Recent advances in the treatment strategy for AAV improved outcomes with intensive GC tapering.

OBJECTIVE: To evaluate trends in results of care and management for antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). METHODS: We employed multicenter cohort data collected during 2011-2021, recruiting 43 patients with granulomatosis with polyangiitis (GPA) and 91 with microscopic polyangiitis (MPA). According to the median registration date of September 2015, patients have split into two groups: an early group and a late group (both of them, n = 67). To prevent bias, a propensity score according to numerous baseline characteristics variables was calculated; 50 matching members of each group were statistically extracted. Their treatments and clinical outcomes were examined at 6, 12, and 24 months after initial remission therapy. RESULTS: Statistics demonstrated that the baseline characteristics were similar. The late group used rituximab (RTX) more often for both remission induction and maintenance therapy, compared with the early group. The mean daily PSL doses of the late group were significantly lower than those of early group at each time point. The late group discontinued PSL 14.0% at 12 months and 23.3% at 24 months. Despite their intensive glucocorticoids (GC) tapering, the remission rates and the relapse rates were significantly fairer in the late group. The Vasculitis Damage Index (VDI) and VDI due to GC at each time point were lower in the late group, and those differences had become wider over time. CONCLUSION: Recent developments in AAV treatment have allowed efficient remission and prevention of relapses, which in turn enabled extensive GC tapering causing fewer sequelae.

Elderly onset atypical Lemierre's syndrome concurrent with a rheumatoid vasculitis sacral ulcer infection: a case report.

BACKGROUND: Typical Lemierre's syndrome is usually secondary to an oropharyngeal infection. Recently, several cases following a primary infection site other than the oropharynx have been reported as atypical Lemierre's syndrome; although, these primary lesions are limited to the head and neck. This is the first case potentially sequential to infectious foci outside the head and neck. CASE PRESENTATION: We describe an atypical Lemierre's syndrome in a 72-year-old woman with rheumatoid arthritis, which occurred during the treatment of Streptococcus anginosus bacteremia acquired from a sacral ulcer infection related to rheumatoid vasculitis. At first, the symptoms resolved after the initial administration of vancomycin for the bacteremia caused by methicillin-resistant Staphylococcus aureus and Streptococcus anginosus that entered via a sacral ulcer. On the 8th day, the patient developed a fever of 40 °C and unexpectedly required 10 L of oxygen due to rapid deterioration of oxygenation temporarily. Immediately contrast-enhanced computed tomography was performed to investigate systemic thrombosis including pulmonary embolism. Afterward, the newly formed thrombi at the right external jugular vein, bilateral internal jugular veins, and the right small saphenous vein were detected, and apixaban was started. On the 9th day, the patient again had an intermittent fever of 39.7 °C, and continuous Streptococcus anginosus bacteremia was revealed; subsequently, clindamycin was administered. On the 10th day, she developed a left hemothorax; consequently, apixaban was discontinued, and a thoracic drain was inserted. She repeatedly had an intermittent fever of 40.3 °C, and contrast-enhanced computed tomography detected an abscess formation at the left parotid gland, pterygoid muscle group, and masseter muscle. After Lemierre's syndrome was diagnosed in combination with the abovementioned jugular vein thrombus, clindamycin was replaced with meropenem, and vancomycin was increased. Swelling of the lower part of the left ear became prominent with delay and peaked at approximately the 16th day. The subsequent treatment course was favorable, and she was discharged on the 41st day. CONCLUSION: Clinicians should consider Lemierre's syndrome as the differential diagnosis of internal jugular vein thrombosis occurring during sepsis, even though an antibiotic is administered or a primary infection site is anything besides the oropharynx.

Clinical course of patients with rheumatoid arthritis who continue or discontinue biologic therapy after hospitalization for infection: a retrospective observational study.

BACKGROUND: To analyse the subsequent clinical course of patients with rheumatoid arthritis (RA) who either continued or discontinued biologic agents after hospitalization for infections. METHODS: We retrospectively reviewed the clinical records of 230 RA patients with 307 hospitalizations for infections under biologic therapy between September 2008 and May 2014 in 15 institutions for up to 18 months after discharge. The risks of RA flares and subsequent hospitalizations for infections from 61 days to 18 months after discharge were evaluated. RESULTS: Survival analyses indicated that patients who continued biologic therapy had a significantly lower risk of RA flares (31.4% vs. 60.6%, P < 0.01) and a slightly lower risk of subsequent infections (28.7% vs. 34.5%, P = 0.37). Multivariate analysis showed that discontinuation of biologic therapy, diabetes, and a history of hospitalization for infection under biologic therapy were associated with RA flares. Oral steroid therapy equivalent to prednisolone 5 mg/day or more and chronic renal dysfunction were independent risk factors for subsequent hospitalizations for infections. CONCLUSIONS: Discontinuation of biologic therapy after hospitalization for infections may result in RA flares. Continuation of biologic therapy is preferable, particularly in patients without immunodeficiency.

