scholarly journals Inflammatory Arthritis, Sacroiliitis, and Morphea: Evidence of a Systemic Inflammatory Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-3
Author(s):  
Mohammed A. Omair ◽  
Sindhu R. Johnson

Morphea is a skin disease characterized by local skin inflammation and fibrosis. Extracutaneous manifestations have been described with this disease including inflammatory arthritis. We describe a case of morphea who developed inflammatory polyarthritis and sacroiliitis coincident with new skin lesions.

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Weber ◽  
D.W Biery ◽  
A Singh ◽  
S Divakaran ◽  
A.N Berman ◽  
...  

Abstract Background Autoimmune systemic inflammatory diseases are associated with an increased risk of cardiovascular disease, particularly myocardial infarction (MI). However, there are limited data on the prevalence and effects of inflammatory disease among U.S. adults who experience an MI at a young age. Purpose We sought to determine the prevalence and prognostic value of inflammatory disease in U.S. adults who experience an MI at a young age. Methods The YOUNG-MI registry is a retrospective cohort study of consecutive patients who experienced a Type 1 MI at or below the age of 50 years from 2000 to 2016 at two large medical centers. A diagnosis of rheumatoid arthritis (RA), psoriasis (PsO), systemic lupus erythematosus (SLE), or inflammatory arthritis was determined through physician review of electronic medical records (EMR). Demographic information, presence of cardiovascular (CV) risk-factors, medical procedures, and medications upon discharge were also ascertained from the EMR. Incidence of death was determined using a combination of EMR and national databases. Cox proportional hazard modeling was performed on a sub-sample following Mahalanobis Distance matching on age, sex, and CV risk factors. Results The cohort consisted of 2097 individuals (median age 45 years, 19% female, 53% ST-elevation MI). Among these, 53 (2.5%) individuals possessed a diagnosis of systemic inflammatory disease at or before their index MI (23% SLE, 9% RA, 64% PsO, 4% inflammatory arthritis). When compared to the remainder of the cohort, patients with a diagnosis of systemic inflammatory disease were more likely to be female (36% vs 19%, p=0.004) and be diagnosed with hypertension (62% vs 46%, p=0.025). There was, however, no significant difference in the prevalence of other CV risk factors – diabetes, smoking, dyslipidemia – or a family history of premature coronary artery disease. Despite these similarities, patients with inflammatory disease were less likely to be prescribed aspirin (88% vs 95%, p=0.049) or a statin (76% vs 89%, p=0.008) upon discharge. Over a median follow-up of 11.2 years, patients with inflammatory disease experienced an increased risk of all-cause mortality when compared with the full-cohort (Figure). Compared to the matched sample (n=138), patients with systemic inflammatory disease exhibited an increased risk of all-cause mortality (HR=2.68, CI [1.18 to 6.07], p=0.018), which remained significant after multivariable adjustment for length of stay and GFR (HR=2.38, CI [1.02 to 5.54], p=0.045). Conclusions Among individuals who experienced an MI at a young age, approximately 2.5% had evidence of a systemic inflammatory disease at or before their MI. When compared with a population of individuals with similar cardiovascular risk profiles, those with inflammatory disease had higher rates of all-cause mortality. Our findings suggest that the presence of a systemic inflammatory disorder is independently associated with worse long-term outcomes. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): 1. 5T32 HL094301 NIH T32 Training Grant, “Noninvasive Cardiovascular Imaging Research Training Program”


2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Gert-Jan Wijnant ◽  
Katrien Van Bocxlaer ◽  
Amanda Fortes Francisco ◽  
Vanessa Yardley ◽  
Andy Harris ◽  
...  

