title: The Natural History of Flare-Ups in Fibrodysplasia Ossificans Progressiva (FOP): A Comprehensive Global Assessment.
abstract: Fibrodysplasia ossificans progressiva (FOP) leads to disabling heterotopic ossification (HO) from episodic flare-ups. However, the natural history of FOP flare-ups is poorly understood. A 78-question survey on FOP flare-ups, translated into 15 languages, was sent to 685 classically-affected patients in 45 countries (six continents). Five hundred patients or knowledgeable informants responded (73%; 44% males, 56% females; ages: 1 to 71 years; median: 23 years). The most common presenting symptoms of flare-ups were swelling (93%), pain (86%), or decreased mobility (79%). Seventy-one percent experienced a flare-up within the preceding 12 months (52% spontaneous; 48% trauma-related). Twenty-five percent of those who had received an intramuscular injection reported an immediate flare-up at the injection site, 84% of whom developed HO. Axial flare-ups most frequently involved the back (41.6%), neck (26.4%), or jaw (19.4%). Flare-ups occurred more frequently in the upper limbs before 8 years of age, but more frequently in the lower limbs thereafter. Appendicular flare-ups occurred more frequently at proximal than at distal sites without preferential sidedness. Seventy percent of patients reported functional loss from a flare-up. Thirty-two percent reported complete resolution of at least one flare-up and 12% without any functional loss (mostly in the head or back). The most disabling flare-ups occurred at the shoulders or hips. Surprisingly, 47% reported progression of FOP without obvious flare-ups. Worldwide, 198 treatments were reported; anti-inflammatory agents were most common. Seventy-five percent used short-term glucocorticoids as a treatment for flare-ups at appendicular sites. Fifty-five percent reported that glucocorticoids improved symptoms occasionally whereas 31% reported that they always did. Only 12% reported complete resolution of a flare-up with glucocorticoids. Forty-three percent reported rebound symptoms within 1 to 7 days after completing a course of glucocorticoids. This study is the first comprehensive global assessment of FOP flare-ups and establishes a critical foundation for the design and evaluation of future clinical trials.
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|The Center for Research in FOP and Related Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Pignolo
authors.affiliation: International FOP Association, Winter Springs, FL, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Bedford-Gay
authors.affiliation: International FOP Association, Winter Springs, FL, USA.
authors.forename: Moira
authors.initials: M
authors.lastname: Liljesthröm
authors.affiliation: Department of Public Health Sciences, School of Medicine, University of California, Davis, Davis, CA, USA.|Department of Biomedical Engineering, University of California, Davis, Davis, CA, USA.
authors.forename: Blythe P
authors.initials: BP
authors.lastname: Durbin-Johnson
authors.affiliation: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|The Center for Research in FOP and Related Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Shore
authors.affiliation: Department of Public Health Sciences, School of Medicine, University of California, Davis, Davis, CA, USA.|Department of Biomedical Engineering, University of California, Davis, Davis, CA, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Rocke
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|The Center for Research in FOP and Related Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Frederick S
authors.initials: FS
authors.lastname: Kaplan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003710:Demography; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D007722:Health Knowledge, Attitudes, Practice; D006801:Humans; D007223:Infant; D038622:Internationality; D008297:Male; D008875:Middle Aged; D009221:Myositis Ossificans / Q000473:pathology*; D000067251:Symptom Flare Up; D055815:Young Adult
keywords: CLINICAL TRIALS; EPIDEMIOLOGY; FIBRODYSPLASIA OSSIFICANS PROGRESSIVA; FOP