scholarly journals A rare hereditary disease: Muckle-Wells syndrome

2016 ◽  
Vol 8 (1) ◽  
Author(s):  
Nitya Ramreddy ◽  
Aviva Hopkins ◽  
Carlos Lozada
Keyword(s):  
Autoinflammatory Disease ◽  
Periodic Fever ◽  
Hereditary Disease ◽  
Genetic Mutation ◽  
Periodic Syndrome ◽  
Familial Cold Autoinflammatory Syndrome ◽  
Neonatal Onset ◽  
Fever Syndromes ◽  
History Of ◽  
Wells Syndrome

Cryopyrin associated periodic syndrome (CAPS) is a dominantly-inherited autoinflammatory disease, which is included in the group of periodic fever syndromes. It is caused by a defect in the regulation of inflammatory cytokines, particularly interleukin-1β. CAPS encompasses a spectrum of three phenotypes of increasing severity: familial cold autoinflammatory syndrome, Muckle-Wells syndrome (MWS) and neonatal onset multisystem inflammatory disease. We report the case of a 58-year-old male, who had migratory joint pains, daily urticaria, chills, and episodic conjunctivitis since childhood and hearing loss in his 20s with a family history of similar symptoms. He was diagnosed with MWS after being found to have a <em>R262W</em> gene mutation in <em>NLRP3</em> gene and successfully treated with canakinumab. After his discovery, other 1<sup>st</sup> and 2<sup>nd</sup> degree family members with similar complaints were found to have the same genetic mutation and were also successfully treated with canakinumab.

scholarly journals Cryopyrin-Associated Periodic Syndromes and Treatment Options

2020 ◽  
Vol 8 (F) ◽  
pp. 241-245
Author(s):  
Lidija Kareva ◽  
Katarina Stavrik ◽  
Kristina Mironska
Keyword(s):  
Periodic Fever ◽  
Treatment Options ◽  
The Body ◽  
Familial Cold Autoinflammatory Syndrome ◽  
Cold Urticaria ◽  
Nlrp3 Gene ◽  
Neonatal Onset ◽  
Persistent Inflammation ◽  
Fever Syndromes ◽  
Wells Syndrome

Cryopyrin-associated periodic syndromes (CAPSs) are a growing family of autoinflammatory diseases, also known as periodic fever syndromes. There are three forms of CAPS: (1) Familial Cold autoinflammatory syndrome or familial cold urticaria, (2) Muckle-wells syndrome, and (3) neonatal-onset multisystem inflammatory disease or chronic infantile neurological cutaneous articular syndrome. Genetic mutations in the NLRP3 gene were found to be present in most patients. The foremost common findings between all the CAPS disorders are rash, fever which is sometimes present at birth or in early childhood, joint problems, and conjunctivitis. More extreme forms of CAPS include more persistent inflammation that can cause hearing loss and meningitis and can lead to mental and developmental delays. Drugs for CAPS target the source of inflammation – which is the over-production of interleukin 1ß by modified cryopyrin inflammasomes. Three drugs are used to treat CAPS: Rilonacept, canakinumab, and anakirna. With these drugs, the prognosis is greatly improved, with most patients having less frequent episodes, decreased buildup of amyloid in the body, and extended life of severe cases up to adulthood.

Hereditary periodic fever syndromes

2020 ◽  
pp. 2207-2218
Author(s):  
Helen J. Lachmann ◽  
Stefan Berg ◽  
Philip N. Hawkins
Keyword(s):  
Clinical Features ◽  
Periodic Fever ◽  
Mevalonate Kinase ◽  
Tnf Receptor ◽  
Aa Amyloidosis ◽  
Periodic Fever Syndromes ◽  
Hereditary Periodic Fever Syndromes ◽  
Hereditary Periodic Fever ◽  
Fever Syndromes ◽  
Wells Syndrome

