Clinical Features at Onset and Genetic Characterization of Pediatric and Adult Patients with TNF-α Receptor—Associated Periodic Syndrome (TRAPS): A Series of 80 Cases from the AIDA Network

This study explores demographic, clinical, and therapeutic features of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in a cohort of 80 patients recruited from 19 Italian referral Centers. Patients’ data were collected retrospectively and then analyzed according to age groups (disease onset before or after 16 years) and genotype (high penetrance (HP) and low penetrance (LP) TNFRSF1A gene variants). Pediatric- and adult-onset were reported, respectively, in 44 and 36 patients; HP and LP variants were found, respectively, in 32 and 44 cases. A positive family history for recurrent fever was reported more frequently in the pediatric group than in the adult group (p<0.05). With reference to clinical features during attacks, pericarditis and myalgia were reported more frequently in the context of adult-onset disease than in the pediatric age (with p<0.01 and p<0.05, respectively), while abdominal pain was present in 84% of children and in 25% of adults (p<0.01). Abdominal pain was significantly associated also to the presence of HP mutations (p<0.01), while oral aphthosis was more frequently found in the LP variant group (p<0.05). Systemic amyloidosis occurred in 25% of subjects carrying HP variants. As concerns laboratory features, HP mutations were significantly associated to higher ESR values (p<0.01) and to the persistence of steadily elevated inflammatory markers during asymptomatic periods (p<0.05). The presence of mutations involving a cysteine residue, abdominal pain, and lymphadenopathy during flares significantly correlated with the risk of developing amyloidosis and renal impairment. Conversely, the administration of colchicine negatively correlated to the development of pathologic proteinuria (p<0.05). Both NSAIDs and colchicine were used as monotherapy more frequently in the LP group compared to the HP group (p<0.01). Biologic agents were prescribed to 49 (61%) patients; R92Q subjects were more frequently on NSAIDs monotherapy than other patients (p<0.01); nevertheless, they required biologic therapy in 53.1% of cases. At disease onset, the latest classification criteria for TRAPS were fulfilled by 64/80 (80%) patients (clinical plus genetic items) and 46/80 (57.5%) patients (clinical items only). No statistically significant differences were found in the sensitivity of the classification criteria according to age at onset and according to genotype (p<0.05). This study describes one of the widest cohorts of TRAPS patients in the literature, suggesting that the clinical expression of this syndrome is more influenced by the penetrance of the mutation rather than by the age at onset itself. Given the high phenotypic heterogeneity of the disease, a definite diagnosis should rely on both accurate working clinical assessment and complementary genotype.

Download Full-text

Multiple Sclerosis in Malaysia: Demographics, Clinical Features, and Neuroimaging Characteristics

Multiple Sclerosis International ◽

10.1155/2013/614716 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

S. Viswanathan ◽

N. Rose ◽

A. Masita ◽

J. S. Dhaliwal ◽

S. D. Puvanarajah ◽

...

Keyword(s):

Multiple Sclerosis ◽

Neuromyelitis Optica ◽

Demyelinating Disease ◽

Age At Onset ◽

Positive Family History ◽

Disease Onset ◽

Demyelinating Diseases ◽

Lesion Length ◽

Relapsing Remitting ◽

Spectrum Disorders

Background. Multiple sclerosis (MS) is an uncommon disease in multiracial Malaysia. Diagnosing patients with idiopathic inflammatory demyelinating diseases has been greatly aided by the evolution in diagnostic criterion, the identification of new biomarkers, and improved accessibility to neuroimaging in the country.Objectives. To investigate the spectrum of multiple sclerosis in Malaysia.Methods. Retrospective analysis with longitudinal follow-up of patients referred to a single tertiary medical center with neurology services in Malaysia.Results. Out of 245 patients with idiopathic inflammatory demyelinating disease, 104 patients had multiple sclerosis. Female to male ratio was 5 : 1. Mean age at onset was 28.6 ± 9.9 years. The Malays were the predominant racial group affected followed by the Chinese, Indians, and other indigenous groups. Subgroup analysis revealed more Chinese having neuromyelitis optica and its spectrum disorders rather than multiple sclerosis. Positive family history was reported in 5%. Optic neuritis and myelitis were the commonest presentations at onset of disease, and relapsing remitting course was the commonest disease pattern observed. Oligoclonal band positivity was 57.6%. At disease onset, 61.5% and 66.4% fulfilled the 2005 and 2010 McDonald’s criteria for dissemination in space. Mean cord lesion length was 1.86 ± 1.65 vertebral segments in the relapsing remitting group as opposed to 6.25 ± 5.18 vertebral segments in patients with neuromyelitis optica and its spectrum disorders.Conclusion. The spectrum of multiple sclerosis in Malaysia has changed over the years. Further advancement in diagnostic criteria will no doubt continue to contribute to the evolution of this disease here.

