Cold Provocation Test Research Articles

Особливості анестезіологічної допомоги хворим на холодову кропивницю (огляд літератури)

Cold urticaria (CU) is an allergic reaction that manifests itself as hives-like rashes or red spots in response to general or local cooling of the body. Th e disease can be acquired or hereditary, and in the cold season it can affect all segments of the population. Th is pathological condition, at first glance, does not seem to be a very dangerous variant of a local cold injury, but in persons who are prone to exposure to low temperatures, especially with a burdened cold history, it may be accompanied by chronicity of the process and complicated by neurovasculitis, obliterating endarteritis and secondary Raynaud’s syndrome, may decrease the quality of life of the victims and become a cause of disability. The pathophysiology of CU is largely unknown, but it is likely to be related to immunoglobulin E (IgE) and mast cell activation. Cooling has been reported to induce the release of neutrophilic and eosinophilic chemotactic factors, prostaglandin D2, and tumor necrosis factor (TNF-α). Less common immunologic fi ndings in patients with CU include cryoglobulinemia consisting of monoclonal IgG and mixed IgG/IgM and IgG/IgA cryoglobulin types. The mechanisms of development of CU are mainly determined by the formation of cryoglobulins (cold hemolysins) and subsequent degranulation of mast cells. Th e diagnosis of CU depends on the patient’s history and the results of cold provocation tests. Patients with CU are recommended first of all not to overcool, to take warm showers, to wear warm clothes and a hat, and not to consume cold food and drinks. Treatment options include second-generation H1 antihistamines and glucocorticosteroids. New promising option is omalizumab, a humanized monoclonal antibody derived from a recombinant DNA molecule that targets and selectively binds to circulating IgE and affects mast cells function. In patients with CU undergoing general anesthesia, premedication including antihistamines and corticosteroids is recommended, along with strict maintenance of perioperative normotermia.

The use of acupuncture in patients with Raynaud's syndrome: a systematic review and meta-analysis of randomized controlled trials.

To assess the effectiveness of acupuncture for the treatment of Raynaud's syndrome by conducting a systematic review and meta-analysis of randomized controlled trials (RCTs). Studies were identified from English and Chinese databases from their inception to September 2020. The outcomes of interest were remission incidence, number of daily attacks, incidence of positive cold stimulation tests and incidence of cold provocation tests. We conducted meta-analysis and network meta-analysis using meta and gemtc. Six trials (n = 272 participants) were included in the meta-analysis. Pairwise meta-analyses show that acupuncture was associated with increased remission incidence (risk ratio (RR) = 1.21, 95% confidence interval (CI) = 1.10 to 1.34), decreased daily number of attacks (weighted mean difference (WMD) = -0.57, 95% CI = -1.14 to -0.01), and increased incidence of positive cold stimulation tests (RR = 1.64, 95% CI = 1.27 to 2.11). There was not enough evidence to associate acupuncture with decreased incidence of positive cold provocation tests. The network meta-analyses did not demonstrate significant results for the effectiveness of any acupuncture treatments (electroacupuncture or manual acupuncture ± moxibustion), compared with controls, in terms of remission incidence or daily number of attacks, possibly due to small sample sizes and a lack of statistical power. The use of acupuncture may be effective for the treatment of Raynaud's syndrome in terms of increasing remission incidence, decreasing daily number of attacks and increasing incidences of positive cold stimulation tests. However, our findings should be interpreted with caution due to small sample sizes, very low quality of evidence and high risk of bias. Future large-scale RCTs are warranted.

Technetium-99m hand perfusion scintigraphy (Raynaud's scan) as a method of verification in hand arm vibration syndrome: a review.

It is important to assess the blood flow of fingers in the verification of hand-arm vibration syndrome. In the Republic of Korea, most assessments of the blood flow in the fingers are performed using a cold provocation test with finger skin color change. However, this test is a non-objective method with a relatively low sensitivity, leading to possible social and legal problems. Thus, we reviewed the characteristics of several tests that assess the blood flow in the fingers. Among these tests, using the radioactive isotope method, Raynaud's scan has a relatively higher sensitivity and specificity than other tests, provides objective results, and is approachable in many hospitals. So we suggest using Raynaud's scan as an alternative test when cold provocation test with finger skin color change is negative in vibration exposed worker.

