scholarly journals Adult-onset systemic autoinflammatory disorders: a clinical approach

Reumatismo ◽  
2020 ◽  
Vol 71 (4) ◽  
pp. 177-188
Author(s):  
T. Borges ◽  
A. Barbosa ◽  
S. Silva
Keyword(s):  
Late Onset ◽  
Interleukin 1 ◽  
Immunosuppressive Agents ◽  
Unknown Origin ◽  
Adult Patients ◽  
Clinical Approach ◽  
Adult Onset ◽  
Autoinflammatory Disorders ◽  
Acute Phase Reactants ◽  
Mixed Pattern

Autoinflammatory disorders (AIDs) are a subgroup of immune-mediated syndromes that result from a primary dysfunction of the innate immune system. AIDs can be either monogenic or polygenic diseases. Unlike organspecific AIDs, systemic AIDs are characterized by fever and/or elevation of acute-phase reactants. This review aims to describe the most common adult-onset systemic AIDs, focusing mostly on polygenic and mixed-pattern diseases which are expected to be more prevalent in adult patients than monogenic AIDs overall. The literature was searched in Medline database. Organ-specific or childhood-onset systemic AIDs were excluded. AIDs were divided in three distinct groups: mixed-pattern, polygenic and adult-onset monogenic AIDs. Most adult-onset AIDs are polygenic but late-onset disease is not rare among monogenic AIDs such as familial Mediterranean fever (FMF). The diagnosis of systemic AIDs in adults is often delayed due to several factors and sometimes it is only established when amyloidosis or other complications are present. Therefore, it probably makes sense to primarily exclude common AIDs in adult patients with fever of unknown origin (and probably different presentations such as polyserositis) since a high prevalence of adult-onset Still’s disease or FMF is usually expected. Colchicine, nonsteroidal anti-inflammatory drugs, steroids, immunosuppressive agents, interleukin-1 inhibitors and tumor necrosis factor antagonists constitute common therapeutic options for systemic AIDs.

scholarly journals Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH

Blood ◽  
2011 ◽  
Vol 118 (22) ◽  
pp. 5794-5798 ◽  
Author(s):  
Kejian Zhang ◽  
Michael B. Jordan ◽  
Rebecca A. Marsh ◽  
Judith A. Johnson ◽  
Diane Kissell ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Late Onset ◽  
Adult Patients ◽  
Adult Onset ◽  
Test Results ◽  
Primary Immunodeficiency Disorder ◽  
Familial Hemophagocytic Lymphohistiocytosis ◽  
Immunodeficiency Disorder ◽  
Splice Site Sequence ◽  
Immunologic Test

Abstract Familial hemophagocytic lymphohistiocytosis (HLH) is a rare primary immunodeficiency disorder characterized by defects in cell-mediated cytotoxicity that results in fever, hepatosplenomegaly, and cytopenias. Familial HLH is well recognized in children but rarely diagnosed in adults. We conducted a retrospective review of genetic and immunologic test results in patients who developed HLH in adulthood. Included in our study were 1531 patients with a clinical diagnosis of HLH; 175 patients were 18 years or older. Missense and splice-site sequence variants in PRF1, MUNC13-4, and STXBP2 were found in 25 (14%) of the adult patients. The A91V-PRF1 genotype was found in 12 of these patients (48%). The preponderance of hypomorphic mutations in familial HLH–causing genes correlates with the later-onset clinical symptoms and the more indolent course in adult patients. We conclude that late-onset familial HLH occurs more commonly than was suspected previously.

scholarly journals Distinct epigenetic signatures between adult-onset and late-onset depression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hirotaka Yamagata ◽  
Hiroyuki Ogihara ◽  
Koji Matsuo ◽  
Shusaku Uchida ◽  
Ayumi Kobayashi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bisulfite Sequencing ◽  
Clinical Symptoms ◽  
Late Onset ◽  
Adult Onset ◽  
Blood Biomarkers ◽  
Major Depressive ◽  
Genome Wide ◽  
Healthy Control ◽  
Epigenetic Signatures

AbstractThe heterogeneity of major depressive disorder (MDD) is attributed to the fact that diagnostic criteria (e.g., DSM-5) are only based on clinical symptoms. The discovery of blood biomarkers has the potential to change the diagnosis of MDD. The purpose of this study was to identify blood biomarkers of DNA methylation by strategically subtyping patients with MDD by onset age. We analyzed genome-wide DNA methylation of patients with adult-onset depression (AOD; age ≥ 50 years, age at depression onset < 50 years; N = 10) and late-onset depression (LOD; age ≥ 50 years, age at depression onset ≥ 50 years; N = 25) in comparison to that of 30 healthy subjects. The methylation profile of the AOD group was not only different from that of the LOD group but also more homogenous. Six identified methylation CpG sites were validated by pyrosequencing and amplicon bisulfite sequencing as potential markers for AOD in a second set of independent patients with AOD and healthy control subjects (N = 11). The combination of three specific methylation markers achieved the highest accuracy (sensitivity, 64%; specificity, 91%; accuracy, 77%). Taken together, our findings suggest that DNA methylation markers are more suitable for AOD than for LOD patients.

