Search

Nail fold videocapillaroscopy (NVC) abnormalities are a characteristic finding of microangiopathy in dermatomyositis (DM). The aim of the present study was to examine long‐term changes in NVC abnormalities and serum fibroblast growth factor 23 (FGF23) and vascular endothelial growth factor (VEGF) levels in DM patients with anti‐melanoma differentiation‐associated gene 5 (MDA5) antibody (Ab). Serum levels of FGF23 and VEGF were measured by enzyme‐linked immunosorbent assay. NVC abnormalities were evaluated by capillaroscopy in 11 DM patients with anti‐MDA5 Ab at baseline and after treatment. NVC abnormalities included irregularly enlarged capillaries, reduced capillaries, hemorrhages, capillary ramifications, disorganization of the vascular array, loss of capillaries and giant capillaries. Serum FGF23 levels were significantly decreased in patients with anti‐MDA5 Ab (0.3 ± 0.3 pmol/L) compared with healthy controls (1.0 ± 0.6 pmol/L, P < 0.01). Serum FGF23 levels significantly increased after treatment (0.3 ± 0.3 vs 1.0 ± 0.7 pmol/L, P < 0.005), but serum VEGF levels were comparable between at baseline and after treatment. At baseline, irregularly enlarged capillaries were observed in 10 of 11 patients, but after treatment, they were significantly reduced in only two (91% vs 18%, P < 0.001). Hemorrhages were observed in all 11 patients at baseline, but disappeared in all after treatment (100% vs 0%, P < 0.001). These results suggest that NVC abnormalities are reversible by treatment and that serum FGF23 levels reflect the degree of microvascular damage in DM patients with anti‐MDA5 Ab. [ABSTRACT FROM AUTHOR]

Eosinophilic fasciitis is a relatively rare cutaneous fibrotic condition affecting the deep fascia of the extremities, with or without peripheral blood eosinophilia. To examine the characteristics of Japanese patients with eosinophilic fasciitis, we conducted a brief, multicenter, retrospective survey at seven university hospitals. In total, 31 patients were identified as having eosinophilic fasciitis, among whom 30 patients fulfilled the Japanese diagnostic criteria. The male : female ratio was 2.3:1, and the mean age was 47.7 years. Three of the patients were under 20 years old. The possible triggering factors included muscle training, sports, walking or sitting for a long time, physical work, insect bite and drug. Co‐occurrence of morphea was observed in nine cases (29%), and malignancies were associated in three (two hematological malignancies and one internal malignancy). Immunological abnormalities in the serum showed positive antinuclear antibody, positive rheumatoid factor, increased aldolase levels and increased immunoglobulin G levels. The patients were treated with either monotherapy or combination therapy by oral prednisolone (20–80 mg/day), methotrexate (6–10 mg/week), cyclosporin (100–150 mg/day), mizoribine, infliximab and phototherapy. Methylprednisolone pulse therapy was performed in six cases. By contrast, spontaneous improvement due to resting only was observed in two cases, and skin hardening was improved by withdrawal of the anticancer drug in one case. This study suggests several characteristics of Japanese patients with eosinophilic fasciitis, namely male predominance, rare pediatric occurrence, immunological abnormalities and coexistence with morphea. Systemic prednisolone is the first‐line therapy, but pulse therapy is occasionally required for severe cases. The triggering events of physical stress are not so frequent as have previously been reported, and various factors or even unknown factors may be associated with the induction of eosinophilic fasciitis. [ABSTRACT FROM AUTHOR]

The presence of anti‐transcriptional intermediary factor (TIF)1‐γ antibody (Ab) is associated with cancer in adult patients with clinically amyopathic dermatomyositis (CADM) or dermatomyositis (DM). In this study, we examined whether anti‐TIF1‐γ Ab levels are associated with disease activity in patients with CADM/DM. Anti‐TIF1‐γ Ab levels were examined in 23 patients with CADM or DM (CADM, n = 6; DM, n = 17). Baseline characteristics and outcomes were recorded, and serial measurements of anti‐TIF1‐γ Ab levels were obtained. Of the 23 patients with detectable anti‐TIF1‐γ Ab, 16 (70%) had an internal malignancy, while two (9%) had interstitial lung disease. Mean initial anti‐TIF1‐γ Ab levels (134 ± 47 index) were significantly decreased after 24 months (54 ± 45 index, P < 0.0001) and remained decreased thereafter. Anti‐TIF1‐γ Ab became negative (index value, <32) in 10 patients (43%) and remained positive (index value, ≥32) in 13 patients (57%) during the clinical course. The frequency of remission in the anti‐TIF1‐γ Ab‐negative conversion group (100%) was significantly higher than in the sustained positive group (0%, P < 0.0001). Furthermore, mortality in the anti‐TIF1‐γ Ab‐negative conversion group (0%) was significantly lower than that in sustained positive group (69%, P < 0.001). This study indicates that anti‐TIF1‐γ Ab levels are a useful and relevant surrogate marker of disease activity during follow‐up monitoring. [ABSTRACT FROM AUTHOR]

