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ID PMID Title PublicationDate abstract
28770709 Timing of onset affects arthritis presentation pattern in antisyntethase syndrome. 2018 Jan OBJECTIVES: To evaluate if the timing of appearance with respect to disease onset may influence the arthritis presentation pattern in antisynthetase syndrome (ASSD). METHODS: The patients were selected from a retrospective large international cohort of ASSD patients regularly followed-up in centres referring to AENEAS collaborative group. Patients were eligible if they had an antisynthetase antibody testing positive in at least two determinations along with arthritis occurring either at ASSD onset (Group 1) or during the course of the disease (Group 2). RESULTS: 445 (70%; 334 females, 110 males, 1 transsexual) out of the 636 ASSD we collected had arthritis, in the majority of cases (367, 83%) from disease onset (Group 1). Patients belonging to Group 1 with respect to Group 2 had an arthritis more commonly polyarticular and symmetrical (p=0.015), IgM-Rheumatoid factor positive (p=0.035), erosions at hands and feet plain x-rays (p=0.036) and more commonly satisfying the 1987 revised classification criteria for rheumatoid arthritis (RA) (p=0.004). Features such as Raynaud's phenomenon, mechanic's hands and fever (e.g. accompanying findings) were more frequently reported in Group 2 (p=0.005). CONCLUSIONS: In ASSD, the timing of appearance with respect to disease onset influences arthritis characteristics. In particular, RA features are more common when arthritis occurs from ASSD onset, suggesting an overlap between RA and ASSD in these patients. When arthritis appears during the follow-up, it is very close to a connective tissue disease-related arthritis. Also, the different prevalence of accompanying features between these two groups is in line with this possibility.
30293157 Etanercept-induced Crohn's disease in ankylosing spondylitis: a case report and review of 2018 Nov Tumor necrosis factor (TNF)-α is a cytokine that plays a well-established, key role as a central mediator of inflammation and immune regulation. TNF-α and its receptors are suggested to play a critical role in a number of chronic inflammatory diseases, including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis (AS), juvenile chronic arthritis, and inflammatory bowel disease (IBD). TNF-α inhibitors are currently used in the treatment of these diseases. We report a 29-year-old male with AS who developed Crohn's disease while taking etanercept. Etanercept treatment was interrupted and a switch to a monoclonal antibody-based anti-TNF treatment using adalimumab was started, which induced a prompt improvement of the gastrointestinal symptoms. We indicate the immunodysregulatory and proinflammatory effects of etanercept and discuss the potential pathogenic mechanisms of the paradoxical effect of TNF-α inhibitors. We also review the related literature on new-onset IBD following anti-TNF treatment for AS.
30156540 A clinical and histopathological analysis of the anti-centromere antibody positive subset 2018 May OBJECTIVES: ACA-positive/primary Sjögren's syndrome (pSS) represents a distinct overlapping entity with intermediate features in between limited systemic sclerosis (lSSc) and pSS. Few data are available on their general risk for lymphoproliferative complications, specifically regarding adverse predictors at the level of minor salivary gland (MSG) histology. The objectives of this work are: a) to characterise, through a detailed immunohistochemistry study, the organisation of the lymphomonocitic infiltrates in ACA-positive/pSS patient vs. ACA-negative/pSS patients focusing on the presence of GC-like structures in minor salivary gland biopsies; b) to compare the frequency of traditional clinical and serological risk factors for lymphoma between the two subgroups. METHODS: We analysed 28 MSG samples from ACA-positive/pSS patients and 43 consecutive MSGs from ACA-negative/pSS, using sequential IHC staining for CD3, CD20 and CD21 in order to define the T/B cell segregation within the periductal infiltrates and presence of ectopic GC-like on the detection of GC-like structures. Clinical and serological data of all the patients were retrieved and analysed. RESULTS: Ectopic lymphoid structures (ELS) with GC-like structures were observed in 7 out of 28 ACA-positive/pSS patients (25%) and in 13 out of 43 ACA-negative/pSS patients (30.2%). Similarly, no statistical significant difference was found between the two groups as far as the classical pSS risk factors for lymphoproliferative complications was concerned (i.e. salivary gland enlargement, purpura, low C4, leukocytopenia, clonal gammopathy). Finally, the 3 cases of non-Hodgkin's lymphoma observed were equally distributed between the two subsets. CONCLUSIONS: Overall, this study indicates that ACA-positive/and ACA-negative pSS patients apparently present a similar risk for lymphoproliferative complications as suggested indirectly by the analogies between the two groups observed at the histopathology level.
