RESUMO
AIM: Familial Mediterranean fever (FMF) is the most common inherited autoinflammatory disease in the world. There are known triggers to initiate an FMF attack, yet potential effects of intrauterine devices (IUD) in women of reproductive age have not been evaluated before. METHOD: Consecutive female patients with FMF who ever used IUD over the age of 18 were enrolled. Female patients with FMF were sub grouped according to the type of IUD they use. FMF attack frequency, severity, duration, presence of dysmenorrhea, severity of dysmenorrhea, having attacks during menstruation before and after IUD use were questioned. Demographic and clinical data were collected from hospital database. RESULTS: When all patients with IUD use were evaluated, it was found that the frequency of attacks increased after IUD insertion at 3rd and 12th months (median [min-max] attack frequency at 3rd month, 1 (0-3) vs 1 (0-6), p = 0.002, median [min-max] attack frequency at 12th month, 2 (0-12) vs 3.5 (0-18), p = 0.028). Attack severity measured by VAS pain was also significantly increased. Attack duration and menstrual pain was similar before and after IUD use. Attack frequency at 3rd and 12th months, attack severity and menstrual pain was all increased significantly in Cu-IUD users, whereas none of these parameters deteriorated in LNG-IUD group. CONCLUSION: IUD use, especially Cu-IUD, may increase the frequency and severity of attacks in female patients with FMF. Clinicians may benefit from considering LGN-IUD if IUDs are preferred as contraception in women of childbearing age with FMF.
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Anticoncepcionais Femininos , Febre Familiar do Mediterrâneo , Dispositivos Intrauterinos de Cobre , Dispositivos Intrauterinos , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Dismenorreia/etiologia , Febre Familiar do Mediterrâneo/complicações , Dispositivos Intrauterinos/efeitos adversos , Anticoncepção , Dispositivos Intrauterinos de Cobre/efeitos adversosRESUMO
BACKGROUND: Long-COVID refers to a variety of symptoms that continue for at least 4 weeks following the onset of acute COVID-19 infection. "Microclots/microvasculopathy" is a potential cutting-edge theory. Nailfold capillaroscopy is a non-invasive method used to assess microvascularity. In this study, we aimed to compare baseline characteristics and capillaroscopic findings of patients with and without long-COVID syndrome. METHODS: Baseline clinical characteristics of 53 patients who tested positive for SARS-CoV-2 were recorded. At the time of COVID-19 diagnosis, patients underwent nailfold capillaroscopy. One year later, patients were rescreened for long-COVID symptoms. Comparisons were made between patients with and without long-COVID syndrome in terms of their baseline characteristics and capillaroscopic findings. RESULTS: There were 35 individuals (66%) with long-COVID syndrome. The most common symptoms related to long-COVID were fatigue (43.4%), myalgia (34%), arthralgia (20.8%), dyspnea (20.8%). In total, 22 patients (41.5%) had abnormal capillaroscopy findings. Like other baseline characteristics, the proportion of patients with abnormal capillaroscopic findings (40% vs 44%, p=0.76) was similar between patients with and without long-COVID syndrome. CONCLUSION: Microvasculopathy and microthrombotic vascular damage are among the strongest hypotheses discussed in this regard. Our results may suggest that factors, rather than baseline microvasculopathy, may drive pathophysiological mechanism underlying the poorly understood long-COVID syndrome (Tab. 2, Ref. 35).
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COVID-19 , Angioscopia Microscópica , Síndrome de COVID-19 Pós-Aguda , Humanos , Angioscopia Microscópica/métodos , Masculino , COVID-19/complicações , Feminino , Pessoa de Meia-Idade , Adulto , SARS-CoV-2 , Idoso , Microvasos/diagnóstico por imagem , Microvasos/patologiaRESUMO
BACKGROUND: Follow-up is crucial to detect asymptomatic complications of familial Mediterranean fever (FMF). The current European League Against Rheumatism recommendations state that patients with FMF should be evaluated at least every 6 months to monitor attacks, acute phase response, and proteinuria. OBJECTIVES: This study aimed to assess compliance of FMF patients with regular follow-up visits and the associated factors. METHODS: Adult patients with a diagnosis of FMF who had their initial visit at least over 1 year ago were included. Demographic and socioeconomic data, family history, and comorbid diseases were obtained from medical records. The International Severity Score for FMF and the Autoinflammatory Disease Damage Index scores were calculated. We defined patients as "compliant with follow-up visits" both if they had at least 2 visits during the previous year and a compatible physician's assessment. The characteristics of the compliant and noncompliant patients were compared, and multivariable logistic regression analysis was used to determine the factors influencing visit compliance. RESULTS: Four hundred seventy-four patients with FMF were included. Two hundred thirty (48.5%) were compliant, and 244 (51.5%) were noncompliant with follow-up visits. A family history of FMF in parents, the absence of a family history of FMF in siblings, treatment with biologic agents, concomitant medication use, multisite involvement during FMF attacks, and treatment satisfaction were independent predictors of visit compliance. CONCLUSIONS: Only half of the patients with FMF were compliant with follow-up visits. Better strategies should be implemented to increase the compliance of FMF patients. Identifying independent predictors would help to build one.
