Clinical Characteristics and Treatment Outcomes of Patients With Newly Diagnosed Takayasu Arteritis in Japan During the First 2 Years of Treatment　- A Nationwide Retrospective Cohort Study.

BACKGROUND: This study aimed to clarify recent clinical features and treatment outcomes in Japanese patients with newly diagnosed Takayasu arteritis (TAK) during the first 2 years of treatment. METHODS AND RESULTS: A nationwide multicenter retrospective cohort study for TAK was implemented to collect data between 2007 and 2014. The primary outcome of the study was clinical remission at Week 24. Of the 184 participants registered, 129 patients with newly diagnosed TAK were analyzed: 84% were female and the mean age at onset was 35 years. Clinical symptoms at diagnosis were mostly associated with large-vessel lesions. Frequent sites of vascular involvement included the carotid artery, subclavian artery, aortic arch, and descending aorta. The mean initial dose of prednisolone administered was 0.68 mg/kg/day, and 59% and 17% of patients received immunosuppressive drugs and biologics, respectively, by Week 104. Clinical remission at Week 24 and sustained clinical remission with daily prednisolone at ≤10 mg at Week 52 were achieved in 107 (82.9%) and 51 (39.5%) patients, respectively. The presence of signs and symptoms linked to large-vessel lesions was associated with failure to achieve sustained clinical remission at Week 52. CONCLUSIONS: We elucidated the clinical characteristics, treatment outcomes, and factors associated with failure to achieve sustained clinical remission in patients with newly diagnosed TAK in Japan during the first 2 years of treatment.

Pregnancy and childbirth in Takayasu arteritis in Japan: A nationwide retrospective study.

OBJECTIVES: This study aimed to understand the status quo of medical treatments of the primary disease and pregnancy outcomes in patients with Takayasu arteritis (TAK) and children's birth outcomes. METHODS: This study retrospectively enrolled patients with TAK who conceived after the disease onset and were managed at medical facilities participating in the Japan Research Committee of the Ministry of Health, Labor, and Welfare for Intractable Vasculitis. RESULTS: This study enrolled 51 cases and 68 pregnancies 2019-2021. Of these, 48 cases and 65 pregnancies (95.6%) resulted in delivery and live-born babies. The median age of diagnosis and delivery was 22 and 31, respectively. Preconception therapy included prednisolone (PSL) in 51 (78.5%, median 7.5 mg/day), immunosuppressants in 18 (27.7%), and biologics in 12 (18.5%) pregnancies. Six cases underwent surgical treatment before pregnancy. Medications during pregnancy included PSL in 48 (73.8%, median: 9 mg/day), immunosuppressants in 13 (20.0%), and biologics in 9 (13.8%) pregnancies. Enlargement of an aneurysm was reported in one pregnancy, which might be associated with increased circulating plasma volume. TAK relapsed in 4 (6.2%) and 8 (12.3%) pregnancies during pregnancy and after delivery, respectively. Additionally, 13/62 (20.9%) preterm infants and 17/59 (28.8%) low birth weight infants were observed, and none had serious postnatal abnormalities. Of the 51 confirmed infants, 42 (82.4%) were exclusively breastfed or mixed with formula. CONCLUSION: Most pregnancies in TAK were manageable with PSL at ≤10 mg/day. Relapse during pregnancy and postpartum occurred in <20% of pregnancies.

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.

Association between the patterns of large-vessel lesions and treatment outcomes in patients with large-vessel giant cell arteritis.

OBJECTIVES: We aimed to identify associations between patterns of large-vessel lesions of large-vessel giant cell arteritis (LV-GCA) and treatment outcomes. METHODS: We extracted data on 68 newly diagnosed patients with LV-GCA from a retrospective, multi-centric, nationwide registry of GCA patients treated with glucocorticoids between 2007 and 2014. Patients with aortic lesions were identified based on the findings from contrast-enhanced computed tomography, magnetic resonance imaging, or positron emission tomography-computed tomography (Group 2, n = 49). Patients without aortic lesions were subdivided into LV-GCA with or without subclavian lesions defined as Group 1 (n = 9) or Group 3 (n = 10), respectively. The primary outcome evaluation was failure to achieve clinical remission by Week 24 and/or relapse within 104 weeks. RESULTS: The mean age and proportion of patients with cranial lesions and polymyalgia rheumatica in Group 2 were numerically lower than in the other two groups. Large-vessel lesions in Group 3 included carotid, pulmonary, renal, hepatic, or mesenteric lesions. The cumulative rate of poor treatment outcomes >2 years was 11.1%, 55.3%, and 88.0% in Groups 1, 2, and 3, respectively (by Kaplan-Meier analysis). The mean time to poor outcome was significantly different between the groups. CONCLUSIONS: Classification by subclavian and aortic lesions may be useful to determine treatment strategy.

