Cracking the Catatonia: Plasma Exchange as Salvage Therapy in Refractory Neuropsychiatric Lupus

Abstract

Neuropsychiatric systemic lupus erythematosus (NPSLE) is an uncommon but severe manifestation of systemic lupus with limited evidence to guide management when standard therapies fail. We report the case of a 19-year-old woman with new-onset SLE with myositis and nephritis overlap, positive for anti-Smith, anti-dsDNA, anti-PL7, and anti-Mi-2 antibodies with hypocomplementemia. Despite treatment with hydroxychloroquine and corticosteroids, she developed progressive weakness, catatonia and psychosis. MRI demonstrated diffuse cerebral volume loss. While hospitalized, she received IV methylprednisolone and mycophenolate mofetil, followed by cyclophosphamide, all with only transient improvement. Given her refractory disease, she underwent five sessions of therapeutic plasma exchange over eight days, which led to gradual resolution of catatonia and restoration of baseline mental and physical function without complications. This case underscores plasma exchange as a potential adjunctive therapy in severe, treatment-resistant NPSLE.

Introduction

Neuropsychiatric systemic lupus erythematosus (NPSLE) is an underrecognized but often severe manifestation of systemic lupus. ¹ Neuropsychiatric symptoms can come in a wide spectrum of manifestations, ranging from common complaints like headaches to rare but debilitating sequelae such as psychosis and seizures.^1,2 These manifestations are frequently difficult to treat, and management typically mirrors that of severe systemic disease. For inflammatory NPSLE, high-dose glucocorticoids remain the cornerstone of initial therapy, with cyclophosphamide added for life-threatening cases and mycophenolate or azathioprine for maintenance, especially in women at risk for gonadotoxicity.^2,3 Nevertheless, some patients fail to adequately respond to these conventional regimens.^1,3

Case Report

19-year-old Nigerian-American woman presented with three-weeks of progressive generalized pain, weakness, and difficulty ambulating. On admission, she was febrile to 102 °F and hemodynamically unstable. Initial evaluation, including CSF analysis and hematologic workup with flow cytometry, was unrevealing. Given multiple clinical features concordant with rheumatic disease, autoimmune serologies were ordered demonstrating a strongly positive antinuclear antibody (ANA 1:1280), markedly elevated anti-dsDNA antibody level (12,000), Smith antibody (>8), RNP (>8) and low complements (C3 28, C4 <2), consistent with new-onset systemic lupus erythematosus. Elevated PL-7 (125) and Mi-2 antibodies prompted MRI of the thighs, showing myositis. Further testing for antiphospholipid syndrome, including anti-cardiolipin antibodies, beta-2 glycoprotein antibodies, lupus anticoagulant with drVVT and hexagonal phase, was negative. Proteinuria was noted, prompting renal biopsy which demonstrated class V lupus nephritis. Despite treatment with hydroxychloroquine, mycophenolate mofetil and prednisone, she continued to decline, presenting from a wheelchair to rheumatology clinic one month later, leading to repeat hospitalization.

Laboratory work was supportive of SLE flare, with the patient showing markedly worsening mental status. CT and MRI brain imaging was obtained which showed diffuse volume loss (Figure 1). Her lupus was treated more aggressively with pulse steroids, leading to significant improvement in her mental status and ambulation. This suggested a diagnosis of neuropsychiatric lupus and excluded differential diagnoses such as primary psychiatric disorders or steroid-induced psychosis. She was discharged on a high dose prednisone taper and maintained on mycophenolate mofetil and hydroxychloroquine.

Figure 1.

Neuroimaging in an 18-year-old female with neuropsychiatric systemic lupus erythematosus and altered mentation. (A) Axial diffusion-weighted MRI demonstrates diffuse, bilateral cortical hyperintensity involving the cerebral gray matter, without a clear vascular territorial distribution, concerning for a global encephalopathic process. (B) Noncontrast CT of the head, sagittal reconstruction, shows enlargement of the lateral and third ventricles without evidence of acute intracranial hemorrhage or mass effect. (C) Noncontrast CT of the head, coronal reconstruction, again demonstrates ventriculomegaly with preserved midline structures and no focal hyperdense lesions

One week after discharge, she relapsed with catatonia, unresponsive to repeat high-dose IV steroids and cyclophosphamide (750 mg/m², NIH protocol). Given her refractory NPSLE, she underwent therapeutic plasma exchange for 5 sessions. She profoundly responded to this therapy, gradually recovering from her severe catatonia and cognitive dysfunction.

Following her hospitalization, she was discharged on hydroxychloroquine and a prednisone taper followed by two monthly cyclophosphamide infusions (750 mg/m2), then transitioned to mycophenolate mofetil. Additionally, belimumab was added due to worsening proteinuria.

Several months after hospitalization, she has remained free of neuropsychiatric symptoms.

Discussion

Neuropsychiatric systemic lupus erythematosus (NPSLE) represents one of the most challenging manifestations of SLE due to its heterogeneous presentations, limited diagnostic biomarkers, and lack of high-quality evidence guiding treatment.^1,2

Despite treatment with methylprednisolone, mycophenolate mofetil, and subsequently cyclophosphamide, this patient developed progressive catatonia, psychosis, and cognitive decline, leading to bedbound status. The lack of clinical response prompted escalation to therapeutic plasma exchange (TPE), which led to marked improvement in her neuropsychiatric symptoms and return to baseline.

The role of TPE in NPSLE remains controversial. Due to lack of formal guidelines, rheumatologists reserve TPE for severe, refractory, or life-threatening cases.^3,4 Evidence for its use is limited: In one retrospective study of 10 patients with severe NPSLE flares unresponsive to corticosteroids and cyclophosphamide, adjunctive TPE was associated with clinical improvement in all cases, with complete remission achieved in more than half.^4,5

The proposed mechanism by which TPE exerts benefit in NPSLE is rapid removal of circulating immune complexes, autoantibodies, and cytokines that contribute to endothelial dysfunction and neuronal injury.⁴ This immunomodulatory effect is particularly useful in acute presentations such as psychosis, catatonia, or rapidly progressive encephalopathy, where conventional immunosuppression is insufficient or too slow-acting.^4,5 Our patient tolerated TPE well, suggesting it can be a safe adjunctive therapy with careful monitoring.

Conclusion

In summary, this case supports the consideration of TPE as a salvage strategy in severe, refractory NPSLE. While encouraging, the use of TPE in this setting is based on low-level evidence, and randomized controlled trials are needed to clarify its efficacy, optimal timing, and patient selection. Until such data are available, its use should be individualized, guided by multidisciplinary discussion and close clinical monitoring.

ORCID iDs

Kuruvilla Rohan https://orcid.org/0009-0007-7823-392X

Bilal Hiba https://orcid.org/0000-0002-3273-2850

Ethical Considerations

Our institution does not require ethical approval for reporting individual cases or case series.

Consent for Publication

Verbal informed consent was obtained from the patient(s) for their anonymized information to be published in this article.