Serositis and lymphopenia are common features of systemic lupus erythematosus following SARS-CoV-2 infection: A case report and literature review.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect a number of human systems, including the respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems. These symptoms persist long after the acute infection has healed and is called "long COVID". Interestingly, there have been a series of reports that SARS-CoV-2 infections trigger the development of various autoimmune diseases such as systemic lupus erythematosus (SLE), inflammatory arthritis, myositis, vasculitis. Here, we report a novel case of SLE characterized by persistent pleural effusion and lymphopenia following SARS-CoV-2 infection. This is the first case in the Western Pacific region to our knowledge. Furthermore, we reviewed 10 similar cases including our case. By looking at the characteristics of each case, we found that serositis and lymphopenia are common features of SLE following SARS-CoV-2 infection. Our finding suggests that patients with prolonged pleural effusion and/or lymphopenia after COVID-19 should be checked for autoantibodies.

Gut dysbiosis is associated with aortic aneurysm formation and progression in Takayasu arteritis.

BACKGROUND: Takayasu arteritis (TAK) is an autoimmune large vessel vasculitis that affects the aorta and its major branches, eventually leading to the development of aortic aneurysm and vascular stenosis or occlusion. This retrospective and prospective study aimed to investigate whether the gut dysbiosis exists in patients with TAK and to identify specific gut microorganisms related to aortic aneurysm formation/progression in TAK. METHODS: We analysed the faecal microbiome of 76 patients with TAK and 56 healthy controls (HCs) using 16S ribosomal RNA sequencing. We examined the relationship between the composition of the gut microbiota and clinical parameters. RESULTS: The patients with TAK showed an altered gut microbiota with a higher abundance of oral-derived bacteria, such as Streptococcus and Campylobacter, regardless of the disease activity, than HCs. This increase was significantly associated with the administration of a proton pump inhibitor used for preventing gastric ulcers in patients treated with aspirin and glucocorticoids. Among patients taking a proton pump inhibitor, Campylobacter was more frequently detected in those who underwent vascular surgeries and endovascular therapy for aortic dilatation than in those who did not. Among the genus of Campylobacter, Campylobacter gracilis in the gut microbiome was significantly associated with clinical events related to aortic aneurysm formation/worsening in patients with TAK. In a prospective analysis, patients with a gut microbiome positive for Campylobacter were significantly more likely to require interventions for aortic dilatation than those who were negative for Campylobacter. Furthermore, patients with TAK who were positive for C. gracilis by polymerase chain reaction showed a tendency to have severe aortic aneurysms. CONCLUSIONS: A specific increase in oral-derived Campylobacter in the gut may be a novel predictor of aortic aneurysm formation/progression in patients with TAK.

Superior mesenteric vein thrombosis and osteoporotic vertebral fractures.

Superior mesenteric vein (SMV) thrombosis is relatively rare disease with unspecific symptoms. Thrombus formation within the SMV eventually leads to congestive intestinal necrosis. In most cases, the lack of specific symptoms makes early diagnosis difficult. Therefore, it is important to suspect the disease and actively investigate it, given a causative factor. Here, we report a case of SMV thrombosis with a novel predisposing factor, compression of SMV by deformed spine, found on contrast medium-enhanced computed tomography. Treatment with intravenous heparin followed by oral anticoagulants resulted in favorable outcome. This is the first picture showing the novel mechanism of SMV thrombus formation relating to spinal deformity. Treating osteoporosis before spinal deformity could prevent SMV thrombosis with such a mechanism.

A mechanistic target of rapamycin inhibitor, everolimus safely ameliorated lupus nephritis in a patient complicated with tuberous sclerosis.

