ABSTRACT
BackgroundPatients with pre-existing rheumatic diseases may be exacerbated during SARS-CoV-2 infection, or may develop new autoimmune features. Furthermore, immunosuppressive agents used to treat autoimmunity-inflammation as well as comorbidities can also affect the disease outcome.ObjectivesTo evaluate the outcome of rheumatic diseases after Covid 19 infection in patients diagnosed with rheumatic diseases, under various immunosuppressive treatment, as well as the effects of vaccines against Covid or antiviral treatment in this sensitive population group.MethodsDuring the pandemic, 1493 patients with autoimmune or autoinflammatory disease who were continuously followed up in two tertiaries hospitals in northern and northwestern Greece were included in the current study. The patients were compared with 769 controls after adjustment for age, sex, weight, vaccination status and comorbidities. Of the 1493 patients, 648 had rheumatoid arthritis, 282 psoriatic arthritis, 173 ankylosing spondylitis, 122 systemic lupus erythematosus, 98 Sjogren's syndrome, 43 polymyalgia rheumatica, 34 mixed connective tissue disease or overlapping syndromes, 31 vasculitis, 27 systemic sclerosis, 18 myositis, 10 Behcet syndrome, 5 primary antiphospholipid syndrome and 2 had Familial Mediterranean Fever. The vast majority of patients and controls were fully vaccinated (82%) and 397 patients received antiviral treatment, 94% of them were fully vaccinated.ResultsCovid 19 disease in vaccinated patients with rheumatic diseases was shown to perform the same or about the same as those in the control group after adjustment for risk factors for severe disease. 19 of our patients required admission in the intensive care unit (62% full vaccinated) while a total of 12 died (66% non vaccinated). Major risk factors for severe disease were previous respiratory failure, chronic renal impairment, obesity, and failure to receive antiviral therapy. It was also shown that infection with Covid led to an exacerbation or induction of autoimmune disorders in 25 of the participants.ConclusionIn this large cohort, Covid 19 disease was shown to affect patients with autoimmune rheumatic diseases the same or approximately the same way as the general population if they are fully vaccinated and if they start timely antiviral treatment where indicated. Further research and monitoring of the results after the multiple mutations of the virus is advisable.ReferencesNone.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
ABSTRACT
FAPDs (Functional Abdominal Pain Disorders) are the most common cause of chronic abdominal pain but are largely diagnoses of exclusion. More specific, but much less common, causes of acute and chronic abdominal pain include COVID-19 (PIMS-TS), Helicobacter pylori infection, Yersinia spp. Infection and Familial Mediterranean Fever. © Springer Nature Switzerland AG 2022. All rights reserved.
ABSTRACT
Background: It is known that the gut microbiome of a healthy person affects the process of COVID-19 after getting infected with SARS-CoV-2 virus. It is also believed that colchicine can alleviate the severity of COVID-19. Objective: Current investigations aimed to evaluate the associations between the baseline gut microbiota composition of healthy and Familial Mediterranean fever (FMF) - carrier Armenian men populations, and the severity of the COVID-19 disease after their infection with the SARS-CoV-2. The study has a purpose of answering three core questions: i. Do the characteristics of gut microbiome of Armenians affect the course of COVID-19 severity? ii. How does the COVID-19 disease course on go for FMF patients who have been taking colchicine as a medication over the years after getting infected with SARS-CoV-2? iii. Is there an initial gut micribiota structure pattern for non-FMF and FMF patients in the cases when COVID-19 appears in mild form? Methods: The gut microbiota composition in non-FMF and FMF patients before the first infection (mild and moderate course of COVID-19) was considered. COVID-19 was diagnosed by SARS-CoV-2 nucleic acid RT-PCR in nasopharyngeal swab and/or sputum. Results: The number of patients with male FMF with mild COVID-19 was approximately two times higher than that of non-FMF male subjects with COVID-19. In addition, an association of COVID-19 disease severity with the baseline gut Prevotella, Clostridium hiranonis, Eubacterium biforme, Veillonellaceae, Coprococcus, and Blautia diversities in the non-FMF and FMF populations were revealed by us, which can be used as risk/prognostic factor for the severity of COVID-19.
ABSTRACT
Colchicine is a cheap easily available and accessible drug that has been tried in different diseases which are not limited to gout, familial Mediterranean fever (FMF), Behcet's disease, and constipation, and has recently been tried for the treatment of COVID-19 and heart diseases. There are many emerging reports of toxicity related to colchicine use. Patients with FMF are using this drug lifelong. We are sounding the alarm for monitoring patients with FMF to guard against chronic colchicine toxicity.
