Bloody Diarrhea in a 27-year-old Man with Adult-onset Still's Disease.

A 27-year-old man presented with quotidian fever, rash, knee arthralgia, sore throat, and bloody diarrhea. Laboratory findings showed neutrophilia, elevated CRP, ferritin, and liver enzyme levels, and decreased hemoglobin levels. Radiological investigations revealed splenomegaly, systemic lymphadenopathy, thickening of the descending colon wall, and an abnormal uptake in the bone marrow and spleen as seen in F-fluorodeoxyglucose positron emission tomography. Malignant lymphoma was initially suspected, but biopsies showed no malignant findings. Colonoscopy revealed mucosal friability, erosions, and shallow ulcers, and pathological findings included crypt abscesses suggestive of either acute infectious colitis or inflammatory bowel disease. The patient was eventually diagnosed with adult-onset Still's disease (AOSD) and started on prednisolone, which resolved bloody diarrhea, leading to the diagnosis of comorbid ulcerative colitis (UC). The combination of AOSD and UC presents a diagnostic challenge due to overlapping symptoms. An accurate diagnosis requires careful exclusion of other diseases and a comprehensive assessment.

Assessment of oral methotrexate intolerance in Japanese adult patients with rheumatoid arthritis.

AIM: The objective of this study was to assess the gastrointestinal side (GI) effects of oral methotrexate (MTX) in Japanese adult patients with rheumatoid arthritis (RA). METHODS: In this single-center retrospective study, 112 Japanese adult patients (over 18 years old) with RA were examined by Methotrexate Intolerance and Severity assessment in Adults (MISA) questionnaire. RESULTS: Forty-five (40.2%) of patients were MTX intolerant (MISA score ≥1). Twelve patients (11.2%) were moderate-to-severe MTX intolerant (MISA cross-product score ≥4). The most common GI side effects of MTX were gastric discomfort (26.8%), followed by loss of appetite or dysgeusia (14.3%), fatigue and lethargy (12.5%), and nausea (10.7%). CONCLUSIONS: Japanese adult patients with RA showed a high prevalence of MTX intolerance even in low-dose oral MTX. The MISA questionnaire was practical for finding patients with MTX intolerance.

The USP7-STAT3-granzyme-Par-1 axis regulates allergic inflammation by promoting differentiation of IL-5-producing Th2 cells.

Uncontrolled type 2 immunity by type 2 helper T (Th2) cells causes intractable allergic diseases; however, whether the interaction of CD4+ T cells shapes the pathophysiology of allergic diseases remains unclear. We identified a subset of Th2 cells that produced the serine proteases granzyme A and B early in differentiation. Granzymes cleave protease-activated receptor (Par)-1 and induce phosphorylation of p38 mitogen-activated protein kinase (MAPK), resulting in the enhanced production of IL-5 and IL-13 in both mouse and human Th2 cells. Ubiquitin-specific protease 7 (USP7) regulates IL-4-induced phosphorylation of STAT3, resulting in granzyme production during Th2 cell differentiation. Genetic deletion of Usp7 or Gzma and pharmacological blockade of granzyme B ameliorated allergic airway inflammation. Furthermore, PAR-1+ and granzyme+ Th2 cells were colocalized in nasal polyps from patients with eosinophilic chronic rhinosinusitis. Thus, the USP7-STAT3-granzymes-Par-1 pathway is a potential therapeutic target for intractable allergic diseases.

Efficient detection of somatic UBA1 variants and clinical scoring system predicting patients with variants in VEXAS syndrome.

OBJECTIVES: To efficiently detect somatic UBA1 variants and establish a clinical scoring system predicting patients with pathogenic variants in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. METHODS: Eighty-nine Japanese patients with clinically suspected VEXAS syndrome were recruited [81 males and 8 females; median onset age (IQR) 69.3 years (62.1-77.6)]. Peptide nucleic acid-clamping PCR (PNA-PCR), regular PCR targeting exon 3 clustering UBA1 variants, and subsequent Sanger sequencing were conducted for variant screening. Partitioning digital PCR (pdPCR) or targeted amplicon deep sequencing (TAS) was also performed to evaluate the variant allele frequency (VAF). We developed our clinical scoring system to predict UBA1 variant-positive and ­negative patients and assessed the diagnostic value of our system using receiver operating characteristic (ROC) curve analysis. RESULTS: Forty patients with reported pathogenic UBA1 variants (40/89, 44.9%) were identified, including a case having a variant with VAF of 1.7%, using a highly sensitive method. Our clinical scoring system considering >50 years of age, cutaneous lesions, lung involvement, chondritis, and macrocytic anaemia efficiently predicted patients with UBA1 variants (the area under the curve for the scoring total was 0.908). CONCLUSIONS: Genetic screening with the combination of regular PCR and PNA-PCR detected somatic UBA1 variants with high sensitivity and specificity. Our scoring system could efficiently predict patients with UBA1 variants.

IgG4-related disease administered dupilumab: case series and review of the literature.