A 26-year-old woman with tuberous sclerosis complex (TSC) received outpatient treatment for the complication of systemic lupus erythematosus (SLE) at our hospital. She visited our hospital with a chief complaint of pitting oedema in bilateral lower legs for 3 days. The urinalysis showed massive proteinuria with a lot of white blood cell casts. The blood tests revealed hypoalbuminaemia, hypercholesterolaemia, hypocomplementaemia, and elevated anti-double-stranded DNA antibody titre. Renal biopsy was not performed because of multiple renal angiomyolipomas, which was one of the features of TSC. She was diagnosed with a nephrotic state due to lupus nephritis. Although she had a standard therapy with high-dose corticosteroid and mycophenolate mofetil and tacrolimus, complete remission had not been achieved leading to a steroid-dependent nephrotic syndrome. During the follow-up, the angiomyolipomas became larger and had a risk of rupture at the age of 29 years. Everolimus, a mechanistic target of rapamycin (mTOR) inhibitor, was started for the treatment of angiomyolipomas, and mycophenolate mofetil and tacrolimus were terminated instead. The activity of lupus nephritis was surprisingly ameliorated, and the amount of corticosteroid successfully tapered. Everolimus has been continued for 6 years without severe side effects. Accumulating evidence suggests that the activated mTOR pathway plays a key role in the pathogenesis of SLE. We reported the long-term efficacy and safety of everolimus for refractory SLE in a patient with TSC for the first time. This case suggests that everolimus can be a promising option for the treatment of lupus nephritis.

Giant cell arteritis with cervical radiculopathy mimicking polymyalgia rheumatica and elderly-onset rheumatoid arthritis: a case report.

BACKGROUND: Giant cell arteritis has a wide variety of clinical symptoms, one of them being cervical radiculopathy, which mainly involves the C5 nerve root. If the patient does not develop typical clinical symptoms of giant cell arteritis but has C5 radiculopathy, it may be misdiagnosed as polymyalgia rheumatica or elderly-onset rheumatoid arthritis due to old age, high serum inflammatory markers, and difficulty in raising both upper limbs. CASE PRESENTATION: A 72-year-old Japanese man with a month-long history of dyspnea on exertion and with difficulty in raising both upper limbs was referred to our hospital because of elevated serum C-reactive protein (12.62 mg/dL). He had no typical symptoms of giant cell arteritis such as headache, jaw claudication, visual loss, and fever. The patient tested negative for rheumatoid factor and anti-cyclic citrullinated peptide antibody, and matrix metalloproteinase-3 was within the normal range (54.3 ng/mL). Musculoskeletal ultrasound examination showed absence of tenosynovitis, bursitis, and synovitis, and the patient did not meet the classification criteria of polymyalgia rheumatica or rheumatoid arthritis; hence, those two diseases were unlikely. A precise neurological examination suggested bilateral C5 and C6 anterior radiculopathy and left C4 radiculopathy. Since cervical magnetic resonance imaging showed no mechanical causality, cervical radiculopathy of unknown origin was suggested. Fluorodeoxyglucose positron emission tomography/computed tomography revealed increased fluorodeoxyglucose lineal uptake along the vessel walls, including temporal arteries, vertebral arteries, and axillary arteries. Results of the biopsy of the left superficial temporal artery were compatible with giant cell arteritis. He was successfully treated with 30 mg of prednisolone, and both upper limbs could be elevated. CONCLUSIONS: If the patient was misdiagnosed with polymyalgia rheumatica or elderly-onset rheumatoid arthritis based on only clinical symptoms and laboratory data, his symptoms might not improve due to insufficient steroid dose and vascular complications may occur later. Although rare, peripheral neuropathy in giant cell arteritis may include cervical radiculopathy. The musculoskeletal ultrasound and precise neurological examination were the turning points for the diagnosis of this case, and making a careful diagnosis using these methods was important.

Spontaneous regression of lung metastases after transarterial chemoembolization for hepatocellular carcinoma.

Spontaneous regressions of primary and/or metastatic lesions have been rarely reported in hepatocellular carcinoma (HCC). Herein, we report the case of a 71-year-old man with HCC, focusing on shape changes of lung metastases over time. Lung metastasis of HCC was histologically diagnosed by percutaneous computed tomography (CT)-guided needle biopsy after the treatment of primary HCC lesion. Lung lesions had been observed on enhanced contrast computed tomography for >3 years without any local or systemic treatment for them. During this period, treatments including surgical procedure for relapsed bladder cancer and transarterial chemoembolization for HCC were performed. Metastatic lung lesions immediately regressed after these treatments. Therefore, accumulation of such cases may help elucidate spontaneous regression mechanisms in primary HCC or its lung metastases.

