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ID PMID Title PublicationDate abstract
33613945 Guideline review: Tofacitinib for adults with moderately to severely active ulcerative col 2021 Tofacitinib is an oral, Janus kinase (JAK) molecule, which selectively inhibits Janus-associated tyrosine kinases JAK1 and JAK3. It has already shown efficacy in the treatment of rheumatoid arthritis and the prevention of organ allograft rejection in kidney transplantation. Two separate phase III placebo-controlled trials, assessing 8-week efficacy of tofacitinib induction for ulcerative colitis (UC), demonstrated superiority when compared with placebo. Tofacitinib also demonstrated robust efficacy versus placebo in the 52-week maintenance component of the same study. Tofacitinib has been recommended by the National Institute for Health and Care Excellence as an effective treatment option for adult patients with moderate to severe UC when conventional therapy or a biological agent cannot be tolerated or the disease has responded inadequately or lost response to treatment. We review the guidelines and provide brief commentary on the post hoc analysis related to lipid increases and thromboembolism risk, which have lead to changes in current therapeutic guidance.
33553231 Dietary Fish, Fish Nutrients, and Immune Function: A Review. 2020 Dietary habits have a major impact on the development and function of the immune system. This impact is mediated both by the intrinsic nutritional and biochemical qualities of the diet, and by its influence on the intestinal microbiota. Fish as a food is rich in compounds with immunoregulatory properties, among them omega-3 fatty acids, melatonin, tryptophan, taurine and polyamines. In addition, regular fish consumption favors the proliferation of beneficial members of the intestinal microbiota, like short-chain fatty acid-producing bacteria. By substituting arachidonic acid in the eicosanoid biosynthesis pathway, long-chain omega-3 fatty acids from fish change the type of prostaglandins, leukotrienes and thromboxanes being produced, resulting in anti-inflammatory properties. Further, they also are substrates for the production of specialized pro-resolving mediators (SPMs) (resolvins, protectins, and maresins), lipid compounds that constitute the physiological feedback signal to stop inflammation and give way to tissue reparation. Evidence from human observational and interventional studies shows that regular fish consumption is associated with reduced incidence of chronic inflammatory conditions like rheumatoid arthritis, and that continuous infusion of fish oil to tube-fed, critically ill patients may improve important outcomes in the ICU. There is also evidence from animal models showing that larger systemic concentrations of omega-3 fatty acids may counter the pathophysiological cascade that leads to psoriasis. The knowledge gained over the last few decades merits future exploration of the potential role of fish and its components in other conditions characterized by deregulated activation of immune cells and a cytokine storm like viral sepsis or COVID-19.
33187031 Dermatomyositis during COVID-19 Pandemic (A Case Series): Is there a Cause Effect Relation 2020 Nov Viruses have been shown to modify the clinical picture of several autoimmune diseases, including type 1 diabetes, systemic lupus erythematosus (SLE), rheumatoid arthritis and multiple sclerosis. Viral infections have also been considered as a possible trigger for autoimmune disorders like myositis through myositis specific antibodies. Dermatomyositis is an acquired inflammatory myopathy which is relatively rare with incidence of 9.3 per 1 million persons. Usually we come across 1-2 patients of dermatomyositis per year, amongst 800-1000 new patients in our tertiary care rheumatology services. A surge in the incidence was noted this year during the months of April-August of 2020, the period coinciding with the occurrence of corona virus (COVID-19) pandemic in the city of Mumbai, the total number of cases encountered being five in a span of six months. The following case series includes five such cases with review of available literature on virus-triggered autoimmunity with special reference to SARS-CoV-2 and the challenges of immunosuppression during this pandemic.
33117385 Non-inflammatory Physiology of "Inflammatory" Mediators - Unalamation, a New Paradigm. 2020 Many small molecules (mostly lipids derived from polyunsaturated fatty acids) and proteins (e. g., cytokines and chemokines) are labeled as inflammatory mediators for their role in eliciting physiological responses to injury. While acute inflammatory events are controlled by anti-inflammatory drugs, lasting damage to the tissues as a result of persistent inflammation is increasingly viewed as the root cause of many chronic diseases that include cardiovascular, neurological, and metabolic disorders, rheumatoid arthritis, and cancer. Interestingly, some of the "inflammatory" mediators also participate in normal developmental physiology without eliciting inflammation. Anti-inflammatory drugs that target the biosynthesis of these mediators are too indiscriminate to distinguish their two divergent physiological roles. A more precise definition of these two physiological processes partaken by the "inflammatory" mediators is warranted to identify their differences. The new paradigm is named "unalamation" ('ə'n'əlAmāSH(ə)n) to distinguish from inflammation and to identify appropriate intervention strategies to mitigate inflammation associated pathophysiology without affecting the normal developmental physiology.