scholarly journals Chronic oral administration of P. gingivalis induces microglial activation and degeneration of dopaminergic neurons possibly through increase in gut permeability and peripheral IL-17A in LRRK2 R1441G mice

2020 ◽  
Author(s):  
Yu-kun Feng ◽  
Yan-Wen Peng ◽  
Qiong-Li Wu ◽  
Feng-Yin Liang ◽  
Hua-Jing You ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Chronic Periodontitis ◽  
Dopaminergic Neurons ◽  
Microglial Activation ◽  
Mononuclear Cells ◽  
Late Onset ◽  
Interleukin 1 ◽  
Peripheral Inflammation ◽  
Peripheral Blood Mononuclear

Abstract Background The R1441G mutation in the leucine-rich repeat kinase 2 (LRRK2) gene results in late-onset Parkinson’s disease (PD). Peripheral inflammation and gut microbiota are closely associated with the pathogenesis of PD. Chronic periodontitis is a common type of peripheral inflammation, which is associated with PD. Porphyromonas gingivalis (Pg), the most common bacterium causing chronic periodontitis, can cause alteration of gut microbiota. It is not known whether Pg-induced dysbiosis plays a role in the pathophysiology of PD. Methods In this study, live Pg were orally administrated to animals, three times a week for one month. Pg-derived lipopolysaccharide (LPS) was used to stimulate peripheral blood mononuclear cells in vitro. The effects of oral Pg administration on the gut and brain were evaluated through behaviors, morphology, and cytokine expression. Results Dopaminergic neurons in the substantia nigra were reduced and activated microglial cells were increased in R1441G mice given oral Pg. In addition, an increase in mRNA expression of tumor necrosis factor (TNF-α) and interleukin-1 β (IL-1β) as well as protein level of α-synuclein together with a decrease in zonula occludens-1 (Zo-1) were detected in the colon in Pg-treated R1441G mice. Furthermore, serum interleukin-17A (IL-17A) and brain IL-17 receptor A (IL-17RA) were increased in Pg-treated R1441G mice. Conclusions These findings suggest that LRRK2 causes gut leakage and further mediates peripheral IL-17A response in Pg-treated animals. We, thus, put forward the hypothesis that IL-17A in the serum may result in activation of the IL-17A-IL-17RA axis that aggravates dysfunction of dopaminergic neurons and provokes microglial activation in LRRK2 R1441G mice.

scholarly journals The impact of Temporal Artery Biopsy for the diagnosis of Giant Cell Arteritis in clinical practice in a tertiary University Hospital

2019 ◽  
Author(s):  
E Kaltsonoudis ◽  
E Pelechas ◽  
A Papoudou-Bai ◽  
E.T. Markatseli ◽  
M Elisaf ◽  
...  
Keyword(s):  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Laboratory Data ◽  
Unknown Origin ◽  
Temporal Artery ◽  
University Hospital ◽  
Temporal Artery Biopsy ◽  
Acute Phase Reactants ◽  
Anemia Of Chronic Disease ◽  
The Impact

ABSTRACTBackgroundTemporal artery biopsy (TAB) is useful in assisting with giant cell arteritis (GCA) diagnosis but lacks sensitivity. The aim of our study was to assess the diagnostic impact of TAB histology in patients with suspected GCA on hospital admission.MethodsA prospectively maintained database was queried for all TABs performed between 1-1-2000 until 31-12-2017 at the University Hospital of Ioannina. Thus, inclusion criteria were made on the grounds of every patient that underwent a TAB during the above-mentioned period, regardless of demographic, clinical and laboratory data.ResultsTwo hundred forty-five TABs were included (149 females and 96 males), with a mean age of 64.5 (±3.5) years. The mean symptoms duration until admission to the hospital was 8.6 (±1.3) weeks and all had elevated acute phase reactants on admission. The reasons of admission were fever of unknown origin (FUO) in 114 (46.5%) patients, symptoms of polymyalgia rheumatica (PMR) in 84 (34.3%), new headache in 33 (13.5%), anemia of chronic disease (ACD) in 8 (3.32%) and eye disturbances in 6 (2.5%) patients. Positive results were found in 49 (20%) TABs. More specifically, in 14% of patients with FUO, 21% in those with PMR, while in patients with a new headache the percentage was 27%. Finally, 5 out of 6 (83.3%) of patients with ocular symptoms and only one (12.5%) of those suffering from ACD. Visual manifestations and FUO are correlated with a positive TAB.ConclusionIt seems that TAB is useful in assisting with GCA diagnosis, but lacks sensitivity.