Systemic Vascular Dysregulation May Be Associated With Lower Peripapillary Vessel Density in Non-glaucomatous Healthy Eyes: A Prospective Cross-Sectional Study.

Objective: To determine whether systemic vascular dysregulation (SVD) evaluated by nailfold capillaroscope and Flammer Syndrome Questionnaire (FSQ) affects retinal peripapillary microcirculation in non-glaucomatous healthy eyes at steady status.Methods: 120 healthy eyes from 63 non-glaucomatous subjects underwent Optical coherence tomography angiography (OCTA) after a rest of 30 minutes. Average retinal peripapillary capillary (RPC) vessel density (VD) and sectoral VD were automatically calculated, and peripapillary retinal nerve fiber layer thickness (RNFLT) was measured. Vasospastic diathesis was assessed using Flammer Syndrome Questionnaire (FSQ). Cold provocation test (CPT) was performed using nail-fold capillaroscope after OCTA. Positive CPT and a score of FSQ higher than 20% were necessary to determine a subject with SVD. Systemic and ocular parameters were compared between subjects with and without SVD.Results: In this study, heart rate (p = 0.042), ocular perfusion pressure (p = 0.014) and average RPC vessel density (p = 0.046) was significantly different between subjects with and without SVD determined by the combination of CPT and FSQ. Generalized estimation equation (GEE) showed lower VD was significantly associated with longer axial length (β = −0.352, p = 0.001), thinner peripapillary retinal nerve fiber layer thickness (RNFLT) (β = 0.296, p < 0.001), SVD determined by CPT and FSQ (β = 0.617, p = 0.003) and high blood pressure (β = −0.879, p < 0.001). In the superotemporal sector, multivariate model showed only SVD was associated with RPC vessel density (β = −0.811, p < 0.001).Conclusion: In subjects with SVD and non-glaucomatous healthy eyes, lower RPC vessel density in the superotemporal sector was observed. SVD determined by CPT and FSQ was significantly associated with attenuated retinal peripapillary microcirculation. Studies on ocular diseases relevant to vasospasms should consider the effects of SVD on the retinal peripapillary capillaries.

Cold Urticaria. Characterizing the population from an urticaria outpatient clinic

IntroductionCold Urticaria (ColdU) is a type of chronic inducible urticaria (CIndU) where recurrent pruritic wheals and/or angioedema occur after exposure to cold stimulus. Although it usually only affects exposed areas, systemic reactions can occur in severe cases. In this study, we seek to characterize the ColdU cases within our Centre's population of patients. Material and methodsRetrospective study based on clinical files of patients diagnosed with ColdU followed in an urticaria outpatient clinic in Portugal prior to October 2020. ResultsWe included 52 patients total (40 women) with median age of 35 years, 19 patients with symptom onset before 18 years-old. ColdU was classified as acquired in all patients. Cold provocation tests were negative in 9 patients and these were classified as atypical ColdU. No significant differences were found between those with pediatric or adult onset of disease. Most of the patients had a localized form of the disease (52%). Despite not being statistically significant, it was found that patient's temperature threshold, assessed with TempTest® 4.0, was higher and stimulation time was shorter in more severe groups. All patients were treated with non-sedating antihistamines (daily or on-demand), finding that those controlled with standard dosages had lower temperature thresholds than those needing higher dosages (p < 0.01). One patient was under treatment with omalizumab. ConclusionColdU is an heterogenous disease that can have life-threatening event consequences. Cold provocation tests and threshold assessment can be an important tool in the management treatment and in identifying severity groups.

Urticaria por frío. Caracterización de la población de una clínica ambulatoria especializada en urticaria

IntroductionCold Urticaria (ColdU) is a type of chronic inducible urticaria (CIndU) where recurrent pruritic wheals and/or angioedema occur after exposure to cold stimulus. Although it usually only affects exposed areas, systemic reactions can occur in severe cases. In this study, we seek to characterize the ColdU cases within our Centre's population of patients. Material and methodsRetrospective study based on clinical files of patients diagnosed with ColdU followed in an urticaria outpatient clinic in Portugal prior to October 2020. ResultsWe included 52 patients total (40 women) with median age of 35 years, 19 patients with symptom onset before 18 years-old. ColdU was classified as acquired in all patients. Cold provocation tests were negative in 9 patients and these were classified as atypical ColdU. No significant differences were found between those with pediatric or adult onset of disease. Most of the patients had a localized form of the disease (52%). Despite not being statistically significant, it was found that patient's temperature threshold, assessed with TempTest® 4.0, was higher and stimulation time was shorter in more severe groups. All patients were treated with non-sedating antihistamines (daily or on-demand), finding that those controlled with standard dosages had lower temperature thresholds than those needing higher dosages (p<0.01). One patient was under treatment with omalizumab. ConclusionColdU is an heterogenous disease that can have life-threatening event consequences. Cold provocation tests and threshold assessment can be an important tool in the management treatment and in identifying severity groups.