Evaluation of changes in oral health-related quality of life over time in patients with Sjögren's syndrome.

OBJECTIVES: To assess oral health-related quality of life (OHRQoL) and changes in OHRQoL in 3 years of patients with Sjögren's symdrome (SS). METHODS: Thirty-five SS patients and 23 non-SS individuals were enrolled. OHRQoL were quantitatively evaluated using the shortened Oral Health Impact Profile (OHIP-14). After 3 years, 22 patients and 14 controls tool the OHIP-14 survey again. RESULTS: The SS group had a significantly higher OHIP-14 score, which indicated a lower OHRQoL, than the non-SS group. Among individual questions in the OHIP-14, scores for 'trouble pronouncing words', 'uncomfortable to eat foods', 'self-conscious', and 'diet unsatisfactory' were markedly higher in the SS group than in the non-SS group. The OHIP-14 score significantly increased in 3 years in the SS group. Furthermore, there was an inverse correlation between the change rate of salivary flow rate and change of OHIP-14 scores in 3 years in patients with SS whose OHIP-14 score increased. Scores for 'irritable with other people', 'difficulty doing usual jobs', 'felt life less satisfying', and 'unable to function' significantly increased in 3 years. CONCLUSION: In SS, OHRQoL decreased in 3 years, which was associated with a decrease in saliva secretion. Moreover, troubles related to psychosocial aspects in SS patients were found to intensify over time.

Impact of adding tacrolimus to initial treatment of interstitial pneumonitis in polymyositis/dermatomyositis: a single-arm clinical trial.

OBJECTIVE: Interstitial pneumonia is common and has high short-term mortality in patients with PM and DM despite glucocorticoid (GC) treatment. Retrospective studies suggested that the early use of immunosuppressive drugs with GCs might improve its short-term mortality. METHODS: A multicentre, single-arm, 52-week-long clinical trial was performed to test whether the initial combination treatment with tacrolimus (0.075 mg/kg/day, adjusted for the target whole-blood trough levels between 5 and 10 ng/ml) and GCs (0.6-1.0 mg/kg/day of prednisolone followed by a slow taper) improves short-term mortality of PM/DM-interstitial pneumonia patients. The primary outcome was overall survival. We originally intended to compare, by using propensity-score matching, the outcome data of clinical trial patients with that of historical control patients who were initially treated with GCs alone. RESULTS: The 52-week survival rate with the combination treatment (N = 26) was 88.0% (95% CI, 67.3, 96.0). Safety profiles of the combination treatment were consistent with those known for tacrolimus and high-dose GCs individually. Serious adverse events occurred in 11 patients (44.0%), which included four opportunistic infections. Only 16 patients, including only 1 deceased patient, were registered as historical controls, which precluded meaningful comparative analysis against the clinical trial patients. CONCLUSION: Our study provided findings which suggest that initial treatment with tacrolimus and GCs may improve short-term mortality of PM/DM-interstitial pneumonia patients with manageable safety profiles. This was the first prospective clinical investigation conducted according to the Good Clinical Practice Guideline of the International Conference on Harmonization for the treatment of this potentially life-threatening disease. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT00504348.

Deterioration in saliva quality in patients with Sjögren's syndrome: impact of decrease in salivary epidermal growth factor on the severity of intraoral manifestations.

