scholarly journals A Three-Generation Muckle-Wells Syndrome Family: Detailed Family History, Physical Examination, and Inter-Departmental Collaboration

2022 ◽  
Author(s):  
Daigo Kato ◽  
Fumiya Yamaide ◽  
Issei Kida ◽  
Yoshinari Takasaki ◽  
Noriko Sato ◽  
...  
Keyword(s):  
Family History ◽  
Treatment Effectiveness ◽  
Laboratory Data ◽  
Pathogenic Mutation ◽  
Heterozygous Mutation ◽  
Nlrp3 Gene ◽  
Inflammatory Reactions ◽  
Eye Symptoms ◽  
Wells Syndrome ◽  
Specific Symptoms

Abstract Cryopyrin-associated periodic syndrome (CAPS) is a rare inherited autoinflammatory disease caused by gain-of-function mutations in the NLRP3 gene, with a genotype-phenotype correlation. The clinical presentation of each mutation has been previously studied. However, very few studies have reported on the clinical characteristics and treatment effectiveness across different generations within a family with the same mutation. A detailed investigation of family members of patients with CAPS may help in the appropriate diagnosis and treatment of undiagnosed CAPS. Herein, we report a 2-year-old boy (proband), his father, and his grandmother who presented with several symptoms of CAPS, such as persistently positive inflammatory reactions and hearing impairment. All three patients had the same pathogenic mutation in the NLRP3 gene (c.1049C>T (p.Thr350Met) heterozygous mutation) and were diagnosed with CAPS. With canakinumab treatment, the laboratory data of all three patients improved, the proband and father’s skin rash disappeared, and his grandmother’s arthropathy improved. The proband’s hearing also showed slight improvement, but not in his father or grandmother. Among the various non-specific symptoms associated with CAPS, chronic ocular hyperemia is a finding that can be easily identified by non-ophthalmologists. Diagnosis of CAPS should be considered when eye symptoms are present in a combination of hyperinflammatory response, arthropathy, or skin symptoms. Thorough family history records, physical examinations, and close collaboration between pediatricians and adult rheumatologists are important for prompt diagnosis and appropriate treatment of inherited autoinflammatory diseases.

scholarly journals SAT0539 MUCKLE-WELLS SYNDROME IN RHEUMATOLOGY PRACTICE, FAMILY CASES: FEDERAL CENTER EXPERIENCE.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1227.1-1227
Author(s):  
S. Salugina ◽  
E. Fedorov ◽  
K. Elena ◽  
E. Zakharova ◽  
S. Palshina
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Autoinflammatory Disease ◽  
Family Members ◽  
Sensorineural Hearing ◽  
Nlrp3 Gene ◽  
Oral Ulcers ◽  
Family Medical History ◽  
Wells Syndrome ◽  
Rheumatology Practice

Background:Muckle-Wells syndrome (MWS) is a monogenic autoinflammatory disease caused by a NLRP3 gene mutation. It is the most common variant of cryopyrin-associated periodic syndromes (CAPSs) and can be observed in rheumatology practice. It manifests itself in fever, urticaria-like rash, arthralgias/arthritides, conjunctivitis/uveitis, sensorineural hearing loss, acute-phase markers (ESR, CRP). The disease’s onset usually takes place in infancy. There are examples of family cases. Targeted therapy: interleukin-1 inhibitors (anakinra, canakinumab).Objectives:to provide characteristics of MWS patients, family cases in the rheumatology practice of the Federal Rheumatology Center in Russia.Methods:in a 10-year period (2009 to 2019), MWS was diagnosed in 42 outpatient and inpatient patients, among them were 24 children, 18 adults, and 9 family cases. All of them underwent a standard rheumatology examination, including a ECR, CRP, ophthalmologist examination, and an audiogram. A molecular genetic test of the NLRP3 gene was carried out for all patients, the diagnosis was confirmed in all of them.Results:Out of 18 adult patients aged between 19 and 59 years, women were prevalent (16 to 2), the onset age was 0 to 53 years, in 88,9% cases the onset took place before a patient was 18 years old. When diagnosed, the disease duration varied from 6 to 46 years. Most patients demonstrated fever, urticarial-like rash, arthralgias/arthritides, which were observed in 16 patients (88.9%), conjunctivitides were observed in 15 patients (83,3%), sensorineural hearing loss – in 8 patients (44,4%), abdominal pain, nausea, vomiting – in 4 patients, headache, dizziness – in 6 patients. There also were rare manifestations, such as: recurrent oral ulcers (8), genital ulcers (3), erythema nodosum (3), sore throat and raids on the tonsils (PFAPA-like phenotype) was observed in 2 patients. In 3 patients manifestations were triggered by cold temperature. All patients had an increased ESR and C-reactive protein concentration. Eight family cases of MWS were identified (in total 26 family members aged between 2.5 and 62 years) with a number of affected in one family ranging from 2 to 6 people of different age (8 children, 18 adults, out of which 20 were female, and 6 were male). Most patients had fever (17), urticarial-like rash (18), conjunctivitides (12), oral ulcers (7), articular syndrome (14), sensorineural hearing loss (5), and 2 patients died of renal insufficiency (probably due to amyloidosis of the kidneys). The heterozygous mutations in NLRP3 have been identified in pts: T348M (3 families), R262W (2 families), A439V (1), V198M (1), Pro294Ser (1). Ten patients received canakinumab for a period of 6 months to 6.5 years, and 5 patients received anakinra before canakinumab.Conclusion:MWS is an orphan autoinflammatory disease, however it sometimes can be observed in rheumatology practice. It is very important to acquire family medical history to identify affected family members and prescribe therapy in a timely manner. IL-1 inhibitors are an effective and safe treatment option for MWS patients.Disclosure of Interests:None declared

