BLAU SYNDROME OR MONOGENOUS SARCOIDOSIS WITH EARLY ONSET: RUSSIAN COHORT OF PATIENTS

2021 ◽  
Vol 100 (5) ◽  
pp. 99-109
Author(s):  
E.S. Fedorov ◽  
◽  
S.O. Salugina ◽  
A.N. Shapovalenko ◽  
E.Yu. Zakharova ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Clinical Picture ◽  
Autoinflammatory Disease ◽  
Age Of Onset ◽  
Decisive Role ◽  
Pathogenic Mutation ◽  
Skin Lesions ◽  
Posterior Uveitis ◽  
Blau Syndrome ◽  
Card15 Gene

Blau syndrome (BS) is a rare monogenic granulomatous autoinflammatory disease (a variant of genetically determined sarcoidosis) caused by a mutation of the NOD2/CARD15 gene, transmitted in an autosomal dominant manner and manifested by a triad of signs: dermatitis, granulomatous arthritis with pronounced exudative component and involvement of periarticular tissues, uveitis. Objective of the study: to present the variants of the clinical picture and the type of pathogenic variants (mutations) in patients with a rare monogenic granulomatous autoinflammatory disease – BS – in the Russian Federation, the clinical picture of which can mimic juvenile idiopathic arthritis. Materials and methods of research: the observational study included patients with BS who were observed in the children's department of the V.A. Nasonova Research Institute of Rheumatology from 2014 to 2021, the diagnosis of which was confirmed by the detection of a pathogenic mutation in the NOD2/CARD15 gene. Results: the study included 8 children: 6 boys and 2 girls. Ethnic Russians were 5 patients, 1 Jew, 1 of mixed origin (peoples of Dagestan/Russians), 1 Tatar female. The age of onset of the disease is from the first days of life to 2,5 years. Skin lesions were observed in 6 (75%) patients. Atypical arthritis (boggy arthritis) was observed in all patients, in all cases the wrist, ankle and knee joints were involved in the pathological process. Uveitis developed after all other manifestations and was detected in 6 (75%) patients. At the onset, 5 patients had anterior uveitis, 2 of them with subsequent involvement of the posterior segment; in 1 child, the first ophthalmic manifestation was posterior uveitis. In 5 patients, there was no increase in acute phase markers (ESR, C-reactive protein). 5 (62,5%) patients had variant p.R334Q (c.1001G>A), 2 (25%) had variant p.R334W (c.1001G>A), 1 patient had variant p.M513T (c.1538T>C) of the NOD2/CARD15 gene. Conclusions: BS can be encountered in the practice of a pediatric rheumatologist in Russia and requires differentiation from polyarticular juvenile idiopathic arthritis. Identification of the pathogenic variant of the NOD2/CARD15 gene plays a decisive role in the diagnosis.

scholarly journals AB0996 FAMILY CASE OF BLAU SYNDROME IN 3 CHILDREN, INITIALLY DIAGNOSED AS JUVENILE IDIOPATHIC ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1791.1-1791
Author(s):  
I. Nikishina ◽  
S. Arsenyeva ◽  
E. Fedorov ◽  
V. Matkava ◽  
A. Shapovalenko ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Clinical Picture ◽  
De Novo ◽  
Specific Treatment ◽  
Blau Syndrome ◽  
Molecular Genetic Study ◽  
The Family ◽  
Family Case ◽  
Card15 Gene ◽  
Genetic Assay