ABSTRACT
Familial Mediterranean fever (FMF) is an inherited autoinflammatory disease associated with the MEFV gene. FMF is common in Mediterranean peoples but not highly recognized in Japan. We herein report two cases of Japanese FMF patients who were diagnosed by genetic testing for the MEFV gene during the Coronavirus disease 2019 (COVID-19) pandemic. Both patients presented with symptoms similar to COVID-19, which delayed the definitive diagnosis. Patients with a confirmed diagnosis of FMF may be eligible for physical, emotional, and financial benefits. Therefore, the COVID-19 pandemic highlights the importance of differentiating the diagnosis by genetic testing.
ABSTRACT
Background: In December 2019, an outbreak of pneumonia caused by the novel coronavirus disease 2019 (COVID-19) became a pandemic and caused a global health crisis. This study evaluates the immunogenic potential of the Mediterranean fever (MEFV) gene in patients with COVID-19. Methods: A cross-sectional study was conducted from March to April 2020 in various COVID-19 referral centers in Ardabil, Iran. Blood samples of 50 hospitalized patients with confirmed COVID-19 were evaluated for MEFV gene mutation using the amplification refractory mutation system polymerase chain reaction (ARMS-PCR) and Sanger sequencing. Statistical analysis was performed using SPSS software, version 22.0. Results: Mutations of the MEFV gene were found in 6 (12%) of the patients. All mutations were heterozygous, and no homozygous or compound heterozygous forms were detected. The total mutant allele frequency was 6% and the carrier rate was 12%. The most common allele of the MEFV variant was E148Q, detected in 3 (6%) patients. No mutant variant of the MEFV gene was detected in deceased patients. None of the mutation carriers had familial Mediterranean fever (FMF) symptoms or a family history of FMF. Conclusion: MEFV gene mutations may have immunogenic potential in patients with COVID-19. A preprint version of this article has already been published at https://www.researchsquare.com/article/rs-69373/latest.pdf.
Subject(s)
COVID-19 , Familial Mediterranean Fever , Humans , Cross-Sectional Studies , Pyrin/genetics , Mutation , Familial Mediterranean Fever/epidemiology , Familial Mediterranean Fever/geneticsABSTRACT
Systemic autoinflammatory diseases (SAIDs) are defined by recurrent febrile attacks associated with protean manifestations involving joints, the gastrointestinal tract, skin, and the central nervous system, combined with elevated inflammatory markers, and are caused by a dysregulation of the innate immune system. From a clinical standpoint, the most known SAIDs are familial Mediterranean fever (FMF); cryopyrin-associated periodic syndrome (CAPS); mevalonate kinase deficiency (MKD); and periodic fever, aphthosis, pharyngitis, and adenitis (PFAPA) syndrome. Current guidelines recommend the regular sequential administration of vaccines for all individuals with SAIDs. However, these patients have a much lower vaccination coverage rates in 'real-world' epidemiological studies than the general population. The main purpose of this review was to evaluate the scientific evidence available on both the efficacy and safety of vaccines in patients with SAIDs. From this analysis, neither serious adverse effects nor poorer antibody responses have been observed after vaccination in patients with SAIDs on treatment with biologic agents. More specifically, no new-onset immune-mediated complications have been observed following immunizations. Post-vaccination acute flares were significantly less frequent in FMF patients treated with colchicine alone than in those treated with both colchicine and canakinumab. Conversely, a decreased risk of SARS-CoV-2 infection has been proved for patients with FMF after vaccination with the mRNA-based BNT162b2 vaccine. Canakinumab did not appear to affect the ability to produce antibodies against non-live vaccines in patients with CAPS, especially if administered with a time lag from the vaccination. On the other hand, our analysis has shown that immunization against Streptococcus pneumoniae, specifically with the pneumococcal polysaccharide vaccine, was associated with a higher incidence of adverse reactions in CAPS patients. In addition, disease flares might be elicited by vaccinations in children with MKD, though no adverse events have been noted despite concurrent treatment with either anakinra or canakinumab. PFAPA patients seem to be less responsive to measles, mumps, and rubella-vaccine, but have shown higher antibody response than healthy controls following vaccination against hepatitis A. In consideration of the clinical frailty of both children and adults with SAIDs, all vaccinations remain 'highly' recommended in this category of patients despite the paucity of data available.
