Prolonged infective SARS-CoV-2 omicron variant shedding in a patient with diffuse large B cell lymphoma successfully cleared after three courses of remdesivir.

We report a case of prolonged shedding of the infective SARS-CoV-2 omicron variant BA.1.1.2 in a 79-year-old male patient with diffuse large B-cell lymphoma, after receiving chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). The patient was admitted to our hospital in late March 2022 for the sixth course of R-CHOP chemotherapy. Initially, the patient tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using an in-hospital loop-mediated amplification assay with a nasopharyngeal swab, both on the day of admission and three days later. However, the patient developed fever and was diagnosed with coronavirus disease (COVID-19) six days after admission and was suspected to have contracted the infection in the ward. Viral shedding continued for more than three months, with confirmed viral infectivity. As compared to the original Wuhan-Hu-1/2019 strain, amino acid substitutions including S36 N in non-structural protein (NSP)2, S148P, S1265del and L1266I in NSP3, G105D in NSP4, G496S, A831V, or V987F in spike protein, and I45T in open-reading frame (ORF)9b were randomly detected in isolated viruses. Although the patient had received two doses of the BNT162b2 vaccine approximately six months earlier and the third dose on day 127 after the infection, both serum anti-spike and anti-nuclear protein IgG and IgM tests were negative at day 92, 114, and 149 after the infection. The patient finally cleared the virus after the third course of remdesivir and did not have further recurrence.

Successful allogeneic hematopoietic stem cell transplantation for myelodysplastic neoplasms complicated with secondary pulmonary alveolar proteinosis and Behçet's disease harboring GATA2 mutation.

Myelodysplastic neoplasms (MDS) are defined by cytopenia and morphologic dysplasia originating from clonal hematopoiesis. They are also frequently complicated with diseases caused by immune dysfunction, such as Behçet's disease (BD) and secondary pulmonary alveolar proteinosis (sPAP). MDS with both BD and sPAP is extremely rare, and their prognosis is poor. In addition, haploinsufficiency of the hematopoietic transcription factor gene GATA2 is recognized as a cause of familial MDS and is frequently complicated by sPAP. Herein, we report a case of MDS combined with both BD and sPAP in association with GATA2 deficiency in a Japanese woman. Because she developed progressive leukopenia and macrocytic anemia during BD treatment at the age of 61, she underwent a bone-marrow examination and was diagnosed with MDS. She subsequently developed sPAP. At the age of 63, she underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Since allo-HSCT, she has maintained complete remission of MDS as well as the symptoms of BD and sPAP. Furthermore, we performed whole exome sequencing and identified the GATA2 Ala164Thr germline mutation. These findings suggest that patients with MDS, BD and sPAP should be considered for early allo-HSCT.

Rapid Clinical Improvement of Multicentric Castleman Disease (MCD) with Renal Involvement Following Treatment with Tocilizumab: AA Amyloidosis as a Possible Renal Involvement of MCD.

Castleman disease (CD) is a lymphoproliferative disorder that manifests as hypergammaglobulinemia and severe inflammation with multiorgan involvement. However, renal involvement has been infrequently described in CD. We present a case of a 63-year-old Japanese male patient with multicentric CD (MCD) in whom kidney involvement, including impaired renal function and massive proteinuria, is present. He had a 2-year history of inflammatory arthritis and was referred to our clinic with newly developed proteinuria, renal dysfunction, and elevated levels of acute-phase proteins. Abdominal computed tomography scan revealed hepatosplenomegaly, including mesenteric and inguinal lymph node enlargements. The patient underwent inguinal lymph node resection. Excisional biopsy of the inguinal lymph node showed multiple lymphoid follicles and expansion of interfollicular areas by marked plasmacytosis consistent with mixed type CD. The patient was diagnosed with human herpes virus 8-negative MCD according to the international diagnostic criteria for CD. Diagnostic renal biopsy was not performed following the medical viewpoint. Tocilizumab (TCZ) treatment was highly effective in reducing proteinuria and stabilizing renal function, as well as improving other clinical symptoms. The patient responded to TCZ treatment, and the renal involvement was rapidly improved. Our preliminary immunohistochemical analysis indicated AA amyloid deposits in urinary epithelial cells suggesting a possible renal involvement of AA amyloidosis. TCZ could potentially be one of the therapeutic options in patients with MCD with renal involvement.