Download Full-text

Abstract TMP94: Frequencies of Hereditary Cerebral Small Vessel Diseases Among Patients With Adult-Onset Leukoencephalopathy

Stroke ◽

10.1161/str.51.suppl_1.tmp94 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Masahiro Uemura ◽

Hiroaki Nozaki ◽

Naoko Sakai ◽

Shouichirou Ando ◽

Masato Kanazawa ◽

...

Keyword(s):

White Matter ◽

Family History ◽

Small Vessel Disease ◽

Age At Onset ◽

Positive Family History ◽

Small Vessel ◽

Adult Onset ◽

Genetic Tests ◽

Neurological Signs ◽

White Matter Disorders

Introduction: Recently, various causative genes have been identified in adult-onset white matter disorders. Some of these genes cause cerebral small vessel disease (CSVD). However, the frequency of genetic CSVD is unknown in the group of adult-onset white matter disorders (leukoencephalopathy). The purpose of this study is to clarify the frequency of genetic CSVD in adult-onset leukoencephalopathy patients and to examine their clinical features. Methods: One hundred patients in the Japanese cohort were included. All patients had neurological symptoms/signs and white matter lesions of grade 3/III classified by Fazekas grade on magnetic resonance imaging. Initially, genetic tests for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), high-temperature requirement A serine peptidase 1 (HTRA1)- related CSVD and retinovasculopathy with cerebral leukoencephalopathy (RVCL) were performed by Sanger method. For the remaining samples, we preformed whole exome sequencing. Patients were divided into groups according to the age at onset of neurological signs/symptoms and family history. Results: In 40 of 100 patients with leukoencephalopathy, we identified genetic mutations that cause CSVD: twenty-five patients with CADASIL,10 patients with HTRA1 -related CSVD, 3 patients with pseudoxanthoma elasticum (PXE), 1 patient with RVCL, and 1 patient with a mutation in COL4A1 . More than 85% patients have mutations in NOTCH3 or HTRA1 . In addition, we identified 3 patients with vanishing white matter disease, and 1 patient with X-linked adrenoleukodystrophy. The hereditary CSVDs other than CADASIL or HTRA1 -related CSVD were identified in the groups of age at onset ≤ 40 years-old irrespective of family history or age at onset ≤ 55 years-old with family history. Conclusions: The frequencies of genetic CSVDs were quite high among patients with leukoencephalopathy with neurological signs/symptoms. Although the genetic tests for CADASIL and HTRA1- related CSVD are sufficient for the most patients, we should consider the other genetic diseases especially for the patients with younger age onset of neurological signs/symptoms or positive family history.

Download Full-text

Clinical Features in a Danish Population-Based Cohort of Probable Multiple System Atrophy Patients

Neuroepidemiology ◽

10.1159/000444325 ◽

2016 ◽

Vol 46 (4) ◽

pp. 261-267 ◽

Cited By ~ 6

Author(s):

Charlotte Starhof ◽

Lise Korbo ◽

Christina Funch Lassen ◽

Kristian Winge ◽

Søren Friis

Keyword(s):

