Rituximab versus azathioprine for maintenance of remission for patients with ANCA-associated vasculitis and relapsing disease: an international randomised controlled trial.

OBJECTIVE: Following induction of remission with rituximab in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) relapse rates are high, especially in patients with history of relapse. Relapses are associated with increased exposure to immunosuppressive medications, the accrual of damage and increased morbidity and mortality. The RITAZAREM trial compared the efficacy of repeat-dose rituximab to daily oral azathioprine for prevention of relapse in patients with relapsing AAV in whom remission was reinduced with rituximab. METHODS: RITAZAREM was an international randomised controlled, open-label, superiority trial that recruited 188 patients at the time of an AAV relapse from 29 centres in seven countries between April 2013 and November 2016. All patients received rituximab and glucocorticoids to reinduce remission. Patients achieving remission by 4 months were randomised to receive rituximab intravenously (1000 mg every 4 months, through month 20) (85 patients) or azathioprine (2 mg/kg/day, tapered after month 24) (85 patients) and followed for a minimum of 36 months. The primary outcome was time to disease relapse (either major or minor relapse). RESULTS: Rituximab was superior to azathioprine in preventing relapse: HR 0.41; 95% CI 0.27 to 0.61, p<0.001. 19/85 (22%) patients in the rituximab group and 31/85 (36%) in the azathioprine group experienced at least one serious adverse event during the treatment period. There were no differences in rates of hypogammaglobulinaemia or infection between groups. CONCLUSIONS: Following induction of remission with rituximab, fixed-interval, repeat-dose rituximab was superior to azathioprine for preventing disease relapse in patients with AAV with a prior history of relapse. TRIAL REGISTRATION NUMBER: NCT01697267; ClinicalTrials.gov identifier.

Nation-wide cohort study of remission induction therapy using rituximab in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis: Effectiveness and safety in the first 6 months.

OBJECTIVES: The aim of this article is to evaluate the effectiveness and safety of rituximab (RTX) for microscopic polyangiitis and granulomatosis with polyangiitis in Japan. METHODS: In this prospective observational study, all patients with microscopic polyangiitis and granulomatosis with polyangiitis administered RTX were enrolled at each institution. During the observation period of 2 years, data up to 6 months were analysed. Cox proportional hazards analysis was used to assess the factors associated with an outcome. RESULTS: Of the 75 patients who received RTX for remission induction therapy, 53 achieved remission by the sixth month and 50 were in remission at the sixth month. During therapy, 38 serious adverse events were observed in 24 patients, 21 serious infections in 16 patients, and 9 patients died. No factors were associated with remission; however, there was a significant difference between patients with and without remission in serious adverse events (22.6% vs. 54.5%), serious infections (11.3% vs. 45.4%), and death (1.9% vs. 36.4%). The hazard ratio (95% confidence interval) for serious infection was 3.49 (1.29-9.74) for patients aged ≥ 75 years and 3.53 (1.31-9.53) for pulmonary complications. Four patients maintained remission for 6 months. CONCLUSIONS: The effectiveness and safety of RTX for microscopic polyangiitis and granulomatosis with polyangiitis for up to 6 months was demonstrated.

Clinical characteristics of patients with spondyloarthritis and inflammatory bowel disease versus inflammatory bowel disease-related arthritis.

