Role of the CCL20/CCR6 axis in tubular epithelial cell injury: Kidney-specific translational insights from acute kidney injury to chronic kidney disease.

This study investigated the role of the axis involving chemokine receptor 6 (CCR6) and its ligand chemokine (C-C motif) ligand 20 (CCL20) in acute kidney disease (AKD) using an ischemia-reperfusion injury (IRI) model. The model was established by clamping the unilateral renal artery pedicle of C57BL/6 mice for 30 min, followed by evaluation of CCL20/CCR6 expression at 4 weeks post-IRI. In vitro studies were conducted to examine the effects of hypoxia and H2 O2 -induced oxidative stress on CCL20/CCR6 expression in kidney tissues of patients with AKD and chronic kidney disease (CKD). Tubular epithelial cell apoptosis was more severe in C57BL/6 mice than in CCL20 antibody-treated mice, and CCR6, NGAL mRNA, and IL-8 levels were higher under hypoxic conditions. CCL20 blockade ameliorated apoptotic damage in a dose-dependent manner under hypoxia and reactive oxygen species injury. CCR6 expression in IRI mice indicated that the disease severity was similar to that in patients with the AKD phenotype. Morphometry of CCL20/CCR6 expression revealed a higher likelihood of CCR6+ cell presence in CKD stage 3 patients than in stage 1-2 patients. Kidney tissues of patients with CKD frequently contained CCL20+ cells, which were positively correlated with interstitial inflammation. CCL20/CCR6 levels were increased in fibrotic kidneys at 4 and 8 weeks after 5/6 nephrectomy. These findings suggest that modulating the CCL20/CCR6 pathway is a potential therapeutic strategy for managing the progression of AKD to CKD.

Erratum: Correction of Author's Affiliation in the Article "Changing Patterns of Medical Visits and Factors Associated With No-show in Patients With Rheumatoid Arthritis During COVID-19 Pandemic".

This corrects the article on p. e423 in vol. 35, PMID: 33316859.

A flare of Still's disease following COVID-19 vaccination in a 34-year-old patient.

Vaccination is a cornerstone for reducing the risk of COVID-19 infection during a pandemic. Although the currently used COVID-19 vaccine is considered safe, some concerns persist regarding the likelihood of flares of rheumatic diseases. Still's disease is a rare auto-inflammatory disorder of unknown etiology, and the data on the flare of Still's disease following COVID-19 vaccination are limited. Therefore, we hereby present the case of a 34-year-old female patient with Still's disease who experienced a flare after a ChAdOx1 nCoV-19 vaccination. The patient visited the emergency department complaining of fever, arthralgia, myalgia, pleuritic chest pain and macular salmon-pink rash on her back for the past 2 days. She had maintained low Still's disease activity with etanercept and low-dose glucocorticoid for 14 years. She received the ChAdOx1 nCoV-19 vaccine 7 days before the flare. Laboratory investigations revealed leucocytosis and elevated serum levels of erythrocyte sedimentation rate, C-reactive protein, and ferritin. Computed tomography showed no specific findings. She received methylprednisolone pulse therapy, etanercept, and methotrexate for treating the Still's disease flare. However, her symptoms were not fully controlled, and she developed pericarditis, pleuritis, fever and macular rashes expanding to her extremities. After excluding infectious conditions by blood culture and pleural fluid analysis, we administered tocilizumab with methotrexate and prednisolone. Her symptoms and laboratory findings improved significantly, and she was discharged without symptoms 7 days later. Although rare, this case of a patient with Still's disease undergoing a flare following vaccination suggests that close observation of disease activity is warranted following COVID-19 vaccination.

Maternal and paternal effects on hyperuricaemia: a cross-sectional study from the seventh Korean National Health and Nutrition Examination Survey.

