Red tattoos,ultraviolet radiation and skin cancer in mice

Ultraviolet radiation (UVR) induces skin cancer. The combination of UVR and red tattoos may be associated with increased risk of skin cancer due to potential carcinogens in tattoo inks. This combination has not been studied previously. Immunocompetent C3.Cg/TifBomTac hairless mice (n=99) were tattooed on their back with a popular red tattoo ink. This often used ink is banned for use on humans because of high content of the potential carcinogen 2‐anisidine. Half of the mice were irradiated with three standard erythema doses UVR thrice weekly. Time to induction of first, second and third squamous cell carcinoma (SCC) was measured. All UV‐irradiated mice developed SCCs. The time to the onset of the first and second tumor was identical in the red‐tattooed group compared with the control group (182 vs 186 days and 196 vs 203 days, P=ns). Statistically, the third tumor appeared slightly faster in the red‐tattooed group than in the controls (214 vs 224 days, P=.043). For the second and third tumor, the growth rate was faster in the red‐tattooed group compared with the control (31 vs 49 days, P=.009 and 30 vs 38 days, P=.036). In conclusion, no spontaneous cancers were observed in skin tattooed with a red ink containing 2‐anisidine. However, red tattoos exposed to UVR showed faster tumor onset regarding the third tumor, and faster growth rate of the second and third tumor indicating red ink acts as a cocarcinogen with UVR. The cocarcinogenic effect was weak and may not be clinically relevant.     

Management of radiodermatitis associated with cetuximab in squamous cell carcinomas of the head and neck

The objective of this review is to report to the medical community the most recent knowledge on prevention and management of dermatitis with the use of cetuximab simultaneously with radiotherapy in the treatment of squamous cell carcinomas of the head and neck. A review was conducted in PubMed of English language publications between 2010 and 2015. The search employed the terms ‘skin toxicity’, ‘radiodermatitis’, ‘cetuximab’, ‘radiotherapy’, and ‘head and neck cancer’. Data related to the classification and management of dermatitis, associated with cetuximab with concomitant radiotherapy (n = 22), were critically reviewed. We conclude that dermatitis associated with bioradiotherapy is a predictable, treatable, and reversible event that does not affect administration of therapy or its clinical outcome when treated appropriately.     

“Assessment of chronic sclerodermoid Graft‐versus‐Host Disease patients,using 20MHz high‐frequency ultrasonography and cutometer methods”

The development of an adverse graft‐versus‐host disease (GvHD) is a major complication of stem cell transplantations, which are widely used to cure increasing number of hematologic malignancies. Patients with chronic GvHD are at risk of joint contractures secondary to sclerodermatous skin changes. Several clinical scores or serologic markers have been used to assess skin sclerosis in scleroderma patients. Evaluation of sclerotic skin changes using biometric tools remains to be challenging. The purpose of this study was to illustrate and exemplify ultrasound measurement and measurement of skin elasticity of five chronic sclerodermoid GvHD patients. There is still a substantial lack of studies using objective and non‐invasive methods helpful in assessment of patients with skin involvement of GvHD. Although ultrasound is not the ideal method, it is worth emphasizing that it is still useful, non‐invasive, and repeatable device in monitoring patients suffering from GvHD. It should also be added, that it seems to be advisable to repeat USG examination at an interval of 3 months after the treatment. In addition, skin echogenicity may be a more sensitive parameter than skin thickness in assessment of cGvHD patients.     

Is there any relation between serum insulin and insulin‐like growth factor‐I in non‐diabetic patients with skin tag?

Background Skin tags are common benign lesion occurring mainly on the neck and major flexures as a small soft pedunculated protrusion. This study evaluate insulin and insulin‐like growth factor‐I (IGF‐I) in non‐diabetic ones. Methods and materials A case–control study was conducted in non‐diabetic persons. Comparing insulin and IGF‐I between matched cases (n = 40) and controls (n = 40) by radioimmunoassay test. Cases and controls were recruited from patients consecutively seen at an academic outpatient dermatology clinic. Results The insulin level in patients with skin tags was significantly higher than controls (P = 0.00) but IGF‐I level was not significantly different (P = 0.43). Conclusion These results show an increased insulin level in non‐diabetics ones and overall importance of insulin effect in pathogenesis of skin tags.     

