Clinical utility of anti-Ro52 antibody confirmation in anti-MDA5 antibody-positive dermatomyositis: A case report.

This case report highlights dermatomyositis (DM) characterised by the concurrent presence of anti-melanoma differentiation-associated protein 5 (anti-MDA5) and anti-Ro52 antibodies. A 64-year-old woman initially presented with erythema on the palms, which later spread to the dorsum of the hands, followed by involvement of the face, forehead, and upper eyelids. The patient reported joint pain, fatigue, and dyspnea. Physical examination revealed characteristic cutaneous manifestations, including heliotrope rash and Gottron's sign, accompanied by skin ulceration and muscle weakness. Blood tests showed elevated levels of creatine phosphokinase and C-reactive protein. A high-resolution computed tomography (HRCT) scan revealed interstitial lung disease (ILD) with an organising pneumonia (OP) pattern. Magnetic resonance imaging (MRI) confirmed the presence of myositis. Autoantibody analysis revealed concurrent positivity for both anti-MDA5 and anti-Ro52 antibodies. At the time of diagnosis, she had no respiratory impairment, but had an elevated C-reactive protein and high levels of anti-MDA5 antibody. She was started on triple combination therapy with glucocorticoids, cyclophosphamide, and tacrolimus. She had worsening oxygenation and elevated ferritin during the first weeks of treatment, but then her symptoms improved. Early detection of a co-positive anti-Ro52 antibody led to early initiation of triple combination therapy and a good prognosis.

Effects of Acupuncture Therapy on Drug-Resistant Fibromyalgia: An Exploratory Single-Arm Nonrandomized Trial.

Introduction: Fibromyalgia is a chronic illness that causes symptoms such as pain. In Japan, although pregabalin and duloxetine are the drugs of choice for fibromyalgia, they may be ineffective or may cause side-effects. Studies have reported on the efficacy of acupuncture against fibromyalgia. However, acupuncture is not always effective in clinical practice, and the reason for this is thought to be the dysfunction of the descending pain control system. This study aimed to determine whether the combined use of electro-scalp acupuncture and conventional electroacupuncture reduces fibromyalgia symptoms and drug dosage requirements. Methods: Patients with intractable fibromyalgia (visual analog scale [VAS] score ≥50 mm; Japanese version of the Fibromyalgia Impact Questionnaire [JFIQ] score ≥50) receiving pregabalin were recruited in this single-arm nonrandomized uncontrolled study. They underwent electroacupuncture on four limbs plus electro-scalp acupuncture once a week for 5 weeks. Drug intake, pain (as determined using VAS), quality of life (QOL; as determined using JFIQ), anxiety, depression, catastrophic thoughts, and sleep were assessed. Results: Although there was no increase in drug intake, 42.8% (3/7) of patients reduced pregabalin intake by approximately 10% (a moderate though insignificant effect). Pain levels significantly declined (VAS 75.4 ± 11.7 mm to 64.3 ± 17.3 mm; P = 0.05) and QOL significantly improved (JFIQ 67.0 ± 13.4 to 50.9 ± 18.3; P = 0.02). The parameters for anxiety, depression, catastrophic thoughts, and sleep did not significantly change. Conclusion: The combination of conventional electroacupuncture plus electro-scalp acupuncture may effectively alleviate pain, improve QOL, and reduce pregabalin dosage requirements in patients with fibromyalgia.

High prevalence of anti-TSH receptor antibody in fibromyalgia syndrome.

AIM: Fibromyalgia syndrome (FMS) is defined as chronic widespread pain that cannot be accounted for by any other medical disorder. Our aim was to explore the prevalence of thyroid autoimmunity in patients with FMS. METHODS: For determining thyroid function in 207 FMS patients, we tested for the titers of free tri-iodothyronine, free thyroxine, thyroid-stimulating hormone (TSH), anti-thyroid peroxidase antibody (TPOAb), anti-thyroglobulin antibody (TgAb) and anti-TSH receptor antibody (TRAb). RESULTS: Twenty-five patients who had either subclinical hyper- or hypothyroidism, or overt hypothyroidism were excluded. Sixty-nine FMS patients with autoimmune thyroid diseases (AITD) (37.9%, 69/182) were identified. The prevalence of positivity for TRAb, TgAb and TPOAb was 20.3% (n = 37), 16.5% (n = 30) and 13.2% (n = 24), respectively. Compared to control populations in previous studies, the prevalence of TRAb positivity was high, and titers of TRAb were low (1.0-1.5 IU/L). The prevalence of TPOAb and TgAb positivity was not significantly higher than that reported in FMS patients in previous studies. Clinical symptom profiles were identical for FMS patients with and without AITD. CONCLUSION: We found a high prevalence of AITD among 207 patients with clinically defined FMS, with TRAb being especially prominent among these patients. Further study is needed to evaluate changes in thyroid function among FMS patients with AITD.