ABSTRACTDisfiguring skin lesions caused by several species of theLeishmaniaparasite characterize cutaneous leishmaniasis (CL). Successful treatment of CL with intravenous (i.v.) liposomal amphotericin B (LAmB) relies on the presence of adequate antibiotic concentrations at the dermal site of infection within the inflamed skin. Here, we have investigated the impact of the local skin inflammation on the pharmacokinetics (PK) and efficacy of LAmB in two murine models of localized CL (Leishmania majorandLeishmania mexicana) at three different stages of disease (papule, initial nodule, and established nodule). Twenty-four hours after the administration of one 25 mg/kg of body weight LAmB (i.v.) dose to infected BALB/c mice (n= 5), drug accumulation in the skin was found to be dependent on the causative parasite species (L. major>L. mexicana) and the disease stage (papule > initial nodule > established nodule > healthy skin). Elevated tissue drug levels were associated with increased vascular permeability (Evans blue assay) and macrophage infiltration (histomorphometry) in the infected skin, two pathophysiological parameters linked to tissue inflammation. After identical treatment of CL in the two models with 5 × 25 mg/kg LAmB (i.v.), intralesional drug concentrations and reductions in lesion size and parasite load (quantitative PCR [qPCR]) were all ≥2-fold higher forL. majorthan forL. mexicana. In conclusion, drug penetration of LAmB into CL skin lesions could depend on the disease stage and the causativeLeishmaniaspecies due to the influence of local tissue inflammation.


2013 ◽  
Vol 35 ◽  
pp. 625-631 ◽  
Author(s):  
Anna Michalak-Stoma ◽  
Joanna Bartosińska ◽  
Małgorzata Kowal ◽  
Maria Juszkiewicz-Borowiec ◽  
Agnieszka Gerkowicz ◽  
...  

Introduction. Psoriasis is a T cell-mediated inflammatory disease in which pathogenesis T helper (Th) lymphocytes (Th1, Th17, and Th22) play an important role. The aim of the study was to assess the serum levels of some cytokines involved in the Th17 and Th22 responses in psoriatic patients.Material and Methods. The study comprised 60 psoriatic patients and 30 healthy controls. In the serum collected from psoriatic patients and healthy controls, the concentrations of IL-6, IL-12, IL-17, IL-20, IL-22, and IL-23 were examined with ELISA kits. Severity of psoriatic skin lesions was assessed by means of PASI, BSA, and PGA scores.Results. IL-6, IL-20, and IL-22 concentrations were significantly higher in psoriatic patients in comparison with the control group. The positive correlations between the concentrations of IL-22 and IL-20 and severity of psoriasis assessed with PASI and BSA scores as well as IL-17 and PASI score were found. There was also a positive correlation between IL-23 and IL-17 concentrations.Conclusions. Results of the conducted studies suggest that Th22 response may contribute to the skin and systemic inflammatory disease in psoriasis. It seems that early identification of soluble biomarkers and initiation of well-matched treatment may prevent exacerbation and progression of psoriasis.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yoonkyeom Shin ◽  
Ji-Man Kang ◽  
Junwon Lee ◽  
Christopher Seungkyu Lee ◽  
Sung Chul Lee ◽  
...  

Abstract Background The early detection of uveitis associated with systemic inflammatory disease in children is important for proper treatment and prognosis. However, the diagnosis may be delayed because of difficulties in childhood examinations and early minor systemic symptoms. The objective of our study was to identify the pattern of childhood uveitis and investigate the frequency and clinical features of rheumatic diseases in pediatric patients with uveitis. Methods This retrospective observational study reviewed the medical records of children (age ≤ 18 years) with uveitis at a Korean tertiary hospital between January 2005 and December 2018. Data collected included the age at onset of uveitis, sex, anatomic location of ocular inflammation, comorbid disease (including systemic inflammatory disease), ocular complications, relevant laboratory data, and treatment. Fisher’s exact test was used to compare categorical variables and the Mann–Whitney U test was used to compare continuous variables. A p-value of < 0.05 was considered statistically significant. Results A total of 155 pediatric patients with uveitis were included in this study. The median age at diagnosis was 13.0 years (interquartile range, 9.5–16.0 years). The male-to-female ratio was 1.09. The process was unilateral in 51.6% of children. Anterior uveitis, panuveitis, intermediate uveitis, and posterior uveitis represented 51.6, 26.5, 6.5, and 1.9% of the cases, respectively. Idiopathic uveitis (65.2%) was the most frequent type of uveitis. Systemic rheumatic disease associations were responsible for 28.4% of the cases, among which juvenile idiopathic arthritis (JIA) was the most frequent cause (14.8%). Human leukocyte antigen (HLA)-B27 and antinuclear antibody (ANA) positive rates were significantly higher in patients with JIA than in those with idiopathic uveitis (p = 0.006 and p = 0.007, respectively). Conclusions Approximately one-third of children with uveitis in Korea have a systemic rheumatic disease, of which JIA accounts for the majority of cases. HLA-B27 and ANA can serve as risk factors for JIA-associated uveitis.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10537-10537
Author(s):  
Michelle J McSweeny ◽  
Susan Montgomery ◽  
Kristen Danielle Whitaker ◽  
Mary Beryl Daly ◽  
Michael J. Hall