BACKGROUND: Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease characterized by lymphocytic infiltration of the exocrine glands, especially the salivary and lacrimal glands. As a result of salivary gland dysfunction, most patients with SS have xerostomia related to a reduced salivary flow rate. In addition to the discomfort due to xerostomia, dry mouth can cause various intraoral manifestations such as refractory stomatitis, ulcer, and atrophic changes in the oral mucosa and tongue, and the patient's quality of life (QoL) is severely impaired. These manifestations are believed to be caused mainly by a decrease in the clearance in the oral cavity owing to hyposalivation. However, because saliva has several beneficial physiological effects on the intraoral environment, qualitative changes in sialochemistry should also be considered a cause of the refractory intraoral manifestations in SS. MAIN TEXT: Salivary epidermal growth factor (EGF) is considered an important cytoprotective factor against injuries. It contributes to wound healing in the oral cavity and to maintenance of mucosal integrity in the oral cavity and gastrointestinal tract. We evaluated changes in salivary EGF levels and assessed the association between salivary EGF levels and the severity of intraoral manifestations in patients with SS. The following novel findings were obtained: (1) salivary EGF levels in SS patients were significantly lower than those in non-SS patients; (2) salivary EGF levels as well as the salivary flow rate decreased with the progression of SS; (3) with prolonged SS disease duration, salivary EGF levels decreased more rapidly than the salivary flow rate; and (4) decreases in salivary EGF levels significantly correlated with exacerbation of the oral health-related QoL in patients with SS. CONCLUSIONS: The deterioration in saliva quality as well as lower intraoral clearance by hyposalivation could play a role in the pathogenesis of refractory intraoral manifestations in patients with SS. Our findings suggest a new target for therapeutic intervention for SS.

Hemophagocytic lymphohistiocytosis with leukoencephalopathy in a patient with dermatomyositis accompanied with peripheral T-cell lymphoma: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis associated with autoimmune diseases is seen in patients with systemic juvenile idiopathic arthritis, adult-onset Still's disease, and systemic lupus erythematosus, whereas it is rarely seen in patients with dermatomyositis. In addition, central nervous system involvement with dermatomyositis is rare. To the best of our knowledge, this is the first case of hemophagocytic lymphohistiocytosis complicated by leukoencephalopathy in a patient with dermatomyositis accompanied with peripheral T-cell lymphoma. CASE PRESENTATION: A 17-year-old Asian male adolescent with dermatomyositis and hemophagocytic lymphohistiocytosis that were controlled with corticosteroid therapy presented to our hospital with high fever and altered consciousness. Brain magnetic resonance imaging revealed multiple cerebral lesions. We diagnosed the central nervous system lesions as leukoencephalopathy secondary to dermatomyositis and hemophagocytic lymphohistiocytosis. Because corticosteroid and cyclophosphamide pulse therapy was ineffective, he was treated with a modified hemophagocytic lymphohistiocytosis-2004 protocol, which resulted in the disappearance of the lesions of his central nervous system. CONCLUSIONS: Our findings suggest that the hemophagocytic lymphohistiocytosis-2004 protocol including etoposide should be initiated immediately in patients with hemophagocytic lymphohistiocytosis who respond poorly to treatment for the underlying disease. Moreover, irrespective of the underlying disease, patients with hemophagocytic lymphohistiocytosis with central nervous system lesions might require bone marrow transplantation.

Salivary epidermal growth factor (EGF) in Sjögren's syndrome: association between salivary EGF levels and the severity of intraoral manifestations.

Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease characterized by lymphocytic infiltration of the exocrine glands, especially the salivary and lacrimal glands. As a result of salivary gland dysfunction, most patients with SS have xerostomia, related to a reduced salivary flow rate. In addition to the discomfort due to xerostomia, dry mouth can cause various intraoral manifestations such as refractory stomatitis, ulcer and atrophic changes in the oral mucosa and tongue, and patients' quality of life (QOL) is impaired severely. These manifestations are believed to be caused mainly by a decrease in the clearance in the oral cavity owing to hyposalivation. However, since saliva has several beneficial physiological effects on the intraoral environment, qualitative changes in sialochemistry should also be considered a cause of the refractory intraoral manifestations in SS. Salivary epidermal growth factor (EGF) is considered an important cytoprotective factor against injuries, and it contributes to wound healing in the oral cavity. We evaluated changes in salivary EGF levels and assessed the association between salivary EGF levels and the severity of intraoral manifestations in SS patients. The results showed that the salivary EGF levels decreased with the progression of SS, and this deterioration in saliva quality as well as hyposalivation could play a role in the pathogenesis of refractory intraoral manifestations in SS patients. Our findings provide new target for therapeutic intervention in SS.

