Progressive multifocal leukoencephalopathy in rheumatoid arthritis and biological therapies: a case report and review of the literature

Bergmans, Barbara; Roks, Gerwin; van Puijenbroek, Eugène; de Vries, Esther; Murk, Jean-Luc

doi:10.1186/s13256-025-05091-8

Journal of Medical Case Reports

Table 1 Summary of the published PML cases in RA patients using biologicals

From: Progressive multifocal leukoencephalopathy in rheumatoid arthritis and biological therapies: a case report and review of the literature

Country	Sex	Age (years)	Comorbidities	Lymphopenia	Corticosteroids	csDMARD	Biological	Biological duration (years)	Pretreatment with biological	Symptom duration (months)	Symptoms	Differential	Diagnostic delay (months)	Mode of diagnosis	Outcome	References
USA	Male	72	Hypertension, benign prostatic hypertrophy, chronic bronchitis		Yes	MTX	Infliximab	5	No	2.5	Memory loss, confusion, falls, right-sided weakness			Histology brain biopsy	Survived with disability	Kumar et al. [21]
USA	Female	66			No	No	Adalimumab	2	No	3	Coordination problems, impaired writing, gait disturbance, dysarthria			PCR CSF	Unknown	Ray et al. [22]
Spain	Female	92					Rituximab	5		2	Sensory–motor syndrome of the right limbs, cognitive impairment			Histology brain biopsy	Death	Sala et al. [23]
USA	Female		Diabetes, hypertension				Rituximab	2.5			Altered consciousness, lack of coordination, abnormal gait, peripheral neuropathy			MRI	Death	Bharat et al. [24]
USA	Female		Colonic polyps, stroke		Yes	No	Rituximab	0.67		1	Speech disorder, aphasia, idiopathic peripheral neuropathy, abnormal gait, lack of coordination, hemiplegia			Unknown	Death	Bharat et al. [24]
USA	Female	75				MTX	Adalimumab				Progressive left hemiplegia, “global decline”	Age-related		Histology brain biopsy	Death	Babi et al. [25]
Japan	Female	74		Yes			Etanercept	0.58		2.5	General malaise, loss of appetite, disorientation, incontinence, deterioration of verbal communication	Encephalomeningitis	3	MRI	Survived with disability	Yamamoto et al. [26]
Japan	Female	72		No			Tocilizumab	3.33			Dementia, abnormal behavior	Infection		MRI	Survived with disability	Kobayashi et al. [27]
Ireland	Male	60		No			Rituximab	10		1	Ataxia, dysarthria, dysphagia			PCR CSF	Survived with disability	Darcy et al. [28]
USA	Female	79	Hypertension, ischemic stroke	No	Yes	No	Rituximab				Falls, gait disturbance, slurred speech, confusion			MRI	Death	Guduru et al. [29]
UK	Female	69				MTX	Infliximab	5		2	Progressive cognitive decline, word-finding difficulties, retrograde and anterograde amnesia, behavioral change, somnolence, apathy			PCR brain biopsy	Survived with disability	Sammut et al. [30]
Japan	Female	61	Anxiety disorder, Sjögren syndrome			MTX	Tocilizumab	1.33	Adalimumab, abatacept	5	Speech disorder and could no longer prepare meals	Worsening anxiety disorder, subacute cerebral infarction, malignant lymphoma	5	Histology brain biopsy	Survived with disability	Anada et al. [31]
USA	Female	51	Sjögren syndrome	Yes		MTX	Rituximab	5				Malignant neoplasm		Histology brain biopsy	Death	Fleischmann et al. [32]
Taiwan	Female	27	SLE		Yes	MTX, HCQ	None^*		Etanercept, tocilizumab, and rituximab sequentially	3	Dizziness, unsteady gait, headache, nausea, vomiting, dizziness, left-hand clumsiness, left hemiparesis	Subacute infarction, vasculitis, refractory neuropsychiatric SLE, rhombencephalitis	2	PCR CSF	Survived with disability	Cheng et al. [20]
USA	Female	73	Hypothyroid, Sjögren syndrome	Yes	Yes	Leflunomide	Rituximab				Focal right-hand dysesthesia, ataxia, dysphasia		1	PCR CSF	Death	Clifford et al. [13]
Sweden	Female	72	Sjögren syndrome	Yes		MTX	Rituximab		Etanercept, adalimumab		Right hemiataxia in arm, leg, and trunk, falls		4	PCR CSF	Death	Clifford et al. [13]
Australia	Female	67	Sjögren syndrome	Yes	Yes	MTX	Rituximab				Cognitive decline, dysphasia		2	PCR CSF	Survived with disability	Clifford et al. [13]
USA	Female	62		Yes		MTX	Rituximab		Etanercept, adalimumab, anakinra		Cortical right hand dystonic tremor, later myoclonus			Histology brain biopsy	Survived with disability	Clifford et al. [13]
Japan	Female	65		Yes	No	MTX	Infliximab	4			Right upper limb weakness, gait disturbance, headache, nausea, dizziness, weight loss, double vision	TIA, cryptococcal meningitis	3	PCR CSF	Survived with disability	Nosaki et al. [33]
Unknown	Female	56			Yes	Leflunomide, MTX	Rituximab	1.92	Adalimumab, etanercept		Unknown	Unknown		Unknown	Unknown	Berger et al. [34]
Unknown	Male	58	SLE, opportunistic infections		Yes	MTX	Rituximab	2.33	Etanercept, infliximab		Unknown	Unknown		Unknown	Death	Berger et al. [34]
nknown	Female	60	SLE		Yes	MMF	Rituximab	4.67	No		Unknown	Unknown		Unknown	Death	Berger et al. [34]
Unknown	Female	83			Yes	MTX	Rituximab	4.75	Denosumab		Unknown	Unknown		Unknown	Death	Berger et al. [34]
USA	Female	55					Rituximab	2	TNF-alpha inhibitor		Unknown	Unknown		Unknown	Survived with disability	Molloy et al. [35]
USA	Female	41			Yes	MTX	Rituximab	1.33	Infliximab		Unknown	Unknown		Unknown	Unknown	Molloy et al. [35]
USA	Male	69			Yes	HCQ, CYC	Infliximab				Unknown	Unknown		Unknown	Death	Molloy et al. [35]
The Netherlands	Male	69	Cataract, COPD		No	MTX	Rituximab	3		1.5	Word-finding difficulties, trouble reading, uncertain gait	Hematoma, vascular	0.25	PCR CSF	Death	Case described in current article, 2022

Blank cells indicate this information was not reported
COPD chronic obstructive pulmonary disease, csDMARD conventional synthetic disease-modifying antirheumatic drug, CSF cerebrospinal fluid, CYC cyclosporine, HCQ hydroxychloroquine, MMF mycophenolate mofetil, MRI magnetic resonance imaging, MTX methotrexate, PCR polymerase chain reaction, SLE systemic lupus erythematosus, TIA transient ischemic attack
^*One patient had no current biological use but had been exposed to etanercept, tocilizumab, and rituximab for up to 2 years before presentation

Back to article page

ISSN: 1752-1947

Contact us

Submission enquiries: Access here and click Contact Us
General enquiries: journalsubmissions@springernature.com