OBJECTIVE: As the heritability of hyperuricaemia remains largely unexplained, we analysed the association between parental and offspring hyperuricaemia at the phenotype level. METHODS: This cross-sectional study included data on 2373 offspring and both-parent pairs from the seventh Korean National Health and Nutrition Examination Survey. Logistic regression and generalised estimating equation analysis were used to evaluate the association between offspring and parental hyperuricaemia adjusting for metabolic risk factors and alcohol intake. RESULTS: Both maternal and paternal hyperuricaemia were associated with offspring hyperuricaemia among teenagers, but from the age of 20 years, a strong association was observed between offspring and paternal, rather than, maternal hyperuricaemia, and this could not be explained by metabolic risk factors such as obesity. However, there was a positive interaction between offspring alcohol intake and parental hyperuricaemia, and there was a stronger association between terciles of offspring alcohol intake and hyperuricaemia in the presence of parental hyperuricaemia: T1 (reference), T2 odds ratio (OR) 1.1 (0.3-4.6), and T3 OR 3.3 (1.4-7.9) (P for trend .017) vs. T1 (reference), T2 OR 0.7 (0.3-1.9), and T3 OR 1.1 (0.6-2.2) (P for trend .974). CONCLUSION: These results suggest a gene-environment interaction, especially with respect to alcohol intake for hyperuricaemia in Korean adults.

Efficacy and tolerability of febuxostat in gout patients on dialysis.

BACKGROUND: There are no sufficient data available on the use of febuxostat in patients undergoing dialysis. AIM: To investigate the efficacy and tolerability of febuxostat in gout patients on dialysis. METHODS: We retrospectively reviewed clinical and laboratory data available from a referral centre from January 2012 to December 2018. We included gout patients who initiated febuxostat during dialysis. Data regarding serum uric acid levels before and after the febuxostat treatment and clinical information such as gout attack after febuxostat initiation, as well as adverse events involving febuxostat treatment, were obtained from medical records. RESULTS: Among 62 patients who were treated with febuxostat for over 3 months, 45 were undergoing haemodialysis (HD) and 17 were undergoing peritoneal dialysis (PD). The mean serum uric acid level was significantly reduced 3 months after treatment (3.71 ± 1.32 mg/dL) compared with that at the pretreatment level (9.36 ± 2.06 mg/dL) (P < 0.001). The serum uric acid level was observed to be significantly reduced at 3 months in both HD and PD patients and subsequently remained at a significantly reduced level for 12 months. Of the 62 patients, only two stopped febuxostat due to its adverse effects. Initial dose of 80 mg/day was associated with higher adverse events compared to dose of 20-40 mg/day (odds ratio 8.25, 95% confidence interval 1.90-35.97, P = 0.006). CONCLUSIONS: Febuxostat is efficacious and well tolerated in gout patients on dialysis. Febuxostat taken at dose of 20-40 mg/day might be appropriate initial dose in patients undergoing dialysis.

Clinically amyopathic dermatomyositis presenting with isolated facial edema complicated by acute respiratory failure: a case report.

BACKGROUND: In clinically amyopathic dermatomyositis, the hallmark cutaneous manifestations are the key to diagnosis. We report a case of clinically amyopathic dermatomyositis which presented with facial edema as the sole cutaneous manifestation and was later complicated by acute respiratory failure leading to death. CASE PRESENTATION: A 58-year-old woman presented with edema of the face that had developed approximately one year ago. There was no weakness in the extremities, and the serum creatine kinase level was within normal range. On MRI, there was diffuse edematous change in the bilateral masticator and extra-ocular muscles, accompanied by subcutaneous fat infiltration in the face. A shared decision was made to defer muscle biopsy in the facial muscles. The facial swelling almost resolved with medium-dose glucocorticoid therapy but relapsed in days at glucocorticoid doses lower than 15 mg/day. Combination therapy with either azathioprine, mycophenolate, or methotrexate was not successful in maintaining clinical remission, and the swelling became more severe after relapses. A US-guided core-needle biopsy was subsequently performed in the right masseter muscle. On pathologic examination, there was a patchy CD4 + T cell-dominant lymphoplasmacytic infiltration in the stroma, necrosis of the myofibrils and prominent perifascicular atrophy. Based on those findings, a diagnosis of clinically amyopathic dermatomyositis was made. Therapy with gamma-globulin was not effective in maintaining remission. In the sixth week after starting rituximab, she presented to emergency room with altered mental state from acute respiratory failure. Despite treatment with antibiotics, glucocorticoid pulse, cyclosporin, and polymyxin B-immobilized fiber column direct hemoperfusion, she died three weeks later from persistent hypoxemic respiratory failure. CONCLUSIONS: This case showed the full spectrum and severity of internal organ involvement of dermatomyositis, although the patient presented exclusively with subcutaneous edema limited to the head. The prognosis may be more closely associated with a specific auto-antibody profile than the benign-looking initial clinical manifestation. Close follow-up of lung involvement with prophylactic treatment for Pneumocystis pneumonia and prompt implementation of emerging therapeutic regimens may improve the outcome.

