Development of Acute Promyelocytic Leukemia in a Patient with Granulomatosis with Polyangiitis: A Case Report.

Granulomatosis with polyangiitis (GPA) is a rare disorder of unknown etiology, which is characterized by necrotizing granulomatous inflammation of the upper respiratory system and kidneys. Immunosuppressive treatment (cyclophosphamide or azathioprine with glucocorticoids) improved the outcome of GPA, however, latent comorbidity (cancers and hematologic malignancies) has become more prevalent in recent years. Here, we present a first case of the patient with GPA complicated by acute promyelocytic leukemia (APL) successfully treated with molecular-targeted therapy. A 77-year-old female was referred to our hospital for nasal obstruction, hearing loss, and fever. Otorhinolaryngological investigation revealed otitis media, and head computed tomography (CT) showed paranasal mucosal thickening with septal perforation. Chest CT showed cavitary granulomatous lesions in both lungs. Biopsy of the nasal mucosa revealed granulomatous lesions, and the patient was finally diagnosed with GPA. Oral administration of prednisolone 50 mg/day was initiated, and oral azathioprine (50 mg/day) was added. After 26 months of azathioprine initiation, pancytopenia developed and azathioprine was stopped. Then sudden elevated levels of blasts appeared in the hemogram (blasts 11%). She was diagnosed with APL via bone marrow examination which revealed plenty of faggot cells with Auer rods and chromosomal mutation. The patient was started on all-trans retinoic acid 60 mg/day following arsenic trioxide 7 mg/day in consideration of elderly onset. Complete remission was achieved and oral prednisolone was successfully reduced to 15 mg/day without a major relapse of GPA. Because GPA can be complicated by APL even during maintenance treatment using azathioprine, careful monitoring should be performed in such patients.

Outcome of rituximab treatment in Japanese patients with ANCA-associated vasculitis in daily clinical practice: A two-centre study in Fukushima, Japan.

OBJECTIVES: Rituximab (RTX) efficacy for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has been reported in large randomized studies; however, the efficacy of RTX in Japanese AAV patients, especially the elderly, is not well known. We aimed to determine the clinical efficacy of RTX in Japanese AAV patients including elderly patients. METHODS: This study included 78 AAV patients newly diagnosed with AAV and treated in Fukushima Medical University Hospital or Ohta-Nishinouchi Hospital from April 2004 to September 2019. Clinical records were retrospectively reviewed, and clinical efficacy and outcome (1-year survival) between the RTX treatment group (23 cases) and the conventional therapy group (immunosuppressive therapy other than RTX, 55 cases) were compared. We also analysed the clinical efficacy and outcome in elderly-onset (>75 years) AAV patients. RESULTS: The RTX group showed similar efficacy and 1-year survival compared to the conventional therapy group. Conversely, after 6 months of treatment, prednisolone doses significantly decreased in the RTX group compared to the conventional therapy group (p < 0.01). In the elderly-onset AAV patients, clinical efficacy and outcome were not significantly different. CONCLUSIONS: RTX was effective in Japanese AAV patients and may be useful for prompt tapering of prednisolone doses, even in elderly-onset AAV patients.

Effectiveness of combination tocilizumab and glucocorticoids as an induction therapy in patients with Takayasu arteritis: An observational study.

BACKGROUND: The efficacy of tocilizumab (TCZ) in the treatment of Takayasu arteritis (TA) was demonstrated in randomized controlled trials. The objective of this study was to analyse the effectiveness of combining TCZ with glucocorticoids (GC) as induction therapy in patients with TA. METHOD: This was a retrospective observational study including 32 patients with newly diagnosed TA. Clinical effectiveness of TCZ in maintaining relapse-free remission and GC-tapering were compared between patients who were treated with TCZ plus GC and those who were treated with GC with or without immunosuppressants. RESULTS: The study comprised 32 patients (27 women/5 men) with a median age of 25.5 years (range, 13-72). In the TCZ group (n = 14), patients received TCZ in combination with GC as an induction therapy. In the non-TCZ group (n = 18), patients were treated with single-agent GC or GC plus immunosuppressant. In the matched analysis, relapse-free survival rate was significantly higher in the TCZ group as compared to the non-TCZ group during GC taper. CONCLUSION: TCZ, in combination with GC, would be an effective alternative induction regimen for patients with TA.