scholarly journals AB1010 CLINICAL SPECTRUM AND IMMUNE ANALYSIS OF PATIENTS WITH CRYOPYRIN-ASSOCIATED AUTOINFLAMMATORY SYNDROME IN TAIWAN

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1798.1-1798
Author(s):  
C. Y. Wu ◽  
P. S. Chu ◽  
H. Y. Yang
Keyword(s):  
Genetic Variants ◽  
Medical Center ◽  
Laboratory Data ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Medical Intervention ◽  
Stimulation Test ◽  
Autoinflammatory Diseases ◽  
Missense Mutations ◽  
Autoinflammatory Syndrome ◽  
Nlrp3 Gene

Background:Cryopyrin-associated periodic syndromes (CAPS) are emerging autoinflammatory diseases with available treatment. No reports have yet been reported from Taiwan.Objectives:We reviewed cases suspected with CAPS to identify its existence in Taiwan.Methods:Genomic DNA from one hundred and ten cases with symptom signs suggestive of CAPS(1) between 2016-2019 were sent for NLRP3 gene analysis. Clinical presentations, laboratory data, treatment regimens, as well as inflammasome activities were analyzed among those treated in a tertiary medical center in northern Taiwan.Results:Among the 110 cases sequenced, 16 of them were found to carry missense mutations within the NLRP3 gene. Fourteen cases harbored known pathogenic genetic variants (c.1316C>T; c.1574A>T; and c.907G>C) and two carried novel NLRP3 missense mutations (c.210G>A, c.1371G>T)(2) with unknown pathophysiological roles. Through chart review, chronic urticarial, systemic juvenile idiopathic arthritis, Behcet’s disease and refractory Kawasaki disease were most likely diagnosed before genetic analysis were arranged. As compared to chronic infantile neurological, cutaneous and articular syndrome (CINCA) and Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS) was the most frequently observed clinical presentation. Plasma serumamyloidA (SAA) and IL-1b were both significantly elevated among the cases diagnosed with CAPS as compared to the controls (p<0.05). IL-18, on the other hand, showed no significant differences between the groups. While the presence of LPS without ATP significantly increased the level of IL-1b in the PBMC stimulation test, IL-18 were significantly elevated in the confirmed CAPS with or without ATP upon LPS stimulation (all p<0.05). Caspase 1 activity were also tested positive among the cases with CAPS. Furthermore, we compared the immune profiles between those CAPS cases harboring pathogenic mutations with the 2 harboring unreported NLRP3 missense mutations and discovered that the PBMC stimulation test in cases with c.210G>A and c.1371G>T mutation did not differ from the healthy controls.Conclusion:The number of NLRP3 gene alterations among patients suspected with CAPS in Taiwan is not low. In order to identify potential patients for proper medical intervention in the future, physician awareness, genetic testing as well as functional analysis are important.References:[1]Kuemmerle-Deschner JB, Ozen S, Tyrrell PN, Kone-Paut I, Goldbach-Mansky R, Lachmann H, et al. Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS). Ann Rheum Dis. 2017;76(6):942-7.[2]Van Gijn ME, Ceccherini I, Shinar Y, Carbo EC, Slofstra M, Arostegui JI, et al. New workflow for classification of genetic variants’ pathogenicity applied to hereditary recurrent fevers by the International Study Group for Systemic Autoinflammatory Diseases (INSAID). J Med Genet. 2018;55(8):530-7Disclosure of Interests:Chao-Yi Wu Speakers bureau: Abbvie, Boehringer Ingelheim International GmbH, Nestle, Pi-Shuang Chu: None declared, Huang-Yu Yang: None declared

