Systematic review of the prevalence and incidence of the photodermatoses with meta-analysis of the prevalence of polymorphic light eruption.

Information about the prevalence of photodermatoses is lacking, despite their substantial impact on life quality. Our objective was to systematically review the literature to establish what is known regarding prevalence and incidence of photodermatoses. We searched Medline, CINAHL and Embase from inception to 2021 to identify original population-based studies in English literature reporting the prevalence and/or incidence of photodermatoses. Information was extracted according to geographical location and risk of bias was assessed using a 10-point risk of bias tool for prevalence studies. Primary outcome was the population prevalence of photodermatoses. Prevalence data for polymorphic light eruption (PLE) were used to calculate the global pooled prevalence of PLE. Twenty-six studies were included; 15 reported prevalence of photodermatoses based on samples of the general population and 11 on prevalence and/or incidence from national and international registry data. The general population studies involved PLE (nine studies), unspecified photosensitivity (2), actinic prurigo (2), juvenile spring eruption (1), chronic actinic dermatitis (1) and variegate porphyria (1), while registry studies reported on cutaneous porphyrias and genophotodermatoses (nine and two studies, respectively). Worldwide the prevalence of PLE between countries ranged from 0.65% (China) to 21.4% (Ireland). The pooled estimated prevalence of PLE was 10% (95% CI 6%-15%) among the general population (n = 19,287), and PLE prevalence increased with distance from the equator (r = 0.78, p < 0.001). While several photodermatoses are rare, photosensitivity can be prevalent at wide-ranging world locations, including Egypt where photosensitivity was found in 4% of children and 10% of adults. This study showed that PLE is highly prevalent in many populations and that its prevalence shows a highly significant correlation with increasing northerly or southerly latitude. Available population-based studies for photodermatoses suggest they can be prevalent at a range of world locations; more attention is required to this area.

Clinicophotobiological Characterization of Photoaggravated Atopic Dermatitis.

Importance: Photoaggravated atopic dermatitis (PAD) is estimated to affect 1.4% to 16% of patients with AD but remains poorly characterized with limited published data. Objective: To provide detailed clinical and photobiological characterization of PAD. Design, Setting, and Participants: This case series study used cross-sectional data collected from 120 consecutive patients diagnosed with PAD from January 2015 to October 2019 at a tertiary center referral unit for photobiology. Main Outcomes and Measures: Routinely collected standardized clinical and photobiological data were analyzed using descriptive statistics, and regression analysis explored associations between demographic and clinical data. Results: Of 869 patients who underwent photoinvestigation, 120 (14%) were diagnosed with PAD (69 female [58%]; median age, 45 [IQR, 31-61] years; range, 5-83 years; skin phototypes [SPTs] I-VI). Of these patients, 104 (87%) were adults. All patients had a history of AD, and most (62 of 104 [60%]) presented with sunlight-provoked or photodistributed eczema; median age at photosensitivity onset was 37 years (range, 1-72 years). Past-year Dermatology Life Quality Index score was greater than 10 for 80 of 103 adults (78%), and 82 of 119 (69%) had vitamin D (25-hydroxyvitamin D) level insufficiency or deficiency (<20 ng/mL; to convert ng/mL to nmol/L, multiply by 2.496). Broadband UV radiation provocation test results were positive for 112 patients (93%). In 28 patients (23%) with abnormal monochromator phototest findings, sensitivity occurred to UV-A, UV-B, and/or visible light, and UV-A of 350 ± 10 nm was the most prevalent wavelength. Photopatch test reactions were positive for 18 patients (15%). Patients with SPTs V to VI (31 [26%]) vs SPTs I to IV (89 [74%]) were younger at photosensitivity onset (median age, 24 years [IQR, 15-37 years] vs 40 years [IQR, 25-55 years]; P = .003), were more likely to be female (23 [74%] vs 46 [52%]; P = .03), and had a lower vitamin D status and a higher frequency of abnormal monochromator phototest findings. Conclusions and Relevance: In this case series study, PAD affected patients with different ages and SPTs and was associated with substantially impaired quality of life. The findings suggest that confirming PAD through phototesting may provide better personalized care for patients through identification of provoking wavelengths, relevant photocontact allergies, and appropriate photoprotection advice.