Total Hip Joint Replacement in a Patient with Colchicine-Resistant Familial Mediterranean Fever under Canakinumab Treatment.

Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent episodes of fever and serositis. Periodic febrile attack can be managed with biologic medication in colchicine-resistant FMF patients, however, no reports or guidelines exist regarding the postoperative management of elective joint surgery in these patients. Although it is not clear how FMF attacks are triggered, they may be precipitated by stress including anesthesia or surgery. This study reports the case of a 51-year-old FMF patient who received total hip replacement under canakinumab (a specific interleukin-1ß monoclonal antibody) treatment. He had highly active FMF, which was resistant to colchicine; however, his recurrent febrile attack with serositis was successfully controlled with canakinumab. Four months later from the start of canakinumab treatment, his hip osteoarthritis was required for total hip replacement (THR) because of the traumatic fracture. THR was successfully done and FMF attack was not occurred after this elective surgery. Discontinuation of canakinumab 3 weeks before surgery and resumption 6 weeks after led to favorable outcome without complications. This case addresses the differential management concerning stopping and restating of canakinumab in the perioperative setting in contrast to the other biologics such as tumor necrosis factor-α (TNF-α) or interleukin-6 (IL-6) blocking agents. This case report suggests that canakinumab may represent a safe and effective therapy for the colchicine-resistant FMF, even in the patients requiring THR therapy.

Anti-Mi-2 and Anti-TIF1-γ Double-Positive Juvenile Dermatomyositis Treated under Diagnosis of Chronic Eczema: A Case Report.

Myositis-specific autoantibodies are relevant factors that define the disease phenotype of dermatomyositis (DM). Anti-Mi-2 antibody-positive DM patients may present with the typical skin lesions and prominent myositis. On the other hand, adult DM patients with anti-TIF-γ antibody seem to be associated with internal malignancy. Here, we report a rare case of juvenile dermatomyositis (JDM) exhibiting anti-Mi-2 and anti-transcriptional intermediary factor-1 gamma (TIF1-γ) antibodies, with no internal malignancy. A 16-year-old female Japanese patient under treatment with a 2-year history of chronic eczematous lesions was admitted to our department with elevated levels of muscle enzymes. Characteristic skin changes, such as Gottron's papules of the hand, heliotrope rash of the eyelids, and poikiloderma-like legions and diffuse pigmentation on the back, were observed. Histologically, the patient's skin was characterized by the presence of lymphocytic vascular inflammation and endothelial swelling, which are consistent with DM. Severe symmetric proximal muscle weakness, elevated serum muscle enzymes and the presence of anti-TIF1-γ and Mi-2 antibodies were noted. The diagnosis of JDM was made according to the European League Against Rheumatism (EULAR) diagnostic criteria. A high dose of corticosteroids and following intravenous cyclophosphamide treatment (750 mg three times) resulted in an improvement in clinical manifestations and functional outcomes, and recurrence did not occur. Estimation of autoantibodies may serve as an ancillary tool in delineating and defining distinct clinical phenotypes in JDM.

A case of Schnitzler's syndrome without monoclonal gammopathy successfully treated with canakinumab.

