TY - JOUR. T1 - Efficacy of etanercept in the tumor necrosis factor receptor-associated periodic syndrome. T2 - A prospective, open-label, dose-escalation study. AU - Bulua, Ariel C.. AU - Mogul, Douglas Bradford. AU - Aksentijevich, Ivona. AU - Singh, Harjot. AU - He, David Y.. AU - Muenz, Larry R.. AU - Ward, Michael M.. AU - Yarboro, Cheryl H.. AU - Kastner, Daniel L.. AU - Siegel, Richard M.. AU - Hull, Keith M.. PY - 2012/3. Y1 - 2012/3. N2 - Objective To investigate the efficacy of etanercept in improving the symptoms and underlying inflammation in patients with tumor necrosis factor receptor-associated periodic syndrome (TRAPS). Methods Fifteen patients with TRAPS were enrolled in a prospective, open-label, dose-escalation study. Patients recorded attacks, symptom severity, and use of ancillary medications in a daily diary. Blood samples were collected during each period and measured for levels of acute-phase reactants. Between 7 years and 9 years after the conclusion of the initial ...
Mor, A. "Familial Mediterranean fever successfully treated with etanercept". J Clin Rheumatol. vol. 13. 2007. pp. 38-40. (This paper is a case report of a patient responding to etanercept who was unable to tolerate colchicine for FMF.). El-Shanti, H. "Familial Mediterranean fever in Arabs". Lancet. vol. 367. 2006. pp. 1016-24. (A review paper of FMF in Arabs.). Barzilai, A. "Erysipelas-like erythema of familial Mediterranean fever: clinicopathologic correlation". J Am Acad Dermatol. vol. 42. 2000. pp. 791-5. (This paper is a clinicopathologic study of erysipelas-like erythema.). Ben-Chetrit, E. "Familial Mediterranean fever in the world". Arthritis Rheum. vol. 61. 2009. pp. 1447-53. (An overview of the epidemiology of FMF.). Yuksel, S. "Clinical improvement with infliximab in a child with amyloidosis secondary to familial Mediterranean fever". Rheumatology (Oxford). vol. 45. 2006. pp. 1307-8. (A case report of an FMF patient who was recalcitrant to colchicine but responded to regular infliximab ...
The most common cause of death in familial Mediterranean fever is renal failure secondary to amyloidosis (1). Despite the occurrence of extrarenal amyloidosis in patients with this disease, failure of other organs is uncommon (1). At least four patients have been treated with transplantation for renal failure, and no recurrence of amyloidosis has been reported in these allograft kidneys (2-5). (While this paper was in press, a similar report appeared: Benson MD, Skinner M, Cohen AS: Amyloid deposition in renal transplant in familal Mediterranean fever. Ann Intern Med 87:31-34, 1977.). A patient with familial Mediterranean fever who received an allograft ...
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. 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
Title: Serum Adiponectin Levels in Patients with Familial Mediterranean Fever. VOLUME: 17 ISSUE: 10. Author(s):Goksal Keskin, Ali Inal and Lale Ozisik. Affiliation:DYBEA Hospital, Head of 4. Internal Medicine Department, Ankara, Turkey.. Keywords:Adiponectin, IL-6, FMF. Abstract: Familial mediterranean fever (FMF) is a systemic disorder characterized by recurrent attacks of fever and polyserositis. In FMF, several pro-inflammatory cytokines, such as IL-6, have been found to be elevated during the attacks. In recent years, it is shown that some proteins originated from adipose tissue play important role in inflammatory process. One of them, adiponectin decreases the expression of adhesion molecules and inhibits the attachment of active macrophages to the endothelial surface, so that it acts antiinflammatory effect. In this study, we analyzed the possible role of serum adiponectin in the pathogenesis of FMF. Thirty five patients with FMF and 13 healthy controls (5 female,8 male; mean age 22.3 ± ...
