Familial Mediterranean fever: overview of pathogenesis, clinical features and management

Migita, Kiyoshi; Asano, Tomohiko; Sato, Shuzo; Koga, Tomohiro; Fujita, Yuya; Kawakami, Atsushi

doi:10.1080/13497413.2018.1481579

Cited by 38 publications

(43 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Activation of NLRP3 inflammasome and uncontrolled production of IL-1β (Migita et al, 2018) (RA) with prominent pro-thrombotic phenotypic features is a strong link of interaction of inflammation and coagulation pathways. Table 1 outlines several such inflammatory disorders with thrombotic features that have demonstrated the involvement of inflammasomes in their pathophysiology.…”

Section: Familial Mediterranean Fevermentioning

confidence: 99%

Understanding Inflammatory Responses in the Manifestation of Prothrombotic Phenotypes

Chanchal

Mishra

Singh

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Inflammasome complex is a multimeric protein comprising of upstream sensor protein of nucleotide-binding oligomerization domain (NOD)-like receptor family. It has an adaptor protein apoptosis-associated speck-like protein and downstream effector cysteine protease procaspase-1. Activation of inflammasome complex is body's innate response to pathogen attack but its abnormal activation results in many inflammatory and cardiovascular disorders including thrombosis. It has displayed a prominent role in the clot formation advocating an interplay between inflammation and coagulation cascades. Therefore, elucidation of inflammasome and its molecular mechanisms in the manifestation of prothrombotic phenotypes becomes pertinent. Thrombosis is the formation and propagation of blood clot in the arterial or venous system due to several interactions of vascular and immune factors. It is a prevalent pathology underlying disorders like venous thromboembolism, stroke and acute coronary syndrome; thus, making thrombosis, a major contributor to the global disease burden. Recently studies have established a strong connection of inflammatory processes with this blood coagulation disorder. The hemostatic balance in thrombosis gets altered by the inflammatory mechanisms resulting in endothelial and platelet activation that subsequently increases secretion of several prothrombotic and antifibrinolytic factors. The upregulation of these factors is the critical event in the pathogenesis of thrombosis. Among various inflammasome, nucleotide-binding domain, leucine-richcontaining family, pyrin domain containing 3 (NLRP3) is one of the best-studied sterile inflammasome strengthening a link between inflammation and coagulation in thrombosis. NLRP3 activation results in the catalytic conversion of procaspase-1 to active caspase-1, which facilitate the maturation of interleukin-1β (IL-1β) and interleukin-18. These cytokines are responsible for immune cells activation critical for immune responses. These responses further results in endothelial and platelet activation and aggregation. However, the exact molecular mechanism related to the pathogenesis of thrombosis is still elusive. There have been several reports that demonstrate Tissue factor (TF)-mediated signaling in the production of pro-inflammatory cytokines enhancing inflammation by activating protease-activated receptors on various cells,

show abstract

Section: Familial Mediterranean Fevermentioning

confidence: 99%

Understanding Inflammatory Responses in the Manifestation of Prothrombotic Phenotypes

Chanchal

Mishra

Singh

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Molecular advances have linked familial Mediterranean fever (FMF) gene mutations to plague immunity. 7,[31][32][33][34] FMF is a rare, recessive disease mostly seen in people of Arab, Armenian, Jewish, or Turkish ancestry. Symptoms of FMF include abdominal pain, arthritis, and fevers lasting 12-72 hours, although those affected are usually completely normal between spells.…”

Section: Familial Mediterranean Fever and Y Pestismentioning

confidence: 99%

“…Symptoms of FMF include abdominal pain, arthritis, and fevers lasting 12-72 hours, although those affected are usually completely normal between spells. 32,33 Pyrin is its gene protein product, from the Greek word for "fever." As an extremely important and versatile immune regulator, pyrin fights infection and cancer.…”

Section: Familial Mediterranean Fever and Y Pestismentioning

confidence: 99%

“…Pyrin activates caspase-1, an enzyme that facilitates programmed cell death, and participates in IL-1b processing for fever production. 8,[31][32][33] Y. pestis reduces production of IL-1b and IL-18, blocking the immune system from mounting a robust immune response. 8,[31][32][33] The bacteria run unchecked as natural defenses are shut off.…”