The purpose of this study was to clarify the clinical characteristics of spondyloarthritis (SpA) patients with inflammatory bowel disease (IBD) compared to those without IBD. Furthermore, among patients with SpA and IBD, we aimed to clarify what clinical characteristics lead rheumatologists to diagnose "IBD-related arthritis." Utilizing SpA and psoriatic arthritis (PsA) patients' data from an international, cross-sectional, observational study, we analyzed information on demographics and disease characteristics, dichotomizing patients by IBD status. The presence or absence of IBD was determined based on data collection of treating rheumatologists. Patients with SpA (including PsA) and IBD were also categorized based on treating rheumatologists' definitive diagnosis in regard to SpA type, and compared by whether the patients had IBD-related arthritis or not. Among 4465 SpA patients, 287 (6.4%, 95%CI 5.7-7.2%) were identified with IBD. Compared to SpA patients without IBD, patients with SpA and IBD had a longer diagnostic delay (5.1 vs. 2.9 years, p < 0.001). In patients with SpA and IBD, 111 (38.7%, 95%CI 33.0-44.6%) were diagnosed with IBD-related arthritis. Multivariable analyses showed that HLA-B27 positivity [OR = 0.35, (95%CI 0.15-0.80)], psoriasis [OR = 0.14, (95%CI 0.04-0.50)], IBD as first symptom of SpA [OR = 3.32, (95%CI 1.84-6.01)], and need for IBD-specific treatment [OR = 5.41, (95%CI 2.02-14.50)] were independently associated with the definitive diagnosis of IBD-related arthritis. Collaboration with gastroenterologists is needed to shorten the diagnostic delay in patients with SpA and IBD. The recognition of the factors for the diagnosis of "IBD-related arthritis" may lead to the elucidation of the pathogenesis.

Nation-wide survey of the treatment trend of microscopic polyangiitis and granulomatosis with polyangiitis in Japan using the Japanese Ministry of Health, Labour and Welfare Database.

OBJECTIVES: In Japan, clinical records of patients with intractable diseases, including microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), are compiled into a database. This study aimed to understand the current treatment status and changes in treatment regimens from our previous survey. METHODS: Using data from 2012 and 2013, patients with new-onset MPA and GPA were extracted and analysed. RESULTS: We analysed 1278 MPA and 215 GPA patients. The average age was 71.7 and 62.7 years, respectively. Methylprednisolone pulse therapy was used in 51.2% of MPA patients and 40.5% of GPA patients; the initial prednisolone-equivalent glucocorticoid dose was 39.5 mg/day in MPA and 46.6 mg/day in GPA. Concomitant intravenous or oral cyclophosphamide (CY) was administered to 22.6% of MPA and 56.3% of GPA. Young age, bloody sputum, low serum creatinine, and high C-reactive protein levels were independently associated with CY use in MPA. Compliance with treatment protocol for Japanese patients with myeloperoxidase (MPO)-anti-neutrophilic cytoplasmic antibody-associated vasculitis study criteria or the 2011 clinical practice guidelines for rapidly progressive glomerulonephritis was 42.7% and 49.7%, respectively. CONCLUSIONS: MPA was more prevalent than GPA in the registry. Compared to patients with GPA, MPA patients were older and used CY less frequently. No apparent changes in treatment trends were observed from the previous survey.

Clinical features of psoriatic arthritis.

Psoriatic arthritis (PsA) is associated with decreased quality of life. As delayed diagnosis may lead to progressive joint destruction and long-term disability, the key clinical features of PsA should be recognizable to a wide range of clinicians to facilitate early diagnosis. In addition to assessment and identification of skin and nail lesions, which occur in up to 85% of those with musculoskeletal manifestations, clinicians should be aware of both the peripheral and axial manifestations of musculoskeletal disease reviewed here. Peripheral joint diseases include polyarticular, oligoarticular, distal, and arthritis mutilans subtypes, and cognizance of these patterns of disease, as well as periarticular manifestations, including dactylitis and enthesitis, is useful for swift diagnosis of PsA. Axial psoriatic arthritis (axial PsA), also known as the spondylitis subtype, may be limited to the spine and sacroiliac joints, but may also affect peripheral structures. Meticulous history-taking and physical examination and familiarity with appropriate imaging studies are often necessary to distinguish axial-PsA from other differential diagnoses. Swift diagnosis and treatment are necessary to both control PsA disease and mitigate the risks of the many associate comorbidities that may accompany it.

Extensive bilateral renal metastases of non-small cell lung carcinoma caused acute kidney injury resulting in end-stage renal disease.