Rapid decrease in salivary epidermal growth factor levels in patients with Sjögren's syndrome: A 3-year follow-up study.

OBJECTIVES: To assess changes in salivary epidermal growth factor (EGF) levels within three years and investigate the correlation between these changes and the severity of intraoral manifestations in patients with Sjögren's syndrome (SS). METHODS: Twenty-three SS patients (14 primary SS and 9 secondary SS) and 14 controls were followed up for three years. Salivary EGF concentration was measured using an enzyme-linked immunosorbent assay, and intraoral manifestations were evaluated using a short version of the Oral Health Impact Profile (OHIP-14). Changes in salivary flow rate, EGF level, and severity of intraoral manifestations were analyzed, along with associations among them. RESULTS: The OHIP-14 score significantly increased and the total salivary EGF output significantly decreased after three years in the SS group (10.2 ± 8.8 vs. 12.6 ± 9.2, p = 0.040; 10158.4 ± 9820.9 vs. 8352.8 ± 7813.3 pg/10 min, p = 0.032), though the salivary flow rate did not change. The decrease in total EGF output was especially high in patients with long disease duration and poor oral health-related quality of life (OHRQoL). In patients with poor OHRQoL, the change in total EGF output significantly correlated with the OHIP-14 score (r = - 0.847, p = 0.008). However, there was no correlation between the change in salivary flow rate and the OHIP-14 score. CONCLUSIONS: The rapid decrease in salivary EGF level contributes to the progression of intraoral manifestations of SS.

Correlation between salivary epidermal growth factor levels and refractory intraoral manifestations in patients with Sjögren's syndrome.

OBJECTIVE: To assess changes in salivary epidermal growth factor (EGF) levels and the correlation between these levels and the severity of intraoral manifestations in Sjögren's syndrome (SS). METHODS: Forty SS patients and 23 controls were enrolled. Salivary EGF concentration was measured using an enzyme-linked immunosorbent assay, and intraoral manifestations were evaluated using a short version of the Oral Health Impact Profile (OHIP-14). The associations among salivary flow rate, EGF levels and the severity of intraoral manifestations were analyzed. RESULTS: The total salivary EGF output was significantly decreased in the SS patients compared with the controls (9237.6 ± 8447.0 vs. 13296.9 ± 7907.1 pg/10 min, respectively, p = 0.033). In the SS patients, total EGF output and salivary flow rate showed a strong positive correlation (rs = 0.824, p = 0.0005), while total EGF output and disease duration showed a negative correlation (rs = -0.484, p = 0.008). Further, total EGF output was significantly correlated with the OHIP-14 score (rs = -0.721, p = 0.012). CONCLUSIONS: The salivary flow rate and EGF levels are decreased in SS, and this deterioration in saliva quality causes refractory intraoral manifestations. Our findings have provided new therapeutic targets for SS.

Baseline anti-citrullinated peptide antibody (ACPA) titers and serum interleukin-6 (IL-6) levels possibly predict progression of bone destruction in early stages of rheumatoid arthritis (ERA).

A prospective study was made to seek for a convenient biomarker to predict progression of bone destruction (PBD) in early stages of rheumatoid arthritis (ERA). All participated patients had definite RA and their radiographic stages were mild less than stage II of the Steinbrocker classification, naïve for treatment of any DMARDs or corticosteroids. After the entry, they were treated according to the 2002 ACR management guideline for RA. The candidate biomarkers (RF-IgM, RF-IgG, CARF, ACPA, CRP, ESR, NTx, MMP-3, IL-6 and osteopontin) were measured at the entry. PBD was assessed radiographically by interval changes in the modified Sharp scores (ΔSHS) for 24 months. The associations between ΔSHS and baseline biomarkers were assessed statistically by multivariate regression analyses. Both the baseline ACPA and IL-6 levels correlated with PBD, suggesting that they could predict PBD in ERA.

Spontaneous perirenal hematoma due to Wegener's granulomatosis after initiation of immunosuppressant.