A Practical Approach to Pediatric Patients Referred With an Abnormal Coagulation Profile

2005 ◽  
Vol 129 (8) ◽  
pp. 1011-1016 ◽  
Author(s):  
Monica Acosta ◽  
Rachel Edwards ◽  
E. Ian Jaffe ◽  
Donald L. Yee ◽  
Donald H. Mahoney ◽  
...  
Keyword(s):  
Family History ◽  
Positive Family History ◽  
Laboratory Data ◽  
Bleeding Risk ◽  
Personal History ◽  
Retrospective Case ◽  
Laboratory Assessment ◽  
Repeat Testing ◽  
Effective Manner ◽  
History Of

Abstract Context.—Workup for prolonged prothrombin time (PT) and activated partial thromboplastin time (PTT) is a frequent referral to a Hematology and Coagulation Laboratory. Although the workup should be performed in a timely and cost-effective manner, the complete laboratory assessment of the coagulation state has not been standardized. Objective.—To determine which clinical and laboratory data are most predictive of a coagulopathy and to formulate the most efficient strategy to reach a diagnosis in patients referred for abnormal coagulation profiles. Design.—Retrospective case review. Medical records of 251 patients referred for prolonged PT and/or PTT to our Hematology Service between June 1995 and December 2002 were reviewed. Results.—The study included 135 males and 116 females with a mean age of 7.0 years. A personal history of bleeding was reported in 137 patients, and a family history of bleeding was reported in 116 patients. Fifty-one patients (20%) had a coagulopathy (ie, a bleeding risk). Factors predictive of a bleeding risk were a positive family history of bleeding (P &lt; .001) and a positive personal history of bleeding (P = .001). Of 170 patients with findings of normal PT and PTT values on repeat testing, 14 were subsequently diagnosed with a coagulopathy. Two of these patients reported no positive personal or family history of bleeding. Conclusions.—Coagulopathy was identified in 20% of the children referred for abnormal PT and/or PTT. In the absence of a personal or family history of bleeding, a normal PT and/or PTT on repeat testing has a negative predictive value of more than 95%.

scholarly journals Clinical and Laboratory Profiles of 75 Hospitalized Patients with Novel Coronavirus Disease 2019 in Hefei, China

2020 ◽  
Author(s):  
Zonghao Zhao ◽  
Jiajia Xie ◽  
Ming Yin ◽  
Yun Yang ◽  
Hongliang He ◽  
...  
Keyword(s):  
T Cell ◽  
Treatment Effectiveness ◽  
Antiviral Treatment ◽  
Laboratory Data ◽  
Clinical Manifestations ◽  
Nasopharyngeal Swab ◽  
The Novel ◽  
Reactive Protein ◽  
Cell Counts ◽  
Novel Coronavirus

AbstractThe outbreak of the novel coronavirus disease 2019 (COVID-19) infection began in December 2019 in Wuhan, and rapidly spread to many provinces in China. The number of cases has increased markedly in Anhui, but information on the clinical characteristics of patients is limited. We reported 75 patients with COVID-19 in the First Affiliated Hospital of USTC from Jan 21 to Feb 16, 2020, Hefei, Anhui Province, China. COVID-19 infection was confirmed by real-time RT-PCR of respiratory nasopharyngeal swab samples. Epidemiological, clinical and laboratory data were collected and analyzed. Of the 75 patients with COVID-19, 61 (81.33%) had a direct or indirect exposure history to Wuhan. Common symptoms at onset included fever (66 [88.0%] of 75 patients) and dry cough (62 [82.67%]). Of the patients without fever, cough could be the only or primary symptom. The most prominent laboratory abnormalities were lymphopenia, decreased percentage of lymphocytes (LYM%), decreased CD4+ and CD8+ T cell counts, elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH). Patients with elevated interleukin 6 (IL-6) showed significant decreases in the LYM%, CD4+ and CD8+ T cell counts. Besides, the percentage of neutrophils, CRP, LDH and Procalcitonin levels increased significantly. We concluded that COVID-19 could cause different degrees of hematological abnormalities and damage of internal organs. Hematological profiles including LYM, LDH, CRP and IL-6 could be indicators of diseases severity and evaluation of treatment effectiveness. Antiviral treatment requires a comprehensive and supportive approach. Further targeted therapy should be determined based on individual clinical manifestations and laboratory indicators.

