Recurrent hemarthrosis in patients with hemophilia leads to an inflammatory joint response, which results in the accumulation of destructive enzymes, hemosiderin, and cytokines leading to eventual joint destruction.2 These arthropathies are debilitating and may be considered the major manifestation of hemophilia. Studies reporting the percentage of joint arthropathy in patients with hemophilia have described, in decreasing frequency, knee, elbow, ankle, hip, and shoulder involvement. The incidence of shoulder arthropathy in these patients is currently estimated at 4%.1,3,4 The changes seen in hemophilic arthropathy have been reported as relatively consistent in these joints leading Pettersson et al7 to design a general grading system to quantify the radiographic changes seen in arthropathy in patients with hemophilia (Table 1).
Because the shoulder is the least commonly affected large joint in hemophilia, the radiographic changes seen in the shoulder rarely have been reported. Two studies3,6 examining arthropathy in patients with hemophilia described elbow arthropathy in detail yet mentioned the glenohumeral joint only briefly. Only one study5 has examined shoulder arthropathy in hemophilia in detail. That study reported that 37% of patients with hemophilia had shoulder symptoms and that 24% of the patients had ultrasound evidence of rotator cuff disease. However, the study focused on soft tissue damage, and, to date, no study has extensively evaluated the radiographic changes associated with shoulder arthropathy in patients with hemophilia.
The purpose of the current study was to determine the type of radiographic changes that result in hemophilic shoulder arthropathy and correlate these radiographic changes with clinical symptoms.
MATERIALS AND METHODS
Eight hundred twenty-two charts from patients with hemophilia seen at our institution from 1969 to the present were reviewed for either shoulder symptoms or evidence of previous shoulder radiographs. The protocol approved for human subjects in research at our institution was strictly followed. Of the 822 patients studied, 93 previously required shoulder evaluation. We were able to obtain the shoulder radiographs for 77 of these 93 patients. The radiographs were assessed for quality and then analyzed by two independent observers according to the radiographic scoring method of Pettersson et al7 (Table 1). The presence of humeral or glenoid osteophytes also was recorded.
The patients’ radiographs were divided into three groups based on their Pettersson score: mild, moderate, or severe. Scores less than four were categorized as mild, scores of four to six were moderate, and a score of seven or more was categorized as severe. For 16 of the 77 patients, radiographs were available at various times during the course of their arthropathy. For such patients with serial radiographs, the progression of disease was observed, and these radiographs also were evaluated according to the scoring method of Pettersson et al.
The incidence of clinical symptoms was documented through a chart review. Specifically, charts were reviewed for history of shoulder hemorrhages, symptoms, range of motion (ROM), function, and prior surgeries. The incidences of arthropathy in joints other than the shoulder also were noted. The hemophilia status, specifically, Factor VIII level, and the presence or absence of inhibitors also was documented. A complete clinical history consisting of these data was available for only 54 of the 77 patients. The information from these 54 patients then was correlated with the level of radiographic disease.
A statistical analysis was done using a chi square test to assess the relationship between radiographic disease and clinical symptoms.
The mean age of the patients at the time of their first radiograph was 32.5 years (range, 9–69 years). All the patients reviewed had either severe (< 1%) hemophilia A or hemophilia B. It has been documented that there is no significant difference in the incidence of arthropathy in these two disorders.2 Only two patients were reported to have an inhibitor.
The severity of shoulder arthropathy also correlated with the extent of arthropathy the patients had in their other joints. Six patients (24%) with mild arthropathy (Pettersson score 1–3) had hemophilia-related arthropathy in at least one other joint. This is considerably less than in the patients with moderate and severe arthropathy of which 19 (66%) and 10 (59%) patients, respectively, had multiple joint arthropathies.
