A novel mutation in early‐onset sarcoidosis/Blau syndrome: an association with Propionibacterium acnes

Autor: Ryuta Nishikomori, Yoshinobu Hoshii, Yoshitaka Honda, Yoshinobu Eishi, Shunji Hasegawa, Nobuyuki Asano, Yuno Korenaga, Shouichi Ohga, Keisuke Uchida, Fumiko Okazaki, Kazushi Izawa, Tsuyoshi Tanabe, Sho-Hei Uchi, Tamaki Nakamura, Hiroyuki Wakiguchi, Hiroki Yasudo, Ryoji Yanai
Rok vydání: 2021
Předmět:
Pathology
lcsh:Diseases of the musculoskeletal system
Biopsy
Nod2 Signaling Adaptor Protein
Dermatitis
Case Report
NF-κB
PAB antibody
030207 dermatology & venereal diseases
0302 clinical medicine
NOD2
Panuveitis
Immunology and Allergy
Medicine
Child
Skin
Granulomatous disease
Granuloma
Synovitis
biology
medicine.diagnostic_test
lcsh:RJ1-570
Immunohistochemistry
Treatment Outcome
Antirheumatic Agents
Prednisolone
Female
Polyarthritis
Sarcoidosis
Granulomatous Dermatitis
medicine.drug
medicine.medical_specialty
Uveitis
03 medical and health sciences
Propionibacterium acnes
Rheumatology
D512V mutation
Humans
Blau syndrome
030203 arthritis & rheumatology
business.industry
Arthritis
lcsh:Pediatrics
medicine.disease
biology.organism_classification
Methotrexate
Mutation
Pediatrics
Perinatology and Child Health
Skin biopsy
Cutibacterium acnes
lcsh:RC925-935
business
Zdroj: Pediatric Rheumatology Online Journal, Vol 19, Iss 1, Pp 1-8 (2021)
Pediatric Rheumatology Online Journal
ISSN: 1546-0096
Popis: BackgroundEarly-onset sarcoidosis (EOS) and Blau syndrome (BS) are systemic inflammatory granulomatous diseases without visible pulmonary involvement, and are distinguishable from their sporadic and familial forms. The diseases are characterized by a triad of skin rashes, symmetrical polyarthritis, and recurrent uveitis. The most common morbidity is ocular involvement, which is usually refractory to conventional treatment. A gain-of-function mutation in the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene has been demonstrated in this disease; however, little is known about the relationship between the activation ofNOD2and the pathophysiology of EOS/BS. Here we describe EOS/BS with a novel mutation in theNOD2gene, as well as detection ofPropionibacterium acnes(P. acnes) in the granulomatous inflammation.Case presentationAn 8-year-old Japanese girl presented with refractory bilateral granulomatous panuveitis. Although no joint involvement was evident, she exhibited skin lesions on her legs; a skin biopsy revealed granulomatous dermatitis, andP. acneswas detected within the sarcoid granulomas by immunohistochemistry withP. acnes-specific monoclonal (PAB) antibody. Genetic analyses revealed that the patient had aNOD2heterozygous D512V mutation that was novel and not present in either of her parents. The mutantNOD2showed a similar activation pattern to EOS/BS, thus confirming her diagnosis. After starting oral prednisolone treatment, she experienced an anterior vitreous opacity relapse despite gradual prednisolone tapering; oral methotrexate was subsequently administered, and the patient responded positively.ConclusionsWe presented a case of EOS/BS with a novel D512V mutation in theNOD2gene. In refractory granulomatous panuveitis cases without any joint involvement, EOS/BS should be considered as a differential diagnosis; genetic analyses would lead to a definite diagnosis. Moreover, this is the first report ofP. acnesdemonstrated in granulomas of EOS/BS. Since intracellularP. acnesactivates nuclear factor-kappa B in aNOD2-dependent manner, we hypothesized that the mechanism of granuloma formation in EOS/BS may be the result ofNOD2activity in the presence of the ligand muramyl dipeptide, which is a component ofP. acnes.These results indicate that recognition ofP. acnesthrough mutantNOD2is the etiology in this patient with EOS/BS.
Databáze: OpenAIRE
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