Detection of inflammation from finger temperature profile in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory tissue disease that leads to cartilage, bone, and periarticular tissue damage. This study aimed to investigate whether the use of infrared thermography and measurement of temperature profiles along the hand fingers could detect the inflammation and improve the diagnostic accuracy of the cold provocation test (0 °C for 5 s) and rewarming test (23 °C for180 s) in RA patients. Thirty RA patients (mean age = 49.5 years, standard deviation = 13.0 years) and 22 controls (mean age = 49.8 years, standard deviation = 7.5 years) were studied. Outcomes were the minimal and maximal: baseline temperature (T1), the temperature post-cooling (T2), the temperature post-rewarming (T3), and the Tmax-Tmin along the axis of each finger. The statistical significance was observed for the thumb, index finger, middle finger, and ring finger post-cooling and post-rewarming. Receiver operating characteristics (ROC) analysis to distinguish between the two groups revealed that for the thumb, index finger, middle finger, and ring finger, the area under the ROC curve was statistically significantly (p < 0.05) post-cooling. The cold provocation test used in this study discriminates between RA patients and controls and detects an inflammation in RA patients by the measurement of temperature profiles along the fingers using an infrared camera.Graphical abstract

Heart rate variability: the comparison between high tension and normal tension glaucoma

RelevanceVascular factors may be involved in the development of both high tension glaucoma (HTG) and normal tension (NTG) glaucoma; however, they may be not exactly the same. Autonomic dysfunction characterized by heart rate variability (HRV) is one of the possible reasons of decrease in mean ocular perfusion pressure (MOPP).PurposeTo compare the shift of the HRV parameters in NTG and HTG patients after a cold provocation test (CPT).MethodsMOPP, 24-hour blood pressure and HRV were studied in 30 NTG, 30 HTG patients, and 28 healthy subjects. The cardiovascular fitness assessment was made before and after the CPT. The direction and magnitude of the average group shifts of the HRV parameters after CPT were assessed using the method of comparing regression lines in order to reveal the difference between the groups.ResultsMOPP and minimum daily diastolic blood pressure were decreased in HTG and NTG patients compared to healthy subjects. There was no difference in MOPP between HTG and NTG before the CPT. However, all HRV parameters reflected the predominance of sympathetic innervation in glaucoma patients compared to healthy subjects (P < 0.05).Before the CPT, the standard deviation of NN intervals (SDNN) of HRV was lower in HTG compared to NTG, 27.2 ± 4.1 ms and 35.33 ± 2.43 ms (P = 0.02), respectively. After the CPT, SDNN decreased in NTG by 1.7 ms and increased in HTG and healthy subjects by 5.0 ms and 7.09 ms, respectively (P < 0.05). The analysis of relative shift of other HRV parameters after the CPT also revealed a significant difference between NTG and HTG in regard to the predominance of sympathetic innervation in NTG compared to HTG.ConclusionPatients with NTG have more pronounced disturbance of autonomic nervous system than HTG patients, which is manifested with the activation of sympathetic nervous system in response to CPT. This finding refers to the NTG pathogenesis and suggests the use of HRV assessment in glaucoma diagnosis and monitoring.

Heart rate variability in normal tension glaucoma: A case-control study.