Seventy-one of the 77 patients had evidence of radiographic disease, whereas six patients did not have any radiographic changes. Thirteen patients had bilateral shoulder disease. The mean score, based on the radiographic scoring method of Pettersson et al, for the patients with radiographic changes, was 4.62 (range, 1–11). Six patients had normal radiographs (score of 0), 25 patients scored in the mild range (< 4), 29 patients scored in the moderate range (between 4 and 6), and 17 patients scored in the severe range (> 6).
Osteophyte formation is not considered a common feature of hemophilic arthropathy, and is not included in the general scoring method of Pettersson et al. However, osteophytes were seen in 58% of patients in the current study. The presence of osteophytes was documented but not included in the scoring process. The osteophytes primarily developed on the inferior aspect of the glenoid, the humeral head, or both (Fig 1). Of the 25 patients with mild arthropathy, four (16%) had osteophytes develop on the inferior glenoid surface only, but no patients had osteophytes develop on the humeral head. Twenty-one patients (72%) with moderate arthropathy had osteophyte formation, including nine patients (31%) with osteophytes on the glenoid and humeral head. Finally, 16 of 17 (94%) patients with severe arthropathy had osteophytes develop, with 11 patients having osteophytes in both locations (Table 2). Therefore, osteophyte formation seems to increase in incidence and severity along with the general progression of shoulder arthropathy in patients with hemophilia.
The most frequent radiographic changes were subchondral cysts and irregularities. Sixty-three patients (82%) had both of these changes. Less common, yet still present in more than 50% of the patients, is joint space narrowing and osteophyte formation. In addition to the aforementioned changes, some patients with severe arthropathy also had marginal erosions, or deformity of the glenohumeral joint, or both develop (Table 2).
Rodriquez-Merchan8 stated that recurrent hemarthroses and hyperemia cause enlargement of the growth plate in children. The current findings were consistent with this hypothesis, as enlarged growth plates were found in the pediatric radiographs that were reviewed. No significant amount of osteopenia was seen in patients included in the current study.
Joint deformity is another manifestation of hemophilia. Thirteen patients (13/77; 17%) had some deformity including incongruence, subluxation, and complete erosion of the head (Fig 2). Four patients also had elevation of the humeral head, which has been referred to as acetabularization (Fig 3).
On review of the complete 54 clinical charts, 36 patients had either pain or decreased ROM. The six patients with no radiographic changes did not experience shoulder pain or decreased function. Of the 25 patients with mild radiographic changes, eight (32%) had a documented history of shoulder pain or decreased ROM. Seventeen of the 29 patients with moderate arthropathy (59%) had a history of shoulder pain or impaired function, and 11 of 17 patients (65%) with severe arthropathy had a history of shoulder dysfunction. Although a trend was seen between increased radiographic changes and clinical symptoms, the difference was not statistically significant (chi square = 2.83; 0.05 < p < 0.1).
Seventeen of the 77 patients had serial radiographs taken of their shoulders. In the majority of patients, the early radiographs showed changes consistent with mild arthropathy. When these patients had radiographs taken of the same shoulder several years later, the majority (11/17) had changes consistent with severe arthropathy, most likely secondary to prolonged inflammation or recurrent bleeding episodes or both.
Finally, 21 (21/77) patients had radiographs taken of both shoulders. Thirteen of these patients had bilateral radiographic changes, with one side more severe than the other, whereas the others had no evidence of arthropathy on the contralateral side.
Only three patients (three of 77; 4%) had surgery for the shoulder arthropathy. This is in contrast to the 19 patients (19/77; 25%) in this group who had surgery for arthropathy of other large joints, specifically the knee, hip, and elbow. The shoulder surgeries included one fusion, one open synovectomy, and one stabilization procedure.
Based on the radiographic changes observed in the three groups, it is possible to describe the radiographic changes that tend to occur in shoulder arthropathy in patients with hemophilia. The most common changes among all the patients and the changes seen most often in patients with mild arthropathy are greater tuberosity cysts (Fig 4) and mild subchondral irregularities. The patients who have a moderate amount of radiographic changes have glenoid osteophytes, subchondral and humeral head cysts, partial joint space narrowing, and marginal erosions (Fig 5). Patients who have severe radiographic changes also have severe marginal erosions, obliteration of the joint space, and humeral head and glenoid osteophytes (Fig 1). Several of the patients with severe arthropathy had deformity of the glenohumeral joint develop (Fig 2).