ABSTRACT
Background: Serious infections are more frequently seen in patients with infam-matory rheumatic diseases, being treated with immunosuppressive or biologic disease-modifying antirheumatic drugs (b-DMARDs). Potential harmful effects of immunosuppressive drugs as well as b-DMARDs were a major concern during the early phases of the Coronavirus disease 2019 (COVID-19) pandemic, and preliminary data documented the worse outcome of COVID-19 associated with B cell depleting treatments (1). On the other hand, limited information has been shared about the course of COVID-19 in patients with monogenic autoinfamma-tory disorders using IL-1 inhibitors. Objectives: We herein aimed to evaluate the course of COVID-19 in adult patients with the most common form of infammasomopathy, Familial Mediterranean Fever (FMF), who were on biologic agents. Methods: In this cross-sectionally study, FMF patients were evaluated by screening their clinical and electronic records in our database in October 2021. The FMF patients with a record of PCR-confrmed COVID-19 were investigated in more detail in our hospital. Characteristics of FMF fndings as well as clinical and laboratory fndings associated with COVID-19 were recorded from the outpatient follow-up cards. Results: We identified 184 FMF patients using biologic agents, and their baseline characteristics are summarized in Table 1. Among them, 36 had PCR-confirmed COVID-19;32 of them were currently on b-DMARD along with colchicine (31 anti-IL-1, 1 anti-TNF), and 4 of them had a previous history of b-DMARD treatment. Data about the course of COVID-19 could be reached in 34 patients. Four (11%) patients had an asymptomatic course. Remaining patients with symptomatic COVID-19 had the following symptoms: cough (50%), headache (47.2%), fever (44.4%), loss of taste and smell (41.6%), myalgia (0.6%), dyspnoea (27.8%), diarrhea (25%) abdominal pain (5.6%). Thorax computed tomography was performed in 10 patients, and findings of pneumonia were documented in 6 (16.7%). The mean values of the laboratory parameters were as follows: C-reactive protein 99.48 ± 112.66 mg/L;ferritin 316 ± 208.3;D-Dimer 2445 ± 3917, Lactate Dehydroge-nase 253 ± 61, troponin T 26 ± 20, procalcitonin 0.348 ± 0.53. Lymphopenia was detected in 5 (13.9%) patients;mean lymphocyte count was 1080 ± 363. Data about the treatment could be reached in 34 patients. Antiviral therapy was prescribed in 25 (69.4%) patients (favipiravir, n=22;and oseltamivir, n=3). Antibiotics were given to 6 (16.7%) patients, and 6 (16.7%) received hydroxychloroquine. Parenteral steroids were administered to 2 patients during the hospitalization. Six (16.7%) patients required hospitalization, and 2 (5.6%) required oxygen support, non-invasive mechanical ventilation, and one of them followed in the intensive care unit. Twenty-two patients were on anakinra treatment, and none of them required additional dose. Only 1 patient, a 61-year-old male patient with a history of lung lobectomy and renal transplantation, received tocilizumab due to macrophage activation syndrome, and he later died of sepsis. This patient was on anakinra until 2 years before, and it was discontinued due to an allergic reaction. Only 4 patients had a history of vaccination before COVID-19, and none of them developed pneumonia and required hospitalization. Six patients had FMF attacks after recovering from COVID-19. None of the patients developed thromboembo-lism and secondary bacterial infections. Conclusion: This survey identified 36 biologic b-DMARD receiving FMF patients, who had COVID-19. All but 1 patient had complete recovery, and b-DMARD usage did not negatively affect the COVID-19 course. None of the patients currently on anti-IL-1 or anti-TNF had a worse outcome. Based on these observations, it can be suggested that refractory FMF patients can continue their b-DMARD treatments when they had COVID-19.
