‘Don’t give up’: Catatonic woman wakes up after 20 years following treatment for lupus
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A woman diagnosed with schizophrenia and psychosis who was nonverbal and nonresponsive for 2 decades recently “woke” after treatment with pulse steroids and cyclophosphamide.
It turned out she had lupus.
The story, which made headlines in the Washington Post and other outlets this past summer, features a pair of chance encounters involving Sander Markx, MD, director of the Precision Psychiatry Initiative at Columbia University. He encountered the patient, April Burrell, in 2000, when he was a trainee and she had just been admitted to Pilgrim Psychiatric Center, a state hospital in Brentwood, N.Y. Her complete lack of responsiveness left a strong impression on him, but he was unable to do anything about her condition at the time.
By 2020, Markx was in charge of his own laboratory. He encouraged his students to visit Pilgrim Psychiatric Center to get a sense of some of the most severe patients they may encounter in their careers. A trainee in the program visited the facility and ran into Burrell, who remained largely unchanged from when Markx first visited her 2 decades prior.
She had been treated with a broad spectrum of medications, including antipsychotics, mood stabilizers and electroconvulsive therapy. None of it was effective.
When Markx became involved with the patient again, he had her sent for a lab panel that included a lupus workup. The eventual diagnosis of lupus was made by his rheumatology collaborator, Anca D. Askanase, MD, MPH, director of the Columbia University Lupus Center, and treatments were promptly administered.
Suddenly, Burrell was back.
The episode highlights a number of relevant topics for the rheumatology community. One pertains to the neuropsychiatric complications often observed in patients with lupus. Another is the need for rheumatologists to collaborate with partners in neurology and neuropsychiatry.
And yet another was articulated by Askanase, who became involved with Burrell throughout the diagnosis and treatment process.
“Don’t give up,” she said.
Healio sat down with Askanase to discuss the events surrounding Burrell’s lupus diagnosis and what they might mean for the broader rheumatology community.
Healio: Thanks for talking with us about this.
Askanase: Well, first I want to mention that this story has been enormously relevant to a lot of people.
Healio: What were some of the particular features of Burrell’s case?
Askanase: April has had a 20-year history of psychiatric illness. She had been diagnosed with schizophrenia and was refractory to antipsychotic medications. Early on, she demonstrated mostly typical features of psychosis.
This was a harder case because it took a long time for anyone to think of the possibility of an autoimmune disease as a potential cause. We came to this after a long history of decline. She was very impaired, with no communication. She was rocking back and forth and had minimal interaction with people.
Healio: How did you become involved?
Askanase: The way it all came together is because Dr. Markx thought her behavior was so atypical and unusual. Patients with psychiatric illness do not usually behave like this. It did not make sense. So, they had her antinuclear antibodies checked and it came back positive. They sent her for a rheumatology consult to better characterize the illness. I was the consultant.
We did a full antibody profile, a full central nervous system workup, an MRI, a lumbar puncture. She had arthritis on the physical exam and her anti-DsDNA was positive. The MRI showed volume loss, which is atypical for people with psychiatric illness. Her cerebrospinal fluid was showing a large number of white cells and a slight increase in protein. Of course, the malignancy and infectious workup were done and were negative. We thought maybe an inflammatory immune mediated process was culpable for her psychosis.
Healio: What was the next step?
Askanase: She was treated with pulse steroids and cyclophosphamide. Within three treatments, she demonstrated a good response in terms of behavior and cognition. It was very rewarding. She came back from this place of almost being non-communicative. It was a very emotional time. She told stories of her childhood.
Healio: What would you say this case means for the connection between rheumatology, psychiatry and neurology?
Askanase: To start, it is important to understand that the connection between lupus and neuropsychiatric manifestations is well established. Psychosis and seizures are part of the initial 1982 diagnostic criteria for lupus. So, rheumatologists should be well positioned to do an immune panel and autoantibody workup in certain patients with psychosis. However, neuropsychiatry will likely be the intake folks for these patients.
Probably the best way to make sure these patients are managed appropriately is to raise awareness in the psychiatry community that unexplained symptoms in their patients may be caused by some kind of autoimmunity.
Healio: How about the connection between neuropsychiatric complications and other rheumatic or autoimmune diseases?
Askanase: It is likely that overlap may extend into Sjögren’s syndrome and antiphospholipid syndrome. However, autoimmune encephalitis, PANDAS and Lyme disease are other areas of immune attack on the brain that rheumatologists may see.
Healio: How can this result inform the treatment of other patients with lupus who are experiencing various neuropsychiatric complications?
Askanase: In lupus, using cyclophosphamide for treating life-threatening conditions could be a way forward. It may also help us tease out more targeted approaches using new therapies. There is a possibility that anti-interferon therapy and CAR T-cell therapy may be important in treating psychiatric manifestations. These could be intriguing approaches.
Healio: What does this mean for other patients with schizophrenia? Might it be possible to treat those patients successfully with lupus medications?
Askanase: I think this information is only useful for the people who have an immune-mediated condition that is responsible for the neuropsychiatric complications. I do not think autoimmunity is the answer to all mental health issues, but it is for a subset.
Healio: Where do we go from here in terms of research?
Askanase: This is a potentially high impact, high reward area, to bring a patient back from the depth of psychosis and cognitive issues. We are hoping that these extraordinary stories of recovery will create or increase interest and provide some much-needed research dollars to better understand these diseases. That may come from traditional sources of funding or private donors. Our psychiatry colleagues have been fortunate to have private donations to move this research forward.
Healio: What would you suggest to other rheumatologists for managing a similar patient?
Askanase: Please collaborate with a neurologist and psychiatrist. Don’t give up on a patient who comes in with unexplained autoimmunity or unexplained psychiatric symptoms.
We put together a series of several similar cases that was published in Arthritis & Rheumatology. There were two younger women and an older man who have similar stories. Several new cases have accumulated since and we are planning on describing and publishing these cases as well. These patients are out there, please look out for them.
Healio: How is the original patient doing today?
Askanase: Dr. Markx and I are planning a field trip to see her and will report back soon.
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Healio interview
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