Non-steroidal anti-inflammatory drug-induced enteropathy as a major risk factor for small bowel bleeding: a retrospective study.

BACKGROUND: Small bowel (SB) bleeding accounts for 5% of all gastrointestinal (GI) bleeding cases and 80% of obscure GI bleeding cases. Although angioectasia is the common etiology of SB bleeding, nonsteroidal anti-inflammatory drug (NSAID)-induced SB lesions are also reported as a major cause in studies from Eastern countries. Herein, we assessed the frequency of occurrence of NSAID-induced SB lesions in Korean patients with obscure GI bleeding. METHODS: We retrospectively analyzed medical records of all consecutive patients aged ≥18 years who underwent capsule endoscopy from March 2018 to February 2019 at Ulsan University Hospital and Kosin University Gospel Hospital. RESULTS: Of the 83 subjects (all Korean; mean age ± standard deviation: 59 ± 18 years; age range: 18-84 years; men: n = 52; women: n = 31), 55 (66.2%) had stool with clear blood and 28 (33.8%) had normal stool with iron deficiency anemia. The detection rate of SB bleeding and lesions using capsule endoscopy was 72.3% (60 of 83 patients). A significantly higher frequency (40 of 51) of ulcerative/erosive lesions than other causes was observed in patients with inactive bleeding but visible SB lesions. As a result, NSAID-induced enteropathy accounted for 30.1% of 83 patients with obscure GI bleeding (25 of the all 60 SB bleeding cases). CONCLUSIONS: Contrary to what is reported for patients in Western countries, this study in Korean patients showed an improved diagnostic yield of capsule endoscopy for obscure GI bleeding and that NSAID-induced enteropathy was the most common etiology of SB bleeding. Aggressive small intestine examination is required for patients with unexplained GI bleeding.

Coronavirus Disease 19 (COVID-19) complicated with pneumonia in a patient with rheumatoid arthritis receiving conventional disease-modifying antirheumatic drugs.

In December 2019, numerous coronavirus disease 2019 (COVID-19) cases were reported in Wuhan, China, which has since spread throughout the world. However, its impact on rheumatoid arthritis (RA) patients is unknown. Herein, we report a case of COVID-19 pneumonia in a 61-year-old female RA patient who was receiving conventional disease-modifying antirheumatic drugs (cDMARDs). The patient presented with a 4-day history of myalgia and febrile sensation. COVID-19 was confirmed by real-time polymerase chain reaction (PCR). Chest X-ray showed increased opacity on the right lower lung area, and C-reactive protein level was slightly elevated. The patient was treated with antiviral agents (lopinavir/ritonavir), and treatment with cDMARDs was discontinued except hydroxychloroquine. Her symptoms and laboratory results gradually improved. Three weeks later, real-time PCR for COVID-19 showed negative conversion, and the patient was discharged without any complications.

Effect of TNF inhibitors on bone mineral density in rheumatoid arthritis patients receiving bisphosphonate: a retrospective cohort study.

