Use of Disease-modifying Antirheumatic Drugs After Cancer Diagnosis in Rheumatoid Arthritis Patients

Objective@#There is no recommendation for the use of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) who developed cancer. We examined changes in the DMARDs prescription patterns associated with cancer diagnosis in RA patients. @*Methods@#We reviewed the medical records of 2,161 RA patients who visited rheumatology clinic between January 2008 and February 2017 and found 40 patients who developed cancer during RA treatment. In these patients, we examined DMARDs prescription patterns before and right after cancer diagnosis and at recent outpatient clinic visits. @*Results@#Before cancer diagnosis, methotrexate (MTX)-combined conventional synthetic DMARDs (csDMARDs) were most commonly prescribed (22, 55.0%) and biological DMARDs (biologics) in nine patients (22.5%). For cancer treatment, 19 patients received chemotherapy (including adjuvant chemotherapy) and 21 patients had surgery only. Right after cancer diagnosis, changes in the DMARDs prescription patterns were similar in discontinuation (13, 32.5%), switching (14, 35.0%), and maintenance (13, 32.5%). DMARDs were discontinued more frequently in the chemotherapy group (9/19, 47.4%) than the surgery only group (4/2, 19.0%) (p<0.05). Among the 13 patients who discontinued DMARDs, nine (69.2%) resumed DMARDs after a median of 5.5 months (interquartile range [IQR] 2.9, 18.3) due to arthritis flare. At a median of 4.6 years (IQR 3.3, 6.7) after cancer diagnosis, 25 patients were evaluated at recent outpatient clinic visits. Four patients received no DMARD, three MTX monotherapies, 11 csDMARDs combination therapies, and seven biologics. @*Conclusion@#A significant number of RA patients who developed cancer during RA treatment were still receiving DMARDs including biologics after cancer diagnosis.

Clinical Implications of Shared Epitope and Anti-citrullinated Peptide Antibody in Patients With Rheumatoid Arthritis

Objective@#The shared epitope (SE) and anti-citrullinated peptide antibody (ACPA) are involved in the pathogenesis of rheumatoid arthritis (RA). This study evaluated the clinical implications of SE and ACPA in terms of disease manifestation and response to biologic disease modifying anti-rheumatic drugs (DMARDs). @*Methods@#Patients with identified human leukocyte antigen (HLA)-DRB1 alleles were included to compare the clinical characteristics and drug survival rate of tumor necrosis factor (TNF) inhibitors or abatacept based on the presence of SE and ACPA. @*Results@#Of the 533 patients with identified HLA-DRB1 alleles, 329 patients (61.7%) with SE alleles showed higher disease activity and erosive changes compared to patients without SE alleles. SE-positive patients were more likely to start biologic (b-) or targeted synthetic DMARDs (tsDMARDs) within the first 5 years (p=0.020). The presence of SE, smoking, dyslipidemia, and higher erythrocyte sedimentation rate were independently associated with the initiation of b- or tsDMARDs (p=0.016, 0.028, 0.031, and 0.001, respectively). The presence of SE and ACPA did not affect the drug survival rate of TNF inhibitors, whereas the abatacept retention rate was higher in ACPA-positive patients (p=0.024). @*Conclusion@#The presence of SE affected disease characteristics and prognosis in Korean patients with RA without a significant impact on drug survival rate of TNF inhibitors and abatacept. ACPA positivity was associated with abatacept drug retention, suggesting that abatacept may be helpful in ACPA-positive patients than in ACPA-negative patients.

Association of Uveitis with Radiographic Progression in Patients with Axial Spondyloarthritis: A Propensity Score Matching Analysis

OBJECTIVE: Acute anterior uveitis (AAU) is the most common extra-articular manifestation in patients with axial spondyloarthritis (axSpA). However, the relationship between AAU and radiographic progression in axSpA remains unclear. Hence, we investigated whether the presence of AAU is associated with radiographic structural damage in patients with axSpA. METHODS: Clinical and radiographic data were obtained from 253 patients with axSpA. Radiographic progression over 2 years was assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Progression was defined as mSASSS worsening by ≥two units. Using propensity score (PS) matching, differences between patients with and without AAU were analyzed. RESULTS: The proportion of progressors among patients with AAU was lower than that of patients without AAU (13.6% vs. 29.5%, p=0.058). The rate of increase in mSASSS and number of syndesmophytes were lower in patients with AAU than patients without AAU (0.57±1.37 vs. 1.02±1.79, p=0.085 and 0.46±1.45 vs. 0.83±1.62, p=0.158). In multivariate regression analysis, presence of AAU was independently associated with slowed radiographic progression (odds ratio [95% confidence interval] 0.21 [0.07, 0.67], p=0.004). CONCLUSION: PS-matched axSpA patients with AAU showed significantly less radiographic progression than those without AAU.