27142563 Tubulointerstitial nephritis and Fanconi syndrome in a patient with primary Sjögren's syn 2018 Sep We describe a 53-year-old woman with primary Sjögren's syndrome and tubulointerstitial nephritis showing distal renal tubular acidosis and Fanconi syndrome. The patient showed high serum IgM levels and positivity for antimitochondrial antibodies, although her liver function was in normal range. According to our literature review, 75% of patients with tubulointerstitial nephritis who were positive for antimitochondrial antibodies showed Fanconi syndrome, suggesting that these antibodies may directly be associated with the pathophysiology of Fanconi syndrome.
30338648 Influence of total glucosides of paeony on PD-1/PD-L1 expression in primary Sjögren's syn 2019 Feb AIM: To study the influence of total glucosides of paeony (TGP) on the expression of peripheral blood programmed cell death protein 1 (PD-1) and its ligand (PD-L1) in patients with primary Sjögren's syndrome (pSS). METHOD: Ten patients with new-onset pSS were selected as the experimental group and were treated with 1.8 g of TGP (the main ingredient is Radix Paeoniae Alba) daily for 3 months; furthermore, 10 physically healthy individuals were selected as the control group. Peripheral blood mononuclear cells were isolated, and flow cytometry was used to detect PD-1 expression on the surface of CD4+ T and CD8+ T lymphocytes and PD-L1 expression on the surface of CD14+ monocytes and CD19+ B cells before and after treatment in the experimental and control groups. Furthermore, plasma levels of soluble PD-1 (sPD-1), interleukin (IL)-10, and IL-17A were also determined using enzyme-linked immunosorbent assay. RESULTS: The PD-1 expression on the surface of CD4+ T and CD8+ T lymphocytes in the peripheral blood of patients with pSS were significantly higher than in the control group (P < 0.001). However, PD-L1 expression on the surface of CD14+ monocytes declined but not significantly (P > 0.05), and PD-L1 expression on the surface of CD19+ B cells increased significantly (P < 0.001). Moreover, sPD-1 and IL-17A levels in the plasma of the experimental group were significantly higher than in the control group (P < 0.001), but the IL-10 level was significantly lower than in the control group (P < 0.001). After TGP treatment, PD-1 expression on the surface of CD4+ T and CD8+ lymphocytes in the peripheral blood of patients with pSS had decreased significantly (P < 0.001); the PD-L1 expression on the surface of CD19+ cells had decreased significantly (P < 0.001); and the PD-L1 expression on the surface of CD14+ monocytes did not differ significantly (P > 0.05). Furthermore, the levels of sPD-1 and IL-17A in plasma had decreased (P < 0.01) and IL-10 levels had increased after TGP treatment (P < 0.01). CONCLUSION: PD-1/PD-L1 molecules expressed on the surface of T cells, B cells, and monokaryon participated in the pathogenesis and development of SS through interactions. Therefore, TGP, which may increase the expression of PD-1 and its relevant ligand PD-L1 in the peripheral blood mononuclear cells, may play a role in the pathogenesis and development of SS through the PD-1/PD-L1 pathway by regulating regulatory T cells/T helper cell 17.