Primary vascular dysregulation (PVD) is believed to be a main cause of local vasospasm and impaired autoregulation as a possible contributing factor in the pathogenesis of normal tension glaucoma (NTG). Subjects with PVD respond stronger to psychological stress. Autonomic dysfunction is another reason of instable ocular blood flow and may be studied by means of assessment of heart rate variability (HRV) especially during a hand-cold provocation test (CPT).To compare the shift of HRV parameters in NTG and healthy subjects after a cold provocation test and to assess the relation between structural damage, circulatory parameters and autonomic dysfunction in NTG.HRV was studied using CPT in 78 NTG patients and 60 health control matches. The ocular blood flow was measured using color Doppler imaging (CDI). The 24 hours blood pressure (BP) monitoring was carried out. The cardiovascular fitness assessment was made to all patients before and after CPT. Mean group difference of HRV parameters was compared between NTG and healthy subjects using the Euclidean metric. The mean ocular perfusion pressure (MOPP) was measured. Optic nerve head and retinal nerve fiber layer (RNFL) were evaluated using spectral-domain optic coherence tomography (SD-OCT). The relation between HRV, CDI, and SD-OCT-parameters was assessed.In contrast to healthy subjects, a predominance of the sympathetic activity after the CPT was revealed in the NTG group. The end diastolic velocity (EDV) in central retinal artery (CRA) and short posterior ciliary artery (SPCA) was significantly reduced in NTG compared to healthy eyes. In NTG, the main HRV parameter characterizing the total effect of autonomic blood circulation regulation (SDNN) correlated with MOPP (0.75, P = .035), SPCA EDV (0.93, P < .001), and CRA EDV (0.9, P < .001). The average daily diastolic BP correlated with RNFL (0.67, P = .009).The NTG patients have the disturbance of the autonomic nervous system, which increases in response to stress provocation and is related to ocular blood flow and structural damage.

Variability in peripheral rewarming after cold stress among 255 healthy Norwegian army conscripts assessed by dynamic infrared thermography

ABSTRACTExposure to cold climate is an inevitable consequence of military training in Norway. Adequate peripheral microcirculation in the extremities is important to maintain temperature, and to protect against freezing cold injuries. The aim of this study was to investigate the variability in skin rewarming ability. The study subjects consisted of 260 healthy Norwegian army conscripts, following a mild cold provocation test (hands immersed in 20°C water for 1 min) using dynamic infrared thermography (DIRT). Thermal images were obtained to investigate any differences in skin rewarming ability of the hand (fingers). DIRT took place under standardised and stable study conditions. Conscripts were characterised as either slow, intermediate or rapid rewarmers. While 90% could recover, partially or completely, within 4 min to the skin temperature values before the provocation test, 10% showed a slow rewarming pattern. In the slow rewarmers, the rewarming ability was correlated with a low average temperature of the hands prior to the cooling test. The healthy young army conscripts in this study showed a large variability in their rewarming ability following a standardised mild cold provocation test.

Health Effects and Work Disability Caused by Exposure to Hand-Transmitted Vibration Among Stone Cutting Workers

There are limited epidemiologic data to allow reliable conclusions about industrial workers’ exposure to hand-transmitted vibration and its disorders in developing countries. This study aimed to investigate the clinical features of hand–arm vibration syndrome (HAVS) and work disability caused by exposure to hand-transmitted vibration in stone cutting workers. The study population consisted of 40 stone cutting workers and 30 metal workers as a control group employed in the workshops located in Hamadan (western province of Iran). Measuring exposure to hand-transmitted vibration (HTV) was performed using a vibration meter (model 2260, B and K) and its analyzer (model 1700). By means of a clinically administered questionnaire, information on HAVS symptoms was obtained. The cold water provocation and touch sensory tests were performed for determining sensorineural and vascular functions. The grip strength and manual dexterity tests were also conducted for diagnosis of work disability. The daily vibration exposures of stone cutting workers were significantly higher than the national exposure limit. The prevalence of fingers’ blanching and fingers’ sensation disorders in stone cutting workers was 37.5 and 35, respectively, but none of the controls had these symptoms. It is revealed that the work abilities of the stone cutting workers have been decreased from 18 to 35 compared with the control group. The findings confirmed that the vascular and sensorineural disorders have significantly reduced the work ability of the stone cutting workers during long-term exposure to HTV. This study covered the lack of information regarding the HAVS symptoms experienced by stone cutting workers and provided a local database for further research about dose–effect relationships. © 2017, Australian Acoustical Society.