Application of machine learning in rheumatic disease research

Over the past decade, there has been a paradigm shift in how clinical data are collected, processed and utilized. Machine learning and artificial intelligence, fueled by breakthroughs in high-performance computing, data availability and algorithmic innovations, are paving the way to effective analyses of large, multi-dimensional collections of patient histories, laboratory results, treatments, and outcomes. In the new era of machine learning and predictive analytics, the impact on clinical decision-making in all clinical areas, including rheumatology, will be unprecedented. Here we provide a critical review of the machine-learning methods currently used in the analysis of clinical data, the advantages and limitations of these methods, and how they can be leveraged within the field of rheumatology.

Comparing Effectiveness Rituximab (Mabthera®) to Other Second-line Biologics for Rheumatoid Arthritis Treatment in Patients Refractory to or Intolerant of First-line Anti-tumor Necrosis Factor Agent: An Observational Study

OBJECTIVE: Failure of first-line anti-tumor necrosis factor (TNF) agents in in rheumatoid arthritis patients leads to decisions among second-line biologic agents. To better inform these decisions, the therapeutic effectiveness of rituximab is compared with other second-line biologic agents in this observational study. METHODS: Between November 2011 and December 2014, study subjects were observed for 12 month periods. Patients with an inadequate response to initial anti-TNF agent received either rituximab or alternative anti-TNF agents (adalimumab/etanercept/infliximab) based on the preference of patients and physicians. The efficacy end point of this study was the change in 28-joint count Disease Activity Score (DAS28) at six and 12 months from baseline. Safety data were also collected. RESULTS: Ninety patients were enrolled in the study. DAS28 at six months did not change significantly whether the patients were treated with rituximab or alternative anti-TNF agents in intention-to-treat analysis (n=34, −1.63±0.30 vs. n=31, −2.05±0.34) and standard population set analysis (n=31, −1.51±0.29 vs. n=24, −2.21±0.34). Similarly, the change in DAS28 at 12 months did not reach statistical significance (−1.82±0.35 in the rituximab vs. −2.34±0.44 in the alternative anti-TNF agents, p=0.2390). Furthermore, the incidences of adverse events were similar between two groups (23.5% for rituximab group vs. 25.8% for alternative anti-TNF agents group, p=0.7851). CONCLUSION: Despite the limitations of our study, switching to rituximab or alternative anti-TNF agents after failure of the initial TNF antagonist showed no significant therapeutic difference in DAS28 reduction.

Applications of systems approaches in the study of rheumatic diseases

The complex interaction of molecules within a biological system constitutes a functional module. These modules are then acted upon by both internal and external factors, such as genetic and environmental stresses, which under certain conditions can manifest as complex disease phenotypes. Recent advances in high-throughput biological analyses, in combination with improved computational methods for data enrichment, functional annotation, and network visualization, have enabled a much deeper understanding of the mechanisms underlying important biological processes by identifying functional modules that are temporally and spatially perturbed in the context of disease development. Systems biology approaches such as these have produced compelling observations that would be impossible to replicate using classical methodologies, with greater insights expected as both the technology and methods improve in the coming years. Here, we examine the use of systems biology and network analysis in the study of a wide range of rheumatic diseases to better understand the underlying molecular and clinical features.

Seropositive rheumatoid arthritis in a female patient with sensory neuropathy

No abstract available.