Non-small cell lung carcinoma unusually causes clinically relevant metastases in the kidney while they are usually found only in autopsy. Acute kidney injury (AKI) due to direct metastatic invasion of a solid tumor is also very rare whereas it usually happens with hematologic malignancy, including lymphoma. We report a case with these two rarities. A 54-year-old man who had a 6.7 × 6.0 cm-sized tumor in the left upper lobe of the lung in computed tomography was diagnosed as squamous cell lung carcinoma with bronchoscopy with biopsy. His renal function was normal and no proteinuria or hematuria was recognized. He underwent left upper lobectomy and the pathologic examination revealed pT4N1M0 stage IIIA disease. Four months after the surgery, a single brain metastasis in the right frontal lobe found in brain magnetic resonance imaging was treated with Gamma Knife radiosurgery. He presented with macroscopic hematuria and AKI (the serum creatinine level was 1.35 mg/dL) nine months after surgery. The cause was enormous bilateral renal metastases, maximally 8 cm-sized lesions with poor enhancement, which were found in enlarged bilateral kidneys in enhanced CT. Intrapulmonary metastatic lesions were also newly detected. Chemotherapy with pembrolizumab, an antibody against anti-programmed cell death protein 1, had little effect and his renal function continued to decline rapidly, resulting in end-stage renal disease and maintenance hemodialysis. Chemotherapy with carboplatin and paclitaxel was additionally performed. However, two months after hemodialysis induction, the patient died with pneumonia and acute respiratory distress syndrome.

Membranous nephropathy with masked polyclonal IgG deposits associated with primary Sjögren's syndrome.

Tubulointerstitial nephritis and renal tubular acidosis are well-known renal involvements with primary Sjögren's syndrome. However, several types of glomerulonephritis such as membranoproliferative glomerulonephritis and membranous nephropathy are also known to develop in patients with this syndrome. We here report a case of membranous nephropathy that developed 8 years after a diagnosis of primary Sjögren's syndrome in a female patient. Interestingly, the deposition was not identified by routine immunofluorescence using snap frozen tissue, but was revealed by immunofluorescence on formalin-fixed paraffin-embedded sections treated with proteinase K. We further performed immunofluorescence analysis on the treated paraffin-embedded sections with the identified antigen but found that the deposited IgG was not monoclonal and that serum amyloid P, a sensitive marker for membranous-like glomerulopathy with masked IgG κ deposits, was not evident in the glomeruli. To the best of our knowledge, this report depicted the first case of masked polyclonal IgG deposits and further analysis is needed to clarify the underlying mechanisms of IgG masking and possible association with autoantibodies.

Nephrotic syndrome due to minimal-change disease superimposed on anti-glomerular basement membrane antibody positive glomerulonephritis; a case report.

BACKGROUND: The prognosis for renal function in anti-GBM glomerulonephritis (anti-GBM GN) is extremely poor, and when renal impairment progresses severely, it is difficult to expect improvement. In addition, it is also known that once the disease activity can be controlled by aggressive treatment, its recurrence is rare. We experienced an anti-GBM GN that improved from severe renal dysfunction and relapsed. A possible cause was the superimpose of nephrotic syndrome due to minimal change disease (MCD). CASE PRESENTATION: A 30-year-old man was admitted to our hospital because of general malaise, fever, oliguria and renal dysfunction. The patient's laboratory data showed serum creatinine as high as 6.6 mg/dl, and severe inflammation (C-reactive protein 20.6 mg/dl). Anti-glomerular basement membrane antibody (anti-GBM Ab) was detected in his serum, which led to the diagnosis of anti-GBM GN. Treatment was initiated with high-dose glucocorticoid (GC) and plasma exchange therapy (PE), and the patient's renal function and oliguria improved rapidly and he was discharged 40 days after admission. Renal biopsy findings showed cellular crescents associated with linear IgG depositions along the glomerular tufts compatible with anti-GBM GN, but only about one-third of the glomeruli was involved, suggesting that it still remains an early stage of the disease. However, 2 months after discharge, he had a relapse and was readmitted due to severe proteinuria with positive anti-GBM Ab. On the second admission, after high-dose GC and PE combined with intravenous cyclophosphamide, and remission was achieved. Despite the relatively minor renal biopsy findings, the patient showed rapid renal dysfunction and relatively rapid improvement with our treatment. Electron microscopy of the renal biopsy tissue showed significant foot process effacement on podocytes in the apparently normal glomeruli, without electron dense deposits. CONCLUSION: On the basis of clinical course and renal pathology, it is suggested that the present case was a rare complication of an early stage of anti-GBM GN and minimal change nephrotic syndrome. Although the simultaneous development of anti-GBM GN and MCD with anti-GBM antibody is unclear, it might have been precipitated by influenza infection or some unknown factor.