Comparison between low cost USB nailfold capillaroscopy and videocapillaroscopy: a pilot study.

OBJECTIVES: Universal serial bus (USB) microscopy (capillaroscopy) could provide all rheumatologists with an easy-to-use, low-cost tool to examine the nailfold capillaries to facilitate early diagnosis of SSc. The objectives of this pilot study were to examine the feasibility of acquiring and analysing images using USB microscopy and to compare results to videocapillaroscopy. METHODS: Videocapillaroscopy and USB microscope images were obtained from the right and left ring fingers of 20 patients with SSc and 20 healthy control subjects. In addition to generating panoramic capillary mosaics from across the whole nailbed, custom software made fully automated measurements of vessel structure including capillary width and density. The area under the receiver operating characteristic curve (AZ) was used to measure separation between the SSc and healthy control groups. RESULTS: High quality images could be generated from the USB microscope, with reconstructed USB images comparing very favourably with those obtained using videocapillaroscopy. Using USB microscope images, the receiver operating characteristic curve AZ for group separation based on mean width was 0.81 (standard error 0.120) compared with 0.81 (standard error 0.095) for the (gold standard) videocapillaroscopy. The receiver operating characteristic curve AZ for group separation using capillary density was 0.48 (standard error 0.16) for USB microscope images, compared with 0.70 (standard error 0.10) for videocapillaroscopy. CONCLUSION: In this pilot study, USB capillaroscopy was able to discriminate between patients with SSc and controls as well as videocapillaroscopy on the basis of capillary width. This finding, together with the high-quality images obtained, highlights the potential of USB capillaroscopy as a low-cost, easily accessible clinical and research tool.

State-of-the-art technologies provide new insights linking skin and blood vessel abnormalities in SSc-related disorders.

OBJECTIVE: A key unanswered question in systemic sclerosis (SSc) is how microvascular abnormality and fibrosis inter-relate. Our aim was to use state-of-the-art non-invasive imaging methods to gain new insights into pathophysiology, comparing patients with different subtypes of SSc, including early dcSSc, not only to healthy controls but also to patients with causes of Raynaud's phenomenon not progressing to fibrosis. METHODS: Laser Doppler imaging, nailfold capillaroscopy, spectroscopy, and ultrasound measured (respectively) perfusion, microvascular structure, oxygenation/oxidative stress, and skin thickening in the hands of 265 subjects: 31 patients with primary Raynaud's phenomenon (PRP), 35 with undifferentiated connective tissue disease (UCTD), 93 with limited cutaneous SSc (lcSSc), 46 with diffuse cutaneous SSc (dcSSc, including 27 'early') and 60 healthy controls. RESULTS: Mean perfusion was reduced in SSc groups compared to controls (lcSSc 172 perfusion units [standard deviation 157], late-dcSSc 90 [145], early-dcSSc 68 [137] vs. controls 211 [146]; p = 0.0002) as was finger-oxygenation (lcSSc 12.1 [13.6] arbitrary units [AU], late-dcSSc 12.2 [8.4], early-dcSSc 11.1 [11.3] vs controls 14.9 [10.5]; p = 0.0049). Oxidative stress was increased at the hand-dorsum in SSc groups (p = 0.0007). Perfusion positively correlated with oxygenation (r = 0.23, p < 0.001), and capillary density negatively with skin thickness (r = -0.26, p < 0.001). CONCLUSION: Our findings lend support to the hypothesis that in SSc, particularly early dcSSc, (but not in PRP or UCTD), reduced perfusion (together with structural microvascular abnormality) associates with reduced oxygenation, with oxidative stress and with skin thickening/fibrosis, most likely driving a vicious cycle which ultimately results in irreversible tissue injury. Findings in skin may mirror alterations in internal organs.

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.

Sun Exposure Behavior, Seasonal Vitamin D Deficiency, and Relationship to Bone Health in Adolescents.