New-onset dermatomyositis following COVID-19: A case report.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most of the infected individuals have recovered without complications, but a few patients develop multiple organ involvements. Previous reports suggest an association between COVID-19 and various inflammatory myopathies, in addition to autoimmune diseases. COVID-19 has been known to exacerbate preexisting autoimmune diseases and trigger various autoantibodies and autoimmune disease occurrence. Here we report a case of complicated COVID-19 with anti-synthetase autoantibodies (ASSs) presenting with skin rash, muscle weakness, and interstitial lung disease (ILD) and subsequently diagnosed with dermatomyositis (DM). A 47-year-old Japanese male patient without any previous history of illness, including autoimmune diseases, presented with a high fever, sore throat, and cough. Oropharyngeal swab for SARS-Cov-2 polymerase chain reaction tested positive. He was isolated at home and did not require hospitalization. However, his respiratory symptoms continued, and he was treated with prednisolone (20 mg/day) for 14 days due to the newly developing interstitial shadows over the lower lobes of both lungs. These pulmonary manifestations remitted within a week. He presented with face edema and myalgia 4 weeks later when he was off corticosteroids. Subsequently, he presented with face erythema, V-neck skin rash, low-grade fever, and exertional dyspnea. High-resolution computed tomography of the chest showed ILD. Biochemical analysis revealed creatine kinase and aldolase elevations, in addition to transaminases. Anti-aminoacyl tRNA synthetase (ARS) was detected using an enzyme-linked immunosorbent assay (170.9 U/mL) (MESACUP™ (Medical & Biological Laboratories, Japan), and the tRNA component was identified as anti-PL-7 and anti-Ro-52 antibodies using an immunoblot assay [EUROLINE Myositis Antigens Profile 3 (IgG), Euroimmun, Lübeck,Germany]. The patient was diagnosed with DM, especially anti- synthase antibody syndrome based on the presence of myositis-specific antibodies, clinical features, and pathological findings. The present case suggests that COVID-19 may have contributed to the production of anti-synthetase antibodies (ASAs) and the development of de novo DM. Our case highlights the importance of the assessment of patients who present with inflammatory myopathy post-COVID-19 and appropriate diagnostic work-up, including ASAs, against the clinical features that mimic DM after post-COVID-19.

Effect of a multitarget therapy with prednisolone, mycophenolate mofetil, and tacrolimus in a patient with type B insulin resistance syndrome complicated by lupus nephritis.

Type B insulin resistance syndrome (TBIR) is a rare autoimmune disease characterised by autoantibodies targeting insulin receptors. TBIR is often complicated by systemic lupus erythematosus (SLE). We describe the case of a 59-year-old Japanese man with TBIR complicated with lupus nephritis (LN), who presented with nephrotic syndrome and severe hypoglycaemia. Treatment with prednisolone (PSL), mycophenolate mofetil (MMF), and tacrolimus (TAC) resulted in improved SLE activity and glucose intolerance with the reduction of anti-insulin receptor autoantibodies. To the best of our knowledge, this is the first reported case of TBIR complicated with LN that was successfully treated using multitarget therapy with PSL, MMF, and TAC.

Intestinal Behçet's disease complicated by myelodysplastic syndrome and secondary pulmonary alveolar proteinosis: a case report.

