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Medicina (Kaunas, Lithuania) Oct 2021Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease with autosomal recessive transmission, characterized by periodic fever attacks with self-limited... (Review)
Review
Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease with autosomal recessive transmission, characterized by periodic fever attacks with self-limited serositis. Secondary amyloidosis due to amyloid A renal deposition represents the most fearsome complication in up to 8.6% of patients. Amyloidosis A typically reveals a nephrotic syndrome with a rapid progression to end-stage kidney disease still. It may also involve the cardiovascular system, the gastrointestinal tract and the central nervous system. Other glomerulonephritis may equally affect FMF patients, including vasculitis such as IgA vasculitis and polyarteritis nodosa. A differential diagnosis among different primary and secondary causes of nephrotic syndrome is mandatory to determine the right therapeutic choice for the patients. Early detection of microalbuminuria is the first signal of kidney impairment in FMF, but new markers such as Neutrophil Gelatinase-Associated Lipocalin (NGAL) may radically change renal outcomes. Serum amyloid A protein (SAA) is currently considered a reliable indicator of subclinical inflammation and compliance to therapy. According to new evidence, SAA may also have an active pathogenic role in the regulation of NALP3 inflammasome activity as well as being a predictor of the clinical course of AA amyloidosis. Beyond colchicine, new monoclonal antibodies such as IL-1 inhibitors anakinra and canakinumab, and anti-IL-6 tocilizumab may represent a key in optimizing FMF treatment and prevention or control of AA amyloidosis.
Topics: Amyloidosis; Colchicine; Familial Mediterranean Fever; Humans; Kidney; Kidney Diseases
PubMed: 34684086
DOI: 10.3390/medicina57101049 -
Frontiers in Immunology 2020Autoinflammatory diseases (AIDs) represent a rare and heterogeneous group of disorders characterized by recurrent episodes of inflammation and a broad range of clinical... (Review)
Review
Autoinflammatory diseases (AIDs) represent a rare and heterogeneous group of disorders characterized by recurrent episodes of inflammation and a broad range of clinical manifestations. The most common symptoms involve recurrent fevers, musculoskeletal symptoms, and serositis; however, AIDs can also lead to life-threatening complications, such as macrophage activation syndrome (MAS) and systemic AA amyloidosis. Typical monogenic periodic fever syndromes include cryopyrin-associated periodic fever syndrome (CAPS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency/hyper IgD syndrome (MKD/HIDS), and familial Mediterranean fever (FMF). However, a number of other clinical entities, such as systemic juvenile idiopathic arthritis (sJIA), adult-onset Still's disease (AOSD), Kawasaki disease (KD) and idiopathic recurrent pericarditis (IRP), display similar phenotypical and immunological features to AIDs. All these diseases are pathophysiologicaly characterized by dysregulation of the innate immune system and the central pathogenic role is attributed to the IL-1 cytokine family (IL-1α, IL-1β, IL-1Ra, IL-18, IL-36Ra, IL-36α, IL-37, IL-36β, IL-36g, IL-38, and IL-33). Therefore, reasonable therapeutic approaches aim to inhibit these cytokines and their pathways. To date, several anti-IL-1 therapies have evolved. Each drug differs in structure, mechanism of action, efficacy for the treatment of selected diseases, and side effects. Most of the available data regarding the efficacy and safety of IL-1 inhibitors are related to anakinra, canakinumab, and rilonacept. Other promising therapeutics, such as gevokizumab, tadekinig alfa, and tranilast are currently undergoing clinical trials. In this review, we provide sophisticated and up-to-date insight into the therapeutic uses of different IL-1 inhibitors in monogenic periodic fever syndromes.
Topics: Anti-Inflammatory Agents; Hereditary Autoinflammatory Diseases; Humans; Interleukin-1
PubMed: 33603750
DOI: 10.3389/fimmu.2020.619257 -
Microbiology Spectrum Oct 2022Duck infectious serositis, also known as Riemerella anatipestifer disease, infects domestic ducks, geese, and turkeys and wild birds. However, the regulatory mechanism...