The hereditary periodic fever syndromes or hereditary autoinflammatory diseases are disorders of innate immunity that mostly present in childhood and are characterized by recurrent, self-limiting, seemingly unprovoked episodes of fever and systemic inflammation that occur in the absence of autoantibody production or identifiable infection. Disorders include (1) familial Mediterranean fever (FMF), due to mutations in the gene encoding pyrin; (2) tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS), due to mutations in a gene for a TNF receptor; (3) mevalonate kinase deficiency and period fever (MKD), caused by mutations in the mevalonate kinase gene; and (4) the cryopyrin-associated periodic syndromes (CAPS), which include (a) familial cold urticarial syndrome, (b) Muckle–Wells syndrome, and (c) chronic infantile neurological, cutaneous, and articular syndrome. With advances in genetics, further syndromes are continually being recognized. These are all extremely rare and in the majority are only known to affect a handful of kindred or individuals. Diagnosis relies on recognition of suggestive clinical features that are almost always accompanied by a substantial acute phase response, and is supported by genetic testing. With the exception of FMF, which is a common disease in certain geographic areas, hereditary periodic fever syndromes are rare and easily overlooked in the differential diagnosis of recurrent fevers. Clinical features and management—attacks can be mild to debilitating and short to prolonged, while their most feared complication is AA amyloidosis. Effective therapies are available for some syndromes, for example: (1) FMF—daily prophylactic colchicine prevents clinical attacks and susceptibility to AA amyloidosis, (2) CAPS—treatment with anti-IL-1 agents produces rapid and often complete clinical and serological remission, and (3) TRAPS—anti-IL therapies are extremely effective.

scholarly journals Inherited Autoinflammatory Disease with Immunodeficiency Combined with IgA Nephropathy

2020 ◽  
Vol 45 (06) ◽  
pp. 574-576
Author(s):  
Zhifeng Jiang ◽  
Aiqiao Feng ◽  
L I Tao
Keyword(s):  
Abdominal Pain ◽  
Iga Nephropathy ◽  
Autoinflammatory Disease ◽  
Chinese Women ◽  
Periodic Fever ◽  
Immune Dysregulation ◽  
Antibody Deficiency ◽  
Intermittent Fever ◽  
Hereditary Factors ◽  
History Of

AbstractThe etiology of unexplained periodic fever is often complex, and hereditary factors play an important role. This article describes a 26-year-old chinese women with intermittent fever for 9 years, with 10-year history of IgA nephropathy. Her fever is relieved during pregnancy, but after a baby is born, fever reappears, accompanied by headache, gasping after activity, chest pain, abdominal pain, blood in the stool, ataxia, intermittent back erythema, skin biopsy suggests amyloidosis, the autoinflammatory PLCG2 associated antibody deficiency and immune dysregulation was diagnosed by genetic testing. The fever was gradually relieved after treatment with rilonacept.

scholarly journals AB1069 CONSIDERATION OF YAO SYNDROME AS A DIFFERENTIAL DIAGNOSIS FOR HEREDITARY PERIODIC FEVER SYNDROMES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1823.1-1824
Author(s):  
Q. Yao
Keyword(s):  
Genetic Testing ◽  
Autoinflammatory Disease ◽  
Periodic Fever ◽  
Nucleotide Binding ◽  
Periodic Fever Syndromes ◽  
Hereditary Periodic Fever Syndromes ◽  
Genes And Environment ◽  
Hereditary Periodic Fever ◽  
Fever Syndromes ◽  
Oligomerization Domain