We aimed to determine whether tumor necrosis factor inhibitors (TNFi) have beneficial effects on bone mineral density (BMD) in rheumatoid arthritis (RA) patients with osteoporosis receiving bisphosphonate. A total of 199 RA patients, who were newly diagnosed with osteoporosis and receiving bisphosphonate between January 2005 and March 2017, were reviewed. Changes in BMD after 1 year were compared between patients treated with and without TNFi. The inverse probability of treatment weighting (IPTW) method using the propensity score was performed to minimize confounding factors, and logistic regression analysis was applied to identify any factors associated with significant BMD improvement (≥ 3%) at the lumbar spine and femur neck. Among patients receiving bisphosphonate, 29 were exposed to TNFi, and 170 patients were not exposed. The percentage change in BMD and the proportion of significant improvements at the lumbar spine and femur neck were similar between patients treated with and without TNFi, before and after IPTW adjustment. In addition, the disease activity score 28 (DAS28) with three variables [adjusted odds ratio (OR) 0.741, 95% confidence interval (CI) 0.592-0.927, p = 0.009] and cumulative steroid dose (adjusted OR 0.639, 95% CI 0.480-0.851, p = 0.002) were inversely associated with an improvement in BMD. Conversely, TNFi use was not associated with any improvement in BMD after adjustment by IPTW using the propensity score. TNFi did not influence BMD improvement in RA patients with osteoporosis receiving bisphosphonate, suggesting that TNFi cannot be considered as a preferred therapeutic option for increasing BMD.

Changing Patterns of Medical Visits and Factors Associated with No-show in Patients with Rheumatoid Arthritis during COVID-19 Pandemic.

BACKGROUND: The main barrier to the effective rheumatoid arthritis (RA) therapy is poor adherence. Coronavirus disease 2019 (COVID-19) pandemic have led to a significant change in the pattern and the number of medical visits. We assessed changing patterns of medical visits and no-show, and identified factors associated with no-show in patients with RA during COVID-19 pandemic. METHODS: RA patients treated with disease-modifying antirheumatic drugs at least 6 months who had been in remission or those with mild disease activity were observed for 6 months from February to July 2020. No-show was defined as a missed appointment that was not previously cancelled by the patient and several variables that might affect no-show were examined. RESULTS: A total of 376 patients and 1,189 appointments were evaluated. Among 376 patients, 164 patients (43.6%) missed appointment more than one time and no-show rate was 17.2% during COVID-19 pandemic. During the observation, face-to-face visits gradually increased and no-show gradually decreased. The logistic regression analysis identified previous history of no-show (adjusted odds ratio [OR], 2.225; 95% confidence interval [CI], 1.422-3.479; P < 0.001) and fewer numbers of comorbidities (adjusted OR, 0.749; 95% CI, 0.584-0.961; P = 0.023) as the independent factors associated with no-show. CONCLUSION: Monthly analysis showed that the no-show rate and the pattern of medical visits gradually changed in patients with RA during COVID-19 pandemic. Moreover, we found that previous history of no-show and fewer numbers of comorbidities as the independent factors associated with no-show.

Dietary and nutritional factors associated with hyperuricemia: The seventh Korean National Health and Nutrition Examination Survey.

BACKGROUND AND OBJECTIVES: The association of dietary and nutritional factors with hyperuricemia and gout is well-known in Western populations. The present study aimed to examine the association of dietary and nutritional factors with hyperuricemia among Korean adults. METHODS AND STUDY DESIGN: This cross-sectional study included 10,175 participants from the seventh Korean National Health and Nutrition Examination Survey 2016-2017. Dietary information was collected using a single 24-hour recall method, and nutritional information was derived from the 9th Korean Food Composition Table. The associations between serum uric acid and intake of meat, seafoods, nuts, and legumes, sugar-sweetened products, dairy products, alcohol, sodium, vitamin A, vitamin B1, vitamin C, and dietary fiber were analyzed using linear regression analysis adjusting for confounding variables. The association with hyperuricemia was analyzed using logistic regression analysis. All analyses were weighted by the sampling design. RESULTS: Alcohol intake was associated with serum uric acid in both men and women. In men, the highest quartile of alcohol intake was associated with a 1.5-times higher prevalence of hyperuricemia (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.16-1.95), while vitamin C and dietary fiber intakes were found to be inversely associated with hyperuricemia. For vitamin C and dietary fiber intake, the ORs for a quartile increase were 0.93 (95% CI 0.86-0.99) and 0.92 (95% CI 0.85-0.99), respectively. CONCLUSIONS: The associations between vitamin C, dietary fiber and alcohol intakes and hyperuricemia in men support the Dietary Approach to Stop Hypertension (DASH)-based approach and attention to alcohol intake for managing hyperuricemia in Korean men.

