Streptococcus agalactiae pyomyositis in a patient with primary biliary cholangitis: A case report.

Pyomyositis is an uncommon clinical scenario; it is usually associated with predisposing factors, including poorly controlled diabetes mellitus, trauma history, and immunocompromise. We discuss the case of an elderly woman with a 20-year history of diabetes mellitus and remissive breast cancer after modified radical mastectomy and subsequent chemotherapy 28 years previously. The patient presented with severe shoulder pain and gradual swelling. After examination, pyomyositis was diagnosed and debridement surgery was performed. Culture of the wound samples showed the growth of Streptococcus agalactiae. During hospitalization, primary biliary cholangitis (PBC) was diagnosed incidentally, accompanied by poor glycemic control. After treatment with antibiotics for pyomyositis and ursodeoxycholic acid for PBC, the infection resolved in 8 weeks, and her glycemic control was improved after PBC treatment. It is possible that the long-term untreated PBC worsened insulin resistance and aggravated diabetes mellitus in this patient. To the best of our knowledge, this is the first reported case of pyomyositis caused by an unusual pathogen, S. agalactiae, in a patient with newly diagnosed PBC.

Corticosteroid-Induced Liver Injury in Adult-Onset Still's Disease.

Background and Objectives: Adult-onset Still's disease (AOSD) is a rheumatic disease characterized by systemic inflammatory symptoms, including intermittent spiking fever, polyarthritis and a distinctive salmon-colored rash. Corticosteroids are the first-line treatment for AOSD. However, corticosteroids are potentially hepatotoxic in certain cases and may complicate the course of the disease. Materials and Methods: A 29-year-old female suffering from fever of unknown origin for two weeks was diagnosed with AOSD according to Yamaguchi's criteria. She received corticosteroids as the first-line treatment for AOSD and developed acute severe hepatitis. A diagnostic protocol has been performed. Results: Corticosteroid-induced liver injury was confirmed by clinical observation and rechallenge of the drug in this case. The result of liver biopsy also supported the diagnosis. Mycophenolic acid, a disease-modifying antirheumatic drug (DMARD) was chosen as an alternative treatment. AOSD remission was achieved under this treatment after three months. Conclusions: Severe acute hepatitis induced by corticosteroids, although very rare, may be observed in patients with AOSD. Drug-induced liver injury needs to be kept in mind when unexpected acute hepatitis is found. Mycophenolic acid could be a proper substitute medication in these cases.

Thymoma-Related Paraneoplastic Syndrome Mimicking Reactive Arthritis.

Background and Objectives: Thymomas are associated with a high frequency of paraneoplastic manifestations. Paraneoplastic syndrome (PNS) with thymoma presents a challenge to clinicians because of the need to decipher the association between the presenting symptoms and the underlying tumor. The condition most commonly noted in patients with PNS with thymoma is myasthenia gravis. Other common autoimmune diseases that may present as PNS include systemic lupus erythematosus, pure red cell aplasia, and Good syndrome. Seventy-six percent of patients with PNS-associated thymoma experience resolution of PNS after curing thymoma. Materials and Methods: A 37-year-old man with a two-month fever accompanied by polyarthritis accidently found thymoma after contrast computed tomography scans of his chest. He accepted Video assisted thoracoscopic surgery with resection of thymoma. Results: Fever and polyarthritis resolved after operation but recurred in five days due to cytomegalovirus viremia, which might be predisposed by previous antibiotics treatment before the diagnosis of thymoma. Conclusion: Patients with a thymoma also have a high frequency of PNS, and the most frequent condition found in patients with PNS-associated thymoma is myasthenia gravis. Fever with polyarthritis has been rarely reported as a symptom of PNS-associated thymoma. Here we reported an unusual case of PNS mimicking reactive arthritis with thymoma, as diagnosed based on the patient's clinical progression, imaging examination, and laboratory tests. The patient died of his comorbidities, and his death may have been related to long-term antibiotic use and consequent intestinal dysbiosis. This challenging case may help to inform clinicians of the need for detailed work-up of fever with unknown origin in the presence of chronic polyarthritis to prevent the overdiagnosis of inflammatory arthritis or rheumatic disease and avoid further comorbidities. Detailed work-up should include the patient's history of infections, inflammation, and malignant or nonmalignant tumors.

