A case of eosinophilic granulomatosis with polyangiitis associated with diffuse alveolar haemorrhage: A case report and case-based review.

A 76-year-old man with bronchial asthma was admitted for respiratory failure and bloody sputum. A significant drop in haemoglobin and multiple consolidations supported clinical diagnosis of diffuse alveolar haemorrhage (AH). Myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) was positive and urinalysis suggested glomerulonephritis. Based on eosinophilia, sinusitis, peripheral nerve involvement, and leukocytoclastic vasculitis, he was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA) associated with AH. Our case-based review suggested that male predominance (65%), high positivity for ANCA (88%) and a high frequency of renal involvement (45%) may be characteristic of AH in EGPA. Although AH is rare in EGPA, we should be aware of this life-threatening complication.

Glucocorticoid-free remission in patients with SLE in the era of biologics: Immune complex disease is likely to benefit from current medications.

OBJECTIVES: In addition to various immunosuppressive agents, belimumab and anifrolumab became available in Japan. We aimed to investigate glucocorticoid-free clinical remission in a single-centre retrospective cohort in October 2023. METHODS: Our cohort included patients with SLE who needed to start or increase glucocorticoids for disease activity and were followed up for more than 1 year. We investigated the rate of achievement of clinical remission off corticosteroids (CR off C), defined as no clinical score on the SLEDAI-2K without glucocorticoids, baseline predictors of CR off C, medications used when CR off C was achieved, and flare rates following CR off C. RESULTS: Out of the 60 patients followed for an average of 5.4 (±2.6) years, 17 (28.3%) achieved CR off C in 3.6 (±1.2) years after enrolment. Use of belimumab and anifrolumab accounted for eight (47.1%) of the achievers. Among the baseline data, male sex, recent enrolment, high glucocorticoid dose, and detection of immune complex (IC) significantly predicted CR off C, while lupus nephritis (LN) and a low C3 level tended to predict it. In the multivariate analysis, IC detection was the only predictor of CR off C. Clinical flares were observed in 5.9% of the achievers during a median 1.2 years after achievement of CR off C. CONCLUSION: In the era of biologics, CR off C was achieved in 28.3% of the patient cohort requiring the start or increase of glucocorticoids for disease activity, with a relatively low rate of flares, suggesting that glucocorticoid-free clinical remission is an achievable target in SLE. IC disease, represented by male sex or nephritis, is likely to benefit from currently available medications.

Anti-nuclear Matrix Protein 2 Antibody-positive Dermatomyositis Associated with Cervical Cancer Recurrence after 6 Years of Stable Disease.

A 79-year-old woman was evaluated for weakness, dysphagia, and elevated levels of creatinine kinase. Her medical history included stage IIIB cervical cancer eight years previously, which improved after undergoing radiotherapy. Two years later, cancer recurred in the right hilar and mediastinal lymph nodes, and the patient was successfully treated with chemotherapy. Physical examinations showed Gottron's sign, the V sign, the Holster sign, and nailfold erythema. Computed tomography revealed left supraclavicular lymphadenopathy, compatible with cancer recurrence. Anti-nuclear matrix protein 2 (NXP2) antibody was found in her sera and a diagnosis of cancer-associated dermatomyositis was thus made. This case suggests that cancer progression over a period of years may have triggered the onset of autoimmunity against NXP2.

Clinical value of cancer-associated myositis-specific antibodies, anti-transcriptional intermediary factor 1-γ, and anti-nuclear matrix protein 2 antibodies in a retrospective cohort of dermatomyositis/polymyositis in a Japanese community hospital.

Among the myositis-specific antibodies (MSA), anti-transcriptional intermediary factor 1 (TIF1)-γ and anti-nuclear matrix protein 2 (NXP2) antibodies are reportedly associated with cancer-associated myositis (CAM). We aimed to investigate patient characteristics of CAM and the clinical role of cancer-associated MSA (caMSA) in a retrospective cohort from a city hospital. All patients visiting our department between April 2014 and October 2021 with newly diagnosed dermatomyositis, polymyositis, and clinically amyopathic dermatomyositis were included. Anti-TIF1-γ and anti-NXP2 antibodies were collectively considered as caMSA. First, we compared clinical characteristics in CAM, defined as cases showing onset or recurrence of malignancy within 5 years, versus non-CAM. Second, we investigated independent risk factors for CAM. Third, we compared clinical characteristics with and without caMSA within CAM. Finally, we investigated whether caMSA was predictive of poor prognosis. The cohort of 39 patients included 12 (30.7%) CAM cases. Compared with non-CAM, CAM had significantly more dermatomyositis and higher frequencies of dysphagia, anti-TIF1-γ antibody, and caMSA. Using logistic regression analysis, caMSA was an independent risk factor for CAM. In a comparison between caMSA and non-caMSA within CAM, caMSA was associated with higher frequencies of stage ≥ II. However, caMSA did not necessarily indicate a poor prognosis. Only caMSA represented an independent risk factor for CAM and showed a significant association with advanced cancer. Key Points • Cancer-associated MSA was an independent risk factor for cancer-associated myositis. • Cancer-associated MSA was associated with advanced cancer.