Role of CPI‐17 in restoring skin homoeostasis in cutaneous field of cancerization: effects of topical application of a film‐forming medical device containing photolyase and UV filters

Cutaneous field of cancerization (CFC) is caused in part by the carcinogenic effect of the cyclobutane pyrimidine dimers CPD and 6‐4 photoproducts (6‐4PPs). Photoreactivation is carried out by photolyases which specifically recognize and repair both photoproducts. The study evaluates the molecular effects of topical application of a film‐forming medical device containing photolyase and UV filters on the precancerous field in AK from seven patients. Skin improvement after treatment was confirmed in all patients by histopathological and molecular assessment. A gene set analysis showed that skin recovery was associated with biological processes involved in tissue homoeostasis and cell maintenance. The CFC response was associated with over‐expression of the CPI‐17 gene, and a dependence on the initial expression level was observed (P = 0.001). Low CPI‐17 levels were directly associated with pro‐inflammatory genes such as TNF (P = 0.012) and IL‐1B (P = 0.07). Our results suggest a role for CPI‐17 in restoring skin homoeostasis in CFC lesions.     

Protoporphyrin IX formation and photobleaching in different layers of normal human skin: Methyl‐ and hexylaminolevulinate and different light sources

Topical photodynamic therapy (PDT) is used for various skin disorders, and selective targeting of specific skin structures is desirable. The objective was to assess accumulation of PpIX fluorescence and photobleaching within skin layers using different photosensitizers and light sources. Normal human skin was tape‐stripped and incubated with 20% methylaminolevulinate (MAL) or 20% hexylaminolevulinate (HAL) for 3 h. Fluorescence microscopy quantified PpIX accumulation in epidermis, superficial, mid and deep dermis, down to 2 mm. PpIX photobleaching by light‐emitting diode (LED, 632 nm, 18 and 37 J/cm²), intense pulsed light (IPL, 500–650 nm, 36 and 72 J/cm²) and long‐pulsed dye laser (LPDL, 595 nm, 7.5 and 15 J/cm²) was measured using fluorescence photography and microscopy. We found higher PpIX fluorescence intensities in epidermis and superficial dermis in HAL‐incubated skin than MAL‐incubated skin (P < 0.001). In mid and deep dermis, fluorescence intensities were higher (37%) in HAL‐treated skin than MAL‐treated skin, although not significant (P = ns). At skin surface, photobleaching was significantly higher (90–98%) after LED illumination (18 and 37 J/cm²) than IPL (29–53%, 36 and 72 J/cm²) and LPDL (43–62%, 7 and 15 J/cm²) (P < 0.001). Within the skin, photobleaching was steady from epidermis to deep dermis by LED illumination (37 J/cm², P = ns), but declined from epidermis to mid and deep dermis for IPL‐treated skin and LPDL‐treated skin (IPL 72 J/cm²: 26–15%; LPDL 15 J/cm²: 37–23%) (P < 0.04). Clinically, erythema correlated linearly with MAL and HAL‐induced photobleaching (r² = 0.175, P < 0.001). In conclusion, selective PpIX accumulation indicates HAL as an alternative to MAL for epidermal‐targeted PDT. In clinically relevant doses, PpIX photobleaching throughout the skin was more profound following LED than LPDL and IPL exposure.     