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.

Effectiveness of neutralizing antibody cocktail in hemodialysis patients: a case series of 20 patients treated with or without REGN-COV2.

The number of patients with SARS-CoV-2 infection continues to increase, and it has become a global pandemic. Although there is an urgent need to establish an effective treatment, the medication available for dialysis patients has been limited. An antibody cocktail containing two SARS-CoV-2-neutrarizing antibodies, REGN-COV2 has been granted special approval for COVID-19 in Japan, since July 2021, and this intravenous preparation can be used for dialysis patients. At our hospital, we had 22 hemodialysis patients with COVID-19, and five of them were treated with REGN-COV2. On admission, four of the five patients had moderate disease (pneumonia but O2 inhalation) and one patient had mild disease (not having pneumonia). The mean duration of hospitalization treated with REGN-COV2 was 10.2 ± 2.86 days (mean ± SD), which was less than half, compared to patients untreated of similar severity on admission (22.12 ± 15.5). The time to fever resolution was average 7 days, and no cases progressed to severe illness or death. Among these patients, no obvious adverse reactions were shown. Although more studies with a larger number of patients could be needed for a rigorous evaluation of the effect, our result suggests that REGN-COV2 may be safe and having the possibilities in preventing severe disease in hemodialysis patients. Given the difficulty in securing inpatient beds tend to be in short supply, the strategy combined with neutralizing antibody could be beneficial for end-stage kidney disease (ESKD) patients with hemodialysis who are at high risk of severe disease.

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.

Two distinct subsets of LDGs (low density granulocytes) in ANCA-associated vasculitis.

OBJECTIVES AND METHODS: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disorder that causes vasculitis in small blood vessels throughout the body. Low-density granulocytes (LDGs) in autoimmune diseases, such as SLE and AAV, might play a critical role in the pathogenesis of these diseases. Here, we aimed to determine the characteristics of LDGs in patients with AAV. We assessed the number of whole white blood cells, neutrophil extracellular traps (NETs) productivity, proportion of cell surface markers (e.g. CD10), responses to immunosuppressants, and proteomics of LDGs in patients with AAV. RESULTS: We found more LDGs in peripheral blood mononuclear cells (PBMCs) of patients with AAV than PBMCs of healthy controls (HCs) and confirmed that these LDGs in AAV produced more NETs than normal density granulocytes (NDGs) in HCs. We identified CD10-positive LDGs with mature neutrophil features and CD10-negative LDGs with immature granulocyte properties; the proportion of the two LDG types decreased and increased, respectively, in the patients during treatment. Proteomic analysis revealed that the two LDG groups shared protein expression that differed from those of NDGs. CONCLUSION: We identified distinct CD10-positive and CD10-negative LDGs in patients with AAV. The roles of these LDGs in AAV pathology will require further investigation.

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.

SAPHO syndrome and pustulotic arthro-osteitis.

Synovitis-Acne-Pustulosis-Hyperostosis-Osteitis (SAPHO) syndrome is a rare inflammatory osteoarticular disorder, which encompassed many diseases, including pustulotic arthro-osteitis (PAO). Musculoskeletal manifestations, including osteitis, synovitis, and hyperostosis, are the hallmarks of the SAPHO syndrome and affect a variety of regions of the body. Recent survey indicated that more than 80% of cases of SAPHO syndrome in Japan were PAO, originally proposed by Sonozaki et al. in 1981, whereas severe acne was the most commonly reported skin ailment amongst participants with SAPHO syndrome in Israel. Prevalence of SAPHO syndrome remains unavailable, whereas the prevalence of palmoplantar pustulosis (PPP) was reported to be 0.12% in Japan, and 10-30% of patients with PPP had PAO. SAPHO syndrome and PAO are predominantly found in patients in the third through fifth decades of life, and a female predominance is seen in both groups. The diagnosis is typically made by a rheumatologist or dermatologist. Identification of a variety of the clinical, radiological, and laboratory features outlined, as well as diagnostic criteria, are used to make the diagnosis. Goals of treatment seek to maximize health-related quality of life, preventing structural changes and destruction, and normalizing physical function and social participation. Finally, we review the non-pharmacological and pharmacological managements.