Immunoglobulin Binding Protein 1 as a Potential Urine Biomarker in Patients with Lupus Nephritis.

We evaluated the role of immunoglobulin binding protein 1 (IGBP1), a phosphoprotein associated with the B cell receptor (BCR) complex, as a urine biomarker in lupus nephritis (LN). The IGBP1 concentrations in plasma and urine of patients with LN, systemic lupus erythematosus (SLE) without nephritis and healthy controls were estimated by ELISA. IGBP1 expression in the kidneys of LN patients and transplantation donors was detected by immunohistochemistry. Microarray-based global gene expression profile of HK-2 cells with IGBP1 knock-down and fluorescence-activated cell sorting (FACS) for intracellular IGBP1 expression in human peripheral blood mononuclear cells (PBMCs) was performed. Urine IGBP1 levels were elevated significantly in LN patients, and it correlated with the clinical activity indices (complement 3 (C3) level, anti-dsDNA antibodies titer, SLE Disease Activity Index-2000 (SLEDAI-2K) and histological activity index. IGBP1 expression was increased in LN patients as compared to the donors and was detected mainly in the tubules by histopathology. In microarray analysis, several genes related to SLE pathogenesis (PPME1, ROCK2, VTCN1, IL-17R, NEU1, HLA-DM, and PTX3) responded to siRNA-mediated IGBP1 silencing. In FACS, IGBP1 was expressed mainly in the CD14+ cells. The overall expression of IGBP1 in PBMCs was higher in LN patients as compared with that in SLE patients without nephritis. Conclusively, urinary IGBP1 may be a novel biomarker reflecting the clinical and histological activities in LN.

The risk of herpes zoster in patients with ankylosing spondylitis: Analysis of the Korean National Health Insurance Service - Sample cohort database.

OBJECTIVES: The aims of our study were to determine whether the use of conventional disease-modifying antirheumatic drugs (cDMARDs) or tumor necrosis factor α (TNFα) inhibitors increase the risk of herpes zoster (HZ) in patients with ankylosing spondylitis (AS). METHODS: We searched the South Korean National Health Insurance Service - National Sample Cohort Database for relevant patient records between 2002 and 2013. We evaluated the incidence of HZ by categorizing patients into in three treatment groups: disease-modifying antirheumatic drug (DMARD) nonusers, cDMARD users and TNFα inhibitor users. RESULTS: Incidence rates of HZ was 11.0 per 1000 person-years in patients with AS. The adjusted hazard ratio of HZ was higher in cDMARD and TNFα inhibitor users than in DMARD nonusers. In subgroup analyses, current treatment with a TNFα inhibitor increased the risk of HZ significantly both in female patients and in patients aged 50 years or older, but not in patients taking steroids, compared to DMARD nonusers. CONCLUSIONS: Treatment with either TNFα inhibitors or cDMARDs is associated with a higher risk of HZ, especially in female patients and older patients, and these two patient groups could therefore benefit from HZ vaccination.

Late-onset IgA vasculitis in adult patients exhibits distinct clinical characteristics and outcomes.