Multiple System Atrophy ◽

Clinical Features ◽

Neurodegenerative Disorder ◽

Age At Onset ◽

Disease Onset ◽

Initial Response ◽

International Classification Of Diseases ◽

Population Based ◽

Classification Of Diseases ◽

Transient Improvement

Background: Multiple system atrophy (MSA) is a rare, sporadic and progressive neurodegenerative disorder. We aimed to describe the clinical features of Danish probable MSA patients, evaluate their initial response to dopaminergic therapy and examine mortality. Methods: From the Danish National Patient Registry, we identified 782 patients diagnosed with conditions potentially compatible with probable MSA (International Classification of Diseases, version 10 (ICD-10) codes G23.2, G23.8 and G23.9) during 1994-2009. Through medical record review, we narrowed our sample to 115 patients who fulfilled the criteria for probable MSA. We recorded clinical features, examined differences by MSA subtype and used Kaplan-Meier survival analysis to examine mortality. Results: The mean age at onset of patients with probable MSA was 60.2 years (range 36-75 years) and mean time to wheelchair dependency was 4.7 years (range 0-15 years). One-third of patients experienced a transient improvement in motor symptoms with use of levodopa. Median survival from disease onset was 6.9 years (range 1-16 years, 95% CI 6.3-7.5) with no apparent variation according to gender or subtype. Conclusions: Our nationwide approach corroborated that MSA is associated with diverse and grave symptoms, only limited response to levodopa, and poor prognosis.

Download Full-text

Association of age at onset and first symptoms with disease progression in patients with metachromatic leukodystrophy

Neurology ◽

10.1212/wnl.0000000000011047 ◽

2020 ◽

pp. 10.1212/WNL.0000000000011047 ◽

Cited By ~ 1

Author(s):

Christiane Kehrer ◽

Saskia Elgün ◽

Christa Raabe ◽

Judith Böhringer ◽

Stefanie Beck-Wödl ◽

...

Keyword(s):

Disease Progression ◽

Metachromatic Leukodystrophy ◽

Age At Onset ◽

Disease Onset ◽

Tube Feeding ◽

Motor Symptoms ◽

Cognitive Symptoms ◽

Adult Onset ◽

Clinical Genetic ◽

Language Functions

Objective:To compare disease progression between different onset forms of Metachromatic Leukodystrophy (MLD) and to investigate the influence of the type of first symptoms on the natural course and dynamic of disease progression.Methods:Clinical, genetic and biochemical parameters were analyzed within a nationwide study of patients with late-infantile (LI, onset ≤ 2.5 years), early-juvenile (EJ, onset 2.6 - < 6 years), late-juvenile (LJ, onset 6 – < 16 years), and adult (onset ≥ 16 years) forms of MLD. First symptoms were categorized as motor symptoms only, cognitive symptoms only, or both.. Standardized clinical endpoints included loss of motor and language functions, as well as dysphagia/tube feeding.Results:97 Patients with MLD were enrolled. Patients with LI (n=35) and EJ (n=18) MLD exhibited similarly rapid disease progression, all starting with motor symptoms (with or without additional cognitive symptoms). In LJ (n=38) and adult-onset (n=6) patients, the course of the disease was as rapid as in the early-onset forms, when motor symptoms were present at disease onset, while patients with only cognitive symptoms at disease onset exhibited significantly milder disease progression, independent of their age at onset. A certain genotype-phenotype correlation was observed.Conclusions:In addition to age at onset, the type of first symptoms predicts the rate of disease progression in MLD. These findings are important for counselling and therapy.Classification of Evidence:This study provides Class II evidence that in patients with MLD, age at onset and the type of first symptoms predict the rate of disease progression.

Download Full-text

Impact of Gender and Age-at-onset on Clinical and Medical Features of Rheumatoid Arthritis in Western Algerian Population

Zahedan Journal of Research in Medical Sciences ◽

10.5812/zjrms.108918 ◽

2021 ◽

Vol In Press (In Press) ◽

Author(s):