Background:Yao syndrome (YAOS, OMIM 617321), formerly termed nucleotide-binding oligomerization domain 2(NOD2)-associated autoinflammatory disease, is characterized by periodic fever, dermatitis, arthritis, and swelling of the distal extremities, as well as gastrointestinal and sicca-like symptoms. This disorder shares similar clinical phenotypes with hereditary periodic fever syndromes (HPFS) and thus can mimic one another.Objectives:This study aimed to exemplify by a comparison of YAOS vs familial Mediterranean fever (FMF).Methods:In this retrospective study, electronic medical records of a series of patients with YAOS were analyzed. All patients underwent genetic testing for periodic fever syndrome 6-gene panel (MEFV, TNFRSF1A, NLRP3, MVK, NLRP12 and NOD2).Results:All patients were Caucasian and had recurrent fever, patchy erythema, arthralgia, and gastrointestinal symptoms (Table 1). With negative DNA sequencing for MEFV, these patients were treated with colchicine for presumed FMF, with a good response in patient 2 and minimal or transient response in other two patients. Further genetic testing identified the NOD2 variants. Unlike HPFS, YAOS is generally sporadic and is mostly reported in adults; spongiotic dermatitis is common; YAOS is associated with the NOD2 variants, IVS8 + 158 in nearly all patients, IVS8 + 158/R702W in up to 30%, and IVS8 + 158/1007fs, G908R or other rarer NOD2 variants in some patients.Conclusion:YAOS can masquerade HPFS like FMF. Molecular analysis should cover NOD2 whole gene sequencing to help distinguish these diseases.References:[1]Yao Q, et al. Dermatitis as a characteristic phenotype of a new autoinflammatory disease associated with NOD2 mutations. J Am Acad Dermatol. 2013;68(4):624-31.Trueb B, et al. Coincidence of NOD2-Associated Autoinflammatory Disease (Yao Syndrome) and HCV Infection With Fatal Consequences: Interaction Between Genes and Environment. J Clin Rheumatol. 2018 Dec 28. doi: 10.1097/RHU.0000000000000963. [Epub ahead of print].China[2]Yao Q. Research letter: Effectiveness of canakinumab for the treatment of Yao syndrome patients. J Am Acad Dermatol. 2019.[3]Yao Q, Shen M, McDonald C, Lacbawan F, Moran R, Shen B. NOD2-associated autoinflammatory disease: a large cohort study. Rheumatology (Oxford). 2015;54(10):1904-12.[4]Yao Q, Shen B. A Systematic Analysis of Treatment and Outcomes of NOD2-Associated Autoinflammatory Disease. Am J Med. 2017;130(3):365 e13- e18.[5]McDonald C, et al. Alterations in nucleotide-binding oligomerization domain-2 expression, pathway activation, and cytokine production in Yao syndrome. Autoimmunity. 2018;51(2):53-61.Acknowledgments:The author is thankful to the statistician, Ms. Erin Taub for her help with making the table.Disclosure of Interests:None declared

scholarly journals POS1326 FAMILIAL PERIODIC FEVER, APHTHOUS STOMATITIS, PHARYNGITIS AND ADENITIS (PFAPA)SYNDROME; IS IT A SEPARATE DISEASE?

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 945.2-945
Author(s):  
Y. Butbul
Keyword(s):  
Family History ◽  
Pediatric Population ◽  
Periodic Fever ◽  
Positive Family History ◽  
Aphthous Stomatitis ◽  
M694v Mutation ◽  
Fever Syndromes ◽  
History Of ◽  
Pfapa Syndrome ◽  
Sporadic Disease

