neurology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany), for help with the article preparation.Supported by the German Research Foundation (Bi 579/8-1) and the EU-FP7–602133, ncRNAPain (European Union).The authors are not supported by, nor maintain any financial interest in, any commercial activity that may be associated with the topic of this article.

Ionospheric electron density response to solar flares as viewed by Digisondes

Solar flares are explosive events on the Sun that release energetic particles, X-rays, EUV, and radio emissions that have an almost immediate impact on Earth's ionosphere-thermosphere (IT) system and/or on operational systems that are affected by IT conditions. To assess such impacts, it is a key that we know how the ionosphere is modified. An objective of this paper is to evaluate how digisondes might serve in this role. Toward this end we utilize data from the Millstone Hill digisonde to reveal the height versus time bottomside F region responses to three X-class flares (X28, X8.3, and X1.7) at a middle latitude site. In terms of percent increase with respect to a preflare hourly mean, the long-lived (> 15–30 min) responses to these flares maximize between about 150 and 250 km and measurably last ~0.75–1.5 h after flare maximum. The relative magnitudes of these responses are complicated by flare position on the solar disk, which determines how much of the EUV solar emissions are attenuated by the solar atmosphere. At Millstone Hill there was little measurable response to these flares near the F2 layer peak; however, at the magnetic equator location of Jicamarca, the F2 peak electron density increased by ~15–40%. Herein, all of these flare response characteristics are interpreted in terms of available modeling results. We propose that such digisonde data, in combination with first-principles models and high-resolution measurements of solar EUV flux emissions (e.g., from Solar Dynamics Observatory/EUV Variability Experiment), can lead us to a deeper understanding of the ionospheric photochemistry and dynamics that underlies a predictive capability.

Systemic ropivacaine diminishes pain sensitization processes: a randomized, double-blinded, placebo-controlled, crossover study in healthy volunteers.

IntroductionRopivacaine is a local anesthetic widely used for regional anesthesia. One of its advantages is low toxicity at plasma concentrations reached systemically during continuous peripheral or central nervous block. The objective of this study was to test the effect of systemic ropivacaine on pain, hyperalgesia, dynamic allodynia, and flare response.MethodsThis randomized, double-blinded, placebo-controlled, crossover study was carried out in at the Clinical Trials Centre, University of Zurich, Switzerland. Twenty healthy male volunteers were included in the study. Exclusion criteria were contraindications or hypersensitivity to local anesthetics, vulnerable subjects (intellectually or mental impaired), drug, alcohol or nicotine abuse, known peripheral neuropathies, diabetes mellitus and/or congestive heart disease. Ropivacaine and saline were infused intravenously during a subcutaneous electrical stimulation. The stimulation software adjusted the stimulus strength according to the rating on a numeric rating scale (NRS; 0–10) maintaining a NRS of 5. Areas of punctate hyperalgesia, dynamic allodynia, and flare response were measured before and after the infusion.ResultsThe area of hyperalgesia increased significantly with saline (303 ± 380%, P < 0.05) and ropivacaine (186 ± 137%, P < 0.05). The area of allodynia (253 ± 299%, P < 0.05) and flare response (112 ± 24%, P < 0.05) increased only during the placebo infusion.ConclusionThe results of this study imply that systemic ropivacaine may diminish pain sensitization processes.Electronic supplementary materialThe online version of this article (doi:10.1007/s40122-013-0021-z) contains supplementary material, which is available to authorized users.

Intraoperative and Immediate Postoperative Outcomes of Cataract Surgery using Phacoemulsification in Eyes with and without Pseudoexfoliation Syndrome.

To compare the intraoperative and immediate postoperative behavior and complications in eyes with pseudoexfoliation (PEX) syndrome with eyes having senile cataract without PEX during cataract surgery using phacoemulsification (PKE). In this prospective study, 68 eyes of 68 patients were divided into two groups: Group 1 (test) comprised 34 eyes with immature senile cataract with PEX and Group 2 (control) included 34 eyes with immature senile cataract without PEX and any coexisting ocular pathology. Phacoemulsification (modern cataract surgery) was performed on both groups through stop and chop technique and comparative analysis of the incidence of intraoperative and immediate postoperative complications was made. There was no significant difference in rates of intraoperative complications between PEX (2.9%) and Control (0%) group. The mean pupil diameter was significantly smaller in Group 1 (p<0.001). No eye in either group had phacodonesis. 58.8% of eyes in Group 1 and 29.4% in Group 2 had a harder cataract (nuclear sclerosis) ≥ grade 3 (p=0.017). PKE was performed in all eyes with cataract in both groups. Intraoperative complication (zonular dialysis (dehiscence) was encountered in only 2.9% (1 case) of eyes with PEX. PC (posterior capsule) tear (rent) with vitreous loss was seen in 2.9% eyes of Group 1 and none in Group 2. Postoperatively, IOP (intraocular pressure) and aqueous flare response were comparable between the groups. Significantly higher inflammatory cell response was observed in Group 1 (p=0.014). BCVA (best corrected visual acuity) using Snellen chart with pinhole on postoperative day1 was significantly better in the control group compared to the group with PEX (p=0.027). Phacoemulsification can be safely performed by experienced hands in cataractous eyes with PEX. The incidence of intraoperative and immediate post-operative complications in eyes with PEX was not significantly different compared to eyes without PEX in our study. Further studies among a larger population are required.