10537 Background: LS is among the most common hereditary cancer (CA) syndromes. PVs in MSH6 are 2-4 fold more common in the population (1/758) than those in MLH1 (1/1946) or MSH2 (1/2841), and are increasingly regarded as lower penetrance for CRC due to published data supporting later mean age of CRC onset and lower CRC risk. Unlike for MLH1/MSH2, NCCN 2020 CA risk estimates recognize only endometrial CA (EC) and CRC risks in MSH6+ carriers as clearly above SEER population estimates. Further, risks of other LS manifestations such as skin disease/Muir-Torre, ovarian CA (OC), and possible rare tumors in LS like sarcoma, have been minimally characterized in MSH6+ carriers. Methods: Pedigree data for 44 MSH6+ index (first-evaluated family member by our program) pts consecutively ascertained since 2009 at Fox Chase (FCCC) were reviewed. 1 pt w/a rare MSH6 uncertain variant w/personal history (PHx) of MSH6-expression deficient EC (age 50) and MSH6-deficient sebaceous skin CA (age 50) and a strong family history (FHx) c/w LS is also included here. 34% (15/44) index pts were referred to FCCC for cascade testing due to a known MSH6 PV in the family. Of the remaining 29 index pts, ascertainment included: 14% w/positive universal LS tumor screening, 21% w/early-onset or synchronous LS CA, 14% w/multi-gene panel for PHx of OC, 10% w/incidental MSH6+ result (2 had testing for PHx breast CA, 1 tumor genomic profiling), and 28% w/PHx and/or FHx of LS CA warranting genetic testing. Age of CA onset and path data were verified in > 90% index pts. Results: Index pts had a mean age of 55.5 yrs, and 77% were female. Overall, 11% (5/44) of MSH6+ index pts were found to have LS at diagnosis of synchronous primary CAs (3 EC/OC, 1 CRC/CRC, 1 CRC/EC), and 4/5 of these occurred <50 yrs. An additional 20% (9/44) index pts reported PHx of >2 metachronous LS CAs. OC was the presenting CA in 14% (6/44) female index pts; 2 additional index pts had rarer OC variants (Mullerian duct @ 41, primary peritoneal CA @ 50). Skin manifestations of LS were documented in 9.1% (4/44) index pts (3 sebaceous, 1 SCC in-situ/Bowen’s disease); 1 other family had documented sebaceous CAs in an FDR (father) but the 2 daughters seen @FCCC (both 30s) had yet to develop skin lesions. 2 index pts were found to have LS after developing early-onset breast CA (age 39) and contralateral breast CA (ages 50 and 54). Finally, 7% (3/44) index pts had a PHx of sarcoma: 2 were liposarcomas (ages 57 and 67), and 1 was a dermatofibrosarcoma. 2 other index pts had siblings w/childhood sarcomas. Conclusions: Our data, encompassing 44 MSH6+ pts evaluated in our clinic and consecutively ascertained, suggest MSH6 PV carriers develop synchronous primaries (11%), common and rare OC histologic types (18%), sarcomas (7%) and skin disease/Muir-Torre (9%). While common in the population and lower penetrance for CRC, MSH6 PV can behave in uncommon ways and may have significant extra-colonic CA risks such as OC, sarcoma and skin manifestations.


2021 ◽  
Author(s):  
Yang Sun ◽  
Yan Ding ◽  
Jiao Qu ◽  
Chenyang Zhang ◽  
Yuyu Zhu ◽  
...  