Siheme Ouali ◽

Khalida Zemri ◽

Khedoudja Kanoun ◽

Harir Noria ◽

Feriel Sellam ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Features ◽

Late Onset ◽

Age At Onset ◽

Laboratory Data ◽

Disease Onset ◽

University Hospital ◽

High Rate ◽

Algerian Population ◽

Gender And Age

Background: This study aimed to demonstrate the gender and age-at-onset differences in rheumatoid arthritis (RA) in the western Algerian population and their impacts on patients' clinical features and medical management. Methods: A retrospective cross-sectional study was carried out at the Internal Medicine and Functional Rehabilitation Departments (University Hospital of Sidi-bel-Abbes region) based on medical records of over 306 RA patients diagnosed between 2016 and 2019 according to ACR 1987 criteria. Late-onset RA (LORA) was deﬁned as disease onset at 51 years of age or older. All data were processed and analyzed via SPSS 22.0. Results: We enrolled 306 rheumatoid arthritis patients (85% women) with a mean age-at-onset of 52.47 ± 12.14. Algerian RA women were more at risk of developing type 2 diabetes (P = 0.035), hypertension (P = 0.003), and thyroid disorders (P = 0.05). We did not find any significant relationship between clinical features, laboratory data, and gender. The LORA group comprised 60.5% of our study population with a higher number of comorbidities such as hypertension (P < 0.001), osteoporosis (P = 0.007), and scleroderma (P = 0.014). Nonetheless, we found evidence of an association between positive anti-CCP, RF rate, and age-at-onset (P = 0.001 and P < 0.001, respectively). Conclusions: Algerian RA women with LORA presented a higher prevalence of comorbidities, while Young-onset RA (YORA) was associated with a high rate of RF.

Download Full-text

Effect of Age at Onset on Disease Characteristics in Vitiligo

Journal of Cutaneous Medicine and Surgery ◽

10.2310/7750.2013.12075 ◽

2013 ◽

Vol 17 (4) ◽

pp. 253-258 ◽

Cited By ~ 7

Author(s):

Amrinder J. Kanwar ◽

Rahul Mahajan ◽

Davinder Parsad

Keyword(s):

Early Onset ◽

Late Onset ◽

Statistical Significance ◽

Age At Onset ◽

Positive Family History ◽

Disease Onset ◽

Disease Characteristics ◽

The Difference ◽

Trauma Stress ◽

Distinguishing Features

Background: Vitiligo is a multifactorial disease in which genetic, immunologic, and environmental factors play an important part. Late-onset vitiligo is a poorly defined entity. Materials and Methods: Case records of patients who attended the pigmentary clinic at our institute from January 2001 to December 2010 were reviewed. Patients with a diagnosis of vitiligo were analyzed with respect to their demographic characteristics with special reference to their age at onset. Results: Patients with disease onset after 30 years had a significantly higher association with precipitating factors such as trauma, stress, and drugs in comparison with early-onset vitiligo ( p < .004). However, the difference did not reach statistical significance when these factors were analyzed individually. There was a significantly higher association with other nonautoimmune diseases ( p = .05), a higher incidence of positive family history ( p < .0001), and a higher association with leukotrichia ( p < .002) in late-onset disease. Early-onset nonsegmental vitiligo was associated with a higher incidence of photosensitivity and pruritus compared to early-onset segmental vitiligo. Conclusion: Late-onset vitiligo has certain distinguishing features compared to early-onset vitiligo.

Download Full-text

P161 A comparative study of childhood-onset SLE with adult-onset patients: a single centre study

Rheumatology ◽

10.1093/rheumatology/keab247.157 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Neil T Morton ◽

Zoe Rutter-Locher ◽

Maumar Durrani ◽

Shirish Sangle ◽

Nick Wilkinson ◽

...

Keyword(s):

