Genetic variants in FBLIM1 gene do not contribute to SAPHO syndrome and chronic recurrent multifocal osteomyelitis in typical patient groups

Gunter Assmann,Michaela Köhm,Michaela Köhm,Rotraut Mössner,Vinzenz Oji,Ulrike Hüffmeier,Ulrike Hüffmeier,Harald Burkhardt,Harald Burkhardt,Nina Magnolo,Volker Schuster,Frank Behrens,Frank Behrens

doi:10.1186/s12881-020-01037-7

Abstract

BackgroundSyndrome of synovitis acne pustulosis hyperostosis osteitis (SAPHO) and chronic recurrent multifocal osteomyelitis (CRMO) present two diseases of a dermatologic and rheumatologic spectrum that are variable in manifestation und therapeutic response. Genetic risk factors have long been assumed in both diseases, but no single reliable factor has been identified yet. Therefore, we aimed to clinically characterize a patient group with syndrome of synovitis acne pustulosis hyperostosis osteitis (SAPHO) (n = 47) and chronic recurrent multifocal osteomyelitis (CRMO)/ chronic non-bacterial osteomyelitis (CNO) (n = 9) and analyze a CRMO candidate gene.MethodsClinical data of all patients were collected and assessed for different combinations of clinical symptoms. SAPHO patients were grouped into categories according to the acronym; disease-contribution by pathogens was evaluated. We sequenced coding exons of FBLIM1.ResultsPalmoplantar pustular psoriasis (PPP) was the most common skin manifestation in CRMO/CNO and SAPHO patients; most SAPHO patients had sterno-costo-clavicular hyperostosis. The most common clinical category of the acronym was S_PHO (n = 26). Lack of pathogen detection from bone biopsies was more common than microbial isolation. We did not identify autosomal-recessive FBLIM1 variants.ConclusionsS_PHO is the most common combination of symptoms of its acronym. Genetic analyses of FBLIM1 did not provide evidence that this gene is relevant in our patient group. Our study indicates the need to elucidate SAPHO’s and CRMO/CNO’s pathogenesis.

Highlights

Syndrome of synovitis acne pustulosis hyperostosis osteitis (SAPHO) and chronic recurrent multifocal osteomyelitis (CRMO) present two diseases of a dermatologic and rheumatologic spectrum that are variable in manifestation und therapeutic response
SAPHO syndrome’s manifestations of the skeleton are manifold; osteitis with hyperostosis is considered as a pathognomonic lesion of SAPHO syndrome [3]
It can present as a sclerosing osteitis originating from the bone marrow, a hyperostosis with increased bone cuff formed by the periost, an ossification of ligaments, accompanied by osteolysis or an erosion of a joint

Summary

Introduction

Syndrome of synovitis acne pustulosis hyperostosis osteitis (SAPHO) and chronic recurrent multifocal osteomyelitis (CRMO) present two diseases of a dermatologic and rheumatologic spectrum that are variable in manifestation und therapeutic response. We aimed to clinically characterize a patient group with syndrome of synovitis acne pustulosis hyperostosis osteitis (SAPHO) (n = 47) and chronic recurrent multifocal osteomyelitis (CRMO)/ chronic non-bacterial osteomyelitis (CNO) (n = 9) and analyze a CRMO candidate gene. Syndrome of synovitis acne pustulosis hyperostosis osteitis (SAPHO) belongs to a group of rare, variable, chronic autoinflammatory diseases of the skeleton often in combination with certain skin manifestations and typically manifests in early adulthood [1,2,3]. Chronic nonbacterial osteomyelitis (CNO) is the more comprehensive name for this entity, so rarely used, while comprising milder/ unifocal osteomyelitis forms [7]

Objectives

Methods

Results

Discussion

Conclusion