Section: Familial Mediterranean Fever and Y Pestismentioning

confidence: 99%

See 1 more Smart Citation

History of the Plague: An Ancient Pandemic for the Age of COVID-19

Glatter

Finkelman

2021

The American Journal of Medicine

125

View full text Add to dashboard Cite

During the fourteenth century, the bubonic plague or Black Death killed more than one third of Europe or 25 million people. Those afflicted died quickly and horribly from an unseen menace, spiking high fevers with suppurative buboes (swellings). Its causative agent is Yersinia pestis, creating recurrent plague cycles from the Bronze Age into modern-day California and Mongolia. Plague remains endemic in Madagascar, Congo, and Peru. This history of medicine review highlights plague events across the centuries. Transmission is by fleas carried on rats, although new theories include via human body lice and infected grain. We discuss symptomatology and treatment options. Pneumonic plague can be weaponized for bioterrorism, highlighting the importance of understanding its clinical syndromes. Carriers of recessive familial Mediterranean fever (FMF) mutations have natural immunity against Y. pestis. During the Black Death, Jews were blamed for the bubonic plague, perhaps because Jews carried FMF mutations and died at lower plague rates than Christians. Blaming minorities for epidemics echoes across history into our current coronavirus pandemic and provides insightful lessons for managing and improving its outcomes.

show abstract

“…The first step in treatment of patients with recurrent attacks, even without fever, is colchicine [21].…”

Section: Treatmentmentioning

confidence: 99%

FMF is not always “fever”: from clinical presentation to “treat to target”

Maggio

Corsello

2020

Ital J Pediatr

View full text Add to dashboard Cite

Familial Mediterranean Fever, a monogenic autoinflammatory disease secondary to MEFV gene mutations in the chromosome 16p13, is characterized by recurrent self-limiting attacks of fever, arthritis, aphthous changes in lips and/or oral mucosa, erythema, serositis. It is caused by dysregulation of the inflammasome, a complex intracellular multiprotein structure, commanding the overproduction of interleukin 1. Familial Mediterranean Fever can be associated with other multifactorial autoinflammatory diseases, as vasculitis and Behçet disease. Symptoms frequently start before 20 years of age and are characterized by a more severe phenotype in patients who begin earlier. Attacks consist of fever, serositis, arthritis and high levels of inflammatory reactants: C-reactive protein, erythrocyte sedimentation rate, serum amyloid A associated with leucocytosis and neutrophilia. The symptom-free intervals are of different length. The attacks of Familial Mediterranean Fever can have a trigger, as infections, stress, menses, exposure to cold, fatrich food, drugs. The diagnosis needs a clinical definition of the disease and a genetic confirmation. An accurate differential diagnosis is mandatory to exclude infective agents, autoimmune diseases, etc. In many patients there is no genetic confirmation of the disease; furthermore, some subjects with the relieve of MEFV mutations, show a phenotype not in line with the diagnosis of Familial Mediterranean Fever. For these reasons, diagnostic criteria were developed, as Tel Hashomer Hospital criteria, the "Turkish FMF Paediatric criteria", the "clinical classification criteria for autoinflammatory periodic fevers" formulated by PRINTO. The goals of the treatment are: prevention of attacks recurrence, normalization of inflammatory markers, control of subclinical inflammation in attacks-free intervals and prevention of medium and long-term complications, as amyloidosis. Colchicine is the first step in the treatment; biological drugs are effective in non-responder patients. The goal of this paper is to give a wide and broad review to general paediatricians on Familial Mediterranean Fever, with the relative diagnostic, clinical and therapeutic aspects.

show abstract

Familial Mediterranean fever: overview of pathogenesis, clinical features and management

Cited by 38 publications

References 45 publications

Understanding Inflammatory Responses in the Manifestation of Prothrombotic Phenotypes

Understanding Inflammatory Responses in the Manifestation of Prothrombotic Phenotypes

History of the Plague: An Ancient Pandemic for the Age of COVID-19

FMF is not always “fever”: from clinical presentation to “treat to target”

Contact Info

Product

Resources

About