scholarly journals Familial Mediterranean fever in the pediatric population

2022 ◽  
Vol 50 (1) ◽  
pp. 25-30
Author(s):  
Pilar LLobet Agulló ◽  
Laura Sanromà-Nogués ◽  
Isabel Maria Salguero-Pérez ◽  
Juan I Aróstegui ◽  
Sonia Corral-Arboledas ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Pediatric Population ◽  
Clinical Manifestations ◽  
Secondary Amyloidosis ◽  
Amyloid A ◽  
Heterozygous Variant ◽  
Mediterranean Origin ◽  
Caucasian Origin ◽  
Mediterranean Fever ◽  
Disorder Treatment

Familial Mediterranean fever (FMF) is the most frequent autoinflammatory disorder characterized by short, repeated, and self-limiting crises of fever and serositis. The disease was described as autosomal recessive hereditary transmission secondary to variants of the MEFV (MEditerranean FeVer) gene, even though a variable proportion of patients only present a heterozygous variant. FMF is very common in certain ethnic groups (Turkish, Armenian, Arab, and Jewish), even though it has been described throughout the Mediterranean and elsewhere in the world. The clinical manifestations are variable, with secondary amyloidosis being the most serious complication of the disorder. Treatment and prophylaxis are mainly based on the administration of colchicine, which prevents the crises and avoids complications in most cases. This study reviews the course of seven pediatric patients diagnosed with FMF during the period 2010–2018 at a district hospital. Most of the patients were of Caucasian origin, with onset at an early age in the form of fever as the main symptom, and some patients moreover presented less frequent manifestations (pericardial effusion, sensorineural hearing loss). Two cases presented plasmatic amyloid A protein elevation that subsided with the treatment. All the patients initially received colchicine, and one of them required prescription of anakinra, which was replaced by canakinumab due to a serious adverse reaction. There were no cases of consanguinity, and all the patients were of Mediterranean origin. The subjects showed a favorable course over the years, which was attributed to the early diagnosis and treatment provided.

Clinical significance of E148Q heterozygous variant in paediatric Familial Mediterranean Fever

Rheumatology ◽  
2021 ◽  
Author(s):  
Irit Tirosh ◽  
Yonatan Yacobi ◽  
Asaf Vivante ◽  
Ortal Barel ◽  
Yishay Ben-Moshe ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
Familial Mediterranean Fever ◽  
Clinical Significance ◽  
Mefv Gene ◽  
Clinical Manifestations ◽  
Leg Pain ◽  
Compound Heterozygous ◽  
Phenotype Correlation ◽  
Heterozygous Variant ◽  
Mediterranean Fever

Abstract Objectives Familial Mediterranean Fever (FMF) results from mutations in the Mediterranean fever (MEFV) gene. The p.E148Q is one of the most frequent protein alternations in the MEFV gene, yet the exact E148Q genotype–phenotype correlation remains unclear. The aim of this study was to examine clinical significance of heterozygous E148Q variant in a paediatric FMF cohort. Methods We compared the clinical manifestations and disease severity score of four genetic sub-groups: (1) patients harboring a single heterozygous p.E148Q variant (n = 6); (2) patients harboring a single p.M694V heterozygous variant (n = 88); (3) patients harboring compound heterozygous p.M694V and p.E148Q variants (n = 36) and (4) homozygotes for p.M694V variant (n = 160). Results Of 646 FMF children from our centre, only 1% (6 patients) of our genetically characterized FMF cohort had a single E148Q variant, most presenting with recurrent fevers and abdominal pain. None of the participants were found to harbor homozygous E148Q. Overall, M694V/E148Q compound heterozygosity did not exhibit a more severe phenotype compared to patients with a single M694V variant. The former group were less likely to have abdominal pain and exertional leg pain (p < 0.004 and p < 0.001 respectively) and more likely to have chest pain (P < 0.01). Both sub-groups showed milder clinical phenotype compared to patients with M694V homozygosity. Conclusion Our findings demonstrate that a single heterozygous E148Q variant is unlikely to cause FMF in children and that E148Q/M694V is clinically indistinguishable from a single M694V variant. Thus, E148Q heterozygosity does not result in clinically meaningful phenotype in children.

scholarly journals Wheat Consumption Leads to Immune Activation and Symptom Worsening in Patients with Familial Mediterranean Fever: A Pilot Randomized Trial

