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Multiple Sclerosis and Related Disorders May 2021Familial Mediterranean fever (FMF) is the most frequent monogenic autoinflammatory disorder; and leads to the uncontrolled production of interleukin (IL)-1β. Multiple...
INTRODUCTION
Familial Mediterranean fever (FMF) is the most frequent monogenic autoinflammatory disorder; and leads to the uncontrolled production of interleukin (IL)-1β. Multiple sclerosis (MS) is an inflammatory disease of the central nervous system; and its development seems to be partly correlated with IL-1β levels. It is hypothesized that FMF could be associated with MS. We aim to describe the features of patients displaying both diseases and to investigate the MEFV mutation rate in MS patients.
METHODS
Patients with definite MS were retrieved from the cohort of FMF patients in the Reference Center for Rare Auto-inflammatory Diseases and Amyloidosis (CEREMAIA). We also performed a systematic literature review of articles from PubMed that were published from 1990 to 2020.
RESULTS
Twenty-four patients were included in the case series: five patients (1.3%) from our cohort of 364 and 19 patients from the literature. The sex ratio was 2:1. The mean age at diagnosis of FMF was 19 years old; and that for MS was 29 years old. Seven studies investigating the MEFV mutation rate in MS patients were included. Three studies found a higher mutation rate in MS patients than in the control group.
CONCLUSION
FMF and MS features were comparable to those of patients with unrelated diseases; and MEFV mutation carriage was not positively correlated with MS. However; MS prevalence in FMF patients was higher than was expected in a healthy population. To a lesser extent; FMF prevalence in MS patients was higher than expected in a healthy population and the difference might not be significant. These data suggest that FMF could be associated with MS; and further studies are needed to investigate a potential causal association.
Topics: Adult; Cohort Studies; Familial Mediterranean Fever; Humans; Multiple Sclerosis; Mutation; Pyrin; Young Adult
PubMed: 33609923
DOI: 10.1016/j.msard.2021.102834 -
The Journal of Allergy and Clinical... Feb 2021Primary immune deficiencies (PIDs) are a heterogeneous group of disorders resulting from defects in immune system. They lead to increased susceptibility to infections...
BACKGROUND
Primary immune deficiencies (PIDs) are a heterogeneous group of disorders resulting from defects in immune system. They lead to increased susceptibility to infections and immune dysregulation. The resulting chronic inflammation can induce long-term complications, including AA amyloidosis (AAA).
OBJECTIVES
To present the French cases of PID-related AAA and perform a systematic literature review to determine its main features and predisposing factors.
METHODS
A systematic literature review was performed by searching MEDLINE up until 2019. New French cases were identified with the help of the Reference Center for Auto-Inflammatory Diseases and AA Amyloidosis and the Reference Center for Hereditary Immune Deficiencies.
RESULTS
Forty patients were identified including 2 new French cases. PIDs were varied: immunoglobulin deficits (n = 30), chronic granulomatous disease (n = 3), hyper-IgM syndrome (n = 3), hereditary complete C4 deficiency (n = 1), leucocyte adhesion deficiency type 1 (n = 1), hyper-IgE syndrome (n = 1), and Chediak-Higashi syndrome (n = 1). The mean age at PID diagnosis was 22.2 ± 16.02 years. Renal involvement was the most common manifestation of AAA (80%). Infections were extremely heterogeneous; bacterial infection with pulmonary involvement was the most frequent. Bronchiectasis was particularly common (52.5%). The delay between the first symptoms of PID and AAA diagnosis was 16.18 ± 7 years. Thirteen concomitant diagnoses were made. Twenty patients died during follow-up.
CONCLUSION
AAA is a rare life-threatening complication of PID, especially in cases of long diagnostic and therapeutic delays. Bronchiectasis should be considered as a warning sign of chronic inflammation and increased risk of AAA.
Topics: Amyloidosis; Bronchiectasis; Humans; Immunoglobulins; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases
PubMed: 33007500
DOI: 10.1016/j.jaip.2020.09.023 -
Rheumatology (Oxford, England) Nov 2022Cryopyrin-associated periodic syndrome (CAPS) is a rare but treatable inherited autoinflammatory condition including familial cold autoinflammatory syndrome (FCAS),...
