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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 -
Cureus Oct 2020Rheumatoid arthritis and systemic lupus erythematosus (SLE) are autoimmune diseases that are commonly seen in the female population. Rheumatoid arthritis mainly consists... (Review)
Review
Rheumatoid arthritis and systemic lupus erythematosus (SLE) are autoimmune diseases that are commonly seen in the female population. Rheumatoid arthritis mainly consists of distal symmetrical deforming polyarthritis. SLE patients have immune complexes that damage the organs and systems of the body, and this can present with one or more symptoms including the characteristic malar rash, serositis, lupus nephritis, photosensitivity, and arthritis of large joints. The onset and progression of the diseases are affected by physiological processes that occur in the body such as menopause and aging. The studies used as evidence were found in the PubMed, ScienceDirect, ProQuest, Taylor & Francis Online, Wiley Online Library, Ovid, and Oxford Academic databases. By analyzing these studies, the effects of aging and menopause on rheumatoid arthritis and SLE were revealed. In relation to menopause and aging, it was found that there was a progression of disease in women who had rheumatoid arthritis. However, aging and menopause caused the progression of SLE to decrease in women. An earlier age of onset of menopause was correlated with an increased chance of developing rheumatoid arthritis and SLE. Furthermore, while some studies showed that a later onset of SLE caused an increase in the progression of the disease, other studies showed that a later onset of SLE led to a decrease in the progression of the disease. Due to the prevalence of rheumatoid arthritis and SLE in females, we believe that the effects of menopause, age, and other factors on these two diseases should be examined in future studies.
PubMed: 33072443
DOI: 10.7759/cureus.10944 -
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 -
RMD Open Jan 2024Systemic lupus erythematosus (SLE) significantly affects the lungs and heart, and pulmonary hypertension (PH) is a severe manifestation that leads to considerable...
BACKGROUND
Systemic lupus erythematosus (SLE) significantly affects the lungs and heart, and pulmonary hypertension (PH) is a severe manifestation that leads to considerable morbidity and mortality.
OBJECTIVES
We aimed to determine the prevalence and risk factors of probable SLE-PH, assess the main echocardiographic predictors and develop a potential screening strategy.
METHODS
A prospective single-centre study was conducted on 201 patients with SLE who underwent transthoracic echocardiography. Patients meeting PH criteria were referred for right heart catheterisation (RHC).
RESULTS
Among patients, 88.56% were women, 85.57% were of Spanish origin and 43.78% had structural heart disease. Out of these, 16 (7.96%) had intermediate or high probability criteria for PH according to European Society of Cardiology (ESC) 2022. Six RHCs confirmed PH with a prevalence of 2.99% for SLE-PH and 1.99% for SLE-pulmonary arterial hypertension (PAH).
KEY RISK FACTORS
Key risk factors included age, cardiorespiratory symptoms, serositis, anti-Ro, cardiac biomarkers and altered pulmonary function tests (PFTs). PH was linked to a higher Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index (SDI) (mean SDI 4.75 vs 2.05, p<0.001) and increased mortality risk in a 2-year follow-up (12.50% vs 1.08%, p=0.002).
CONCLUSION
In our cohort, 7.96% of patients with SLE had an intermediate or high PH probability. By RHC, six patients (2.99%) met the ESC/European Respiratory Society criteria for PH and four (1.99%) for PAH. The main risk factors were older age, cardiorespiratory symptoms, serositis, anti-Ro, cardiac biomarkers and altered PFTs. PH was a severe SLE complication, suggesting the need for earlier diagnosis through data-driven screening to reduce associated morbidity and mortality.
Topics: Humans; Female; Male; Hypertension, Pulmonary; Prevalence; Prospective Studies; Serositis; Echocardiography; Lupus Erythematosus, Systemic; Biomarkers
PubMed: 38191213
DOI: 10.1136/rmdopen-2023-003674 -
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 -
Trends in Cardiovascular Medicine Jul 2021Recurrent pericarditis (RP) is a troublesome and debilitating complication of acute pericarditis. Although the etiopathogenesis of this condition remains unknown, an... (Review)
Review
Recurrent pericarditis (RP) is a troublesome and debilitating complication of acute pericarditis. Although the etiopathogenesis of this condition remains unknown, an intricate overlap of autoimmune and autoinflammatory pathways has been hypothesized to explain its beginning and recurrence over time. The majority of cases are defined as "idiopathic", reflecting our awkwardness to unravel the intimate mechanisms of RP. Given the possible occurrence of anti-nuclear, anti-heart and anti-intercalated disk antibodies as well as the association with peculiar human leukocyte antigen haplotypes, an autoimmune contribution has been claimed to specify the nature of RP. However, the most innovative pathogenic scenario of RP has been conferred to the innate immune system, mainly involving neutrophils and macrophages that produce a large amount of interleukin (IL)-1 via inflammasome activation. The clinical resemblance of RP with autoinflammatory diseases that may be marked by symptomatic serositis, high fevers and strikingly increased inflammatory parameters further suggests a similar inflammasome-mediated pathogenesis. Aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) remain the mainstay of therapy in RP, whereas colchicine is recommended on top of standard anti-inflammatory therapy, due to its role in inhibiting the IL-1 converting enzyme (caspase 1) within the inflammasome as well as the release of additional pro-inflammatory mediators and reactive oxygen species. With regard to treatment of RP refractory to NSAIDs and colchicine, blockade of IL-1 is the most relevant advance achieved in the last decade: the outstanding effect of the short-acting IL-1 receptor antagonist anakinra has been first recognized in the pediatric population, giving a proof of its practical feasibility. Over a more recent time, a growing experience with anakinra deriving from both large and small studies has further confirmed that RP might be regarded as an IL-1-mediated disease. This review aims to provide a contemporary insight into the mechanisms leading to RP as well as into the most recent literature data showing the beneficial approach originating from IL-1 blockade in this intriguing disorder.