Assuntos
Febre Familiar do Mediterrâneo , Adulto , Colchicina/uso terapêutico , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Febre Familiar do Mediterrâneo/epidemiologia , Seguimentos , Humanos , ProteinúriaRESUMO
OBJECTIVES: To investigate the association between vascular inflammation, as detected by positron emission tomography (PET) imaging and interleukin-6 (IL-6), pentraxin3, and B-cell-activating factor (BAFF) in subjects with LVV. METHODS: The study included newly diagnosed giant cell arteritis (GCA, n = 27) or Takayasu arteritis (n = 9) patients and healthy control (HC, n = 31) subjects. PET scan and blood samples were obtained before the introduction of treatments. IL-6, PTX3, and BAFF levels were determined quantitatively by enzyme-linked immunosorbent assay kits. RESULTS: Thirty-six patients with LVV (20 females, 16 males; age 64.5 ± 16.6 years) and 31 HC (14 females, 17 males; age 37.1 ± 9.6 years) were included. Serum levels of IL-6, PTX3, and BAFF were increased in patients with newly diagnosed LVV compared with healthy control subjects. In receiver operating characteristics (ROC) analysis, serum IL-6 and BAFF provided excellent discrimination of newly diagnosed LVV patients from HC (area under the ROC curve of >0.90 and >0.80, respectively). None of the inflammatory markers correlated with vascular inflammatory activity determined by PET scanning. CONCLUSIONS: Our results suggest that IL-6 and BAFF may serve as markers of large vessel vasculitis, while PTX3 is not useful. None of the inflammatory markers correlated with PET assessed vasculitis activity.
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Arterite de Células Gigantes , Arterite de Takayasu , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Feminino , Fluordesoxiglucose F18 , Arterite de Células Gigantes/diagnóstico por imagem , Humanos , Interleucina-6 , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Arterite de Takayasu/diagnóstico por imagemRESUMO
OBJECTIVE: Persistent inflammation is an insidious and less studied feature of FMF. We investigated clinical determinants of persistent inflammation and its associations with individual damage items. METHODS: This is a cross-sectional analysis of 917 FMF patients, who fulfilled the Tel Hashomer criteria and had at least 6 months' follow-up. Patients were stratified based on whether they had persistent inflammation. We used logistic regression analysis to investigate independent predictors of persistent inflammation and the associated individual damage items. RESULTS: One hundred and forty-two (15%) patients had persistent inflammation. Active FMF (54%) was the most prominent reason for the persistent inflammation. Spondylarthritis (16%), other inflammatory arthritis (8%) and IBD (2%) were other frequent reasons. Male gender, history of exertional leg pain, inflammatory comorbidities, M694V homozygosity, colchicine resistance, lower education levels and musculoskeletal attack dominance were found to be the independent predictors of persistent inflammation. Earlier disease onset led to a tendency towards persistent inflammation. Patients with persistent inflammation were more likely to suffer damage. There is an increased risk of developing proteinuria, amyloidosis and renal insufficiency. CONCLUSION: We identified, for the first time, the predictors of persistent inflammation in adult FMF patients and related individual damage items of the Autoinflammatory Disease Damage Index. Persistent inflammation is insidious and one of the chief causes of damage; therefore, especially patients with these predictors should be followed up more closely. If detected, underlying inflammatory comorbidities should be assessed meticulously as early detection and proper treatment strategies may favourably impact the natural history of the disease.