29981509 Age trajectories of musculoskeletal morbidities in adults with cerebral palsy. 2018 Sep BACKGROUND: Individuals with cerebral palsy (CP) are at an increased risk for age-related morbidities due to functional impairments, maladapted growth, and altered body composition. While musculoskeletal (MSK) deficits are present in children, little is understood about MSK morbidity throughout the lifespan in those with CP. The purpose of this study was to examine the age-related trajectories of MSK morbidity and multimorbidity throughout adulthood in those with CP. METHODS: A clinic-based sample of adults with CP (n = 1395; ≥18 years) was examined to determine prevalence of MSK morbidities at the University of Michigan Medical Center. Logistic regression was used to determine the effects of age on individual MSK morbidities and multimorbidity (i.e., ≥2 morbidities) after adjusting for sex, race, weight, and smoking. RESULTS: With the 18-30 year age group as the reference, the adjusted odds of osteopenia was lower in the 41-50 and >50 year age groups, the odds of osteoporosis and rheumatoid arthritis was higher in 41-50 and >50 year age groups, and the odds of osteoarthritis was higher in 31-40, 41-50, and >50 year age groups. The adjusted odds of MSK multimorbidity increased substantially with increasing age for 31-40 year olds (OR: 1.919; 95% CI 1.05-3.52), 41-50 year olds (OR: 4.30; 95% CI 2.40-7.69), and >50 year olds (OR: 6.05; 95% CI 3.56-10.27). CONCLUSIONS: Adults with CP are at high risk for MSK morbidities across all ages. Future studies are needed to examine the global aging trajectories of MSK health among adults with CP. Study findings highlight the importance of maximizing MSK accretion, and developing programs to assist individuals with CP and their caregivers to maintain MSK mass and function throughout the lifespan.
30269510 Lower Bone Density on Preoperative Computed Tomography Predicts Periprosthetic Fracture Ri 2019 Jan BACKGROUND: The effect of bone mineral density (BMD) on outcomes from total ankle arthroplasty (TAA) has not been studied. BMD can be estimated by measuring Hounsfield units (HU) on standard computed tomography (CT), which is frequently performed prior to TAA. We aimed to identify whether tibial and talar HU measured from preoperative CT scans were associated with periprosthetic fracture or revision risk in patients undergoing TAA. METHODS: A prospectively collected database was used to retrospectively screen all patients undergoing primary TAA. Only patients with a preoperative CT within 1 year of surgery were included. Primary outcomes were periprosthetic fracture and prosthetic revision. HU were measured on axial CT cuts in the distal tibia and talus. Additional patient factors analyzed included age, sex, weight, body mass index (BMI), tobacco use, presence of rheumatoid arthritis, and preoperative deformity. A total of 198 ankles were included, with a mean 2.4 years of follow-up. RESULTS: There were 7 intraoperative and 9 postoperative periprosthetic fractures (3.5% and 4.5%, respectively). Seven patients (3.5%) underwent prosthetic removal or revision. Lower tibial and talar HU, lower weight, and lower BMI were associated with periprosthetic fractures ( P < .05). After controlling for age, sex, and weight, only tibial HU was significantly associated with periprosthetic fracture ( P = .018). All intraoperative fractures occurred in patients with tibial HU less than 200. None of the patient factors analyzed were associated with revision. CONCLUSIONS: Lower tibial HU on preoperative CT was strongly associated with periprosthetic fracture risk with TAA. In patients with tibial HU less than 200, surgeons may consider prophylactic internal fixation of the medial malleolus. LEVEL OF EVIDENCE: Level III, retrospective cohort study.