Patients with dermatomyositis (DM) frequently have myositis‐specific autoantibodies (MSA), which are closely associated with different clinical features. Patients with anti‐aminoacyl‐tRNA synthetase antibody (ARS‐Ab) and anti‐melanoma differentiation‐associated gene 5 (MDA5)‐Ab often have interstitial lung disease (ILD). Recently, anti‐MDA5‐Ab levels have been shown to correlate with disease activity in DM patients. Thus, B cells that are stimulated by excess B‐cell activating factor (BAFF) play an important role in the pathogenesis of DM through auto‐Ab production. In this study, we investigated the role of BAFF in DM patients. We measured the serum BAFF levels in 56 adult DM patients (14 with anti‐ARS‐Ab, 18 with anti‐MDA5‐Ab, seven with anti‐Mi‐2‐Ab and 17 with anti‐transcriptional intermediary factor‐1γ‐Ab). For a longitudinal study, 130 serum specimens from 10 DM patients with anti‐MDA5‐Ab were analyzed. Serum BAFF levels were significantly higher in DM patients than in healthy controls. DM patients with elevated serum BAFF levels more frequently had ILD. In subgroup analysis, DM patients with anti‐ARS‐Ab and DM patients with anti‐MDA5‐Ab exhibited increased BAFF levels compared with controls, while DM patients with other MSA showed BAFF levels comparable with controls. In the longitudinal study, serum BAFF levels in DM patients with anti‐MDA5‐Ab were decreased after immunosuppressive therapy along with serum levels of anti‐MDA5‐Ab and ferritin, which are biomarkers of disease activity. These results suggest that BAFF plays an important role in the pathogenesis of ILD in DM patients with anti‐ARS and anti‐MDA5‐Ab. Furthermore, serum BAFF level is associated with disease activity in DM patients with anti‐MDA5‐Ab. [ABSTRACT FROM AUTHOR]

Abstract: We established diagnostic criteria and severity classification of localized scleroderma because there is no established diagnostic criteria or widely accepted severity classification of the disease. Also, there has been no clinical guideline for localized scleroderma, so we established its clinical guideline ahead of all over the world. In particular, the clinical guideline was established by clinical questions based on evidence‐based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guideline easy to use and reliable based on the newest evidence, and to present guidance as specific as possible for various clinical problems in treatment of localized scleroderma. [ABSTRACT FROM AUTHOR]

Abstract: Several effective drugs have been identified for the treatment of systemic sclerosis (SSc). However, in advanced cases, not only their effectiveness is reduced but they may be also harmful due to their side‐effects. Therefore, early diagnosis and early treatment is most important for the treatment of SSc. We established diagnostic criteria for SSc in 2003 and early diagnostic criteria for SSc in 2011, for the purpose of developing evaluation of each organ in SSc. Moreover, in November 2013, the American College of Rheumatology and the European Rheumatology Association jointly developed new diagnostic criteria for increasing their sensitivity and specificity, so we revised our diagnostic criteria and severity classification of SSc. Furthermore, we have revised the clinical guideline based on the newest evidence. In particular, the clinical guideline was established by clinical questions based on evidence‐based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guideline easy to use and reliable based on the newest evidence, and to present guidance as specific as possible for various clinical problems in treatment of SSc. [ABSTRACT FROM AUTHOR]

Abstract: Localized scleroderma (LoS) involves dermal but not internal inflammation and fibrosis. Cosmetic changes often impact quality of life (QOL), however, impairment of activities of daily living (ADL) in LoS patients has not been investigated. To determine what factor(s) are associated with ADL in adult patients with LoS, we performed a retrospective observational study in 177 Japanese adult LoS patients using a novel LoS disability score based on Barthel's indices of ADL: feeding, bathing, grooming, dressing, bowels, bladder, toilet use, transfers, mobility and stairs. LoS disability scores increased in proportion to the number of affected body parts but were not correlated to age and duration of illness. The presence of leg lesions significantly impaired ADL of LoS patients compared with lesions on other body parts. Patients treated with systemic medications, who tended to have multiple lesions, presented higher LoS disability scores than those without systemic treatments. Our study proposes that physicians evaluate ADL, not only QOL, in LoS patients. Our findings using LoS disability scoring indicate that multiple affected body parts and leg lesions are risk factors for ADL impairment. [ABSTRACT FROM AUTHOR]