Evaluation of Peripheral Vascular Impairment in the Fingers of Baseball Players

PURPOSE: Digital vessel trauma from repetitive impact on the fingers and hand is a concern for baseball players (BPs). Laser-Doppler blood perfusion imaging (LDPI) is a technique that employs two-dimensional horizontal scanning of the blood flow in a specific tissue, without the necessity for surface contact. The LDPI method may have the benefit of detecting vasospastic abnormalities and occlusion of the digital arteries, which generally appears as an inhomogeneous reaction to the cold. This study used LDPI to investigate whether the changes in finger skin blood flow that occurred in response to a cold water immersion test depended on the position of BPs. METHODS: The study included 57 male university BPs, aged 20 ± 1 years, who play at 3 different positions. From this study subject group, there were: 18 pitchers, 23 infielders (InF), and 16 outfielders (OtF). A cold provocation test was carried out by immersing a subject’s catching hand into cold water (10°C) for 10 min. Repeated image scanning of skin blood flow on the palm was performed every 2 min before, during, and after cold water immersion, by using LDPI. The mean blood perfusion values in the index finger area were calculated on each color-coded image. A numerical perfusion reading was also obtained for each measurement site in terms of the voltage (V). From the perfusion reading and the mean blood pressure, we calculated the cutaneous vascular conductance (CVC). The finger skin temperature was recorded by using an electrode thermistor attached to the skin on the dorsal side of the index finger. RESULTS: CVC values of the InF were significantly lower compared with those of the OtF at pre-immersion (2.4 ± 0.6 V/mmHg vs. 3.3 ± 1.0 V/mmHg, p < 0.01) and at early post-immersion (1.2 ± 0.4 V/mmHg vs. 1.5 ± 0.5 V/mmHg, p < 0.05). However, the index finger skin temperature did not significantly differ among the different player positions at any measurement point. CONCLUSIONS: These findings suggest that the changes in finger skin blood flow that occurred in response to cold water immersion, as measured by using LDPI, were dependent on the position of the BP. Repetitive trauma caused by the impact of a baseball also leads to peripheral vascular impairment in the index finger on the gloved hand of InF. Therefore, this method can be used for the assessment of peripheral circulatory function in BPs.

The relationship between clinical and standardized tests for hand-arm vibration syndrome.

Standardized laboratory tests are undertaken to assist the diagnosis and staging of hand-arm vibration syndrome (HAVS), but the strength of the relationship between the tests and clinical stages of HAVS is unknown. To assess the relationship between the results of thermal aesthesiometry (TA), vibrotactile (VT) thresholds and cold provocation (CP) tests with the modified Stockholm scales for HAVS and to determine whether the relationship is affected by finger skin temperature. Consecutive records of workers referred to a Tier 5 HAVS assessment centre from 2006 to 2015 were identified. The diagnosis and staging of cases was undertaken from the clinical information contained in the records. Cases with alternative or mixed diagnoses were excluded and staging performed according to the modified Stockholm scale without knowledge of the results of the standardized laboratory tests. A total of 279 cases of HAVS were analysed. Although there was a significant trend for sensorineural (SN) and vascular scores to increase with clinical stage (P < 0.01), there was no significant difference in scores between 2SN early and 2SN late or between 2SN late and 3SN. There was moderate correlation between the TA and VT scores and the clinical SN stages (r = 0.6). This correlation did not change when subjects were divided into those with a finger skin temperature <30 and >30°C. CP scores distributed bimodally and correlated poorly with clinical staging (r = 0.2). Standardized SN tests distinguish between the lower Stockholm stages, but not above 2SN early. This has implications for health surveillance and UK policy.

A cross sectional study on hand-arm vibration syndrome among a group of tree fellers in a tropical environment.

This study aimed to explore the clinical characteristics of hand arm vibration syndrome (HAVS) in a group of tree fellers in a tropical environment. We examined all tree fellers and selected control subjects in a logging camp of central Sarawak for vibration exposure and presence of HAVS symptoms utilizing vibrotactile perception threshold test (VPT) and cold water provocation test (CWP). None of the subjects reported white finger. The tree fellers reported significantly higher prevalence of finger coldness as compared to the control subjects (OR=10.32, 95%CI=1.21–87.94). A lower finger skin temperature, longer fingernail capillary return time and higher VPT were observed among the tree fellers as compared to the control subjects in all fingers (effect size >0.5). The VPT following CWP of the tree fellers was significantly higher (repeated measures ANOVA p=0.002, partial η2=0.196) than the control subject. The A (8) level was associated with finger tingling, numbness and dullness (effect size=0.983) and finger coldness (effect size=0.524) among the tree fellers. Finger coldness and finger tingling, numbness and dullness are important symptoms for HAVS in tropical environment that may indicate vascular and neurological damage due to hand-transmitted vibration exposure.