Application of classification criteria of Sjogren syndrome in patients with sicca symptoms: Real-world experience at a medical center.

BACKGROUND: Patients who have symptoms of sicca, such as dry eyes and mouth, may have Sjögren's syndrome (SS). However, the conservative culture makes patients hesitate to undergo an invasive biopsy, which contributes to the difficulty of confirming a diagnosis. We aimed to identify the characteristics of patients with sicca symptoms to develop a better predictive value for each item included in the three different diagnostic criteria for SS and clarify the best diagnostic tools for the local population. METHODS: This is a single-center retrospective case-control study from January 2016 to December 2017. Patients who underwent sialoscintigraphy because of clinical symptoms of xerostomia and xerophthalmia at one medical center were reviewed via the patients' electronic medical records. RESULTS: Of 515 patients enrolled, the severity of results for sialoscintigraphy and Schirmer's test was correlated with a diagnosis of SS and generated receiver operator characteristic curve. The area under curve (AUC) was 0.603 for positive Schirmer's test, 0.687 for positive anti-Ro/La results, 0.893 for a positive salivary gland biopsy. The AUC was 0.626 and 0.602 for Schirmer's test which is redefined as <10 mm/5 minutes in either eye and according to 2016 the American College of Rheumatology/ European League Against Rheumatism criteria, respectively. CONCLUSION: Our results indicate the cut-off point for defining a positive test result in the Schirmer's test is worth modified to <10 mm/5 minutes in either eye.

Interleukin-6 and interleukin-17 are related to depression in patients with rheumatoid arthritis.

AIM: Mood disorders are a serious issue for patients with rheumatoid arthritis (RA) because poor mental health can exacerbate the disease course. This study aimed to identify the effect of proinflammatory cytokines on the mood of patients with RA. METHODS: This study was conducted at a rheumatology clinic in Northern Taiwan. In total, 113 patients with RA and 42 healthy controls were assessed for anxiety and depression symptoms using Hospital Anxiety and Depression Scale (HADS). RA was assessed using the Disease Activity Score of 28 joints (DAS28). Serum proinflammatory cytokine levels, including interleukin (IL)-1ß, IL-6, IL-17 and tumor necrosis factor alpha (TNF-α) were measured and compared between different patient groups according to disease activity and pain level. RESULTS: Serum IL-1ß, IL-6, IL-17 and TNF-α levels were significantly higher in patients with RA than in healthy controls, as were the mean anxiety and depression subscale scores. In patients with RA who had different disease activities, pain severity correlated with both anxiety and depression symptoms. When HADS scores were analyzed according to pain levels, age was correlated with depression in the severe pain group. In the mild pain group, patients with higher IL-6 or higher IL-17 had a higher risk of depression. There was no correlation between mood symptoms and cytokine levels in healthy controls. CONCLUSION: Elevated serum IL-6 and IL-17 levels in patients with RA induce arthritis and cause mood symptoms, especially depression symptoms.

The increase in total knee replacement surgery in Taiwan: A 15-year retrospective study.

Total knee replacement (TKR) is considered as one of the most success among clinical interventions for patients with who suffering from knee osteoarthritis (OA). We sought to estimate the incidence of TKR using demographics, incidence rates, lengths of hospital stay, and costs from 1996 to 2010 by analyzing Taiwan's National Health Insurance Research Database. A total of 154,553 patients obtained primary TKR surgery between 1996 and 2010. The diagnosis code for knee OA and the procedure code for TKR were selected from the records. To compare the rate of TKR between covariables, we calculated the TKR risk ratios and 95% confidence interval (CI) of these variables (gender, age, age group, and primary diagnoses). A 2-tailed P-value of .05 was considered statistically significant. The statistical package SPSS version 20.0 (SPSS, Chicago, IL) was used to conduct all the statistical analyzes. We analyzed 154,553 TKRs performed by surgeons in Taiwan from 1996 to 2010. The overall crude incidence increased from 26.4 to 74.55 TKR per 100,000 inhabitants from 1996 to 2010. TKR incidence for the 70 to 79 years age group increased from 227 to 505 per 100,000 people from 1996 to 2010. The age-standardized rate ratios for TKR of women to men ranged from 2.5 to 3.0. The mean average length of stay in hospital was 15 days in 1996 and decreased to 8 days in 2010. During the study period, the adjusted mean cost per patient decreased from US$7485 to US$4827. Health expenditures for TKR were 5% of total National Health Insurance expenditure every year. Over the 15-year period, Taiwan's TKR incidence tripled, which is consistent with population ageing. Arthritis will be a major public health issue in the ageing population in the future.