Hypertension and dyslipidemia are risk factors for herpes zoster in patients with rheumatoid arthritis: a retrospective analysis using a medical information database.

This study used data from a large-scale multicenter medical information database in Japan to estimate the incidence rate of herpes zoster (HZ) and to examine the relationship between hypertension, dyslipidemia, and diabetes mellitus (DM), and the risk of HZ among patients with rheumatoid arthritis (RA). The research dataset consisted of 221,196 records of potential target patients with RA extracted between April 1, 2008 and August 31, 2017 from the Medical Data Vision database. To assess the association between hypertension, dyslipidemia, and DM and the risk of HZ, a case-control study was set up. Records of 101,498 study subjects met the inclusion criteria. During the observation period, 2566 patients developed HZ and the overall incidence rate was 5.2 (95% confidence interval: 5.0-5.4 per 1000 patient-years). Hypertension, dyslipidemia, and DM were significantly associated with an increased risk of HZ after adjustment for sex, age, hospital size, and use of anti-rheumatic drugs. When mutual adjustment was made for hypertension, dyslipidemia, and DM, the positive associations between hypertension and dyslipidemia and the risk of HZ remained significant; however, the positive association with DM completely disappeared. RA patients with hypertension or dyslipidemia may be at higher risk of HZ.

Outcomes of methotrexate-associated lymphoproliferative disorders in rheumatoid arthritis patients treated with disease-modifying anti-rheumatic drugs.

Recently, the use of targeted synthetic or biological disease-modifying anti-rheumatic drugs (ts/bDMARDs) in addition to conventional synthetic (cs)DMARDs including methotrexate (MTX) for rheumatoid arthritis (RA) has increased. However, whether ts/bDMARDs are associated with the development and clinicopathological features of MTX-associated lymphoproliferative disorder (MTX-LPD) in patients with RA remains unknown. Therefore, we evaluated the clinical outcomes of 121 patients with MTX-LPD. Results showed that prior use of ts/bDMARDs was not associated with the different histopathological subtypes of MTX-LPD. Patients with polymorphic-type LPD had a better event-free survival than those with diffuse large B-cell lymphoma (DLBCL), classical Hodgkin lymphoma and peripheral T-cell lymphoma. The pathological subtype of lymphoma could predict the clinical outcome of MTX-LPD. In patients with DLBCL, the use of tumour necrosis factor-alpha (TNF-α) inhibitors prior to MTX-LPD onset was associated with a higher non-relapse mortality. Further, patients with RA previously treated with Janus kinase (JAK) inhibitors more commonly required chemotherapy than those treated with csDMARDs alone, indicating disease aggressiveness. Hence, special caution should be observed when managing patients with MTX-LPD previously treated with JAK or TNF-α inhibitors for RA.

The Association of Airway Comorbidities With the Clinical Phenotypes and Outcomes of Patients With Antineutrophil Cytoplasmic Autoantibody-associated Vasculitis.

OBJECTIVE: We investigated the association of airway comorbidities with the clinical phenotypes and outcomes of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibodies (ANCA)-positive ANCA-associated vasculitis (AAV). METHODS: An AAV patient multicenter cohort trial was established in 13 hospitals in western Japan between 2012 and 2018. We examined 143 of the new-onset MPO-ANCA-positive AAV patients. Their clinical characteristics and comorbidities at disease onset were compared based on clinical phenotypes. Multivariate analysis was performed to identify factors predictive of remission and death. RESULTS: Twenty-seven cases with granulomatosis with polyangiitis (GPA), 10 with eosinophilic GPA (EGPA), 81 with microscopic polyangiitis (MPA), and 25 with unclassified AAV were identified. The average age of MPO-ANCA-positive patients was 71.4 years. Comorbidity (87.4%) and airway comorbidity (70.6%) were frequently observed in these patients. Examination of the clinical phenotypes revealed that the cases of GPA were frequently accompanied by infectious airway comorbidity (upper airway disease, bronchiectasis, pulmonary infections), and most of the cases of MPA and unclassified AAV were accompanied by fibrotic interstitial lung disease (fILD) or emphysema. Among MPO-ANCA-positive patients, infectious airway comorbidity was predictive of both remission (HR 1.58, P = 0.03) and mortality (HR 2.64, P = 0.04), and fILD was predictive of mortality (HR 7.55, P = 0.008). The combination of infectious airway comorbidities and fILD caused the worst survival outcomes in patients. CONCLUSION: MPO-ANCA-positive AAV was frequently accompanied by airway comorbidities. In addition to fILD, infectious airway comorbidities were closely associated with those clinical phenotypes and outcomes.

