Autoinflammatory Disease Damage Index Research Articles

Effects of interleukin-1 antagonists on de novo and pre-existing damage in patients with familial Mediterranean fever.

Colchicine is the mainstay of familial Mediterranean fever treatment and interleukin (IL-1) antagonists are the treatment of choice in resistant patients. We aimed to investigate efficacy of IL-1 antagonists in the prevention of damage, as well as the causes of treatment failure. A total of 111 patients fulfilling Euro fever and Tel-Hashomer criteria and treated with IL-1 antagonists were included in the study. Patients were grouped according to their recent damage status; no damage, pre-existing damage and de novo damage that developed under IL-1 antagonist treatment. The degree of damage was determined using Auto Inflammatory Disease Damage Index (ADDI). Total damage score was calculated separately as its original definition and with excluding chronic musculoskeletal pain, creating modified ADDI (mADDI). Forty-six patients (43,2 %) had damage according to mADDI. Damage was commonly observed at musculoskeletal, renal and reproductive domains. Median duration of treatment was forty-five months. Two patients developed de novo damage; one musculoskeletal and one reproductive in this time-period. Five patients had worsening of their damage while using IL-1 antagonists. De novo damage with IL-1 antagonist treatment was associated with acute phase protein levels. We evaluated change in damage accrual while using IL-1 antagonists in patients with FMF. Physicians should pay attention to controlling inflammation to prevent further damage, especially in those with pre-existing damage.

Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance

Background/aimFamilial 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 methodsAll 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.ResultsAmong 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).ConclusionOur 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.

Work productivity impairment in patients with familial Mediterranean fever and effects of interleukin-1 antagonists.

Familial Mediterranean fever (FMF) is characterized by recurrent attacks of fever, serositis, and arthritis. Some patients suffer from associated inflammatory conditions and damage related to FMF that may potentially impair work productivity which have not been studied to date. Consecutive FMF patients who were attending a tertiary referral center and age-and sex-matched healthy subjects enrolled into the study. Disease activity was assessed with autoinflammatory disease activity index (AIDAI) and patient global assessment. Damage was evaluated using Autoinflammatory Disease Damage Index (ADDI). Quality of life (QoL) and work productivity were determined with 36-Item Short Form Health Survey (SF-36) and Work Productivity and Activity Impairment Specific Health Problem v2.0 (WPAI:SHP), respectively. There were 111 FMF patients, 60 female (54%), mean age 32.7±8.7 years. There were significant impairments in all domains of the SF-36 QoL in FMF patients. Of the 111 patients enrolled, 65 (58.6%) were employed in a paid work. Mean% ±SD impairment in work productivity both assessed as absenteeism (9.3±23.2% vs. 0.7±2.6, p=0.013) and presenteeism (35.2±32.6% vs. 9.6±14.7, p<0.001) were significantly higher in FMF patients compared to healthy subjects. Impairment in work productivity was correlated with the number of attacks, disease activity, colchicine resistance, and disease-associated damage. Impairment was most significant in colchicine-resistant FMF patients but lower in those on interleukin (IL)-1 antagonist treatments. FMF causes significant work impairment and reduced QoL which is associated with disease activity and damage. The use of IL-1 antagonists may help to improve work productivity and QoL in FMF patients with frequent attacks. Key points • Work productivity is impaired in patients with FMF. • Disease activity was an independent predictor for impaired work productivity. • IL-1 antagonists may improve work productivity and quality of life in FMF patients with frequent attacks.

Compliance of Familial Mediterranean Fever Patients With Regular Follow-up Visits and Associated Factors.

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. This study aimed to assess compliance of FMF patients with regular follow-up visits and the associated factors. 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. 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. 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.

Predictors of persistent inflammation in familial Mediterranean fever and association with damage.

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. 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. 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. 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.

