Myositis Ossificans in Hemophilia A

Author: Faria Ali, 04/26/2022
Category: Hemostasis and coagulation > Bleeding disorders > Inherited Coagulation disorders > Hemophilia A (Factor VIII deficiency)
Published Date: 06/06/2022

Abstract:

Myositis ossificans refers to non-neoplastic heterotopic soft tissue ossification and is rarely encountered in patients with hemophilia, despite the frequent bleeds. We are reporting one such case, in which an African American male with a history of Hemophilia A was incidentally found to have myositis ossificans (MO) in both his lower extremities. In this case report we will also review the underlying pathophysiology, preventive interventions and management of this extremely rare and under-reported condition.

Case Report:

A 36-year-old African American male with past medical history of Hemophilia A presented to the ED with thigh pain and swelling. The patient started noticing pain after a bike ride 2 days prior to presentation. On arrival to the ER, he was hemodynamically stable, and his right upper thigh was noted to be swollen and tender. There was no neurovascular compromise noted and range of motion of the right hip joint was preserved. Of note, patient was lost to follow up for about a year and did not have access to factor VIII. He was supposed to be on recombinant factor (3000 units), on an as needed basis and historically was using it up to 2 to 3 times a month. Labs were significant for Hemoglobin of 13.6 gm/dL (Range: 13.5 - 17.0 g/dL), Factor VIII activity of 2.02% (Range: 50 - 150 %) and quantitative inhibitor level of 0.30 (Range: 0.00 Bethesda Units). Because of the high likelihood of an underlying bleed, patient was empirically given recombinant factor VIII at a dose of 50U/kg body weight and this was repeated once in 12 hours from the first dose. Soon after receiving the first dose of recombinant factor and pain medications, his symptoms improved, and he underwent imaging to confirm and localize the bleed. CT of the right femur showed an intramuscular hematoma in the right adductor brevis muscle belly along with intramuscular and peripheral ossification throughout the muscle. The largest area of ossification measured approximately 8 x 4.4 cm.

Discussion:

Myositis ossificans (MO) is a rare benign disorder characterized by heterotopic non-neoplastic bone formation in skeletal muscle and soft tissue (2, 5). It is of three types: Traumatic MO (most common, comprises 60-75% of all cases), non-traumatic MO (associated with hemophilia, neurological disorders and burns) and MO progressive (hereditary and severe generalized form) (3, 5). Hemophilic MO at the site of previous hemorrhage is a well-recognized entity (7). Intramuscular bleeding may develop after minor trauma, following intramuscular injections and during activity. Usually, fibrosis, which follows the bleeding, is not ordinarily followed by ossification. However, the hemorrhage may extend to involve the periosteum if the muscle has a broad attachment to bone by Sharpey’s fibers (8). In instances where the intramuscular hematoma is related to periosteal attachment, bone producing elements from the periosteum may escape into the hematoma, setting the stage for bone formation (6). Also, metaplasia of tissue developed during the healing process causes bone formation (6). Histological findings in MO vary according to the stage of evolution (5). In the early phase, MO is characterized by a proliferative mesenchymal response (may mimic a fibrosarcoma or myosarcoma). This is followed by development of a typical three-zone pattern: a peripheral zone composed of mature bone, a middle zone with osteoblasts and immature osteoid formation and a center with rapidly proliferating fibroblasts. Peripheral bone formation begins usually around 6 weeks after injury. With further maturation, the lesion may either regress in size or completely ossify along with forming cortex and marrow spaces (5). Of note, 30% of cases may resolve spontaneously (7).

 

MO in hemophilia typically affects the lower half of the body, but the most commonly affected sites include the brachial biceps and the quadriceps (2). Persistent symptoms after an acute phase in a patient might prompt radiological assessment and lead to discovery of MO (4). Anatomic localization of bone foci is often difficult in conventional radiographs and CT scan is possibly the best imaging modality to demonstrate and localize MO ossification patterns the earliest (5). MRI can provide further delineation of the extent of bone marrow and soft tissue changes (5, 9, 10). MO in hemophilia patients is under-reported and according to some reports, its true incidence might be as high 15 %. (4)

 

To prevent ectopic ossification, hemophiliacs who present with bleeding into the soft tissues must receive appropriate Factor VIII or IX replacement (8). Conservative therapy is appropriate given the benign natural history of MO (4). If it causes severe limitation of range of motion unresponsive to conservative treatment, surgical excision of heterotopic bone might be indicated (4). However, it is typically recommended to withhold surgical excision until complete bone maturation occurs (as evidenced by bone scintigraphy and CT findings [1]). A favourable prognosis may be anticipated by withholding surgery until maturation of the lesion to minimize early recurrence risk during healing (1, 4), and when all surgical prerequisites for the heterotopic ossification resection have been considered, including an interdisciplinary approach to coordinate management (Surgery, Hematology and Anesthesia) (13). Although very rare, secondary malignancy including osteosarcoma and osteochondroma have been reported in unresected MO lesions and therefore, changes in symptoms warrant prompt re-evaluation (11, 12).

Conclusion:

To summarize, MO in hemophiliacs begins with an intramuscular hematoma, followed by the development of dysplastic metaplasia at the site of healing, along with the ossification of periosteal hemorrhagic lesions (6). In the absence of inflammation and severe pain, persistently decreased range of motion should prompt the search for MO in these patients. MO occurs primarily in large muscle groups during the second decade of life, is often preceded with trauma and usually has a benign course. Conservative therapy is usually indicated because spontaneous resolution may occur, while surgery is only reserved for cases with severe functional limitation (1).

References:

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