CONTEXT: Vitamin D is essential for bone health in adolescence, when there is rapid bone mineral content accrual. Because cutaneous sun exposure provides vitamin D, there is no recommended oral intake for UK adolescents. OBJECTIVE: Our objective was to assess seasonal vitamin D status and its contributors in white Caucasian adolescents and examine bone health in those found deficient. DESIGN: Prospective cohort study was undertaken. SETTING: Six schools in Greater Manchester, UK, were included. PARTICIPANTS: Participants were 131 adolescents between 12 and 15 years of age. INTERVENTION(S): Seasonal assessment of circulating 25-hydroxyvitamin D (25OHD), personal sun exposure, and dietary vitamin D. Adolescents deficient (25OHD <10 ng/ml/25 nmol/liter) in at least one season underwent dual-energy X-ray absorptiometry (lumbar spine, femoral neck), with bone mineral apparent density correction for size, and peripheral quantitative computed tomography (distal radius) for volumetric bone mineral density (BMD). MAIN OUTCOME MEASURE: Serum 25OHD and BMD measurements. RESULTS: Mean 25OHD was highest in September: 24.1 (SD, 6.9) ng/ml and lowest in January: 15.5 (5.9) ng/ml. Over the year, 16% were deficient in ≥ one season and 79% insufficient (25OHD <20 ng/ml/50 nmol/liter) including 28% in September. Dietary vitamin D was low year-round, whereas personal sun exposure was seasonal and predominantly across the school week. Holidays accounted for 17% variation in peak 25OHD (P < .001). Nineteen adolescents underwent bone assessment, which showed low femoral neck bone mineral apparent density vs matched reference data (P = .0002), three with Z less than or equal to -2.0 distal radius trabecular volumetric BMD. CONCLUSIONS: Sun exposure levels failed to provide adequate vitamin D, with approximately one-quarter of adolescents insufficient even at summer peak. Seasonal vitamin D deficiency was prevalent and those affected had low BMD. Recommendations on vitamin D acquisition are indicated in this age-group.

Synovial tissue volume: a treatment target in knee osteoarthritis (OA).

BACKGROUND: Synovitis occurring frequently in osteoarthritis (OA) may be a targeted outcome. There are no data examining whether synovitis changes following intra-articular intervention. METHODS: Persons aged 40 years and older with painful knee OA participated in an open label trial of intra-articular steroid therapy. At all time points they completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. They had a contrast-enhanced (CE) MRI immediately prior to an intra-articular steroid injection with a repeat scan within 20 days. Response status was assessed using the Osteoarthritis Research Society International (OARSI) response criteria. OARSI responders were followed until their pain relapsed either within 20% of baseline or 6 months, shortly after which a third MRI was performed. Synovial tissue volume (STV) was measured on postcontrast knee images. We looked at changes in the STV and in pain, and their association. RESULTS: 120 subjects with preinjection and postinjection CE MRI were followed. Their mean age was 62.3 years (SD=10.3) and 62 (52%) were women. The median time between injection and follow-up scan was 8 days (IQR 7-14 days). 85/120 (71%) were OARSI responders. Pain decreased (mean change in KOOS=+23.9; 95% CI 20.1 to 27.8, p<0.001) following steroid injection, as did mean STV (mean change=-1071 mm(3); 95% CI -1839 mm(3) to -303 mm(3), p=0.01). Of the 80 who returned for a third MRI, pain relapsed in 57, and in the 48 of those with MRI data, STV increased between follow-up and final visit (+1220 mm(3); 95% CI 25 mm(3) to 2414 mm(3), p=0.05). 23 were persistent responders at 6 months and, in these, STV did not increase (mean change=-202 mm(3); 95% CI -2008 mm(3) to 1604 mm(3), p=0.83). Controlling for variation over time, there was a significant association between synovitis volume and KOOS pain (b coefficient-change in KOOS pain score per 1000 mm(3) change in STV=-1.13; 95% CI -1.87 to -0.39, p=0.003), although STV accounted for only a small proportion of the variance in change in pain. CONCLUSIONS: Synovial tissue volume in knee OA shrinks following steroid therapy, and rebounds in those whose pain relapses. It can be considered a treatment target in symptomatic knee OA. TRIAL REGISTRATION NUMBER: ISRCTN07329370.

