My Odyssey With a Very Rare Disease

The story of Jeanette

I have a rare disease that makes me very sensitive to cold, and not just the extremities like hands, feet, nose, ears. My body reacts to cold everywhere that cold contacts my skin. I turn blue, purple, splotchy, and those areas go numb. I’ve had the condition for lots of years, but finally got a definitive diagnosis about a year and a half ago.

I have a disease called Cold Agglutinin Disease (CAD), an autoimmune disease in which auto-antibodies called Cold Agglutinins (CAs) attach to red blood cells and cause them to clump, or “agglutinate,” so that blood can’t get to the tiny capillaries on the surface of the skin, and eventually they can destroy red blood cells.

I have the primary form of this disease, which means it isn’t associated with some other disease or disorder, and the cause of these particular antibodies going rogue is unknown. Statistics are hard to come by because of the rarity of this disease, but one study showed an incidence rate of one case per million people each year. My primary care physician (PCP) had never heard of the disease, and even when I was referred to a hematologist/oncologist she had seen only three cases, all secondary CAD, no primary cases, and they were all during her training, so she had never dealt with it in her clinical practice.

I have undergone the only treatment that is medically recommended for CAD, which is a rigorous course of chemotherapy – the same treatment that is used for leukemia. I am now waiting the several months that it may take to see if this alleviates my severe cold reaction.

So let me tell you more about my strange, and lonely, odyssey. I have experienced the cold reaction since about 2007, so I was about 66 when it started, and I’m 81 now. Until the middle of 2021 I thought I had another cold-reaction disease that is also rare but more common than CAD, Raynaud’s Disease. Raynaud’s is a different mechanism, occurs at colder temperatures, and only affects extremities. My reaction has progressed over the years to where it’s now triggered even by temperatures in the low 70s. And my whole body reacts, not just extremities. Even under layers of clothes where I sweat and there is evaporative cooling, the skin turns a mottled purple.

Early on, I had self-diagnosed myself as having Raynaud’s because it was the only cold-reaction disease that I found in my extensive research. In 2013, I consulted my dermatologist, and he sent me to a rheumatologist, who, based on my symptoms, confirmed Raynaud’s and ordered tests to see if I had other autoimmune diseases that might be causing Raynaud’s. Those tests were negative, and I was left with a Primary Raynaud’s diagnosis. I just decided I had a weird case of Raynaud’s and had to prevent my skin from getting cold. It wasn’t easy because I’m an outdoors person. I walk five miles a day no matter the weather. I also camp, hike, bike. I just covered up, including a warm hat with ear flaps, warm face mask, good gloves. With the help and understanding of my husband/outdoors companion, I was able to accommodate and continue my active lifestyle, plus spending the winters in a warm climate in Mexico.

I myself made the discovery that led to my CAD diagnosis in mid-2021. I was preparing for my annual checkup with my PCP, reviewing blood test results from the previous year, and noticed several references to “cold agglutinins.” I saw this notation: “CBC (Complete Blood Count) results reported were obtained after the specimen had been warmed to 37 degrees C. Red blood cells appear slightly agglutinated.”

I did some internet research on CAD and told my PCP that I thought we needed to consider I may have this condition. I looked at lab results from 2018 and 2019, and they also mentioned CAs in the CBC values. I started looking back at my experience with supposed Raynaud’s and realized I always had questions because certain things didn’t fit. It’s usually young women who have Raynaud’s and it’s temporary. My cold reaction is chronic, and every time my skin gets cold it reacts.

My PCP was apologetic about not recognizing the CAD signs, but he did his research, and was quick to order several appropriate tests. The results supported a CAD diagnosis, and my doctor referred me to a hematologist/oncologist.

The hematologist was well prepared when I saw her in early August of 2021, having checked my entire medical history as well as all the lab results my PCP provided. She was fascinated and very engaged with my case because it was new to her. She ordered a battery of blood tests, and later, imaging and bone marrow biopsy to rule out some association with blood cancer or other autoimmune diseases. The blood tests again confirmed the CAD diagnosis, with a pretty high level of CAs. The good news was that I didn’t have any of the cancers or autoimmune diseases that CAD can be associated with. And I was only slightly anemic, so it didn’t appear the CAs were doing significant damage to my red blood cells.

The hematologist was concerned about possible ill effects of my CAD over time, especially if the cold sensitivity continued to worsen. She recommended the chemotherapy treatment which she was pretty confident would destroy the CAs and prevent future blood problems. It would involve infusions two days a month for a period of four months.

I agonized over the decision of whether to undergo chemo while we were spending the winter of 2021-22 in Mexico. (When the doctor had first mentioned it, my reaction was a shocked, “Absolutely not!”) But with time for me to consider possible worsening, as well as both the hematologist and my husband advising me to do it, I finally decided I needed to try it, and that I was healthy and fit enough to handle the chemo.

So I started the treatments in early May last year and finished the fourth one in late July. I actually got a combination of two drugs – Rituximab and the chemotherapy drug Bendamustine. My body handled the toxic effects of chemo quite well, and I didn’t experience serious side effects. I do believe that being healthy and fit going in, plus mustering a positive attitude and maintaining my active lifestyle helped immensely. I never missed a day of walking my five miles.

There were interesting experiences with medical personnel because no one had dealt with CAD before. An example is the weird phenomenon that when I have a blood draw, the vials have to immediately be kept warm or the blood coagulates almost as soon as it hits air. Before each treatment, I had blood draws, and each time my husband and I had to educate the nurses, who were puzzled but eventually said they appreciated the learning experience. They also had to warm the infusion. At my first treatment, after we had instructed my nurse, she said she had gotten a call from my oncologist in a panic at the last minute telling her that if they didn’t warm the drugs, I would turn blue. I do have a warning in my medical records that if I ever need a blood transfusion, the blood needs to be warmed.

Of course, I am very glad that I dealt well with the chemo, but both the doctor and I were disappointed that I did not show early improvement in my severe reaction to cold. Blood tests a month after the end of treatments showed that I still had the same number of those nasty CAs as I started with. My doctor told me that in some cases it can take months, even up to a year, to get results. I am working on being patient and hopeful.

My next checkup is scheduled in May soon after we return from our winter in Mexico. We will be checking on the CA numbers again, checking to see if all my blood counts are returning to normal after chemo, and monitoring any possible risk of further CA damage or progression.

So it’s wait and see, and continue to cover all of my skin in cold temperatures.