BACKGROUND: Schnitzler's syndrome (SchS) is a rare autoinflammatory syndrome with diagnostic challenge and be characterized by chronic urticaria, a monoclonal gammopath, periodic fever and bone pain. In addition to the monoclonal gammopathy, bone abnormalities are often found at the site of bone pain in patients with SchS. The remarkable efficacy of interleukin-1 (IL-1) inhibition was also demonstrated in this syndrome. CASE PRESENTATION: We describe a case of refractory chronic urticaria presenting with clinical manifestations consistent with SchS without monoclonal gammopathy. A 43-year-old female patient suffering from recurring of urticaria with periodic fever as well as bone pain for the past 4 years. The patient had leukocytosis and elevated levels of C-reactive protein (CRP) and serum amyloid A (SAA). PET/CT (positron emission tomography/computed tomography) and MRI (magnetic resonance imaging) examination revealed hyper-metabolism areas in both femoral bone marrow. Although bone marrow histology revealed no abnormality, urticarial skin lesions shows neutrophilic infiltrations without evidence of vasculitis. We could not exclude the possibility of SchS. The patient had been treated with antihistamines, steroids, omarizumab, colchicine and cyclosporine A, no therapeutic effect was observed. She was started on canakinumab 150 mg subcutaneous injection with 4 weeks interval. Within 48 h after the first injection, the urticarial rash disappeared, and febrile attack and bone pain had not recurred. Elevated levels of serum CRP and SAA were normalized within a week after the first injection of canakinumab. CONCLUSIONS: The current case suggests an important role for IL-1 as a mediator in the pathophysiology of SchS-like refractory urticaria with bine pain. It had been presumed that monoclonal gammopathy may not always present in SchS. It is important to avoid delay in diagnosis and initiation of proper treatment in SchS or autoinflammatory conditions resembling SchS.

Clinical Characteristics of Japanese Patients with Elderly-Onset Adult-Onset Still's Disease.

The aim of this study was to compare the characteristics of Japanese patients with elderly-onset Adult-onset Still's disease (AOSD) and those with younger-onset AOSD. Patients were classified into elderly-onset (≥ 65 years, n = 20) and younger-onset (< 65 years, n = 62) groups according to age at AOSD diagnosis. Analyses included the comparison of clinical features, treatments, and Pouchot and modified Pouchot (mPouchot) scores between the two groups. The frequencies of sore throat, lymphadenopathy, and splenomegaly were significantly lower in the elderly-onset group than in the younger-onset group (30.5% vs. 80.6%, p = 0.0004; 15.0% vs. 54.8%, p = 0.0019; 30.0% vs. 61.3%, p = 0.0203; respectively). There were no significant differences in the frequencies of complications, such as macrophage activation syndrome and disseminated intravenous coagulation, between the patients with elderly-onset or younger-onset AOSD. Serum ferritin levels were higher in the elderly-onset group than in the younger-onset group, albeit without statistical significance (median, 9,423 vs. 4,164 ng/mL, p = 0.1727). Pouchot score was lower in the elderly-onset group than in the younger-onset group (median score, 5.5 vs. 4.0, p = 0.0008); however, there was no significant difference in the mPouchot score between the two groups. Our analyses revealed that elderly-onset AOSD was associated with certain characteristics that were distinct from those of younger-onset AOSD and that the disease severity in patients with elderly-onset AOSD, determined by Pouchot score at the time of AOSD diagnosis, was similar to or less than that in patients with younger-onset AOSD.

Vascular Behcet's Disease Preceded by Fever of Unknown Origin: Usefulness of Ultrasonography for the Detection of Large-Vessel Vasculitis.

Behcet's disease is a systemic vasculitis characterized by oral and genital ulcers, erythema nodosum, and ocular involvement. Fever of unknown origin is a relatively rare event in Behcet's disease. We present the case of a 17-year-old male patient who suffered from prolonged fever for two months. The patient tested positive for HLA-B52 and levels of acute phase reactants were elevated. He complained of sore throat and neck pain that were evaluated by cervical ultrasonography, which revealed thickening of the carotid arterial wall and narrowing of the vessel lumen. The patient was diagnosed with vascular Behcet's disease and treated with glucocorticoid, which improved the clinical symptoms and thickening of the carotid arterial wall as detected by color duplex ultrasonography. Since vascular Behcet's disease may lead to morbidity and mortality, we suggest the early use of ultrasonography to help detect medium/large-vessel vasculitis. Prolonged fever in patients with Behcet's disease should be promptly evaluated for vascular involvement.

Adult-Onset Still's Disease Complicated by Immunoglobulin A Vasculitis and anti-CCP Antibody-Positive Arthritis.