Family History ◽

Renal Involvement ◽

Positive Family History ◽

Disease Onset ◽

Adult Onset ◽

Childhood Onset ◽

Number Of Patients ◽

Dsdna Antibody ◽

History Of ◽

Mixed Ethnicity

Abstract Background/Aims Childhood-onset SLE (cSLE) was once associated with significant mortality but 5-year survival rates have now improved significantly. We retrospectively compared the clinical features and outcomes of cSLE patients with an adult-onset SLE (aSLE) group. Methods We retrospectively studied data from 30 patients from our cSLE patients (onset before age 16) compared with 65 aSLE randomly selected in a 2:1 ratio, from our Lupus clinic patients fulfilling the 1997 ACR SLE criteria. Data regarding ethnicity, age of onset, family history, serology, complications, medications and outcomes were recorded. Results Of cSLE patients 24 were female and 6 male (F:M ratio 4:1), with 16 patients (53%) Afro-Caribbean, 8 Caucasian, 5 Asian and 1 of mixed ethnicity. In the aSLE group, 60 patients were female and 5 male (ratio 9:1), with 29 (44%) Afro-Caribbean, 13 Asian, 21 Caucasian and 2 of mixed ethnicity. Median age at disease onset was 14 years (10-16) in cSLE and 29 years (17-50) in aSLE. A positive family history of SLE was seen in 37% (11/30) of cSLE patients compared to 11% (7/65) of aSLE [p = 0.003]. There was no difference in family history of other autoimmune rheumatic diseases (10% vs 14% [p = 0.57]). Table 1 shows frequency of different autoantibodies, with anti-dsDNA and anti-cardiolipin antibodies significantly more frequent in the cSLE group [p = 0.017, p = 0.016 respectively]. Lupus nephritis appears to be more common in cSLE but not significantly (80% renal involvement vs 69% aSLE).There was no difference between involvement of chest, haematological, VTE or APS. Standard of care treatment was used in both groups, including oral prednisolone (>80% patients), anti-malarial and immunosuppressive medications. Renal flares were significantly more frequent in cSLE (23% vs 8%, [p = 0.027]). Of those deceased, only 1 was directly due to SLE. P161 Table 1:Serological markercSLE (n = 30)aSLE (n = 65)Number of patients%Number of patients%ANA2790%6498%dsDNA23*77%33*51%ENA1447%3655%RNP827%2335%Anti-Ro1033%2132%Anti-Sm827%1218%C1Q14**64%19**63%ACL17*57%20*31%LAC930%1828%RF517%69%Comparison of serological markers.*p < 0.05 (Chi-square used).**10 patients’ data missing. Conclusion More cSLE patients had a positive SLE family history and had higher anti-dsDNA antibody positivity compared to aSLE. Renal involvement was observed more commonly in cSLE than aSLE patients but was not statistically significant. Our results suggest that the cSLE cohort have a higher prevalence of specific lupus serology and a positive family history of SLE which may point towards more aggressive disease. Disclosure N.T. Morton: None. Z. Rutter-Locher: None. M. Durrani: None. S. Sangle: None. N. Wilkinson: None. D. D'Cruz: None.

Download Full-text

Validation of the new classification criteria for hereditary recurrent fever in an independent cohort: experience from the JIR Cohort Database

Rheumatology ◽

10.1093/rheumatology/keaa031 ◽

2020 ◽

Vol 59 (10) ◽

pp. 2947-2952

Author(s):

Glory Dingulu ◽

Sophie Georgin-Lavialle ◽

Isabelle Koné-Paut ◽

Pascal Pillet ◽

Anne Pagnier ◽

...

Keyword(s):

Periodic Fever ◽

Classification Criteria ◽

Recurrent Fever ◽

Mevalonate Kinase Deficiency ◽

Periodic Syndrome ◽

Mevalonate Kinase ◽

New Classification ◽

Clinical Criteria ◽

Clinical Variables ◽

Independent Cohort

Abstract Objective The new classification criteria for the hereditary recurrent fever (HRF) syndrome [cryopyrin-associated periodic syndrome (CAPS), TNF-α receptor-associated periodic syndrome (TRAPS), FMF and mevalonate kinase deficiency] have been published recently. These criteria define two core sets of criteria for each HRF: mixed criteria, including genetic and clinical variables, and clinical criteria, relying on clinical variables only. Our aim was to validate the criteria for HRF in an independent cohort, the JIR Cohort database, an international repository of systemic inflammatory diseases. Methods We enrolled patients with HRF, periodic fever, adenitis, pharyngitis and aphthous stomatitis syndrome (PFAPA) and syndrome of undefined recurrent fever (SURF). A score ranging from zero to two was attributed to their respective genotypes: zero (no mutation), one (non-confirmatory genotype) or two (confirmatory genotype). The criteria were applied to all patients based on genotype scoring. The treating physician’s diagnosis served as the gold standard for the determination of specificity. Results We included 455 patients. The classification criteria showed excellent specificity for CAPS and TRAPS (98% specificity each), fair specificity for FMF (88%), but poor specificity for mevalonate kinase deficiency (58%). Sub-analysis showed excellent accuracy of the mixed criteria for all four HRFs. Misclassification was mainly attributable to clinical criteria sets, with false-positive patients in all four HRF clinical criteria sets. Conclusion This study represents the final validation step of the HRF classification criteria as recommended by the ACR. Genetic data appear to be necessary to classify patients with HRF correctly.

