Diffuse cutaneous systemic sclerosis following SARS-Co V-2 vaccination.

The largest world-wide vaccination rollout ever is currently underway to tackle the covid-19 pandemic. We report a case of diffuse cutaneous systemic sclerosis (SSc) in a 70-year-old male with rapidly progressive skin thickening which developed two weeks after receiving the first dose of the ChAdOx1 nCOV-19 vaccine. As the onset of SSc skin was in close temporal proximity to the administration of the first dose vaccine with no other triggers, we suspected a possible adverse reaction to the ChAdOx1 nCOV-19 vaccine. We hypothesise that the recombinant adenoviral vector encoding the spike protein antigen of SARS-CoV-2 triggered an unexpected immune activation resulting in an atypical presentation of late-onset SSc, within the well-recognised ANA positive, ENA negative subgroup of patients.We review the possible mechanisms underlying autoimmunity when provoked by vaccination and other published rheumatological phenomenon occurring shortly after COVID vaccination.

Nailfold capillaroscopy-how many fingers should be examined to detect abnormality?

Objectives: Nailfold capillaroscopy is being increasingly used by rheumatologists in the diagnosis of SSc. However, assessment of all nailfolds can be time-consuming in a busy outpatient clinic. Our aim was to answer the question as to how many (and which) fingers a clinician should routinely assess to capture accurately the true state. Methods: A total of 2994 assessments (by an international panel of expert observers) of 1600 images from 173 participants (101 with SSc, 22 with primary RP and 50 healthy controls) were included in this analysis. Seven single-finger or finger combinations (derived from the middle and ring fingers) were then tested for sensitivity for the presence of two markers of capillary abnormality [presence of giant capillaries and an SSc grade (early, active or late)] compared with assessment of all eight fingers. Results: For the eight-finger gold standard, sensitivity against the diagnostic criteria was 74.6% (53.0% for the presence of giants alone and 73.1% for image grade alone). Examining only one finger gave low sensitivity (ranging from right middle 31.7% to left ring 46.6%). Examining both ring fingers gave a sensitivity of 59.8%, whereas examining the four-finger combination of both ring and both middle fingers gave a sensitivity of 66.7%. Conclusion: During routine capillaroscopic examination, ideally all eight nailbeds (excluding thumbs) should be examined, otherwise some abnormalities will be missed. Examining only four fingers reduces capillaroscopy sensitivity.

Intra-and inter-observer reliability of nailfold videocapillaroscopy - A possible outcome measure for systemic sclerosis-related microangiopathy.

OBJECTIVES: Our aim was to assess the reliability of nailfold capillary assessment in terms of image evaluability, image severity grade ('normal', 'early', 'active', 'late'), capillary density, capillary (apex) width, and presence of giant capillaries, and also to gain further insight into differences in these parameters between patients with systemic sclerosis (SSc), patients with primary Raynaud's phenomenon (PRP) and healthy control subjects. METHODS: Videocapillaroscopy images (magnification 300×) were acquired from all 10 digits from 173 participants: 101 patients with SSc, 22 with PRP and 50 healthy controls. Ten capillaroscopy experts from 7 European centres evaluated the images. Custom image mark-up software allowed extraction of the following outcome measures: overall grade ('normal', 'early', 'active', 'late', 'non-specific', or 'ungradeable'), capillary density (vessels/mm), mean vessel apical width, and presence of giant capillaries. RESULTS: Observers analysed a median of 129 images each. Evaluability (i.e. the availability of measures) varied across outcome measures (e.g. 73.0% for density and 46.2% for overall grade in patients with SSc). Intra-observer reliability for evaluability was consistently higher than inter- (e.g. for density, intra-class correlation coefficient [ICC] was 0.71 within and 0.14 between observers). Conditional on evaluability, both intra- and inter-observer reliability were high for grade (ICC 0.93 and 0.78 respectively), density (0.91 and 0.64) and width (0.91 and 0.85). CONCLUSIONS: Evaluability is one of the major challenges in assessing nailfold capillaries. However, when images are evaluable, the high intra- and inter-reliabilities suggest that overall image grade, capillary density and apex width have potential as outcome measures in longitudinal studies.

