Patients with neuropsychiatric lupus symptoms ‘diverse ... not unique’
Although patients with neuropsychiatric manifestations of systemic lupus erythematosus can exhibit a diverse range of rare manifestations, these symptoms are not necessarily unique to lupus, according to a presenter here.
“I don’t think I need to prove to anyone in this room that patients with lupus are diverse,” Joan T. Merrill, MD, director of clinical projects in the Arthritis & Clinical Immunology Program at the Oklahoma Medical Research Foundation, told attendees at the 2021 Congress of Clinical Rheumatology-West. “Even when we are trying to focus on neuropsychiatric symptoms – which are quite rare in lupus – there is immense diversity in what has been reported. In fact, there are 19 syndromes put together by the ACR described as ‘CNS lupus’. That is what we are facing: A very diverse population.”
“On the other hand, people with lupus are not unique and almost every one of the manifestations that we see in lupus can be found on their own in people without other manifestations of lupus, and also found not that uncommonly in related disorders,” she added. “To make matters more complicated, the presenting features and even some of the diagnostic results that we get working up these patients overlap a great deal. We can’t always tell by the symptoms, we can’t always tell by the diagnostic work-up, and to some extent, the edges between these syndromes are very blurry.”
‘Lupus headache’ has long stood out as a stereotypical neuropsychiatric manifestation and remains a disease-related entity in the Systemic Lupus Erythematosus Disease Activity Index. However, due to its lack of a detailed definition, debate has continued over whether this represents a valid neuropsychiatric symptom of lupus. For Merrill, this is not a debate worth having.
“I’m here to tell you guys there is no lupus headache, which is something we have been saying for years,” she told attendees. “I think what happened was that sometime between when people thought there was a lupus headache and now, we developed much better treatments for classic migraines and all those lupus headaches went away.”
Among the most commonly reported neuropsychiatric syndromes among lupus patients are headache, cognitive, anxiety and depression. However, Merrill noted that these are “rarely caused by lupus, yet all of them are on the list because, once in a while, that is how someone is going to present.”
For headache, Merrill said that it’s “probably not from lupus,” but could be a presenting sign of meningitis, pseudotumor or cranial neuropathy. “But these syndromes tend to present in a more complex way, so it’s pretty unlikely that you would think an isolated headache would be not due to lupus,” she said.
Another common syndrome is cognitive dysfunction – “again, usually not due to lupus”. However, Merrill noted that a “big exception” to this is multi-infarct dementia, a common cause of memory loss in the elderly, which has been observed in patients with antiphospholipid syndrome.
“It’s very sad because its insidious onset, slow, and you could say its due to lupus or due to microthrombi, but either way you want to look at it in the context of lupus,” Merrill said. “You want to consider the patient’s age, whether they are very tired, which is of course one of the most common complaints for patients with lupus; it’s a very exhausting disease. It can certainly affect your ability to focus.”
Clinicians should also rule out whether patients have a mood disorder, a cardiovascular risk factor and whether these symptoms could be due to thyroid disease.
“Anxiety syndromes are usually situational or unrelated to lupus but could always be part of a complex SLE-related syndrome,” Merrill said. “I think you want to think of these things: Is this in isolation or am I seeing something else going on here? If you rule out something else going on, you kind of assume it’s probably not due to lupus. The same thing with depression, as it’s usually not related to SLE flare.”
Aside from lupus, there are several more common potential causes of certain neuropsychiatric syndromes that clinicians may not be familiar with, according to Merrill.
“For example, if there’s a seizure, it’s very hard to know what caused it,” she said. “It could be diffuse CNS lupus, it could be brain inflammation, it could be due to vasculitis, or it could be due to antiphospholipid syndromes, which have been reported quite a few times in the literature. Seizure is very hard to figure out.”
Cerebrovascular disease, on the other hand, “once we diagnose it, is usually due to vasculitis or antiphospholipid syndrome.”
Merrill noted that an “acute confusional state” could be diffuse general brain inflammation, CNS lupus “or it could easily be vasculitis but again it usually wouldn’t just occur by itself with nothing else to suggest vasculitis.”
Lastly, myelopathy and demyelinating syndrome could also be potential causes of neuropsychiatric syndromes in neuromyelitis optica spectrum disorder, which is commonly associated with lupus, Sjogren’s syndrome and antiphospholipid syndrome.