32975053 The design of ibuprofen-loaded microbeads using polymers obtained from Xanthosoma sagittif 2020 Jan BACKGROUND: Ibuprofen is used both for acute and chronic disorders, such as ankylosing spondylitis, osteoarthritis and rheumatoid arthritis; however, ibuprofen causes gastrointestinal disturbances. Therefore, it would be desirable to design it as a sustained-release preparation. OBJECTIVES: To design ibuprofen microbeads using polymers obtained from Xanthosoma sagittifolium starch and Dillenia indica mucilage to provide sustained-release delivery of ibuprofen. MATERIAL AND METHODS: The polymers were extracted using standard methods and characterized by their material, physicochemical, elemental, and rheological profiles. Microbeads loaded with ibuprofen were prepared using the ionotropic gelation method utilizing blends of the polymers and sodium alginate. The microbeads were evaluated using particle shape, particle size, swelling index, entrapment efficiency, and release assays. RESULTS: The results showed that the polymers have distinct material and physicochemical properties unique to their botanical sources. The microbeads were spherical and free-flowing, and they rolled without friction. The swelling properties ranged from 47.62 ±2.74% to 79.49 ±3.66%. The particle size of the microbeads ranged from 88.14 ±68.57 μm to 214.90 ±66.95 μm, while the encapsulation efficiencies ranged from 20.67 ±4.66% to 83.61 ±6.35%. The dissolution times suggested that the concentration of the natural polymers in the bead formulation could be used to modulate the dissolution properties. Generally, formulations containing the mucilage yielded higher dissolution times than those containing the starch. The kinetics of drug release from the microbeads containing the polymer blends generally fitted the Korsmeyer-Peppas model. The highest similarity was found between formulations C6 and D4 with f2 of 81.07. CONCLUSIONS: The microbeads prepared with polymers obtained from Xanthosoma and Dillenia showed acceptable physicochemical properties, dependent upon polymer type, blend and concentration.
32935064 Chloroquine to fight COVID-19: A consideration of mechanisms and adverse effects? 2020 Sep The COVID-19 outbreak emerged in December 2019 and has rapidly become a global pandemic. A great deal of effort has been made to find effective drugs against this disease. Chloroquine (CQ) and hydroxychloroquine (HCQ) were widely adopted in treating COVID-19, but the results were contradictive. CQ/HCQ have been used to prevent and treat malaria and are efficacious anti-inflammatory agents in rheumatoid arthritis and systemic lupus erythematosus. These drugs have potential broad-spectrum antiviral properties, but the underlying mechanisms are speculative. In this review, we re-evaluated the treatment outcomes and current hypothesis for the working mechanisms of CQ/HCQ as COVID-19 therapy with a special focus on disruption of Ca(2+) signaling. In so doing, we attempt to show how the different hypotheses for CQ/HCQ action on coronavirus may interact and reinforce each other. The potential toxicity is also noted due to its action on Ca(2+) and hyperpolarization-activated cyclic nucleotide-gated channels in cardiac myocytes and neuronal cells. We propose that intracellular calcium homeostasis is an alternative mechanism for CQ/HCQ pharmacology, which should be considered when evaluating the risks and benefits of therapy in these patients and other perspective applications.