Topics: Animals; Anti-Inflammatory Agents; Autoimmunity; Humans; Immunity, Innate; Inflammasomes; Inflammation Mediators; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Monocytes; Myocardium; Neutrophils; Pericarditis; Recurrence; Signal Transduction; Treatment Outcome
PubMed: 32376492
DOI: 10.1016/j.tcm.2020.04.006 -
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 -
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 -
Lupus Science & Medicine Dec 2022SLE, primary Sjögren's syndrome (pSS) and systemic sclerosis (SSc) are heterogeneous autoimmune diseases with a dysregulated type I interferon (IFN) system. The...
Autoantibodies associated with systemic sclerosis in three autoimmune diseases imprinted by type I interferon gene dysregulation: a comparison across SLE, primary Sjögren's syndrome and systemic sclerosis.
OBJECTIVE
SLE, primary Sjögren's syndrome (pSS) and systemic sclerosis (SSc) are heterogeneous autoimmune diseases with a dysregulated type I interferon (IFN) system. The diseases often show overlapping clinical manifestations, which may result in diagnostic challenges. We asked to which extent SSc-associated autoantibodies are present in SLE and pSS, and whether these link to serum IFN-α, clinical phenotypes and sex. Samples with clinical data from patients with SSc and healthy blood donors (HBDs) served as controls. Finally, the diagnostic performance of SSc-associated autoantibodies was evaluated.
METHODS
Samples from well-characterised subjects with SLE (n=510), pSS (n=116), SSc (n=57) and HBDs (n=236) were analysed using a commercially available immunoassay (EuroLine Systemic Sclerosis Profile (IgG)). IFN-α was quantified by ELISA. Self-reported data on Raynaud's phenomenon (RP) were available.
RESULTS
With exceptions for anti-Ro52/SSA and anti-Th/To, SSc-associated autoantibodies were more frequent in SSc than in SLE, pSS and HBDs regardless of sex. IFN-α levels correlated with the number of positive SSc-associated autoantibodies (r=0.29, p<0.0001) and associated with Ro52/SSA positivity (p<0.0001). By using data from SLE, SSc and HBDs, RP was significantly associated with topoisomerase I, centromere protein (CENP)-B, RNA polymerase III 11 kDa, RNA polymerase III 155 kDa and PM-Scl100 whereas Ro52/SSA associated inversely with RP. In SLE, CENP-A was associated with immunological disorder, CENP-B with serositis and Ku with lupus nephritis. By combining analysis of ANA (immunofluorescence) with SSc-associated autoantibodies, the diagnostic sensitivity reached 98% and the specificity 33%.
CONCLUSIONS
The 13 specificities included in the EuroLine immunoassay are commonly detected in SSc, but they are also frequent among individuals with other diseases imprinted by type I IFNs. These findings are valuable when interpreting serological data on patients with suspected SSc, especially as patients may present with disease manifestations overlapping different rheumatological diseases. In SLE, we observed associations between manifestations and SSc-associated autoantibodies which have not previously been reported.
Topics: Humans; Autoantibodies; Sjogren's Syndrome; Interferon Type I; RNA Polymerase III; Lupus Erythematosus, Systemic; Scleroderma, Systemic
PubMed: 36581379
DOI: 10.1136/lupus-2022-000732 -
Reumatologia Clinica Oct 2022To evaluate the correlation of quantitative anti-dsDNA level with proteinuria levels in patients with lupus nephritis in a tertiary care hospital.
OBJECTIVE
To evaluate the correlation of quantitative anti-dsDNA level with proteinuria levels in patients with lupus nephritis in a tertiary care hospital.
STUDY DESIGN
In this prospective cross-sectional study, 76 patients of newly diagnosed SLE coming to Fatima Memorial Hospital were included in the study period between January 2020 to June 2020. Demographic data such as age, gender, lupus manifestations such as serositis, arthritis, mucocutaneous disease, and neuropsychiatric manifestations were recorded. Quantitative anti-dsDNA was measured by enzyme-linked immunosorbent assay and proteinuria was estimated by 24h urinary protein collection. Data was analyzed by SPSS 23. Association between categorical variables was assessed using chi-square test. For comparison of categorical independent and continuous dependent variable t-test or Mann-Whitney U test was applied.
RESULTS
The median age of the cohort was 29 (with inter quartile range - IQR - of 13) years. The female gender comprised of 68 (89.4%) of the cohort population. The median anti-dsDNA level was 54.9 (183.6 IQR) IU, and baseline proteinuria of the cohort was 520mg/dL (1.49 IQR). There was a significant association of anti-dsDNA level with systemic features such as arthritis (p=<0.01), serositis (p=<0.01) and, Raynaud's phenomenon (p=<0.01). NPSLE and mucocutaneous features did not show statistically significant association (p=0.91 and 0.14 respectively). Baseline anti-dsDNA showed a statistically significant correlation with baseline proteinuria levels (p=<0.01).
CONCLUSION
Quantitative anti-dsDNA is directly correlated with nephritis measured as proteinuria, and can be detected even before organ involvement. Hence, it can determine disease course and guide early treatment.
Topics: Adolescent; Antibodies, Antinuclear; Arthritis; Cross-Sectional Studies; DNA; Female; Humans; Lupus Erythematosus, Systemic; Prospective Studies; Proteinuria; Serositis
PubMed: 36210140
DOI: 10.1016/j.reumae.2021.06.005