Duck infectious serositis, also known as Riemerella anatipestifer disease, infects domestic ducks, geese, and turkeys and wild birds. However, the regulatory mechanism of its pathogenicity remains unclear. The PhoPR two-component system (TCS) was first reported in Gram-negative bacteria in our previous research and was demonstrated to be involved in virulence and gene expression. Here, DNA affinity purification sequencing (DAP-seq) was applied to further explore the regulation of PhoPR in relation to pathogenicity in R. anatipestifer. A conserved motif was identified upstream of 583 candidate target genes which were directly regulated by PhoP. To further confirm the genes which are regulated by PhoR and PhoP, single-gene-deletion strains were constructed. The results of transcriptome analysis using next-generation RNA sequencing showed 136 differentially expressed genes (DEGs) between the Δ strain and the wild type (WT) and 183 DEGs between the Δ strain and the WT. The candidate target genes of PhoP were further identified by combining transcriptome analysis and DAP-seq, which revealed that the main direct regulons of PhoP are located on the membrane and PhoP is involved in regulating aerotolerance. Using the duck model, the pathogenicity of Δ and Δ mutants was found to be significantly lower than that of the WT. Together, our findings provide insight into the direct regulation of PhoP and suggest that is essential for the pathogenicity of R. anatipestifer. The gene deletion strains are expected to be candidate live vaccine strains of R. anatipestifer which can be used as ideal genetic engineering vector strains for the expression of foreign antigens. Riemerella anatipestifer is a significant pathogen with high mortality in the poultry industry that causes acute septicemia and infectious polyserositis in ducks, chickens, geese, and other avian species. Previously, we characterized the two-component system encoded by and found that R. anatipestifer almost completely lost its pathogenicity for ducklings when was deleted. However, the mechanism of PhoPR regulation of virulence in R. anatipestifer had not been deeply explored. In this study, we utilized DAP-seq to explore the DNA-binding sites of PhoP as a response regulator in the global genome. Furthermore, and were deleted separately, and transcriptomics analysis of the corresponding gene deletion strains was performed. We identified a series of directly regulated genes of the PhoPR two-component system. The duckling model showed that both PhoP and PhoR are essential virulence-related factors in R. anatipestifer.
Topics: Animals; Bacterial Proteins; Chickens; Ducks; Flavobacteriaceae Infections; Poultry Diseases; Vaccines, Attenuated; Virulence; Virulence Factors; Genome, Bacterial
PubMed: 36197298
DOI: 10.1128/spectrum.01883-22 -
Respirology Case Reports Nov 2021A 63-year-old female presented with chest pain and fever, and was found to have recurrent pleuropericardial effusions. Extensive investigations including infection...
A 63-year-old female presented with chest pain and fever, and was found to have recurrent pleuropericardial effusions. Extensive investigations including infection screen and serologies, autoimmune screen and pleural and pericardial biopsy revealed no secondary aetiologies. She was diagnosed with idiopathic recurrent serositis (IRS). Our patient developed rash to naproxen, so she was started on colchicine monotherapy and responded well clinically. A review of the literature demonstrated that pleuropericardial effusions are rare occurrences, with patients occasionally being perceived as a medical enigma. This case study recommends an approach to guide physicians in their diagnosis and management of patients with pleuropericardial syndrome. Our case had an inflammatory phenotype, either autoimmune or seronegative serositis of unclear aetiology, which was recurrent and required pharmacological treatment. While the treatment for IRS lies in combined therapy with Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and colchicine, monotherapy with colchicine was effective in the treatment and preventing recurrence in our unique case.
PubMed: 34667614
DOI: 10.1002/rcr2.859 -
World Journal of Gastrointestinal... Nov 2014Extraintestinal manifestations occur commonly in inflammatory bowel diseases (IBD). Pulmonary manifestations (PM) of IBD may be divided in airway disorders, interstitial... (Review)
Review
Extraintestinal manifestations occur commonly in inflammatory bowel diseases (IBD). Pulmonary manifestations (PM) of IBD may be divided in airway disorders, interstitial lung disorders, serositis, pulmonary vasculitis, necrobiotic nodules, drug-induced lung disease, thromboembolic lung disease and enteropulmonary fistulas. Pulmonary involvement may often be asymptomatic and detected solely on the basis of abnormal screening tests. The common embryonic origin of the intestine and the lungs from the primitive foregut, the co-existence of mucosa associated lymphoid tissue in both organs, autoimmunity, smoking and bacterial translocation from the colon to the lungs may all be involved in the pathogenesis of PM in IBD. PM are mainly detected by pulmonary function tests and high-resolution computed tomography. This review will focus on the involvement of the airways in the context of IBD, especially stenoses of the large airways, tracheobronchitis, bronchiectasis, bronchitis, mucoid impaction, bronchial granulomas, bronchiolitis, bronchiolitis obliterans syndrome and the co-existence of IBD with asthma, chronic obstructive pulmonary disease, sarcoidosis and a1-antitrypsin deficiency.