29445869 Guidelines for management of rheumatic diseases in developing countries from basics to rea 2018 Apr Guidelines or recommendations help to provide uniform standards in medical practice. The development of guidelines requires adherence to pre-defined norms prescribed by different international organizations such as the European League against Rheumatism (EULAR). We searched Pubmed and LILACS to identify published papers in five major rheumatic diseases (rheumatoid arthritis, systemic lupus erythematosus, spondyloarthropathies, osteoarthritis, and scleroderma) from different countries based on their economic prosperity and could find a lack of published literature from most economically weaker regions. Similarly, published guidelines in these rheumatic diseases were sparse from Asia and Africa, which are economically developed to a lesser extent than other regions of the world. Considering differing economic realities driving patient care in different regions of the world, unique challenges in certain geographic areas such as musculoskeletal manifestations of infectious diseases like leprosy and tuberculosis, as well as distinct risk of malignancies and other comorbid conditions, National Rheumatology societies should work towards developing more guidelines for rheumatic diseases from regions such as Asia and Africa, while following strictly the prescribed norms for the same. With a paucity of guidelines for such regions currently, an alternative (although less preferable) suggestion would be that major international societies, whose guidelines are widely read and followed the world over, should consider inputs from experts from diverse regions of the world while developing these guidelines.
31559208 A Study on Etiopathogenesis of Vocal Cord Paresis and Palsy in a Tertiary Centre. 2019 Sep To identify patients of vocal cord paresis and palsy and to establish an etiological diagnosis based on a study performed in a tertiary centre. Study was done prospectively in the Department of ENT in KIMS Hospital, Bangalore, for 1 year, from June 2016 to June 2017. 100 patients with vocal cord paresis and palsy were identified and examined by using various tests and investigations to establish the etiology. Most of the patients presented with complaints of change in voice (92%). Some of the other common presenting complaints included noisy breathing and difficulty in swallowing, difficulty in voice production and vocal fatigue and cough. Unilateral paralysis (82%) was found to be more common than bilateral paralysis (18%), of which left (52%) was more commonly affected than right (48%) vocal cord. The most common age group affected was 51-60 years (24%) followed by 61-70 years (19%). Males (60%) were affected more than females (40%) in a ratio of 3:2 and among the affected males 73% were known smokers. The most common cause of vocal cord paresis and palsy was found to be idiopathic (38%), followed by primary laryngeal growths (27%). Other causes included carcinomas of lung, thyroid and oesophagus, traumatic, inflammatory, systemic diseases like Rheumatoid arthritis, Hypertension leading to stroke. Identifying the exact etiopathogenesis of vocal cord paresis and palsy in patients has been difficult and is very important in order to establish a proper diagnostic and treatment protocol for these patients.
30647742 Efficacy of clarithromycin as a protective agent in the methotrexate-induced pulmonary fib 2018 Dec INTRODUCTION: Methotrexate is a cytotoxic agent used in leukemia, and several other cancer types and at lower doses in auto-inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis and psoriasis. Macrolide antibiotics are effective against gram-positive and Gram-negative bacteria. They have anti-inflammatory activities as well. Clarithromycin is a macrolide with anti-inflammatory activity through blockage of the p38 MAPK signal cascade, which is involved in methotrexate-induced pulmonary toxicity. AIM: In this study, the efficacy of clarithromycin in protecting against pulmonary fibrosis was investigated in the rat model for methotrexate-induced pulmonary fibrosis. MATERIAL AND METHODS: A total of 30 female rats were divided into three groups. Group I was administered intraperitoneal and intragastric saline; group II was administered oral 3 mg/kg methotrexate; and group III was administered oral 3 mg/kg methotrexate + intraperitoneal 200 mg/kg clarithromycin for 28 days. Histopathological analyses of the lung tissues were performed under light microscopy. RESULTS: Normal histopathological changes were observed in the control group. Pulmonary fibrosis was significantly higher in the methotrexate group than in the other groups (p < 0.005). CONCLUSIONS: Clarithromycin was shown to be effective in protecting against methotrexate-induced pulmonary fibrosis; further studies should be performed to determine the dosage and safety.