Familial Mediterranean fever (FMF) is a hereditary inflammatory disorder. FMF is an autoinflammatory disease caused by mutations in Mediterranean fever gene, which encodes a 781-amino acid protein called pyrin. While all ethnic groups are susceptible to FMF, it "usually occurs in people of Mediterranean origin-including Sephardic Jews, Mizrahi Jews, Armenians, Azerbaijanis, Arabs, Greeks, Turks and Italians". The disorder has been given various names, including familial paroxysmal polyserositis, periodic peritonitis, recurrent polyserositis, benign paroxysmal peritonitis, periodic disease or periodic fever, Reimann periodic disease or Reimanns syndrome, Siegal-Cattan-Mamou disease, and Wolff periodic disease. Note that "periodic fever" can also refer to any of the periodic fever syndromes. There are seven types of attacks. Ninety percent of all patients have their first attack before they are 18 years old. All develop over 2-4 hours and last anywhere from 6 hours to 4 days. Most attacks involve ...
Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory genetic disorder resulting in recurrent attacks of fever, serositis, arthritis and rash. Late complications of untreated FMF include the development of renal amyloidosis. FMF is a rare orphan disease in the United States. Treatment with colchicine is effective in reducing the frequency of episodes in most patients and the development of amyloidosis in nearly all patients. However, there are still 5-15% of patients who continue to have acute FMF attacks despite colchicine therapy or are intolerant of colchicine, usually from gastrointestinal adverse effects. Currently there are no effective alternatives to colchicine. Pyrin, the mutated protein in FMF has an important role in the regulation of IL-1 beta production and activity. Mutations in pyrin result in increased IL-1 beta levels in mice and humans. IL-1 beta is an important pro-inflammatory cytokine. Thus, we hypothesize that inhibition of IL-1 will decrease acute ...
The purpose of this protocol is to study the genetics and pathophysiology of familial Mediterranean fever (FMF) and other related diseases. FMF is a recessively inherited condition characterized by episodes of fever and serositis or synovitis; some patients also develop systemic amyloidosis. Our laboratory has identified the FMF gene and several disease-related mutations. The FMF gene encodes a protein called pyrin that is the prototype of a family of molecules involved in the regulation of apoptosis (cell-death) and inflammation. The precise biochemical mechanism by which these proteins function, and by which mutations cause disease, is still unknown.. There are a number of other conditions, sometimes referred to as autoinflammatory syndromes because of the lack of high-titer autoantibodies or antigen-specific T-cells that are also characterized by episodic inflammation. Seven are caused by mutations in five other genes: the TNF-receptor associated periodic syndrome (TRAPS) is caused by ...
Familial Mediterranean fever (FMF) is a disease of early onset which can lead to significant morbidity. In 2012, Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched with the aim of optimising and disseminating diagnostic and management regimens for children and young adults with rheumatic diseases. The objective was to establish recommendations for FMF focusing on provision of diagnostic tools for inexperienced clinicians particularly regarding interpretation of MEFV mutations. Evidence-based recommendations were developed using the European League against Rheumatism standard operating procedure. An expert committee of paediatric rheumatologists defined search terms for the systematic literature review. Two independent experts scored articles for validity and level of evidence. Recommendations derived from the literature were evaluated by an online survey and statements with less than 80% agreement were reformulated. Subsequently, all recommendations were ...
Familial Mediterranean fever (FMF) is the earliest known autoinflammatory disease, characterized by symptoms such as arthritis, peritonitis, pleuritis, erysipelas-like erythema, and most importantly amyloidosis. This disease is very common in populat
To Familial Mediterranean Fever (FMF) is an autoinflammatory disorder with genetic origin. Pleuritis is most common in FMF. Long-term sequelae of respiratory system havent been described in FMF. We documented pulmonary manifestations in patient with FMF. A 61-year- old woman presented with dyspnea, unilateral chest pain, generalized myalgia and FMF. Physical examination was unremarkable. Radiological data showed left-sided pleuritis, minimal pleural effusion. Pleural effusion resolved spontaneously in one week later but patient had still dyspnea. Pulmonary function tests (PFT) was normal. Further examination detected respiratory muscle weakness and decreased functional capacity. Patient then underwent inspiratory muscle training (IMT) for six weeks. After training, inspiratory muscle strength and functional capacity increased. Perception of dyspnea and fatique decreased. In long-term follow-up, frequency of attacks decreased. To our knowledge, there is no study on respiratory muscle weakness ...