The Safety and Impact of a Model of Intermittent, Time-Restricted Circadian Fasting (“Ramadan Fasting”) on Hidradenitis Suppurativa: Insights from a Multicenter, Observational, Cross-Over, Pilot, Exploratory Study

Hidradenitis suppurativa (HS) is a chronic-relapsing and debilitating disease, which affects the components of the folliculopilosebaceous unit and severely impacts on the perceived health-related quality of life. Among the possible treatments, dietary interventions, such as fasting, have been described to positively impact on HS. However, nothing is known about the effects of circadian, intermittent fasting, such as the Ramadan fasting. A sample of 55 HS patients (24 males (43.6%) and 31 females (56.4%), mean age 39.65 ± 8.39 years, average disease duration 14.31 ± 7.03 years) was recruited in the present study. The “Severity of International Hidradenitis Suppurativa Severity Score System” (IHS4) decreased significantly from 11.00 ± 5.88 (before Ramadan) to 10.15 ± 6.45 (after Ramadan), with a mean difference of −0.85 ± 0.83 (p < 0.0001). At the univariate analyses, the improvement was associated with HS phenotype (with a prominent improvement among those with ectopic type), treatment (with the improvement being higher in patients receiving topical and systemic antibiotics compared to those treated with biologics), the “Autoinflammatory Disease Damage Index” (ADDI), and Hurley scores. At the multivariate regression analysis, only the Hurley score (regression coefficient = 0.70, p = 0.0003) was found to be an independent predictor of change in the IHS4 score after fasting. The improvement in the IHS4 score was not, however, associated with weight loss. In conclusion, the Ramadan fasting proved to be safe and effective in HS patients. Considering the small sample size and the exploratory nature of the present investigation, further studies in the field are warranted, especially longitudinal, prospective and randomized ones.

Nonalcoholic fatty liver disease prevalence in an Italian cohort of patients with hidradenitis suppurativa: A multi-center retrospective analysis.

BACKGROUNDNonalcoholic fatty liver disease (NAFLD) includes two distinct conditions, with different histologic features and prognosis: non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Furthermore, NASH is the more aggressive necro-inflammatory form, which may accumulate fibrosis and result in End stage liver disease (ESLD). NAFLD is also linked to systemic inflammatory conditions such as psoriasis. NAFLD is currently the most common cause of ESLD in Western countries, becoming a serious public health concern. Hidradenitis suppurativa (HS) is a systemic inflammatory/autoinflammatory disease of the terminal follicular epithelium of the apocrine gland with a prevalence of 0.05% to 4.10%. Due to its systemic inflammatory behavior several comorbidities were recently associated, however liver ones were scarcely assessed.AIMTo evaluate the prevalence and characteristics of NASH/NAFL in HS patients.METHODSThis retrospective study is a sub-analysis of a larger study carried out in 4 Italian dermatological centers. In this cohort, there were 83 patients: 51 patients with HS only, 20 patients with HS/NAFL and 12 with HS/NASH.RESULTSInflammatory comorbidities were present in 3.9% of HS only patients, 25% of HS/NAFL patients and 58.3% of HS/NASH patients (P < 0.001). Similarly, mean Autoinflammatory Disease Damage Index (ADDI) was significantly higher among patients with HS/NASH (5.3 ± 2.2, P < 0.001) compared to patients with HS/NAFL or HS only (2.8 ± 1.6 and 2.6 ± 1.4 respectively). Furthermore, ADDI correlates with IHS4 in HS, HS/NAFL and HS/NASH. Diabetic patients have higher Hurley score than not diabetic ones. Ultrasound examination was significantly different in the three groups.CONCLUSIONHS patients displayed a high prevalence of NASH/NAFLD and ultrasound examination should be particularly addressed to patients that display high ADDI scores.

In silico validation of the Autoinflammatory Disease Damage Index

IntroductionAutoinflammatory diseases can cause irreversible tissue damage due to systemic inflammation. Recently, the Autoinflammatory Disease Damage Index (ADDI) was developed. The ADDI is the first instrument to quantify damage in...

Development of the autoinflammatory disease damage index (ADDI)

ObjectivesAutoinflammatory diseases cause systemic inflammation that can result in damage to multiple organs. A validated instrument is essential to quantify damage in individual patients and to compare disease outcomes in...

Development of the autoinflammatory disease damage index (ADDI)

Autoinflammatory diseases cause systemic inflammation which can result in damage to multiple organs. Organ damage can occur before the start of therapy, or when patients experience ongoing inflammation. A validated instrument to measure damage is essential to quantify damage in individual patients, and to compare disease outcomes in clinical studies. At this moment, there is no such instrument. In the context of the RaDiCEA project, a common damage index for Familial Mediterranean Fever (FMF), Cryopyrin Associated Periodic Syndromes (CAPS), Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) and Mevalonate Kinase Deficiency (MKD) will be developed.