Quantitative outcome measures for systemic sclerosis-related Microangiopathy - Reliability of image acquisition in Nailfold Capillaroscopy.

BACKGROUND: Nailfold capillaroscopic parameters hold increasing promise as outcome measures for clinical trials in systemic sclerosis (SSc). Their inclusion as outcomes would often naturally require capillaroscopy images to be captured at several time points during any one study. Our objective was to assess repeatability of image acquisition (which has been little studied), as well as of measurement. METHOD: 41 patients (26 with SSc, 15 with primary Raynaud's phenomenon) and 10 healthy controls returned for repeat high-magnification (300×) videocapillaroscopy mosaic imaging of 10 digits one week after initial imaging (as part of a larger study of reliability). Images were assessed in a random order by an expert blinded observer and 4 outcome measures extracted: (1) overall image grade and then (where possible) distal vessel locations were marked, allowing (2) vessel density (across the whole nailfold) to be calculated (3) apex width measurement and (4) giant vessel count. Intra-rater, intra-visit and intra-rater inter-visit (baseline vs. 1week) reliability were examined in 475 and 392 images respectively. A linear, mixed-effects model was used to estimate variance components, from which intra-class correlation coefficients (ICCs) were determined. RESULTS: Intra-visit and inter-visit reliability estimates (ICCs) were (respectively): overall image grade, 0.97 and 0.90; vessel density, 0.92 and 0.65; mean vessel width, 0.91 and 0.79; presence of giant capillary, 0.68 and 0.56. These estimates were conditional on each parameter being measurable. CONCLUSION: Within-operator image analysis and acquisition are reproducible. Quantitative nailfold capillaroscopy, at least with a single observer, provides reliable outcome measures for clinical studies including randomised controlled trials.

Clinical features and management of erythromelalgia: long term follow-up of 46 cases.

OBJECTIVES: To review our clinical experience of this rare condition and describe the clinical features and response to therapy in a cohort of patients with erythromelalgia (EM), a rare condition, characterised by paroxysmal hyperthermia of the extremities with erythema, pain and intense burning. METHODS: A review was made of the electronic and paper medical records of patients with the diagnosis of EM, with a telephone interview to verify and complete clinical information relating treatment and outcome. RESULTS: 46 patients (41 females) were included in this study. Mean age was 57 years and mean duration of symptoms was 16 years. Raynaud's phenomenon was present in 36 patients (80%) and 4 patients (9%) had systemic sclerosis. Smoking (current or previous) was identified as a possible risk factor in 26 cases and exposure to chronic vibration in 3 cases. Overall, the effect on quality of life was mild in 15% of cases, moderate in 30% and severe in 48%. The most common symptoms were burning (96%), heat (93%), pain (87%), and redness (83%). Symptoms affected the lower limbs in 98% of cases, upper limbs in 76%, face in 20% and trunk in 11%. Triggers included heat (85%), exercise (78%) and time of day (76%). Various medications were tried, showing poor effect in most cases. Intravenous iloprost was given to 27 patients, with benefit in 17 patients (63%). CONCLUSIONS: Erythromelalgia is a rare chronic debilitating condition. Exercise, heat and night time are common triggers. Current medical therapies are seldom effective and further research is sorely needed.

The effect of ambient temperature on infrared thermographic images of joints in the distal forelimbs of healthy racehorses.

The aim of the study was to describe the dependence on ambient temperature of distal joint temperature at the forelimbs of racehorses. The study also investigated the influence of differing ambient temperatures on the temperature difference between joints: this was measured ipsilaterally (i.e. between the carpal and fetlock joints along each forelimb) and contralaterally (i.e. between the same joints of the left and right forelimbs). Sixty-four healthy racehorses were monitored over 10 months. At each session, three thermographic images were taken of the dorsal, lateral and medial aspects of the distal forelimbs. Temperature measurements were made from regions of interest (ROIs) covering the carpal and fetlock joints. There was a strong correlation between ambient temperature and absolute joint temperature at all ROIs. The study also observed a moderate correlation between ambient temperature and the ipsilateral temperature differences between joints when measured from the medial and lateral aspects. No significant correlation was noted when measured dorsally. The mean contralateral temperature differences between joints were all close to 0°C. The data support previous reports that the temperature distribution between the forelimbs of the healthy equine is generally symmetric, although some horses differ markedly from the average findings.