ABSTRACT
Background: To prevent COVID-19 disease SARS-CoV 2 vaccines put into use worldwide with emergency use authorizations despite ongoing safety concerns. Since pyrin mediated infammasome response is dysregulated in FMF, exposure to SARS-CoV 2 proteins via vaccination may potentially trigger infammation, leading to attacks and/or increased rate of adverse events (AE). Objectives: Aim of this study to investigate frequency of adverse events and attacks related to vaccination in recipients of CoronaVac and BNT162b2 comparatively in our FMF patients. Methods: Data regarding, number of vaccine doses, types of vaccines (Coro-naVac or BNT162b2), presence of AEs and/or FMF attacks after any vaccine dose within a month, history of COVID-19 infection before or after vaccination, adherence to FMF treatment during vaccination were collected from hospital database or via telephone. Results: A total of 161 vaccinated FMF patients were included. Mean ± SD age was 40.5 ± 11.7 years. 57.1% was female. 10.6% of the patients had chronic kidney disease and 9.3% had amyloidosis. Most common MEFV mutations were M694V heterozygous (27%) and M694V homozygous (21.6%). 93.2% of the patients were under colchicine, 21.8% under anti-interleukin 1 agents, 2.5% under TNF-a inhibitors. 96.3% of the patients adhered to FMF treatment during vaccination. Vaccination properties and data regarding adverse events are presented in Table 1. 57.8% of patients reported to suffer from an AE/attack after a vaccine dose. Number of patients with AE after BNT162b2 was signifcantly higher (p<0.001). None of the patients had severe AEs. 39 patients had COVID-19 infection prior to primary vaccination. 61.5% of these suffered from an adverse reaction/attack after vaccination, in comparison to 56.6% of the patients without prior COVID-19 infection (p=0.584). When patients with and without AEs/attacks were compared, no signifcant differences were observed regarding age, gender, body mass index, comorbidities, FMF treatments and total vaccine doses. Conclusion: We observed considerable number of FMF patients suffered from vaccine related AEs/attacks, particularly with BNT162b2. However, no serious AE was detected. Demographics, clinical characteristics and prior history of vaccination did not signifcantly affect AE/attack occurrence.
ABSTRACT
Background: Autoinfammatory diseases (AID) are characterized by severe systemic and organ infammation as well as high burden of disease for patients and their families. Treatment with the monoclonal antibody canakinumab (CAN), an interleukin-1β inhibitor, has been proven to be safe and effective in clinical trials and real-life. Objectives: The present study explores the long-term efficacy and safety of CAN in routine clinical practice conditions in pediatric (age ≥2 years) and adult patients with CAPS (cryopyrin-associated periodic syndromes), FMF (familial Mediterranean fever), TRAPS (tumor necrosis factor receptor-associated periodic syndrome) and HIDS/MKD (hyperimmunoglobulinemia D syndrome/meva-lonate kinase defciency). Methods: RELIANCE is a prospective, non-interventional, observational study based in Germany. Patients with clinically confrmed diagnoses of AID routinely receiving CAN are enrolled. Besides efficacy parameters regarding disease activity and remission, safety parameters were recorded at baseline and assessed at 6-monthly intervals. Results: Here, we present the interim analysis of patients with AID (N=199) enrolled in the RELIANCE Registry between October 2017 and December 2021. Mean age in this cohort was 24.4 years (2-79 years) and the proportion of female patients was 53% (N=104). At baseline, median duration of prior CAN treatment was 2 years (0-12 years). A total of 123 patients (62%) experienced any AE (N=653) among which naso-pharyngitis, increase of infammatory markers and pyrexia were the most frequent AE with incidence rates per 100 patient years (IR) of 8.3, 6.2, and 6.2, respectively. 29 patients (15%) were affected by severe AE (SAE, total number N=90) including 11 patients (6%) with SAE suspected to be drug-related (SADR;total number N=30) with IR from 0.2 to 0.7 (Table 1). Overall, 16 AE comprised upper respiratory tract infections (URI). One death (COVID-19, not related) and one malignancy (skin papilloma, not related) were reported. No vertigo and no hyper-sensitivity reactions were observed. N=10 (IR 2.36) vaccination reactions were reported (no SAE). Conclusion: The interim data from the RELIANCE study, the longest running real-life canakinumab registry, confrm safety of long-term canakinumab treatment across the entire study population. A trend for dose-related increase of SAE/SADR requires continuous close monitoring and awareness in patient groups (children, severe phenotypes, certain genotypes) requiring greater than standard dose treatment regimens.