BACKGROUND: Gastrointestinal lesions, which sometimes develop in Behçet's disease (BD), are referred to as intestinal BD. Although rare, intestinal BD can be accompanied by myelodysplastic syndrome (MDS) with abnormal karyotype trisomy 8, which is refractory to immunosuppressive therapy. Pulmonary alveolar proteinosis is a rare lung complication of BD and MDS. Herein, we present an extremely rare case of intestinal BD presenting with MDS and several chromosomal abnormalities, followed by secondary pulmonary proteinosis. CASE PRESENTATION: A 58-year-old Japanese woman with a 3-year history of genital ulcers and oral aphthae was admitted to our hospital. The patient developed abdominal pain and persistent diarrhea. Colonoscopy revealed multiple, round, punched-out ulcers from the terminal ileum to the descending colon. Intestinal BD was diagnosed and the patient was treated with colchicine, prednisolone, and adalimumab. However, her symptoms were unstable. Bone marrow examination to investigate the persistent macrocytic anemia revealed the presence of trisomy 8, trisomy 9, and X chromosome abnormalities (48, + 8, + 9, X, i(X) (q10) in 12 out of the examined 20 cells). Based on her hypoplastic bone marrow, the patient was diagnosed with low-risk MDS (refractory anemia). At the age of 61, the patient developed pneumonia with fever and diffuse ground-glass opacities on the lung computed tomography (CT). Chest high-resolution CT and histopathology via transbronchial lung biopsy revealed the presence of pulmonary alveolar proteinosis (PAP). These findings combined with the underlying disease led to the diagnosis of secondary PAP. CONCLUSIONS: Secondary pulmonary proteinosis may accompany intestinal BD with MDS and several chromosomal abnormalities. Physicians should pay attention to lung complications, such as PAP, in patients with intestinal BD complicated by MDS. Genetic abnormalities may be associated with the development of such diseases.

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.

Acute retrobulbar optic neuritis with anti-myelin oligodendrocyte glycoprotein antibody-associated disease complicated with microscopic polyangiitis: A case report.

RATIONALE: Anti-myelin oligodendrocyte protein antibody-associated disease (MOGAD) is a new disease entity with various clinical phenotypes. MOGAD often present with recurrent optic neuritis (ON), and it can also develop as a compartment of neuromyelitis optica spectrum disorder (NMOSD). Moreover, multiple autoantibodies such as an anti-myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) had been reported in the serum of patients with NMOSD. PATIENT CONCERNS: We report an 86-year-old woman with a 2-year history of microscopic polyangiitis (MPA). The patient had a rapid loss of vision in her left eye. No abnormal findings were observed on her left fundus, and she tested negative for MPO-ANCA upon admission. However, anti-MOG antibodies were observed in the patient's serum and cerebrospinal fluid. DIAGNOSIS: A diagnosis of MOGAD complicated with MPA was made. INTERVENTIONS: The patient received twice steroid pulse therapy and oral azathioprine as maintenance therapy. OUTCOMES: Her vision rapidly recovered, and no subsequent relapse was observed during the 8-month observation period. CONCLUSION: To the best of our knowledge, this is the first case of MOGAD complicated with MPA, and steroid pulse therapy and azathioprine therapy were effective for ON caused by MOGAD.

A case of dermatomyositis complicated with pleural effusion and massive ascites.

We report a patient with dermatomyositis (DM) complicated with progressive pleural effusion and ascites. A 40-year-old woman was hospitalized in our department because of severe myalgia and dysphagia, complicated with pleural effusion and massive ascites. Elevated muscle enzymes, Gottron's papules, and electromyography (EMG) confirmed the diagnosis of DM. Combined immunosuppressive treatment consisting of intravenous immunoglobulin (IV-IG), intravenous-cyclophosphamide (IV-CY) and tacrolimus resolved her myopathy and dysphagia as well as pleural effusion and massive ascites. Her clinical course and the absence of other factors that cause pleural effusion and ascites suggest that these symptoms were related to the pathophysiology of DM.

Long-term outcome and efficacy of cyclophosphamide therapy in Japanese patients with ANCA-associated microscopic polyangiitis: a retrospective study.

OBJECTIVE: The aim of this study was to elucidate the efficacy of cyclophosphamide (CY) in Japanese patients with antineutrophil cystoplasmic antibody (ANCA)-associated microscopic polyangiitis (MPA). METHODS: Sixty-four patients, newly diagnosed with ANCA-associated MPA were included in this retrospective study. The patients were divided into two groups based on whether they received combination therapy of CY and corticosteroid (CS) (CY group, n=29) or CS alone (CS group, n=35) for remission induction. The primary outcome was all-cause mortality. RESULTS: Most patients in the CY group were treated with oral CY. Between the two groups, there were no differences in the baseline characteristics except for a higher proportion of male patients in the CY group. The remission rate was not substantially different between the two groups (86.2% in the CY group vs. 91.4% in the CS group). The survival rate was slightly higher in the CY group than in the CS group (not statistically significant; 0.86 vs. 0.77 at 1 year and 0.73 vs. 0.64 at 5 years, p=0.648). In the CY group, the hazard ratio after adjusting for age, sex, Birmingham vasculitis activity score values, serum albumin levels and C-reactive protein (CRP) levels was 0.657 (95% CI, 0.254-1.699; p=0.386). CONCLUSION: We observed no increased efficacy of CY in ANCA-positive MPA in the Japanese patients, and hence, its efficacy may be limited in these patients.