Thermographic imaging in sports and exercise medicine: A Delphi study and consensus statement on the measurement of human skin temperature.

The importance of using infrared thermography (IRT) to assess skin temperature (tsk) is increasing in clinical settings. Recently, its use has been increasing in sports and exercise medicine; however, no consensus guideline exists to address the methods for collecting data in such situations. The aim of this study was to develop a checklist for the collection of tsk using IRT in sports and exercise medicine. We carried out a Delphi study to set a checklist based on consensus agreement from leading experts in the field. Panelists (n = 24) representing the areas of sport science (n = 8; 33%), physiology (n = 7; 29%), physiotherapy (n = 3; 13%) and medicine (n = 6; 25%), from 13 different countries completed the Delphi process. An initial list of 16 points was proposed which was rated and commented on by panelists in three rounds of anonymous surveys following a standard Delphi procedure. The panel reached consensus on 15 items which encompassed the participants' demographic information, camera/room or environment setup and recording/analysis of tsk using IRT. The results of the Delphi produced the checklist entitled "Thermographic Imaging in Sports and Exercise Medicine (TISEM)" which is a proposal to standardize the collection and analysis of tsk data using IRT. It is intended that the TISEM can also be applied to evaluate bias in thermographic studies and to guide practitioners in the use of this technique.

The Application of Infrared Thermography in the Assessment of BEMER Physical Vascular Therapy on Body Surface Temperature in Racing Thoroughbreds: A Preliminary Study.

The study aimed to evaluate the impact of BEMER (Physical Vascular Therapy) on body surface temperature using infrared thermography (IRT) in the distal parts of the forelimbs in Thoroughbreds. The study tested the hypothesis that BEMER therapy leads to an increase in body surface temperature and blood vessel diameter in the distal parts of the forelimbs. The study involved 16 horses, split into 2 groups: active BEMER (n = 8) and sham (n = 8). The active BEMER group had BEMER boots applied to the distal parts of the forelimbs, whereas the sham group had BEMER boots applied without activation of the device. Both groups underwent IRT examination to detect changes in body surface temperature, followed by ultrasonographic examination to assess changes in vein and artery diameter before (BT) and just after (JAT) therapy. The IRT examination was repeated 15 min after BEMER therapy (15AT). There were no significant body surface temperature differences between BT and JAT in any regions of interest (ROIs) in either group. In the active BEMER group, the ROIs did not change significantly at 15AT, compared to the temperatures measured at BT (except for the hooves). At 15AT the temperature of all the ROIs (except the fetlock bone) dropped significantly in the sham group. In the ultrasonographic examination, there was a significant increase in vein and artery diameter in the study group JAT, whereas the sham group had a significant increase only in artery diameter JAT. These results suggest an effect of BEMER on stimulating blood circulation in the distal parts of the forelimbs in clinically healthy horses. IRT did not identify changes in skin surface temperature after BEMER therapy at the distal parts of the forelimbs.

Photothermal Effects of High-Intensity Laser Therapy on the Superficial Digital Flexor Tendon Area in Clinically Healthy Racehorses.

The aim of the present study was to assess the photothermal effects of high-intensity laser therapy (HILT) on the superficial digital flexor tendon (SDFT) of the hindlimb in racehorses. It was conducted on 18 clinically healthy thoroughbreds that were subjected to thermographic examination to measure surface temperature changes in the SDFT. This was performed before and immediately after HILT. This revealed statistically significant differences in the temperature of the skin surface overlying the flexor tendons (p < 0.001). The surface temperature of the area examined was higher by an average of 3.5 °C after HILT, compared with the temperature measured before HILT. Our results prove that HILT has a photothermal effect in treating soft tissue. This finding can be helpful in determining the appropriate parameters for monitoring the short- and long-term effects of HILT.