Familial Mediterranean Fever is an inherited disease, characterized by recurrent attacks of fever, inflammation, painful, swollen joints, and ankle rash.
Familial Mediterranean fever information including symptoms, diagnosis, misdiagnosis, treatment, causes, patient stories, videos, forums, prevention, and prognosis.
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Autoinflammatory disorders are recently recognized syndromes believed to be due to overactive immune systems, rather than an immune deficiency. These disorders include periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome, familial Mediterranean fever (FMF), the cryopyrinopathies (cryopyrin-associated periodic syndromes, or CAPS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS) and hyper-IgD syndrome/mevalonic kinase deficiency (HIDS/MKD), among others.. Five Signs of Autoinflammation:. ...
Results The relative expression levels of miR-4520a were variable among FMF patients and not significantly different between patients and controls. Stratification of patients group by genotype revealed an intriguing difference in miR-4520a relative expression. Specifically, miR-4520a expression was lower in carriers of M694V variant (combined group of homo- and heterozygotes), whereas the rest of FMF genotypes had higher levels (p,0.05). Subsequent comparison between the M694V-group and healthy controls showed a significant reduction in miR-4520a expression levels (p,0.01). Interestingly, one of the homozygote M694V patients with the highest fold change in miR-4520a expression experienced an FMF-attack while on study. Quantitative real time PCR analysis of the miRNA-enriched fraction of total RNA isolated from FMF patients monocytes during the attack revealed a surprisingly increased miR-4520a expression (FC=0.85) compared to the attack-free period (FC=5.2). Bioinformatic analyses showed that ...
Recurrent fever in adults may be a periodic fever syndrome. Here is in depth info on periodic fever syndromes in adults; symptoms, diagnosing, pregnancy and more.
in PLoS ONE (2009), 4(9), 7154. BACKGROUND AND AIMS: The familial Mediterranean fever (FMF) gene (MEFV) encodes pyrin, a major regulator of the inflammasome platform controlling caspase-1 activation and IL-1beta processing. Pyrin has ... [more ▼]. BACKGROUND AND AIMS: The familial Mediterranean fever (FMF) gene (MEFV) encodes pyrin, a major regulator of the inflammasome platform controlling caspase-1 activation and IL-1beta processing. Pyrin has been shown to interact with the gene product of NLRP3, NALP3/cryopyrin, also an important active member of the inflammasome. The NLRP3 region was recently reported to be associated with Crohns disease (CD) susceptibility. We therefore sought to evaluate MEFV as an inflammatory bowel disease (IBD) susceptibility gene. METHODOLOGY AND RESULTS: MEFV colonic mucosal gene expression was significantly increased in experimental colitis mice models (TNBS p,0.0003; DSS p,0.006), in biopsies from CD (p,0.02) and severe ulcerative colitis (UC) patients ...
16 patients (12H, 4F) with a median age of 41 years [29-61] were included. Patients were Sefarad Jews (n=9), Turkish (n=2) and Arabic (n=5). Seven of them had a familial history of FMF, none had a familial history of auto-immune diseases. Their FMF was symptomatic during childhood except for two patients; most of them had colchicine. They displayed various type of vasculitis such as: HSP (n=7), PAN (n=4; two of them with viral B hepatitis), Granulomatosis with Polyangitis (GPA) (n=1), Microscopic Polyangitis (MPA) (n=1) and unclassified (n=3). Their vasculitis was diagnosed at a median age of 32 [5-43]. For one patient the diagnosis of vasculitis was made before the diagnosis of FMF. Patients with PAN mostly displayed weight loss, fever, myalgia, abdominal pain, arthralgia, with evidence of vasculitis of small or medium-sized blood vessels on a skin biopsy (n=3) or renal arterial aneurysms on an angiography (n=1). MEFV sequencing showed: homozygous M694V/M694V mutations (n=2), homozygous ...