There was a correlation between the stage of progression of radiographic changes and clinical symptoms. The radiographic changes described above correlated with symptomatology because only 32% of patients in the mild radiographic group had symptoms compared with the patients in the moderate and severe groups with symptoms in 59% and 65%, respectively.
For patients with serial radiographs, early radiographs were compared with those taken later. The radiographic changes seen in serial radiographs of one patient (Fig 6) were almost identical to changes described from looking at the cross-sectional data (Table 2). For instance, the first radiograph of this patient (Fig 6A) shows an arthropathy similar to that seen on radiographs from patients with mild arthropathy whereas the later radiographs (Fig 6B,6C) look similar to the radiographs from the patients with moderate and severe arthropathy, respectively.
Although MacDonald et al5 reported that 37% of patients in their study had shoulder symptoms and of those patients, 24% had abnormal rotator cuff ultrasounds, only four patients in our study had findings suggestive of rotator cuff arthropathy (Fig 3). However, patients may have rotator cuff tears without glenohumeral elevation, which only can be evaluated accurately with ultrasound or MRI. If the prevalence of rotator cuff damage in patients with hemophilia with shoulder symptoms is approximately 25%, it may be that the mechanism of this rotator cuff disorder is intraarticular hemorrhage leading to inflammatory changes and rotator cuff damage similar to rheumatoid arthritis. We currently are initiating an MRI study to show the incidence of rotator cuff disease in patients with hemophilia. Clinically, we recommend an MRI or ultrasound early in the treatment of patients with hemophilia who have shoulder symptoms.
Because of the retrospective nature of this study, and the lack of complete clinical charts, it is impossible to accurately correlate clinical symptomatology and radiographic changes. A thorough history of bleeding with the age of onset of bleeding into the shoulder and the number of incidents of bleeding into the shoulder per patient was not obtained, therefore, the relationship of intraarticular hemorrhages to this disease entity cannot be described accurately. Also, the lack of standardized radiographs made it more difficult to evaluate radiographic changes such as joint space narrowing or to describe the progression of radiographic disease.
Osteopenia is one of the common early findings of hemophilic arthropathy because of hyperemia and limited weightbearing. Our findings did not concur. It is possible that because the shoulder is not a weightbearing joint, osteopenia in these patients is less prevalent than described in other joints. Osteopenia also is difficult to assess on plain radiographs. Therefore, a bone density scan would determine the presence of osteopenia more accurately.
Despite the significant radiographic and clinical findings, only a small percentage of patients had surgery. Surgery of other joints (knee, hip, elbow) was more common. This disparity may be because the shoulder is not a weightbearing joint, therefore clinical symptoms may be less debilitating. Also, because shoulder disease in patients with hemophilia often has gone unrecognized, patients’ symptoms may be ignored. With early recognition, perhaps surgical options such as rotator cuff repair may improve the clinical function of these patients.
The prevalence of hemophilic shoulder arthropathy in our patient population is greater than previously reported,1,2,4 with the exception of the study by MacDonald et al.5 In addition, a consistent pattern of radiographic changes was observed, similar to those described in other joints with hemophiliac arthropathy. Additionally, there was an increase in clinical symptoms in patients with increased radiographic changes. We hope that by showing the type and possibly the progression of radiographic changes seen in shoulder arthropathy in patients with hemophilia, the pathophysiology of this disease process may be understood better leading to early and appropriate clinical intervention.
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© 2004 Lippincott Williams & Wilkins, Inc.
8. Rodriquez-Merchan EC: Effects of hemophilia on articulations of children and adults. Clin Orthop 328:7–13, 1996.