A case of giant cell arteritis lacking typical symptoms presenting with recurrent cerebellar infarctions: A case report and case-based review.

Giant cell arteritis (GCA) occasionally presents with ischaemic stroke. Generally, symptoms related to GCA or elevated levels of inflammation markers would be a clue for the diagnosis of GCA. However, we encountered a rare case of GCA that presented with recurrent cerebellar infarctions without symptoms related to GCA (headache, fever, or jaw claudication). Furthermore, C-reactive protein levels, measured at the time of two of the stroke attacks, were within the normal range. On physical examination, the temporal arteries were prominent and weakly pulsatile. Temporal artery ultrasonography showed halo signs, and temporal artery biopsy revealed GCA. To our knowledge, this is the first case of GCA presenting with recurrent ischaemic stroke lacking GCA features but diagnosed before death. Considering this case-based review, we suggest that GCA may have been missed in elderly patients with ischaemic stroke, especially in those with posterior circulation infarction. Therefore, physical examination of the temporal arteries, temporal artery ultrasonography, and vessel wall magnetic resonance imaging may be useful in those patients.

Temporal arteritis as an initial manifestation of eosinophilic granulomatosis with polyangiitis: a case report and a literature review.

A 79-year-old woman was admitted for suspected giant cell arteritis (GCA). She had suffered from dizziness, headache, jaw claudication and visual disturbance. Her medical history included bronchial asthma and parasinusitis. Her superficial temporal arteries were markedly enlarged with tenderness. Laboratory data showed eosinophilia (6968/µL) and a positive result of myeloperoxidase-ANCA. A histological examination of the biopsied artery revealed granulomatous inflammation consisting of lymphocytes and eosinophils with a multinucleated giant cell. Her conditions met both the criteria for GCA and eosinophilic granulomatosis with polyangiitis (EGPA). We finally considered that she had temporal arteritis as an initial manifestation of EGPA after a comprehensive literature review. To our knowledge, this is the first case in which temporal arteritis with a giant cell developed as an initial and sole manifestation of EGPA.

A case of systemic lupus erythematosus associated with cerebral arteritis: a case report and case-based literature review.

A 62-year-old female patient with systemic lupus erythematosus (SLE) was admitted for cerebral infarction. The magnetic resonance angiography showed focal narrowing of the cerebral arteries that was initially considered as atherosclerosis due to her cardiovascular risk factors. Ten weeks later, she was again admitted for multiple cerebral infarctions. Vessel wall magnetic resonance imaging revealed gadolinium enhancement of the arterial walls of the narrowing lesions, leading to a diagnosis of cerebral arteritis. Based on a literature review, cerebral medium-sized arteritis in SLE likely progresses insidiously during the active phase of SLE, which may later result in occlusion irrespective of disease activity.

Aseptic meningitis as an initial presentation of Sjögren syndrome: a report of two cases and literature review.

Sjögren syndrome (SS) is one of several collagen vascular diseases that occasionally involve the central nervous system. We report two cases of SS involving young patients who initially presented with aseptic meningitis. A male with recurrent AM was found to have anti-Ro/SSA and La/SSB antibodies in a screening test for autoimmune process. A minor salivary gland biopsy revealed lymphocytic infiltrations compatible with SS, although the patient did not exhibit sicca symptoms. A female presenting with AM and polyarthritis also reported xerophthalmia. Anti-Ro/SSA antibody testing and a positive result in a minor salivary gland biopsy led to the diagnosis of SS. In the literature review, we found that AM or aseptic meningoencephalitis (AME) preceded or had a concomitant onset with SS in approximately 70% of cases. Screening for anti-Ro/SSA antibody, as well as systemic assessment for rheumatic symptoms, may be useful for diagnosing AM/AME of unknown etiology.

Temporal artery involvement in AL amyloidosis: an important differential diagnosis for giant cell arteritis. A case report and literature review.

