Post-COVID-19 exacerbation of fibrodysplasia ossificans progressiva with multiple flare-ups and extensive heterotopic ossification in a 45-year-old female patient

Abstract

Fibrodyplasia ossificans progressiva (FOP) is a rare hereditary disease, which has a variable course characterized by occasional flare-ups of heterotopic ossification (HO) in soft tissues that are followed by swelling, stiffness, pain and warmth. Here, we report for the first time a case of a 45-year-old female patient with known FOP recovering from COVID-19 with disease progression potentially linked with the viral illness. In December 2020 the patient contracted a mild form of COVID-19 infection without need for hospital admission. Since January 2021, the patient felt unwell, with occasional abdominal pain which progressively intensified. In March 2021 she presented with new onset of HO, complaining of pain, swelling and thickening sensation in the lower abdomen and left part of the neck. Computerized tomography (CT) and cytokine analysis were performed. CT scan revealed new heterotopic bone formation in multiple soft tissue areas of the neck indicating clear radiological progression. Radiotherapy, which has proven to be an efficient tool to control HO in this patient, was not able to halt HO formation after COVID-19 infection. Cytokine analysis of a plasma sample obtained during a flare-up after COVID-19 infection showed a significantly elevated pro-inflammatory cytokines compared to a flare-up panel prior to infection. Of the 23 analyzed levels of cytokines, a staggering number of 21 were above normal levels. This case is the first confirmation of uncontrolled post-COVID-19 effects in a FOP patient, which manifested with flare-ups followed by progressive HO, possibly caused by a thus far, never described form of post-COVID syndrome.

Benign Fasciculation Syndrome and Migraine Aura without Headache: Possible Rare Side Effects of the BNT162b2 mRNA Vaccine? A Case Report and a Potential Hypothesis

“…Autoimmune channelopathies are a group of disorders which are associated with autoantibodies directed against ion channels. It is also possible that spike proteins caused a more generalized immune response similar to that seen in post-COVID-19 syndrome [32][33][34]. Such a "widespread" immune reaction might be revealed in the presence of anti-thyroid antibodies that were found in our patient's blood sample (in addition to the theorized anti-ion-channel antibodies).…”

Extensive progressive heterotopic ossification post-Covid-19 in a man

“…Several possible mechanisms have been suggested, including direct invasion of muscle tissue by the virus, activation of proinflammatory transcription factors, and autoimmune processes [13] , [18] . Grgurevic L et al described the first report of a 45-year-old female patient with FOP exacerbation approximately 4 weeks post-COVID-19 convalescence [15] . The patient was diagnosed with FOP at the age of four with multiple flare-ups affecting paravertebral muscles, right arm and both knees, masticatory muscle, right femur, infraclavicular region, neck, and right hemithorax and anterior neck until her 44 years of age.…”

“…Nevertheless, is necessary to establish a stronger base of evidence regarding the association. HO was associated with local inflammation, which affects mesenchymal stem cells present in soft tissues [15] , [20] . In the early stages, there is an intense perivascular lymphocytic infiltration into seemingly normal skeletal muscle followed by the death of skeletal muscle and fibrovascular tissue proliferation [21] .…”

“…In addition, it was described a middle-aged onset FOP in a woman following a brief, seemingly viral, illness [14] . Further, it has been reported a case of FOP exacerbation after COVID-19 infection [15] .…”

Heterotopic ossification vs. fracture healing: Extracellular vesicle cargo proteins shed new light on bone formation

“…The accumulating HO leads to decreased mobility, cumulative and progressive disability, as well as thoracic insufficiency syndrome, which over time often becomes fatal ( Kaplan et al, 2008 ; Kaplan and Glaser, 2005 ). Disease flare-ups are reported to be triggered by several factors, such as small tissue injuries, intramuscular injections, muscle fatigue and even viral infections ( Kaplan et al, 2008 ; Scarlett et al, 2004 ; Lanchoney et al, 1995 ; Grgurevic et al, 2021 ). As inflammation is an important component of HO, innate and adaptive immunity, as well as inflammatory cytokines have an important role in HO occurrence and progression ( Matsuo et al, 2019 ; Grgurević et al, 2019 ).…”