Background:Periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome (PFAPA) is the most common periodic fever syndrome in the pediatric population. Unlike other periodic fever syndromes, the pathogenesis and genetics of PFAPA is unknown. Until recently, PFAPA was believed to be a sporadic disease, yet family clustering has been widely observed and current research indicates that heredity is likely.Objectives:To identify demographic and clinical differences between patients with PFAPA who have a positive family history (FH+) compared to those with PFAPA with no family history (FH-) that can reveal if heritable and sporadic subtypes of this disorder exist.Methods:In a database comprising demographic and clinical data of 273 pediatric PFAPA patients treated at two tertiary centers in Israel, 31(14.3%) of patients were PFAPA FH+. Data from patients with FH+ for PFAPA was compared to data from those with FH- of the disorder. Furthermore, family members (FMs) of those with FH+ were contacted via telephone for more demography and clinical details.Results:FH+ group had more headaches (32% vs.2%; p= 0.016), myalgia (56% vs. 19%; p= 0.001), higher carrier frequency of M694V mutation (54% vs. 25%; p=0.053), greater family history of FMF (30% vs. 15%; p=0.096) and better outcomes with colchicine (82% vs. 52%; p=0.096) compared to those with FH-. FMs displayed almost identical characteristics to the FH+ group except for greater arthralgia during flares (64% vs. 23%; p=0.008) and compared to the FH- group, more oral aphthae (68% vs. 43%; p=0.002), myalgia/arthralgia (64% vs. 19%/16%; p<0.0001), and higher rates of FH of FMF (45% vs.15%; p=0.003).Conclusion:Our findings suggest that FH+ had probably different subset of disease with higher frequency of family history of FMF arthralgia, myalgia and better response to colchicine. Colchicine prophylaxis for PFAPA should be considered in FH+.Disclosure of Interests:None declared

scholarly journals Rare Autoinflammatory Diseases: A Single Center Experience of 47 Patients

2021 ◽  
pp. 27-35
Author(s):  
Sema Nur Taşkın ◽  
Ayşenur Paç Kısaarslan ◽  
Sümeyra Özdemir Çiçek ◽  
Nihal Şahin ◽  
Şeyda Doğantan ◽  
...  
Keyword(s):  
Autoinflammatory Disease ◽  
Clinical Laboratory ◽  
Periodic Fever ◽  
Innate Immune ◽  
Autoinflammatory Diseases ◽  
Mevalonate Kinase Deficiency ◽  
Single Center Experience ◽  
Neonatal Onset ◽  
Early Onset Sarcoidosis ◽  
Recurrent Inflammation

Autoinflammatory diseases include a group disease characterized by recurrent systemic inflammatory attacks due to failure in the regulation of the innate immune system. The beginning time of autoinflammatory disease are the most commonly in childhood. Autoinflammatory disease which having different clinical forms are rare, therefore diagnosis is often delayed. To determine the clinical, laboratory and radiological characteristics of children with rare autoinflammatory diseases and in which patients to consider autoinflammatory disease. Forty seven patients diagnosed with rare autoinflammatory diseases between 2010 and 2020 were analyzed retrospectively. Demographic characteristics, clinical courses, laboratory and imaging findings of the patients were recorded. Forty-seven with rare autoinflammatory patients evaluated. Twenty-three patients had Chronic Nonbacterial Osteomyelitis (CNO), seven patients had Mevalonate Kinase Deficiency (MKD), six patients had Blau Syndrome / Early-Onset Sarcoidosis (BS/EOS) Syndrome, three patients had Cryopyrin-associated periodic fever syndrome (CAPS), three patients had Autoinflammatory Vasculitis, one patient had Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) syndrome, one patient had Neonatal Onset Pancytopenia, Autoinflammation, Rash and Episodic HLH (NOARCH) syndrome. Three of our patients were being followed up with a diagnosis of undiferantiated systemic autoinflammatory disease (uSAID).Autoinflammatory diseases may have different presentations. Steril and recurrent inflammation should be warning clinicians.

scholarly journals Recognising and understanding cryopyrin-associated periodic syndrome in adults

2019 ◽  
Vol 28 (18) ◽  
pp. 1180-1186 ◽  
Author(s):  
René Williams ◽  
Philip Hawkins ◽  
Thirusha Lane
Keyword(s):  
Quality Of Life ◽  
Interleukin 1 ◽  
Poor Quality ◽  
Periodic Syndrome ◽  
Familial Cold Autoinflammatory Syndrome ◽  
Hereditary Autoinflammatory Diseases ◽  
Cinca Syndrome ◽  
Wells Syndrome