Rituximab as therapy to induce remission after relapse in ANCA-associated vasculitis.

OBJECTIVES: Evaluation of rituximab and glucocorticoids as therapy to induce remission after relapse in ANCA-associated vasculitis (AAV) in a prospective observational cohort of patients enrolled into the induction phase of the RITAZAREM trial. METHODS: Patients relapsing with granulomatosis with polyangiitis or microscopic polyangiitis were prospectively enrolled and received remission-induction therapy with rituximab (4×375 mg/m2) and a higher or lower dose glucocorticoid regimen, depending on physician choice: reducing from either 1 mg/kg/day or 0.5 mg/kg/day to 10 mg/day by 4 months. Patients in this cohort achieving remission were subsequently randomised to receive one of two regimens to prevent relapse. RESULTS: 188 patients were studied: 95/188 (51%) men, median age 59 years (range 19-89), prior disease duration 5.0 years (range 0.4-34.5). 149/188 (79%) had previously received cyclophosphamide and 67/188 (36%) rituximab. 119/188 (63%) of relapses had at least one major disease activity item, and 54/188 (29%) received the higher dose glucocorticoid regimen. 171/188 (90%) patients achieved remission by 4 months. Only six patients (3.2% of the study population) did not achieve disease control at month 4. Four patients died in the induction phase due to pneumonia (2), cerebrovascular accident (1), and active vasculitis (1). 41 severe adverse events occurred in 27 patients, including 13 severe infections. CONCLUSIONS: This large prospective cohort of patients with relapsing AAV treated with rituximab in conjunction with glucocorticoids demonstrated a high level of efficacy for the reinduction of remission in patients with AAV who have relapsed, with a similar safety profile to previous studies.

Associated factors of poor treatment outcomes in patients with giant cell arteritis: clinical implication of large vessel lesions.

BACKGROUND: Relapses frequently occur in giant cell arteritis (GCA), and long-term glucocorticoid therapy is required. The identification of associated factors with poor treatment outcomes is important to decide the treatment algorithm of GCA. METHODS: We enrolled 139 newly diagnosed GCA patients treated with glucocorticoids between 2007 and 2014 in a retrospective, multi-center registry. Patients were diagnosed with temporal artery biopsy, 1990 American College of Rheumatology classification criteria, or large vessel lesions (LVLs) detected by imaging based on the modified classification criteria. Poor treatment outcomes (non-achievement of clinical remission by week 24 or relapse during 52 weeks) were evaluated. Clinical remission was defined as the absence of clinical signs and symptoms in cranial and large vessel areas, polymyalgia rheumatica (PMR), and elevation of C-reactive protein (CRP) levels. A patient was determined to have a relapse if he/she had either one of the signs and symptoms that newly appeared or worsened after achieving clinical remission. Re-elevation of CRP without clinical manifestations was considered as a relapse if other causes such as infection were excluded and the treatment was intensified. Associated factors with poor treatment outcomes were analyzed by using the Cox proportional hazard model. RESULTS: Cranial lesions, PMR, and LVLs were detected in 77.7%, 41.7%, and 52.5% of the enrolled patients, respectively. Treatment outcomes were evaluated in 119 newly diagnosed patients who were observed for 24 weeks or longer. The mean initial dose of prednisolone was 0.76 mg/kg/day, and 29.4% received any concomitant immunosuppressive drugs at baseline. Overall, 41 (34.5%) of the 119 patients had poor treatment outcomes; 13 did not achieve clinical remission by week 24, and 28 had a relapse after achieving clinical remission. Cumulative rates of the events of poor treatment outcomes in patients with and without LVLs were 47.5% and 17.7%, respectively. A multivariable model showed the presence of LVLs at baseline was significantly associated with poor treatment outcomes (adjusted hazard ratio [HR] 3.54, 95% CI 1.52-8.24, p = 0.003). Cranial lesions and PMR did not increase the risk of poor treatment outcomes. CONCLUSION: The initial treatment intensity in the treatment algorithm of GCA could be determined based upon the presence or absence of LVLs detected by imaging at baseline.