Rituximab therapy is more effective than cyclophosphamide therapy for Japanese patients with anti‐topoisomerase I‐positive systemic sclerosis‐associated interstitial lung disease

Systemic sclerosis‐associated interstitial lung disease (SSc‐ILD) is the most frequent cause of death for SSc but there is still no sufficient treatment available. Although cyclophosphamide (CYC) therapy is a common treatment which has shown statistical efficacy against SSc‐ILD to date, its effects are temporary and not enough. Rituximab (RTX), the anti‐CD20 monoclonal antibody, has recently shown efficacy in many autoimmune diseases. In SSc‐ILD, RTX is also considered to be one of the novel treatment candidates. However, studies of SSc‐ILD in Japanese treated with RTX have only a few case reports. Therefore, in this study, we retrospectively compared nine patients treated with RTX and 30 patients treated with CYC to investigate the efficacy of RTX treatment for Japanese anti‐topoisomerase I‐positive SSc‐ILD patients. At the 24‐month evaluation, the improvement rates of percent predicted of forced vital capacity and percent predicted of diffusing capacity of the lung carbon monoxide in the RTX‐treated group were significantly higher than those in the CYC‐treated group (20.6 ± 8.8% vs 1.1 ± 3.9%; P < 0.05 and 34.0 ± 6.0% vs ?1.5 ± 2.8%; P < 0.01, respectively). In addition, skin thickness scores also showed a marked improvement from 13.5 points before the start of treatment to 5.8 points after 24 months by RTX therapy (P < 0.05). These results suggest that RTX treatment is more effective for Japanese SSc‐ILD patients than CYC treatment. In the future, it is expected that large‐scale clinical trials will show the usefulness of RTX treatment for SSc‐ILD.     

Topical 4% nicotinamide vs. 1% clindamycin in moderate inflammatory acne vulgaris

Nicotinamide and clindamycin gels are two popular topical medications for acne vulgaris. This study aimed to compare efficacy of the topical 4% nicotinamide and 1% clindamycin gels in these patients. In this randomized, double‐blind clinical trial, patients with moderate inflammatory facial acne vulgaris were randomly allocated to receive either topical 4% nicotinamide (n = 40) or 1% clindamycin gels (n = 40) twice daily. In each group, they were further categorized in two subgroups with oily and non‐oily types of facial skin. The Cook's acne grade was determined at baseline and at weeks 4 and 8 post treatment. Acne grade decreased from an average of 5.93 ± 0.83 at baseline to 4.03 ± 1.33 at week 4 and 2.08 ± 1.59 at week 8 in nicotinamide receivers, and from an average of 5.70 ± 0.94 at baseline to 3.85 ± 1.66 at week 4 and 2.03 ± 1.53 at week 8 in the clindamycin group (within‐group P < 0.001, between‐group P > 0.05). Comparing with each other, nicotinamide and clindamycin gels were significantly more efficacious in oily and non‐oily skin types, respectively. No major side effect was encountered by any patient. Skin type is a significant factor in choosing between topical nicotinamide and clindamycin in patients with acne vulgaris.     

Clinical clues for differential diagnosis between verruca plana and verruca plana‐like seborrheic keratosis

Sometimes the clinical differentiation between verruca plana (VP) and VP‐like seborrheic keratosis (SK) could be challenged. However, there have been no studies on this issue to date. The aim of this study was to elucidate clinical and dermoscopic differences between these two diseases, and also to suggest a diagnostic algorithm of VP and VP‐like SK without skin biopsy. The patients who had lesions clinically considered as VP or VP‐like SK were the target of our study. We took clinical and dermoscopic photos with informed consent and conducted a questionnaire. All patients had their diagnoses confirmed by biopsy. Thirty‐three patients were enrolled in our study. Seventeen patients were finally diagnosed with VP (51.5%) and 16 patients with VP‐like SK (48.5%). In clinical findings, VP‐like SK showed significantly more scattered distribution than VP (P = 0.039), which exhibited more clustered or grouped distribution (P = 0.039). In dermoscopic findings, brain‐like appearance was more commonly observed in VP‐like SK (P = 0.003) whereas VP showed more red dots or globular vessels (P = 0.017) and even‐colored light brown to yellow patch (P < 0.001). Sex, onset age, the size of each lesion, location, color and shape showed no significant differences between them (P > 0.05). Based on our results, we suggest a diagnostic algorithm using Koebner's phenomenon, dermoscopic findings, distribution of each lesion and biopsy for multiple VP‐like lesions in adults, and we think it will be a very useful diagnostic tool in daily clinical dermatological practice.     