30562654 Seizures as a clinical manifestation in somatic autoimmune disorders. 2019 Jan The risk of epileptic seizures seems increased in several systemic autoimmune disorders including systemic lupus erythematosus, type 1 diabetes mellitus, myasthenia gravis, celiac disease, rheumatoid arthritis, Hashimoto's encephalopathy, psoriasis, multiple sclerosis, neuromyelitis optica, and bullous pemphigoid. Immune dysfunction may be partly responsible for this association. Elevated levels of pro-inflammatory cytokines, autoantibodies seen in these autoimmune disorders and antibodies against neuronal antigens may contribute to the etiopathogenesis of seizures and epilepsy associated to immune conditions. Other unknown factors, the effect of different co-morbid conditions of epilepsy as well as shared risk factors such as common etiological factors, environmental triggers, or a common genetic predisposition may also explain the association. We review different autoimmune disorders which may present with co-morbid seizures and discuss possible underlying mechanisms of this co-occurrence focusing on a potential role of immune system dysfunction.
30396816 The diagnostic value of clinical examinations when diagnosing carpal tunnel syndrome assis 2019 Mar BACKGROUND: Our study aims to evaluate the reliability of clinical findings in diagnosing carpal tunnel syndrome (CTS), with the help of nerve conduction studies (NCSs) and the detection of comorbidities likely to be risk factors. METHODS: 512 patients were included in the study who described pain or paresthesia in the median nerve sensory distribution. Sensory and motor NCSs were performed on the median and ulnar nerves of all patients. 49 patients who showed pathological abnormalities of the ulnar nerve were excluded. Demographic information, clinical findings and comorbidities were recorded. According to the results of the NCSs, the patients were divided and analyzed as either positive and negative for the diagnosis of CTS. RESULTS: The highest sensitivity was seen from the Durkan test (95.6%) and the lowest was from thenar atrophy (22.1%). The highest specificity and positive predictive values were seen for thenar atrophy (100%) and the lowest were from the Tinel test (40.9% and 59.1%). The highest negative predictive value was the Durkan test (94%) and thenar atrophy was the lowest (57.4%). There was a significant difference in NCSs groups for clinical findings and comorbidities. CONCLUSIONS: Thenar atrophy and sensory loss were highly specific in CTS but had limited value in early detection. Due to their low specificity, provocative tests do not appear sufficient enough to establish a definite CTS diagnosis. Only Durkan's test could possibly be considered initially as it has more balanced values. Diabetes, obesity, rheumatoid arthritis, hypothyroidism and gout significantly increase the risk of CTS.
30323370 Clinical and immunological profile in patients with mixed connective tissue disease. 2018 Jun Mixed connective tissue disease (MCTD) is a rare disease and presents with varied overlapping symptoms of different connective tissue disorders. Many patients evolve into other connective tissue disorders with the passage of time. The case series included 20 patients with the diagnosis of MCTD, registered at the Rheumatology Clinic of Jinnah Postgraduate Medical Centre (JPMC), Karachi, from June 2010 to May 2015. Of these, 16 (80.0%) were female and 4 (20.0%) patients were male. The mean age was 30.5±8.9 years and the mean duration of illness was 4.5±2 years. Commonest presenting symptom was arthralgia in 17 (85%) patients. All the patients had positive ANA and anti-RNP antibodies. Over the disease course of 6 years, 2 (10%) patients evolved into Systemic lupus erythematosus (SLE); One each (5%) into Sjogren's syndrome, Scleroderma and Rheumatoid arthritis.
30290988 Discovery of a novel series of pyridine and pyrimidine carboxamides as potent and selectiv 2018 Nov 15 Btk is an attractive target for the treatment of a range of Bcell malignancies as well as several autoimmune diseases such as murine lupus and rheumatoid arthritis. Several covalent irreversible inhibitors of Btk are currently in development including ibrutinib which was approved for treatment of B-cell malignancies. Herein, we describe our efforts using X-ray guided structure based design (SBD) to identify a novel chemical series of covalent Btk inhibitors. The resulting pyridine carboxamides were potent and selective inhibitors of Btk having excellent enzymatic and cellular inhibitory activity.