The most severe and feared complication of FMF is the development of amyloidosis. This may occur in the setting of inadequately controlled disease and/or persistently elevated serum inflammatory markers. SAA is produced by the liver in acute inflammatory states and AA amyloid deposits in tissues to result in pathology. Initial amyloid deposits may occur without consequence, however, once a critical burden is reached, the rate of further amyloid deposition rapidly increases with resultant organ damage.. Renal amyloid deposition was the most common cause of death in patients prior to colchicine and remains the organ contributing to the highest amount of clinical pathology. However, deposition may also occur in the GI tract, lungs, testes, thyroid, and adrenal glands. Amyloidosis usually occurs after long-standing inflammatory disease.. Other risk factors include homozygosity for the M694V mutation and country of residence, with Armenia, Turkey and Arab countries showing the highest risks of renal ...
Vaitla, P. M., Radford, P. M., Tighe, P. J., Powell, R. J., McDermott, E. M., Todd, I. and Drewe, E., Role of interleukin-6 in a patient with tumor necrosis factor receptor-associated periodic syndrome: assessment of outcomes following treatment with the anti-interleukin-6 receptor monoclonal antibody tocilizumab. Arthritis Rheum. 2011. 63: 1151-1155 ...
In 1945, Dr. Sheppard Siegal, an allergist at Mount Sinai Hospital in New York, reported in Annals five cases of "recurrent paroxysms of severe abdominal pain with fever … as high as 105 °F," all in men and all starting early in life. He named the syndrome benign paroxysmal peritonitis [1]. The peritoneal signs were so severe that "emergency operation [had] been repeatedly urged." Pleuritic chest pain often accompanied the attacks. At least one of the patients had "urticarial" lesions near the ankle, and another had intermittent joint pains, usually monoarticular. As an allergist, Siegal approached these cases from his own vantage point, and the history of this condition is replete with references to potential allergens and allergic relatives. Unfortunately, except for noting that all of the patients were white men, he provided no other ethnic background data. Although an occasional similar case was found in previous published series, including some in which such manifestations were ...
Familial Mediterranean Fever pipeline analysis report gives comprehensive insight on various drugs being developed for the treatment of Familial Mediterranean Fever.
Research paper discusses the application of the molecular genetics method for identifying this disease, which has primarily been diagnosed on a clinical basis. (October 01, 1998) ...
Jnetics, formerly Jewish Genetic Disorders UK (Jnetics) is a registered charity dedicated to improving the awareness, prevention and management of Jewish genetic disorders across the Jewish, healthcare professional and wider community.
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Typically, episodes of FMF are short (,3 days), resolve spontaneously, and can be triggered by several different factors such as stress, physical activity, or viral illness. Episodes can occur as often as once per week, but tend to decrease in frequency with patient age. Prodromal symptoms can occur around episodes; these include headache, nausea, vomiting, diarrhea, constipation, dyspnea, and low back pain. Apart from fever, the most common feature of FMF is serositis, which manifests as abdominal pain due to peritonitis in up to 90% of patients. Peritonitis can cause abdominal pain that mimics an acute surgical abdomen or renal colic. FMF can also present as arthritis due to synovitis (up to 75% of patients), which presents as pain and swelling of joints and can lead to chronic degenerative arthritis, or chest pain due to pleuritis (45% of patients). In up to 50% of cases, recurrent erysipelas-like erythema affecting the lower extremities occurs ...
This gene encodes a protein, also known as pyrin or marenostrin, that is an important modulator of innate immunity. Mutations in this gene are associated with Mediterranean fever, a hereditary periodic fever syndrome. [provided by RefSeq, Jul 2008 ...
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AIM: Familial Mediterranean fever (FMF) is the most common autoinflammatory disease. One of the common characteristics of this disease is its young age predominance. Nearly 90% of patients experience disease flares during early adult age periods. Currently there are limited data for the comparison of early versus late onset FMF and therefore the primary aim of this study was to investigate these two subsets with regard to their certain demographic, clinical and genetic differences. METHODS: Early (≤ 20 years, Group 1) and late (, 20 years, Group 2) onset FMF patients were identified from the national FMF registry that involves 2246 patients from 15 adult rheumatology clinics located in different geographical areas of Turkey ...
