TREATMENT OF PATIENTS WHO HAVE FIBRODYSPLASIA OSSIFICANS PROGRESSIVA WITH ISOTRETINOIN

Retinoids are a plausible family of therapeutic agents for fibrodyspla sia ossificans progressiva due to their ability to inhibit differentia tion of mesenchymal tissue into cartilage and bone, A prospective stud y was conducted to assess the efficacy of isotretinoin (13-cis-retinoi c acid) in the prevention of heterotopic ossification in patients who had fibrodysplasia ossificans progressiva. Eleven anatomic regions wer e assessed in each of 21 patients by clinical examination, radiographs , and bone scans. An anatomic region was considered to be involved if there was clinical, radiographic, or radionuclide evidence of orthotop ic or heterotopic ossification anywhere in the region. There were 143 involved anatomic regions and 88 uninvolved anatomic regions at the be ginning of the study. Only one of the 88 anatomic regions that was com pletely uninvolved at the beginning of the study became involved durin g isotretinoin therapy. However, 16 of the 21 patients (76 %) had majo r flare ups develop in 38 of 143 (27 %) previously involved anatomic r egions while administered isotretinoin therapy. Isotretinoin at steady state doses of 1 to 2 mg/kg per day decreased the incidence of hetero topic ossification at uninvolved anatomic regions compared with an ext ernal control group, as long as the medication was started before the appearance of any orthotopic or heterotopic ossification in that anato mic region. The data did not allow the determination of whether isotre tinoin was effective or detrimental in preventing disease flareups in regions that had even minimal orthotopic or heterotopic ossification a t the time the therapy began. Extreme caution should be exercised when using this medication in patients who have fibrodysplasia ossificans progressiva.