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Swiss Medical Weekly 2012The monogenic autoinflammatory syndromes are conditions caused by mutations of genes coding for proteins that play a pivotal role in the regulation of the inflammatory... (Review)
Review
The monogenic autoinflammatory syndromes are conditions caused by mutations of genes coding for proteins that play a pivotal role in the regulation of the inflammatory response. Due to their genetic nature, most of these disorders have an early onset. Clinically they are characterised by recurrent flares of systemic inflammation presenting most of the time as sudden fever episodes associated with elevation of acute phase reactants and with a number of clinical manifestations such as rash, serositis, lymphadenopathy and arthritis. Symptom-free intervals are characterised by complete wellbeing, normal growth and complete normalisation of acute phase reactants. Familial Mediterranean fever (FMF), mevalonate-kinase deficiency (MKD) and tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) are the three monogenic disorders subsumed under the term periodic fevers, while a systemic inflammation dominated by a characteristic urticarial rash associated with a number of other clinical manifestations is typical of familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and chronic infantile neurological cutaneous and articular syndrome (CINCA). These diseases represent the clinical spectrum of different mutations of a gene named cold-induced autoinflammatory syndrome 1 (CIAS-1, or NLRP3) coding for a protein called cryopyrin. Hence these disorders are also known as cryopyrin-associated periodic syndromes (CAPS). Other conditions are characterised by typical granulomatous formations (granulomatous disorders). Blau's syndrome (familial juvenile systemic granulomatosis) presents with non-caseating granulomatous inflammation affecting the joint, skin, and uveal tract (the triad of arthritis, dermatitis and uveitis) and is associated with mutations of the NACHT domain of the gene CARD15 (or NOD2).
Topics: Granulomatous Disease, Chronic; Hereditary Autoinflammatory Diseases; Humans; Inflammation
PubMed: 22714396
DOI: 10.4414/smw.2012.13602 -
Italian Journal of Pediatrics Jan 2020Familial Mediterranean Fever, a monogenic autoinflammatory disease secondary to MEFV gene mutations in the chromosome 16p13, is characterized by recurrent self-limiting... (Review)
Review
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, fat-rich 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.
Topics: Biomarkers; Child; Colchicine; Diagnosis, Differential; Familial Mediterranean Fever; Humans; Phenotype; Tubulin Modulators
PubMed: 31941537
DOI: 10.1186/s13052-019-0766-z -
Clinical and Experimental Rheumatology Sep 2022Familial Mediterranean fever (FMF) is a hereditary auto-inflammatory disease, characterised by recurrent episodes of fever and serositis. Since 1972, colchicine is the... (Review)
Review
Familial Mediterranean fever (FMF) is a hereditary auto-inflammatory disease, characterised by recurrent episodes of fever and serositis. Since 1972, colchicine is the drug of choice for FMF. It is effective in preventing the attacks and withholding amyloidosis in most patients with FMF. Colchicine blood and tissue levels are regulated by a glycoprotein pump (GLP) and by Cytochrome P450 3A4 (CYP450 3A4). It is secreted through the bile system and the kidneys. Over the years several problems have been raised following the use of colchicine in FMF. These include potential side effects (particularly gastrointestinal), non-compliance, inefficacy due to drug resistance, many drug-drug interactions and high risk for intoxication due to a narrow therapeutic range. In addition, colchicine does not prevent protracted febrile myalgia or exertional leg pain. Based upon our current understanding of the pathogenesis of FMF, it seems that anti-interleukin-1 (anti-IL-1) agents can solve many of the aforementioned problems related to colchicine therapy. The gastrointestinal side effects of colchicine are extremely uncommon with anti-IL-1 biologics. Drug-drug interactions are also unlikely, and their therapeutic window is not narrow. The once daily injection of anakinra, the once weekly injection of rilonacept, and the once monthly injection of canakinumab result in a better compliance to therapy. Nevertheless, there are no controlled trials showing the efficacy of anti-IL-1 agents in preventing amyloidosis or their safety in pregnancy. Therefore, it is still needed to give IL-1 blockers with concomitant colchicine in its tolerable dose effective in preventing amyloidosis (1.5 mg daily in adult).
