Nearly one-third of persons with hemophilia had neuropathic pain or altered central pain mechanisms, investigators in a small study found.
Among 30 patients with hemophilia, 9 (30%) had scores of 4 or greater on the 10-point Diabetic Neuropathy 4 (DN4) scale, indicating significant neuropathic pain, reported Nathalie Roussel, PhD, from the University of Antwerp (Belgium), at the annual congress of the European Association for Haemophilia and Allied Disorders.
“The results of this study show us that a large difference exists in pain assessments when we have consecutive sample of patients with hemophilia. These results also show that there are subgroups of patients with altered central pain mechanisms and other subgroups with neuropathic pain, and patients with neuropathic pain have a significantly worse quality of life that is not associated with joint structure and joint function,” she said.
Dr. Rajiv K. Pruthi
“This is a very good abstract in my opinion, and it deserves more study,” commented hemophilia specialist Rajiv K. Pruthi, MBBS, from the Mayo Clinic in Rochester, Minn., who was not involved in the study.
Structural and functional tests
To get a better understanding of the complexities of ankle pain in persons with hemophilia, Dr. Roussel and colleagues recruited 30 adults followed at their center for moderate or severe hemophilia A or B who were on replacement therapy with factor VIII or factor IX concentrate.
They used MRI without contrast to look for structural alterations in both the talocrural and subtalar joints of both ankles in all patients using the International Prophylaxis Study Group Score, adapted for subtalar joint assessment.
The investigators also used the hemophilia joint health score to assess joint funding, and tests for limits on physical activity, including the Timed Up and Go Test, 2-minute walk test, and Hemophilia Activities Lists.
In addition, they assessed pain with Quantitative Sensory Testing, a noninvasive method for evaluating patient responses to heat, cold, and mechanical pressure. Other measures included questionnaires regarding neuropathic pain and quality of life.
The participants included 23 patients with severe and 3 with moderate hemophilia A, and 1 patient with severe and 3 with moderate hemophilia B. The mean patient age was 39.4 years.
In all, 24 of the 30 patients (80%) were on prophylaxis, and 9 (30%) reported using pain medications; 25 patients reported having some degree of pain.
On MRI, 48/60 (80%) of talocrural joints imaged had pathological findings, as did 41 of 60 (68%) subtalar joints.
“Despite the fact that these patients do not all suffer from ankle joint pain, a lot of them have signs of joint pathology,” Dr. Roussel said.
On the Brief Pain Inventory, only 5 patients had no reported pain, but 14 patients reported either three, five, or six painful locations, and 20 out of 30 patients reported that their ankles were the most affected joints.
Although the sample size was not large enough for statistical comparisons, there were also large variations in pain perception across hemophilia severity.
“This is an important finding, that also patients with moderate hemophilia can have intense pain,” Dr. Roussel said.
On the DN4 questionnaire, nine patients had scores of 4 or greater, indicating that their pain was neuropathic in origin.
When they compared the patients with neuropathic pain with those suffering from nonneuropathic pain, the investigators observed similar structural and joint function between the groups, but significantly worse reported quality of life for patients with neuropathic pain.
“This is a finding that merits further attention,” she commented.
In correlation analyses, the investigators also found that MRI scores did not correlate significantly with either hemophilia joint health score, physical function, participation in activities, or pressure pain thresholds.
Why the discrepancies?
Dr. Pruthi said in an interview that he has seen evidence from other studies showing that some patients with hemophilia who were on prophylaxis had MRI evidence of joint damage, while others who used on-demand therapy had none.
“That opens up a whole can of worms as to what are we dealing with here. Why do some patients end up with damage and others don’t?” he asked.
He said that the finding that the origin of pain in a large proportion of patients was neuropathic rather than arthritic in origin was new to him.
“It raises a lot of good questions: maybe we need to be managing pain in these patients with nonnarcotic approaches, and in this day and age with the opioid crisis it’s even more important to do that,” he said.
He hypothesized that degenerative arthritis may irritate nearby nerves, resulting in neuropathic pain.
The study was funded by EAHAD, with support from participating institutions. Dr. Roussel and Dr. Pruthi reported no conflicts of interest to declare.