Molecular genetic investigation, clinical features, and response to treatment in 21 patients with Schnitzler syndrome

Rowczenio, Dorota; Pathak, Shelly; Aróstegui, Juan I.; Mensa‐Vilaró, Anna; Omoyinmi, Ebun; Brogan, Paul A.; Lipsker, Dan; Scambler, Thomas; Owen, Roger G.; Trojer, H; Baginska, Anna; Gillmore, Julian D.; Wechalekar, Ashutosh; Lane, Thirusha; Williams, Ruth; Youngstein, Taryn; Hawkins, Philip N.; Savic, Sinisa; Lachmann, HJ

doi:10.1182/blood-2017-10-810366

Cited by 85 publications

(105 citation statements)

References 29 publications

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“…No germline pathogenic mutations have been identified so far in patients with Schnitzler syndrome, but somatic mosaicism of NLRP3 involving the myeloid lineage has been reported in two patients with variant Schnitzler syndrome . Yet, these results were not confirmed in a larger cohort of patients with Schnitzler syndrome …”

Section: Pathogenesis and Associated Diseasesmentioning

confidence: 92%

“…Since its original description, NUD has been accepted as an autonomous entity. Numerous new cases have been reported, and associated diseases have been confirmed and expanded . Table summarizes the associated diseases that have been published since our original publication in 2009.…”

Section: Introduction and Epidemiologymentioning

confidence: 97%

“…Numerous new cases have been reported, and associated diseases have been confirmed and expanded. 1,[3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] Table 1 summarizes the associated diseases that have been published since our original publication in 2009. NUD can also occur without any underlying disease, as an entity on its own.…”

Section: Introduction and Epidemiologymentioning

confidence: 99%

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Neutrophilic urticarial dermatosis: an entity bridging monogenic and polygenic autoinflammatory disorders, and beyond

Gusdorf

Lipsker

2019

Acad Dermatol Venereol

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Neutrophilic urticarial dermatosis (NUD) has been described in 2009. Clinically, it is an eruption of rose or red macules or slightly elevated plaques, vanishing within 24 h. It occurs mostly on the trunk and the limbs. Extracutaneous signs such as fever or joint pain can be associated. The histopathological findings are a dense perivascular and interstitial infiltrate of neutrophils with leucocytoclasia but without vasculitis. It is often associated with other systemic diseases such as Schnitzler syndrome, adult‐onset Still disease (AOSD), cryopyrin‐associated periodic syndrome (CAPS) and Lupus erythematosus (LE). The pathogenesis of NUD is not well established but its association with CAPS and AOSD suggests that NUD is linked to autoinflammation. The management of NUD depends on the clinical findings and the potential associated systemic condition. Neutrophil migration inhibitors, such as dapsone or colchicine, and IL‐1 antagonists, in particular, anakinra, are the main therapeutic options for the treatment of NUD. The prognostic value of NUD, especially when occurring in the setting of LE is not known and needs to be further investigated.

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Section: Pathogenesis and Associated Diseasesmentioning

confidence: 92%

Section: Introduction and Epidemiologymentioning

confidence: 97%

Section: Introduction and Epidemiologymentioning

confidence: 99%

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Neutrophilic urticarial dermatosis: an entity bridging monogenic and polygenic autoinflammatory disorders, and beyond

Gusdorf

Lipsker

2019

Acad Dermatol Venereol

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“…Through sequencing the entirety of the NLRP3 gene, we excluded the notion that NLRP3 mutations are responsible for the pathologic development of SchS, which strengthens our previous findings. Including the 21 patients in our previous study , we have now excluded somatic NLRP3 mutations in 32 SchS patients. Nevertheless, NLRP3 activation still likely plays a part in the etiology of SchS, given previous data establishing elevated levels of ASC aggregates and IL‐18 in SchS patients; similar quantities were found in CAPS patients, which not only reinforced the similar pathology between the 2 diseases, but was also highly indicative of inflammasome activation .…”

Section: Discussionmentioning

confidence: 99%

“…Lately, cases of late‐onset acquired CAPS (aCAPS) have been characterized, caused by somatic mutations in the NLRP3 gene . Results of one study suggested that myeloid‐restricted somatic mutations in NLRP3 may contribute to the pathogenesis of SchS , although a larger study of 21 SchS patients failed to identify any somatic mutations in either NLRP3 or 31 other genes associated with autoinflammatory disorders .…”

Section: Introductionmentioning

confidence: 99%

Exploratory Study of MYD88 L265P, Rare NLRP3 Variants, and Clonal Hematopoiesis Prevalence in Patients With Schnitzler Syndrome

Pathak¹,

Rowczenio

Owen

et al. 2019

Arthritis & Rheumatology

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Objective. To assess the prevalence of the MYD88 L265P mutation and variants within NLRP3 and evaluate the status of oligoclonal hematopoiesis in 30 patients with Schnitzler syndrome (SchS).Methods. Thirty patients with SchS were recruited from 3 clinical centers. Six patients with known acquired cryopyrin-associated periodic syndromes (aCAPS) were included as controls. Allele-specific oligonucleotidepolymerase chain reaction was used for the detection of the MYD88 L265P variant, next-generation sequencing was applied to analyze NLRP3 and 28 genes associated with myelodysplastic syndrome, and gene scanning was performed for the detection of X chromosome inactivation.Results. Activating NLRP3 mutations were not present in 11 SchS patients who had not been sequenced for this gene previously. The MYD88 L265P variant was present in 9 of 30 SchS patients, and somatic mutations associated with clonal hematopoiesis were identified in 1 of 30 patients with SchS and 1 of 6 patients with aCAPS. Evidence of nonrandom X chromosome inactivation was detected in 1 female patient with SchS and 1 female patient with aCAPS.Conclusion. A shared molecular mechanism accounting for the pathogenesis of inflammation in SchS remains elusive. Clonal hematopoiesis is not associated with other somatic mutations found in individuals with SchS or aCAPS.

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A Man With Recurrent Fever, Episodic Rash, and Pain

Aslam

Wiedmeier

DiCaudo

2021

Arthritis Care & Research

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Molecular genetic investigation, clinical features, and response to treatment in 21 patients with Schnitzler syndrome

Abstract: Key Points We found no evidence of somatic NLRP3 mosaicism in the pathogenesis of Schnitzler syndrome. Pathogenic inflammasome activation is supported by increased ASC, IL-18, IL-6, and anakinra response.

Cited by 85 publications

References 29 publications

Neutrophilic urticarial dermatosis: an entity bridging monogenic and polygenic autoinflammatory disorders, and beyond

Neutrophilic urticarial dermatosis: an entity bridging monogenic and polygenic autoinflammatory disorders, and beyond

Exploratory Study of MYD88 L265P, Rare NLRP3 Variants, and Clonal Hematopoiesis Prevalence in Patients With Schnitzler Syndrome

A Man With Recurrent Fever, Episodic Rash, and Pain

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