ABSTRACT
Background: Although there have been expansion of knowledge about the course of COVID-19 in rheumatologic diseases, it still remains unclear the effect of vaccination status and variants on the disease course. Objectives: We aimed to investigate the general clinical characteristics of our patients with infammatory rheumatic disease (IRD) who had COVID-19 disease, their vaccination status and the time periods in which different variants were dominant during the disease. Methods: During the routine follow-up of our patient's with IRD, whether the patients had COVID-19 disease, when they were vaccinated (Pfzer/Biontech or Sinovac in our Country) and main clinical characteristics and their comor-bid diseases were recorded. The last patient was included in the study on January 25, 2022. They were divided into those who received insufficient or no vaccine and those who received a full dose of vaccine. The patients were divided into 3 groups according to the period they had the disease: Those who had the disease between March 2020 and June 2021accepted as '1st period patietns', the period when the Alpha and Beta variants, the initial forms of the disease, were dominant variants in populations;those who had the disease between July 2021 and November 2021, when the Delta variant dominated the World and in our country accepted as '2nd period patients';and those who had the disease in December 2021 and later, when the Omicron variant was dominant throughout the world and in our country, was accepted as ' 3rd period' patients. Results: Total 463 (294 woman) IRD patients enrolled to the study. Distrubution of these patients included Behcet's syndrome:15;familial mediterranean fever: 5 7, rheumatoid arthritis:134, Sjogren's syndrome:24, systemic lupus erythema-tosus:26, Spondyloarthritis:141, necrotising vasculitis:6 and Others:50 cases. Mean age of patients were 46±13,2 (18-83) years. 354 (77%) of our patients got sick in the 1st period, 80 (17%) in the 2nd period and 28 (6%) in the 3rd period. When patients were compared in terms of their clinical complaints in these periods, dyspnea was signifcantly higher in patients in the 1st period (1st. period 36% vs 3rd period 18%;p:0.039), but there was no difference between other complaints including lung involvement and the frequency of hospitalization (p>0.05). 53% of patients had received at least 2 doses of mRNA vaccine. 84% of the patient has had COVID19 before full vaccination with any valid vaccine. When the patients who were full vaccinated and those who were not vaccinated or inadequately vaccinated at the time of illness were compared in terms of clinical features, lung involvement frequency and hospitalization frequency, no difference was found between them. (p>0.05, for all). However, hospitalization and lung involvement were less in those who received a booster dose of any valid vaccine (p: 0.03). While the average hospitalization rate was 17% for all groups, this rate was 50% for necrotizing vasculitis and was signifcantly higher (p:0,005). The probability of lung involvement and hospitalization were found to be sig-nifcantly higher in patients using prednisolone 5mg (or equivalents) or more;(p:0.008 and p:0.000, respectively). Pulmonary involvement was signifcantly higher among patients receiving sulphasalasine (p:0.008). Among the patients on Rituximab, the probability of hospitalization was higher than those who did not (p: 0.01). There was no statistical difference in terms of hospitalization and pulmonary involvement between patients who took other drugs (p>0.05, for all). A total of 5 cases died, including 2 GPA, 1 EGPA, 1 RA and 1 FMF patients. Only 8 patients had a second history of COVID19. Conclusion: The frequency of COVID-19 among IRD cases seems to decrease over time. Full vaccination seems effective for the prevention of COVID-19. It should be recommended that IRD patients have the full dose of vaccines and boosters. The risk of lung involvement and hospitalization increases in patients using certain drugs, such as corticosteroids, sulphasalasine and ituximab. These patients should be followed more closely.