A randomised trial of a brace for patellofemoral osteoarthritis targeting knee pain and bone marrow lesions.

OBJECTIVE: Braces used to treat (PF) osteoarthritis (OA) may reduce contact stress across the PF joint. We hypothesised that in PF OA, braces would decrease knee pain and shrink PF bone marrow lesions (BMLs). METHODS: Eligible subjects had painful PF OA. Subjects were randomly allocated to brace or no brace for 6 weeks. Knee MRIs were acquired at baseline and 6 weeks. We measured BMLs on post-contrast fat suppressed sagittal and proton density weighted axial images. The primary symptom outcome was change in pain at 6 weeks during a preselected painful activity, and the primary structural outcome was BML volume change in the PF joint. Analyses used multiple linear regression. RESULTS: We randomised 126 subjects aged 40-70 years (mean age 55.5  years; 72 females (57.1%)). Mean nominated visual analogue scale (0-10 cm) pain score at baseline was 6.5 cm. 94 knees (75%) had PF BMLs at baseline. Subjects wore the brace for a mean of 7.4 h/day. 6 subjects withdrew during the trial. After accounting for baseline values, the brace group had lower knee pain than the control group at 6 weeks (difference between groups -1.3 cm, 95% CI -2.0 to -0.7; p<0.001) and reduced PF BML volume (difference -490.6 mm(3), 95% CI -929.5 to -51.7; p=0.03) but not tibiofemoral volume (difference -53.9 mm(3), 95% CI -625.9 to 518.2; p=0.85). CONCLUSIONS: A PF brace reduces BML volume in the targeted compartment of the knee, and relieves knee pain. TRIAL REGISTRATION NUMBER: UK. ISRCTN50380458.

The relationship between the OSTEODENT index and hip fracture risk assessment using FRAX.

OBJECTIVES: The OSTEODENT index is a predicted probability of osteoporosis derived from a combination of an automated analysis of a dental panoramic radiograph and clinical information. This index has been proposed as a suitable case-finding tool for identification of subjects with osteoporosis in primary dental care; however, no data exist on the relationship between OSTEODENT index and fracture risk. The aims of this study were to assess the relationship between the OSTEODENT index and hip fracture risk as determined by FRAX and to compare the performance of the OSTEODENT index and FRAX (without femoral BMD data), in determining the need for intervention as recommended in UK national treatment guidance. STUDY DESIGN: The study was a retrospective analysis of data from 339 female subjects (mean age 55.3 years), from 2 centers: Manchester (UK) and Leuven (Belgium). Clinical information and femoral neck BMD were available for FRAX, and dental panoramic radiographic data and clinical information were available to calculate the OSTEODENT index. Subjects were classified into "treat" or "lifestyle advice and reassurance" categories using the National Osteoporosis Guideline Group (NOGG) threshold. RESULTS: The OSTEODENT index result was significantly related to the 10-year probability of hip fracture derived from the reference standard FRAX tool (Rs = 0.67, P < .0001); 84 patients (24.8%) were allocated to the "treat" category on the basis of FRAX and the UK national guidance. Using this "treatment/no treatment" classification as the reference standard, ROC analysis showed no significant difference between areas under the curves for the OSTEODENT index (0.815) and the 10-year probability of hip fracture derived from the FRAX index without BMD (0.825) when used as tests for determining therapeutic intervention. CONCLUSION: The results suggest that the OSTEODENT index has value in prediction of hip fracture risk. Prospective trials are needed to confirm this finding and to examine the feasibility for its use in primary dental care.

Is self-reported alcohol consumption associated with osteoporotic mandibular bone loss in women?

The aim of this study was to determine whether alcohol consumption would predict mandibular bone quality and quantity in a large European female population. In total, 672 middle-aged and elderly women (45-70 yr of age; standard deviation = 6) were recruited in the study. Alcohol consumption was recorded through a self-reported questionnaire. Mandibular cortical width was measured, by five observers, in the mental foramen region on panoramic radiographs. Mandibular bone density, expressed as aluminium thickness, was recorded on intra-oral radiographs. Alcohol consumption was associated with a reduction of mandibular bone density and cortical width. This association was higher in subjects with excessive alcohol consumption, defined in the present study as > 14 units consumed per week. This study showed reduced jaw-bone quality in older individuals and in those with increased alcohol consumption.

