The unpredictable nature of flare-ups in fibrodysplasia ossificans progressiva (FOP)

Commissioned by Ipsen and developed for Medthority. This content is intended for healthcare professionals only and has been reviewed by Ipsen for scientific accuracy.

DSFOP-UK-000020 Date of preparation December 2021

Overview

Are you treating a patient who is experiencing sporadic and unpredictable episodes of soft-tissue swellings associated with pain, reduced movement, stiffness, fever, and functional loss? This could be a flare-up of FOP. Read on to find out how to provide appropriate care…

Recognizing FOP flare-ups

In the ultra-rare genetic disease FOP, ‘flare-ups’ are soft-tissue swellings, concomitant with pain, decreased mobility, stiffness, and fever¹. These typically present in the upper limbs, head and back of patients less than 8 years of age, and in the lower limbs of those over 8 years of age¹. Although flare-ups can regress without sequalae, most result in heterotopic ossification (HO), which often begins to accumulate in infancy². Overall, the frequency, duration, and rate of disease progression varies by patient and by flare-up location¹.

The occurrence of flare-ups is unpredictable and spontaneous, but in most cases, they manifest following injury, viral infection, or limb overuse¹. Therefore, confirming a diagnosis of FOP is important in disease management; it means that certain activities and medical interventions that may cause trauma, such as biopsies, can be avoided to prevent painful new bone growth³.

If you suspect a FOP flare-up, avoid biopsies, removal of heterotopic bone, and all non-emergent surgical procedures, as these can exacerbate recurrence and expansion of HO³

The effects of flare-ups in FOP

Flare-ups affecting the hips are associated with the greatest pain and often take longer to resolve than flare-ups affecting other regions¹. The severity of pain in patients with FOP is negatively correlated with overall quality of life, physical health measures (including increased pain and decreased mobility) and emotional health measures (including increased anxiety, depression, and irritability)⁴. Although flare-ups are episodic, their effects are likely cumulative and may result in chronic background pain⁴. The precise mechanisms that drive pain during, and between, flare-ups are unclear; therefore, providing patients with FOP with effective analgesia remains an important challenge⁴. To date, there are no known curative treatments for FOP; medical intervention is currently supportive, and flare-ups are managed with non-steroidal anti-inflammatory medications².

Could you identify a FOP flare-up?

Focusing on the presentation and location of soft-tissue swellings, along with common flare-up symptoms such as pain, immobility, stiffness, and fever, will support early diagnosis of FOP and help to avoid unnecessary interventions, thus limiting disability accumulation.

To learn more about HO and its impact on patients' quality of life, please keep an eye out for the next article of the series (available next month).

Knowledge check

Abbreviations

FOP=fibrodysplasia ossificans progressiva; HO=heterotopic ossification

References

1. Pignolo RJ, Bedford-Gay C, Liljesthröm M, et al. The Natural History of Flare-Ups in Fibrodysplasia Ossificans Progressiva (FOP): A Comprehensive Global Assessment. J Bone Miner Res. 2016;31(3):650-656. doi:10.1002/jbmr.2728
2. Pignolo RJ, Shore EM, Kaplan FS. Fibrodysplasia ossificans progressiva: diagnosis, management, and therapeutic horizons. Pediatr Endocrinol Rev. 2013;10 Suppl 2(0 2):437-448.
3. Kaplan FS, et al. The medical management of fibrodysplasia ossificans progressiva: current treatment considerations. Proc Intl Clin Council FOP 1:1-111, 2019
4. Peng K, Cheung K, Lee A, Sieberg C, Borsook D, Upadhyay J. Longitudinal Evaluation of Pain, Flare-Up, and Emotional Health in Fibrodysplasia Ossificans Progressiva: Analyses of the International FOP Registry. JBMR Plus. 2019;3(8):e10181. Published 2019 Mar 1. doi:10.1002/jbm4.10181