OBJECTIVES: The aim of this study was to determine whether adult IgA vasculitis patients who developed the disease at an older age differ from early-onset patients in terms of clinical features and outcomes. METHODS: All consecutive adult patients who were diagnosed with IgA vasculitis between January 1997 and December 2014 were reviewed retrospectively. Patients who developed the disease at an older age (≥60 years; late-onset) were compared with those with an earlier onset of disease (<60 years; early-onset). Renal insufficiency was defined as an estimated glomerular filtration rate <60 ml/minute. RESULTS: In total, 100 adult patients were diagnosed with IgA vasculitis (mean age, 45.61 ± 17.24 years), of whom 31 (31%) had late-onset disease. Compared to early-onset patients, late-onset patients were less likely to have a preceding upper respiratory tract infection (0/31, 0.0% vs. 14/69, 20.3%; p=0.004), and more likely to have renal involvement at presentation (27/31, 87.1% vs. 43/69, 62.3%; p=0.017). At the last follow-up visit, late-onset patients were more likely to have chronic renal insufficiency, including end-stage renal disease (18/28, 64.3% vs. 7/62, 11.3%; p=0.000). Multivariate Cox analysis revealed that late-onset was a significant risk factor for renal insufficiency at follow-up (hazard ratio, 16.980, 95% confidence intervals, 4.380-65.830; p=0.000). CONCLUSIONS: Patients with late-onset IgA vasculitis in adults exhibit distinct clinical features characterized by greater renal involvement and worse renal outcomes. Thus, watchful follow-up might be needed for adult IgA vasculitis patients, in particular those with late-onset disease.

Association between knee osteoarthritis and mortality: a serial propensity score-matched cohort study.

BACKGROUND/AIMS: The association between symptomatic knee osteoarthritis (OA) and higher cardiovascular disease (CVD) mortality is established; however, findings from studies that utilized regression analysis were limited, attributed to the strong association between OA and metabolic risk factors. This study aimed to evaluate the association between knee OA and mortality through propensity score matching. METHODS: This was a cohort study including Korean National Health and Nutrition Examination Survey (2010-2013) participants aged ≥ 50 years. By linking the survey data to cause of death data (through 2019) from Statistics Korea, mortality and cause-specific mortality data were obtained. Radiographic knee OA (ROA) was defined as bilateral Kellgren-Lawrence grade ≥ 2. Propensity score matching (1:1) was conducted between asymptomatic ROA, knee pain, and symptomatic ROA groups and normal groups, balancing the confounding factors. Time to death was analyzed using Cox proportional hazard modeling. RESULTS: A higher CVD mortality was observed in the symptomatic ROA group, but not in others; the risk estimates were asymptomatic ROA (hazard ratio [HR] 1.12; 95% confidence interval [CI] 0.77-1.65), knee pain (HR 0.61; 95% CI 0.27-1.38), and symptomatic ROA (HR 1.39; 95% CI 0.89-2.17). No association was found between the all-cause/cancer mortality and other groups. CONCLUSION: When propensity score matching controls metabolic risk factor imbalances, the association between symptomatic knee OA and higher CVD mortality was weaker compared to results of prior studies that used regression adjustment. The results may be more precise estimates of the total risk of knee OA for mortality in Koreans.

Disease Flare of Systemic Lupus Erythematosus in Patients With Endstage Renal Disease on Dialysis.

OBJECTIVE: Although systemic lupus erythematosus (SLE) disease activity diminishes after starting dialysis, flares have been documented during dialysis. Hence, we studied the various clinical and therapeutic variables of patients with SLE who had a disease flare while on dialysis. METHODS: The medical records of patients with SLE who received dialysis at 2 tertiary referral hospitals in South Korea were reviewed. The disease activity was analyzed in terms of the nonrenal SLE Disease Activity Index (SLEDAI), and the factors associated with SLE flares were evaluated. RESULTS: Of the total of 121 patients with SLE on dialysis, 96 (79.3%) were on hemodialysis (HD) and 25 (20.7%) were on peritoneal dialysis (PD). During a median follow-up of 45 months (IQR 23-120) after the initiation of dialysis, 32 (26.4%) patients experienced an SLE flare (HD, n = 25; PD, n = 7). The most common features of SLE flare were hematologic (40.6%; thrombocytopenia [31.2%] and leukopenia [21.8%]) and constitutional manifestations (40.6%). Fever was the most common (34.3%) feature among the constitutional symptoms. Treatments for disease flares were based on corticosteroids, and 11 (34.3%) patients required additional immunosuppressants, including cyclophosphamide and mycophenolate mofetil. Nonrenal SLEDAI score before dialysis initiation (HR 1.24, 95% CI 1.12-1.36; P = 0.001) was a significant risk factor for disease flare during dialysis. CONCLUSION: More than a quarter of the patients with SLE experienced a disease flare during dialysis, which most commonly had hematologic manifestations, particularly thrombocytopenia. Continued follow-up and appropriate treatments, including immunosuppressants, should be considered for patients with SLE receiving dialysis.