A 38-year-old male was admitted to our hospital for arthralgia, fever, skin rash, and purpura. He was diagnosed as having adult-onset Still's disease (AOSD) based on Yamaguchi's criteria. Skin biopsy revealed immunoglobulin A (IgA) vasculitis. He was also found to have anti-cyclic citrullinated peptide (CCP) antibody-positive inflammatory arthritis on a shoulder joint, however he did not fulfill classification criteria for rheumatoid arthritis. Elevated serum cytokine such as serum IL-18 supported the diagnosis of AOSD. His symptoms improved with 40 mg of prednisolone plus cyclosporin A (200 mg/day). Two years after hospitalization, AOSD was relapsed with pleurisy and hyperferritinemia. Finally, he was diagnosed with multicyclic systemic type of AOSD complicated by IgA vasculitis and seropositivity of anti-CCP antibody. Clinicians need to consider the complication of multiple rheumatic diseases, even if the disease-specific autoantibody is positive.

Hemophagocytic Lymphohistiocytosis Associated with Disseminated Nontuberculous Mycobacterial Infection in a Patient with Mesenteric Panniculitis.

Mesenteric panniculitis is a chronic inflammatory disease characterized by non-specific inflammation of the adipose tissue in the mesentery. Hemophagocytic lymphohistiocytosis is a life-threating disease associated with aberrant macrophage overactivation, in which infections can be a leading cause in immunocompromised hosts. Here, we report a rare case of mesenteric panniculitis and hemophagocytic lymphohistiocytosis complicated by disseminated Mycobacterium intracellulare. A 71-year-old male with mesenteric panniculitis was admitted to our hospital for fever and pancytopenia. He was treated with oral prednisolone (15 mg/day) and cyclosporin A (150 mg/day) at presentation. Physical and laboratory examinations revealed disseminated infection with nontuberculous mycobacteria; Mycobacterium intracellulare was detected in cultures of cerebrospinal fluid, blood, sputum, and gastric fluid. Patient signs and symptoms fulfilled the five criteria for a diagnosis of hemophagocytic lymphohistiocytosis, including fever, cytopenia, hemophagocytosis, hyperferritinemia, and high soluble interleukin-2 receptor levels. Therefore, the diagnosis of nontuberculous mycobacteria-associated hemophagocytic lymphohistiocytosis was established. An anti-mycobacterial chemotherapy including chloramphenicol (800 mg/day), rifampin (450 mg/day) and ethambutol (750 mg/day) together with streptomycin (750 mg twice per week) was initiated at 30 days after admission; maintenance doses of prednisolone were increased to 60 mg/day. Fever and pancytopenia improved in response to anti-mycobacterial chemotherapy. The present case suggests that mesenteric panniculitis could be complicated with hemophagocytic lymphohistiocytosis caused by immunosuppressive therapy-associated infections as well as underlying disease activity. In conclusion, the possibility of disseminated nontuberculous mycobacteria infection with hemophagocytic lymphohistiocytosis should be considered if unexplained fever or hematological dyscrasia were presented in patients of mesenteric panniculitis.

Immunoglobulin A Vasculitis in a Japanese Patient with Complete Familial Mediterranean Fever Carrying MEFV Exon 10 Mutation.

Immunoglobulin A (IgA) vasculitis is a systemic small-vessel vasculitis involving the skin, kidney, joints, and gastrointestinal tract. Familial Mediterranean fever (FMF) is the most common autoinflammatory disease characterized by periodic fever, peritonitis, pleuritis, or arthritis. It is well known that FMF may coexist with vasculitis, especially small and medium vessel vasculitis. Here we present a Japanese male patient with FMF who later developed IgA vasculitis and a relapsing disease course. A 51-year-old Japanese male was referred because of upper abdominal pain, arthralgia, and bilateral purpura of the lower limbs. He fulfilled the criteria for IgA vasculitis, which was successfully treated by corticosteroid and immunosuppressive therapy. He had a medical history of periodic fever since the age of 10 years old. The Mediterranean fever (MEFV) gene analysis revealed that he was heterozygous for M694I and E148Q mutations. Colchicine therapy resolved his periodic febrile attacks. To our knowledge, coexistence of FMF with IgA vasculitis has not been reported in East Asia, including Japan. Our case suggests that MEFV gene exon 10 mutations could be related to the development of IgA vasculitis and affects its clinical course.