Assuntos
Febre Familiar do Mediterrâneo/complicações , Inflamação/etiologia , Espondilartrite/complicações , Adolescente , Adulto , Criança , Estudos Transversais , Escolaridade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais , Adulto JovemRESUMO
OBJECTIVES: Anakinra and canakinumab are the most commonly used agents in colchicine resistant/intolerant patients. In this study we investigated long-term efficacy and safety of anakinra and canakinumab. METHODS: In this retrospective study, we enrolled 101 adult patients with familial Mediterranean fever (FMF). Clinical and laboratory parameters before and after treatment with anakinra/canakinumab and the side effects observed during the treatment were recorded. All patients received anakinra initially and switched to canakinumab, in case of inadequate response/intolerance. RESULTS: The median (IQR) duration of treatment with anti-IL-1 agents was 35 (24-47.5) months. 101 patients were treated with anakinra and 27 patients with canakinumab. The autoinflammatory diseases activity and attacks decreased with both anakinra and canakinumab. Anakinra was effective in decreasing proteinuria and canakinumab was not effective in decreasing proteinuria in anakinra unresponsive patients. The modified FMF score was achieved in 76.2% of anakinra and 88.9% of canakinumab group. Injection site reactions (ISRs, n:15) was the most common reason of discontinuation of anakinra and most of ISRs developed in first 3 months of treatment. One severe skin rash, two anaphylactic reactions and one severe neutropenia were observed with anakinra; in the first, eighth, twelfth and fiftieth months, respectively. No severe side effects or side effect-related discontinuation of canakinumab were observed. CONCLUSIONS: Anakinra and canakinumab seem to be effective in long-term management of FMF patients. Canakinumab had a favourable safety/tolerability profile. Anakinra is also generally safe, but the serious side effects that may be observed in the short and long-term use should be taken into account.
Assuntos
Febre Familiar do Mediterrâneo , Proteína Antagonista do Receptor de Interleucina 1 , Adulto , Anticorpos Monoclonais Humanizados , Colchicina , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Humanos , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Sometimes, the underlying causes of inflammation cannot be established despite meticulous investigation, including medical history, physical examination, laboratory tests, and radiologic procedures. Rheumatologists are often faced with patients whose condition is known as inflammation of unknown origin (IUO). Differential diagnosis of IUO is diverse, and investigation of these cases is challenging and time-consuming. OBJECTIVE: The study aimed to assess the diagnostic role of positron emission tomography/computed tomography (PET/CT) in the evaluation of patients with IUO. METHODS: The study sample consisted of 97 adult patients with IUO who have not been previously diagnosed with an infectious, inflammatory, or malignant disease. The necessary data were collected from January 2015 to June 2018 with a 6-month follow-up period. The patients were screened using PET/CT after a specific diagnosis could not be established with detailed laboratory and radiologic evaluations. RESULTS: A final diagnosis was established at follow-up, and 47 (54%) of the 97 patients had inflammatory diseases, 30 (34.4%) had malignancies, and 10 (11.4%) had infections. Despite meticulous investigation, 10 patients were left undiagnosed in the follow-up. PET/CT aided diagnosis in 59 patients (60.8%), but it was not helpful in 38 patients (39.2%). PET/CT was positive in 30 (63%) of the 47 patients with inflammatory diseases, whose final diagnosis was inflammatory rheumatic disease, as follows: large-vessel vasculitis in 19 patients, polymyalgia rheumatica in 7 patients, and seronegative arthritis or other rare miscellaneous diseases in 4 patients. The sensitivity of PET/CT was 67% with a specificity and diagnostic accuracy of 100% and 71%, respectively. CONCLUSIONS: Investigation of the underlying etiology of IUO is time-consuming and challenging. PET/CT may help identify the final diagnosis more quickly by locating an obscure inflammatory site; thus, it may reduce the number of unnecessary biopsies, diagnostic time, anxiety, work loss, morbidity, and mortality.
