We encountered two cases of HO, both of which were mimicking pyomyositis from laboratory and imaging findings. The two cases presented here highlight many similarities and differences between the immature HO and pyomyositis in laboratory, imaging and clinical findings. When patients present with numerous medical comorbidities predisposing them to infectious conditions, immature HO can be extremely difficult to distinguish from deep infections such as pyomyositis, cellulitis and osteomyelitis. We investigated the longitudinal change (trajectory) of biomarkers along with basal examinations and imaging findings. For prevention and early diagnosis, it is necessary to differentiate from other mimicking conditions and to track the emergence and maturation of HO. Therefore, our two cases can be used as a detailed clinical template which has been interpreted with intercorrelation and the comparison of each trajectory.
Previous studies found that elevated alkaline phosphatase (ALP), ESR and CK levels are associated with HO.3
Elevation of ALP is a hallmark of HO and is considered a sensitive and convenient tool for early detection.3
ALP level may be elevated in the early stages of bone formation and returns to normal as the bone becomes mature. The change of serum ALP in our two cases was found only after confirmation of heterotopic ossification radiographically (). CK level was significantly increased along with CRP in case 1 and then normalized before the elevation of ALP (). In case 2, the CK level was not checked frequently to make the trajectory for its change, but we can also notice the increase of CRP and CK followed by the elevation of ALP (). It is known that elevated serum levels of CK have value in predicting the HO,6
and in anticipating a more severe state of HO7
Therefore, CK level could be a more sensitive marker to diagnose early HO than ALP level.
Fig. 4 Chronologic changes in the levels of parameters in Case 1 (A) and Case 2 (B). (A) Serum CRP and CK levels increased ahead of the development of swelling followed by the change of serum ALP after confirmation of heterotopic ossification radiographically. (more ...)
Conventional radiographs usually show the evolution of HO lesions with a detectable calcific density present 4-6 weeks after the results of the 3-phase bone scintigraphy have become positive.1
Three-phase bone scintigraphy is the most sensitive imaging modality for early detection of HO. Specifically, flow studies and blood-pool images detect incipient HO approximately 2.5 weeks after injury, with findings on delayed scan becoming positive approximately 1 week later.1
Scintigraphic findings may not be specific between the soft tissue infection and early HO. Both simple radiographic study and three-phase bone scintigraphy for our two cases were not helpful for early diagnosis when performed initially and only follow-up studies demonstrated evidence of HO. With maturation of HO, T2 signal intensity and contrast enhancement were decreased, and fat and cortical bone-equivalent signal intensity was increased. These findings are consistent with the literature.8
On MR imaging of our cases, the affected muscles appeared enlarged with heterogeneous areas of low signal intensity on T1-weighted images. On T2-weighted images, high signal intensity within the muscle was poorly marginated and hyperintense signal along the fascia was shown. Also, diffusely increased thickness and high signal intensity was noted in subcutaneous tissues. After intravenous administration of gadolinium contrast, we could see heterogenous and feature-like enhancement revealing intramuscular fluid collections with hypointensity and peripheral rim enhancement. Immature ossification lesions with central hyperintense signal intensity and marked rim enhancement may be confused with septic bursitis or abscess and immature HO with diffuse enhancement can be mistaken for soft-tissue infection.10
Therefore, correct recognition of HO is hindered by the insensitivity of MRI in the detection of matrix calcification in immature HO.
The principal findings upon examination were similar to those seen in the deep infection of the hip. The clinical findings were characterized by pain in the hip and features of systemic infection. Lab findings which reveal an elevated ESR, CRP and leukocytosis can be seen in both conditions.6
Nonetheless, we need to pay attention to a number of distinguishing features. Pyomyositis does not reduce hip movement so dramatically, and is associated with more discrete areas of tenderness.6
It may not be related to the elevation of ALP and CK. Therefore, the diagnosis of HO should be made with thorough information including a careful history, physical examination, specific biomarkers and imaging findings. Furthermore, initially negative examinations should be repeated if clinical suspicion remains. Even without any increase of ALP level, other biomarkers such as CK level could help to diagnose early HO.
One must keep in mind that increasing number of patients undergoing acute care and rehabilitation treatment are aging and thus have more medical comorbidities and chronic underlying conditions accompanying the neurologic and orthopedic problems. In clinical circumstances, it is practical to prescribe empirical antibiotics before identifying the exact microorganism. The current study suggest that we should predict the possibility of HO development later based on findings from thorough history taking, physical examination and serial biomarkers check-up as well as imaging studies and therefore, take preventive measures against HO by gentle remobilization and use of anti-inflammatory agents. A regular serum CK and ALP screening test for HO in prolonged immobilized patients may be an effective way to identify the early development of HO. Controversy remains as to which of the available therapy options are better for the prophylaxis.
The two cases described here cannot be used to generalize the characteristics of immature HO. More intensive studies including serial biomarkers and imaging studies will enhance our understandings and help to differentiate HO from other conditions.