Ankle Joint Damage in Hemophilia Common, But Not Linked to Pain

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Structural joint damage and significant pain are evident in the ankles of people with hemophilia, but the two were not found to be related to one another in a recent study.

Researchers suspect that ankle pain may originate in the somatosensory nervous system, which relays nerve signals from the body to the brain via the spinal cord, rather than with the ankle itself.

“Structural joint damage is present in many ankles but is not related to pain in [people with hemophilia]. Further studies should consider somatosensory nervous system dysfunction in [patients] as contributing factor to painful ankle [joint disease],” they wrote.

The study, “Gaining more insight into ankle pain in haemophilia: A study exploring pain, structural and functional evaluation of the ankle joint,” was published in the journal Haemophilia.

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Hemophilia’s hallmark feature of prolonged, excessive bleeding can occur internally, leading to painful swelling and damage to the joints, a condition known as arthropathy. Ankle arthropathy is prevalent among patients, leading to significant pain and disability.

To further explore the mechanisms and consequences of ankle arthropathy among people with hemophilia, a research team in Belgium assessed ankle structure and function, physical activity, pain, and quality of life in 30 adult males who were recruited from the Haemophilia Comprehensive Centre in Brussels.

Among these men, 26 had hemophilia A — 23 with severe disease and three with moderate disease — and the remaining four patients had hemophilia B, which was considered as severe in one case.

The structure of two ankle joints — the talocrural (TCJ) or the subtalar (STJ) — was evaluated in both ankles of each patient for 60 total evaluations. TCJ abnormalities were observed in 76% of cases, whereas STJ changes were seen in 55% of ankles. Damage in both joints occurred in 49% of all ankles evaluated.

In both joints, more significant abnormalities were observed in the osteochondral tissue — bone and cartilage — than in soft tissue components of the joints, such as supportive and connective tissues like muscle, fat, nerves, and tendons.

Ultrasound examinations, given to look at structural changes in joints, showed disease-associated abnormalities in 93% of patients’ ankles. A clinical assessment of joint function using the Haemophilia Joint Health Score (HJHS) indicated joint dysfunction in 50 out of 60 ankles, and in 40 out of 60 knees.

Structural abnormalities (using MRIs and ultrasound) significantly correlated with poorer joint function on the HJHS.

Physical function tests found that participants moved more slowly and could not walk as far in a short time as expected for their age category, although it was not clear whether this can be explained by poorer ankle joint mobility or other factors, the team noted. Daily activities and life quality were also disrupted, with patients reporting problems with mobility, usual activities, and pain or discomfort.

A majority, 83%, of study participants reported at least one painful joint, with the ankle the most painful joint in 20 out of these 30 adults. The team observed large variations in pain sensitivity, measured using the pressure pain threshold test, with some patients showing hyperalgesia, or a highly sensitive pain response.

Higher pain sensitivity was also evident for some not just at the injured ankle but in other undamaged areas as well. Researchers hypothesized that pain might be arising from problems with the nervous system, which mediates pain responses in the brain, rather than from inflammation and tissue damage in the ankle itself. This could cause perceptions of pain in several areas, they said.

Two types of pain can arise from damage to or problems within the nervous system. Neuropathic pain is caused by nerve damage, while nociplastic pain arises from altered processing in the somatosensory nervous system that influences pain perception.

Consistent with the team’s hypothesis, nine patients had high scores on a questionnaire used to determine if pain is neuropathic or nociplastic in origin. All four patients who reported experiencing pain at five or more body locations also had high scores, indicating a likelihood of neuropathic or nociplastic pain.

Neither perceived ankle pain nor pain sensitivity correlated with structural ankle abnormalities, which could also be explained by pain arising from an altered pain perception in the nervous system, rather than the damaged ankle tissue itself.

“The results of this study suggest that the ankle is affected in the majority of [people with hemophilia] and confirm that pain is an important problem” in adult patients, the researchers wrote.

“Lack of meaningful correlations between structural assessment and pain outcomes should be further explored, and dysfunction of the somatosensory nervous system should also be considered in [people with hemophilia],” they added.