Sustained Long-Term Retention Rates of Abatacept in Combination with Conventional Synthetic Disease-Modifying Antirheumatic Drugs in Elderly Patients with Rheumatoid Arthritis.

Background and Objectives: Treatment for elderly (aged ≥75 years) patients with rheumatoid arthritis (RA) is important because they usually have several complications and organ dysfunction and are more susceptible to drug-related adverse events. Abatacept (ABT) treatment is relatively safe in elderly RA patients; however, the real-world data of efficacy and long-term retention of ABT is sparse in such patients. This study aimed to investigate the clinical efficacy and long-term retention rates of ABT in elderly Japanese RA patients. Materials and Methods: This 10-year retrospective observational cohort study was performed in two centers in Fukushima, Japan. We reviewed the clinical features of elderly RA patients who received ABT and investigated the differences in retention rates with concomitant administration of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Results: The clinical characteristics of younger (<75 years old, 39 cases) and elderly (≥75 years old, 20 cases) RA patients were generally similar. Although the efficacy was also similar, the concomitant administration of csDMARDs with ABT differed between the two groups. Younger patients significantly decreased methotrexate (MTX) administration than elderly patients (p < 0.01), and elderly patients significantly received tacrolimus (TAC) (p < 0.01) or salazosulfapyridine (SASP; p = 0.01) than younger patients. The overall retention and infection-free survival rates were similar between the two groups. Conclusion: Elderly RA patients showed sustained retention rates compared to younger RA patients. TAC and SASP can help to maintain sustained retention rates in elderly RA patients.

IgG4-Related Disease Complicated by Brain Parenchymal Lesions Successfully Treated with Corticosteroid Therapy: A Case Report.

Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is distinguished by the infiltration of IgG4-positive plasma cells in a variety of tissues and organs including the pancreas, salivary glands, retroperitoneal lesions, kidney, and lymph nodes with elevated serum IgG4 levels. Even so, central nervous system (CNS) lesions such as brain parenchymal lesions associated with IgG4-RD are scarce. So far, only six cases of IgG4-RD in relation with brain parenchymal lesions have been described, with its characteristics still being not clear. Here we have detailed a case of IgG4-RD with brain parenchymal lesions and reviewed previously-reported cases of IgG4-RD with brain parenchymal lesions. A 62-year-old Japanese male suffering from lung silicosis was admitted to our hospital for abdominal discomfort and altered consciousness. He has shown no major neurologic abnormalities except for drowsiness, urinary retention, and fecal incontinence. Brain magnetic resonance imaging has shown scattered hyperintense signals in the brain parenchyma. The serum IgG4 levels were elevated and systemic lymph nodes were enlarged. Biopsy from inguinal lymph nodes has shown massive infiltration of IgG4-positive plasma cells: the ratio of IgG4-positive/IgG-positive plasma cells was nearly 100%. Based on clinical courses, images, laboratory data, and pathological findings, a diagnosis of IgG4-RD that was complicated by brain parenchymal lesions and sacral nerve disturbance was confirmed. The patient was then given methylprednisolone pulse therapy (1g for 3 days) succeeding oral prednisolone (1 mg per body weight). The clinical and radiological improvements together with steroid therapy proposed IgG4-RD to be the cause of the lesions.

Regressed coronary ostial stenosis in a young female with Takayasu arteritis: a case report.