30171835 Gut microbiota, cannabinoid system and neuroimmune interactions: New perspectives in multi 2018 Nov The gut microbiota plays a fundamental role on the education and function of the host immune system. Immunological dysregulation is the cause of numerous human disorders such as autoimmune diseases and metabolic disorders frequently associated with inflammatory processes therefore is critical to explore novel mechanisms involved in maintaining the immune system homeostasis. The cannabinoid system and related bioactive lipids participate in multiple central and peripheral physiological processes that affect metabolic, gastrointestinal and neuroimmune regulatory mechanisms displaying a modulatory role and contributing to the maintenance of the organism's homeostasis. In this review, we gather the knowledge on the gut microbiota-endocannabinoids interactions and their impact on autoimmune disorders such as inflammatory bowel disease, rheumatoid arthritis and particularly, multiple sclerosis (MS) as the best example of a CNS autoimmune disorder. Furthermore, we contribute to this field with new data on changes in many elements of the cannabinoid system in a viral model of MS after gut microbiota manipulation by both antibiotics and probiotics. Finally, we highlight new therapeutic opportunities, under an integrative view, targeting the eCBS and the commensal microbiota in the context of neuroinflammation and MS.
30142811 Two case reports of pyoderma gangrenosum and systemic lupus erythematosus: A rare but nonf 2018 Aug RATIONALE: Pyoderma gangrenosum (PG), like other neutrophilic dermatosis, may be associated with a variety of systemic disorders including inflammatory bowel diseases, rheumatoid arthritis, and hematologic disorders. Conversely, the association between PG and systemic lupus erythematosus (SLE) has rarely been reported. PATIENT CONCERNS: We report here 2 cases of this association. DIAGNOSES: The first case involves a 32-year-old woman who developed, 1 year after SLE diagnosis, 3 painful nodular lesions of PG on her face, and cervical area. The second case was observed in a 37-year-old woman referred for ulcerative nodular papules of PG on her legs, whereas she had been diagnosed with SLE 10 years before. SLE was inactive in the first case, whereas PG occurred during a lupus flare up in the second one. INTERVENTIONS: We found 23 previous cases of SLE and PG in the literature with most cases (12/20) occurring during a lupus flare. OUTCOMES: Although rare, this association may be supported by common innate immunity dysregulation and abnormal neutrophil activation. LESSONS: PG and other neutrophilic diseases reported in patients with SLE may be added to the large clinical spectrum of cutaneous lesions observed in SLE.
30116953 The pivotal role of microRNA-21 in osteoclastogenesis inhibition by anthracycline glycosid 2019 Jan Osteopenic disorders such as osteoporosis and rheumatoid arthritis are characterized by excessive bone resorption by osteoclasts relative to bone formation by osteoblasts. MicroRNAs are emerging as key players in bone remodeling, modulating the functions of both osteoblasts and osteoclasts. Among them, miR-21 is highly expressed in osteoclast precursors and is known to regulate genesis, differentiation, and apoptosis of osteoclasts. The pro-osteoclastogenic nature of miR-21 makes it a potential candidate as a therapeutic target to treat bone disorders. We had previously demonstrated that anthroglycoside aloin derived from Aloe vera was effective in promoting osteoblastogenesis and inhibiting osteoclastogenesis. The present study investigated the role of miR-21 in aloin's inhibitory effect on osteoclast differentiation. Aloin effectively suppressed receptor activator of nuclear factor kappa-B (NFĸB) ligand (RankL)-induced miR-21 expression via repression of NFĸB activation. MiR-21 suppression resulted in upregulation of osteoclast suppressor programmed cell death protein 4 (PDCD4), and downregulation of osteoclast marker cathepsin K. Knockdown or gain-of-function studies revealed that miR-21 was pivotal to aloin's inhibitory effect on osteoclastogenesis. This study also highlights the dynamic potential of aloin as a therapeutic agent to treat osteopenic disorders.