Multidrug-resistance Acinetobacter baumannii pneumonia in a rheumatoid arthritis patient receiving tumor necrosis factor inhibitor: A case report.

INTRODUCTION: Multidrug-resistant Acinetobacter baumannii (MDRAB) pneumonia with severe sepsis in a patient with rheumatoid arthritis (RA), who is predisposed after treatment with tumor necrosis factor inhibitor (TNFI), is a rare severe infection and can be successfully treated with prompt antibiotics. CASE PRESENTATION: A 75-year-old woman was diagnosed with RA >30 years previously. After inadequate treatment responses to conventional disease-modifying antirheumatic drugs (DMARDs), she developed progressive RA, including swollen joints in both hands, and had a high disease activity score of 4.96 when presenting at our rheumatology clinic. She had started taking the TNFI, golimumab (50 mg/month), 3 years before and developed a productive cough 4 weeks before this admission. One week after admission, she developed fever, dyspnea, hypoxemia, tachycardia, and increased serum C-reactive protein level. DIAGNOSIS: Chest plain film (CxR) and computed tomography of the chest showed hospital-acquired pneumonia; microbial examination of the sputum showed the presence of MDRAB. THERAPEUTICS: She was prescribed a full course of antibiotics with cefoperazone sulbactam. OUTCOMES: CxR showed complete remission of pneumonia. CONCLUSION: Biological DMARDs, such as TNFI, act as a double-edged sword: these drugs are used to treat autoimmune diseases, but they increase the risk of infection. The trend toward antibiotic resistance and persistent environmental survival of MDRAB is an emerging problem in countries with high rates of antibiotic abuse. TNFI may affect intestinal immunity by inducing dysbiosis, which affects T helper 17-mediated mucosal immunity and can contribute to A baumannii colonization and the development of MDRAB in frequently hospitalized patients.

Treatment of multiple refractory ankle ulcerations in thromboangiitis obliterans: A case report.

RATIONALE: Thromboangiitis obliterans (TAOs, or Buerger's disease) present as a non-atherosclerotic segmental occlusive vasculitis within medium- and small-sized blood vessels. TAO frequently occurs in young adults and is associated with cigarette smoking. At present, there are no accurately defined treatments for TAO. PATIENT CONCERNS: A 34-year-old Asian woman with a 20-year history of heavy cigarette smoking and recurrent, small, and self-limited lower limb ulcerations since adolescence, presented with persisting unhealed ulcerations on both ankles for 6 months. Her wound healing response was poor following the 2-month administration of colchicine, prednisolone, hydroxychloroquine, and mycophenolic acid. DIAGNOSIS: The patient was diagnosed with TAO with hyperimmunoglobulin E and refractory ulcerations on her ankles. INTERVENTIONS: The patient received monthly omalizumab (300 mg) and previous medications for 2 months and shifted to omalizumab and colchicine without mycophenolic acid and hydroxychloroquine because of onychomadesis, which was considered to be a possible adverse drug reaction. OUTCOMES: The wounds healed almost completely. The administration of omalizumab and colchicine will be continued until they the wounds are fully healed. LESSONS: Mycophenolic acid has a limited function in TAO treatment, especially in cases of refractory skin ulcerations. Omalizumab can be a valuable treatment option for patients with TAO and hyperimmunoglobulin E.

Combination of resveratrol-containing collagen with adipose stem cells for craniofacial tissue-engineering applications.

