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Impact of Cold Agglutinin Disease on Patients - AJMC.com Managed Markets Network

Neil Minkoff, MD: Both of you have mentioned at some point that this, especially the cold agglutinin disease, is a pretty rare disorder. How prevalent is it actually, and where do we end up seeing it mostly? Is it in particular geographic climates or something?

Jeremy Lorber, MD: Yes, it is quite rare. Different studies looking at the prevalence are all done in different countries, which is important, the point that you just mentioned, so you’ll see variation. The prevalence in countries that typically have colder climates will be a little higher than those that have warmer climates closer to the equator. But roughly 5 to 20 per million has been described as the prevalence in various studies.

Neil Minkoff, MD: We’ve had sort of a technical discussion. We’ve talked a lot about pathophysiology and IgG [immunoglobulin G] and IgM [immunoglobulin M] and intravascular hemolysis and so on, but let’s try to kind of humanize this a little bit if we can. What does this do to the patient? How does this affect quality of life? How does it affect their ability to do activities of daily living or to engage in certain activities and so on? Can we try to put a face on it?

Mihir Raval, MD, MPH: Definitely. I think the biggest challenge the patient experiences from this disease is anemia-related symptoms. Many times that’s the leading cause of presentation, so patients have this undiagnosed, for which they don’t really know what is going on, anemia, fatigue, tiredness, and that has been going on for months, for years, before actually the diagnosis is established. They will be actually referred to their primary care provider; a common diagnosis that they establish would be an anemia, iron deficiency or something, they start the patient on iron treatment without any benefit. But the other major symptom that patients also experience, especially in winter months, is actually symptoms in their extremities. When they are exposed to cold, they end up having something called acrocyanosis, which means they have this purplish discoloration of the extremity. Sometimes they have purple patches, which is what we call livedo reticularis, and sometimes they have Raynaud-like presentation. Those are the 2 biggest presenting symptoms for the patients: anemia leading to fatigue, tiredness, not being able to do the activity they like doing, along with their shortness of breath while doing minimum exertion or any form of activity like exercise. Also, these extremity-related symptoms when they’re exposed to cold. Sometimes, that happens in younger patients, while most of the time it is in patients who are in their 50s and 60s. In younger patients when that happens, they do feel isolated, so that does impact their self-image. They do feel depressed, and they do feel like that they are not fitting in with their peers. That can definitely impact mental health, especially because it’s such a rare disease, and all of the symptoms do not lead to an early diagnosis unless there is an astute physician who picks up on them and sends them to a hematologist for evaluation.

Jeremy Lorber, MD: To expand on a couple of points that Dr Raval made, the delay in diagnosis itself is a burden on the patients. Many of the patients, like he mentioned, are on prolonged ineffective treatments like iron, or I’ve even seen prolonged treatment with corticosteroids, which are typically ineffective and have their own large adverse effect burden. Thus, the patients become frustrated about this prolonged treatment without any benefit. Then, in addition to the fatigue from the anemia, there’s thought to be also fatigue separate from the anemia due to activation of the complement cascade. We see this in some other diseases like PNH [paroxysmal nocturnal hemoglobinuria] that are complement driven, where anemia does obviously contribute to fatigue, but it’s not just the anemia. There are other things going on that can contribute to lack of well-being in the patient.

Transcript edited for clarity.

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Impact of Cold Agglutinin Disease on Patients - AJMC.com Managed Markets Network
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