Microvasculopathy in spinal muscular atrophy is driven by a reversible autonomous endothelial cell defect.

Spinal muscular atrophy (SMA) is a neuromuscular disorder due to degeneration of spinal cord motor neurons caused by deficiency of the ubiquitously expressed SMN protein. Here, we present a retinal vascular defect in patients, recapitulated in SMA transgenic mice, driven by failure of angiogenesis and maturation of blood vessels. Importantly, the retinal vascular phenotype was rescued by early, systemic SMN restoration therapy in SMA mice. We also demonstrate in patients an unfavorable imbalance between endothelial injury and repair, as indicated by increased circulating endothelial cell counts and decreased endothelial progenitor cell counts in blood circulation. The cellular markers of endothelial injury were associated with disease severity and improved following SMN restoration treatment in cultured endothelial cells from patients. Finally, we demonstrated autonomous defects in angiogenesis and blood vessel formation, secondary to SMN deficiency in cultured human and mouse endothelial cells, as the underlying cellular mechanism of microvascular pathology. Our cellular and vascular biomarker findings indicate microvasculopathy as a fundamental feature of SMA. Our findings provide mechanistic insights into previously described SMA microvascular complications, and highlight the functional role of SMN in the periphery, including the vascular system, where deficiency of SMN can be addressed by systemic SMN-restoring treatment.

Comparison of the Effect of High-Intensity Laser Therapy (HILT) on Skin Surface Temperature and Vein Diameter in Pigmented and Non-Pigmented Skin in Healthy Racehorses.

The aim of the study was to assess differences in the influence of high-intensity laser therapy (HILT) on the skin surface temperature and vein diameter of the lateral fetlock joint region in a group of racehorses with pigmented and non-pigmented skin in the treatment area. Twenty Thoroughbreds were divided into two equal groups: pigmented and non-pigmented skin groups. Each horse received the same HILT treatment. Just before and immediately after HILT, thermographic examination was performed to measure the skin surface temperature and ultrasonographic examination assessed the lateral digital palmar vein diameter. After HILT, the pigmented skin surface temperature increased, while the non-pigmented skin surface temperature decreased, and the difference between both groups was significant (p < 0.001). The vein diameter increased after HILT in horses with pigmented and non-pigmented skin, but the difference between both groups was not significant (p = 0.14). In conclusion, melanin content in the epidermis plays an important role in light energy absorption and photothermal effects. The vein diameter changes after HILT application indicated that the increase in vessel diameter may partly depend on photothermal mechanisms occurring in irradiated tissue. Further research is necessary to describe the physiological and clinical effects of HILT performed on pigmented and non-pigmented skin.

Changes in Body Surface Temperature Associated with High-Speed Treadmill Exercise in Beagle Dogs Measured by Infrared Thermography.

Evaluation of body surface temperature change in response to exercise is important for monitoring physiological status. The aim of the study was to assess the influence of high-speed treadmill exercise on body surface temperature using infrared thermography (IRT) in selected body regions of healthy Beagle dogs, taking into account gait and recovery time. Thermographic images of the dogs were taken before exercise (BE), after walk (AW), after trot (AT), after canter (AC), just after second walk (JAE), 5 min after exercise (5 AE), 15 min after exercise (15 AE), 30 min after exercise (30 AE), 45 min after exercise (45 AE), and 120 min after exercise (120 AE). Body surface temperature was measured at the neck, shoulder, upper forearm, back, chest, croup, and thigh. Statistical analysis indicated the highest temperature at the upper forearm, shoulder, and thigh, and the lowest on the croup, back, and neck. The peak values of surface temperature in all ROIs were at AC and JAE and the lowest at 120 AE. The study demonstrated that body surface temperature was influenced by high-speed physical exercise on a treadmill and IRT was a viable imaging modality that provided temperature data from specific body regions. The proximal forelimb and hindlimb were the most influenced by exercise.

