المؤلفون: Michaela Brichova, Aneta Klimova, Jarmila Heissigerova, Petra Svozilkova, Manuela Vaneckova, Pavla Dolezalova, Dana Nemcova, Marcela Michalickova, Jana Jedlickova, Lubica Dudakova, Petra Liskova

المصدر: Genes, Vol 15, Iss 6, p 799 (2024)

مصطلحات موضوعية: Blau syndrome, early onset sarcoidosis, uveitis, NOD2, autoinflammation, neurosarcoidosis, Genetics, QH426-470

الوصف: The aim of this study was to describe the clinical and molecular genetic findings in seven individuals from three unrelated families with Blau syndrome. A complex ophthalmic and general health examination including diagnostic imaging was performed. The NOD2 mutational hot spot located in exon 4 was Sanger sequenced in all three probands. Two individuals also underwent autoinflammatory disorder gene panel screening, and in one subject, exome sequencing was performed. Blau syndrome presenting as uveitis, skin rush or arthritis was diagnosed in four cases from three families. In two individuals from one family, only camptodactyly was noted, while another member had camptodactyly in combination with non-active uveitis and angioid streaks. One proband developed two attacks of meningoencephalitis attributed to presumed neurosarcoidosis, which is a rare finding in Blau syndrome. The probands from families 1 and 2 carried pathogenic variants in NOD2 (NM_022162.3): c.1001G>A p.(Arg334Gln) and c.1000C>T p.(Arg334Trp), respectively. In family 3, two variants of unknown significance in a heterozygous state were found: c.1412G>T p.(Arg471Leu) in NOD2 and c.928C>T p.(Arg310*) in NLRC4 (NM_001199139.1). In conclusion, Blau syndrome is a phenotypically highly variable, and there is a need to raise awareness about all clinical manifestations, including neurosarcoidosis. Variants of unknown significance pose a significant challenge regarding their contribution to etiopathogenesis of autoinflammatory diseases.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2073-4425/15/6/799Test; https://doaj.org/toc/2073-4425Test

الوصول الحر: https://doaj.org/article/c98878a6b1f7490aa0f850fb73890ce5Test

المؤلفون: Gabriel T. Doctor, Caroline Dudreuilh, Ranmith Perera, Anthony Dorling

المصدر: Journal of Clinical Medicine, Vol 13, Iss 12, p 3427 (2024)

مصطلحات موضوعية: granulomatous tubulointerstitial nephritis, early-onset sarcoidosis, cryopyrin-associated periodic syndrome, interleukin-6 antagonist, tocilizumab, clazakizumab, Medicine

الوصف: Granulomatous tubulointerstitial nephritis (GTIN) attributed to early onset sarcoidosis is an ultrarare finding in an allograft kidney biopsy. We present the case of a young man with allograft dysfunction who had GTIN upon biopsy. We performed a thorough case review based on recovered records from early childhood and reassessed genetic testing results. We revised his underlying diagnosis from cryopyrin-associated periodic syndrome to early-onset sarcoidosis with wild-type NOD2 and established a rationale to use the interleukin-6 (IL-6) receptor blocker tocilizumab (TCZ). This suppressed his inflammatory disease and stabilised kidney function. We performed a literature review related to the emerging role of IL-6 pathway blockade in kidney transplantation. We identified 18 reports with 417 unique patients treated with TCZ for indications including HLA-desensitisation, transplant immunosuppression induction, treatment of chronic antibody-mediated rejection, and treatment of subclinical rejection. Both TCZ and the direct IL-6 inhibitor clazakizumab are being studied in ongoing randomised control trials.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2077-0383/13/12/3427Test; https://doaj.org/toc/2077-0383Test

الوصول الحر: https://doaj.org/article/9936c23f21e94c1690a202ba0e67b080Test

المؤلفون: ZHENG Yi, JIA Tao, YAN Cong, ZHANG Xinyue, DU Xueshan, ZHOU Tong, SONG Xiangjin, GENG Songmei