An epidemiologic internet survey of fibromyalgia and chronic pain in Japan.

OBJECTIVE: To determine the epidemiologic features and symptom characteristics of fibromyalgia (FM) in Japan, and compare them with those for other chronic pain (CP) diagnoses. METHODS: An internet survey was conducted in June and July 2011. The questionnaire consisted of 111 questions, including assessments of the Japanese version of the 2010 American College of Rheumatology preliminary diagnostic criteria for FM, the Japanese Fibromyalgia Impact Questionnaire, and additional questions regarding pain and lifestyle. RESULTS: The questionnaire was completed by 20,407 male and female respondents in all prefectures of Japan. Of the survey population, 2,524 respondents (12.4%) reported symptoms consistent with CP; of these, 425 (2.1%) reported symptoms consistent with FM. Among respondents with FM and CP, 61% and 53%, respectively, were women. Pain severity and Widespread Pain Index scores were significantly higher in respondents meeting the diagnostic criteria for FM than in those meeting the criteria for CP. In terms of symptom severity scores, the proportions of respondents reporting the 3 major symptoms as "highly applicable" and greater numbers of 41 somatic symptoms were higher among respondents with FM than among those with CP. The incidence of FM in the present survey was similar to that reported (1.7%) in a study of FM in Japan in 2003, despite the use of the newer, easier to use 2010 diagnostic criteria. CONCLUSION: Because FM usually presents with more severe and more widely distributed pain, as well as more nonpainful symptoms than CP, our results suggest that FM is a different clinical phenotype of CP.

Bibliographical investigation of complementary alternative medicines for osteoarthritis and rheumatoid arthritis.

BACKGROUND: A variety of complementary and alternative medicine (CAM) treatments are provided to the elderly. We investigated the efficacy and safety of CAM substances that are available to patients with osteoarthritis (OA) and rheumatoid arthritis (RA), both in Japan and overseas. METHODS: Information on CAM products was collected from the World Wide Web, using the keywords "arthritis" and "supplement" in five languages (Japanese, English, French, Italian and German) using a popular search engine for each of the languages. References to published work on the products were researched using PubMed with the keywords of "arthritis", "anti-inflammatory" and "analgesics". Such published work was classified according to the evidence levels established by the Cochrane Library. RESULTS: Two-hundred and sixty CAM products for OA or RA were available in Japan, of which 41 CAM products had been tested in randomized controlled trials (RCT); there was no scientific evidence for the remaining 219 CAM products. Most of the previous RCT suggested that CAM was effective in OA or RA. Herein, we confirmed the significant OA relieving effects of chondroitin sulfate through a meta-analysis. Effectiveness was assessed using subjective scores, not disease-specific immunological or serological markers for assessment. Toxicological investigations had only been performed for a few CAM products. CONCLUSION: Some CAM products that are effective against RA may be used together with biological therapy. However, some of the CAM products available in Japan should be tested using objective markers. Some CAM products for OA could be used for the relief of pain.

Pulmonary-renal syndrome in systemic sclerosis: a report of three cases and review of the literature.

We describe three cases of acute renal failure with diffuse alveolar hemorrhage, which is designated pulmonary-renal syndrome (PRS), in systemic sclerosis (SSc) and review the literature to better define this rare but severe complication of SSc. The clinical course of three SSc patients with acute renal failure and concomitant diffuse alveolar hemorrhage are reported, and the literature published between 1967 and 2005 is reviewed following a PubMed search. Including our cases, a total of 19 SSc patients with acute renal failure and concomitant diffuse alveolar hemorrhage have been reported. Pulmonary-renal syndrome developing in SSc patients can be categorized clinicopathologically into three entities: PRS with thrombotic microangiopathy, PRS with small vessel vasculitides accompanied with SSc, and d-penicillamine-induced Goodpasture-like syndrome. Patients with scleroderma PRS with thrombotic microangiopathy, to which group our all patients belong, often developed diffuse alveolar hemorrhage after receiving high-dose corticosteroid therapy. Pulmonary-renal syndrome is a fatal complication of SSc and results from different pathogenic processes. Prompt differential diagnosis between the subsets is critical, because therapeutic strategy may differ in the use of high-dose corticosteroid and plasma exchange between the subsets of PRS. Clinical courses of the patients with PRS with thrombotic microangiopathy suggest that high-dose corticosteroid therapy is a trigger of diffuse alveolar hemorrhage in patients with diffuse SSc with signs of thrombotic microangiopathy.

Histopathological investigation of salivary glands in the asymptomatic elderly.