A multicenter, open-label study was performed to investigate the safety and tolerability of bosentan in Japanese patients with systemic sclerosis ( SSc) and secondary digital ulcers. Twenty-eight patients were enrolled. The safety and tolerability of bosentan was monitored over 52 weeks of study treatment (primary end-point), while incidence and healing of digital ulcers were also assessed up to week 16. The following adverse events occurred in 5% or more of patients during the 52-week treatment period: upper respiratory tract infection (50.0%), abnormal liver function tests (42.9%), digital ulcers (25.0%), anemia (17.9%), peripheral edema (14.3%), diarrhea (10.7%), urinary tract infection (7.1%), arthralgia (7.1%), constipation (7.1%) and herpes zoster (7.1%). Eight patients experienced at least one serious adverse event, including drug-related serious adverse events in two patients, which were abnormal liver function tests and fluid retention (pericardial effusion) in one patient each. During the 16-week observation period, seven out of 28 patients (25%) developed new digital ulcers. In this study, adverse events were comparable with those previously reported with bosentan. Approximately half of the patients had adverse events associated with abnormal liver function tests, thus we conclude that liver function should be monitored regularly during treatment with bosentan. [ABSTRACT FROM AUTHOR]

A 75‐year‐old man presented with a 1‐cm large elastic soft subcutaneous nodule on the left side of the umbilicus, which when excised showed presence of a helminthic form within the granulomatous lesions. Morphologically, the helminth was considered to be of the genus Dirofilaria, and the patient showed increased serum antibody titer against canine filaria. The partial DNA sequence of the mitochondrial 12S rRNA gene locus of this clinical isolate showed the highest nucleotide identity (89.6%) with Dirofilaria repens; however, the phylogenetic analysis addressed the haplotype and Dirofilaria ursi as outgroups of the clusters of D. repens and Dirofilaria immitis, which are the causal agents of most human dirofilariasis. As like bear filaria D. ursi, a wide variety of other carnivore‐parasitizing filaria species have rarely been reported in humans. The newly detected genetic haplotype in this case may correspond to one of these species of Dirofilaria, though the genetic references are not available thus far. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about chemokines.

We established diagnostic criteria and severity classification of lichen sclerosus et atrophicus, because there is no established diagnostic criteria or widely accepted severity classification of the disease. Also, there is no clinical guideline for lichen sclerosus et atrophicus in Japan, so we proposed its clinical guideline. The clinical guidelines were formulated by clinical questions and recommendations on the basis of evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guidelines easy to use and reliable including the newest evidence, and to present guidance for various clinical problems in treatment of lichen sclerosus et atrophicus., (© 2017 Japanese Dermatological Association.)

We established diagnostic criteria and severity classification of eosinophilic fasciitis because there is no established diagnostic criteria or widely accepted severity classification of the disease. Also, there has been no clinical guideline for eosinophilic fasciitis, so we established its clinical guideline ahead of all over the world. In particular, the clinical guideline was established by clinical questions based on evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guideline easy to use and reliable based on the newest evidence, and to present guidance as specific as possible for various clinical problems in treatment of eosinophilic fasciitis., (© 2017 Japanese Dermatological Association.)

We describe a patient with drug-induced hypersensitivity syndrome (DIHS) associated with human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV) infection induced by sulfasalazine. Two weeks after starting sulfasalazine to treat a rectal ulcer, the patient developed disseminated macular erythema accompanied by fever, liver injury, and lymphadenopathy. Seroconversion of antibodies to HHV-6 was observed. Systemic steroid treatment was not effective against the eruptions. Five months after the onset, he presented with an acute febrile disease. The detection of CMV antigen on peripheral blood leukocytes and positive staining for CMV on cutaneous endothelium indicated active CMV infection. Furthermore, he developed a bacteremia of methicillin resistant Staphylococcus aureus. An association the CMV reactivation with DIHS was suggested, although there remains the possibility that the systemic steroid treatment precipitated CMV reactivation. Recently, HHV-6 has been documented to have immunomodulating effects and to be associated with CMV reactivation. Therefore, we should pay attention to the possibility of CMV reactivation in patients with DIHS in whom the immunomodulating virus of HHV-6 has been reactivated.