Download Full-text

A polymyalgia rheumatica-mimicking case with young adult onset

Journal of Case Reports in Medicine ◽

10.25149/case-reports.v8i1.158 ◽

2019 ◽

Vol 8 (1) ◽

pp. 3

Author(s):

Shoichi Sasaki

Keyword(s):

Young Adult ◽

Clinical Features ◽

Polymyalgia Rheumatica ◽

Age Of Onset ◽

Morning Stiffness ◽

Disease Onset ◽

Steroid Treatment ◽

Dramatic Improvement ◽

Adult Onset ◽

Low Dosage

The diagnosis of polymyalgia rheumatica (PMR) is made primarily on clinical features and laboratory evidence of inflammation. Among the criteria for diagnosing PMR, disease onset at an age of 50 years or over is one of the major premises. The present case with 35-year-old onset showed clinical features of symmetric proximal myalgias (shoulder and pelvic girdle) with pronounced stiffness for more than 3 weeks, morning stiffness lasting more than 45 minutes combined with laboratory abnormalities (elevated CRP and ESR), and a dramatic improvement with steroid treatment at a low dosage (20mg/day), which is quite compatible with PMR except for the age of onset of the disease. This case shows that PMR-mimicking conditions can occur in patients even under 50 years of age.

Download Full-text

Clinical features of dystonia in atypical parkinsonism

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2008000600004 ◽

2008 ◽

Vol 66 (4) ◽

pp. 800-804 ◽

Cited By ~ 17

Author(s):

Clecio Godeiro-Junior ◽

Andre C. Felício ◽

Orlando G.P. Barsottini ◽

Patricia M. de Carvalho Aguiar ◽

Sonia M.A. Silva ◽

...

Keyword(s):

Clinical Features ◽

Disease Duration ◽

Age At Onset ◽

Disease Onset ◽

Corticobasal Degeneration ◽

Atypical Parkinsonism ◽

Resonance Imaging ◽

Yahr Scale ◽

Few Data ◽

Hand Dystonia

BACKGROUND: The association between Dystonia and Parkinson's disease (PD) has been well described especially for foot and hand dystonia. There is however few data on dystonic postures in patients with atypical parkinsonism. OBJECTIVE: To evaluate the frequency and pattern of dystonia in a group of patients with atypical parkinsonism (multiple system atrophy - MSA, progressive supranuclear palsy - PSP, and corticobasal degeneration - CBD) and to investigate whether dystonia could be the first presenting symptom at disease onset in those patients. METHOD: A total of 38 medical charts were reviewed (n=23/MSA group; n=7/CBD group; n=8/PSP group) and data values were described as means/standard deviations. The variables evaluated were sex, age at onset, disease duration, first symptom, clinical features of dystonia and other neurological signs, response to levodopatherapy, Hoehn&Yahr scale >3 after three years of disease, and magnetic resonance imaging findings. RESULTS: The overall frequency of dystonia in our sample was 50% with 30.4% (n=7) in the MSA group, 62.5% (n=5) in the PSP group, and 100% (n=8) in the CBD group. In none of these patients, dystonia was the first complaint. Several types of dystonia were found: camptocormia, retrocollis, anterocollis, blepharoespasm, oromandibular, and foot/hand dystonia. CONCLUSION: In our series, dystonia was a common feature in atypical parkinsonism (overall frequency of 50%) and it was part of the natural history although not the first symptom at disease onset. Neuroimaging abnormalities are not necessarily related to focal dystonia, and levodopa therapy did not influence the pattern of dystonia in our group of patients.

Download Full-text