A case of Myhre syndrome mimicking juvenile scleroderma.

BACKGROUND: Myhre syndrome is a genetic disorder caused by gain of function mutations in the SMAD Family Member 4 (SMAD4) gene, resulting in progressive, proliferative skin and organ fibrosis. Skin thickening and joint contractures are often the main presenting features of the disease and may be mistaken for juvenile scleroderma. CASE PRESENTATION: We report a case of a 13 year-old female presenting with widespread skin thickening and joint contractures from infancy. She was diagnosed with diffuse cutaneous systemic sclerosis, and treatment with corticosteroids and subcutaneous methotrexate recommended. There was however disease progression prompting genetic testing. This identified a rare heterozygous pathogenic variant c.1499 T > C (p.Ile500Thr) in the SMAD4 gene, suggesting a diagnosis of Myhre syndrome. Securing a molecular diagnosis in this case allowed the cessation of immunosuppression, thus reducing the burden of unnecessary and potentially harmful treatment, and allowing genetic counselling. CONCLUSION: Myhre Syndrome is a rare genetic mimic of scleroderma that should be considered alongside several other monogenic diseases presenting with pathological fibrosis from early in life. We highlight this case to provide an overview of these genetic mimics of scleroderma, and highlight the molecular pathways that can lead to pathological fibrosis. This may provide clues to the pathogenesis of sporadic juvenile scleroderma, and could suggest novel therapeutic targets.

Validation of a protocol for the assessment of skin temperature and blood flow in childhood localised scleroderma.

BACKGROUND/PURPOSE: Localised scleroderma (LS) is the most common form of scleroderma seen in children, and usually presents unilaterally. Infrared thermography (IRT) and laser Doppler (LD) have both been reported to be useful in assessing the active, inflammatory stage of LS. We developed and validated a protocol using these techniques for the assessment of unilateral LS activity in children. METHOD: We investigated the spatial variability and repeatability of LD measurements from adult control forearm skin, and the inter- and intra-operator reproducibility of both LD blood flow trace analysis and IRT skin temperature analysis. Software was developed to produce overlay images of thermograms onto digital photographs of skin sites. In a group of seven adult control subjects, we established the normal range for skin temperature and LD blood flow at six standardised sites (forehead, cheek, abdomen, back, arm and leg), and measured contralateral differences in readings. In a group of 34 children with LS, we investigated the skin temperature and LD blood flow in unaffected skin at the same six sites. RESULTS: In adults, physiological variability in LD blood flow and skin temperature between the two sides of the body was found to be greater than the uncertainty introduced into the measurements by (inter alia) limited intra- or inter-operator reproducibility. The cheek displayed the highest mean asymmetry in both skin temperature (0.5 degrees C) and LD blood flow (40%). CONCLUSION: Our protocol combines IRT, LD and photography for LS assessment in children, and establishes a normal range of readings in line with other authors.

Optimisation of botulinum toxin type a treatment for the management of Raynaud's phenomenon using a dorsal approach: a prospective case series.

INTRODUCTION: Raynaud's phenomenon (RP) is a common condition and causes pain, paraesthesia, ulceration and gangrene. Botulinum toxin A (Btx-A) is effective when injected via a digital palmar approach, in the treatment of severe RP. However, hand weakness resulting from lumbrical malfunction is a recognized complication. This study aimed to determine the effect of Btx-A injected via a dorsal approach. METHOD: Forty patients received 100 units of Btx-A, injected across both hands via a dorsal approach. Each patient had a baseline, 6- and 12-week hand assessment and thermographic image (FLIR E60bx) performed for the study. RESULTS: Eighty-eight percent of patients reported an improvement in symptoms including reduction in pain, improved colour change with reduced swelling and edema at 6 weeks. Of these patients, 80% reported an improvement in cold intolerance with a reduction in the frequency and severity of Raynaud's attacks. There was a significant improvement in both the DASH score (p = 0.001), Kapandji score (p = 0.001) and hand strength (p < 0.05). No patients reported weakness. Improvements in hand function and symptoms of RP were still evident at 12 weeks. CONCLUSIONS: Btx-A injected via a dorsal approach improves symptoms and reduces the number of RP. We have shown an effective non-surgical approach technique to treat RP.Key Points• Raynaud's phenomenon is a common vasospastic disorder of the digital vessels, which can cause severe pain, restrictions to hand function and ulceration.• Dorsal botulinum toxin type A injections can improve the symptoms of secondary Raynaud's phenomenon and hand function for approximately 3 months.