Elevated fecal calprotectin and lactoferrin associated with small intestinal lesions in patients with Behçet disease.

BACKGROUND AND AIMS: Small intestinal lesions in patients with Behçet disease (BD) have a risk of perforation and hemorrhage requiring surgery. However, no screening strategy for such lesions has been established. We investigated small intestinal lesions in BD patients with video capsule endoscopy (VCE) and analyzed clinical characteristics to identify noninvasive biomarkers of such lesions. METHODS: This study included 33 BD patients who underwent VCE (PillCam® SB3) at our institution from June 2016 to January 2019. Clinical characteristics, including age, sex, disease duration, body mass index, gastrointestinal symptoms, eye involvement, and blood examinations, were obtained from the medical records of 27 of the 33 patients. Fecal immunochemical tests for hemoglobin, fecal calprotectin (FC), and fecal lactoferrin (FL) were measured. VCE findings of 145 healthy Japanese individuals from a previous report were used as controls. RESULTS: Two intestinal BD patients were included in the 27 patients. We observed that BD patients exhibit more small intestinal lesions compared with healthy individuals, including erosions, ulcers, and total lesions (erosions or ulcers). FC and FL levels were significantly higher in patients with versus without small intestinal lesions (P = 0.034 and P = 0.046, respectively). Receiver operating characteristic analyses demonstrated that FC (cutoff value = 119 µg/g) and FL (cutoff value = 17 µg/g) were biomarkers for small intestinal lesions in patients with BD. CONCLUSION: The present study using VCE showed that patients with BD had more small intestinal lesions than healthy individuals. FC and FL could be useful for screening BD patients who may have small intestinal lesions.

Adult-onset Still's disease-like manifestation accompanied by the cancer recurrence after long-term resting state.

A 72-year-old woman presented 9 months ago with skin rash on her bilateral forearms, which was followed by intermittent high fever, and stiffness and swelling of her bilateral fingers. She was diagnosed with seronegative rheumatoid arthritis (RA). She had a past history of breast cancer and had undergone breast preservation surgery 13 years previously. During admission in our hospital, she developed high fever and leukocytosis with a relapsing skin rash, sore throat, polyarthralgia and increased levels of serum ALT/AST and ferritin, all of which fulfilled Yamaguchi's criteria for adult-onset Still's disease (AOSD). While we tried to exclude other diseases that may show AOSD-like manifestations, pancytopenia rapidly developed and bone marrow biopsy strongly suggested the diagnosis of macrophage activating syndrome (MAS). Accordingly, steroid pulse therapy was begun, followed by oral glucocorticoid therapy. Thereafter, all of her symptoms improved, but systemic rash, inflammatory signs and pancytopenia gradually progressed. The results of bone marrow pathology, which returned 2 weeks after the beginning of treatment, revealed hemophagocytosis with CK7-positive/CK20-negative atypical cells that suggested recurrence of breast cancer in the bone marrow, thus all of her AOSD-like symptoms were considered to be paraneoplastic manifestations of late-onset metastatic breast cancer. She was treated successfully with chemotherapy. When we see the patients showing AOSD-like symptoms with a history of malignancy, we should consider the possibility of paraneoplastic syndrome due to cancer recurrence.