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Febre de Causa Desconhecida , Fluordesoxiglucose F18 , Adulto , Febre de Causa Desconhecida/diagnóstico , Febre de Causa Desconhecida/etiologia , Humanos , Inflamação/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de PósitronsRESUMO
Background/aim: Peritonitis attacks of Familial Mediterranean Fever (FMF) usually requires emergency medical admissions and it's hard to distinguish a typical abdominal attack from surgical causes of acute abdomen. Therefore, history of abdominal surgery, particularly appendectomy, is very common in patients with FMF. However, history of appendectomy might also give some clues about the course of FMF in the adulthood. This study was to determine whether the history of appendectomy help to anticipate disease course of FMF in the adulthood. Materials and methods: All patients recruited from FMF in Central Anatolia (FiCA) cohort, comprising 971 adult subjects. All patients fulfilled the Tel Hashomer criteria. Demographic data, FMF disease characteristics, co-morbid conditions, past medical history, surgical history and disease complications were meticulously questioned and laboratory features and genotype data (if available) were recruited from patient files. Results: Appendectomy history was evident in 240 (24.7%) subjects. Disease onset was earlier and peritonitis is strikingly more prevalent (97.1% vs. 89.6%, p < 0.001) in appendectomized patients. These patients had reported almost two fold more frequent attacks in the last year compared to appendix intact patients (median 3.5 vs. 2 attacks, p = 0.001) without a difference in frequency of musculoskeletal and skin attacks. Severe disease was more common (10% vs. 5.9%, p = 0.038) due to involvement of more attack sites throughout the life and more frequent attacks. Appendectomy patients had used higher daily doses of colchicine to control disease (1.43 ± 0.6 mg vs. 1.27 ± 0.52 mg, p = 0.002) but colchicine resistance was also more common in these patients, 15% vs. 6.7% respectively, p < 0.001. Conclusion: Appendectomy history is common in FMF patients and associated with frequent serositis attacks in adulthood. These patients require higher colchicine doses with a lower rate of response and more need for Interleukin-1 antagonist therapies.
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Apendicectomia , Colchicina/uso terapêutico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Peritonite , Adulto , Colchicina/efeitos adversos , Febre Familiar do Mediterrâneo/epidemiologia , Febre Familiar do Mediterrâneo/genética , Genótipo , HumanosRESUMO
Background/aim: Familial Mediterranean Fever (FMF) is the prototype of hereditary autoinflammatory disorders and caused by mutations on the MEFV gene located on the short arm of chromosome 16. Although some MEFV variants are clearly associated with disease phenotype, there are numerous variants with unknown clinical association which are termed as variants of uncertain significance (VUS). Here, we present clinical correlations of VUS in a large cohort of adult FMF patients from three tertiary centers located in Central Anatolia. Materials and methods: All patients were recruited from FMF in Central Anatolia (FiCA) cohort. Demographic (sex, age at disease onset) and clinical features (disease characteristics, attack frequency, mean colchicine dose, colchicine nonresponsiveness, amyloidosis, and persistent inflammation) of patients with VUS were compared with those harboring pathogenic variants. Disease severity and damage were also evaluated using international severity score for FMF (ISSF) and autoinflammatory disease damage index (ADDI), respectively. Results: Among 971 participants included, MEFV gene analysis results were available for 814 patients. Twenty-six (3.2%) patients had single heterozygous VUS and 54 (6.6%) had pathogenic/VUS complex heterozygous variants. Patients with single heterozygous VUS had similar demographic/clinical features, ISSF and ADDI scores compared to those with single heterozygous pathogenic variant (p > 0.05 for all). No difference was observed in the demographic and clinical features of patients with single heterozygous pathogenic mutation and pathogenic/VUS complex heterozygous variant (p > 0.05 for all). ISSF and ADDI scores were lower in pathogenic/VUS complex heterozygous patients than those harboring single pathogenic mutation (p = 0.006 and 0.004, respectively). Conclusion: Our findings suggest that patients with single heterozygous VUS has mild FMF phenotype similar to those with single pathogenic mutation. Pathogenic/VUS complex heterozygosity does not lead to a more severe clinical phenotype than having a single pathogenic variant.