Systems Approach to Rheumatoid Arthritis

Phenotypic characteristics of complex diseases such as rheumatoid arthritis are a consequence of interactions of genetic and environmental factors. Biomolecules closely interact with other molecular components and form functional modules, resulting in significant biologic action capability. While traditional biochemical research focuses on a single disease using narrowly constrained data, systems biology aims to interpret large volumes of highly complex and multilevel data obtained from high-through-put technologies to understand how biological systems function as a whole. Such a systems approach to complex diseases, so-called network medicine, can shape our comprehensive understanding of disease mechanisms by identifying modules temporally and spatially perturbed in the context of health and diseases. Given the unmet needs for diagnosis, monitoring, and treatment in rheumatoid arthritis, systems biology is obviously an emerging powerful tool to gain insight into disease mechanisms, study comorbidities, analyze therapeutic drugs and their targets, and discover novel network-based biomarkers.

Spontaneous Remission of Hodgkin's Lymphoma in a Patient with Systemic Lupus Erythematosus after Withdrawal of Methotrexate

Methotrexate is often used in patients with systemic lupus erythematosus for effective disease controlsand steroid-sparing, and has been known to involve the development of lymphoproliferative disorders for patients with autoimmune diseases. We report a case of spontaneous regression of Epstein-Barr virus-positive methotrexate-associated Hodgkin's lymphoma in a 24-year-old woman with systemic lupus erythematosus. Following 6 months of treatment with low-dose methotrexate, the patient developed a neck mass in the right submandibular area. A computed tomography scan of the neck, chest and abdomen revealed multiple enlarged lymph nodes. Excisional biopsy of the neck masses confirmed infiltrations of malignant lymphoid cells that were positive for CD15, CD30, and Epstein-Barr virus-encoded RNA. Reduction of the mass was observed 3 weeks after withdrawing from the methotrexate treatment. At 7 months after initial presentation, computed tomography revealed near-complete regression of lymphadenopathy. After 30 months, the patient was still in complete clinical remission.

Role of placenta growth factor in cancer and inflammation

Accumulating evidences have documented that angiogenesis is closely linked to inflammation and regulators of angiogenesis play key roles in various inflammatory conditions. PlGF is an angiogenic protein belonging to the VEGF family and is upregulated mainly in pathologic conditions. Recently, PlGF was discovered having a proinflammatory role in inflammatory arthritis and its serum level drew attention not only as a useful surrogate biomarker but also a potential therapeutic target in atherosclerosis and various cancers. Particularly, PlGF has attractive clinical values because endogenous PlGF is redundant for vascular development and physiological vessel maintenance in healthy adults. However, there have been conflicting results about the efficacy of PlGF inhibition depending on the experimental and clinical settings. Further close investigations for resolving the puzzle of PlGF biology are required.

Diabetic Cheiroarthropathy / 대한류마티스학회지

No abstract available.

Infective endocarditis in hemodialized patient with end-stage renal disease / 대한내과학회지

No abstract available.

A Case of Fatal Tracheobronchial Aspergillosis in a Neutropenic Patient / 감염과화학요법

Tracheobronchial aspergillosis is an uncommon clinical form of invasive aspergillosis, particularly found in patients with AIDS and in lung transplant recipients than in other immunocompromised patients. The rapidity of the disease progression can result in fatal airway obstruction in a short period of time that the patient may need emergency tracheostomy without knowing the cause of the obstruction. We describe a case of fatal tracheobronchial aspergillosis which developed in a 43- year-old female patient with acute lymphoblastic leukemia. Dyspnea and stridor developed on the 20th day after 2nd consolidation chemotherapy, which was during the prolonged neutropenic period. Airway narrowing was observed on the computed tomograph scan of neck and emergency tracheostomy was performed. Infiltration with aspergillus hyphae was found in the tracheal ring and bronchial mucosa. Despite the use of amphotericin B, the patient died of bleeding and airway obstruction.

A Case of Fatal Tracheobronchial Aspergillosis in a Neutropenic Patient / 감염과화학요법

Tracheobronchial aspergillosis is an uncommon clinical form of invasive aspergillosis, particularly found in patients with AIDS and in lung transplant recipients than in other immunocompromised patients. The rapidity of the disease progression can result in fatal airway obstruction in a short period of time that the patient may need emergency tracheostomy without knowing the cause of the obstruction. We describe a case of fatal tracheobronchial aspergillosis which developed in a 43- year-old female patient with acute lymphoblastic leukemia. Dyspnea and stridor developed on the 20th day after 2nd consolidation chemotherapy, which was during the prolonged neutropenic period. Airway narrowing was observed on the computed tomograph scan of neck and emergency tracheostomy was performed. Infiltration with aspergillus hyphae was found in the tracheal ring and bronchial mucosa. Despite the use of amphotericin B, the patient died of bleeding and airway obstruction.