Tenosynovitis with Rice Body Formation Due to Mycobacterium Intracellulare Infection After Initiation of Infliximab Therapy.

BACKGROUND Rheumatoid arthritis tenosynovitis is difficult to discriminate from non-tuberculous tenosynovitis on the basis of radiological and pathological findings. CASE REPORT A 74-year-old woman with a 4-year history of rheumatoid arthritis was referred to our hospital to undergo treatment for uncontrollable tenderness and swelling in her right third metacarpophalangeal joint, right wrist, and left knee joint. In the previous year, she underwent surgery at a local hospital for the swelling in her right metacarpophalangeal joint, the information of which was not known precisely, but the swelling subsided in due course after an operation. We treated the patient with infliximab (monthly intravenous infusions of 150 mg), but 2 months later, she complained of exacerbation of the swelling in her right third metacarpophalangeal joint and right wrist, and fluid discharge that contained Mycobacterium intracellulare. After synovectomy and aggressive debridement in the palmar side of the right wrist, she was diagnosed as having granulomatous tenosynovitis caused by the M. intracellulare infection and abundant rice body formation in the right carpal tunnel area. We considered the rice bodies inside and outside the bursa, along with a history of tenosynovitis exacerbation after initiation of infliximab therapy (tumor necrosis factor alpha inhibitor [TNFi]), to be related to the M. intracellular infection. CONCLUSIONS Tenosynovitis caused by atypical mycobacteria is uncommon and usually affects the hand or wrist. Therefore, for early diagnosis, mycobacterial infection should be considered in cases of indolent chronic granulomatous tenosynovitis, especially in RA cases that recur after TNFi therapy is started.

Efficacy of high-dose intravenous immunoglobulin therapy for peripheral neuropathy in the remission stage of eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome).

BACKGROUND: Most patients with eosinophilic granulomatosis with polyangiitis (EGPA ; Churg-Strauss syndrome) suffer from peripheral neuropathy. The neuropathy affects ADLs in not only the active stage, but also the remission stage of EGPA. Recently, high-dose intravenous immunoglobulin therapy (IVIg) is known to be effective for peripheral neuropathy in the active stage of EGPA. However, the effect of IVIG for peripheral neuropathy in the remission stage remains obscure. OBJECTIVE: This study assessed the efficacy of high-dose IVIg for peripheral neuropathy in the remission stage of EGPA. PATIENTS & METHODS: Six patients with peripheral neuropathy (duration : 3 months~7 years) in the remission stage of EGPA were investigated. IVIg was performed with an immunoglobulin dose of 400 mg/kg daily (intravenous drip) for 5 days. Neuropathy was evaluated with the manual muscle strength test (MMT) and the visual analogue scale (VAS). RESULTS: MMT improved in 4 of 7 patients (57.1%). MMT score increased 10.0±7.2 after IVIG. VAS (Numbness and neuralgia) improved in 6 of 7 patients (85.7%). Average VAS improved in the range of 46 mm to 61 mm. Side effect was detected in one patient (headache) only even though all patients underwent this therapy. CONCLUSION: These results suggested that IVIg therapy was safe and effective in patients with persistent peripheral neuropathy even in the remission stage of EGPA.

AP-VAS 2012 case report: a case of systemic MPO-ANCA-associated vasculitis that demonstrated brain infarction and immunohistochemically MPO-positive capillaries.