Comorbidity between depression and inflammatory bowel disease explained by immune-inflammatory, oxidative, and nitrosative stress; tryptophan catabolite; and gut–brain pathways

CNS Spectrums ◽  
2015 ◽  
Vol 21 (2) ◽  
pp. 184-198 ◽  
Author(s):  
Marta Martin-Subero ◽  
George Anderson ◽  
Buranee Kanchanatawan ◽  
Michael Berk ◽  
Michael Maes
Keyword(s):  
Inflammatory Bowel Disease ◽  
Acute Phase ◽  
Bowel Disease ◽  
Nitrosative Stress ◽  
Transforming Growth Factor ◽  
Interleukin 1 ◽  
Oxidative And Nitrosative Stress ◽  
Acute Phase Reactants ◽  
Inflammatory Bowel ◽  
Brain Pathways

The nature of depression has recently been reconceptualized, being conceived as the clinical expression of activated immune-inflammatory, oxidative, and nitrosative stress (IO&NS) pathways, including tryptophan catabolite (TRYCAT), autoimmune, and gut–brain pathways. IO&NS pathways are similarly integral to the pathogenesis of inflammatory bowel disease (IBD). The increased depression prevalence in IBD associates with a lower quality of life and increased morbidity in IBD, highlighting the role of depression in modulating the pathophysiology of IBD.This review covers data within such a wider conceptualization that better explains the heightened co-occurrence of IBD and depression. Common IO&NS underpinning between both disorders is evidenced by increased pro-inflammatory cytokine levels, eg, interleukin-1 (IL-1) and tumor necrosis factor-α, IL-6 trans-signalling; Th-1- and Th-17-like responses; neopterin and soluble IL-2 receptor levels; positive acute phase reactants (haptoglobin and C-reactive protein); lowered levels of negative acute phase reactants (albumin, transferrin, zinc) and anti-inflammatory cytokines (IL-10 and transforming growth factor-β); increased O&NS with damage to lipids, proteinsm and DNA; increased production of nitric oxide (NO) and inducible NO synthase; lowered plasma tryptophan but increased TRYCAT levels; autoimmune responses; and increased bacterial translocation. As such, heightened IO&NS processes in depression overlap with the biological underpinnings of IBD, potentially explaining their increased co-occurrence. This supports the perspective that there is a spectrum of IO&NS disorders that includes depression, both as an emergent comorbidity and as a contributor to IO&NS processes. Such a frame of reference has treatment implications for IBD when “comorbid” with depression.

Autoinflammatory Syndromes

2012 ◽  
Author(s):  
Arturo Diaz
Keyword(s):  
Differential Diagnosis ◽  
Muscular Atrophy ◽  
Periodic Fever ◽  
Interleukin 1 ◽  
Macrocytic Anemia ◽  
Unknown Origin ◽  
Autoinflammatory Syndromes ◽  
Papa Syndrome ◽  
Hyper Igd Syndrome ◽  
Mediterranean Fever

The autoinflammatory syndromes are a group of diseases characterized by apparently spontaneous episodes of fever and inflammatory manifestations in several organs. Some of these conditions, such as familial Mediterranean fever (FMF), have been known for over a century, but others have only recently been defined. The discovery of the genetic defects underlying the pathophysiology of these diseases has been critical for their understanding and eventual grouping in a new category of diseases. Despite their rarity, the monogenic autoinflammatory syndromes are relevant because identification of the causative genetic variants has greatly expanded our understanding of the inflammatory process and the innate immune system and defined new diseases and their treatment. In addition, the autoinflammatory syndromes have been incorporated in the differential diagnosis of fever of unknown origin. In this chapter, the following selected syndromes are reviewed: FMF; cryopyrin-associated periodic syndromes; tumor necrosis factor–associated periodic fever syndrome; hyper-IgD syndrome; pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome; Blau syndrome; deficiency of the interleukin-1 receptor antagonist; Majeed syndrome; cherubism; joint contractures, muscular atrophy, macrocytic anemia, and panniculitis-associated lipodystrophy (JMP) syndrome; CANDLE syndrome; systemic-onset juvenile idiopathic arthritis; and adult-onset Still disease. Each syndrome is broken down by epidemiology, etiology, pathogenesis, diagnosis, differential diagnosis, management, complications, and prognosis. This review contains 4 highly rendered figures, 5 tables, and 96 references.