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Febre Familiar do Mediterrâneo/genética , Mutação/genética , Pirina/genética , Adulto , Colchicina/uso terapêutico , Estudos Transversais , Febre Familiar do Mediterrâneo/etnologia , Feminino , Heterozigoto , Humanos , Masculino , Fenótipo , TurquiaRESUMO
INTRODUCTION: Systemic lupus erythematosus (SLE) is associated with an increased risk of pulmonary infections, as well as a rare condition known as shrinking lung syndrome (SLS). The diaphragm has an important role to play in lung physiology and might also play a role in these adverse events. Here, we aimed to investigate whether SLE patients have impairment in their diaphragmatic muscle thickness and function with respect to another connective-tissue disease: primary Sjögren's syndrome (pSS). METHOD: Patients diagnosed with SLE who were in remission or who had minimal disease activity and had at least one year of follow-up were included in this study. Patients with known lung pathology and smokers were excluded. Patients with pSS constituted the second experimental group. Ultrasonographic evaluation of the diaphragmatic muscle was conducted by an experienced independent sonographer at three time points, diaphragmatic thickness during deep and quiet inspiration and maximum expiration being measured. Diaphragmatic muscle function was evaluated with maximum expiratory pressure (MEP) and maximum inspiratory pressure (MIP). RESULTS: A total of 115 patients were studied (n = 39 SLE; n = 76 pSS). The mean ± standard deviation (SD) thickness of the diaphragmatic muscles during quiet inspiration was significantly reduced in patients with SLE compared to patients with pSS (2.32 mm vs. 2.81 mm; p < 0.05). Similarly, the thickness during deep inspiration and at maximum deep expiration were significantly lower in SLE patients (2.88 mm vs. 3.29 mm and 1.92 mm vs. 2.33 mm, respectively; p < 0.01). MIPs and MEPs, defined as the percentages of expected values, were significantly lower in patients with SLE compared to those with pSS (80% vs. 92% and 76% vs. 120%, respectively; p < 0.05). Diaphragmatic muscle thickness during deep inspiration demonstrated a moderate correlation with MIP (r = 0.434; p = 0.001). CONCLUSION: SLE patients had reduced diaphragmatic muscle thickness compared to those with pSS, which was associated with impaired functional tests. Further prospective studies are needed to investigate whether structural and functional impairments in diaphragmatic muscle play a role in an increased risk of pulmonary infections and SLS in patients with SLE.
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Diafragma/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Síndrome de Sjogren/diagnóstico por imagem , Adulto , Estudos Transversais , Diafragma/fisiopatologia , Feminino , Seguimentos , Humanos , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Testes de Função Respiratória , Índice de Gravidade de Doença , Síndrome de Sjogren/fisiopatologia , Ultrassonografia , Adulto JovemRESUMO
OBJECTIVES: Defining predictors of damage would improve patient care. We applied damage indexes to patients with familial Mediterranean fever (FMF) and identified the predictors of damage. METHODS: This is a cross-sectional analysis of 926 FMF patients, who fulfilled the Tel-Hashomer criteria and had at least six months of follow-up. Patients were stratified according to their damage status (damage vs. no damage) defined with autoinflammatory disease damage index (ADDI) and modified ADDI (excluding musculoskeletal pain). We used logistic regression analysis to investigate independent predictors of damage for both indexes. RESULTS: Mean disease duration was 21.6±11.9 years. 527 patients (57%) had damage according to ADDI. Median ADDI score was 1 (0-11). Most common FMF-related damages were observed in musculoskeletal, reproductive and kidney domains. Female gender, inflammatory comorbidity, colchicine resistance, colchicine nonadherence, musculoskeletal attack dominance, diagnostic delay, follow-up time, and smoking history remained independent predictors of damage according to ADDI score. The rate of patients with damage defined by modified ADDI was only to 23%. M694V/M694V homozygosity, female gender, musculoskeletal attack dominance, colchicine resistance, persistent inflammation, follow up time and family history of amyloidosis were found to be predictors of damage according to modified ADDI score. CONCLUSIONS: Our study is the first to apply comprehensive damage indexes to FMF patients and identified predictors of damage. Factors linked to a severe FMF phenotype, including M694V homozygosity and persistent inflammation, were associated with only modified ADDI. Our findings justify the concerns about musculoskeletal pain and might point to the need for re-evaluation of ADDI for FMF patients.
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Febre Familiar do Mediterrâneo , Colchicina/uso terapêutico , Estudos Transversais , Diagnóstico Tardio , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Febre Familiar do Mediterrâneo/epidemiologia , Feminino , Homozigoto , Humanos , Mutação , Pirina/genéticaRESUMO
Familial Mediterranean fever is characterized by self-limited attacks of serositis and arthritis. However, substantial number of patients suffer from chronic complications of this disease, primarily involving musculoskeletal system. Treatment for these complications is challenging due to limited evidence. Interleukin-1 (IL-1) antagonists, tocilizumab and anti-tumor necrosis factor (anti-TNF) agents are off-label treatment options for the management of chronic manifestations of FMF, such as secondary (AA) amyloidosis, chronic arthritis and sacroiliitis. This paper presents a case series of four FMF patients who are refractory to IL-1 antagonists, anti-TNF agents and tocilizumab, who responded well to tofacitinib. The authors also conducted a comprehensive literature search for studies investigating tofacitinib use in FMF patients. Although still limited, current data suggest that tofacitinib could be a useful treatment option for FMF patients with associated inflammatory comorbid conditions and chronic manifestations of disease.