Background:Juvenile Idiopathic Arthritis (JIA) is heterogeneous group of diseases which may include genetically determined conditions. Extremely rare monogenic hereditary autoinflammatory disease, such as Blau syndrome (BS) is usually difficult to recognize and JIA is initially established. BS is caused by a mutation in the NOD2/CARD5 gene and phenotypically characterized by triad of granulomatosis polyarthritis, uveitis and skin rash.Objectives:To present the family case of genetically confirmed BS in 2 siblings, initially diagnosed as patients with JIA.Methods:Two brothers of 15 and 3 years old were examined in our clinic. Additional genetic assay was performed because of unusual clinical picture.Results:Case report.Older brother, 15 y.o. developed arthritis of both wrist joints at the age of two. There was erythematous maculo-micropapular scaly rash on the trunk and extremities before the onset of arthritis. By 2009 (5 y.o.), the knees, ankles, and three PIP joints of the left hand were involved. Polyarthritis was characterized by severe effusion and periarticular tissues swallowing. He was treated in regional hospital by NSAID, methotrexate, cyclosporine A without significant positive effect. Since 2012 etanercept was added for treatment with variable result. Inactive status of the disease is never reached. Repeated intra-articular GC injections were needed from 4 to 10 times per year. The patient was admitted to our clinic in November 2019. He was suffering from severe polyarthritis and uveitis de novo (granulomatous chorioretinitis) was detected. At the same time his younger 3 y. o. brother with recently started disease was hospitalized in our clinic. He had polyarthritis with typical features of “boggy” synovitis and tenosynovitis of wrists, ankles and knees, anterior uveitis was determined. The onset of arthritis was preceded by a small-spotted rash with desquamation. This classical clinical features in younger brother let us suggest the BS. There was no increasing of ESR and CRP in both sibs throughout the course of the disease. A molecular genetic study of the NOD2/CARD15 gene in both brothers revealed the same mutation of c.1001G>A (p. Arg334Gln). Because of the absence of specific treatment for this disease and due to insufficient effect of etanercept with uveitis de novo therapy was changed to golimumab and good initial effect is reached. The youngest brother has started his therapy by methotrexate. It should be noted that the family has the eldest brother (20 y.o.), who has been suffering from arthritis since an early childhood with similar clinical picture. We are going to perform genetic analysis of the NOD2/CARD15 gene for the eldest brother.Conclusion:Our clinical case shows that extremely rare BS may be misdiagnosed as JIA. Lack of efficacy of the etanercept therapy and uveitis de novo developing may be caused by genetic (non-idiopathic) nature of disease. Classic triad of boggy-arthritis, granulomatous uveitis and/or skin lesions without acute phase markers is required to perform genetic assay for the detection of a pathogenic mutation of the NOD2/CARD15 gene. This case is remarkable by the presence of BS in two (or 3) children of the family.References:[1]Wouters C.H, Maes A, Foley K, et al. Blau Syndrome, the prototypic auto-inflammatory granulomatous disease. Pediatric Rheumatology. 2014; 12: 33.Disclosure of Interests:None declared

scholarly journals NOD2 Mutation-Associated Case with Blau Syndrome Triggered by BCG Vaccination

Children ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 117
Author(s):  
Akiko Arakawa ◽  
Naotomo Kambe ◽  
Ryuta Nishikomori ◽  
Akiyo Tanabe ◽  
Masamichi Ueda ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Topical Corticosteroid ◽  
Genetic Background ◽  
Skin Lesions ◽  
Blau Syndrome ◽  
Nod2 Mutation ◽  
Bcg Vaccination ◽  
Cystic Tumors ◽  
Ophthalmologic Examination ◽  
Inflammatory Changes

We describe a patient who developed multiple granulomatous skin lesions after Bacille de Calmette et Guérin (BCG) vaccination without significant effect by topical corticosteroid, followed by painless cystic tumors on the bilateral knees and hands and inflammatory changes on ophthalmologic examination. A functional mutation in NOD2 was detected by a genetic analysis, and he was diagnosed as sporadic Blau syndrome. Since NOD2 acts as a sensor for the BCG component, it is possible that BCG vaccination may trigger granuloma formation in Blau syndrome patients with such genetic background.

Molecular pathogenesis and clinical implications of eczema herpeticum

2008 ◽  
Vol 10 ◽  
Author(s):  
Caroline Bussmann ◽  
Wen-Ming Peng ◽  
Thomas Bieber ◽  
Natalija Novak
Keyword(s):  
Atopic Dermatitis ◽  
Age Of Onset ◽  
Current Knowledge ◽  
Allergen Challenge ◽  
Skin Lesions ◽  
Molecular Pathogenesis ◽  
Type I Interferons ◽  
Total Serum ◽  
Type I ◽  
Eczema Herpeticum

A subgroup of patients with atopic dermatitis develops one or more episodes of a severe viral skin infection caused by herpes simplex virus superimposed on eczematous skin lesions. This condition is named atopic dermatitis complicated by eczema herpeticum. Characteristic features of patients developing eczema herpeticum include an early age of onset of atopic dermatitis with a persistent and severe course into adulthood, predilection for eczematous skin lesions in the head and neck area, elevated total serum IgE levels and increased allergen sensitisation. Deficiencies at the level of both the innate and the adaptive immune system, which have been identified in atopic dermatitis, are much more pronounced in this subgroup. Predisposing cellular factors include a reduced number of plasmacytoid dendritic cells in the epidermis and a modified capacity of these cells to produce type I interferons after allergen challenge. In addition, lower levels of antimicrobial peptides in the skin of atopic dermatitis patients, resulting in part from a Th2-prone micromilieu, contribute to the lack of an effective defence against viral attack. In this review, we summarise the current knowledge of the molecular pathogenesis of eczema herpeticum.