AIM: Familial Mediterranean fever (FMF) is the most common autoinflammatory disease. One of the common characteristics of this disease is its young age predominance. Nearly 90% of patients experience disease flares during early adult age periods. Currently there are limited data for the comparison of early versus late onset FMF and therefore the primary aim of this study was to investigate these two subsets with regard to their certain demographic, clinical and genetic differences. METHODS: Early (≤ 20 years, Group 1) and late (, 20 years, Group 2) onset FMF patients were identified from the national FMF registry that involves 2246 patients from 15 adult rheumatology clinics located in different geographical areas of Turkey ...
It may at first seem strange, but many genes responsible for common genetic disorders show evidence of positive selection. In other words, the genes that cause these disorders were favored by evolution at some point because they presumably provided a survival advantage. For example, the sickle cell anemia gene protects against malaria, but if you inherit two copies of it, you end up with a serious and life-threatening disorder (1). The cystic fibrosis gene may have been selected to protect against one or more infectious diseases, but again if you get two copies of it, quality of life and lifespan are greatly curtailed (2, 3). Familial Mediterranean fever is a very common disorder in Mediterranean populations, involving painful inflammatory attacks of the digestive tract, and sometimes a deadly condition called amyloidosis. It shows evidence of positive selection and probably protected against intestinal disease due to the heightened inflammatory state it confers to the digestive tract (4, 5). ...
Objective Familial Mediterranean fever (FMF) is thought to be a rare disorder in Japan, and the clinical features of Japanese patients with FMF remain unclear. Our aim was to elucidate the clinical characteristics of FMF in Japanese patients. Methods We analyzed clinical and genetic data of 80 patients based on the results of a nationwide questionnaire survey and review of the literature. Results From clinical findings of 80 Japanese patients, high-grade fever was observed in 98.8%, chest attacks (pleuritis symptoms) in 61.2%, abdominal attacks (peritonitis symptoms) in 55.0%, and arthritis in 27.5%. Twenty-four percent of patients experienced their first attacks before 10 years of age, 40% in their teens, and 36% after age 20 years. Colchicine was effective in many patients at a relatively low dose (, 1.0 mg/day). AA amyloidosis was seen in only 1 patient. Common MEFV mutation patterns were E148Q/M694I (25.0%), M694I alone (17.5%), and L110P/E148Q/M694I (17.5%), and no patient carried the M694V ...
Colchicine is a natural alkaloid which is derived from the colchium autumnale plant. It is used in the treatment of familial Mediterranean fever, amyloidosis, gout, Behçets disease, and inflammatory bowel disease. In this article, we present four colchicine intoxication cases who were admitted to our clinic last year. While two patients ingested colchicine accidentally, other two took it for attempted suicide. First patients clinical signs were gastroenteritis, fever, and alopecia. This patient developed renal, hepatic dysfunction, and rebound leucocytosis. Patient was given support treatment and discharged. Second patients physical examination was normal except for tachycardia. Twenty hours after taking the medication, patient developed leucocytosis. The patient was performed plasmapheresis and leukapheresis. Thirty-nine hours after intake, patient developed sudden cardiac arrest and died. Third patients clinical signs were gastroenteritis, fever, and alopecia. Patient developed hepatic ...
Colchicine is an oral medication used for the treatment of gout symptoms or attacks of familial Mediterranean fever. Read this article to learn more about colchicine.
DEAR DR. ROACH: After an intestinal virus, I ended up in the hospital with a sed rate of 110 and a high white blood count. I was feeling crippled with severe joint pain and was diagnosed with reactive arthritis. I was discharged with steroids and colchicine. Im still taking the colchicine because my doctor said I have familial Mediterranean fever, and the colchicine is helping. I am a full-blooded Italian. She also said I have the HLA-B27 antigen. Two months later, my sed rate is back to normal, but Ill be taking colchicine for another month and then ... ...
DEAR DR. ROACH: After an intestinal virus, I ended up in the hospital with a sed rate of 110 and a high white blood count. I was feeling crippled with severe joint pain and was diagnosed with reactive arthritis. I was discharged with steroids and colchicine. Im still taking the colchicine because my doctor said I have familial Mediterranean fever, and the colchicine is helping. I am a full-blooded Italian. She also said I have the HLA-B27 antigen. Two months later, my sed rate is back to normal, but Ill be taking colchicine for another month and then ... ...