Topics: Adult; Amyloidosis; Colchicine; Familial Mediterranean Fever; Female; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Motivation; Pregnancy
PubMed: 36062765
DOI: 10.55563/clinexprheumatol/obb2ds -
Genetics in Medicine : Official Journal... Jun 2011Familial Mediterranean fever is inherited in an autosomal recessive manner. There are two phenotypes: types 1 and 2. Familial Mediterranean fever type 1 is characterized... (Review)
Review
Familial Mediterranean fever is inherited in an autosomal recessive manner. There are two phenotypes: types 1 and 2. Familial Mediterranean fever type 1 is characterized by recurrent short episodes of inflammation and serositis, including fever, peritonitis, synovitis, pleuritis, and, rarely, pericarditis. The symptoms and severity vary among affected individuals, sometimes even among members of the same family. Amyloidosis, which can lead to renal failure, is the most severe complication. Familial Mediterranean fever type 2 is characterized by amyloidosis as the first clinical manifestation of familial Mediterranean fever in an otherwise asymptomatic individual. Routine treatment of end-stage renal disease, including renal transplantation, is advised. Lifelong treatment with colchicine is required for homozygotes for the p.Met694Val mutation or compound heterozygotes for p.Met694Val and another disease-causing allele; this prevents the inflammatory attacks and the deposition of amyloid. Individuals who do not have the p.Met694Val mutation and who are only mildly affected should be either treated with colchicine or monitored every 6 months for the presence of proteinuria. Molecular genetic testing of the MEFV gene, the only gene currently known to be associated with familial Mediterranean fever, can be offered to family members, especially when the p.Met694Val allele is present, because renal amyloidosis can be prevented by colchicine.
Topics: Cytoskeletal Proteins; Diagnosis, Differential; Familial Mediterranean Fever; Genetic Association Studies; Humans; Mutation; Pyrin
PubMed: 21358337
DOI: 10.1097/GIM.0b013e3182060456 -
BMJ Clinical Evidence Jul 2009Systemic lupus erythematosus (SLE) occurs predominantly in young women, but also in children. The prevalence of SLE varies widely worldwide, ranging from about 1 in 3500... (Review)
Review
INTRODUCTION
Systemic lupus erythematosus (SLE) occurs predominantly in young women, but also in children. The prevalence of SLE varies widely worldwide, ranging from about 1 in 3500 women (regardless of race) in the UK, to 1 in 1000 women in China, to 1 in 250 African-American women in the USA.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments on joint symptoms (arthralgia/arthritis) and other non-organ-threatening symptoms (such as serositis and fatigue) in people with systemic lupus erythematosus? What are the effects of interventions for cutaneous involvement in people with systemic lupus erythematosus? What are the effects of treatments in people with proliferative lupus nephritis (WHO grades 3-5)? What are the effects of treatments for neuropsychiatric involvement in people with systemic lupus nephritis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 11 systematic reviews or RCTs that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: acitretin; antipsychotic drugs; chloroquine; combination corticosteroids plus immunosuppressants; corticosteroids; hydroxychloroquine; intravenous immunoglobulin; methotrexate; non-steroidal anti-inflammatory drugs (NSAIDs); plasmapheresis; and sunblock.
Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Chloroquine; Humans; Hydroxychloroquine; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lupus Nephritis
PubMed: 21696649
DOI: No ID Found -
Pediatric Surgery International Aug 2022Acute appendicitis is the most common surgical emergency in children. Diagnosis and management are often straightforward. However, familial Mediterranean fever is an... (Review)
Review
Acute appendicitis is the most common surgical emergency in children. Diagnosis and management are often straightforward. However, familial Mediterranean fever is an important condition to consider in the assessment of children with acute abdominal pain, particularly in children with an origin in eastern Mediterranean basin where the disease is common. The key feature of familial Mediterranean fever is relapsing episodes of fever and serositis including peritonitis, pleurisy, or arthritis. The disease is treated with colchicine that prevents acute attacks, control subclinical inflammation between the attacks and the long-term complication of amyloidosis. The acute attacks may be a challenge to identify and distinguish from other causes of acute abdomen, including acute appendicitis, but also small bowel obstruction. Ultrasound and CT scan findings are nonspecific during acute attacks of familial Mediterranean fever, but imaging is useful to identify acute appendicitis and small bowel obstruction. The purpose of this article was to increase the awareness and knowledge of familial Mediterranean fever and provide support for the paediatric surgeon in the clinical care of these children in parts of the world where familial Mediterranean fever is rare.
Topics: Abdominal Pain; Acute Disease; Appendicitis; Child; Colchicine; Familial Mediterranean Fever; Fever; Humans; Intestinal Obstruction
PubMed: 35737103
DOI: 10.1007/s00383-022-05153-8 -
Clinical and Experimental Rheumatology 2017Familial Mediterranean fever (FMF) is characterised by recurrent attacks of fever and serositis. It may affect the peritoneum, pleura, synovia and the skin. Usually the... (Review)
Review
OBJECTIVES
Familial Mediterranean fever (FMF) is characterised by recurrent attacks of fever and serositis. It may affect the peritoneum, pleura, synovia and the skin. Usually the liver is intact in FMF. Recently, this concept was challenged by some groups which claimed that hepatitis is a feature of FMF and that non-alcoholic liver disease (NAFLD) and cryptogenic cirrhosis are more common among FMF patients. Scope of this paper is to critically review the relevant literature and to answer the question whether or not the liver is involved in FMF.