A Case of Bladder Cancer in a Patient with Systemic Lupus Erythematosus Treated with Oral Cyclophosphamide / 대한류마티스학회지

Cyclophosphamide, a cytotoxic alkylating agent, is widely used in various benign diseases like systemic lupus erythematosus (SLE), Wegener's granulomatosis, rheumatoid arthritis, nephrotic syndrome as well as in malignancies and organ transplantation. Cyclophosphamide is metabolized in the liver to various chlormethine metabolites and acrolein, which mediates the toxic effect to the urothelium and can cause hemorrhagic cystitis, bladder fibrosis, and has also been associated with urothelial malignancies including bladder cancer. It is known that SLE is not associated with an increased risk for the development of most of the solid tumors. But it has been suggested that the risk of the bladder cancer increases in patients with benign diseases such as SLE treated by cyclophosphamide. There are only very few reports of cyclophosphamide-induced bladder cancer in SLE so far. We report a case of a patient who developed bladder cancer 13 years after cyclophosphamide was given as therapy for SLE. This case shows that careful observation and urologic evaluation is undoubtedly important for patients treated with cyclophosphamide.

A Case of Central Diabetes Insipidus in Patient with Non-small Cell Lung Cancer / 결핵및호흡기질환

Central diabetes insipidus (DI) is a disease caused by insufficient release of antidiuretic hormone. Central DI with lung cancer is very rare. Most of them are caused by the pituitary metastasis, and rarely, by the paraneoplastic syndromes. Central DI is diagnosed by the water deprivation test. The treatment consists of surgical resection, radiotherapy and administration of desmopressin. We report an unusual case of central DI with non-small cell lung cancer. The diagnosis was confirmed by water deprivation test. After the administration of desmopressin, the urine osmolarity was increased. The patient's symptoms and urine osmolarity were improved by intranasal desmopressin.

A Case of Vancomycin-Induced Agranulocytosis in a Hemodialysis Patient: Successful Treatment with G-CSF / 대한신장학회잡지

Vancomycin induced agranulocytosis is a rare but life-threatening complication. We here report a case of vancomycin induced agranulocytosis in a patient with chronic renal failure. A 36-year-old woman receiving hemodialysis via jugular cannulation developed staphylococcus sepsis. The catheter was removed and she was started on vancomycin therapy (1.0 g/week). New catheter was inserted for next hemodialysis. Second sepsis of same organism developed 12 days after initial sepsis inspite of vancomycin therapy. We removed this catheter and continued vancomycin therapy. After 19 days of vancomycin treatment, the patient developed a severe agranulocytosis with white blood cell count of 1, 600/ mm3 and the complete absence of neutrophil. Vancomycin was discontinued and teicoplanin was substituted for vancomycin therapy and G-CSF (granulocyte colony stimulating factor) therapy was begun. White blood cell count including neutropil was completely recovered after 13 days of discontinuation of vancomycin.

Minimally Dilated Obstructive Nephropathy Initially Suspected as Pre-renal Azotemia in a Kidney Donor with Volume Depletion

Although ultrasonography is regarded as the gold standard in the diagnosis of obstructive nephropathy, dilatation is sometimes not observed by ultrasonography. We report upon a case of minimally dilated obstructive nephropathy due to an ureter stone in a kidney donor with volume depletion. A 54-year-old man was admitted due to anuria and abdominal pain of 2 days duration. Ten years previously, his right kidney was donated for transplantation, and one month before admission, he abstained from all food except water and salt, for 30 days for religious reasons. He had lost 8 kg of body weight. On admission, he had clinical signs of volume depletion, i.e., a dehydrated tongue and decreased skin turgor. Laboratory data confirmed severe renal failure, his blood urea nitrogen level was 107.3 mg/dL, and his serum creatinine 16.5 mg/dL. The plain X-ray was unremarkable and ultrasonography showed only minimal dilatation of the renal collecting system. On follow-up ultrasonography, performed on the 5th hospital day, the dilatation of the collecting system had slightly progressed and a small stone was found at ureter orifice by cystoscopy. Removal of stone initiated dramatic diuresis with a rapid return of renal function to normal by the third day.