scholarly journals GOUGEROT-HAILEY-HAILEY’S FAMILIAL BENIGN CHRONIC PEMPHIGUS: A CASE REPORT

2019 ◽  
Vol 22 (3-4) ◽  
pp. 86-92
Author(s):  
O. V Grabovskaya ◽  
N. P Teplyuk ◽  
Yuliya V. Kolesova
Keyword(s):  
Case Report ◽  
Family History ◽  
Clinical Case ◽  
Treatment Effectiveness ◽  
Diagnosis And Treatment ◽  
Review Of The Literature ◽  
Ozone Therapy ◽  
Treatment Methods

The review of the literature on epidemiology, pathogenesis, diagnosis and treatment methods for chronic familial benign pemphigus Gougerot-Haley-Haley, as well as a clinical case of a patient with this disease with family history are presented. The manifestation of the disease occurred at the age of 24, after childbirth. Later there were numerous relapses. Remission was quickly achieved after treatment with antibiotics and oxygen-ozone therapy. In recent years, there has been an increase in the frequency of exacerbations of the disease, and a decrease in treatment effectiveness.

scholarly journals Syndecan-1, an indicator of endothelial glycocalyx degradation, predicts outcome of patients admitted to an ICU with COVID-19

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Dong Zhang ◽  
Liubing Li ◽  
Yu Chen ◽  
Jie Ma ◽  
Yanli Yang ◽  
...  
Keyword(s):  
Laboratory Data ◽  
Endothelial Damage ◽  
Endothelial Glycocalyx ◽  
Rank Test ◽  
Inflammatory Reactions ◽  
Log Rank Test ◽  
Survivor Group ◽  
Kaplan Meier ◽  
Factor Α ◽  
Necrosis Factor

Abstract Background We investigated the feasibility of two biomarkers of endothelial damage (Syndecan-1 and thrombomodulin) in coronavirus disease 2019 (COVID-19), and their association with inflammation, coagulopathy, and mortality. Methods The records of 49 COVID-19 patients who were admitted to an intensive care unit (ICU) in Wuhan, China between February and April 2020 were examined. Demographic, clinical, and laboratory data, and outcomes were compared between survivors and non-survivors COVID-19 patients, and between patients with high and low serum Syndecan-1 levels. The dynamics of serum Syndecan-1 levels were also analyzed. Results The levels of Syndecan-1 were significantly higher in non-survivor group compared with survivor group (median 1031.4 versus 504.0 ng/mL, P = 0.002), and the levels of thrombomodulin were not significantly different between these two groups (median 4534.0 versus 3780.0 ng/mL, P = 0.070). Kaplan–Meier survival analysis showed that the group with high Syndecan-1 levels had worse overall survival (log-rank test: P = 0.023). Patients with high Syndecan-1 levels also had significantly higher levels of thrombomodulin, interleukin-6, and tumor necrosis factor-α. Data on the dynamics of Syndecan-1 levels indicated much greater variations in non-survivors than survivors. Conclusions COVID-19 patients with high levels of Syndecan-1 develop more serious endothelial damage and inflammatory reactions, and have increased mortality. Syndecan-1 has potential for use as a marker for progression or severity of COVID-19. Protecting the glycocalyx from destruction is a potential treatment for COVID-19.

scholarly journals A Case of a Child with an APC Pathogenic Mutation, Aberrant Expression of Splice Variants and Positive Family History of FAP

2014 ◽  
Vol 44 (6) ◽  
pp. 602-606 ◽  
Author(s):  
Keiko Taki ◽  
Yasuyoshi Sato ◽  
Yuri Sato ◽  
Yuumi Ashihara ◽  
Akiko Chino ◽  
...  
Keyword(s):  
Family History ◽  
Splice Variants ◽  
Positive Family History ◽  
Pathogenic Mutation ◽  
Aberrant Expression ◽  
History Of