Rituximab maintenance therapy for patients with antineutrophil cytoplasmic antibody-associated vasculitis in Japan.

OBJECTIVES: We examined the efficacy and safety of rituximab (RTX) maintenance therapy for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japan. METHODS: We conducted a retrospective study using a multi-center cohort database of vasculitis patients. All maintenance treatment courses were divided into three groups: a RTX group, a group treated with other immunosuppressant drugs (IS) and a group receiving glucocorticoid monotherapy (GC). The primary endpoint was the comparison of relapse-free survival after 1 year. We also analyzed the occurrence of severe adverse events (SAEs) to assess safety. RESULTS: We included 123 courses of 107 patients (RTX n = 14, IS n = 64, GC n = 45). Twelve of 14 in the RTX group patients were diagnosed with granulomatosis with polyangiitis (GPA). The relapse-free survival of RTX maintenance therapy was comparable to that in the other groups (p = .122). After 1 year of treatment, the RTX group was administered lower steroid doses and one-third of them could withdraw corticosteroid. The overall incidence of SAE was 0.54/patient-year in the RTX group, 0.39/patient-year in the IS group and 0.34/patient-year in the GC group. CONCLUSION: RTX maintenance therapy could be effective and safe in Japanese GPA patients.

Infected Thoracic Aortic Aneurysm Caused by Helicobacter cinaedi.

The causative organism is not identified in some cases of infected aneurysms, a life-threatening condition. A 68-year-old man presented with chest/back pain and a 1-year history of intermittent fever and fatigue. Computed tomography revealed a thoracic aortic aneurysm. After several negative blood cultures, he was eventually diagnosed with an infected aneurysm caused by Helicobacter cinaedi via gene analysis of an aortic tissue specimen. As H. cinaedi is a low-virulence bacterium, infection with this pathogen should be suspected in cases of aortic aneurysms with unidentified causative organism and a long history of subjective symptoms. Detailed examinations, including polymerase chain reaction, should be conducted in such cases.

Renal Insufficiency in Concert with Renin-angiotensin-aldosterone Inhibition Is a Major Risk Factor for Hyperkalemia Associated with Low-dose Trimethoprim-sulfamethoxazole in Adults.

OBJECTIVE: Low-dose trimethoprim-sulfamethoxazole (TMP-SMX) is commonly used to prevent pneumocystis pneumonia in daily practice. Previous reports have shown a relationship between high- or standard-dose of TMP-SMX and hyperkalemia, however it remains unclear whether this is true for low-dose TMP-SMX. In this study we sought to determine the risk factors for hyperkalemia associated with low-dose TMP-SMX. METHODS: In this retrospective cohort study, 186 consecutive adult patients who received TMP-SMX as prophylaxis for pneumocystis pneumonia from January 2014 to January 2015 were evaluated. Data on the patients' age, gender, baseline estimated glomerular filtration rate (eGFR), baseline serum potassium, maximum serum potassium, duration reaching the maximal serum potassium level, dosage, and concomitant use of angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB), ß-blockers, non-steroidal anti-inflammatory drugs and potassium-sparing diuretics were retrospectively collected. Hyperkalemia was defined as a serum potassium level ≥5 mEq/L. Univariate and multivariate analyses were performed. RESULTS: The median age of the patients was 66 years and 51.1% were men. Hyperkalemia associated with low-dose TMP-SMX was observed in 32 patients (17.2%). The median duration to reach the maximal serum potassium level was 12 days. The multivariate logistic regression analysis identified renal insufficiency to be a major risk factor for hyperkalemia associated with low-dose TMP-SMX (eGFR <60 mL/min/1.73 m(2), adjusted OR 4.62). Moreover, in the subpopulation of patients with renal insufficiency, ACEi/ARB use was considered to be a major risk factor for hyperkalemia (adjusted OR 3.96). CONCLUSION: Renal insufficiency in concert with ACEi/ARB use is a major risk factor for hyperkalemia induced by low-dose TMP-SMX.

Quality of life in Japanese female patients with systemic lupus erythematosus: Evaluation using the Short Form 36 Health Survey.