30080442 Exploring the binding dynamics of etoricoxib with human hemoglobin: A spectroscopic, calor 2019 Jul Etoricoxib, widely used for the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and related conditions has ample affinity to bind with globular proteins. Here, the molecular interaction between purified human hemoglobin (HHb), a major heme protein and etoricoxib, a cyclooxygenase-2 inhibitor was studied by various spectroscopic, calorimetric, and molecular modeling techniques. The binding affected hypochromic changes in the Soret band of hemoglobin (Hb) and induced remarkable quenching of the intrinsic fluorescence property of protein molecules. Synchronous fluorescence studies revealed alterations in tryptophan (Trp) and tyrosine (Tyr) microenvironments of HHb molecule in presence of etoricoxib. Flouremetric and isothermal titration calorimetric studies suggested two binding sites in HHb for etoricoxib at three different temperatures (298.15, 303.15, and 310.15 K). Negative values of Gibbs energy change (ΔG(0)) and enthalpy change (ΔH(0)) strongly suggest that it is spontaneous and exothermic reaction, mainly stabilized by hydrogen bonding as evidenced by sucrose binding assay. These findings support our in silico molecular docking study, which specified the binding site and the non-covalent interactions involved in the association. Moreover, the interaction impacts on structural integrity and functional aspects of HHb as confirmed by decreased α helicity, increased free iron release, increased rate of co-oxidation, and decreased rate of esterase activity. Overall, these studies conclude that etoricoxib leads to a remarkable alteration in the conformational aspects of binding to HHb. Communicated by Ramaswamy H. Sarma.
29915656 A deadly prescription: combination of methotrexate and trimethoprim-sulfamethoxazole. 2018 Methotrexate (MTX) is a chemotherapeutic synthetic(s) phase cell cycle inhibitor, and its role has evolved as an immunological agent in autoimmune diseases like rheumatoid arthritis, psoriasis, and systemic lupus erythematosus, etc. Trimethoprim-sulfamethoxazole (TS) is one of the most widely prescribed antibiotics commonly used for urinary tract infections, exacerbations of chronic bronchitis, traveler's diarrhea, and pneumocystis pneumonia. Both MTX and TS can have significantly overlapping side effects involving dermatologic, renal, and hematological systems, and the combination of these can be deadly. Our case is about the combination of MTX and TS that leads to mucocutaneous ulceration, leukopenia, and renal insufficiency. The purpose of this case is to increase awareness of potentially significant toxicity from the combination of MTX with TS. Abbreviations: MTX: methotrexate; TS: trimethoprim-sulfamethoxazole; ED: emergency department; IV: intravenous; GI: gastrointestinal; NSAIDs: nonsteroidal anti-inflammatory drugs.
29914252 Saliva levels of caspase-1, TNF-α, and IFN-γ in primary Sjögren's syndrome: oral mucosa 2018 Jun 14 Background/aim: Abnormalities in oral mucosal immunity contribute to complex pathogenesis of primary Sjögren's syndrome (pSjS). We aimed to measure saliva and serum levels of caspase-1, tumor necrosis factor-alpha (TNF-α) and interferon gamma (IFN-γ) in patients with pSjS. Materials and methods: We studied 43 pSjS patients fulfilling the AECG criteria and 30 age/sex-matched healthy controls, as well as 39 rheumatoid arthritis (RA) patients as a disease control group. ESSDAI scores were less than seven in all patients with pSjS, indicating low disease activity. Quantitative analyses were made in serum and whole saliva samples. The statistical analysis was performed using SPSS 19.0. Results: While no significant difference was found in serum measurements, saliva levels of TNF-α and caspase-1 were significantly higher in pSjS patients versus healthy controls when using the Mann-Whitney U test. On the other hand, in the pSjS group, saliva levels of TNF-α and caspase-1 were also significantly higher compared to the RA group using Student's t-test. In the pSjS group, those parameters did not show any correlation with disease duration, seropositivity, and smoking. Conclusion: Despite low disease activity, saliva TNF-α and caspase-1 levels were found to be significantly higher in the pSjS group, which may suggest a possible advantage of local anticytokine treatments in selected cases.