المصدر: 罕见病研究, Vol 2, Iss 2, Pp 170-177 (2023)

مصطلحات موضوعية: blau syndrome, early-onset sarcoidosis, clinical manifestations, histopathology features, gene mutation diversity, Medicine

الوصف: Objective To summarize the clinical manifestations, pathological features and gene mutation diversity of Blau syndrome/early-onset sarcoidosis. Methods We collected general data, clinical manifestations, and auxiliary examination results from 8 patients who were diagnosed of Blau syndrome/early-onset sarcoidosis and treated in our hospital from January 2011 to December 2022, and then summarized and analyzed their characteristics and diversity. Results Among the 8 patients, 4 were males and 4 were females. The onset age was 3 to 8 months old. Rash was the first symptom in 7 patients(87.5%). 6 patients(75.0%) had papules and erythema.3 cases(37.5%) had arthritis. 2 cases(25.0%) had uveitis and other eye inflammation. 4 cases (50.0%) also showed intermittent fever. 3 cases (37.5%) showed symptoms in nerve and respiratory system, and hypertension respectively. The skin histopathology of 8 patients showed non-caseous granuloma formation. In laboratory detection, CRP and TNF-α were significantly increased before treatment, while IL-6, IL-8, TNF-α and IL-2 receptor(IL-2R) were significantly decreased in 5 patients after glucocorticoid therapy. The results of genetic testing showed that 4 of the 7 patients had p.R334W(c.1000C > T) mutation, 1 had p.H313R(c.938A > G) and p.R471C(c.1411C > T)double mutation, and 1 had p.476_477del (c.1427_1429delcct). Conclusions Blau syndrome/early-onset sarcoidosis has significant features in clinical manifestations, histopathology and gene mutation, but it also has diversity.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2097-0501Test

الوصول الحر: https://doaj.org/article/67132f2102494857bcf6d01668dfc2b3Test

المؤلفون: Mary Ellen Jensen, Katelin Harrell, Jeffrey D. McBride

المصدر: Frontiers in Immunology, Vol 14 (2023)

مصطلحات موضوعية: Blau syndrome, early-onset sarcoidosis, hydroxychloroquine, methotrexate, arthritis, Immunologic diseases. Allergy, RC581-607

الوصف: Mutations in nucleotide binding oligomerization domain containing 2 receptor (NOD2) are associated with Blau syndrome (also known as early-onset sarcoidosis)—a rare autosomal dominant, chronic granulomatous disease that typically presents before 5 years of age. Blau syndrome is characterized by the clinical triad of arthritis, granulomatous dermatitis, and recurrent uveitis. Here, we report a case of NOD2-mutation-associated early-onset sarcoidosis in which a combination of methotrexate and hydroxychloroquine was used to achieve improvement in arthritis, granulomatous dermatitis, and uveitis. A 13-month-old boy presented with a sudden-onset cutaneous eruption affecting the face, trunk, and extremities that initially mimicked papular atopic dermatitis but progressively worsened despite topical steroid therapy. The patient had no other known medical comorbidities or abnormalities except for heterochromia of the right eye. However, prior to presentation to dermatology, the patient began experiencing frequent falls, conjunctival injection, and apparent eye and joint pain. Skin biopsy from the right shoulder demonstrated rounded aggregates of epithelioid histiocytes and multinucleated giant cells without a significant lymphocytic component (“naked granulomas”), consistent with sarcoidal granulomatous dermatitis. Given the concern for Blau syndrome, the patient was sent for evaluation by ophthalmology and was found to have bilateral subconjunctival nodules. Our patient underwent genetic testing and was found to have a mutation in codon 1000 C > T (protein R334W) in the NOD2 gene. The patient responded to oral prednisolone 2 mg/kg/day for 8 weeks, but quickly relapsed, requiring a second 8-week course with taper upon starting methotrexate 7.5 mg subcutaneously weekly with 1 mg folic acid orally daily. After 8 weeks on methotrexate, due to persistent arthritis, conjunctival injection, and pruritus, and in consultation with rheumatology, the patient was started on hydroxychloroquine 75 mg orally daily along with continuation of 7.5 mg methotrexate subcutaneously weekly for 8 weeks, achieving significant reduction in arthritis, pruritus, and uveitis. After 8 weeks of this combination therapy, due to concerns of long-term macular toxicity, hydroxychloroquine was discontinued in favor of continuing methotrexate alone. The patient has remained free of significant side effects and stable with good disease control on 7.5 mg methotrexate weekly injected subcutaneously.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1279329/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/6637fac02dff4bb89185fe5c3353cce4Test