ABSTRACT
Background: Since frst emerged in December 2019, the COVID-19 pandemic has resulted in a death toll surpassing 5.5 million worldwide and had severe consequences on the global economy, environment, public health and social life [1, 2]. Multiple potential vaccines against COVID-19 have been developed swiftly and as shown in several phase 3 clinical trials, they demonstrated considerable efficacy without an unusual safety signal in healthy individuals. Objectives: In this study, we aimed to evaluate vaccine reactivity and disease fare following vaccination with either Sinovac/CoronaVac or Pfzer/BioNTech among BS and FMF patients compared with patients with various diagnosis of RD and healthy controls. Methods: Only those patients and healthy controls who rece,ved at least one single shot of either CoronoVac or BioNTech against COVID-19 were included in the study. We tried to contact all of these patients and controls consecutively by telephone and attempted to make interviews with the eligible ones. Results: We studied the efficacy, side effects and disease fares after COVID-19 vaccination in 256 patients with Behcet's syndrome (BS), 247 with familial Mediterranean fever (FMF), 601 with rheumatic diseases (RD) and 612 healthy controls (HC). Study participants were vaccinated either with CoronaVac (BS:109, FMF: 90, RD: 343, and HC: 334) or BioNTech (BS: 147, FMF:157, RD: 258 and HC: 278). BioNTech ensured a signifcantly better efficacy than CoronaVac against COVID-19 in all patient groups (BS: 1.4% vs 10.1%;FMF: 3.2% vs 12.2%, RD:2.7% vs 6.4%). Those with at least one adverse event (AE) were signifcantly more frequent among those vaccinated with BioNTech than those with Coro-naVac (BS: 86.4% vs 45%;FMF: 83.4% vs 53.3%;RD: 83.3% vs 45.5% and HC: 86.3% vs 52.1%). The majority of AEs were mild to moderate and transient and this was true for either vaccine. There were also AEs that required medical attention in all study groups following CoronaVac (BS:5.5%, FMF:3.3%, RD:2.9% and HC:3.3%) or BioNTech (BS:5.4%, FMF:1.9%, RD:4.7% and HC:4.7%). The main causes for medical assistance were disease fare, and cardiovascular events. Disease fares after vaccination were signifcantly more frequent among BS (41/256;16.0%) and FMF (43/247;17.4%) patients compared to patients with RD (36/601;6.0%). This was true for both CoronaVac (BS: 11.0%, FMF: 24.4% and RD: 5.2%, p<0.001) and BioNTech (BS: 19.7%, FMF: 13.4% and RD: 7.0%, p=0.001)(Table 1). Conclusion: Our study demonstrates that BS and FMF patients vaccinated with either CoronaVac or BioNTech demonstrated almost similar AE profile and frequency compared to RD patients and HC. AEs that required physician consultation or hospitalization occurred in all study groups after either CoronaVac or BioNTech. Caution should be required when monitoring these patients after vaccination. Increased frequency of fares in BS and FMF compared to that seen in RD might refect defects in innate immunity and deserves further investigation.
ABSTRACT
Background: Vaccines are the safest and most effective method to prevent invasive and life-threatening infections. Vaccines against infuenza, pneumococcal disease, herpes zoster, and human papillomavirus are the main recommended vaccines for adults. In addition, rheumatology patients are advised to receive adult vaccinations according to the vaccines available in their country and local guidelines. In Turkey, both infuenza and pneumococcal disease vaccines are commercially available. In addition, these vaccines are strongly recommended for rheumatology patients in local guidelines. Although familial Mediterranean fever (FMF) is one of the most common rheu-matological diseases in Turkey, it is often neglected in vaccination recommendations. Objectives: In this study, we surveyed the vaccination practice against infuenza or pneumococcal diseases of adult FMF patients in our cohort. In addition, we evaluated the factors related to favorable vaccination practice. Methods: We included 360 FMF patients over 18 years of age. All patients ful-flled the Tel-Hashomer criteria for FMF. We asked them if they had ever been vaccinated against pneumococcal or infuenza, and how often they received them. In addition, we dichotomised patients in terms of vaccinated against at least one of infuenza or pneumococcal diseases. We then compared the groups for demographic (age gender and comorbidities) and disease related characteristics (disease duration, disease activity calculated by ISSF and colchicine dose). We used qi-square test to compare categorial variables and Mann-Whitney U test to compare continuous variables. P<0.05 was accepted as signifcant. Results: Of 360 FMF patients, 238 (66.1%) were female. The mean age of the patients was 34.5±10.7 years. Disease duration of the patients was 9.38±0.7 years. In addition, the mean ISSF score of the patients was 1.83±1.5. The mean dose of colchicine received by the patient was 1.23 ± 0.47 mg. Only 54 (15.0%) of the patients had at least one comorbidity. In our cohort, 22 (6.1%) patients were vaccinated against infuenza or pneumococcal disease. Only 18 (5.0%) of the patients have been vaccinated against infuenza at least once so far. Half of these patients (9/18) were vaccinated against infuenza each year. In addition, 8/360 (2.2%) patients were fully vaccinated against pneumococcal diseases. Here, six of them received the pneumococcal vaccine after the start of the COVID-19 outbreak. There was no statistically signifcant difference between the groups in terms of demographic and disease related characteristics. Conclusion: We found that vaccination practice of FMF patients in our cohort was unsatisfactory. Few patients follow adult vaccination recommendations. In addition, clinicians should be concerned about the importance of vaccination and guide their patients to get the adult vaccines available in their country.