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1127 ◽  
Author(s):  
Antonio Carroccio ◽  
Pasquale Mansueto ◽  
Maurizio Soresi ◽  
Francesca Fayer ◽  
Diana Di Liberto ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Clinical Symptoms ◽  
Inflammatory Diseases ◽  
Activity Index ◽  
Clinical Manifestations ◽  
University Hospital ◽  
Double Blind ◽  
Amyloid A ◽  
Tnf Α ◽  
Mediterranean Fever

We have identified a clinical association between self-reported non-celiac wheat sensitivity (NCWS) and Familial Mediterranean Fever (FMF). Objectives: A) To determine whether a 2-week double-blind placebo-controlled (DBPC) cross-over wheat vs. rice challenge exacerbates the clinical manifestations of FMF; B) to evaluate innate immune responses in NCWS/FMF patients challenged with wheat vs. rice. The study was conducted at the Department of Internal Medicine of the University Hospital of Palermo and the Hospital of Sciacca, Italy. Six female volunteers with FMF/NCWS (mean age 36 ± 6 years) were enrolled, 12 age-matched non-FMF, NCWS females, and 8 sex- and age-matched healthy subjects served as controls. We evaluated: 1. clinical symptoms by the FMF-specific AIDAI (Auto-Inflammatory Diseases Activity Index) score; 2. serum soluble CD14 (sCD14), C-reactive protein (CRP), and serum amyloid A (SSA); 3. circulating CD14+ monocytes expressing interleukin (IL)-1β and tumor necrosis factor (TNF)-α. The AIDAI score significantly increased in FMF patients during DBPC with wheat, but not with rice (19 ± 6.3 vs. 7 ± 1.6; p = 0.028). sCD14 values did not differ in FMF patients before and after the challenge, but were higher in FMF patients than in healthy controls (median values 11357 vs. 8710 pg/ml; p = 0.002). The percentage of circulating CD14+/IL-1β+ and of CD14+/TNF-α+ monocytes increased significantly after DBPC with wheat vs. baseline or rice challenge. Self-reported NCWS can hide an FMF diagnosis. Wheat ingestion exacerbated clinical and immunological features of FMF. Future studies performed on consecutive FMF patients recruited in centers for auto-inflammatory diseases will determine the real frequency and relevance of this association.

scholarly journals Amyloidosis and Glomerular Diseases in Familial Mediterranean Fever

Medicina ◽  
2021 ◽  
Vol 57 (10) ◽  
pp. 1049
Author(s):  
Rossella Siligato ◽  
Guido Gembillo ◽  
Vincenzo Calabrese ◽  
Giovanni Conti ◽  
Domenico Santoro
Keyword(s):  
Nephrotic Syndrome ◽  
Familial Mediterranean Fever ◽  
Periodic Fever ◽  
Rapid Progression ◽  
Secondary Amyloidosis ◽  
Aa Amyloidosis ◽  
Glomerular Diseases ◽  
Amyloid A ◽  
Serum Amyloid A Protein ◽  
Mediterranean Fever

Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease with autosomal recessive transmission, characterized by periodic fever attacks with self-limited serositis. Secondary amyloidosis due to amyloid A renal deposition represents the most fearsome complication in up to 8.6% of patients. Amyloidosis A typically reveals a nephrotic syndrome with a rapid progression to end-stage kidney disease still. It may also involve the cardiovascular system, the gastrointestinal tract and the central nervous system. Other glomerulonephritis may equally affect FMF patients, including vasculitis such as IgA vasculitis and polyarteritis nodosa. A differential diagnosis among different primary and secondary causes of nephrotic syndrome is mandatory to determine the right therapeutic choice for the patients. Early detection of microalbuminuria is the first signal of kidney impairment in FMF, but new markers such as Neutrophil Gelatinase-Associated Lipocalin (NGAL) may radically change renal outcomes. Serum amyloid A protein (SAA) is currently considered a reliable indicator of subclinical inflammation and compliance to therapy. According to new evidence, SAA may also have an active pathogenic role in the regulation of NALP3 inflammasome activity as well as being a predictor of the clinical course of AA amyloidosis. Beyond colchicine, new monoclonal antibodies such as IL-1 inhibitors anakinra and canakinumab, and anti-IL-6 tocilizumab may represent a key in optimizing FMF treatment and prevention or control of AA amyloidosis.

scholarly journals Familial Mediterranean Fever: an unusual cause of liver disease