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.

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.

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.

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.

Immunopathologic co-localization of MPO, IgG, and C3 in glomeruli in human MPO-ANCA-associated glomerulonephritis.

Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)- associated glomerulonephritis (GN) is characterized by pauci-immune necrotizing glomerulonephritis(NGN). Although it has been thought that MPO-ANCA is involved in the pathogenesis of capillary injuries in NGN via activation of neutrophils, recent studies suggest a possible role of other factors such as immunoglobulins precipitated on the glomeruli. Here we performed a pathological study investigating a relationship of deposition of MPO, IgG, complements with regard to MPO-positive cells and glomerular capillaries in human MPO-ANCA-associated GN. Renal specimen including 317 glomeruli obtained from 20 patients with MPOANCA- associated GN were analyzed. All of the specimens showed significant focal segmental deposition of IgG. There was a significant glomerular infiltration of MPO-positive cells along with deposition of extracellular MPO in the active lesions of segmental and global NCG, with CD34 staining being decreased in the adjacent areas. IgG deposits were almost colocalized with C3 and partly with MPO, which are also associated with a decrease in CD34 staining, suggesting that immune complex formation and the resultant capillary injuries. Actually occurred, the colocalization of MPO, IgG and C3 was seen only in the glomerular lesions with low severity and activity. These results suggest that not only MPO itself released from the neutrophils but also immune complexes composed of MPO and anti-MPO antibody may play some pathogenetic roles for the glomerular injuries especially in the early phase of human MPO-ANCA-associated GN.

The role of myeloperoxidase and myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCAs) in the pathogenesis of human MPO-ANCA-associated glomerulonephritis.

It is well known that antineutrophil cytoplasmic antibodies (ANCAs) are pathogenic and have a diagnostic value for ANCA-associated vasculitis. We demonstrated that a rise in myeloperoxidase (MPO)-ANCA titers during remission is often predictive of a future relapse in MPO-ANCA-associated vasculitis. Pathological examination of renal biopsies indicated that not only MPO-ANCAs, but also extracellular MPO, an in situ immune complex composed of MPO and MPO antibodies, may play important roles in the pathogenesis of glomerular capillary injury in MPO-ANCA-associated vasculitis.

Upadacitinib for moderate-to-severe atopic dermatitis, in adults and adolescents 12 years and older: review of international and Japanese populations.

INTRODUCTION: Atopic dermatitis is one of the most prevalent chronic skin diseases. Topical therapies continue to be the mainstay of treatment but are limited by noncompliance and side-effects from inappropriate or long-term use. Systemic therapies including cyclosporine and dupilumab have been the treatments of choice for refractory cases. However, outcomes may remain less than satisfactory, and cyclosporine use is further limited by nephrotoxicity.Upadacitinib, an oral Janus kinase inhibitor, is widely used for treating rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis and has recently received approval for atopic dermatitis in the United States, Europe, Japan, and other countries. These approvals were based on results from several randomized controlled trials in which upadacitinib demonstrated better and faster response versus placebo or dupilumab. AREA COVERED: Therapies for atopic dermatitis are reviewed, with emphasis on drug profile, efficacy, and safety profile of upadacitinib for atopic dermatitis. In the review of the clinical trials, special focus is placed on efficacy in the Japanese population. EXPERT OPINION: Currently, there are several treatment options for atopic dermatitis refractory to topical therapies. However, appropriate utilization of Janus kinase inhibitors in clinical practice remains challenging, especially with regard to proper case selection, optimal timing, and appropriateness of use.

MPO-ANCA-positive Microscopic Polyangiitis Following COVID-19 Infection.

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a systemic disease that causes vasculitis in various organs. Although the cause of the onset is unknown, infection has been reported to be a causative factor. The subsequent cytokine storm triggered by the immune response against SARS-CoV-2 infection has been reported to lead to symptoms being more severe. We herein report our experience with the onset of AAV following COVID-19 infection. We also report the course of anti-SARS-CoV-2 serum antibody titers following induction therapy, which suggests that vaccination and education concerning standard precautions are necessary in patients who require immunosuppressive therapy, even after COVID-19 infection.