ABSTRACT
Background: Several anti-inflammatory drugs which were targeted different mechanisms and investigated for both prevention and treatment for COVID-19. Objectives: The current study aimed to investigate whether patients regularly using colchicine or hydroxychloroquine (HCQ) have an advantage of protection from COVID-19 or developing less severe disease. Methods: Patients who were taking colchicine or HCQ regularly for a rheumatic disease including Familial Mediterranean Fever, Behçet's syndrome, Systemic Lupus Erythematosus, Rheumatoid Arthritis and Sjogren's syndrome as well as their healthy household contacts as the control group were included into the study. The clinical data regarding COVID-19 were collected using a standard form, and serum samples were analyzed for anti-SARS-COV-2 nucleocapsid IgG. Patients treated with any biologic or immunosuppressive treatments were not included into the study. Results: A total of 635 regular colchicine users with their 643 household contacts and 317 regular HCQ users with their 333 household contacts were analyzed. Anti-SARS-Cov2 IgG was positive in 43 (6.8%) regular colchicine users and 35 (5.4%) household contacts (OR=1.3;95% CI:0.8-2;p=0.3) (Table 1). COVID-19 related symptoms were described by 29 (67.4%) of the patients and 17 (48.6%) household contacts (OR=2.2;95% CI:0.9-5.5;p=0.09), and hospital admission was observed in five (11.6%) and one (2.9%) of these subjects (OR=4.5;95% CI:0.5-40.2;p=0.1), respectively (Figure 1). Seropositive subjects were observed in 22 (6.9%) regular HCQ users and 24 (7.2%) household contacts (OR=1.1;CI:0.6-1.9;p=0.8) (Table 1). COVID-19-related symptoms occurred in 16 (72.7%) of the 22 patients and 12 (50%) of 24 household contacts (OR=2.7;95% CI:0.8-9.1;p=0.1). Three patients (13.6%) were admitted to hospital, while one household contact (4.2%) was hospitalized (OR=3.6;95% CI:0.3-37.8;p=0.2) (Figure 1). Disease-specific analyses disclosed that there was no significant difference in terms of COVID-19 frequency and severity between a particular disease subset and household contacts (Table 1). Univariate logistic regression analysis showed no effect of age and gender on the SARS-CoV-2 seroprevalence rate among regular colchicine or HCQ users and household contacts (p=0.2 and p=0.7, respectively for colchi-cine users versus contacts, p=0.7 and p=0.3, respectively for HCQ users versus contacts). Conclusion: Being on a regular treatment of colchicine or HCQ was not resulted in the prevention of COVID-19 or amelioration of its manifestations.
ABSTRACT
Background: The Familial Mediterranean Fever (FMF) Program at the University of California, Los Angeles is the only dedicated FMF diagnostic and treatment clinic in the United States, receiving global referrals. FMF is a rare autosomal recessive genetic disorder characterized by recurrent febrile polyserositis. Serious complications from untreated FMF are easily preventable with early diagnosis and treatment. The COVID-19 pandemic constrained educational and interdisciplinary in-person visits and prompted exploration of innovative telehealth solutions. Objective: This study aimed to explore the feasibility and clinical process outcomes associated with a multidisciplinary telemedicine model to deliver consultative and continuing care to FMF patients. Our secondary objectives included assessing provider, patient, and trainee satisfaction. Study design: We implemented a multidisciplinary telemedicine clinic with gastroenterologists, a medical geneticist, and trainees. All patients with suspected FMF referred to our clinic during the pandemic were included. Patients were sent a HIPAAcompliant Zoom link for their clinic appointment. We mirrored our in-person academic teaching model, first with the trainee interviewing the patient virtually and then later presenting to the team, along with family members, who joined for the case presentation and consensus on diagnostic impressions and management recommendations. Patient characteristics and clinical process outcomes were assessed during the visit and from the electronic medical record (EMR). Post-visit surveys of patients, physicians and trainees were then taken to assess effectiveness and desirability of the approach. Results: 86 patients were enrolled in the multidisciplinary telemedicine model from March 2020 to March 2021. In comparison, 87 pre-pandemic visits occurred between March 2019 to March 2020. No significant difference was found in patient volume seen with telehealth and surveys showed increased provider, patient, and trainee satisfaction. The telehealth model enabled health care delivery to a variety of locations that lacked expert experience with this rare disease. Patients could also avoid costly travel to UCLA and risk exposure to COVID-19. Surveys showed increased satisfaction with Zoom than the integrated video functionality in our in-house EMR by allowing for inclusion of multiple specialists and interested family members. Sample collection for indicated laboratory tests could still be ordered at a local phlebotomy center. Conclusion: A multidisciplinary telemedicine model for outpatient management of FMF patients resulted in rates of ambulatory management similar to those seen pre-pandemic and resulted in improved patient and physician satisfaction. FMF is especially amendable to this approach, as patients are asymptomatic between attacks, making hands-on physical exam less pertinent.