32934857 PD-1 Inhibitor Therapy in a Patient with Preexisting P-ANCA Vasculitis: A Case Report and 2020 BACKGROUND: Recurrent endometrial cancer after definitive therapy is a lethal disease. Recently, immune checkpoint inhibitors (ICI) have improved the management of mismatch repair-deficient (MSI-H) endometrial cancer. Autoimmune side effects are known to occur with ICI. As a result, patients with preexisting autoimmune diseases are excluded from studies involving these drugs. This has led to challenges in clinical practice regarding the use of ICI in otherwise eligible patients with underlying autoimmune disease. Case Presentation. We present the case of an 81-year-old woman with an underlying autoimmune vasculitis and recurrent, metastatic endometrial adenocarcinoma with microsatellite instability, who was treated with an immune checkpoint inhibitor. This patient received pembrolizumab, an immune checkpoint inhibitor that targets the programmed cell death-1 immune checkpoint. Ultimately, she was treated for 4 months with pembrolizumab and benefited from stable disease during this period. She remained asymptomatic from her underlying autoimmune P-ANCA vasculitis. A review of the scientific literature reveals several cases of the successful use of immune checkpoint inhibitors in patients with autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease. CONCLUSION: This is one of the first reports of a patient with an underlying autoimmune vasculitis successfully treated with an immune checkpoint inhibitor without exacerbating her underlying autoimmune condition. Carefully selected patients with underlying autoimmune vasculitis can be safely treated with ICI.
32922569 Critical roles of super-enhancers in the pathogenesis of autoimmune diseases. 2020 The super-enhancer (SE) is a cluster of enhancers involved in cell differentiation via enhanced gene expression that determines cell identity. Meanwhile, genome-wide association studies (GWASs) have reported the presence of gene clusters containing single nucleotide polymorphisms (SNPs) susceptible to various diseases. According to cell types, these disease-susceptible SNPs are frequently detected in activated SE domains. However, the roles of SEs in the pathogenesis of various diseases remain unclear. This review first presents various functions of enhancer RNAs (eRNAs) transcribed from SEs. Next, it describes how SNPs and eRNAs are involved in the pathology of each autoimmune disease, with a focus on typical diseases such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. This review aims to describe the roles of SEs in the pathogenesis of autoimmune diseases through multiple interactions of these factors, as well as a future outlook on this issue.
32753567 Synovial Cell Migration is Associated with B Cell Activating Factor Expression Increased b 2020 Sep 1 Fibroblast-like synoviocytes (FLS) play a crucial role in initiating rheumatoid arthritis. B-cell activating factor (BAFF) plays a role in FLS survival as well as in B cell maturation and maintenance. Here, we investigated whether tumor necrosis factor (TNF)-α- induced BAFF expression controls FLS migration and whether BAFF expression in FLS could be regulated by KR33426 which is the inhibitor of BAFF binding to BAFF receptors (BAFF-R) by using MH7A synovial cells transfected with the SV40 T antigen. More TNF-α-treated cells migrated compared to the control. TNF-α increased BAFF expression in FLS, significantly. FLS migration was inhibited by the transfection with BAFF-siRNA. KR33426 also inhibited BAFF expression increased by TNF-α treatment in FLS as judged by western blotting, PCR, and transcriptional activity assay. Kinases including JNK, p38 and Erk were activated by TNF-α treatment. While JNK and p38 were inhibited by KR33426 treatment, no changes in Erk were observed. Transcription factors including p65, c-Fos, CREB and SP1 were enhanced by TNF-α treatment. Among them, c-Fos was inhibited by KR33426 treatment. Small interference(si)-RNA of c-fos decreased BAFF transcriptional activity. FLS migration induced by TNF-α was inhibited by the transfection with BAFF-siRNA. KR33426 increased Twist, Snail, Cadherin-11 and N-Cadherin. In contrast, KR33426 decreased E-cadherin and TNF-α-enhanced CCL2. Taken together, our results demonstrate that synovial cell migration via CCL2 expression could be regulated by BAFF expression which is decreased by KR33426 and c-Fos-siRNA. It suggests for the first time that the role of BAFF-siRNA on FLS migration might be matched in the effect of KR33426 on BAFF expression.
