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. 2016 Mar;31(3):650-6.
doi: 10.1002/jbmr.2728. Epub 2015 Nov 14.

The Natural History of Flare-Ups in Fibrodysplasia Ossificans Progressiva (FOP): A Comprehensive Global Assessment

Robert J Pignolo  1   2   3 , Christopher Bedford-Gay  4 , Moira Liljesthröm  4 , Blythe P Durbin-Johnson  5   6 , Eileen M Shore  2   3   7 , David M Rocke  5   6 , Frederick S Kaplan  1   2   3
Affiliations

The Natural History of Flare-Ups in Fibrodysplasia Ossificans Progressiva (FOP): A Comprehensive Global Assessment

Robert J Pignolo et al. J Bone Miner Res. 2016 Mar.

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.

Keywords: CLINICAL TRIALS; EPIDEMIOLOGY; FIBRODYSPLASIA OSSIFICANS PROGRESSIVA; FOP.

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Figures

Figure 1
Figure 1
Onset of physical impairment in FOP. The number of patients with an affected body region is shown within each bar of the histogram. Note that FOP progresses from axial to appendicular regions and within each appendicular region from proximal to distal locations.
Figure 2
Figure 2
FOP is progressive through the lifespan of most patients. Shown are the number of partially affected body regions (A), ankylosed regions (B), and all affected regions (C) over time.
Figure 3
Figure 3
Characterization of flare-ups in FOP. (A) The majority of patients report swelling, pain, decreased movement, warmth, and redness as prominent symptoms of a flare-up. (B) Time to subjective confirmation of a flare-up. Most patients reported confirmation of a flare-up within two days of onset of symptoms.
See this image and copyright information in PMC

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