AL amyloidosis (AL) is a systemic disorder due to extracellular tissue deposition of amyloid fibrils, composed of immunoglobulin light chains. Since the description of AL involving temporal arteries in 1986, this disorder has been known as one of the differential diagnoses of giant cell arteritis (GCA). We encountered a case of an elderly female presenting with headache and tender and enlarged temporal arteries, that was pathologically diagnosed with temporal artery involvement of AL due to Bence-Jones-type MM. To our knowledge, this was the first case of AL with temporal artery involvement in Japan, that presented with GCA-like features. Literature review of AL cases with temporal artery involvement showed close similarity between these disorders, but suggested that vasculature involvement (extremity claudication, kidney or heart), macroglossia, carpal tunnel syndrome and normal or low (<0.5 mg/dL) CRP levels may predict AL rather than GCA. Physicians should keep in mind that AL involving temporal arteries can be a pitfall in the diagnosis of GCA, as seen in our and previous cases.

Continuation Rate, Safety and Efficacy of Hydroxychloroquine Treatment in a Retrospective Cohort of Systemic Lupus Erythematosus in a Japanese Municipal Hospital.

Objective We investigated the continuation rate, safety and efficacy of treatment with hydroxychloroquine (HCQ) in a retrospective cohort of systemic lupus erythematosus (SLE) in a Japanese municipal hospital. Methods All of the patients with SLE who started treatment with HCQ were included in this study. A retrospective chart review was performed. Our primary outcomes were the continuation rate of HCQ treatment for 1 year and adverse events (AEs) during the treatment. We also investigated the efficacy of HCQ treatment in cases in which treatment with immunosuppressive therapies remained unchanged for the preceding six months. Results Forty-seven patients with SLE were included in this study. Twenty-five patients (53.2%) had AEs. Eleven (64.7%) of the 17 patients who tried the readministration of HCQ could continue HCQ treatment. The continuation rate of HCQ for a period of 1 year was 78.3% (36 of 46 patients). The development of cutaneous lesions was the most frequent adverse event (25.5%) followed by gastrointestinal symptoms (8.5%). In the 16 cases in which the immunosuppressive therapies remained unchanged for at least six months prior to starting HCQ treatment, the SLE disease activity index, anti-DNA antibody, immune complex, and serum complement activity significantly decreased over a period of 1 year, while the prednisolone dose significantly decreased. Conclusion The continuation rate of HCQ treatment was high in an SLE cohort of a Japanese municipal hospital. Although more than half of the patients experienced AEs, the readministration of HCQ was often successful. HCQ treatment provided benefits regarding the clinical and immunological findings in Japanese patients with SLE, which would likely lead to glucocorticoid tapering.

Provisional seven-item criteria for the diagnosis of polyarteritis nodosa.

Polyarteritis nodosa (PAN) is a potentially life-threatening systemic vasculitis, which predominantly involves medium arteries. However, it may be difficult to diagnose PAN in its early stage. The aim of our study was to investigate the sensitivity and specificity of the American College of Rheumatology (ACR) and the Japanese Ministry of Health, Labour and Welfare (MHLW) criteria for the diagnosis of PAN in a single-centre retrospective cohort in Japan and to develop simplified criteria with favourable diagnostic performance. All patients with "PAN" or "suspicion of PAN," as indicated on insurance forms, were included. The patient population was classified into PAN and non-PAN groups based on a retrospective chart review. The sensitivity and specificity of the ACR and MHLW criteria were calculated. Items that favourably discriminated the PAN group from the non-PAN group were determined and used as items for our provisional criteria. Thirteen cases of PAN and 24 cases without PAN were included in this study. The sensitivities of the ACR and MHLW criteria were 61.5% (8/13) and 30.8% (4/13), respectively, whereas the specificities were 79.2% (19/24) and 87.5% (21/24), respectively. We developed provisional criteria consisting of seven items, and found that a cut-off of ≥ 4 items had a sensitivity of 92.3% (12/13) and specificity of 91.7% (22/24) (p < 0.000001). The provisional seven-item criteria, developed in our real-world cohort of patients suspected of having PAN, had a high sensitivity and specificity and may be useful in the diagnosis of PAN, although it should be validated in additional patient populations.

Polyarteritis Nodosa with Marked Eosinophilia, Associated with Severe Gastrointestinal Tract Involvement and Recurrent Venous Thrombosis.

A 45-year-old man was admitted with acute abdominal pain and eosinophilia. Abdominal computed tomography revealed thickness of the ascending and transverse colon with decreased contrast enhancement and a small amount of ascites. In an emergency operation, the necrotic colon was resected. Histopathology showed subserous medium-sized arteritis with abundant eosinophil infiltrates and thrombosis in the portal vein branches. He was diagnosed with polyarteritis nodosa (PAN), and immunosuppressive therapy improved his condition. Two years later, the disease recurred with ischemic cutaneous lesions and marked eosinophilia. Our experience suggests that marked eosinophilia in PAN may imply severe organ involvement, including gastrointestinal necrosis, as well as the association of venous thrombosis.