المؤلفون: Coad Thomas Dow, Nancy W. Lin, Edward D. Chan

المصدر: Microorganisms; Volume 11; Issue 4; Pages: 829

مصطلحات موضوعية: sarcoidosis, Mycobacterium avium subsp. paratuberculosis, MAP, non-caseating granuloma, caseating granuloma, Blau syndrome, early onset sarcoidosis, Crohn’s disease, cell wall deficient (CWD), L-form, Mycobacterium tuberculosis, acid-fast bacilli, SLC11a1 ( NRAMP1 ), NOD2 ( CARD15 )

جغرافية الموضوع: agris

الوصف: Clinical and histological similarities between sarcoidosis and tuberculosis have driven repeated investigations looking for a mycobacterial cause of sarcoidosis. Over 50 years ago, “anonymous mycobacteria” were suggested to have a role in the etiology of sarcoidosis. Both tuberculosis and sarcoidosis have a predilection for lung involvement, though each can be found in any area of the body. A key histopathologic feature of both sarcoidosis and tuberculosis is the granuloma—while the tuberculous caseating granuloma has an area of caseous necrosis with a cheesy consistency; the non-caseating granuloma of sarcoidosis does not have this feature. This article reviews and reiterates the complicity of the infectious agent, Mycobacterium avium subsp. paratuberculosis (MAP) as a cause of sarcoidosis. MAP is involved in a parallel story as the putative cause of Crohn’s disease, another disease featuring noncaseating granulomas. MAP is a zoonotic agent infecting ruminant animals and is found in dairy products and in environmental contamination of water and air. Despite increasing evidence tying MAP to several human diseases, there is a continued resistance to embracing its pleiotropic roles. “Who Moved My Cheese” is a simple yet powerful book that explores the ways in which individuals react to change. Extending the metaphor, the “non-cheesy” granuloma of sarcoidosis actually contains the difficult-to-detect “cheese”, MAP; MAP did not move, it was there all along.

وصف الملف: application/pdf

العلاقة: Medical Microbiology; https://dx.doi.org/10.3390/microorganisms11040829Test

الإتاحة: https://doi.org/10.3390/microorganisms11040829Test

المؤلفون: Brichova, Michaela, Klimova, Aneta, Heissigerova, Jarmila, Svozilkova, Petra, Vaneckova, Manuela, Dolezalova, Pavla, Nemcova, Dana, Michalickova, Marcela, Jedlickova, Jana, Dudakova, Lubica, Liskova, Petra

المصدر: Genes (Basel) ; ISSN:2073-4425 ; Volume:15 ; Issue:6

مصطلحات موضوعية: Blau syndrome, NOD2, autoinflammation, early onset sarcoidosis, neurosarcoidosis, uveitis