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Febre Familiar do Mediterrâneo/tratamento farmacológico , Inibidores de Janus Quinases/uso terapêutico , Piperidinas/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Colchicina/uso terapêutico , Resistência a Medicamentos , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Masculino , Pessoa de Meia-Idade , Falha de Tratamento , Resultado do Tratamento , Moduladores de Tubulina/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
Familial Mediterranean fever (FMF) is characterized by recurrent short-lived/self-limiting inflammatory attacks. Besides these, a substantial number of patients with FMF present with a variety of other inflammatory diseases; however, this issue has not been systematically studied previously. Hence, we aimed to investigate the frequency of inflammatory comorbid diseases in a large FMF cohort. All patients were recruited from "FMF in Central Anatolia (FiCA) Cohort", comprising 971 (mean age 35.3 ± 12 years, 61.5% female) adult subjects. All patients fulfilled Tel Hashomer criteria. Demographic data, FMF disease characteristics, MEFV gene mutations, and comorbid inflammatory diseases were meticulously questioned, and laboratory features and genotype data were retrieved from hospital records. There were comorbid inflammatory diseases in 205 (21.1%) patients. The most common inflammatory disease was spondyloarthritis (12.9%). Other remarkable inflammatory disorders were psoriasis, immunoglobulin A vasculitis/Henoch-Schönlein purpura, Behçet's disease and inflammatory bowel diseases. Cryptogenic organizing pneumonia is a newly defined entity in our cohort which is seemed to be associated with FMF (0.3%). Number of patients with persistent inflammation was higher in those with comorbid diseases (p < 0.001). Our results suggest that FMF is commonly associated with other inflammatory diseases. Therefore, clinicians should be cautious about comorbid inflammatory diseases in FMF patients, particularly in those with persistent inflammation. Identification of pathogenic pathways linking FMF to these diseases warrants further investigations.
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Síndrome de Behçet/epidemiologia , Pneumonia em Organização Criptogênica/epidemiologia , Febre Familiar do Mediterrâneo/epidemiologia , Vasculite por IgA/epidemiologia , Doenças Inflamatórias Intestinais/epidemiologia , Psoríase/epidemiologia , Espondiloartropatias/epidemiologia , Vasculite/epidemiologia , Adulto , Estudos de Coortes , Comorbidade , Febre Familiar do Mediterrâneo/genética , Febre Familiar do Mediterrâneo/fisiopatologia , Humanos , Imunoglobulina A/imunologia , Pessoa de Meia-Idade , Pirina/genética , Turquia/epidemiologia , Vasculite/imunologia , Adulto JovemRESUMO
OBJECTIVE: We aimed to present our single-center real-life experience of canakinumab use in adult patients with familial Mediterranean fever (FMF). METHODS: Data were derived from the Gazi FMF cohort, which was established in 2010. From that year, all patients with FMF were registered. The impact of FMF on their lives was tracked by either an FMF diary or mobile phone application (FMF-AIDD, free to download in App Store and Google Play). The records of patients who were treated with canakinumab were reviewed. RESULTS: Twenty-three adult patients with FMF (65% female) were enrolled in this study. The median age was 32 years (min-max, 24-58 years), and the disease duration was 26 years (14-59 years). A total of 86% of patients harbored homozygous or compound heterozygous exon 10 MEFV mutations. Indications for interleukin 1 inhibitor use were colchicine resistance (n = 12) or intolerance (n = 2), amyloidosis (n = 7), and chronic manifestations of the disease (n = 2). All patients used anakinra before. The median duration of canakinumab use was 7 months (min-max, 1-44 months). Pre- and post-canakinumab periods were compared. Attack severity, duration, frequency, C-reactive protein level, and erythrocyte sedimentation rate were significantly improved (p ≤ 0.01), whereas serum creatinine and alanine aminotransferase levels remained the same (p = 0.27 and p = 0.74, respectively). Canakinumab achieved complete disease remission in 14 patients (60%). Canakinumab was discontinued in 7 patients. The reasons for discontinuation were pregnancy (n = 2), dominance of axial spondyloarthropathy (n = 2), inflammatory bowel disease, patient's refusal, and weight gain. CONCLUSIONS: Canakinumab is effective in the prevention of FMF bouts without severe adverse effects. Treatment with canakinumab in an individualized dose and interval may be a reasonable choice for colchicine- and anakinra-resistant or -intolerant adult patients with FMF and those with chronic manifestations of disease.