32714114 A Pharmacological Interactome between COVID-19 Patient Samples and Human Sensory Neurons R 2020 May 4 The SARS-CoV-2 virus infects cells of the airway and lungs in humans causing the disease COVID-19. This disease is characterized by cough, shortness of breath, and in severe cases causes pneumonia and acute respiratory distress syndrome (ARDS) which can be fatal. Bronchial alveolar lavage fluid (BALF) and plasma from mild and severe cases of COVID-19 have been profiled using protein measurements and bulk and single cell RNA sequencing. Onset of pneumonia and ARDS can be rapid in COVID-19, suggesting a potential neuronal involvement in pathology and mortality. We sought to quantify how immune cells might interact with sensory innervation of the lung in COVID-19 using published data from patients, existing RNA sequencing datasets from human dorsal root ganglion neurons and other sources, and a genome-wide ligand-receptor pair database curated for pharmacological interactions relevant for neuro-immune interactions. Our findings reveal a landscape of ligand-receptor interactions in the lung caused by SARS-CoV-2 viral infection and point to potential interventions to reduce the burden of neurogenic inflammation in COVID-19 disease. In particular, our work highlights opportunities for clinical trials with existing or under-development rheumatoid arthritis and other (e.g. CCL2, CCR5 or EGFR inhibitors) drugs to treat high risk or severe COVID-19 cases.
32566265 The Role of Th17 Cells and IL-17 in Th2 Immune Responses of Allergic Conjunctivitis. 2020 Allergic conjunctivitis (AC) is a common allergic disease that is often associated with the onset of rhinitis or asthma. The incidence of AC has increased significantly in recent years possibly due to air pollution and climate warming. AC seriously affects patients' quality of life and work efficiency. Th (T-helper) 2 immune responses and type I hypersensitivity reactions are generally considered the basis of occurrence of AC. It has been found that new subpopulations of T-helper cells, Th17 cells that produce interleukin-17 (IL-17), play an important role in the Th2-mediated pathogenesis of conjunctivitis. Studies have shown that Th17 cells are involved in a variety of immune inflammation, including psoriasis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and asthma. However, the role of Th17 and IL-17 in AC is unclear. This paper will focus on how T-helper 17 cells and interleukin-17 are activated in the Th2 immune response of allergic conjunctivitis and how they promote the Th2 immune response of AC.
32463807 Prevalence of and Changes in Tooth Loss Among Adults Aged ≥50 Years with Selected Chroni 2020 May 29 Extensive tooth loss can lead to poor diet resulting in weight loss or obesity (1). It can also detract from physical appearance and impede speech, factors that can restrict social contact, inhibit intimacy, and lower self-esteem (1). Chronic medical conditions and oral conditions share common risk factors (2). Persons with chronic conditions are more likely to have untreated dental disease, which can result in tooth loss. Three measures of tooth loss during 1999-2004 and 2011-2016 were estimated by comparing data from the National Health and Nutrition Examination Survey (NHANES) for each period among adults aged ≥50 years with selected chronic conditions.* The three measures were 1) edentulism (having no teeth); 2) severe tooth loss (having eight or fewer teeth) (3); and 3) lacking functional dentition (having <20 teeth out of 28, which is considered a full set for the purpose of NHANES assessments) (4). During 2011-2016, prevalences of edentulism and severe tooth loss were ≥50% higher among adults with fair or poor general health, rheumatoid arthritis, asthma, diabetes, emphysema, heart disease, liver condition, or stroke than among those with those adults without the chronic condition. Lack of functional dentition was also more prevalent among adults with chronic conditions than among persons without these conditions. Tooth loss is preventable with self-care and routine dental visits (1). To encourage these behaviors, public health professionals can educate the public about the association between having a chronic condition and tooth loss, and primary care providers can educate their patients about the importance of healthy behaviors and screen and refer them for needed dental care.
32351667 Role of the eNOS Uncoupling and the Nitric Oxide Metabolic Pathway in the Pathogenesis of 2020 Atherosclerosis and its clinical complications constitute the major healthcare problems of the world population. Due to the central role of endothelium throughout the atherosclerotic disease process, endothelial dysfunction is regarded as a common mechanism for various cardiovascular (CV) disorders. It is well established that patients with rheumatic autoimmune diseases are characterized by significantly increased prevalence of cardiovascular morbidity and mortality compared with the general population. The current European guidelines on cardiovascular disease (CVD) prevention in clinical practice recommend to use a 1,5-factor multiplier for CV risk in rheumatoid arthritis as well as in other autoimmune inflammatory diseases. However, mechanisms of accelerated atherosclerosis in these diseases, especially in the absence of traditional risk factors, still remain unclear. Oxidative stress plays the major role in the endothelial dysfunction and recently is strongly attributed to endothelial NO synthase dysfunction (eNOS uncoupling). Converted to a superoxide-producing enzyme, uncoupled eNOS not only leads to reduction of the nitric oxide (NO) generation but also potentiates the preexisting oxidative stress, which contributes significantly to atherogenesis. However, to date, there are no systemic analyses on the role of eNOS uncoupling in the excess CV mortality linked with autoimmune rheumatic diseases. The current review paper addresses this issue.