Detailed Colchicine dosage information for adults, the elderly and children. Includes dosages for Acute Gout, Gout - Prophylaxis and Familial Mediterranean Fever; plus renal, liver and dialysis adjustments.
The relationship between high ADMA and CRP is context dependent. Indeed, in acute sepsis, ADMA is downregulated (34), whereas high ADMA levels are consistently associated with biomarkers of inflammation in a variety of chronic conditions including untreated essential hypertension (35), glucose intolerance (36), familial Mediterranean fever (33), and inflammatory bowel diseases (37). In vitro, ADMA induces TNF-α production via reactive oxygen species/NF-κB-dependent pathway (38). On the other hand, the generation of reactive oxygen species, an important initial event in inflammation, inhibits the enzyme that degrades ADMA (dimethylarginine dimethylaminohydrolase), facilitating local and/or systemic ADMA accumulation. ADMA in turn increases the generation of the downstream pro-inflammatory mediators TNF-α and IL-8 and activates the NF-κB pathway and the binding of monocytes to endothelial cells (39). Even although an independent prognostic value of ADMA and inflammation was described in the ...
Neutropenia is a blood disorder characterized by an unusually low number of a certain type of white blood cell called neutrophils. Cyclic neutropenia (or cyclic neutropenia) is a form that tends to cause episodes that occur every 3 weeks or so and last 3 to 6 days at a time due to varying rates of cell production in the bone marrow. Treatment for this disorder is to administer granulocyte colony stimulating factor (G-CSF or G-CSF). GCSF is a hormone made by several different tissues that causes bone marrow to produce granulocytes and stem cells. It then also stimulates the bone marrow to release it into the blood. It promotes the endurance, multiplication, differentiation and effectiveness of neutrophil precursors and mature neutrophils. This condition generally improves puberty hits once.. Familial Mediterranean fever is most common in childhood. The episodes presenting symptoms often occur without warning. Usually these are attacks last 2 to 3 days and peak intensity in the first 12 to 24 ...
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Mean ages of patients and controls were 24.3 ±4.9, 25.8± 5.5 years (p=0.338). Fourteen (48.2%) of FMF patients had reported arthralgia and/or arthritis during attacks. In 7 of 15 patients who had not reported joint problems, a sonographic pathology was found (4 of them was mild effusion at knee and 3 of them was retrocalcaneal bursitis and medial tenosynovitis. No PDS was found in knee or ankle joint. But there was no pathology in controls. ...
List of 6 disease causes of Bacterial infections causing recurrent fever, patient stories, diagnostic guides. Diagnostic checklist, medical tests, doctor questions, and related signs or symptoms for Bacterial infections causing recurrent fever.
Question - Child get recurrent fever. Cause and treatment?. Ask a Doctor about diagnosis, treatment and medication for Ear pain, Ask a Pediatrician
PERIODIC FEVER, FAMILIAL, AUTOSOMAL DOMINANT description, symptoms and related genes. Get the complete information in our medical search engine for ph
A 30-year-old female who is 34 weeks pregnant was admitted with a 3 day history of fever associated with rigors, chills, nausea, and vomiting. Her blood pressure was norm..
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Hereditary periodic fever syndromes are defined by the presence of recurrent incapacitating episodes or fluctuating degrees of fever and inflammation in the absence of infection. Unlike autoimmune diseases, hereditary periodic fever syndromes are marked by the absence of significant levels of autoantibodies and autoreactive T-cells. As a consequence, the name autoinflammatory syndromes has been advocated as a common descriptive denominator for this group of rare disorders.1,2 Since 1997, ten of the major syndromes have been linked to mutations in seven specific genes, facilitating the specific diagnosis of these conditions rather than relegating them to diagnoses of exclusion3 (Table 61-1). The nomenclature of the various autoinflammatory syndromes is complicated, comprising a mix of syndromes described by various typical manifestations and syndromes characterized by identification of specific genetic defects. Most terms originated from the period preceding the discovery of the implicated ...