METHODS
We used Medline, Embase, Scopus and Web of Science database for searching articles dealing with FMF and the liver since 1960. We also reviewed some manuscripts which were not identified by the above searching engines.
RESULTS
Some cases reported that hepatitis is a feature of FMF based upon transaminase elevations without liver biopsy. Due to this questionable diagnosis and the paucity of similar reports, it seems that hepatitis is not a feature of FMF. Cryptogenic cirrhosis is considered as the end stage of NAFLD. Since NAFLD is prevalent in 25% of the general population it is more plausible to relate the occurrence of cryptogenic cirrhosis in FMF patients to NAFLD rather than to FMF. M694V mutation carriage was relatively more frequent among FMF patients with cryptogenic cirrhosis or "hepatitis".
CONCLUSIONS
The literature review indicates that FMF and liver disease are not generally associated. However, carriage of M694V mutations may play a role in the pathogenesis of liver disease.
Topics: Animals; Familial Mediterranean Fever; Genetic Predisposition to Disease; Hepatitis; Humans; Liver Cirrhosis; Mutation; Non-alcoholic Fatty Liver Disease; Phenotype; Prevalence; Pyrin; Risk Factors
PubMed: 28598780
DOI: No ID Found -
Internal Medicine (Tokyo, Japan) Mar 2022Autoinflammatory diseases are systemic disorders caused by genetic or acquired abnormalities in certain signaling pathways of the innate immune system. Dysregulated...
Autoinflammatory diseases are systemic disorders caused by genetic or acquired abnormalities in certain signaling pathways of the innate immune system. Dysregulated activation of the inflammasome, i.e. molecular platforms responsible for the activation of caspase-1 and production of interleukin-1β, causes autoinflammation. Familial Mediterranean fever (FMF), the most common genetic autoinflammatory disease, is characterized by a periodic fever and serositis. The complex and heterogeneous genetic background of Japanese FMF patients, accompanied by potential overlap with other rheumatic diseases, suggests crosstalk between genetic and environmental factors. Recently, FMF has been recognized as being part of a spectrum of autoinflammatory syndromes named pyrin-associated autoinflammatory diseases. The discovery of a new monogenic autoinflammatory disease, A20 haploinsufficiency, may provide novel insights into early-onset Behçet's-like diseases. In contrast, adult-onset Still's disease and Schnitzler's syndrome are acquired autoinflammatory diseases without a monogenic abnormality. Although the concept of autoinflammatory diseases originally applied to monogenic hereditary recurrent fevers, it has been expanded to include non-genetic complex autoinflammatory diseases. Information concerning monogenic autoinflammatory diseases may prove useful for elucidating the molecular mechanisms underlying non-genetic autoinflammatory diseases.
PubMed: 35314554
DOI: 10.2169/internalmedicine.9279-21 -
Orphanet Journal of Rare Diseases Apr 2022Gorham-Stout syndrome (GSS) is a rare disorder with various presentations and unpredictable prognoses. Previous understandings of GSS mainly focused on progressive bone...
BACKGROUND
Gorham-Stout syndrome (GSS) is a rare disorder with various presentations and unpredictable prognoses. Previous understandings of GSS mainly focused on progressive bone destruction, while we identified a group of GSS patients with serous effusion as the first symptom. This study aimed to investigate the clinical characteristics of patients with GSS having serous effusion as the first symptom.
METHODS
Patients diagnosed with GSS were identified through the Peking Union Medical College Hospital Medical Record System. The demographic, clinical, laboratory, and imaging data were collected. Patients who first presented with serous effusion were recruited into the serous group, while those with bone destruction were recruited into the bone group.
RESULTS
Of the 23 patients with GSS enrolled, 13 were in the bone group and 10 in the serous group. The median disease duration was shorter and exercise tolerance was lower in the serous group. Despite less frequent bone pain in the serous group, the frequency of bone involvement was similar to that in the bone group. Patients in the serous group had higher rates of bilateral pleural effusion and multiple serous effusion. However, serous effusion also developed with disease progression in the bone group. Of the 17 patients treated with bisphosphonates, 14 reached bone-stable state. However, 5 out of 10 patients with serous effusion still had refractory effusions after bisphosphonates treatment. Three patients received sirolimus treatment, with an improvement in serous effusion. Seventeen patients were followed up; three patients died, two in the bone group and one in the serous group.
CONCLUSIONS
This study discovered that GSS could first be presented with serous effusion. We believe that this may be a new phenotype of the disease. Sirolimus might help in controlling serous effusion and improving prognosis.
Topics: Diphosphonates; Humans; Osteolysis, Essential; Prognosis; Serositis; Sirolimus
PubMed: 35379268
DOI: 10.1186/s13023-022-02307-8