BACKGROUND: Takayasu arteritis is a rare systemic vasculitis, which affects the aorta and its major branches, especially in young females. Diagnosis and treatment for Takayasu arteritis with coronary stenosis are important to prevent fatal complications. Immunosuppressive treatment such as corticosteroid is a common treatment for this condition. However, the effects of immunosuppressive treatment on inflammatory coronary stenosis caused by Takayasu arteritis remains unknown. CASE PRESENTATION: An 18-year-old female had chest oppression on effort and was referred to our hospital due to ST-segment depression in I, aVL, and V2-4 on electrocardiogram. Coronary angiography showed severe stenosis in the ostium of both the left main trunk and the right coronary artery. 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography showed isolated inflammation of the aortic root. She was diagnosed with Takayasu arteritis and treated with combined immunosuppressive treatment with corticosteroid and tocilizumab, which decreased the FDG uptake in the aortic root. Four months after initiation of the immunosuppressive treatment, coronary angiography showed regression of the coronary ostial stenosis. Coronary artery bypass surgery was considered, but the patient rejected invasive revascularization for coronary artery disease. She did not have chest oppression or ST-segment depression after the immunosuppressive treatment. She had no cardiac events for 6 months after discharge. CONCLUSIONS: We described regressed coronary ostial stenosis in a young female patient with Takayasu arteritis. Immunosuppressive treatment might have a favorable effect on coronary ostial stenosis in Takayasu arteritis.

HLA-DQB1 DPB1 alleles in Japanese patients with adult-onset Still's disease.

Objective: HLA class II alleles are major determinants of genetic predisposition to rheumatic diseases. Predisposing effects of HLA had been suggested in AOSD, however, ethnic differences may account for variations in AOSD association with HLA. We determined the contribution of HLA-DQB1, DPB1 alleles to susceptibility to Adult-onset Still's disease (AOSD) in the Japanese population. Methods: HLA-DQB1 and DPB1 alleles were analyzed in 87 Japanese patients with AOSD and 413 Japanese healthy subjects. Results: We found significant association between HLA-DQB1*06:02 (Pc = 0.010, odds ratio: 2.54) and AOSD, whereas there was no association between the DQB1*06:02 allele and disease phenotypes of AOSD. Moreover, we did not find a predisposing effect of the HLA-DPB1 allele to AOSD. Haplotype analysis showed that presence of DRB1*15:01-DQB1*06:02 was associated with Japanese patients with AOSD. However, conditional logistic regression tests were unable to demonstrate independent association between DRB1*1501 or DQB1*0602 and AOSD. Conclusions: Our results show significant association between AOSD and the HLA DQB1*06:02 allele, and between the DRB1*1501-DQB1*06:02 haplotype and AOSD susceptibility. These findings suggest that genetic susceptibility to AOSD depends on the genotype combinations of HLA DRB1 and DQB1 alleles.

Severe Enteritis after Cyclophosphamide Administration in a Patient with Microscopic Polyangiitis: A Case Report and Literature Review.

Severe enteritis is a rare side effect of cyclophosphamide (CPA) therapy, and only two cases have been reported to date. We herein report a 60-year-old man who developed severe enteritis after intravenous CPA administration for microscopic polyangiitis. He was successfully treated by discontinuation of CPA administration and long-term intensive supportive care. A diagnosis of CPA-associated enteritis was made based on the clinical course and imaging and pathological findings. This review of three cases of CPA-related enteritis, including our case, suggests that prompt CPA discontinuation and intensive systemic management are necessary when patients have gastrointestinal symptoms after CPA administration.

The expression of Ets-1 and Fli-1 is associated with interferon-inducible genes in peripheral blood mononuclear cells from Japanese patients with systemic lupus erythematosus.

Transcription factors E26 transformation-specific-1 (Ets-1) and Friend leukemia insertion site-1 (Fli-1) and type I interferon (IFN) have been implicated in systemic lupus erythematosus (SLE). We examined the expression of these genes in peripheral blood mononuclear cells (PBMCs) from Japanese patients with SLE and analyzed their association with SLE. We enrolled 53 Japanese patients with SLE, 42 patients with rheumatoid arthritis (RA), and 30 healthy donors (HDs) (as controls) in this study. PBMCs were collected from all participants, and the expressions of Ets-1, Fli-1, and three interferon-inducible genes (IFIGs) (interferon-inducible protein with tetratricopeptide 1 [IFIT1], interferon-inducible protein 44 [IFI44], and eukaryotic translation initiation factor 2 alpha kinase 2 [EIF2AK2]) were measured using real-time polymerase chain reaction (PCR). The relationships of each molecule with clinical symptoms, laboratory data, and treatments were analyzed. The expression of Ets-1 and Fli-1 was significantly lower in the PBMCs from patients with SLE than that in the PBMCs from patients with RA and HDs. The expression of the three IFIGs was significantly higher in the PBMCs from patients with SLE than that in the PBMCs from patients with RA and HDs. For patients with SLE, significantly positive correlations were found between Ets-1 and three IFIGs; a similar trend was observed between Fli-1 and IFIGs. IFIG expression in the PBMCs was significantly higher in patients with SLE than that in other participants, and the expression of Ets-1 and Fli-1 was positively associated with IFN expression. Therefore, it was suggested that Ets-1 and Fli-1 were associated with the pathophysiology of SLE by regulating the type I IFN pathway.