32289395 Characterizing the adverse dermatologic effects of hydroxychloroquine: A systematic review 2020 Aug BACKGROUND: Hydroxychloroquine is associated with myriad adverse dermatologic effects, most of which are poorly characterized by the literature, with unknown frequencies and risk factors. OBJECTIVE: To conduct a systematic review of the adverse dermatologic effects and predisposing factors of hydroxychloroquine toxicity. RESULTS: The review included 94 articles comprising 689 dermatologic adverse effects. A total of 21 unique dermatologic reactions were reported, most commonly drug eruption or rash (358 cases), cutaneous hyperpigmentation (116), pruritus (62), acute generalized exanthematous pustulosis (27), Stevens-Johnson syndrome or toxic epidermal necrolysis (26), hair loss (12), and stomatitis (11). Almost all underlying conditions were rheumatologic or autoimmune in nature, composed primarily of lupus erythematous (72% of all cases) and rheumatoid arthritis (14%). The range of reported mean cumulative dosages was wide, with some adverse reactions found after as little as 3 g or as much as 2500 g. LIMITATIONS: Dermatologic adverse events and primary diagnoses related to the use of hydroxychloroquine may be under-reported as only case reports and clinical trials that reported at least 1 dermatologic adverse effect were included. CONCLUSION: Although hydroxychloroquine is generally well tolerated, dermatologic adverse effects involving the skin, hair, or nails are a frequent and significant complication. Most of these reactions occurred after treatment of autoimmune conditions, often manifesting on the skin after a wide range of cumulative dosages.
32280720 Peripheral B Cell Subsets in Autoimmune Diseases: Clinical Implications and Effects of B C 2020 Antibody-secreting cells (ASCs) play a fundamental role in humoral immunity. The aberrant function of ASCs is related to a number of disease states, including autoimmune diseases and cancer. Recent insights into activated B cell subsets, including naïve B cell to ASC stages and their resultant cellular disturbances, suggest that aberrant ASC differentiation occurs during autoimmune diseases and is closely related to disease severity. However, the mechanisms underlying highly active ASC differentiation and the B cell subsets in autoimmune patients remain undefined. Here, we first review the processes of ASC generation. From the perspective of novel therapeutic target discovery, prediction of disease progression, and current clinical challenges, we further summarize the aberrant activity of B cell subsets including specialized memory CD11c(hi)T-bet(+) B cells that participate in the maintenance of autoreactive ASC populations. An improved understanding of subgroups may also enhance the knowledge of antigen-specific B cell differentiation. We further discuss the influence of current B cell therapies on B cell subsets, specifically focusing on systemic lupus erythematosus, rheumatoid arthritis, and myasthenia gravis.
32075269 The Role of Th17-Related Cytokines in Atopic Dermatitis. 2020 Feb 15 T helper-17 (Th17) cells, which mainly produce IL-17, are associated with development of various autoimmune diseases such as rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and psoriasis. IL-17 and related cytokines are therapeutic targets of these diseases. In atopic dermatitis (AD), Th2 cytokines such as IL-4 and IL-13 are regarded to be the main player of the disease; however, Th17 cytokines are also expressed in AD skin lesions. Expression of IL-22 rather than IL-17 is predominant in AD skin, which is contrary to cytokine expression in psoriasis skin. Relatively low IL-17 expression in AD skin can induce relatively low antimicrobial peptide expression, which may be a reason why bacterial infection is frequently seen in AD patients. Failure of clinical trials for investigating the efficacy of anti-IL-12/23 p40 in AD has suggested that IL-17 expressed in skin lesions should not be the main player but a bystander responding to barrier dysfunction.