2019 ◽  
Vol 45 (1) ◽  
Author(s):  
Maria Cristina Maggio ◽  
Maria Castiglia ◽  
Giovanni Corsello
Keyword(s):  
Abdominal Pain ◽  
Liver Disease ◽  
Familial Mediterranean Fever ◽  
Serum Amyloid A ◽  
Mefv Gene ◽  
Serum Amyloid ◽  
Aphthous Stomatitis ◽  
Homozygous Mutation ◽  
Amyloid A ◽  
Mediterranean Fever

Abstract Background Familial Mediterranean Fever is an autoinflammatory disease typically expressed with recurrent attacks of fever, serositis, aphthous stomatitis, rash. Only a few reports describe the association with hepatic involvement. Case presentation We describe the clinical case of a child affected, since the age of 1 year, by recurrent fever, aphthous stomatitis, rash, arthralgia, associated with abdominal pain, vomiting, lymphadenopathy. The diagnosis of Familial Mediterranean Fever was confirmed by the genetic study of MEFV gene; the homozygous mutation M694 V in exon was documented. A partial control of attacks was obtained with colchicine. The child continued to manifest only recurrent episodes of abdominal pain without fever, however serum amyloid A persisted high, in association with enhanced levels of CRP, AST and ALT (1.5 x n.v.). The dosage of colchicine was increased step by step and the patient achieved a better control of symptoms and biochemical parameters. However, the patient frequently needed an increase in the dose of colchicine, suggesting the possible usefulness of anti-interleukin-1 beta treatment. Conclusions The unusual presentation of Familial Mediterranean Fever with liver disease suggests the role of inflammasome in hepatic inflammation. Colchicine controls systemic inflammation in most of the patients; however, subclinical inflammation can persist in some of them and can manifest with increased levels of CRP, ESR, serum amyloid A also in attack-free intervals.

scholarly journals Serum Amyloid A Type 1 Gene Polymorphism in Egyptian Children with Familial Mediterranean Fever

Pathobiology ◽  
2016 ◽  
Vol 83 (6) ◽  
pp. 295-300 ◽  
Author(s):  
Manal Wilson ◽  
Amany A. Abou-Elalla ◽  
Mervat Talaat Zakaria ◽  
Huda Marzouk ◽  
Hala Lotfy Fayed ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Gene Polymorphism ◽  
Serum Amyloid A ◽  
Serum Amyloid ◽  
Amyloid A ◽  
Egyptian Children ◽  
Mediterranean Fever

scholarly journals Evaluation of E148Q and Concomitant AA Amyloidosis in Patients with Familial Mediterranean Fever

2021 ◽  
Vol 10 (16) ◽  
pp. 3511
Author(s):  
Zehra Serap Arici ◽  
Micol Romano ◽  
David Piskin ◽  
Ferhat Guzel ◽  
Sezgin Sahin ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Clinical Phenotype ◽  
Clinical Manifestations ◽  
Histopathological Diagnosis ◽  
Close Monitoring ◽  
Aa Amyloidosis ◽  
Homozygous Genotype ◽  
Age Of Diagnosis ◽  
Mediterranean Fever

The aim of the study was to compare the clinical phenotype of patients with familial Mediterranean fever (FMF)-related AA amyloidosis, according to the age of FMF diagnosis and E148Q genotype. Patients with biopsy-confirmed FMF-related AA amyloidosis were included in the study. Tel-Hashomer criteria were applied in the diagnosis of FMF. All patients had detailed baseline assessment of clinical features, renal functions, genetic testing, histopathological diagnosis of amyloidosis, and treatment received. Multiple comparisons were performed according to the age of diagnosis, disease phenotype, mutation, and mortality. Our study included 169 patients with a diagnosis of AA amyloidosis. There were 101 patients diagnosed with FMF < 18 years of age and 68 patients diagnosed who were ≥18 years of age. The three most common clinical manifestations were fever (84.6%), abdominal pain (71.6%), and arthritis (66.9%). The most common allele among FMF patients was M694V (60.6%), followed by E148Q (21.4%), and M680I (10.3%). The most frequent genotypes were M694V/M694V (45.0%), M694V/E148Q (14.8%), and E148Q/E148Q (11.2%) among 169 patients in our cohort. During the follow-up period, 15 patients (10 male, 5 female) died, of whom 14 had M694V homozygous genotype and one was homozygous for E148Q. Clinicians should be aware of patients with homozygous E148Q genotype for close monitoring and further evaluation. The possible relationship between E148Q and AA amyloidosis needs to be confirmed in other ethnicities.

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