OBJECTIVE: Aspects of health-related quality of life (HRQoL) are important for assessing perceived health status and treatment burden. We evaluated HRQoL using Short Form 36 Health Survey (SF-36) and factors associated with HRQoL. METHODS: We collected basic and lifestyle-related, clinical, and treatment characteristics among 119 female Japanese patients with systemic lupus erythematosus (SLE). Odds ratios (ORs) and their 95% confidence intervals were assessed for associations between HRQoL and selected factors. RESULTS: Irregularity of sleep was significantly associated with risk of lower role physical (RP) (OR = 8.27), vitality (VT) (OR = 8.45), and role emotional (OR = 10.7) domains. Compared with clerical work, non-clerical work was significantly associated with risk of lower RP (OR = 7.39), and unemployment was significantly associated with risk of lower VT (OR = 41.0). Daily soybean intake was associated with improved General Health or GH (OR = 0.17). Compared with Systemic Lupus Collaborative Clinics Damage Index (SDI) = 0, SDI > 2 was associated with risk of lower PF (OR = 7.88), RP (OR = 4.29), and bodily pain (OR = 3.06) domains. CONCLUSION: Reduced HRQoL was observed in our SLE patients. Interventions addressing sleep and work disturbances, as well as daily soybean consumption, could alter the HRQoL of SLE patients.

Successful Treatment of Lupus Cerebrovascular Disease with Mycophenolate Mofetil.

We report a case of neuropsychiatric systemic lupus erythematosus successfully treated with mycophenolate mofetil (MMF). The patient was a 40-year-old female who maintained with 7 mg of prednisolone plus 100 mg of azathioprine (AZ) per day. According to transient ischemic attack that occurred repeatedly and an elevated level of interleukin-6 (IL-6) in spinal fluid, she was diagnosed as having neuropsychiatric systemic lupus erythematosus (NPSLE). Initial increase in doses of prednisolone and AZ to 20 mg and 150 mg per day, respectively, was ineffective. After switching from AZ to MMF, her symptoms of NPSLE completely resolved with marked improvement of the IL-6 level in her spinal fluid, suggesting that MMF was effective.

A Case of Immunoglobulin G4-Related Disease with Extensive Multiorgan Involvements.

We report a case of IgG4-related disease (IgG4-RD) with multiple ten-organ involvement. This case showed many clinical findings, such as bilateral swelling of salivary and lacrimal glands, autoimmune pancreatitis, interstitial nephritis, retroperitoneal fibrosis, periaortitis, systemic swelling of lymph nodes, pulmonary lesions, splenomegaly, and jejunal lesions. He was suspected as having SLE or malignant lymphoma but diagnosed as having IgG4-RD by the elevated serum IgG4 level and histological findings from kidney and lymph node. We report a case of IgG4-RD with multiple ten-organ involvement that was successfully treated with prednisolone therapy.

Pleuritis clinically diagnosed as aspergillosis during the course of microscopic polyangiitis.

Pleural aspergillosis is a rare fungal infection. We herein report a case of pleuritis clinically diagnosed as aspergillosis without apparent Aspergillus lung lesions. A 75-year-old man receiving immunosuppressive therapy due to microscopic polyangiitis was admitted for treatment of massive pleural effusion. Histology of the parietal pleura revealed septate hyphae. In addition, a hematological marker of Aspergillus indicated Aspergillus pleuritis. The pleural effusion resolved after administration of the voriconazole. The trigger for invasion of Aspergillus into the pleura was thought to be spontaneous pneumothorax, which had occurred five months earlier.

Reduced carotid intima-media thickness in systemic lupus erythematosus patients treated with cyclosporine A.

BACKGROUND: Patients with systemic lupus erythematosus (SLE) are at risk of atherosclerosis. An increased carotid intima-media thickness (IMT) is considered to be a marker of early atherosclerosis. Objective To determine influential factors for increased carotid IMT in SLE patients. METHODS: We evaluated the impact of conventional risk factors for atherosclerosis on carotid IMT in 427 healthy controls and of clinical factors on carotid IMT in 94 SLE patients. Carotid IMT was measured by using a newly developed computer-automated system. Unconditional logistic regression was used to assess the adjusted odds ratios (ORs) and 95 % confidence intervals (95 % CI). RESULTS: Multivariate-adjusted mean carotid IMT (mm) was significantly reduced in SLE patients (0.51, 95 % CI = 0.36-0.66) compared to healthy controls (0.55, 95 % CI = 0.40-0.70) (P = 0.003). The SLE Disease Activity Index (SLEDAI) was associated with carotid IMT in a dose-dependent manner (Ptrend = 0.041). The current use of cyclosporine A (adjusted OR = 0.02, 95 % CI = 0.01-0.40, P = 0.011) and a history of steroid pulse therapy (adjusted OR = 0.01, 95 % CI = 0.01-0.25, P = 0.006) were significantly associated with a decreased risk of increased carotid IMT. CONCLUSIONS: Our findings suggest that the current use of cyclosporine A can protect against increased carotid IMT, leading to a decreased risk of arteriosclerosis. Future studies with a larger sample size need to confirm that this association holds longitudinally.