Real-world comparative effectiveness of bDMARDs and JAK inhibitors in elderly patients with rheumatoid arthritis.

In this retrospective cohort study, we compared the retention rates and effectiveness of biologic disease modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (targeted disease modifying antirheumatic drug [tsDMARDs]: Janus kinase inhibitors [JAKi]) in elderly patients with RA. One hundred thirty-four elderly RA patients (≥65 years) who were initiated with bDMARDs (n = 80) or JAKi (n = 54) between 2016 and 2020 in our institute were enrolled in this analysis. Follow-up was conducted at 4-week intervals from the start of bDMARDs or JAKi. We compared the drug retention and clinical response at 24 week between elderly RA patients treated with bDMARDs and JAKi. In the demographic data, more disease duration, the proportion of previous bDMARDs use and less the proportion of glucocorticoid use in JAKi group was significantly observed compared to the bDMARDs group. Otherwise, there was no significant difference in the other variables between the bDMARDs and JAKi groups. In the JAKi group, drug retention rate was not significantly different compared to the bDMARDs group (HR: 0.723, 95% CI: 0.406-1.289, P = .266). Also, there was no significant difference in the proportion of patients achieving good or moderate European alliance of associations for rheumatology (EULAR) response at 24 week between these two groups (bDMARDs; 88.6% vs JAKi; 91.8%, P = .158). In elderly RA patients initiated with bDMARDs or JAKi, drug retention rates of these targeted therapies did not differ significantly between these two groups. These findings suggest that elderly RA patients can achieve similar clinical improvement after initiating bDMARDs or JAKi.

Increased CEACAM1 expression on peripheral blood neutrophils in patients with rheumatoid arthritis.

Altered expression of adhesion molecules in immune cells has been demonstrated in rheumatoid arthritis (RA). Carcinoembryonic-antigen-related cell-adhesion molecule 1 (CEACAM1) is an adhesion molecule that acts as a coinhibitory receptor in the immune system. We investigated the role of CEACAM1 in immune cell subsets of patients with RA. Peripheral blood was obtained from 37 patients with RA and 20 healthy controls (HC). The expression of CEACAM1 and T-cell immunoglobulin mucin domain molecule (TIM) -3 on peripheral blood mononuclear cells and neutrophils was analyzed by flow cytometry. Intracellular TIM-3 expression was analyzed using cellular lysates by Western blot analysis. Serum levels of soluble CEACAM1 (sCEACAM1) were estimated by an enzyme-linked immunosorbent assay. CEACAM1 expression was not detected in peripheral blood mononuclear cells, including in CD14(+) monocytes and CD3(+) lymphocytes isolated from patients with RA or HC. However, substantial cell-surface expression of CEACAM1 was detected in peripheral blood neutrophils, and it was significantly elevated in samples from patients with RA without remission compared to those in remission. There was no significant difference in serum levels of sCEACAM1 between patients with RA and HC. Cell-surface expression of TIM-3 was not detected in peripheral blood neutrophils from patients with RA or HC but was seen in CD14(+) monocytes. However, there was no significant difference in TIM-3 expression on monocytes between patients with RA and HC. Our data indicate that cell-surface expression of CEACAM1 on peripheral blood neutrophils are higher in patients with RA and that it is associated with rheumatoid inflammation. Further studies are needed to explore the potential role of CEACAM1 in rheumatoid inflammatory pathways.