ABSTRACT
OBJECTIVE: Aim of the study is to evaluate the impact of Familial Mediterranean Fever (FMF) features on clinical course and outcomes of Coronavirus disease-19 (COVID-19) and clinical course of FMF after COVID-19. METHODS: Consecutive FMF patients with COVID-19 were enrolled from three referral hospitals. Clinical features of FMF and detailed COVID-19 information were obtained from patient interviews and medical records. RESULTS: Seventy-three FMF patients were included in the study. Sixty-nine patients had clinical symptoms of COVID-19, and 90.4% of patients received COVID-19 specific treatment. We found 24.7% hospitalization, %12.3 respiratory support, 4.1% ICU admission, 6.8% complication, and 1.4 % mortality rate in patients. Male gender and older age were significantly frequent in inpatients compared to outpatients (male gender 77.8 % vs 25.8%, p<0.001; median age 39.5 vs 32 years, p:0.043). FMF features were similar in both groups. The risk factors of hospitalization for respiratory support were male gender (OR: 7.167 (95% CI:1.368-37.535)), greater age (OR:1.067 (95% CI:1.016-1.121)) and non-adherence to colchicine treatment before the infection (OR:7.5 (95% CI: 1.348-41.722)). One-third of patients (33.3%) had reported attacks after COVID-19. The patterns of triggered attacks were fever, peritonitis, pleuritis, transient arthritis, chronic knee mono-arthritis, and protracted febrile myalgia. CONCLUSION: FMF characteristics were not associated with worse outcomes of COVID-19. Colchicine non-adherence was the risk factor of hospitalization for oxygen support. The rate of FMF attacks after COVID-19 is prominently increased with some of them be protracted and destructive.
ABSTRACT
Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disorder characterized by recurrent attacks of fever and serosal inflammation. The clinical features consist of especially abdominal pain, chest pain and arthralgias, plus erysipelas-like manifestations. According to the available literature, most patients with FMF experience their first attack in early childhood, before the ages of 10 and 20 years in 65 and 90% of cases, respectively. Rarely, the initial attack can occur in individuals older than 50 years of age. We report our experience with FMF during the last 14 yrs [1], following case #1 aged 36 yrs. [2]. In the regions of Apulia and Basilicata, we could identify several family clusters due to historical and geographical roots. In the initial series of 60 cases, the five most frequent MEFV variants were E148Q/R761H (41.9%, compound heterozygosity), K695R (10.2%, heterozygosity), E148Q (8.2%, heterozygosity), E148Q/R761H/A744S (6.1% compound heterozygosity), and P369S (6.1%, heterozygosity). Notably, the mean disease onset was 22 yrs and the diagnostic delay was 15 yrs. The severity of symptoms was generally mild/intermediate but about 30% of this initial series had undergone unnecessary abdominal surgery. Females were significantly older than males (median 40 vs. 30 yrs., respectively, P = 0.03). Symptoms including fever were largely responsive to the average dose of colchicine 1 mg/day ad libitum. Only one case required canakinumab for resistance/intolerance to colchicine. We did not observe severe cases of secondary amyloidosis and kidney damage. Later, we extended our observations and concluded that the combination of available expert information with sensitive predictor tools could result in a more accurate interpretation of clinical consequences of MEFV gene variants, and a better genetic counselling and patient management, with respect to symptom severity as well [3, 4]. We recently reported the rare case of a very late onset of FMF symptoms in a patient aged 86 [5]. Further studies in FMF have focused the attention on environmental factors including intestinal microbiota [6], COVID-19 pandemic [7], blood-based test for diagnosis and functional subtyping of FMF by the ex vivo colchicine assay [8], and histopathological characteristics of synovitis in FMF [9]. Following these seminal observations, we conclude that the Apulia region represents a new endemic area for FMF, a puzzling inherited autoinflammatory disorder. Clinical presentation of FMF can be misleading and requires a complete and early workup to recognize the disease and avoid unjustified surgery. Colchicine remains the gold standard therapy to prevent FMF attacks and fatal long-term complications [10, 11].