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Colchicina/uso terapêutico , Resistência a Múltiplos Medicamentos , Febre Familiar do Mediterrâneo/tratamento farmacológico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Adulto , Estudos de Coortes , Bases de Dados Factuais , Febre Familiar do Mediterrâneo/diagnóstico , Feminino , Seguimentos , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Oriente Médio , Retratamento , Estudos Retrospectivos , Medição de Risco , Estatísticas não Paramétricas , Resultado do Tratamento , Adulto JovemRESUMO
Background/aim: Colchicine is the mainstay of treatment in FMF. However, in daily practice it is not easy to maintain effective colchicine doses in a substantial number of patients due to its side effects. In this study, we aimed to investigate prevalence and risk factors for colchicine side effects that limit optimal drug dosing and cause permanent discontinuation. Materials and methods: All patients were recruited from "FMF in Central Anatolia" (FiCA) cohort, 915 adults with a minimum follow- up time of 6 months during which they had obeyed all treatment instructions. Demographic and anthropometric data, FMF disease characteristics, disease severity, complications, and treatment features were recorded on a web-based registry. Prevalence of colchicine intolerance and characteristics of intolerant patients were analyzed. Results: Effective colchicine doses cannot be maintained in 172 (18.7%) subjects. Main side effects that limit optimal dosing were as follows: diarrhea in 99 (10.8%), elevation in transaminases in 54 (5.9%), leukopenia in 10 (%1.1), renal impairment in 14 (1.3%), myopathy in five (0.5%), and allergic skin reaction in two. Colchicine had to be permanently ceased in 18 (2%) patients because of serious toxicity. Male sex and obesity were found to be associated with liver toxicity, and having a normal body weight was associated with diarrhea. Chronic inflammation and proteinuria were more common in colchicine-intolerant patients, and they had reported more frequent attacks compared to those tolerating optimal doses. Conclusion: Colchicine intolerance is an important problem in daily clinical practice, mainly due to diarrhea and liver toxicity. Suboptimal colchicine dosing is associated with complications.
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Anti-Inflamatórios , Colchicina , Febre Familiar do Mediterrâneo/tratamento farmacológico , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Estudos de Coortes , Colchicina/administração & dosagem , Colchicina/efeitos adversos , Colchicina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Avascular necrosis (AVN), also known as osteonecrosis, is characterized by death of the osteocytes due to inadequate blood supply caused by various mechanisms. The hip is the most common affected joint followed by knee. Incidence of AVN in rheumatic diseases is variable and high corticosteroid (CS) therapy is a known major risk factor for development of AVN. Data on the AVN in Behçet disease (BD) are limited. The purpose of this study is to examine the clinical and treatment characteristics of BD patients with diagnosis of AVN. Retrospective medical records of 337 BD patients were reviewed. Nine BD patients with AVN were detected. The clinical data of these patients with AVN have been reviewed. All patients had MRI of the symptomatic joints compatible with AVN. All of the nine patients who were diagnosed with AVN were male. Median duration of BD was 7 years. Median time between diagnosis of BD and detection of AVN was 3 years (1-16 years). Multiple joints were involved in seven patients. Six patients had bilateral knee AVN. Six patients had vascular BD. The median time interval between initial CS dose and AVN development was 24 months (range = 2-100). The median highest daily CS dose was 64 mg/day (range = 32-80) and median cumulative CS dose prior to AVN was 18 g. All of patients had intravenous pulse steroids. CS treatment, smoking and vascular involvement may predispose to AVN in patients with BD. According to this cohort, AVN in BD frequently tended to be in the knee joint and bilateral.