Evaluation of the antihistamine effects of olopatadine and levocetirizine during a 24‐h period: A double‐blind, randomized, cross‐over, placebo‐controlled comparison in skin responses induced by histamine iontophoresis

The antihistamine effects of olopatadine and levocetirizine, in standard-dose application described in their information (5mg twice a day for olopatadine; 5mg once daily for levocetirizine), were examined from 11.5 to 24h after application. The test was designed in a double-blind, randomized, cross-over, placebo-controlled study of 12 healthy volunteers on histamine-induced flare and wheal response using an iontophoresis technique. The suppressive effect of olopatadine on the wheals induced by a 0.1-mA histamine iontophoresis lasted for 24h after dosing. Both drugs inhibited flare induced by histamine iontophoresis almost completely until 24h after the first administration. Suppression of the 0.2-mA-induced wheal response by levocetirizine, taken once daily, decreased with time, although 0.1-mA-induced flare was almost completely suppressed by the drug. Olopatadine completely suppressed even the wheal response induced by a 0.2-mA histamine iontophoresis. Compared with the placebo, the two drugs significantly suppressed the subjective itching assessed by visual analog scale at all intervals. There were no significant differences in subjective drowsiness and objective cognitive function between drug- and placebo-treated subjects. These results demonstrate that olopatadine seems to be more potent than levocetirizine when administrated in a standard dose. In conclusion, mild to moderate urticaria could be controlled by standard application as described in their information. On the other hand, severe urticaria could be managed by a standard application of olopatadine, but levocetirizine may need an additional dose to control severe urticaria.

Objective Assessment of C-Fiber Function by Electrically Induced Axon Reflex Flare in Patients With Axonal and Demyelinating Polyneuropathy

A simple test to evaluate the peripheral C-fiber function is the measurement of axon reflex flare area. In this study, we compared the flare area in healthy subjects and in two groups of patients with predominantly axonal or demyelinating polyneuropathy. We examined 42 control subjects and 33 patients. The flare responses were elicited by the application of transcutaneous electrical stimulation and recorded by laser Doppler imaging. There was a significant reduction of electrically induced flare area in both groups of neuropathy patients (P < 0.001; analysis of covariance). Interestingly, patients with an axonal neuropathy had a significantly stronger reduction of flare size as compared to patients with demyelinating neuropathy (P = 0.03). The evaluation of the axon flare response in the arm can be used as a screening test of impaired C-fiber function in polyneuropathy patients with the advantages of simplicity of the procedure and time economy.

The Rate of Decline in Small Fibre Function Assessed Using Axon Reflex-Mediated Neurogenic Vasodilatation and the Importance of Age Related Centile Values to Improve the Detection of Clinical Neuropathy

BackgroundThe LDIflare technique (LDIflare) is a simple non-invasive test of small fibre function in dorsal foot skin involving skin heating and measuring the size of the resulting axon reflex-mediated vasodilator (flare) response using a laser Doppler imager (LDI). This study establishes age-related normative reference ranges for the test and determines the rate of decline in small fibre function per decade. Additionally, the potential value of using age related centiles rather than Receiver Operator Curves (ROC) was explored by comparison of the sensitivity and specificity of each analytic technique in identifying clinical neuropathy.MethodsLDIflare areas were assessed in 94 healthy controls and 66 individuals with diabetes with (DN+, n = 31) and without clinical neuropathy (DN-, n = 35); neuropathy defined as a Neuropathy Disability Score ≥3. The age specific 5th centile values were used as the ‘cut-offs’ for the diagnosis of neuropathy from which sensitivity and specificity were calculated.ResultsThere was a significant age dependant decrease in LDIflare size (r = −0.42, p<0.0001) with no significant gender differences. The LDIflare size reduced 0.56 cm2 per decade which gives a percentage reduction of approximately 5.5% per decade. Using the normative 5th centiles as the cut-offs, the technique had a sensitivity of 77%, specificity of 90%, positive predictive value of 82% and negative predictive value of 87%.The ROC analysis gave a threshold of <3.66 cm2 for the cut-off, resulting in a sensitivity of 75%, specificity of 85%, positive predictive value of 74% and negative predictive value of 86%.ConclusionsThere is an age dependent decrease in small fibre function in the foot of 5.5% per decade. Both analytic techniques demonstrate good sensitivity and specificity for detecting clinical neuropathy but the technique based on age centiles offers better diagnostic accuracy and is therefore proposed as the method of choice.

Up‐dosing with bilastine results in improved effectiveness in cold contact urticaria

BackgroundCold contact urticaria (CCU) is characterized by itchy wheal and flare responses due to the release of histamine and other pro-inflammatory mediators after exposure to cold. The treatment of choice is nonsedating antihistamines, dosages of which may be increased up to fourfold if standard doses are ineffective. Here, we assess the effects of a standard 20 mg dose and up-dosing to 40 and 80 mg of bilastine in reducing the symptoms of CCU and inflammatory mediator release following cold challenge.MethodsTwenty patients with CCU were included in this randomized, crossover, double-blind, placebo-controlled 12-week study. They received placebo, 20, 40 or 80 mg of bilastine daily each for 7 days with 14-day washout periods. The primary readout was change in critical temperature thresholds (CTT). Secondary readouts were changes in pruritus, levels of histamine IL-6, IL-8 and TNF-α collected by skin microdialysis and safety and tolerability of bilastine.ResultsBilastine 20 mg was highly effective (P < 0.0001) in reducing CTT. Up-dosing to 80 mg significantly (P < 0.04) increased its effectiveness. At this dose, 19 of 20 (95%) patients responded to treatment, with 12 of 20 (60%) becoming symptom free. Only one patient was refractory to treatment. Microdialysis levels of histamine, IL-6 and IL-8 assessed 1–3 h after cold challenge were significantly (P < 0.05) decreased following up-dosing with 80 mg bilastine. Bilastine treat-ment was well tolerated without evidence of increased sedation with dose escala-tion.ConclusionsBilastine was effective in reducing the symptoms of patients with CCU. Increased efficacy of bilastine with fourfold up-dosing was without sedation and supports urticaria treatment guidelines.