Spontaneous perirenal hematoma (SPH) is a rare, life-threatening condition. We present a patient with Wegener's granulomatosis (WG) who developed SPH soon after the initiation of immunosuppressant therapy. Few cases of SPH as a complication of WG have been reported, though a rupture of an aneurysm in patients with polyarteritis nodosa can lead to SPH. Though immunosuppressant therapy is considered to be the first-line therapy for SPH with vasculitis, SPH could still occur after the initiation of an adequate treatment regimen.

[Construction of a system for proper TS-1 application].

TS-1 is an oral anti-tumor drug, which contains 5-chloro-2, 4-dihydroxypyridine (CDHP), a compound mainly excreted in urine. Since the CDHP concentration is increased among patients with impaired renal function, the frequency of side effects of TS-1 increases in such patients. Therefore, we constructed a computer-aided system that enables prompt monitoring of creatinine clearance (Ccr) calculated from the serum creatinine levels of patients prescribed TS-1 at the time pharmacists prepare the medicine. With this system, we found two cases who were prescribed TS-1, despite their decreased Ccr. One was a patient whose estimated Ccr was less than 30 mL/min/m2. With such renal malfunction, pharmacokinetics of the drug was considerably changed compared with normal control, and the dosage should be reduced. The other case presented with severe jaundice and had only a mild decrease of renal function (Ccr: 50 mL/min/m2). So we measured the concentration of uracil in the urine and performed a drug lymphocyte stimulation test for further investigation of concomitant affecting factors. Our system is useful because it can show pharmacists both the dosage TS-1 patients take and their renal function at a glance in real time. This system can be adapted for every medicine which might accumulate in patients with renal dysfunction.

A case of Mikulicz's disease with Th2-biased cytokine profile: possible feature discriminable from Sjögren's syndrome.

This article concerns a male patient with Mikulicz's disease (MD) accompanied with marked elevation of serum immunoglobulin (Ig)G4 and IgE levels. His peripheral blood mononuclear cells (PBMC) showed markedly enhanced in vitro production of interleukin (IL)-4, IL-5, IL-13, but not interferon gamma (IFN-gamma) compared with patients with Sjögren's syndrome (SS) and healthy donors, suggesting distinct Th2 bias in this MD patient. Besides the prominent infiltration of IgG4-producing plasma cells, the enhanced expression of both CD40 and CD40 ligand (CD40L) were observed in the swollen salivary gland of the MD patient, suggesting enhanced signaling pathways for the induction of IgG4 and IgE switching. Possible differences between MD and SS in light of their underlying pathogenesis are discussed.

[Clinical pathway for management of patients with acute asthma attack].

BACKGROUND: There have been few reports of clinical pathway (CP) for treatment of asthma attack, because patients with asthma always admit emergently and the severity varies. We introduced CP so that standard asthma treatment can be widely used, and investigated its clinical usefulness. METHODS: We designed a new CP for treating asthma attack according to the guideline (Japanese guideline (JGL) and Global Initiative for Asthma (GINA)). 136 patients who admitted to our hospital due to asthma attack from January 1999 to November 2006, were enrolled our study. Excluding cases complicated with pneumonia, COPD or cardiac failure, we evaluated 46 cases treated with the CP comparing with 19 cases treated without the CP. The clinical evaluations include systemic and inhaled steroid use, FEV1.0%, history of asthma, and the duration of asthma attack. Furthermore, we investigated difference between cases with and without prolonged admission. RESULTS: While the rates of systemic and inhaled steroid use in cases without the CP were 57.9% and 52.6% respectively, those in cases with the CP were approximately 100%. Employing the CP, FEV 1.0% at discharge time was elevated from 71.7% to 76.3% and the duration of hospitalization was shortened from 14.2 days to 11.5 days. Mean age of the cases with prolonged admission was higher than the rest. CONCLUSION: The asthma CP is an effective way for the standard treatment according to the guideline to be used widely even by doctors who are not familiar with asthma treatment. It improves the efficacy of in-hospital treatment.