32060846 CCL20 Signaling in the Tumor Microenvironment. 2020 CCL20, as a chemokine, plays an important role in rheumatoid arthritis, psoriasis, and other diseases by binding to its receptor CCR6. Recent 10 years' research has demonstrated that CCL20 also contributes to the progression of many cancers, such as liver cancer, colon cancer, breast cancer, pancreatic cancer, and gastric cancer. This article reviews and discusses the previous studies on CCL20 roles in cancers from the aspects of its specific effects on various cancers, its remodeling on tumor microenvironment (TME), its synergistic effects with other cytokines in tumor microenvironment, and the specific mechanisms of CCL20 signal activation, illustrating CCL20 signaling in TME from multiple directions.
32031205 Sec-O-glucosylhamaudol suppressed inflammatory reaction induced by LPS in RAW264.7 cells t 2020 Feb 28 As a major bioactive compound from the Saposhnikovia divaricata (Turcz.) Schischk, sec-O-glucosylhamaudol (SOG), has been reported to have anti-nociceptive activity and high 5-lipoxygenase (5-LOX) activity. Nevertheless, the mechanism of the potential anti-inflammatory effects of SOG is unclear. The anti-inflammatory impacts of SOG in RAW 264.7 cell lines stimulated by LPS were explored in the present study. It was found that SOG dose-dependently reduced the emergence of inflammation cytokines, such as IL-6 and TNF-α in Raw264.7 murine macrophages stimulated by LPS. Real-time PCR assay demonstrated the SOG dose-dependently inhibited transcription of these cytokines as well. In addition, it was also found that NF-κB activation and MAPKs phosphorylation including p38, JNK and ERK1/2 induced by LPS were suppressed by SOG. Due to its anti-inflammatory activity, our results suggest that SOG might have therapeutic effects on inflammatory disease, such as acute lung injury or rheumatoid arthritis.
33408923 Surgical treatment of complete fifth lumbar osteoporotic vertebral burst fracture: A retro 2020 BACKGROUND: Due to its rarity, surgical treatments for a complete fifth lumbar osteoporotic vertebral burst fracture (L5 OVBF) have yet to be well documented as compared to that for osteoporotic vertebral fractures of the thoracolumbar spine. The current case report discusses details of the surgical outcomes following posterior decompression and fusion for a complete L5 OVBF. CASE DESCRIPTION: Three women, ranging in age from 69 years to 82 years, were surgically treated for a complete L5 OVBF. Two of these patients were being treated for rheumatoid arthritis. Surgery was performed using the L5 shortening osteotomy or vertebroplasty, with one- or two-level posterior lumbar interbody fusion, and posterior spinal fixation for the L2 or L3 to the pelvis. Although the spinal alignment parameters, which included lumbar lordosis (LL), pelvic incidence-lumbar lordosis, T1 pelvic angle, and sagittal vertical axis, were better as compared to that observed before the surgery, these worsened at the final follow-up due to clinical fractures that occurred at the adjacent vertebral body and proximal junctional kyphosis. Compared to preoperative Japanese Orthopaedic Association (JOA) scores, postoperative JOA scores were improved and maintained at the final follow-up. CONCLUSION: Posterior surgery of a complete L5 OVBF led to improvement of both the JOA score and spinal alignment after the surgery. Despite a worsening of the spinal alignment parameters, the JOA score was maintained at the final follow-up.
33344486 Secondary Membranous Nephropathy. A Narrative Review. 2020 Membranous nephropathy (MN) is a common cause of proteinuria and nephrotic syndrome all over the world. It can be subdivided into primary and secondary forms. Primary form is an autoimmune disease clinically characterized by nephrotic syndrome and slow progression. It accounts for ~70% cases of MN. In the remaining cases MN may be secondary to well-defined causes, including infections, drugs, cancer, or autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), urticarial vasculitis, sarcoidosis, thyroiditis, Sjogren syndrome, systemic sclerosis, or ankylosing spondylitis. The clinical presentation is similar in primary and secondary MN. However, the outcome may be different, being often related to that of the original disease in secondary MN. Also, the treatment may be different, being targeted to the etiologic cause in secondary MN. Thus, the differential diagnosis between primary and secondary MN is critical and should be based not only on history and clinical features of the patient but also on immunofluorescence and electron microscopy analysis of renal biopsy as well as on the research of circulating antibodies. The identification of the pathologic events underlying a secondary MN is of paramount importance, since the eradication of the etiologic factors may be followed by remission or definitive cure of MN. In this review we report the main diseases and drugs responsible of secondary MN, the outcome and the pathogenesis of renal disease in different settings and the possible treatments.