Anaphylaxis to tocilizumab in patients with rheumatic disease.

Background: Anaphylaxis to tocilizumab has been reported anecdotally. Therefore, we evaluated the incidence of anaphylaxis in patients starting tocilizumab. Materials & methods: This retrospective study included patients with rheumatic disease who were administered tocilizumab from 2013 to 2020. The incidence of anaphylaxis was examined during the first 6 months. Results: During follow-up, four of 171 patients developed anaphylaxis within the third course of infusions. The incidence of anaphylaxis to tocilizumab was higher in patients with adult-onset Still's disease (AOSD) than in those with other rheumatic disease (21.4% in AOSD vs 0.7% in rheumatoid arthritis vs 0% in Takayasu arteritis). Conclusions: When we consider tocilizumab treatment, especially in AOSD, we should keep in mind that intensive monitoring for anaphylaxis is necessary.

Lay abstract Anaphylaxis is a life-threatening allergic reaction that can be triggered by food, latex and drugs. Tocilizumab is widely used to treat rheumatic disease, including rheumatoid arthritis (RA), adult-onset Still's disease (AOSD) and Takayasu arteritis (TAK). As case reports of tocilizumab-induced anaphylaxis have previously been reported, we evaluated the incidence of anaphylaxis in patients starting tocilizumab treatment. Over the course of 6 months, four of 171 (21.4% in AOSD vs 0.7% in RA vs 0% in TAK) patients developed anaphylaxis within the third course of infusions. An AOSD patient with anaphylaxis, who presented with active disease status persistently, was successfully treated with tocilizumab again after desensitization. In conclusion, when considering tocilizumab treatment, especially in AOSD patients, we should keep in mind that intensive monitoring for anaphylaxis is necessary.

Risk of progression of idiopathic pulmonary fibrosis to connective tissue disease: a long-term observational study in 527 patients.

OBJECTIVE: Connective tissue disease (CTD) might occur during the course of idiopathic pulmonary fibrosis (IPF). Clinical factors associated with CTD development in IPF patients have still not been identified. We investigated which antibodies have a significant association with the development of CTD during the clinical course of IPF. METHODS: We retrospectively reviewed the records of 527 patients with a first diagnosis of IPF between January 2007 and March 2014 and investigated the time to CTD development after IPF diagnosis in these patients. RESULTS: CTD developed in 15 patients at a median of 2.1 years (range 1.2-4.8) after IPF diagnosis. All patients had anti-neutrophil cytoplasmic antibodies (ANCA) or autoantibodies that met the serology criteria for interstitial pneumonia with autoimmune features (IPAF). Survival duration for IPF patients with progression to CTD was 5.3 (3.8, 6.7) years, which was significantly longer than for IPF patients without progression to CTD [2.9 (1.7, 4.8), p = 0.001]. Independent risk factors for CTD development in IPF patients included female gender [adjusted hazard ratio (HR) 5.319, p = 0.0082], titer of rheumatoid factor (RF; adjusted HR, 1.006; p = 0.022), titer of anti-citrullinated protein antibody (ACPA; adjusted HR, 1.009; p = 0.0011), and titer of myeloperoxidase (MPO)-ANCA (adjusted HR, 1.02; p < 0.0001). CONCLUSION: Progression to CTD is uncommon in IPF patients. However, a significant number of IPF patients with high titers of RF, ACPA, or MPO-ANCA progressed to CTD. RF, ACPA, and MPO-ANCA might be significantly associated with CTD development in IPF patients. Key Points • A significant number of IPF patients with high titers of RF, ACPA, or MPO-ANCA progressed to CTD. • IPF/UIP with high titers of RF, ACPA, or MPO-ANCA might be the initial clinical manifestation of CTD. • RF, ACPA, and MPO-ANCA may be significantly associated with the development of pulmonary fibrosis in patients with CTD.