Real‐time three‐dimensional imaging of epidermal splitting and removal by high‐definition optical coherence tomography

While real‐time 3‐D evaluation of human skin constructs is needed, only 2‐D non‐invasive imaging techniques are available. The aim of this paper is to evaluate the potential of high‐definition optical coherence tomography (HD‐OCT) for real‐time 3‐D assessment of the epidermal splitting and decellularization. Human skin samples were incubated with four different agents: Dispase II, NaCl 1 M, sodium dodecyl sulphate (SDS) and Triton X‐100. Epidermal splitting, dermo‐epidermal junction, acellularity and 3‐D architecture of dermal matrices were evaluated by High‐definition optical coherence tomography before and after incubation. Real‐time 3‐D HD‐OCT assessment was compared with 2‐D en face assessment by reflectance confocal microscopy (RCM). (Immuno) histopathology was used as control. HD‐OCT imaging allowed real‐time 3‐D visualization of the impact of selected agents on epidermal splitting, dermo‐epidermal junction, dermal architecture, vascular spaces and cellularity. RCM has a better resolution (1 μm) than HD‐OCT (3 μm), permitting differentiation of different collagen fibres, but HD‐OCT imaging has deeper penetration (570 μm) than RCM imaging (200 μm). Dispase II and NaCl treatments were found to be equally efficient in the removal of the epidermis from human split‐thickness skin allografts. However, a different epidermal splitting level at the dermo‐epidermal junction could be observed and confirmed by immunolabelling of collagen type IV and type VII. Epidermal splitting occurred at the level of the lamina densa with dispase II and above the lamina densa (in the lamina lucida) with NaCl. The 3‐D architecture of dermal papillae and dermis was more affected by Dispase II on HD‐OCT which corresponded with histopathologic (orcein staining) fragmentation of elastic fibres. With SDS treatment, the epidermal removal was incomplete as remnants of the epidermal basal cell layer remained attached to the basement membrane on the dermis. With Triton X‐100 treatment, the epidermis was not removed. In conclusion, HD‐OCT imaging permits real‐time 3‐D visualization of the impact of selected agents on human skin allografts.     

Cardiovascular biomarkers in patients with psoriasis

Psoriasis is a systemic inflammatory disease of the skin with associated comorbidity. Severe forms of psoriasis are associated with increased mortality, which might be due to cardiovascular (CV) comorbidity. In this study, we investigated in 79 patients with psoriasis compared to 80 healthy volunteers different biomarkers that play a role in vascular disease and inflammation, such as C‐reactive protein (CRP), human soluble CD40 ligand (sCD40L), oxidized low‐density lipoprotein (ox‐LDL), human matrix Gla protein (MGP) and fetuin‐A. Our results showed that CRP (P < 0.0001), sCD40L (P < 0.0001) and MGP (P < 0.0001) were increased in the patient cohort. Fetuin‐A showed decreased serum levels in patients with psoriasis (P < 0.0001), whereas ox‐LDL did not show any significant difference. In multivariate analyses controlling for sex, age and BMI, these findings were confirmed. Thus, CV biomarkers are altered in patients with psoriasis. If the decrease in fetuin‐A as well as the increase in sCD40L can be proven in further studies, these biomarkers may help to characterize a subgroup of patients who are at risk to develop CVD and/or monitor the effect of therapeutic antipsoriatic strategies on concomitant diseases. This knowledge may be useful in the management of high‐need patients with psoriasis.     