Diagnostic Performance of a Temporal Artery Biopsy for the Diagnosis of Giant Cell Arteritis in Japan-A Single-center Retrospective Cohort Study.

Objectives To investigate the sensitivity and specificity of a temporal artery biopsy (TAB) in the diagnosis of giant cell arteritis (GCA) in a single-center retrospective cohort in Japan. Methods A retrospective chart review was performed on consecutive patients who visited our hospital between April 2009 and October 2018 and underwent a TAB. The sensitivity and specificity were calculated for the three pathological standards for a TAB, predetermined according to the pathological criterion of the 1990 American College of Rheumatology (ACR) criteria: A) vasculitis characterized by predominant mononuclear cell infiltration; B) vasculitis with granulomatous inflammation; and C) vasculitis with multinucleated giant cells. We also analyzed the clinical parameters predicting the diagnosis of GCA and the impact of a diagnostic delay of ≥3 months on cardiovascular complications of GCA. Results Our study population was 16 cases in the GCA group and 13 in the non-GCA group. The sensitivity and specificity for Standard A of a TAB were 81% and 85%, respectively, while those for stricter Standards B or C were identical, at 75% and 100%, respectively. These pathological standards, but not any other parameters, significantly predicted the diagnosis. A diagnostic delay tended to cause cardiovascular complications (p=0.057). Conclusion The sensitivity and specificity of the pathological standards of a TAB were favorable in our cohort and were the only predictors for the diagnosis of GCA. Considering the possible impact of a diagnostic delay on cardiovascular complications, the early recognition and prompt initiation of glucocorticoid therapy is needed, even in Japan, where GCA is uncommon.

Muscle weakness as a presenting symptom in ANCA-associated vasculitis.

Muscle weakness is rarely a presenting symptom of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), although the disease frequently involves the lungs, skin, neurons, and kidneys. Here we describe a case of AAV presenting with muscle weakness in which only muscle biopsy could confirm the diagnosis. The literature review, including three similar cases, suggested that patients with ANCA-associated muscle vasculitis likely had myalgia, normal levels of creatine kinase, pulmonary fibrosis, rheumatoid factor, and muscle edema on MRI.

Idiopathic Interstitial Pneumonia as a Possible Cause of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Case Report.

There are conflicting data to date on the causal relationship between idiopathic interstitial pneumonia and antineutrophil cytoplasmic antibody (ANCA): (1) myeloperoxidase-ANCA may play a pathogenetic role in pulmonary fibrosis, or (2) pulmonary fibrosis may induce production of the antibody. In this article, we describe a case of an elderly female patient with microscopic polyangiitis that developed after positive conversion of myeloperoxidase-ANCA during the course of idiopathic interstitial pneumonia. Our experience as well as similar case reports may suggest that idiopathic interstitial pneumonia may induce production of ANCAs and even ANCA-associated vasculitis.

Clinical value of autoantibodies for lupus myelitis and its subtypes: A systematic review.

OBJECTIVE: We conducted a systematic review to investigate the clinical value of clinical characteristics and autoantibodies, especially lupus-specific antibodies, for lupus myelitis and its subtypes. METHODS: We searched PubMed, EMBASE, and ICHUSHI without language restrictions for case reports or series of lupus myelitis. We focused on cases reported since 1997, when the revised classification criteria for systemic lupus erythematosus were published. Associations between patient characteristics including autoantibodies and functional outcome, survival, subtypes of myelitis (grey and white matter myelitis), and treatment were examined. We attempted to contact authors to supplement missing information for analysis. RESULTS: Our search identified 224 cases from 105 articles. White matter myelitis predicted favorable function (odds ratio = 15.18; 99% confidence interval, 3.09-151.31; p < 0.0001). Grey matter myelitis was associated with longitudinally extensive transverse myelitis (p < 0.001) and anti-double-stranded DNA (p = 0.003), and tended to be associated with anti-ß2-glycoprotein I (p = 0.011). White matter myelitis tended to be associated with optic neuritis and anti-neuromyelitis optica antibodies. Although our study might be susceptible to under-reporting of original cases and selection bias, we aimed to provide a conservative interpretation by setting the statistical significance threshold at p < 0.01. CONCLUSIONS: This systematic review confirmed that grey matter myelitis predicted poor functional outcome and was associated with longitudinally extensive transverse myelitis and anti-double-stranded DNA antibodies. White matter myelitis was associated with favorable functional outcomes and may partially represent a complication of neuromyelitis optica.