Prevalence and risk factors of vertebral fracture in female Japanese patients with systemic lupus erythematosus.

OBJECTIVE: We examined the prevalence and risk factors of vertebral fracture in female Japanese patients with systemic lupus erythematosus (SLE). METHODS: We performed lateral radiographs of the thoracic and lumbar spine and bone mineral density (BMD) measurements and collected demographic, lifestyle, clinical, and treatment characteristics of 52 SLE patients. Vertebral fractures were defined as a >20% reduction of vertebral body height. Odds ratios (ORs) and their 95% confidence intervals (CIs) were computed to assess the strength of associations between vertebral fractures and selected factors among SLE patients. RESULTS: At least one vertebral fracture was detected in 50% of SLE patients. A history of previous bone fracture was significantly associated with an increased risk of vertebral fractures among SLE patients (adjusted OR = 14.8, 95% CI = 1.62-134; P = 0.017). Daily use of tea or coffee was marginally associated with a decreased risk of vertebral fractures among SLE patients (adjusted OR = 0.11, 95% CI = 0.01-1.01; P = 0.051). CONCLUSION: The high prevalence of vertebral fracture in SLE patients (50%) indicates that we need to assess the lateral spine radiograph in more female Japanese SLE patients regardless of BMD and use of corticosteroids, although additional studies are warranted to confirm the findings suggested in this study.

Prevalence of and risk factors for low bone mineral density in Japanese female patients with systemic lupus erythematosus.

To examine the prevalence of and risk factors for low bone mineral density (BMD) (osteoporosis or osteopenia) in Japanese female patients with systemic lupus erythematosus (SLE). We performed BMD measurements by dual X-ray absorptiometry at the lumbar spine and the hip and collected basic and lifestyle-related, clinical and treatment characteristics among 58 SLE patients. Odds ratios (ORs) and their 95% confidence intervals (CIs) were assessed for associations between low BMD and selected factors among SLE patients. The mean BMD ± SD was 0.90 ± 0.17 g/cm(2) at the lumbar spine and 0.76 ± 0.17 g/cm(2) at the hip. The prevalence of osteopenia (2.5 SD < T score < 1 SD) was 50.0% and that of osteoporosis (T score < 2.5 SD) was 13.8% in our SLE patients. After adjustment for age and disease duration, we found the number of deliveries (OR = 5.58, 95% CI = 1.31-26.06; P = 0.02) to be a risk factor for overall low BMD (T score < 1 SD) and a maximal dosage of >50 mg/day of oral corticosteroids (OR = 0.25, 95% CI = 0.07-0.91; P = 0.035) as a preventive factor for low BMD at the lumbar spine. Reduced BMD, especially in spinal trabecular bone, was pronounced in Japanese female patients with SLE, particular in those with a history of delivery. A history of high-dose oral corticosteroids was associated with the preservation of BMD at the lumbar spine, however, further study is needed considering the limited sample size.

Wegener's granulomatosis detected initially by integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography.

Early diagnosis is crucial for effective treatment of Wegener's granulomatosis, although this disease shows only atypical symptoms in the primary stage. This report describes a patient suspected of having a malignancy based on integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT), which showed increased uptake in pulmonary nodules and nasopharyngeal mucosa. Integrated PET/CT is therefore considered to be useful to confirm the distribution and determine the optimal site for biopsy.

Successful treatment of rapidly progressive interstitial pneumonia with autologous peripheral blood stem cell transplantation in a patient with dermatomyositis.

Aggressive autoimmune diseases are often treated by intensive immunosuppressive treatment such as high-dose methylprednisolone and intravenous cyclophosphamide. Autologous hematopoietic stem cell transplantation can facilitate high-dose immunosuppressive therapy (HDIT), which is myeloablative. We describe a 54-year-old female patient with rapidly progressive and refractory interstitial pneumonia due to dermatomyositis, which was successfully treated with high-dose cyclophosphamide and autologous blood stem cell transplantation. Following transplantation, dyspnea disappeared, and arterial blood gas analysis and respiratory function test showed marked improvement. This improvement was confirmed by diminished interstitial shadows on chest X-ray and computed tomography scans. Eighteen months after transplantation, the patient is doing well without symptoms and signs of interstitial pneumonia.