الوصف: The aim of this study was to describe the clinical and molecular genetic findings in seven individuals from three unrelated families with Blau syndrome. A complex ophthalmic and general health examination including diagnostic imaging was performed. The NOD2 mutational hot spot located in exon 4 was Sanger sequenced in all three probands. Two individuals also underwent autoinflammatory disorder gene panel screening, and in one subject, exome sequencing was performed. Blau syndrome presenting as uveitis, skin rush or arthritis was diagnosed in four cases from three families. In two individuals from one family, only camptodactyly was noted, while another member had camptodactyly in combination with non-active uveitis and angioid streaks. One proband developed two attacks of meningoencephalitis attributed to presumed neurosarcoidosis, which is a rare finding in Blau syndrome. The probands from families 1 and 2 carried pathogenic variants in NOD2 (NM_022162.3): c.1001G>A p.(Arg334Gln) and c.1000C>T p.(Arg334Trp), respectively. In family 3, two variants of unknown significance in a heterozygous state were found: c.1412G>T p.(Arg471Leu) in NOD2 and c.928C>T p.(Arg310*) in NLRC4 (NM_001199139.1). In conclusion, Blau syndrome is a phenotypically highly variable, and there is a need to raise awareness about all clinical manifestations, including neurosarcoidosis. Variants of unknown significance pose a significant challenge regarding their contribution to etiopathogenesis of autoinflammatory diseases.

العلاقة: https://doi.org/10.3390/genes15060799Test; https://pubmed.ncbi.nlm.nih.gov/38927735Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11203189Test/

الإتاحة: https://doi.org/10.3390/genes15060799Test
https://pubmed.ncbi.nlm.nih.gov/38927735Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11203189Test/

المؤلفون: Akiko Arakawa, Naotomo Kambe, Ryuta Nishikomori, Akiyo Tanabe, Masamichi Ueda, Chikako Nishigori, Yoshiki Miyachi, Nobuo Kanazawa

المصدر: Children; Volume 8; Issue 2; Pages: 117

مصطلحات موضوعية: NOD 2, Blau syndrome, early-onset sarcoidosis, lichen scrofulosorum, BCG vaccination

الوصف: 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.

وصف الملف: application/pdf

العلاقة: Pediatric Allergy and Immunology; https://dx.doi.org/10.3390/children8020117Test

الإتاحة: https://doi.org/10.3390/children8020117Test

المؤلفون: Shaoling Zheng, Pui Y. Lee, Yukai Huang, Aiwu Wang, Tianwang Li

المصدر: Frontiers in Pediatrics, Vol 7 (2019)

مصطلحات موضوعية: giant cell tumor of tendon sheath, tendinopathy, early onset sarcoidosis, Blau syndrome, tumor, Pediatrics, RJ1-570

الوصف: Giant cell tumor of tendon sheath (GCTTS) is characterized by diffuse proliferation of synovial-like cells and multinucleated giant cells along tendon sheaths. This benign tumor typically presents in the third to fourth decade of life and is exceeding rare in children. Here we describe a case of a 10-years-old girl with a history of soft tissue swelling involving the third digit of left hand, bilateral wrists and ankles. Pathology of the finger mass revealed abundant multinucleated giant cells consistent with GCTTS. Resection of the tendinous masses from the ankles also showed multinucleated giant cells along with chronic bursitis. She began to show features of polyarticular arthritis by age 7. Due to progression of arthritis, whole exome sequencing was performed and found a de novo heterozygous mutation in NOD2 (p. R334Q). This variant is the most common mutation responsible for early onset sarcoidosis (EOS)/Blau syndrome, an autoinflammatory disease characterized by granulomatous inflammation of joints, skin and eyes. The early onset of symptoms and presence of multinucleated giant cells and granuloma in this case are in keeping with a diagnosis of EOS/Blau syndrome. The patient responded well to treatment with methotrexate and etanercept. This case extends the clinical spectrum of EOS/Blau syndrome, which should be considered for GCTTS and other unusual presentations of tendon inflammation in children, even in the absence of the characteristic triad of arthritis, dermatitis and uveitis.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/article/10.3389/fped.2019.00480/fullTest; https://doaj.org/toc/2296-2360Test

الوصول الحر: https://doaj.org/article/98d1d0b8c37547d2a8d85571198ae3c8Test

المؤلفون: Brian Chiu, Jackie Chan, Sumit Das, Zainab Alshamma, Consolato Sergi

المصدر: Diagnostics; Volume 9; Issue 4; Pages: 160

مصطلحات موضوعية: Paediatric sarcoidosis, high-risk sarcoidosis, early-onset sarcoidosis, diagnostics, Blau syndrome