Repair and regeneration of craniofacial tissues is particularly challenging because they comprise a complex structure of hard and soft tissues involved in intricate functions. This study combined collagen scaffolds and human adipose stem cells (hASCs) for oral mucosal and calvarial bone regeneration by using resveratrol (RSV), which affects the differentiation of mesenchymal stem cells. We have evaluated the effect of collagen scaffold-containing RSV (collagen/RSV) scaffolds both in vitro and in vivo for their wound healing and bone regeneration potential. Scanning electron microscopy and immunostaining results reveal that hASCs adhere well to and proliferate on both collagen scaffolds and collagen/RSV scaffolds. Oral mucosal lesion experiments demonstrated that the collagen/RSV scaffold is more effective in wound closure and contraction than the collagen scaffold. The micro-computed tomography (µCT) images of calvarial bone display regenerating bone in defects covered with hASCs on collagen/RSV scaffolds that are more visible than that in defects covered with hASCs on a collagen scaffolds. RSV was more effective at inducing hASC differentiation on the collagen scaffold, suggesting that collagen/RSV scaffolds can provide useful biological cues that stimulate craniofacial tissue formation.

Predictable biomarkers of developing lymphoma in patients with Sjögren syndrome: a nationwide population-based cohort study.

Sjögren syndrome (SS) is commonly known to be correlated with lymphoma. This study included 16,396 individuals in the SS cohort and 65,584 individuals in the non-SS cohort, all of whom were enrolled in the Taiwan National Health Insurance database between 2000 and 2010. We evaluated the risk factors of non-Hodgkin's lymphoma (NHL) in the primary SS cohort by applying a Cox multivariable proportional-hazards model. We increased the correlation of patients with SS and NHL, with an adjusted HR of 4.314 (95% CI 2.784 - 6.685). Of the 16,396 SS patients, 66 individuals had salivary gland slices without NHL development, while the other 16,330 individuals that did not have salivary gland slices revealed 30 individuals that developed NHL. Of the 16,396 SS patients, 128 individuals underwent immunomodulator agent therapy (including hydroxychloroquine, azathioprine, cyclosporine, methotrexate, and rituximab) without NHL development. None of the 30 individuals that developed NHL from SS received immunomodulator agents. We found that patients with SS were at an increased risk of developing NHL, with the most common NHL subgroup being diffused large B-cell lymphoma. SS patients who were candidates for salivary gland slices or immunomodulator agents were associated with a lower risk of developing lymphoma over time. We recommend that patients at a higher risk upon diagnosis of SS receive close follow-up and aggressive treatment.

Gene-gene interactions between TGF-ß/Smad3 signalling pathway polymorphisms affect susceptibility to knee osteoarthritis.

OBJECTIVE: Transforming growth factor/Smad family member 3 (TGF)-ß/Smad3 signalling is essential for maintaining articular cartilage. A relationship between the genetic variants of TGF-ß itself, TGF-ß signalling and binding molecules, and osteoarthritis (OA) has been reported. Although variants of candidate genes have become prime targets for genetic analysis, their detailed interplay has not been documented. Our goal was to establish whether single nucleotide polymorphisms (SNPs) of TGF-ß1, TGF-ßRI, Smad3 and tissue inhibitor of metalloproteinases 3 (TIMP3), and their interactions, are associated with knee OA. DESIGN: We performed a case-control association study and genotyped 518 knee patients with OA and 468 healthy controls. All participants were genotyped for TGF-ß1 (rs1800469C/T), TGF-ßRI (rs1590A/G), Smad3 (rs12901499A/G and rs6494629T/C), and TIMP3 (rs715572G/A and rs1962223G/C) polymorphisms by polymerase chain reaction-restriction fragment length polymorphism analysis. Multifactor dimensionality reduction (MDR) was used to identify gene-gene interactions. RESULTS: Significant associations were observed for TIMP3 rs715572G/A polymorphisms in knee patients with OA and healthy individuals. The GA heterozygote in TIMP3 (rs715572G/A) was significantly associated with OA (p=0.007). Patient stratification using the Kellgren-Lawrence grading scale showed significant differences in TIMP3 rs715572G/A genotypes between grade 4 knee OA and controls. By MDR analysis, a two-locus model (Smad3 rs6494629T/C and TIMP3 rs715572G/A) of gene-gene interaction was the best for predicting knee OA risk, and its maximum testing accuracy was 57.55% and maximum cross-validation consistency was 10/10. CONCLUSIONS: TIMP3 rs715572G/A is a candidate protective gene for severe knee OA. Gene-gene interactions between Smad3 rs6494629T/C and TIMP3 rs715572G/A polymorphisms may play more important protective roles in knee OA.

