Iatrogenic Harm Caused by Diagnostic Errors in Fibrodysplasia Ossificans Progressiva

Abstract

ABSTRACT. Background. Little is known about diagnostic errors for a disease worldwide. Such errors could alter the disease's natural history, especially if unwarranted interventions cause irreversible harm. Fibrodysplasia ossificans progressiva (FOP), a rare, autosomal dominant genetic disease characterized by episodes of permanent heterotopic ossification of soft tissues, occurs worldwide without racial, ethnic, or geographic predilection. There is no effective treatment, and soft-tissue trauma (eg, biopsies, surgical procedures, intramuscular injections, or mandibular blocks for dental procedures) and viral illnesses are likely to induce episodes of rapidly progressive heterotopic ossification, with resultant permanent loss of motion in the affected area. Accurate diagnoses can be made on the basis of the clinical findings of tumor-like swellings on the head, neck, back, or shoulders and characteristic short great toes with hallux valgus-like malformations and missing interphalangeal joints. On the basis of conversations with numerous individuals with FOP, we suspected that diagnostic errors with FOP are common and often associated with inappropriate and harmful diagnostic and therapeutic procedures.Objective. To document the frequency of diagnostic errors with FOP and complications resulting from misdiagnoses.Design. A questionnaire requesting detailed demographic, diagnostic, and treatment information was sent to all 269 patient-members of the International FOP Association; the sampling frame included >90% of all known FOP patients worldwide. We received 138 replies (51% response) from 25 countries. The age range was 2 to 71 years; there were 78 female subjects and 60 male subjects. In addition, to assess the availability and adequacy of information about FOP, we reviewed 184 English-language textbooks in relevant specialties published in the past 20 years.Results. Incorrect diagnoses were given initially to 87% of individuals with FOP. This astonishing rate of diagnostic errors occurred worldwide, regardless of ethnicity, geographic background, or misdiagnosing physician's specialty. The most common incorrect diagnosis was cancer (32%). The mean period from the onset of symptoms to correct diagnosis was 4.1 years, and the median number of physicians consulted before the correct diagnosis of FOP was 6. For 67% of patients, unnecessary invasive procedures (biopsies) were performed; 68% received inappropriate therapies. Forty-nine percent of all patients reported permanent loss of mobility resulting from invasive medical interventions that caused posttraumatic ossification. Notably, only 8% of the 184 textbooks that were reviewed contained adequate descriptions of FOP, including the caution that trauma can accelerate the process of heterotopic ossification.Conclusions. T he accurate diagnosis of disease has been a basic principle of medical care since antiquity. Mistaken or delayed diagnosis can lead to morbidity or death through use of inappropriate procedures or through withholding of necessary treatments. R...

Molecular Consequences of the ACVR1R206H Mutation of Fibrodysplasia Ossificans Progressiva

“…At the time of birth no specific disability or skeletal deformity is apparent, except for a malformed big toe; however, once heterotopic ossification begins in the first decade of life, it progresses with aggravation, leading to ankylosis of the major joints or fusion of the rib cage with subsequent severe disability and fatal respiratory failure (1)(2)(3)(4). Moreover, surgical attempts to remove heterotopic bone or incisional biopsies commonly lead to episodes of explosive and painful new bone growth (5)(6). Thus, the difficulties in obtaining human tissues for study have limited the molecular and biochemical understanding of the disease.…”

Fibrodisplasia ossificante progressiva: diagnóstico em atenção primária

“…It is important to take into account and inform the patients suffering from this disease that minor trauma such as intramuscular immunizations, mandibular blocks, muscular trauma, falls, or colds could trigger a new episode of inflammatory swellings that will result in the ossification of these soft tissues (disease flare-up) (4,14) . Surgical attempts to obtain samples using biopsy or to remove a heterotopic bone could lead to episodes of explosive bone growth, which could be even much more severe that those caused by disease flareups (14) .…”

“…Surgical attempts to obtain samples using biopsy or to remove a heterotopic bone could lead to episodes of explosive bone growth, which could be even much more severe that those caused by disease flareups (14) . Therefore, it is necessary to control the environment of affected people, preventing, whenever possible, their exposure to situations that could exacerbate the disease, as well as avoiding invasive procedures in case of suspected FOP, which constitutes actions of primary care that can be performed in the primary health care level.…”

Fibrodisplasia ossificante progressiva: relato de caso

“…Moreover, dental treatments are contraindicated, since they frequently bring about ossifications in the region. Recent data revealed that 67% of patients with FOP were submitted to invasive procedures and 68% received unnecessary treatments (5) , as in the case of the patient in question. Hallux shortening was not PROGRESSIVE OSSIFYING FIBRODYSPLASIA: CASE REPORT observed in some of the evaluations performed, while in others it was observed, but was not related to FOP.…”