Evaluation of anti‐wrinkle effects of a novel cosmetic containing niacinamide

Niacinamide is known to have effectiveness on sallowness, wrinkling, red blotchiness and hyperpigmented spots in aging skin. In this study, we have evaluated the anti‐wrinkle effects of a new cosmetic containing niacinamide. A randomized, placebo‐controlled, split face study was performed in 30 healthy Japanese females who had wrinkles in the eye areas. The tested cosmetic containing 4% niacinamide was applied on wrinkles of one side for 8 weeks, and a control cosmetic without niacinamide on another site. Anti‐wrinkle effects were evaluated with two methods: (i) doctors’ observation and photographs based on the guideline of the Japan Cosmetic Industry Association; and (ii) average roughness of skin surface (Ra value) using skin replica. This cosmetic showed marked and moderate improvement in 64% of the subjects with a significant difference as compared with the control site (P < 0.001). Wrinkle grades in the tested area significantly reduced more than pre‐application (P < 0.001) and the control (P < 0.001). Reduction in Ra value on the tested area was more than pre‐application (P < 0.01) and the control site (P < 0.05) with significant differences Only one subject stopped the study with minimal irritation. These results indicated that the tested lotion was well tolerated and may be an optional preparation for the treatment of wrinkles in the eye areas.     

Objective and non‐invasive evaluation of photorejuvenation effect with intense pulsed light treatment in Asian skin

Background Intense pulsed light (IPL) has been widely used for photorejuvenation. Although previous literature has shown clinical effectiveness of IPL treatments on cutaneous photoaging, the associated changes in the biophysical properties of the skin following IPL treatments have not been fully elucidated. Objective The aim of this study was to evaluate changes in skin biophysical properties in patients with photoaging after IPL treatments, using non‐invasive, objective skin measuring devices. Patients and methods A total of 26 Korean women with facial dyschromias underwent three sessions of IPL treatment at 4‐week intervals. Outcome assessments included standardized photography, global evaluation by blinded investigators, patients’ self‐assessment and objective measurements of colour (Mexameter MX18, Chromatometer), elasticity (Cutometer), roughness (Visiometer), sebum (Sebumeter) and skin hydration (Corneometer). Results Intense pulsed light treatments produced a 15% decrease in the size of representative pigmented lesions (P < 0.05). Patients’ self‐assessment revealed that 84% and 58% of subjects considered their pigmented lesions and wrinkles were improved respectively. Objective colorimetric measurement demonstrated significant improvements following IPL treatments that were most remarkable after one session of IPL. Moreover, skin elasticity showed significant improvements at the end of the study. Skin wrinkles as measured using Visiometer showed a mild improvement without statistical significance. Sebum secretion and water content of skin remained unchanged. Conclusions Intense pulsed light provided significant improvement in the appearance of facial pigmented lesions in Korean patients. These effects appeared to be more remarkable in improving pigmentation, skin tone and elasticity.     

物理抗菌剂（洁悠神）防治急性放射性皮炎临床研究

目的应用具有长效物理抗菌功能的洁悠神喷洒于放射性皮炎发生区域的皮肤,观察洁悠神防治放射性皮炎的临床效果。方法将接受放射治疗过程中出现急性放射性皮炎的258例头颈部恶性肿瘤患者随机分为对照组122例和治疗组136例。治疗组采用洁悠神治疗,对照组采用涂抹烧伤膏和氢地油治疗,2组治疗时间均为6周。评价6周后治疗组与对照组2级及以上放射性皮炎的发生率。结果治疗组和对照组2级以上急性放射性皮炎的发生率分别为52．94％和65．57％,治疗组与对照组差异有显著性（X^2=4．24,P〈0．05）。结论洁悠神可预防继发感染、止痒止痛,促进创面愈合,能有效降低急性放射性皮炎的发生率。     