Kimura's disease associated necrotizing eosinophilic vasculitis presenting with recurrent peripheral arterial occlusive disease: a case report and review of the literature.

A 33-year-old Chinese man with 9-year history of Kimura's disease (KD) was admitted with a 1-month history of recurrent claudication. He did not have any clinical discomfort and had not taken any preventive medication in the past. He accepted percutaneous transluminal angioplasty and the pathologic diagnosis was reportedly consistent with necrotizing eosinophilic vasculitis. This is the rare reported case of KD associated necrotizing eosinophilic vasculitis presenting with recurrent peripheral arterial occlusive disease and the difficulties encountered in establishing an accurate diagnosis with unusual presentations. This case also highlights the possibility of recurrent complications without aggressive medical treatment in such unusual eosinophilic disorders.

Clinical dilemma over low-dose methotrexate therapy in dialysis patients: a case report and review of literature.

Myelosuppression is the life-threatening adverse effect of methotrexate. Impaired kidney function is a major aggravating factor of methotrexate-induced myelosuppression. In end-stage renal disease patients, methotrexate therapy must be with cautious because the efficacy of removal of methotrexate by means of dialysis is in doubt. In clinical practice, low-dose methotrexate is still used by clinicians in treatment of dialysis patients with immunological disorders. We reported a 61-year-old woman on continued ambulatory peritoneal dialysis who developed pancytopenia with a nadir leukocyte count of 0.03 x 109/L, leading to severe sepsis after 3 doses of methotrexate, 7.5 mg weekly. We highlighted that methotrexate therapy in dialysis patients, even with low doses could impose the risk of myelosuppression, causing a fatal outcome. Alternative medications to methotrexate might be recommended in dialysis patients.

Heart blockage in a patient with cavitary lung lesions.

Cavitary lesions on a chest radiograph can be the manifestations of various diseases. The etiologies include abscess, mycobacterial infections, fungal infections, parasite infection, cavitary tumors, septic pulmonary embolism and vasculitis. While in comparison with the causes that could simultaneously develop a complete heart block, the differential diagnosis is limited. A 43-year-old man presented to the emergency department with a two-week history of dry cough, chest tightness and presyncopal symptoms.A chest radiograph showed patchy opacities in both lower lungs. A computed tomography of the chest revealed cavitary lesions bilaterally. The electrocardiogram showed a complete atrioventricular block. He was later diagnosed with Wegener's granulomatosis that involved nose, lung and heart. Cardiac involvements are not rare in Wegener's granulomatosis, but are not usually clinically apparent. A complete atrioventricular block is a rare but treatable manifestation of cardiac involvement usually indicating early active systemic disease. Patients presenting with cardiac abnormalities and evidence of systemic inflammation should be screened for Wegener's by history, radiographic and laboratory assessment.

Epigallocatechin-3-gallate prevents lupus nephritis development in mice via enhancing the Nrf2 antioxidant pathway and inhibiting NLRP3 inflammasome activation.