OBJECTIVE
Cryopyrin-associated periodic syndrome (CAPS) is a rare but treatable inherited autoinflammatory condition including familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and chronic infantile neurologic cutaneous articular syndrome (CINCA). Our objective was to describe the main features of CAPS AA amyloidosis (AA-CAPS) associated and the efficacy of IL-1 inhibitors in this indication.
METHODS
Retrospective study in France associated with a systematic literature review.
RESULTS
Eighty-six patients were identified: 23 new French cases and 63 from the literature, with a median age at amyloidosis diagnosis of 39 years old. CAPS subtypes were MWS (n = 62), FCAS (n = 9), frontier forms between MWS and FCAS (n = 12) and between CINCA and MWS (n = 3). NLRP3 had been sequenced in 60 patients (70%) and the most frequent mutation was R260W (60%). Three AA-CAPS patients displayed somatic NLRP3 mutations. Death occurred in 35 patients (41%), none of whom having ever received IL-1 inhibitors. Twenty-eight patients (33%) received IL-1 inhibitors, with a >50% decrease in proteinuria in 89% of cases.
CONCLUSION
AA amyloidosis can occur in nearly all CAPS subtypes. IL-1 inhibitors are effective, underlining the necessity of an early diagnosis of CAPS in order to start this treatment as soon as possible among AA-CAPS patients.
Topics: Humans; Adult; Cryopyrin-Associated Periodic Syndromes; NLR Family, Pyrin Domain-Containing 3 Protein; Retrospective Studies; Mutation; Amyloidosis; Interleukin-1
PubMed: 35262642
DOI: 10.1093/rheumatology/keac145 -
Seminars in Arthritis and Rheumatism Dec 2021Deficiency of adenosine deaminase 2 (DADA2) is a rare autoinflammatory disease usually presenting before the age of 10 years. Non-specific clinical features or...
BACKGROUND
Deficiency of adenosine deaminase 2 (DADA2) is a rare autoinflammatory disease usually presenting before the age of 10 years. Non-specific clinical features or late-onset presentation may delay its diagnosis until adulthood.
OBJECTIVE
To determine whether DADA2 diagnosed in adulthood is associated with specific characteristics compared to DADA2 diagnosed in childhood.
METHODS
We pooled a cohort of 12 adult DADA2 patients followed in France with cases identified through a systematic literature review. For each patient, we determined the type of clinical presentation and assessed six key organ involvements.
RESULTS
A total of 306 cases were included. Among the 283 patients with available data regarding age at diagnosis, 140 were diagnosed during adulthood and 143 during childhood. The vascular presentation of DADA2 was more frequent in the adult diagnosis group (77.9% vs. 62.9%, p < 0.01), whereas the hematological presentation (bone marrow failure) prevailed in the pediatric diagnosis group (10.0% vs. 20.3% p = 0.02). In patients with vasculopathy, severe skin manifestations developed in 35% and 10% of the adult and pediatric diagnosis groups, respectively. Conversely, fewer strokes occurred in the adult group presenting with systemic vasculopathy (54% vs. 81%). Symptomatic humoral immune deficiency (HID) was rarely a clinical presentation in itself (5% and 2.8%) but accompanied other phenotypes of DADA2, especially the hematological phenotype in the adult group (33% vs. 4%).
CONCLUSION
DADA2 diagnosed in adulthood presents more often with a vascular phenotype and less often with bone marrow failure than DADA2 diagnosed in childhood. Adults diagnosed with DADA2 vasculopathy display more severe skin involvement but fewer strokes.
Topics: Adenosine Deaminase; Adult; Child; Humans; Immunologic Deficiency Syndromes; Intercellular Signaling Peptides and Proteins; Mutation; Phenotype
PubMed: 34571400
DOI: 10.1016/j.semarthrit.2021.09.001 -
Leukemia & Lymphoma 2023
Topics: Humans; Amyloidosis; Lymphoma; Serum Amyloid A Protein
PubMed: 37493601
DOI: 10.1080/10428194.2023.2239971