A Multicenter Study of the Validity and Reliability of Responses to Hand Cold Challenge as Measured by Laser Speckle Contrast Imaging and Thermography: Outcome Measures for Systemic Sclerosis-Related Raynaud's Phenomenon.

OBJECTIVE: Reliable and objective outcome measures to facilitate clinical trials of novel treatments for systemic sclerosis (SSc)-related Raynaud's phenomenon (RP) are badly needed. Laser speckle contrast imaging (LSCI) and thermography are noninvasive measures of perfusion that have shown excellent potential. This multicenter study was undertaken to determine the reliability and validity of a hand cold challenge protocol using LSCI, standard thermography, and low-cost cell phone/mobile phone thermography (henceforth referred to as mobile thermography) in patients with SSc-related RP. METHODS: Patients with RP secondary to SSc were recruited from 6 UK tertiary care centers. The patients underwent cold challenge on 2 consecutive days. Changes in cutaneous blood flow/skin temperature at each visit were imaged simultaneously using LSCI, standard thermography, and mobile thermography. Measurements included area under the curve (AUC) for reperfusion/rewarming and maximum blood flow rate/skin temperature after rewarming (MAX). Test-retest reliability was assessed using intraclass correlation coefficients (ICCs). Estimated latent correlations (estimated from multilevel models, taking values between -1 and 1; denoted as rho values) were used to assess the convergent validity of LSCI and thermography. RESULTS: In total, 159 patients (77% with limited cutaneous SSc) were recruited (84% female, median age 63.3 years). LSCI and standard thermography both had substantial reliability, with ICCs for the reperfusion/rewarming AUC of 0.67 (95% confidence interval [95% CI] 0.54, 0.76) and 0.68 (95% CI 0.58, 0.80), respectively, and ICCs for the MAX of 0.64 (95% CI 0.52, 0.75) and 0.72 (95% CI 0.64, 0.81), respectively. Very high latent correlations were present for the AUCs of LSCI and thermography (ρ = 0.94; 95% CI 0.87, 1.00) and for the AUCs of standard and mobile thermography (ρ = 0.98; 95% CI 0.94, 1.00). CONCLUSION: This is the first multicenter study to examine the reliability and validity of cold challenge using LSCI and thermography in patients with SSc-related RP. LSCI and thermography both demonstrated good potential as outcome measures. LSCI, standard thermography, and mobile thermography had very high convergent validity.

The influence of breed, age, gender, training level and ambient temperature on forelimb and back temperature in racehorses.

A previous thermographic study of racehorses identified 13 regions of interest (ROIs) for monitoring the impact of training. However, that investigation did not consider the influence of breed, age, gender or training intensity level on the temperature of ROIs. The present study adopted a multivariate analysis approach to determine whether the aforementioned factors, along with ambient temperature, significantly influenced ROI temperature in the key body regions. Thermography measurements were obtained from 53 racehorses of three breeds. Horses were in regular training for over 10 months, having 13 thermographic examinations in each racing season. Backward stepwise multiple linear regression indicated that ambient temperature and breed contributed significantly to the model for predicting ROI temperature at all 13 ROIs. Training intensity level contributed significantly to the model only at the thoracic vertebrae, the left third metacarpal bone and left fetlock joint. Neither gender nor age contributed to the model significantly at any ROI. Our data suggest that ambient temperature, breed and training level affect racehorse body surface temperature in some areas of the distal parts of the forelimbs and the back. This contributes to a better understanding of the normal range of thermographic findings in racehorses undergoing intensive training.