Hand-arm vibration syndrome: Clinical characteristics, conventional electrophysiology and quantitative sensory testing

ObjectiveWorkers exposed to vibrating tools may develop hand-arm vibration syndrome (HAVS). We assessed the somatosensory phenotype using quantitative sensory testing (QST) in comparison to electrophysiology to characterize (1) the most sensitive QST parameter for detecting sensory loss, (2) the correlation of QST and electrophysiology, and (3) the frequency of a carpal tunnel syndrome (CTS) in HAVS. MethodsQST, cold provocation tests, fine motor skills, and median nerve neurography were used. QST included thermal and mechanical detection and pain thresholds. ResultsThirty-two patients were examined (54±11years, 91% men) at the more affected hand compared to 16 matched controls. Vibration detection threshold was the most sensitive parameter to detect sensory loss that was more pronounced in the sensitivity range of Pacinian (150Hz, x12) than Meissner’s corpuscles (20Hz, x3). QST (84% abnormal) was more sensitive to detect neural dysfunction than conventional electrophysiology (37% abnormal). Motor (34%) and sensory neurography (25%) were abnormal in HAVS. CTS frequency was not increased (9.4%). ConclusionFindings are consistent with a mechanically-induced, distally pronounced motor and sensory neuropathy independent of CTS. SignificanceHAVS involves a neuropathy predominantly affecting large fibers with a sensory damage related to resonance frequencies of vibrating tools.

Raynaud-Phänomen bei einer beruflichen Vibrationsbelastung

A 34-year-old female stonemason was referred for expert opinion. The question at issue was, whether she suffered from vibration-induced white finger disease. She was exposed to high-frequency hand-arm vibrations for many years. She reported white finger attacks at the long fingers, which were associated with cold weather. Until this point, physical findings were normal. The cold water provocation test showed a slight delay of the rewarming for the long fingers of the right hand. The nailfold capillary microscopy was normal. The slight Raynaud's phenomenon was recognized as an occupational disease with a diagnosis of vibration-induced white finger disease. About three years later, the symptoms of the Raynaud's phenomenon had deteriorated, although the patient had finished working with vibrating tools. The cold water provocation test confirmed the deterioration. At this time, the patient had inflamed swellings of some joints caused by rheumatoid arthritis. The differential diagnosis of a Raynaud's phenomenon should include occupational causes. Occupational history is diagnostically indicative. If an occupational disease is assumed, a report must be filed. With respect to German social law, the deterioration of the Raynaud's phenomenon was caused by the rheumatoid arthritis, which is regarded as independent from the job.

Three-Grade Classification of Photoplethysmography for Evaluating the Effects of Treatment in Raynaud Phenomenon

We assessed the utility of a 3-grade classification of photoplethysmography (PPG) with cold water provocation test in Raynaud phenomenon (RP). A total of 35 patients with RP and 38 healthy volunteers were recruited. In healthy volunteers, PPG was measured twice at intervals of 30 minutes for evaluating reproducibility of test. Percentage variation of the PPG amplitude in post- versus precold provocation was expressed on a 3-grade scale at 1, 3, and 5 minutes (reflection index: RI) in patients with RP. The improvement pattern of the PPG (IPPPG) was evaluated by summing the score differences from RI1min to RI3min and RI5min. After a therapeutic period of 8 weeks with nifedipine, the decreases in posttherapeutic RI3min and RI5min were statistically significant (P < .05). Subgroup analysis of IPPPG showed statistical significance in patients with negative fluorescent antinuclear antibody (P < .05). The analysis of cold-provoked PPG waves demonstrated and quantified improvements in peripheral arterial circulation in RP.