Cryopyrin-associated periodic syndrome (CAPS) is a group of rare hereditary autoinflammatory diseases characterised by recurrent flares of mild to severe systemic inflammation and fever. CAPS is the umbrella term for a spectrum of individual conditions, namely familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal-onset multisystem inflammatory disease (NOMID), also known as chronic infantile neurologic, cutaneous and articular (CINCA) syndrome. The flare symptoms include fever, fatigue, rashes, headaches, arthralgia and myalgia that can last for a few hours or for several days. These symptoms are debilitating, contributing to poor quality of life for patients if left untreated. Serious life-changing complications such as hearing loss, blindness and AA amyloidosis resulting in kidney failure can occur. Until recently, treatment of the disease was symptomatic using non-steroidal anti-inflammatory and immunosuppressant drugs with limited success. In contrast, biological treatments targeting interleukin 1 (IL-1) have proved remarkably effective, often associated with complete and sustained disease remission, vastly improved quality of life and avoidance of serious long-term complications.

scholarly journals Reasons for canakinumab initiation among patients with periodic fever syndromes: a retrospective medical chart review from the United States

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Peter Hur ◽  
Kathleen G. Lomax ◽  
Raluca Ionescu-Ittu ◽  
Ameur M. Manceur ◽  
Jipan Xie ◽  
...  
Keyword(s):  
Safety Profile ◽  
Periodic Fever ◽  
Previous Treatment ◽  
The United States ◽  
Periodic Syndrome ◽  
Perceived Efficacy ◽  
Periodic Fever Syndromes ◽  
Favorable Safety Profile ◽  
Fever Syndromes ◽  
Favorable Safety

Abstract Background Although canakinumab has demonstrated efficacy in multiple trials in patients with periodic fever syndromes (PFS), the evidence on initiation of canakinumab among PFS patients in real world setting is not well understood. We aimed to characterize the reasons for canakinumab initiation among patients with PFS, specifically, cryopyrin-associated periodic syndrome (CAPS), hyperimmunoglobulin D syndrome/mevalonate kinase deficiency (HIDS/MKD), TNF receptor-associated periodic syndrome (TRAPS) and familial Mediterranean fever (FMF). Methods Physicians retrospectively reviewed the medical charts of PFS patients prescribed canakinumab between 2016 and 2018. Information collected included patient clinical characteristics, reasons for previous treatment discontinuation and canakinumab initiation. The results were summarized for overall patients, and by children (< 18 years) and adults and by subtype of PFS. Results Fifty-eight physicians in the US (rheumatologists, 44.8 %; allergists/immunologists, 29.3 %; dermatologists, 25.9 %) abstracted information for 147 patients (children, 46.3 %; males, 57.1 %; CAPS, 36.7 %; TRAPS, 26.5 %; FMF, 26.5 %; HIDS/MKD, 6.8 %; Mixed, 3.4 %). Overall, most patients (90.5 %) received treatment directly preceding canakinumab (NSAIDs, 27.8 % [40.0 % in HIDS/MKD]; anakinra, 24.1 % [32.7 % in CAPS]; colchicine, 21.8 % [35.9 % in FMF]), which were discontinued due to lack of efficacy/effectiveness (39.5 %) and availability of a new treatment (36.1 %). The common reasons for canakinumab initiation were physician perceived efficacy/effectiveness (81.0 %; children, 75.0 %; adults, 86.1 %), lack of response to previous treatment (40.8 %; children, 38.2 %; adults, 43.0 %) and favorable safety profile/tolerability (40.1 %; children, 42.6 %; adults, 38.0 %). Within subtypes, efficacy/effectiveness was the most stated reason for canakinumab initiation in HIDS/MKD (90.9 %), lack of response to previous treatment in FMF (52.4 %) and convenience of administration/dosing in CAPS (27.1 %). Conclusions This study provided insights into how canakinumab is initiated in US clinical practice among PFS patients, with physician perceived efficacy/effectiveness of canakinumab, lack of response to previous treatment and favorable safety profile/tolerability of canakinumab being the dominant reasons for canakinumab initiation in all patients and in children and adults and PFS subtypes. Notably, the favorable safety profile/tolerability of canakinumab was more often the reason for initiation among children versus adults.