Psoriasis is a chronic inflammatory disease which infiltrated a large number of neutrophils among skin lesions. Here, we investigated the contribution of tyrosine phosphatase SHP2 in neutrophils, as well as its pathogenesis in psoriasis. We combined single-cell RNA sequencing with experimental verification to declare that SHP2 in neutrophils could promote the NETs formation through the ERK5 pathway, and resulted in the infiltration of inflammatory immune cells, which leads to psoriasis. Our study provides evidence for the role of SHP2 in NETosis in the progression of psoriasis, and SHP2 may be a potential therapeutic target for the treatment of psoriasis.


Author(s):  
Mariko Seishima ◽  
Yasuko Yamamoto ◽  
Masashi Sakurai ◽  
Rika Sakai ◽  
Kento Fujii ◽  
...  

Aim: Chronic inflammation is closely associated with tryptophan (TRP)-kynurenine (KYN) metabolic pathway. However, TRP-KYN pathway has not been fully elucidated in psoriasis, a systemic inflammatory disease with skin lesions and extracutaneous manifestations. Herein, we studied comprehensively serum profiles of TRP-KYN pathway metabolites in psoriatic patients (PSOs) to clarify the involvement of this pathway in the pathophysiology of psoriasis and to evaluate serum biomarkers reflecting systemic inflammation in PSOs. Methods: The concentrations of main TRP metabolites, TRP, KYN, 3-hydroxykynurenine (3HK), kynurenic acid (KYNA), 3-hydroxyanthranilic acid (3HAA), and anthranilic acid (AA), were determined by high-performance liquid chromatography in the sera from 65 PSOs and 35 healthy controls (HCs). The levels of these metabolites and the ratios of metabolites were compared between these subjects. The correlations between these values and the psoriasis area severity index (PASI) scores were analyzed. Skin samples from PSOs and HCs were subjected to immunohistochemical staining for kynureninase. Cytokine concentrations were comprehensively measured in the same samples and the correlations between the cytokine levels and TRP-KYN pathway metabolite levels were examined. Results: Serum TRP, KYN, and KYNA concentrations were lower and the 3HAA concentrations were higher in PSOs than in HCs. The ratios of 3HK/KYN, 3HAA/3HK, and 3HK/AA were higher in PSOs than in HCs. The AA levels and the ratio of AA/KYN were weakly positively correlated, and TRP, KYNA, and 3HK levels and the ratios of KYNA/KYN and 3HAA/AA were weakly negatively correlated with the PASI scores. The AA, KYN, and KYNA levels were positively correlated with the interferon gamma-induced protein 10 (IP-10) concentrations. Kynureninase expression was enhanced in the epidermis, both involved and uninvolved skin. Conclusions: Serum profiles of TRP-KYN pathway metabolites differed between PSOs and HCs. TRP-KYN pathway-associated processes, including kynureninase activation, may be involved in the pathogenesis of psoriasis, and thus serve as targets for psoriasis therapy.


2016 ◽  
Vol 213 (10) ◽  
pp. 2147-2166 ◽  
Author(s):  
Juhan Yoon ◽  
Juan Manuel Leyva-Castillo ◽  
Guoxing Wang ◽  
Claire Galand ◽  
Michiko K. Oyoshi ◽  
...  

Atopic dermatitis (AD) is a Th2-dominated inflammatory skin disease characterized by epidermal thickening. Serum levels of IL-22, a cytokine known to induce keratinocyte proliferation, are elevated in AD, and Th22 cells infiltrate AD skin lesions. We show that application of antigen to mouse skin subjected to tape stripping, a surrogate for scratching, induces an IL-22 response that drives epidermal hyperplasia and keratinocyte proliferation in a mouse model of skin inflammation that shares many features of AD. DC-derived IL-23 is known to act on CD4+ T cells to induce IL-22 production. However, the mechanisms that drive IL-23 production by skin DCs in response to cutaneous sensitization are not well understood. We demonstrate that IL-23 released by keratinocytes in response to endogenous TLR4 ligands causes skin DCs, which selectively express IL-23R, to up-regulate their endogenous IL-23 production and drive an IL-22 response in naive CD4+ T cells that mediates epidermal thickening. We also show that IL-23 is released in human skin after scratching and polarizes human skin DCs to drive an IL-22 response, supporting the utility of IL-23 and IL-22 blockade in AD.


BMJ ◽  
2018 ◽  
pp. j5145 ◽  
Author(s):  
Jose C Clemente ◽  
Julia Manasson ◽  
Jose U Scher

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