The significance of labial gland biopsies (LGBs) in the diagnosis of Sjögren's syndrome (SS) in the elderly has been a controversial subject since it is complicated by age-related histopathological changes. In an attempt to clarify the appropriateness of LGBs in present diagnosis criteria, we evaluated the specificity of LGBs using autopsied tissues. This was done by taking labial, sublingual and submandibular salivary glands from 53 autopsy subjects (24 males and 29 females) with an average age of 84 years, and testing them histopathologically with reference to a previously reported grading system. None had any sicca symptoms (oral dryness or dry eye). In subjects up to 75 years old, acinar atrophy was more frequent in labial glands than in the two major salivary glands (P=0.0098 for sublingual and P=0.0009 for submandibular glands). Also, while there were significant differences in frequency of such atrophy between the sublingual and submandibular salivary glands of subjects younger and older than 75, the labial glands showed no such variation. Taking grade 3 (focus score of 1) as the diagnosis criterion, two subjects were determined to have SS in which case the specificity was 95%. Using contemporaneous serological test results for anti-SSA/Ro antibodies as a diagnostic criterion raised specificity to 98%. For both major and minor glands, these appeared to be no relationship between degree of lymphocytic infiltration and age. Our results thus suggest that it is appropriate to adopt a focus score of 1 as a diagnostic criterion for SS in the elderly, and that serological test results can improve specificity.

Clinical and epidemiologic analysis of giant cell (temporal) arteritis from a nationwide survey in 1998 in Japan: the first government-supported nationwide survey.

OBJECTIVE: To elucidate epidemiologic and clinical manifestations of Japanese patients with giant cell arteritis (GCA), the first nationwide survey for GCA was conducted in 1998 in Japan. METHODS: The first questionnaire on GCA for patients treated in 1997 was sent to 10,717 medical departments in Japan. A total of 177 patients were reported. Among the 177 patients, 66 GCA patients with detailed clinical and epidemiologic features on second survey were analyzed. RESULTS: Prevalence in patients 50 years of age and older in 1997 was 1.47 per 100,000 population in Japan. The average age at onset was 71.5 years old. The male:female ratio was 1:1.7. The association with permanent and complete visual loss (6.5%), jaw claudication (15.2%), and polymyalgia rheumatica (PMR) (30.3%) were low in frequency compared with those reported from other countries. All patients were treated with corticosteroids. Only 3 (4.5%) patients were reported as deceased due to other causes. CONCLUSION: The prevalence of GCA in Japan was revealed to be extremely low compared with other countries. Clinical findings of permanent and complete visual loss, jaw claudication, and PMR were infrequent among Japanese patients with GCA.

Transforming growth factor beta1 gene polymorphism in patients with systemic sclerosis.

OBJECTIVE: To determine whether transforming growth factor beta1 (TGFbeta1) gene DNA polymorphism is associated with pathogenesis in the fibrosis of patients with systemic sclerosis (SSc). METHODS: Eighty-seven Japanese patients with SSc including 30 with diffuse type and 57 with limited type together with 110 unrelated controls were investigated. Pulmonary fibrosis was determined in 34 SSc patients using high-resolution chest computed tomography. TGFbeta1 genetic polymorphisms were analyzed in 2 loci; T869C (Leu10Pro) in codon 10 at exon 1, and C-509T in the promoter region using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Neither the genotype of T/C polymorphism in T869C nor C/T polymorphism in C-509T revealed any difference in distribution between SSc and controls. In the group of SSc patients with pulmonary fibrosis, a weak but significantly high frequency (p = 0.05) of TC+CC (the presence of C allele) in T869C, and CT+TT (the presence of T allele) in C-509T was found. Compared with controls, the pulmonary fibrosis group showed no difference in the highly frequent alleles. CONCLUSION: Our results suggest that TGFbeta1 polymorphisms do not play a role in the pathogenesis of SSc, even though there remains the possibility of a risk factor for genetic susceptibility to pulmonary fibrosis.

[The rheumatoid vasculitis and malignant rheumatoid arthritis(MRA)].

The inflammatory process characteristic of rheumatoid arthritis is typically targeted to the synovial membrane. In a subset of patients, rheumatoid disease is complicated by an inflammatory destruction of blood vessels, rheumatoid vasculitis. Rheumatoid vasculitis has been understood to be the result of severe disease extending beyond the joint, possibly caused by immune complex deposition. However, in Japan malignant rheumatoid arthritis(MRA) is designated as rheumatoid arthritis with vasculitis. Rheumatoid arthritis patients can be separated into two groups: individuals with synovial disease and individuals with synovial plus extra-articular disease, MRA. The model is supported by immunogenetic analysis describing an accumulation of vasculitis patients with rheumatoid arthritis among HLA-DRB10401 homozygotes. Therapy depends upon the clinical manifestation of rheumatoid vasculitis. Then, MRA is usually treated with steroid, and steroid pulse therapy and immunosuppressants are useful for severe MRA.