Cold agglutinin disease, nephritis develop secondary to lupus
Researchers: Few cases of CAD with SLE reported in literature
A woman in Costa Rica developed cold agglutinin disease (CAD) secondary to a diagnosis of systemic lupus erythematosus (SLE) that was complicated by nephritis, a serious kidney inflammation that often occurs with this form of lupus.
CAD “is exceptionally rare in SLE, with few cases being reported in the literature,” researchers wrote in “Systemic Lupus Erythematosus Presenting With Cold-Antibody Autoimmune Hemolysis and Nephritis: A Case Report,” which was published in Cureus.
In SLE, the immune system mistakenly attacks the body’s tissues, driving a lasting inflammatory response. The attacks are caused by self-reactive antibodies made by immune B-cells. When they take place in the kidneys, they can cause nephritis.
A known complication of SLE is autoimmune hemolytic anemia (AIHA), where the immune system attacks and destroys red blood cells. In most cases, antibodies active at normal body temperatures are responsible for this destruction. In rare instances, however, this can be caused by cold agglutinins, the self-reactive antibodies that are a hallmark of CAD and that bind to red blood cells in colder temperatures, marking them for destruction by the immune system.
Diagnosing CAD secondary to SLE
Here, researchers described the case of a 53-year-old Hispanic woman with SLE who developed both secondary CAD and lupus nephritis. Unlike primary CAD, which occurs for unknown reasons, secondary CAD results from an underlying condition, generally a blood cancer, an infection, or an autoimmune disease.
The woman, who had a history of high blood pressure and high cholesterol, visited the emergency room due to chest pain. She had been managing her health with her primary care doctor for five years due to metabolic syndrome, a group of conditions that increase the risk of cardiovascular disease and diabetes. The woman had been taking iron supplements for a year after being diagnosed with moderate anemia during a routine check. Anemia can occur when red blood cells are destroyed too rapidly and there’s a drop in hemoglobin, the iron-containing protein that carries oxygen in red blood cells.
Six months before her visit, the woman began having weight loss, night sweats, and fatigue, which gradually worsened. The symptoms progressed to difficulty breathing during moderate activity and swelling in her lower legs. She reported no skin rashes, mouth sores, or joint pain.
At the emergency department, the woman said her chest pain appeared suddenly and radiated to her lower jaw. Her heart rate and blood pressure were slightly high, and she had swelling in her legs and eyelids. An electrocardiogram of the electrical activity of her heart showed a fast, but regular heartbeat.
Blood tests showed low hemoglobin, indicating severe anemia. Her kidney function was impaired and there were signs her red blood cells, which were seen to clump at cold temperatures, were being destroyed. The woman tested positive for a direct Coombs test, which checks if circulating red blood cells are covered with antibodies. Cold agglutinin titers, which measure cold agglutinin levels, were very high. The findings led to a diagnosis of CAD.
The woman was given an urgent blood transfusion and admitted to the hospital for testing. She started the steroid prednisone and rituximab, a medication that depletes antibody-making B-cells. Rituximab is sold as Rituxan, among other brand names, and biosimilars are available. The treatment quickly improved her hemoglobin levels and stopped the destruction of her red blood cells.
The woman’s vitamin B12, folate, and iron levels tested normal, but ferritin, a protein that stores iron, keeping it off circulation, was high. Doctors ruled out an infection as the underlying cause of CAD and tests on her bone marrow showed no signs of blood cancer.
A urine test did reveal proteinuria, which refers to the presence of excess protein in urine, a sign of kidney problems. Further blood tests found high levels of a certain type of antibodies, with positive results for markers of autoimmune disease.
“Based on the clinical presentation and laboratory studies, SLE was suspected,” the researchers wrote.
A kidney biopsy, where a small piece of tissue is removed for examination under a microscope, confirmed severe lupus nephritis. The woman was started on oral hydroxychloroquine, an antimalarial used for treating lupus, while her steroid dose was gradually reduced, and she received cyclophosphamide injections, which are used for certain autoimmune disorders.
After six months, her clinical condition improved significantly, with red blood cell destruction stopping, hemoglobin levels returning to normal, and kidney function improving, as shown by a rapid drop in protein levels in the urine.
“This case underscores the rarity of [CAD] in the context of SLE, particularly when coupled with nephritis, and highlights the need for tailored treatment strategies,” wrote the researchers, who noted rituximab “appears to be one of the mainstays in disease control.”
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