Late-onset versus early-onset systemic lupus: characteristics and outcome in a national multicentre register (RELESSER)

Rheumatology ◽  
2020 ◽  
Author(s):  
Anne Riveros Frutos ◽  
Susana Holgado ◽  
Arantza Sanvisens Bergé ◽  
Irma Casas ◽  
Alejandro Olivé ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Early Onset ◽  
Clinical Course ◽  
Late Onset ◽  
Immunosuppressive Agents ◽  
Diagnostic Delay ◽  
Clinical Manifestations ◽  
Diagnostic Errors ◽  
Systemic Lupus ◽  
Female Ratio

Abstract Objective The aim of the present study was to describe the demographic, clinical and immunological characteristics of patients with late-onset (≥50 years) SLE vs patients with early-onset SLE (&lt;50 years). Methods We performed a cross-sectional retrospective study of 3619 patients from the RELESSER database (National Register of Patients with Systemic Lupus Erythematosus of the Spanish Society of Rheumatology). Results A total of 565 patients (15.6%) were classified as late-onset SLE and 3054 (84.4%) as early-onset SLE. The male-to-female ratio was 5:1. Mean (s.d.) age at diagnosis in the late-onset group was 57.4 (10.4) years. At diagnosis, patients with late-onset SLE had more comorbid conditions than patients with early-onset SLE; the most frequent was cardiovascular disease (P &lt;0.005). Furthermore, diagnostic delay was longer in patients with late-onset SLE [45.3 (3.1) vs 28.1 (1.0); P &lt;0.001]. Almost all patients with late-onset SLE (98.7%) were Caucasian. Compared with early-onset SLE and after adjustment for time since diagnosis, patients with late-onset SLE more frequently had serositis, major depression, thrombotic events, cardiac involvement and positive lupus anticoagulant values. They were also less frequently prescribed immunosuppressive agents. Mortality was greater in late-onset SLE (14.3% vs 4.7%; P &lt;0.001). Conclusion Late-onset SLE is insidious, with unusual clinical manifestations that can lead to diagnostic errors. Clinical course is generally indolent. Compared with early-onset disease, activity is generally reduced and immunosuppressants are less commonly used. Long-term prospective studies are necessary to determine whether the causes of death are associated with clinical course or with age-associated comorbidities in this population.

Systematic Analysis of the Impact of Diagnostic Delay on Bowel Damage in Paediatric Versus Adult Onset Crohn’s Disease

2019 ◽  
Vol 13 (10) ◽  
pp. 1334-1342 ◽  
Author(s):  
Alain Schoepfer ◽  
Jessica Santos ◽  
Nicolas Fournier ◽  
Susanne Schibli ◽  
Johannes Spalinger ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Diagnostic Delay ◽  
Perianal Fistula ◽  
Adult Patients ◽  
Adult Onset ◽  
Systematic Analysis ◽  
Internal Fistula ◽  
The Impact

Abstract Background and Aims Length of diagnostic delay is associated with bowel strictures and intestinal surgery in adult patients with Crohn’s disease [CD]. Here we assessed whether diagnostic delay similarly impacts on the natural history of paediatric CD patients. Methods Data from the Swiss IBD Cohort Study were analysed. Frequency of CD-related complications [bowel stenosis, perianal fistula, internal fistula, any fistula, resection surgery, fistula/abscess surgery, any complication] at diagnosis and in the long term [up to 30 years after CD diagnosis] was compared between paediatric patients [diagnosed <18 years] and adult patients [diagnosed ≥18 years] using multivariate Cox proportional hazard regression modelling. Results From 2006 to 2016, 387 paediatric and 1163 adult CD patients were included. Median [interquartile range: IQR] diagnostic delay was 3 [1–9] for the paediatric and 6 [1–24] months for the adult group, respectively. Adult onset CD patients presented at diagnosis more frequently with bowel stenosis [p <0.001] and bowel surgery [p <0.001] compared with paediatric CD patients. In the long term, length of diagnostic delay was significantly associated with bowel stenosis [p = 0.001], internal fistula [p = 0.038], and any complication [p = 0.024] in the adult onset CD population. No significant association between length of diagnostic delay and CD-related outcomes in the long term was observed in the paediatric population. Conclusions Adult CD patients have longer diagnostic delay compared with paediatric CD patients and present at diagnosis more often with bowel stenosis and surgery. Length of diagnostic delay was found to be predictive for CD-related complications only in the adult but not in the paediatric CD population.

Sign in / Sign up

Export Citation Format

Share Document