Pulmonary hypertension confirmed histologically five months prior to scleroderma renal crisis onset.

A 69-year-old man presented shortness of breath and acute renal failure. He had undergone pulmonary partial resection for lung cancer 5 months prior. On examination, severe hypertension, skin sclerosis of his forearms, and anticentromere antibody were observed. A renal biopsy specimen showed characteristic findings for scleroderma renal crisis, and a right heart catheterization revealed severe pulmonary arterial hypertension. Re-examination of the resected lung specimen revealed sclerodermatous vascular involvement was present.

[Sleeveresection of the left main bronchus for bronchogenic carcinoid for preserving lung parenchyma].

UNLABELLED: We performed bronchoplasty for a bronchogenic tumor of low-grade malignancy without lung parenchyma resection. A 69-year-old man visited our hospital in March 2008 because of cough. Chest computed tomography (CT) revealed atelectasis of the entire left upper lobe and a 2-cm mass with strong contrast enhancement in the lumen of the left main bronchus. Bronchoscopy identified a polypoid mass in the left main bronchus, about 3 cm distal to carina, obstructing the lumen. Biopsy led to a diagnosis of typical carcinoid tumor. Surgery : Thoracotomy showed complete atelectasis of the left upper lobe. After lymph node dissection, resection of the left main bronchus including the site of tumor origin was performed. From the extent of expansion, the left upper lobe was decided to be possible to be spared, and end-to-end anastomosis of the bronchus was performed. Postoperative respiratory rehabilitation resulted in improved aeration of the left upper lobe and markedly improved respiratory function. CONCLUSION: The judgment of whether the long-standing atelectatic left upper lobe could be spared or not was a key in choosing this procedure.

Usefulness of intraoperative esophagogastroduodenoscopy in a patient with lupus enteritis.

A 19-year-old Japanese woman had melena 2 months after systemic lupus erythematosus was diagnosed. Colonoscopy showed diffuse ulceration with bleeding in the ileum, suggesting that the melena was due to ischemic enteritis associated with lupus enteritis. Because treatment with high doses of steroid, anticoagulants, and cyclophosphamide pulse was ineffective, surgical intervention was planned. On exploration, it was impossible to determine the extent of resection visually. Intraoperative esophagogastroduodenoscopy clearly revealed the border between the ulcer and normal area, permitting successful resection of the ileum and ileostomy. This is the first report to document the usefulness of esophagogastroduodenoscopy in surgical treatment of ischemic enteritis in a patient with systemic lupus erythematosus.

Doppler sonographic analysis of synovial vascularization in a patient with rheumatoid arthritis treated with leukocytapheresis.

Synovial vascularization in metacarpophalangeal joints of a patient with rheumatoid arthritis treated with leukocytapheresis (LCAP) was evaluated by Doppler sonography. After the treatment with LCAP, evaluation with American College of Rheumatology core set showed improvement, and the levels of C-reactive protein and serum amyloid A protein decreased. Power Doppler sonography demonstrated a reduction of color flow signals of the joints, and spectral Doppler sonography demonstrated an increase in vascular resistant, indicating a reduction of vessel's permeability. This is the first report evaluating a synovial vascularization and blood flow of the joints by Doppler sonography before and after LCAP therapy. Doppler sonography might be one of the useful methods for evaluating the therapeutic response of LCAP.

A case of steroid-refractory ulcerative colitis complicated with cytomegalovirus pneumonia.