Assuntos
Corticosteroides/uso terapêutico , Síndrome de Behçet/complicações , Osteonecrose/complicações , Adolescente , Adulto , Síndrome de Behçet/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Osteonecrose/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Colchicine is the mainstay of the treatment of familial Mediterranean fever (FMF). However, 10% of FMF patients do not respond well to colchicine. Efficacy of interleukin (IL)-1 inhibitors in reducing attacks have been demonstrated in colchicine-resistant FMF (crFMF) patients recently. Colchicine is still the only approved drug for the prevention of amyloidosis in FMF and utility of IL-1 inhibitors in crFMF cases who already has amyloidosis remain to be elucidated. Herein, we evaluated efficacy and safety of IL-1 inhibitors in patients with crFMF-associated AA amyloidosis in a relatively large single center study. METHODS: Medical records of FMF patients complicated with AA amyloidosis in our dedicated FMF center were retrospectively reviewed and those patients who ever treated with IL-1 inhibitors were enrolled into the study. Patient global, physician global assessments (on 0-10 cm visual analog scale), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum creatinine and 24-h urinary protein excretion values for each visit were recruited from computer-based hospital records. Treatment response of patients were assessed with clinical symptoms, serum albumin, CRP and ESR values. Renal outcome parameters were analyzed on those not receiving renal replacement therapy. RESULTS: Seventeen patients were identified with crFMF-amyloidosis that ever treated with IL-1 inhibitors. Background colchicine therapy was continued in all patients in maximal-tolerated dose along with IL-1 inhibitors. All patients benefit from IL-1 antagonists assessed by patient and physician global assessments. Inflammatory markers, CRP and ESR, were significantly reduced in all and normalized in 12 out of 17 patients. More importantly, the amount of proteinuria was remarkably improved following IL-1 inhibitor therapy (1606 mg/day to 519 mg/day, p = .008). Both anakinra and canakinumab were well-tolerated without severe side effects. All patients were initially treated with anakinra but switched to canakinumab in seven patients (one leukopenia, four injection site reaction, two inefficacy). CONCLUSION: We evaluated the clinical and laboratory responses to IL-1 inhibitors in crFMF-associated amyloidosis patients. We found significant decreases in CRP, ESR and proteinuria after IL-1 inhibitor therapy. This study confirmed that IL-1 inhibitors are effective for controlling attacks and inflammatory activity in FMF patients complicated with AA amyloidosis. Moreover, they reduce or stabilize amount of proteinuria and preserve renal function in short-term follow-up. Prolonged prospective clinical trials are warranted to assess their long-term efficacy in this particular patient group.
Assuntos
Amiloidose , Anticorpos Monoclonais , Colchicina , Febre Familiar do Mediterrâneo , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-1/antagonistas & inibidores , Adulto , Amiloidose/diagnóstico , Amiloidose/tratamento farmacológico , Amiloidose/epidemiologia , Amiloidose/etiologia , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Sedimentação Sanguínea/efeitos dos fármacos , Proteína C-Reativa/análise , Colchicina/administração & dosagem , Colchicina/efeitos adversos , Monitoramento de Medicamentos/métodos , Resistência a Medicamentos , Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/tratamento farmacológico , Febre Familiar do Mediterrâneo/epidemiologia , Febre Familiar do Mediterrâneo/imunologia , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Rim/patologia , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Proteinúria/diagnóstico , Proteinúria/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Turquia/epidemiologiaRESUMO
Background/aim: We aimed to assess the association between retinal vascular caliber (RVC) scores and disease activity in rheumatoid arthritis (RA) patients. Materials and methods: Forty-seven RA patients, 32 systemic lupus erythematosus (SLE) patients, and 45 healthy people were enrolled. RA and SLE patients were subdivided into groups according to C-reactive protein (CRP) levels. RA patients were also grouped according to Disease Activity Score-28 (DAS-28). Fundus photography was performed for all patients. RVC was summarized as the central retinal artery and vein equivalents (CRAE and CRVE). Results: Mean CRVE for RA patients was 213.3 ± 17.8 µm compared with 209.2 ± 14.1 µm for SLE and 217.5 ± 26.2 µm for the control group (P = 0.17). RVC scores did not differ between the CRP-high and CRP-low groups. As the RA disease activity increased, the widening of CRVE became more prominent and statistically significant. When the DAS-28 > 5.1 (CRVE, 220.4 (211.8246.5) µm) group and DAS-28 ≤ 3.2 (CRVE, 214.4 (172.4242.3) µm) group were compared, statistical significance was more pronounced (P = 0.03) than when comparing the DAS-28 > 3.2 and DAS-28 ≤ 3.2 groups (P = 0.05). Conclusions: CRVE, which reflects systemic inflammation and possibly increased cardiovascular risk, was significantly increased in active RA patients. The association between retinal venular widening and disease activity, regardless of CRP, may be a sign that RA-related inflammation may have systemic vascular effects even with normal levels of CRP.