Distinguishing Blau Syndrome from Systemic Sarcoidosis

Kaufman, Katherine; Becker, Mara L.

doi:10.1007/s11882-021-00991-3

Cited by 29 publications

(37 citation statements)

References 94 publications

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“…As a prototypic autoinflammatory granulomatous disease, dermatitis, polyarthritis, and uveitis are the classical triad of BS/EOS with rash being the first feature [ 1 , 2 , 15 ]. Usually painless and non-pruritic, non-caseating granulomas is the typical findings seen in skin biopsy of BS/EOS and our index case [ 5 ]. This is different from the caseating granulomas seen in CGD, ANCA-associated vasculitis and granuloma forming infections, such as tuberculosis, leprosy, atypical mycobacteria, or fungal infection [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…More than 200 cases of BS/EOS have been reported worldwide since its first discovery [ 5 ]. While many of the cases presented with its classical triad, variability of clinical features between cases harboring different NOD2 mutations was noted [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…While many of the cases presented with its classical triad, variability of clinical features between cases harboring different NOD2 mutations was noted [ 10 ]. Overlapping clinical features of BS/EOS with other inflammatory and granulomatous conditions such as juvenile idiopathic arthritis (JIA), systemic sarcoidosis, anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, mycobacterial infection and chronic granulomatous disease (CGD) can sometimes complicate the diagnosis [ 5 , 10 , 11 ]. NOD2 genetic testing is recommended for the diagnosis of cases suspicious of BS/EOS [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Incomplete penetrance of NOD2 C483W mutation underlining Blau syndrome

et al. 2022

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Background Blau syndrome (BS) is a rare autoinflammatory disorder with NOD2 gain-of-function mutation and characterized by autoactivation of the NFκB pathway. Classically considered a disease of high penetrance, reports on NOD2 mutations underlining BS with incomplete penetrance is limited. Case presentation The proband is a 9-year-old girl presented with brownish annular infiltrative plaques and symmetric boggy polyarthritis over bilateral wrists and ankles. Her skin biopsy revealed noncaseating granulomas inflammation with multinucleated giant cells. A novel C483W NOD2 mutation was identify in the proband and her asymptomatic father. Functional examinations including autoactivation of the NFκB pathway demonstrated by in vitro HEK293T NOD2 overexpression test as well as intracellular staining of phosphorylated-NFκB in patient’s CD11b+ cells were consistent with BS. Conclusions We reported a novel C483W NOD2 mutation underlining BS with incomplete penetrance. Moreover, a phosphorylated-NFκB intracellular staining assay of CD11b+ was proposed to assist functional evaluation of NFκB autoactivation in patient with BS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Incomplete penetrance of NOD2 C483W mutation underlining Blau syndrome

et al. 2022

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“… 93 Diagnosis is made definitively by genetic testing confirming a disease-causing mutation of NOD2 , and is supported by the presence of noncaseating granulomas on biopsy of skin lesions or affected synovia. 94 …”

Section: Imaging In Pediatric Uveitismentioning

confidence: 99%

Multimodal imaging in pediatric uveitis

et al. 2021

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Pediatric uveitis accounts for up to 10% of all uveitis cases, so special attention must be paid to ensure early diagnosis as well as treatment and follow-up of these young patients in order to decrease the risk of possible ocular complications and consequently vision loss. Multimodal imaging has been an effective and important adjunct in the diagnoses and management of uveitis, especially in children. Reviewed here are the currently utilized modalities, advances, as well as their applications in juvenile idiopathic arthritis–associated uveitis, pars planitis, retinal vasculitis, tubulointerstitial nephritis and uveitis syndrome, Behçet disease, Blau syndrome, and Vogt–Koyanagi–Harada syndrome.

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“…The clinical features in these cases were the absence of bilateral hilar lymphadenopathy, and the presence of joint symptoms. Hence, these cases were occasionally referred to as early-onset sarcoidosis (EOS), and the difference from idiopathic sarcoidosis debated ( 8 ). Initially no gene abnormalities were found in two solitary cases of EOS ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

Potential Benefits of TNF Targeting Therapy in Blau Syndrome, a NOD2-Associated Systemic Autoinflammatory Granulomatosis

et al. 2022

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Blau syndrome is a systemic autoinflammatory granulomatous disease caused by mutations in the nucleotide-binding oligomerization domain 2 (NOD2) gene. NOD2 is an intracellular pathogen recognition receptor. Upon binding to muramyl dipeptide (MDP), NOD2 activates the NF-κB pathway, leading to the upregulation of proinflammatory cytokines. Clinical manifestations of Blau syndrome appear in patients before the age of four. Skin manifestations resolve spontaneously in some cases; however, joint and eye manifestations are progressive, and lead to serious complications, such as joint contracture and blindness. Currently, there is no specific curative treatment for the disease. Administration of high-dose oral steroids can improve clinical manifestations; however, treatments is difficult to maintain due to the severity of the side effects, especially in children. While several new therapies have been reported, including JAK inhibitors, anti-IL-6 and anti-IL-1 therapies, anti-TNF therapy plays a central role in the treatment of Blau syndrome. We recently performed an ex vivo study, using peripheral blood and induced pluripotent stem cells from patients. This study demonstrated that abnormal cytokine expression in macrophages from untreated patients requires IFNγ stimulation, and that anti-TNF treatment corrects the abnormalities associated with Blau syndrome, even in the presence of IFNγ. Therefore, although the molecular mechanisms by which the genetic mutations in NOD2 lead to granuloma formation remain unclear, it is possible that prior exposure to TNFα combined with IFNγ stimulation may provide the impetus for the clinical manifestations of Blau syndrome.

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Distinguishing Blau Syndrome from Systemic Sarcoidosis

Cited by 29 publications

References 94 publications

Incomplete penetrance of NOD2 C483W mutation underlining Blau syndrome

Incomplete penetrance of NOD2 C483W mutation underlining Blau syndrome

Multimodal imaging in pediatric uveitis

Potential Benefits of TNF Targeting Therapy in Blau Syndrome, a NOD2-Associated Systemic Autoinflammatory Granulomatosis

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