We present a case of late-onset ulcerative colitis (UC) complicated with cytomegalovirus (CMV) pneumonia revealed by autopsy. A 77-year-old woman had a diagnosis of UC, and received high-dose steroids and leukocytapheresis. Then she received ganciclovir because CMV-pp65 antigenemia test revealed positive which suggested systemic or colonic CMV infection. But ganciclovir was discontinued because of thrombocytopenia and liver dysfunction. After that she had interstitial pneumonia and died of a respiratory failure. Autopsy revealed CMV colitis based on UC, and CMV pneumonia with diffuse alveolar damage. Evaluation of CMV infection in patients with steroid-refractory UC should be considered before proceeding with immunosuppressive therapy or surgery, especially in elderly patients.

Endosonographic diagnosis and follow-up of phlegmonous gastritis.

We report a case of phlegmonous gastritis in a 36-year-old man presenting with anorexia, epigastralgia, and high fever. Endoscopy showed an edematous lesion suggesting a submucosal lesion. Endosonography revealed thickening of the gastric wall, mainly involving the submucosa, with a few anechoic areas. The separation between the submucosa and the muscularis propria was unclear. The patient was treated with antibiotics and endoscopic mucosal resection. Culture of the aspirated pus from the lesion revealed Streptococcus pyogenes. Follow-up endosonography performed 1 week later showed significant improvement.

Anti-triosephosphate isomerase antibodies in cerebrospinal fluid are associated with neuropsychiatric lupus.

We detected anti-triosephosphate isomerase antibodies (anti-TPI) in cerebrospinal fluid (CSF) in 5 of 12 neuropsychiatric lupus patients (41.6%) by Western blotting. C3d index was significantly higher in anti-TPI-positive patient (n=5, median 0.446) than in anti-TPI-negative patient (n=7, median 0.098) (p=0.019) CSF samples. TPI was detected from immune complexes (IC) isolated from CSF in 2 of 2 anti-TPI-positive patients tested and was not detected from IC in 5 of 5 anti-TPI-negative patients tested. Our results suggest that anti-TPI form IC in CSF and contribute to the pathogenesis of neuropsychiatric lupus by activating the complement system.

A case of idiopathic portal hypertension associated with rheumatoid arthritis.

A 53-year-old woman who had been diagnosed with rheumatoid arthritis was found to have thrombocytopenia, splenomegaly, and gastric varices. She was diagnosed as having idiopathic portal hypertension on the basis of liver biopsy and angiography. Treatment with prednisolone was not sufficiently effective for thrombocytopenia. After transabdominal devascularization with splenectomy, thrombocytopenia subsided and gastric varices disappeared. In this case, the autoimmune mechanism as well as hypersplenism was suspected of being involved in the mechanism of thrombocytopenia.

A case of systemic lupus erythematosus complicated by pure red cell aplasia and idiopathic portal hypertension after thymectomy.

We describe a 49-year-old woman who presented in 2002 with pure red cell aplasia (PRCA), systemic lupus erythematosus (SLE), and idiopathic portal hypertension (IPH) that developed following a thymectomy. She underwent a thymectomy at 40 years of age to treat myasthenia gravis. PRCA developed 3 years after the thymectomy and she was successfully treated with cyclosporin. Systemic lupus erythematosus and IPH were diagnosed 6 years later. We conclude that immunological dysfunction resulting from the thymectomy contributed significantly to the subsequent development of PRCA, SLE, and IPH in this patient. This is the first report to describe this extremely rare occurrence.

A case of primary biliary cirrhosis complicated by Behçet's disease and palmoplantar pustulosis.

A 46-year-old woman was diagnosed with palmoplantar pustulosis (PPP) at the Department of Dermatology, Fukushima Medical University Hospital in 2000, and was treated with ointment. However, because liver dysfunction developed in 2003, she was referred to our department, where primary biliary cirrhosis (PBC) was also diagnosed on the basis of clinical findings. One year later, at the age of 49, she developed manifestations of Behçet's disease (BD), including erythema nodosum in the lower extremities. Because she had a history of uveitis, recurrent oral ulceration was present, and the HLA typing was positive for B51, BD was additionally diagnosed. Liver function normalized within three months of the start of treatment with ursodesoxycholic acid (UDCA). This is the first case of PBC associated with BD and PPP.