Patients with lupus nephritis show an impaired oxidative status and increased levels of interleukin (IL)-1ß and IL-18, which are closely linked to inflammation and correlated with disease activity. Although epigallocatechin-3-gallate (EGCG), the major bioactive polyphenol present in green tea with antioxidant and free radical scavenging activities, has been reported to have anti-inflammatory effects by inhibiting nuclear factor-kappa B (NF-κB)-mediated inflammatory responses in vivo, its effectiveness for the treatment of lupus nephritis is still unknown. In the present study, 12-week-old New Zealand black/white (NZB/W) F1 lupus-prone mice were treated daily with EGCG by gavage until sacrificed at 34 weeks old for clinical, pathological, and mechanistic evaluation. We found that the administration (1) prevented proteinuria, renal function impairment, and severe renal lesions; (2) increased renal nuclear factor E2-related factor 2 (Nrf2) and glutathione peroxidase activity; (3) reduced renal oxidative stress, NF-κB activation, and NLRP3 mRNA/protein expression and protein levels of mature caspase-1, IL-1ß, and IL-18; and (4) enhanced splenic regulatory T (Treg) cell activity. Our data clearly demonstrate that EGCG has prophylactic effects on lupus nephritis in these mice that are highly associated with its effects of enhancing the Nrf2 antioxidant signaling pathway, decreasing renal NLRP3 inflammasome activation, and increasing systemic Treg cell activity.

Inverse association of general joint hypermobility with hand and knee osteoarthritis and serum cartilage oligomeric matrix protein levels.

OBJECTIVE: Extensive joint hypermobility, lower serum cartilage oligomeric matrix protein (COMP) levels, and early-onset osteoarthritis (OA) are phenotypes of inherited pseudoachondroplasia and multiple epiphyseal dysplasia. However, few studies have evaluated the association between articular hypermobility and primary OA. We undertook the present study to evaluate this association and to test the hypothesis that COMP levels are associated with hypermobility in patients with OA and individuals without OA. METHODS: Two separate cohorts were available for analysis, the CARRIAGE (CARolinas Region Interaction of Aging Genes and Environment) extended family and a subset of the GOGO (Genetics of Generalized Osteoarthritis) sibpair cohort. In the CARRIAGE family, we performed hand and knee examinations and hypermobility evaluations (Beighton criteria) and obtained sera for measurement of COMP and hyaluronan (HA). Data on COMP and HA levels and extensive joint radiographic and hypermobility data were also available for the GOGO cohort. RESULTS: The prevalence of hypermobility was 13% in the CARRIAGE family and 5% in the GOGO cohort. In the CARRIAGE family, hypermobility was associated with a significantly reduced prevalence of hand (especially proximal interphalangeal joint) and knee OA and lower mean serum COMP levels, both in the total cohort and in non-hand-OA subgroups. These results were further validated in the GOGO subsets without radiographic OA, in which hypermobility was also associated with a significantly reduced mean serum COMP level (P < 0.0001 adjusted for age). Serum HA levels did not differ in relation to hypermobility in either cohort. CONCLUSION: The present results indicate that there is an inverse relationship between hypermobility and hand and knee OA, and that hypermobility is associated with lower serum COMP levels. Genetic variations of the COMP gene may account for some subgroups of benign joint hypermobility.

Autoimmune hepatitis with raised alpha-fetoprotein level as the presenting symptoms of systemic lupus erythematosus: a case report.

Systemic lupus erythematosus (SLE) and autoimmune hepatitis are distinct clinical disorders, which rarely occur, in the same patient. We describe a 59-year-old woman with coexistence of both conditions. Photosensitivity, arthritis, positive ANA, and extreme elevation of anti-dsDNA concluded the diagnosis of SLE. Hyperbilirubinemia, high serum value of liver function, and elevation of alpha-fetoprotein were also prominent. By a review of pertinent literature, clinical investigation, calculation of autoimmune hepatitis score, and pathology of liver biopsy specimen, we were in favor of autoimmune hepatitis. Awareness of this rare presentation may be beneficial to clinicians in identifying and treating patients with both SLE and autoimmune hepatitis.

Thymoma and hypogammaglobulinemia (Good's syndrome): a case report.

Good's syndrome is extremely rare and refers to an acquired B and T cell immunodeficiency in thymoma patients. We report a 51-year-old female thymoma patient who presented with recurrent herpes zoster, pneumonia, diarrhea and opportunistic infections. She was found to have acquired hypogammaglobulinemia with absent B cells. Despite repeat intravenous immunoglobulin replacement and antibiotic therapy, she died of bacterial pneumonia-induced acute respiratory distress syndrome. Clinicians should look for evidence of immunologic dysfunction in thymoma patients presenting with recurrent infections.