The use of visual assessment of dental radiographs for identifying women at risk of having osteoporosis: the OSTEODENT project.

OBJECTIVE: The objective of this study was to investigate the diagnostic accuracy of visual assessment of the trabecular pattern in intraoral periapical radiographs to identify female subjects at risk of having osteoporosis. STUDY DESIGN: Six hundred female subjects underwent intraoral periapical radiography of the maxillary and mandibular premolar region. Five observers assessed the trabecular pattern as dense, heterogeneous, or sparse, with the aid of reference images. All patients received a central dual energy x-ray absorptiometry (DXA) examination of the hip and lumbar spine. RESULTS: With sparse trabecular pattern as indicative of osteoporosis, mean specificity was high (91.6 for the upper jaw and 90.8 for the lower jaw) while the sensitivity was low (28.2 for the upper and lower jaw). The mean intraobserver agreement was comparable for radiographs of the upper and lower jaw (median kappa(w) 0.53 and 0.57, respectively). CONCLUSION: Visual assessment of the trabecular pattern in intraoral periapical radiographs of premolar regions is a potential method to identify women at risk of having osteoporosis.

Diagnosing osteoporosis by using dental panoramic radiographs: the OSTEODENT project.

OBJECTIVES: Measurement of cortical thickness and subjective assessment of cortical porosity on panoramic radiographs are methods previously reported for diagnosing osteoporosis. The aims of this study were to determine the relative efficacy of the mandibular cortical index and cortical width in detecting osteoporosis, both alone and in combination, and to determine the optimal cortical width threshold for referral for additional osteoporosis investigation. STUDY DESIGN: Six hundred seventy-one postmenopausal women 45 to 70 years of age were recruited for this study. They received dual energy x-ray absorptiometry (DXA) scans of the left hip and lumbar spine (L1 to L4), and dental panoramic radiographic examinations of the teeth and jaws. Three observers separately assessed the mandibular cortical width and porosity in the mental foramen region of the mandible. Cortical width was corrected for magnification errors. Chi-squared automatic interaction detection analysis (CHAID) software was used (SPSS AnswerTree, version 3.1, SPSS Inc., Chicago, IL). RESULTS: Chi-squared automatic interaction detection analysis showed that the cortical porosity was a poorer predictor of osteoporosis than mandibular cortical width. For the 3 observers, a mandibular cortical width of <3 mm provided diagnostic odds ratios of 6.51, 6.09, and 8.04. The test is therefore only recommended in triage screening of individuals by using radiographs made for purposes other than osteoporosis. CONCLUSION: When evaluating panoramic radiographs, only those patients with the thinnest mandibular cortices (i.e., <3 mm) should be referred for further osteoporosis investigation.

The mandibular cortex on radiographs as a tool for osteoporosis risk assessment: the OSTEODENT Project.

The aim of this study was to measure the accuracy of porosity of the mandibular cortex on dental panoramic radiographs (DPRs) in diagnosis of osteoporosis, alone and in combination with a clinical risk index. Six hundred seventy-one women (45-70yr) were recruited in the study, and dual-energy X-ray absorptiometry of the hip and lumbar spine was performed. A clinical index of osteoporosis risk (OSIRIS) and a DPR were obtained for each subject. The cortical appearance on the DPR was classified using the mandibular cortical index (MCI) by 5 observers. receiver operating characteristic (ROC) curve analysis was performed with calculation of area under the ROC curve (AUC) and sensitivity and specificity at various thresholds. Complete data were available for 653 subjects, of whom 21.6% had osteoporosis. The AUC for OSIRIS was 0.838. When used alone as the diagnostic test, MCI AUC for the 5 observers ranged from 0.560 to 0.670, significantly less than OSIRIS. Intraobserver and interobserver repeatability of MCI assessment was inconsistent. We conclude that MCI has limited value for osteoporosis diagnosis, being most appropriate as a method of fortuitous case-finding.