DNA repair germline pathogenic mutation associations with treatment duration and family history in prostate cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 245-245
Author(s):  
James Vu ◽  
Marcus Marie Moses ◽  
Lahiru Ranasinghe ◽  
Patrick Cotogno ◽  
Charlotte Manogue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Dna Repair ◽  
Family History ◽  
Treatment Outcomes ◽  
Treatment Duration ◽  
Pathogenic Mutation ◽  
Germline Mutations ◽  
Cancer Type ◽  
History Of

245 Background: Germline mutation testing for metastatic prostate cancer patients creates a potential opportunity to personalize targeted therapies to improve treatment outcomes. The goal of this study was to characterize cancer family history, and evaluate treatment outcomes, in mCRPC patients with DNA repair pathogenic germline alterations. Methods: A retrospective study of metastatic PCa patients at Tulane Cancer Center identified 246 patients undergoing germline testing using panels (30-80 genes) (Color.com or Inviate.com). Clinical annotations included family history, life-extending treatments, and treatment duration. Statistical analyses including chi-square and Wilcoxon Rank Sum. Results: In the 246 patients tested for germline mutations, 27 patients (11.0%) had ≥1 DNA repair germline pathogenic mutation (BRCA2 = 11, BRCA1 = 3, CHEK2 = 5, ATM = 3, NBN = 1, PMS2 = 2, MSH2 = 1, PALB2 = 1) while 219 patients (89.0%) possessed no pathogenic mutation in these genes. Patients with a DNA repair pathogenic mutation were more likely to have > 2 family members affected by cancer, regardless of cancer type or degree of relationship (p = 0.04). In the DNA repair population, 5 pathogenic patients had no family history of cancer (18.5%, n = 5). Patients were more likely to have a germline alteration if they had 1 or more first degree relatives affected with breast cancer (p = 0.00001). Median lines of life-extending treatments to date between the pathogenic and non-pathogenic population were equal at 2. There were no significant differences in treatment duration for abiraterone (p = 0.49), enzalutamide (p = 0.99), docetaxel (p = 0.28), cabazitaxel (p = 0.53), carboplatin+docetaxel (p = 0.41), or radium-223 (p = 0.59) between the two groups. Conclusions: In this study, DNA repair pathogenic germline mutations did not affect treatment durations or lines of therapy but these studies are underpowered. The relationship between a family history of breast cancer and a DNA repair pathogenic mutation has not previously been reported.

scholarly journals Granulocyte-Colony Stimulating Factor–Producing Gallbladder Carcinoma

2014 ◽  
Vol 99 (5) ◽  
pp. 577-583 ◽  
Author(s):  
Kazuhiro Suzumura ◽  
Yuji Iimuro ◽  
Yasukane Asano ◽  
Nobukazu Kuroda ◽  
Tadamichi Hirano ◽  
...  
Keyword(s):  
Gallbladder Carcinoma ◽  
General Condition ◽  
Fdg Pet ◽  
Leukocyte Count ◽  
Laboratory Data ◽  
Right Hemicolectomy ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Inflammatory Reactions ◽  
Stimulating Factor

Abstract A 78-year-old man was admitted to our hospital with right upper abdominal pain and fever. His general condition was poor. The laboratory data showed severe inflammatory reactions. Computed tomography revealed an irregular tumor in the gallbladder. 18F-fluorodeoxy-glucose positron emission tomography (FDG-PET) showed high uptake by the tumor, with diffuse uptake in the spine. Based on the elevated leukocyte count and FDG-PET findings, a granulocyte-colony stimulating factor (G-CSF)–producing tumor was diagnosed (G-CSF 120 pg/mL). We performed cholecystectomy with central bisegmentectomy of the liver, lymph node dissection and right hemicolectomy. Histologically, the tumor was an adenosquamous cell carcinoma of the gallbladder. Immunohistochemical staining of the tumor cells was positive for G-CSF. Postoperatively, the general condition of the patient was improved. The fever subsided, the leukocyte count and serum G-CSF level normalized, and FDG-PET showed no uptake in the spine postoperatively. The patient showed no signs of recurrence at 27 months after undergoing surgery. FDG-PET is a useful method for diagnosing G-CSF–producing gallbladder carcinoma. Aggressive curative resection for G-CSF–producing gallbladder carcinoma may improve patients' general condition and prognosis.

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