We present a case of an aged male with myeloperoxidase anti-neutrophil cytoplasmic autoantibody (MPO-ANCA)-associated vasculitis with onset of brain infarction that demonstrated immunohistochemically MPO-positive capillaries at autopsy. The patient initially presented with gait difficulty and right-sided weakness. Since an imaging study revealed brain infarction, he was admitted to our hospital and medicated by antiplatelet agents. Continuous fever and elevated serum C-reactive protein (CRP), hematuria of glomerular origin, renal dysfunction, and high serum titer of MPO-ANCA were detected. Systemic toxicoderma appeared, and skin biopsy revealed small-vessel vasculitis; thus, he was diagnosed with MPO-ANCA-associated vasculitis. Steroid therapy (methylprednisolone 30 mg/day) was started, and general status improved. However, he died of shock 6 days after the start of the therapy. Autopsy revealed massive retroperitoneal hemorrhage with necrotizing small-vessel vasculitis in systemic organs including retroperitoneum, skin, brain, testes, and kidneys. Immunohistochemically, infiltration of MPO-positive white blood cells into the capillaries was occasionally observed, along with the features of MPO-positive capillaries. Cerebrovascular involvement of MPO-ANCA-associated vasculitis is rare compared with renal and pulmonary manifestations, having been reported to occur in up to 4 % of patients. Furthermore, as we have recently reported, MPO-immunopositive capillaries may appear only during the hyperacute stage of the disease. Therefore, the present case represents the unique combination of these two rare manifestations.

Granulomatosis with polyangiitis associated with IgA nephropathy.

Granulomatosis with polyangiitis (GPA), previously referred to as Wegener's granulomatosis, is a rare necrotizing granulomatous vasculitis, especially in children. GPA affects small- to medium-sized vessels, leading to involvement of multiple organs, including the upper and lower respiratory tracts and kidneys. Glomerular lesions associated with GPA typically present as crescentic glomerulonephritis with necrotizing lesions, with little or no staining for immunoglobulins and complement proteins. We report a unique pediatric case of GPA associated with IgA nephropathy, a representative immune-mediated glomerular disease. The initial renal biopsy specimen revealed fibrous sclerosis and mild mesangial proliferation without deposition of IgA. However, after clinical remission of GPA by treatment, the serum IgA level continued to be significantly higher than normal, and her paranasal sinusitis was poorly controlled. An acute upper respiratory infection resulted in worsened urinary findings without any systemic signs of GPA. The second renal biopsy specimen revealed deposition of IgA and C3 in the mesangium. The patient was treated with oral prednisolone alone, which led to complete remission of proteinuria within 1 month. IgA nephropathy is possibly associated with GPA during remission stage, and serum IgA level may be a valuable indicator to predict its association.

AP-VAS 2012 case report: MPO-ANCA-negative relapse of MPO-ANCA-associated vasculitis.

A 79-year-old female was admitted to our hospital with fever, proteinuria, hematuria, high levels of C-reactive protein (CRP), and high titer of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA). Our diagnosis was microscopic polyangiitis (MPA) and she was treated with steroid pulse therapy. Clinical remission was induced; however, the disease relapsed with saddle nose and necrotizing vasculitis of the nasal cavity mucosa 1 year later. Although there was no elevation of the MPO-ANCA titer, we diagnosed the patient with relapse of MPO-ANCA-positive granulomatosis with polyangiitis (GPA). Remission was induced again with steroids and azathioprine. It has been reported that the number of MPO-ANCA-positive patients in Asian countries is relatively higher than in Western countries. We checked 29 GPA patients in our hospital and 9 patients (31.0 %) were MPO-ANCA-positive. In addition, it is not rare that an ANCA-associated vasculitis (AAV) patient who has been in remission with negative ANCA relapses without any elevation of ANCA titer. We checked the transition of ANCA titer of 24 AAV patients in our hospital who relapsed and 6 patients (25 %) relapsed without any elevation of ANCA titer. We should be careful for a relapse, even if the ANCA titer remains negative. It is also possible that ANCA had been changed so as not to be detected by the same enzyme-linked immunosorbent assay (ELISA) kit. Thus, it is also important to change the detection system if clinical symptoms are worsened while ANCA is still negative.