PubMed: 25400999
DOI: 10.4291/wjgp.v5.i4.560 -
Lupus Science & Medicine Apr 2023SLE is an autoimmune disease that predominantly affects women. As most epidemiological and interventional studies are on populations with a clear female prevalence, the...
BACKGROUND
SLE is an autoimmune disease that predominantly affects women. As most epidemiological and interventional studies are on populations with a clear female prevalence, the influence of gender in disease course, drug response and damage accrual is yet to be fully explored and comprehended.
OBJECTIVES
To describe gender differences in disease course, comorbidities, use of medications and long-term outcomes of a large cohort of patients with SLE.
METHODS
Retrospective gender-based analysis of prospectively collected data from a monocentric cohort of Caucasian patients with SLE with at least 1 year of follow-up.
RESULTS
417 patients were included, 51 men and 366 women. Men displayed a significantly higher median age at disease onset and diagnosis and a higher prevalence of late-onset SLE, serositis at disease onset, antiphospholipid syndrome (APS) and use of mycophenolate within the first year of disease. Women had a higher prevalence of haematological abnormalities, a higher cumulative exposure to azathioprine and higher cumulative dose of glucocorticoids at 5 years. Male patients had a shorter time to first damage item and a higher prevalence of damage at 1 and 5 years, but this association was no longer significant when late-onset patients were excluded. No differences were found in prevalence of childhood onset, delay between onset and diagnosis, time to renal involvement and histology, cumulative autoantibody positivity, number of flares and hospitalisations, median SLE Damage Index score, type of damage, age and time to first cardiovascular event, chronic kidney disease and death.
CONCLUSIONS
In our cohort, clinical manifestations and disease course were similar in male and female patients; however, male patients displayed higher prevalence of APS and early damage accrual probably due to the later disease onset. These data highlight the importance of an intensive follow-up, prevention and treatment of complications in this category of patients, especially in the first years of disease.
Topics: Humans; Male; Female; Retrospective Studies; Sex Factors; Lupus Erythematosus, Systemic; Antiphospholipid Syndrome; Glucocorticoids; Disease Progression
PubMed: 37185240
DOI: 10.1136/lupus-2022-000880 -
Journal of Clinical Tuberculosis and... May 2023Tuberculosis (TB) is among the most common cause of serositis. There are many uncertainties in diagnostic and therapeutic approach to serous membranes tuberculosis. Our... (Review)
Review
Tuberculosis (TB) is among the most common cause of serositis. There are many uncertainties in diagnostic and therapeutic approach to serous membranes tuberculosis. Our aim in the present review is to discuss the regional facilities for timely diagnosis, rapid decision-making and appropriate treatment regarding to serous membranes tuberculosis; with emphasis on situation in Iran. A comprehensive literature searches about the status of serous membranes tuberculosis in Iran were performed in English databases including Google Scholar, Science Direct, Scopus, Pub Med, and Web of Sciences, Persian SID databases, between 2000 and 2021. The main findings of the present review are as follow: a) pleural tuberculosis is more common than pericardial or peritoneal tuberculosis. b) Clinical manifestations are non-specific and so non-diagnostic. c) Smear and culture, PCR and characteristic granulomatous reaction have been used for definitive TB diagnosis by physicians. d) With Adenosine Deaminase Assays and Interferon-Gamma Release Assays in mononuclear dominant fluid, a possible diagnosis of TB is proposed by experienced physicians in Iran. e) In area of endemic for tuberculosis including Iran, a possible diagnosis of TB is enough to begin empirical treatment. f) In patients with uncomplicated tuberculosis serositis, treatment is similar to pulmonary tuberculosis. First line drugs are prescribed unless evidence of MDR-TB is detected. g) The prevalence of drug resistant tuberculosis (MDR-TB) in Iran is between 1% and 6%, and are treated by empirical standardized treatment. h) It is not known whether adjuvant corticosteroids are effective in preventing long term complication. i) Surgery may be recommended for MDR-TB. Tamponade or constrictive pericarditis and intestinal obstruction. In conclusion, it is recommended to consider serosal tuberculosis in patients who have unknown mononuclear dominant effusion and prolonged constitutional symptoms. Experimental treatment with first line anti-TB drugs can be started based on possible diagnostic findings.