Tumor‐to‐bone distance of invasive subungual melanoma: An analysis of 30 cases

Subungual melanoma (SUM) is rare and represents approximately 2–3% and 20% of all cutaneous melanomas in Caucasians and Asians, respectively. Amputation has usually been performed for invasive SUM; however, not all invasive SUMs invade or attach to the distal phalanx. To investigate the possibility of non‐amputative surgery for patients with invasive SUM, the distances between the deepest base of the melanoma cells and the bony surface in the surgical specimens of invasive SUM were measured. Thirty surgical specimens of invasive SUM were retrospectively reviewed. The contents of the specimens were as follows: 14 first toes, 10 thumbs, three second fingers, two third fingers, and one fifth finger. Four specimens showed bone invasion, and the tumor was attached to the bone in four specimens. The tumor‐to‐bone distance exceeded 0.9 mm in all the specimens with thicknesses <4 mm. In the non‐ulcerated SUMs (nine specimens), only one SUM specimen showed bone attachment. There was a higher likelihood of bone attachment or invasion when tumor thickness (TT) exceeded 4 mm (Pearson chi‐square test, P = 0.009; Fisher exact test, P = 0.004; student t test, 0.033). Univariate and multivariate analysis also revealed that thick TT had a statistically significant affect (odds ratio 1.807 and 1.865, 95% CI 1.11–3.01 and 1.11–3.13, P = 0.023 and 0.018). Non‐amputative surgery may be possible for SUM tumors that are of intermediate‐thickness. However, there has been little evidence demonstrating survival with non‐amputative surgery for invasive SUM. A large, randomized, prospective clinical study is required to address this issue.     

Mitochondrial dysfunction in affected skin and increased mitochondrial DNA in serum from patients with psoriasis

Psoriasis is characterized by keratinocyte proliferation and chronic inflammation, but the pathogenesis is still unclear. Dysregulated mitochondria (mt) could lead to reduced apoptosis and extracellular secretion of mtDNA, acting as “innate pathogen” triggering inflammation. Serum was obtained from healthy volunteers and psoriatic patients. Mitochondrial DNA was extracted from the serum and amplified with quantitative PCR (qPCR). Punch biopsies were obtained from lesional and non‐lesional psoriatic skin (10 cm apart) and from healthy volunteers, were placed in RNA later and were stored at ?80°C until RNA was extracted and cDNA was synthesized; gene expression of uncoupling protein 2 (UCP2), Dynamin‐related protein 1 (Drp1) and calcineurin, involved in the regulation of mitochondria function, was detected with qPCR. Mitochondrial DNA was significantly increased (7s, P = 0.0496 and Cytochrome B, CytB, P = 0.0403) in the serum of psoriatic patients (n = 63) as compared to controls (n = 27). Gene expression was significantly reduced for UCP2 (P = 0.0218), Drp1 (P = 0.0001) and calcineurin (P = 0.0001) in lesional psoriatic skin, as compared to non‐lesional or control skin. Increased serum extracellular mtDNA in psoriatic patients and decreased expression of mitochondrial regulatory proteins in psoriatic skin suggest increased inflammation and reduced keratinocyte apoptosis, respectively. Inhibitors of mtDNA secretion and/or UCP2 stimulants may be potential treatment options.     

UVB‐ and NGF‐induced cutaneous sensitization in humans selectively augments cowhage‐ and histamine‐induced pain and evokes mechanical hyperknesis