The first scientific meeting of the doctors of the Yelabuga District Hospital dated March 20, 1934

1934 ◽  
Vol 30 (5) ◽  
pp. 477-478
Keyword(s):  
Abdominal Aorta ◽  
Clinical Picture ◽  
District Hospital ◽  
Decisive Role ◽  
Scientific Meeting ◽  
Spontaneous Abortions ◽  
Cardiac Defect

Dr. Ter-Ayrapetyan G.S. Demonstrated a patient with lupus erytematdes. Localization and clinical picture of the disease are usual. But the patient undoubtedly has hereditary syphilis. Anamnesis: progressive paralysis in the mother, four spontaneous abortions, guttschinsonism, cardiac defect with sharply pronounced early vascular sclerosis, especially of the abdominal aorta. This circumstance prompted the speaker to hold the idea that hereditary syphilis played a decisive role in the etiology of this disease.

scholarly journals Does multilocus inherited neoplasia alleles syndrome have severe clinical expression?

2018 ◽  
Vol 56 (8) ◽  
pp. 521-525 ◽  
Author(s):  
Agostina Stradella ◽  
Jesús del Valle ◽  
Paula Rofes ◽  
Lídia Feliubadaló ◽  
Èlia Grau Garces ◽  
...  
Keyword(s):  
Hereditary Cancer ◽  
Age Of Onset ◽  
Clinical Manifestations ◽  
Pathogenic Mutation ◽  
Gene Panel ◽  
Cancer Genes ◽  
Pathogenic Mutations ◽  
Predisposing Genes ◽  
Definition Of ◽  
Gene Panels

ImportanceGenetic testing of hereditary cancer using comprehensive gene panels can identify patients with more than one pathogenic mutation in high and/or moderate-risk-associated cancer genes. This phenomenon is known as multilocus inherited neoplasia alleles syndrome (MINAS), which has been potentially linked to more severe clinical manifestations.ObjectiveTo determine the prevalence and clinical features of MINAS in a large cohort of adult patients with hereditary cancer homogeneously tested with the same gene panel.Patients and methodsA cohort of 1023 unrelated patients with suspicion of hereditary cancer was screened using a validated panel including up to 135 genes associated with hereditary cancer and phakomatoses.ResultsThirteen (1.37%) patients harbouring two pathogenic mutations in dominant cancer-predisposing genes were identified, representing 5.7% (13/226) of patients with pathogenic mutations. Most (10/13) of these cases presented clinical manifestations associated with only one of the mutations identified. One case showed mutations in MEN1 and MLH1 and developed tumours associated with both cancer syndromes. Interestingly, three of the double mutants had a young age of onset or severe breast cancer phenotype and carried mutations in moderate to low-risk DNA damage repair-associated genes; two of them presented biallelic inactivation of CHEK2. We included these two patients for the sake of their clinical interest although we are aware that they do not exactly fulfil the definition of MINAS since both mutations are in the same gene.Conclusions and relevanceGenetic analysis of a broad cancer gene panel identified the largest series of patients with MINAS described in a single study. Overall, our data do not support the existence of more severe manifestations in double mutants at the time of diagnosis although they do confirm previous evidence of severe phenotype in biallelic CHEK2 and other DNA repair cancer-predisposing genes.

scholarly journals Prevalence, clinical features and treatment pattern of patients with concurrent diagnoses of rheumatoid arthritis and psoriatic disease: results of a 14-year retrospective study in a tertiary referral center

2019 ◽  
Vol 10 ◽  
pp. 204062231984790
Author(s):  
Kai-Lung Chen ◽  
Hsien-Yi Chiu ◽  
Jui-Hsiang Lin ◽  
Jian-De Ye ◽  
Yi-Hsuan Cho ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Features ◽  
Age Of Onset ◽  
Medical Center ◽  
Skin Lesions ◽  
Tertiary Referral ◽  
Female Ratio ◽  
Tertiary Referral Center ◽  
Referral Center ◽  
Psoriatic Disease

Background: Multiple comorbidities, including rheumatoid arthritis (RA), have been reported to be associated with psoriasis. Objective: This study aimed to determine the prevalence and the clinical features of RA among patients with psoriasis in a tertiary referral center. Methods: Between January 2000 and December 2013, all patients coded with psoriatic disease (ICD-9 CM 696.0 OR ICD-9 CM696.1) and RA (ICD-9 CM 714.0) in a tertiary medical center were enrolled. Results: There were 10,844 patients and 9073 patients with psoriatic disease and RA identified by diagnostic codes, respectively. Among patients with psoriasis, 111 patients had claim-based diagnosis of RA (1.02%). By reviewing medical records and telephone interview or clinic visits, 25 of the 111 patients (0.23%) was identified unequivocally as having concurrent RA. Among them, 17 (68%) were female and 16 (64%) patients developed arthritis prior to the onset of psoriasis with a mean lag of 6.3 years (1–19 years); 8 (32%) had psoriasis skin lesions prior to the onset of arthritis with a mean lag of 6.9 years (3–20 years); 1 (4%) had skin lesions and arthritis in the same time; 17 (68%) patients also fulfilled the CASPAR classification criteria for psoriatic arthritis. The mean age of onset for arthritis was 49.6 years old. Conclusions: The prevalence of RA in psoriasis might be overestimated in some previous studies using claimed database. Patients with concurrent RA and psoriasis showed a comparable age of onset and male to female ratio, but had more axial involvements compared to patients without psoriasis.