Dupilumab (DUP) is a monoclonal antibody that acts on the interleukin (IL)-4 receptor alpha, which inhibits IL-4 and IL-13 signalling and is approved for type 2 inflammatory diseases such as asthma, chronic rhinosinusitis with nasal polyposis and atopic dermatitis; however, the efficacy of DUP to IgG4-related disease (IgG4-RD) is under discussion due to the controversial outcomes based on the several case reports. Here, we reviewed the efficacy of DUP in four consecutive patients with IgG4-RD in our institute and the previous literature.All patients administered DUP fulfilled the 2019 ACR/EULAR classification criteria for IgG4-RD complicated with severe asthma and chronic rhinosinusitis with nasal polyposis. Two cases were administered DUP without systemic glucocorticoids (GCs), and in 6 months, the volume of swollen submandibular glands (SMGs) was reduced by approximately 70%. Two cases receiving GCs successfully reduced their daily dose of GCs (10 and 50% reduction, respectively) with dupilumab in 6 months. In all four cases, serum IgG4 concentration and IgG4-RD responder index decreased in 6 months.DUP reduced the volume of the swollen SMGs, serum IgG4 levels, responder index and the daily dose of GCs in patients with IgG4-RD with severe asthma or eosinophilic rhinosinusitis in 6 months.The efficacy of DUP to IgG4-RD is under discussion due to the limited case reports with controversial outcomes. Here, we demonstrated that two patients with IgG4-RD treated by DUP without systemic GCs, showed volume reduction of swollen SMGs and two cases showed GC-sparing effects by DUP. DUP can ameliorate the disease activity and be a steroid-sparing agent in patients with IgG4-RD.

A Tumefactive Fibroinflammatory Lesion of the Head and Neck Mimicking Immunoglobulin G4-related Disease.

A 67-year-old woman with a 5-year history of recurrent swollen eyelids and epistaxis, diagnosed as immunoglobulin G4-related diseases (IgG4-RD) based on hyper-IgG4-emia and IgG4-positive cell infiltration to the lesion, was referred to our department due to recurrent symptoms despite corticosteroid therapies. Computed tomography revealed an osteoclastic sinus mass with prominent neutrophil infiltration and necrosis that was incompatible with IgG4-RD histopathologically. Finally, she was diagnosed with a tumefactive fibroinflammatory lesion (TFIL) of the head and neck and treated with high-dose corticosteroids. Physicians should remember that TFIL can mimic IgG4-RD in the head and neck region with prominent neutrophil infiltration and necrosis.

Recurrent Optic Perineuritis With Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease Complicated With Granulomatous Polyangiitis.

Optic perineuritis (OPN) is an intraorbital inflammatory disease that targets the optic nerve sheath, which can cause severe vision loss. OPN has been recently reported to be sometimes caused by myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD). MOGAD is rarely reported to be complicated with other autoimmune diseases. We report the first rare case of MOG-associated OPN complicated with granulomatous with polyangiitis (GPA). The vision loss, in this case, was initially considered to be caused by cavernous sinusitis in GPA. However, she was diagnosed with MOGAD with serial MRI findings and positive MOG antibody and had been successfully treated with glucocorticoid and tocilizumab for one and half years. This case emphasized the importance of evaluating the MOG antibody in a patient with recurrent OPN, complicated with vasculitis.

Abnormal [18F]fluorodeoxyglucose accumulation to tori tubarius in IgG4-related disease.

OBJECTIVES: Tubarial glands (TGs) are recently refocused gland tissues localized near the tori tubarius in the nasopharynx and their clinical relevance is not clear yet. IgG4-related disease (IgG4-RD) is a progressive fibrosing condition and salivary glands are well-affected lesions. The aim of the present study is to examine [18F]fluorodeoxyglucose ([18F]FDG) accumulation to the tori tubarius in IgG4-related disease (IgG4-RD). METHODS: 48 patients with IgG4-RD who underwent positron emission tomography (PET) scanning with [18F]FDG were included and semi-quantitative analysis of [18F]FDG accumulation to tori tubarius was performed along with the clinical features and histopathological analysis. RESULTS: Of the 48 patients, abnormal [18F]FDG accumulation (metabolic tumour volume ≥ 1) to tori tubarius was observed in 15 (31.3%), all of whom had lesions in other head and neck glands. IgG4-RD patients with abnormal [18F]FDG accumulation to tori tubarius showed swollen nasopharyngeal walls around tori tubarius and forceps biopsy of the lesion revealed acinar cells and IgG4-positive plasma cells histologically. Abnormal [18F]FDG accumulation (maximum standard uptake value, metabolic tumour volume and total lesion glycolysis) to tori tubarius correlated with higher IgG4 and lower IgA serum concentrations. CONCLUSIONS: Abnormal [18F]FDG accumulation to tori tubarius can be observed in patients with IgG4-RD and the abnormal [18F]FDG accumulation to tori tubarius can be a clue of TG involvement in IgG4-RD.