Hereditary periodic fever syndromes

2010 ◽  
pp. 1760-1766
Author(s):  
Helen J. Lachmann ◽  
Philip N. Hawkins
Keyword(s):  
Periodic Fever ◽  
Mevalonate Kinase ◽  
Tnf Receptor ◽  
Gene Encoding ◽  
Kinase Gene ◽  
Periodic Fever Syndromes ◽  
Hereditary Periodic Fever Syndromes ◽  
Hereditary Periodic Fever ◽  
Fever Syndromes ◽  
Wells Syndrome

The hereditary periodic fever syndromes are autoinflammatory diseases that mostly present in childhood and are characterized by recurrent, self-limiting, seemingly unprovoked episodes of fever and systemic inflammation that occur in the absence of autoantibody production or identifiable infection. Disorders include (1) familial Mediterranean fever (FMF), due to mutation in the gene encoding pyrin; (2) tumour necrosis factor (TNF) receptor associated periodic syndrome (TRAPS), due to mutation in a gene for a TNF receptor; (3) Mevalonate kinase deficiency and period fever (MKD), caused by mutations in the mevalonate kinase gene; and (4) the cryopyrin associated periodic syndromes (CAPS), which include (a) familial cold urticarial syndrome, (b) Muckle–Wells syndrome, and (c) chronic infantile neurological, cutaneous and articular syndrome. Understanding of the molecular pathogenesis of these disorders provides unique insights into the regulation of innate immunity and inflammation....

scholarly journals Familial Mediterranean Gene (MEFV) Mutation in Parents of Children with Familial Mediterranean Fever: What Are the Exceptions?

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Leila Shahbaznejad ◽  
Sayed-Reza Raeeskarami ◽  
Raheleh Assari ◽  
Abbas Shakoori ◽  
Hamidreza Azhideh ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Periodic Fever ◽  
Mefv Gene ◽  
Cross Sectional Study ◽  
Compound Heterozygote ◽  
Mefv Mutation ◽  
Cross Sectional ◽  
Fever Syndromes ◽  
History Of ◽  
Mediterranean Fever

Objectives. Familial Mediterranean Fever (FMF) is one of the most prevalent periodic fever syndromes; MEFV, the responsible gene for the disease, is in the short arm of chromosome16. In the considerable count of the FMF patients, only one mutation is found in the MEFV and parents, who were the obligatory carriers for that mutation, were asymptomatic. The aim of this study was to evaluate these asymptomatic parents in regard to mutation in MEFV gene and similarity between parents and offspring patients. Methods. In this cross-sectional study, asymptomatic parents of FMF patients enrolled the study were referred to periodic fever clinic or pediatric rheumatology clinic of Tehran University of Medical Sciences. The patients should have at least one mutation in MEFV gene and none of them had any family history of autoinflammatory disease. Twelve mutations in MEFV gene were assessed in the parents by Vienna Lab FMF Strip Assay kit by MAS PCR/Reverse hybridization. Results. Forty-three patients and their parents participated in the study. Sixty-three percent (27) of patients were male. Onset of disease symptoms in 31 patients (72%) was before 4 years of old. Nine (21%) of the patients had homozygote, 16 (37%) compound heterozygote, and 17(40%) heterozygote for MEFV mutation; there was a case of complex alleles mutations (2%). M694V/M694V in 4 patients (9%) was the most homozygote genotype, and M694V/R761H in 4 (9%) and E148Q in 7 (16%) were the most compound heterozygote and heterozygote genotype, respectively. M694V, M680I, and E148Q were the most mutation in the parents. Overall, 41 patients had mutations similar to their parents’ mutation, except 2 whose parents had no mutation, but a patient did. Conclusion. It seems that occurrence of new mutations in offspring is not prevalent among FMF patients and there are other reasons for different clinical presentation in similar mutation carriers. On the other hand, in ethnicities with high prevalence of FMF, new mutation in descendant may occur, infrequently.

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