Exaggerated itch responses to pruritic chemical provocations and mechanical stimuli are evident in patients with chronic itch, for example, in atopic dermatitis. Currently used human models of itch do not account for such itch sensitization features, and the mechanisms underlying clinical itch sensitization are unknown. This study utilized two established human models of cutaneous nociceptive sensitization to explore how pre‐established inflammatory hyperalgesia (ultraviolet‐B‐irradiation; “UVB”) and non‐inflammatory neurotrophic pain sensitization (nerve growth factor; “NGF”) alter sensitivity to chemical and mechanically evoked itch. Twenty healthy volunteers participated in the UVB experiment. Six volar forearm areas (2 cm diameter) were UVB irradiated with ≤2 × minimal erythemal dose, and two non‐irradiated areas were used as controls. Sixteen healthy volunteers participated in the NGF experiment and had 2 μg intradermally injected (4 × 50 μL in 2 cm diameter areas) into both volar forearms. Isotonic saline was applied as control. Pain sensitivity measurements (mechanical and heat pain thresholds) were conducted to validate the models. Subsequently, itch was evoked using histamine and cowhage spicules in the sensitized skin areas, and itch/pain was rated using visual analogue scales. Mechanical hyperknesis (increased itch to punctuate stimuli) was probed with von Frey filaments before/after each itch provocation. Both UVB‐ and NGF models induced robust primary mechanical hyperalgesia (P < .01) and hyperknesis (P < .05). Neither of the models augmented itch in response to chemical itch provocations but significant increases specifically for pain ratings were observed for both histamine and cowhage (P < .05). This suggests that these models are of limited value as proxies for itch sensitization to pruritogens observed, e.g., in inflammatory dermatoses.     

Cross‐sectional multicenter observational study of psoriatic arthritis in Japanese patients: Relationship between skin and joint symptoms and results of treatment with tumor necrosis factor‐α inhibitors

Psoriatic arthritis (PsA) is an inflammatory arthritis with as yet unclear pathophysiology. This retrospective, multicenter, cross‐sectional study was conducted in 19 facilities in western Japan and aimed to identify patients’ characteristics and factors that affect the results of treatment with biologic agents. Of 2116 patients with psoriasis, 285 (13.5%) had PsA. Skin manifestations preceded joint manifestations in 69.8%, the onset was simultaneous in 17.2%, whereas PsA preceded skin manifestations in 2.5%. Peripheral arthritis was most common, occurring in 73.7%, compared with axial disease in 21.8%, enthesitis in 23.5% and dactylitis in 35.4%. Patients with severe skin manifestations were significantly younger at onset (P = 0.02) and more frequently had axial disease (P < 0.01). Biologic agents were used in 206 patients (72.3%), anti‐tumor necrosis factor (TNF)‐α antibodies being prescribed first to 157 of them. Anti‐TNF‐α antibodies were continued by 105 participants and discontinued by 47, the remaining five patients being lost to follow up. Patients who discontinued anti‐TNF‐α antibodies were significantly older than those who continued (55 vs 51 years, P = 0.04) and significantly older at onset of joint manifestations (50 vs 44 years, P = 0.01). Multivariate analysis revealed that patients over 50 years significantly more frequently terminated anti‐TNF‐α antibodies (P < 0.01). In conclusion, patients with PsA and severe skin manifestations have earlier onset and axial disease, which seriously impacts on quality of life. Anti‐TNF‐α antibodies were generally effective enough to continue but less so in patients aged over 50 years. Further detailed research is needed.     

No association of atherosclerosis with digital ulcers in Japanese patients with systemic sclerosis: Evaluation of carotid intima‐media thickness and plaque characteristics

Patients with systemic sclerosis (SSc) usually develop Raynaud's phenomenon, persistent digital ischemia and sometimes develop digital ulcers (DU). Several studies have reported an association of carotid artery atherosclerosis with SSc by evaluating carotid intima‐media thickness (IMT) in SSc patients. However, none of those studies analyzed the association between DU and carotid artery atherosclerosis in SSc patients. We examined the association of carotid artery atherosclerosis with digital ulcers by comparing SSc patients with (n = 48, 29.5%) and without (n = 206, 70.5%) DU. The demographic and clinical features of the SSc patients showed that young age, male sex, anti‐topoisomerase I antibody positivity, severe skin sclerosis, interstitial lung disease complication and cardiac involvements were significantly prevalent in patients with DU. In addition, diffuse cutaneous type, anti‐RNA polymerase III antibody positivity and severe skin sclerosis are more frequent in SSc patients with DU at the extensor surface of joints than SSc patients with DU at the digital tip. There were no differences in serum lipid level, carotid IMT or plaque score between SSc patients with and without DU, suggesting that atherosclerotic changes are not primarily involved in the development of DU.