scholarly journals A gyermekkori uveitis klinikai jellemzői és terápiája

2019 ◽  
Vol 160 (34) ◽  
pp. 1335-1339
Author(s):  
Judit Kiss ◽  
Valéria Gaál ◽  
Zoltán Nyul ◽  
Bernadett Mosdósi
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Autoimmune Diseases ◽  
Single Case ◽  
Severe Disease ◽  
Significant Proportion ◽  
Middle Layer ◽  
Underlying Disease ◽  
Posterior Uveitis ◽  
Study Data ◽  
Multidisciplinary Cooperation

Abstract: Introduction: Uveitis is characterized by inflammation of the middle layer of the eye. Its overall incidence is low. Autoimmune diseases and infections are the most common underlying diseases. Out of the autoimmune diseases, juvenile idiopathic arthritis is associated most frequently with uveitis. The topical ophthalmological treatment may fail in a significant proportion of the patients and immunomodulatory therapy may be required. Aim and method: In a retrospective study, data of 33 children diagnosed and treated with uveitis at the Department of Pediatrics and Ophthalmology, University of Pécs during the last 5 years were collected and analyzed. Results: The mean age of the patients was 9.3 (0.3–17.8) years. Boys and girls were equally affected with an exception of patients with juvenile idiopathic arthritis where female predominance was found. An underlying disease could be identified in 60% of the cases (20/33). Uveitis was associated in 12 patients with juvenile idiopathic arthritis, in 2 patients with Behcet’s disease and in a single case with inflammatory bowel disease. Infections have been proven in 5 patients. The autoimmune diseases caused an eye inflammation typically in anterior localization, in contrast to the infections that resulted in posterior uveitis. The majority of the patients required systemic treatment. 3 of them received systemic corticosteroid and 18 patients methotrexate as disease-modifying antirheumatic drug. 13 children with severe disease activity required biological therapy (adalimumab injection). Remission could be achieved in 1.45 (0.75–2.5) months. Conclusion: Pediatric uveitis is of great importance. Early diagnosis, adequate therapy and follow-up require multidisciplinary cooperation. Orv Hetil. 2019; 160(34): 1335–1339.

Prior knowledge of the clinical picture does not introduce bias in the histopathologic diagnosis of melanocytic skin lesions

2015 ◽  
Vol 42 (12) ◽  
pp. 953-958 ◽  
Author(s):  
Gerardo Ferrara ◽  
Giorgio Annessi ◽  
Zsolt Argenyi ◽  
Giuseppe Argenziano ◽  
Helmut Beltraminelli ◽  
...  
Keyword(s):  
Prior Knowledge ◽  
Clinical Picture ◽  
Skin Lesions ◽  
Histopathologic Diagnosis

scholarly journals CANDLE Syndrome: Case Report of a Rare Type of Auto- Inflammatory Disease

2021 ◽  
Vol 44 (3) ◽  
pp. 174-177
Author(s):  
Md Asif Ali ◽  
Mohammad Imnul Islam ◽  
Shahana Akhtar Rahman
Keyword(s):  
Case Report ◽  
Autoinflammatory Disease ◽  
Failure To Thrive ◽  
Skin Lesions ◽  
Recurrent Fever ◽  
Rare Type ◽  
Auto Inflammatory Disease ◽  
Laboratory Investigations ◽  
Generalized Lymphadenopathy ◽  
Psmb8 Gene

CANDLE syndrome (chronic atypical neutophilic dermatosis with lipodystrophy and elevated temperature) is an autoinflammatory disease/syndrome characterized by recurrent fever, skin lesions, and multisystem inflammatory manifestations. Most of the patients have shown mutation in PSMB8 gene. Here, we report a 9-year-old girl with recurrent fever, atypical facies, widespread skin lesions, generalized lymphadenopathy, hepato-splenomegaly, lipodystrophy, and failure to thrive. Considering the clinical features and laboratory investigations including skin biopsy findings, diagnosis was consistent with CANDLE syndrome. Therefore, it is recommended to consider CANDLE syndrome in a young child who presents with recurrent fever, characteristics rashes, organomegaly and failure to thrive. Bangladesh J Child Health 2020; VOL 44 (3) :174-177

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