الوصف: Sarcoidosis is a non-necrotizing granulomatous inflammatory syndrome with multisystemic manifestations. We performed a systematic review of sarcoidosis in the pediatric population with particular emphases on early onset sarcoidosis, high-risk sarcoidosis, and newly reported or unusual sarcoid-related diseases. Blau Syndrome and early onset sarcoidosis/ BS-EOS are seen in children younger than five years old presenting with extra-thoracic manifestations but usually without lymphadenopathy and/or pulmonary involvement. The prevalence of high-risk sarcoidosis is very low in children and is further limited by the difficulty of diagnosis in symptomatic children and underdiagnosis in subclinical or asymptomatic patients. Reports of sarcoidal syndromes in users of E-cigarette/marijuana/other flavorings and their induction in cancer immunotherapies are of interests and may be challenging to differentiate from metastatic malignancy. The diagnostic considerations in pediatric sarcoidosis are to support a compatible clinicoradiographic presentation and the pathologic findings of non-necrotizing granulomas by ruling out granulomas of infective etiology. There is no absolutely reliable diagnostic test for sarcoidosis at present. The use of endoscopic bronchial ultrasound (EBUS) and transbronchial fine needle aspiration (TBNA) sampling of intrathoracic lymph nodes and lung, and for superficially accessible lesions, with cytopathological assessment and pathological confirmations provide fair diagnostic yield and excellent patient safety profile in children.

وصف الملف: application/pdf

العلاقة: Pathology and Molecular Diagnostics; https://dx.doi.org/10.3390/diagnostics9040160Test

الإتاحة: https://doi.org/10.3390/diagnostics9040160Test

المؤلفون: Woojoong Kim, Eujin Park, Yo Han Ahn, Jiwon M. Lee, Hee Gyung Kang, Byung Joo Kim, Il-Soo Ha, Hae Il Cheong

المصدر: Korean Journal of Pediatrics, Vol 59, Iss Suppl 1, Pp S5-S9 (2016)

مصطلحات موضوعية: Blau syndrome, Early-onset sarcoidosis, Single nucleotide polymorphism, Nucleotide oligomerization domain 2, Pediatrics, RJ1-570

الوصف: Blau syndrome (BS) is a rare autosomal dominant, inflammatory syndrome that is characterized by the clinical triad of granulomatous dermatitis, symmetric arthritis, and recurrent uveitis. Mutations in the nucleotide oligomerization domain 2 (NOD2) gene are responsible for causing BS. To date, up to 30 Blau-associated genetic mutations have been identified within this gene. We report a novel NOD2 genetic mutation that causes BS. A girl, aged 8 years, and her brother, aged 10 years, developed erythematous skin rashes and uveitis. The computed tomography angiogram of the younger sister showed features of midaortic dysplastic syndrome. The brother had more prominent joint involvement than the sister. Their father (38 years) was also affected by uveitis; however, only minimal skin involvement was observed in his case. The paternal aunt (39 years) and her daughter (13 years) were previously diagnosed with sarcoidosis. Mutational analysis revealed a novel c.1439 A>G mutation in the NOD2 gene in both siblings. The novel c.1439 A>G mutation in the NOD2 gene was found in a familial case of BS. Although BS is rare, it should always be considered in patients presenting with sarcoidosis-like features at a young age. Early diagnosis of BS and prompt multisystem workup including the eyes and joints can improve the patient's outcome.

وصف الملف: electronic resource

العلاقة: http://kjp.or.kr/upload/pdf/kjped-59-S5.pdfTest; https://doaj.org/toc/1738-1061Test; https://doaj.org/toc/2092-7258Test

الوصول الحر: https://doaj.org/article/f2fef62ccfad4550b4b0283ebf951a39Test