PubMed: 36874623
DOI: 10.1016/j.jctube.2023.100354 -
BMC Rheumatology Dec 2022NLRP3-associated autoinflammatory diseases (NLRP3-AID) are rare genetic autoinflammatory diseases characterized by chronic inflammation and an urticaria-like rash. We...
BACKGROUND
NLRP3-associated autoinflammatory diseases (NLRP3-AID) are rare genetic autoinflammatory diseases characterized by chronic inflammation and an urticaria-like rash. We report an unusual presentation of severe NLRP3-AID resulting in a significant diagnostic delay of more than three decades.
CASE PRESENTATION
The patient presented with early-onset serositis as well as prominent peripheral eosinophilia with organ infiltration, in the absence of the classic urticaria-like rash. DNA analysis by next generation sequencing revealed a sporadic class 4 mutation c.1991T > C (p.Met662Thr) in the NLRP3 gene, confirming a diagnosis of NLRP3-AID at 36 years old. Although treatment with anti-interleukin 1 agent led to clinical remission, irreversible sequelae, namely intellectual disability and deafness, remained.
CONCLUSION
This case highlights unique manifestations of NLRP3-AID, namely the absence of urticaria-like rash, eosinophilic organ infiltration, and pseudoseptic serositis. In order to avoid diagnostic delay and its dire consequences, NLRP3-AID should be suspected in patients displaying autoinflammatory features combined with serum and tissue eosinophilia and/or marked serositis, regardless of skin involvement.
PubMed: 36510304
DOI: 10.1186/s41927-022-00321-8 -
European Heart Journal Mar 2009Colchicine has been effectively used in the treatment of several inflammatory conditions, such as gouty attacks, serositis related to familial Mediterranean fever,... (Review)
Review
Colchicine has been effectively used in the treatment of several inflammatory conditions, such as gouty attacks, serositis related to familial Mediterranean fever, Behçet syndrome, and more recently also in acute and recurrent pericarditis. Growing evidence has shown that the drug may be useful to treat an acute attack and may be a way to cope with the prevention of pericarditis in acute and recurrent cases and after cardiac surgery. Nevertheless, clinicians are often sceptical about the efficacy of the drug, and concerns have risen on possible side effects and tolerability. In this review, we analyse current evidence to support the use of the drug, as well as possible harms and risks related to drug interactions, reaching the conclusion that colchicine is safe and useful in recurrent pericarditis, if specific precautions are followed, although less evidence supports its use for the treatment of acute pericarditis, where colchicine remains optional and there is a need for further multicentre confirmatory studies. This paper also reviews specific dosing and precautions for the clinical use.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Drug Administration Schedule; Drug Interactions; Humans; Pericarditis; Randomized Controlled Trials as Topic
PubMed: 19190012
DOI: 10.1093/eurheartj/ehn608 -
Singapore Medical Journal Mar 2009Familial Mediterranean fever (FMF) is an autosomal recessively-transmitted disease characterised by attacks of fever and serositis. Articular involvement is the second... (Review)
Review
Familial Mediterranean fever (FMF) is an autosomal recessively-transmitted disease characterised by attacks of fever and serositis. Articular involvement is the second most common manifestation following abdominal pain. Patients with FMF are considered to have an increased risk of sacroiliitis, while the association of such abnormalities with FMF has not been accepted uniformly. We report two cases of FMF with accompanying seronegative spondyloarthropathy, a 18-year-old boy and a 29-year-old man, and review the literature for FMF-related seronegative spondyloarthropathy.
Topics: Adolescent; Adult; Familial Mediterranean Fever; Fever; Humans; Male; Serositis; Spondylarthropathies; Young Adult
PubMed: 19352557
DOI: No ID Found