Nailfold capillaroscopic examination and T786C endothelial nitric oxide synthase polymorphism in normal tension glaucoma patients

AbstractPurpose The purpose of this study was assessment of nailfold capillary changes and their possible relation to polymorphism of a gene encoding endothelial nitric oxide synthase (eNOS) in normal tension glaucoma (NTG) patientsMethods The study included 35 normal‐tension glaucoma (NTG) patients (23 female and 12 male). Capillaroscopic examination of the nailfold capillaries of II to V fingers of both hands was performed (before and after the cold provocation test) by means of a videocapillaroscope. T786C eNOS gene polymorphism was determined by RT‐ PCR methods.Results 31 (88.6%) patients suffered from cold extremities. In 24 (68.5%) patients nailfold capillaroscopy was within normal limits, in 11 (31.5%) patients the results were abnormal, 4 (11.4%) of them mimicked changes observed in sclerodermia. The cold provocation test was positive in 43.5% of NTG patients. The patients with NTG presented the following nailfold capillaries: megacapilaries or dilatated capillaries (44.4%), ramified/bushy (18.9%), coiled (17.1%). Assessing the T786C polymorphism of eNOS gene in NTG patients, TT genotype was present in 36% patients, TC in 52.6% and CC in 11.3%. There were no correlation between SNP variants and capillaroscopy results nor cold provocation test ( p=0.9 and 0.5, respectively).Conclusion The T786C polymorphism of eNOS gene does not influence the capillaroscopy results. The high incidence of sclerodermia ‐ like changes in capillaroscopy in NTG needs further studies.

Autonomic nerve system responses for normal and slow rewarmers after hand cold provocation: effects of long-term cold climate training

Differences among individuals concerning susceptibility to local cold injury following acute cold exposure may be related to function of the autonomic nervous system. We hypothesized that there are differences in heart rate variability (HRV) between individuals with normal or more pronounced vasoconstriction following cold exposure and that there is an adaptation related to prolonged cold exposure in autonomic nervous system response to cold stimuli. Seventy-seven young men performed a cold provocation test, where HRV was recorded during cold hand immersion and recovery. Forty-three subjects were re-examined 15 months later, with many months of cold weather training between the tests. Subjects were analyzed as 'slow' and 'normal' rewarmers according to their thermographic rewarming pattern. For the 'pre-training' test, before cold climate exposure, normal rewarmers had higher power for low-frequency (PLF) and high-frequency (PHF) HRV components during the cold provocation test (ANOVA for groups: p = 0.04 and p = 0.005, respectively). There was an approximately 25 % higher PHF at the start in normal rewarmers, in the logarithmic scale. Low frequency-to-high frequency ratio (PLF/PHF) showed lower levels for normal rewarmers (ANOVA for groups: p = 0.04). During the 'post-training' cold provocation test, both groups lacked the marked increase in heart rate that occurred during cold exposure at the 'pre-training' setting. After cold acclimatization (post-training), normal rewarmers showed lower resting power values for the low-frequency and high-frequency HRV components. After winter training, the slow rewarmers showed reduced low-frequency power for some of the cold provocation measurements but not all (average total PLF, ANOVA p = 0.05), which was not present before winter training. These HRV results support the conclusion that cold adaptation occurred in both groups. We conclude that further prospective study is needed to determine whether cold adaptation provides protection to subjects at higher risk for cold injury, that is, slow rewarmers.

Erythromelalgia: Incidence and clinical experience in a single centre in Sweden

Erythromelalgia (EM) incidence has not been well studied and there are only two studies published on this subject as far as we know. The aims are to study the incidence of this rare condition in the south of Sweden, to report the clinical experience from a single centre including characterisation of comorbidity and to report on prognosis. Retrospective study of a population-based analysis of data from the southernmost part of Sweden corresponding to the median age of the patients (Statistics Sweden). The diagnosis of EM is based on the medical record reflecting the triad of redness, burning pain and increased temperature of the feet or hands or both. We evaluated the presence or absence of EM triad by recording the history, physical examination, laboratory analysis, cold provocation test and laser Doppler imaging, and by searching for any confounding disease in cases of suspected EM. During a 10.5 year period we clinically identified 27 patients with EM. Median age was 49 [IQR (34 - 68)] years, 19 (70 %) were women. The mean delay from the onset of the symptoms to the time of diagnosis was 4.5 (SD ± 3.9) years. Gender and age adjusted incidence of EM for our region was calculated to be 0.36 per 100 000 persons per year. Three patients developed intraabdominal cancer during the follow up, but there was no mortality directed related to EM. The overall population-based incidence of erythromelalgia was 0.36 per 100 000 which is identical with a previous report in a Scandinavian population.