Bianka Sobolewska1, Eva Angermair2, Christoph Deuter2, Deshka Doycheva2, Jasmin Kuemmerle-Deschner2, Manfred Zierhut2. 1. From the Center for Ophthalmology, and the Division of Pediatric Rheumatology, Department of Pediatrics, Eberhard-Karls University Tuebingen, Tuebingen, Germany.B. Sobolewska, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; E. Angermair, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; C. Deuter, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; D. Doycheva, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; J. Kuemmerle-Deschner, MD, Division of Pediatric Rheumatology, Department of Pediatrics, Eberhard-Karls University Tuebingen; M. Zierhut, MD, PhD, Center for Ophthalmology, Eberhard-Karls University Tuebingen. Dr. Kuemmerle-Deschner and Dr. Zierhut contributed equally to this report and should be considered as co-senior authors. Bianka.sob@gmx.de. 2. From the Center for Ophthalmology, and the Division of Pediatric Rheumatology, Department of Pediatrics, Eberhard-Karls University Tuebingen, Tuebingen, Germany.B. Sobolewska, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; E. Angermair, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; C. Deuter, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; D. Doycheva, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; J. Kuemmerle-Deschner, MD, Division of Pediatric Rheumatology, Department of Pediatrics, Eberhard-Karls University Tuebingen; M. Zierhut, MD, PhD, Center for Ophthalmology, Eberhard-Karls University Tuebingen. Dr. Kuemmerle-Deschner and Dr. Zierhut contributed equally to this report and should be considered as co-senior authors.
Abstract
OBJECTIVE: Cryopyrin-associated periodic syndrome (CAPS) is a group of inherited autoinflammatory disorders caused by mutations in the NLRP3 gene resulting in the overproduction of interleukin 1β. NLRP3 mutations cause a broad clinical phenotype of CAPS. The aims of the study were to evaluate clinical, laboratory, and genetic features of a 5-generation family with CAPS focusing in detail on ocular symptoms. METHODS: In a retrospective observational cohort study, consecutive family members were screened for the presence of the NLRP3 mutation. Patients underwent standardized clinical, laboratory, and ophthalmological assessments. The genotype-specific risk of ophthalmological findings and other organ symptoms was determined. RESULTS: Twenty-nine patients were clinically affected. The A439V mutation encoded by exon 3 of the NLRP3 gene was found in 15 of 37 family members (41%). The most common clinical features were musculoskeletal symptoms, headaches, and ophthalmological symptoms. The mutation-positive patients were characterized by more frequent skin rashes, ocular symptoms, arthralgia, arthritis, and severe Muckle-Wells syndrome (MWS) Disease Activity Score. Rosacea was diagnosed in 8 patients. CONCLUSION: The NLRP3 mutation A439V is associated with a heterogeneous clinical spectrum of familial cold autoinflammatory syndrome/MWS-overlap syndrome. Skin rash and eye diseases, such as conjunctivitis and uveitis, were positively correlated with this mutation.
OBJECTIVE:Cryopyrin-associated periodic syndrome (CAPS) is a group of inherited autoinflammatory disorders caused by mutations in the NLRP3 gene resulting in the overproduction of interleukin 1β. NLRP3 mutations cause a broad clinical phenotype of CAPS. The aims of the study were to evaluate clinical, laboratory, and genetic features of a 5-generation family with CAPS focusing in detail on ocular symptoms. METHODS: In a retrospective observational cohort study, consecutive family members were screened for the presence of the NLRP3 mutation. Patients underwent standardized clinical, laboratory, and ophthalmological assessments. The genotype-specific risk of ophthalmological findings and other organ symptoms was determined. RESULTS: Twenty-nine patients were clinically affected. The A439V mutation encoded by exon 3 of the NLRP3 gene was found in 15 of 37 family members (41%). The most common clinical features were musculoskeletal symptoms, headaches, and ophthalmological symptoms. The mutation-positive patients were characterized by more frequent skin rashes, ocular symptoms, arthralgia, arthritis, and severe Muckle-Wells syndrome (MWS) Disease Activity Score. Rosacea was diagnosed in 8 patients. CONCLUSION: The NLRP3 mutation A439V is associated with a heterogeneous clinical spectrum of familial cold autoinflammatory syndrome/MWS-overlap syndrome. Skin rash and eye diseases, such as conjunctivitis and uveitis, were positively correlated with this mutation.
Authors: Micol Romano; Z Serap Arici; David Piskin; Sara Alehashemi; Daniel Aletaha; Karyl Barron; Susanne Benseler; Roberta A Berard; Lori Broderick; Fatma Dedeoglu; Michelle Diebold; Karen Durrant; Polly Ferguson; Dirk Foell; Jonathan S Hausmann; Olcay Y Jones; Daniel Kastner; Helen J Lachmann; Ronald M Laxer; Dorelia Rivera; Nicola Ruperto; Anna Simon; Marinka Twilt; Joost Frenkel; Hal M Hoffman; Adriana A de Jesus; Jasmin B Kuemmerle-Deschner; Seza Ozen; Marco Gattorno; Raphaela Goldbach-Mansky; Erkan Demirkaya Journal: Arthritis Rheumatol Date: 2022-05-27 Impact factor: 15.483
Authors: Jasmin Beate Kuemmerle-Deschner; Raju Gautam; Aneesh Thomas George; Syed Raza; Kathleen Graham Lomax; Peter Hur Journal: RMD Open Date: 2020-07