Lupus (2018) 27, 18–20

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Neuropsychiatric symptoms in lupus

Patients with lupus experience a high burden of neuropsychiatric symptoms. While some
patients have frank neurological complications, this represents a minority. Most neuropsy-
chiatric symptoms are chronic and not associated with brain imaging abnormalities, for
example, fatigue, ‘brain fog’ and altered mood. Factors which contribute to these symptoms
may include medications, infections, the psychological burden of chronic unpredictable dis-
ease, and the direct effects of inflammation on the brain. This article summarizes our current
understanding of psychological symptoms in lupus, and how this informs our approach to
management. Lupus (2018) 27, 18–20.

Key words: Neuropsychiatric symptoms; fatigue; headache; altered mood; cognitive impair-
ment; lupus; neuroimmunology

What neuropsychiatric symptoms are associated What causes psychological symptoms in lupus?
with lupus?
Symptoms such as fatigue, low mood and cognitive
It is well-known that patients with chronic inflam- impairment are invariably multifactorial. In some
matory and autoimmune conditions suffer a high patients, the inflammatory pathology of lupus con-
burden of neuropsychiatric symptoms.1,2 Patients tributes to neuropsychiatric symptoms and may
with systemic lupus erythematosus (SLE) are par- respond to immunosuppression. Other patients
ticularly affected – more so than patients with other will simply experience psychiatric symptoms unre-
chronic diseases. The American College of lated to their underlying condition, by virtue of the
Rheumatologists lists 19 recognized neuropsychi- high rates of psychiatric morbidity in those with
atric syndromes (Table 1),3 which occur at a preva- (any) chronic illness. Several important consider-
lence of over 50% in SLE.4 This is a daunting list of ations are as follows:
presentations, but although some patients with . Lupus poses particular psychological challenges.
SLE will experience frank neurological complica- Patients point to the stress of never knowing
tions such as thrombosis, seizures or myelopathy, when the next flare will come, the unpredictabil-
this is the minority. The larger burden of neuro- ity of symptoms from day to day, disability
psychiatric symptoms in lupus is chronic, of unclear resulting from fatigue and pain, and the fact
cause and not associated with abnormalities on that many symptoms are not visible to others.
brain imaging. The most common neuropsychiatric Those symptoms which are visible can have a
symptoms are fatigue, headache, altered mood and strong negative impact on body image, as can
cognitive impairment (or ‘brain fog’). These so- corticosteroid-induced weight gain.
called ‘minor’ neuropsychiatric symptoms have a . Corticosteroids have complicated and underap-
dramatic effect on quality of life and predict preciated negative effects on psychological
patient-reported disease activity more than clin- health. Corticosteroid use is associated with an
ician disease activity scores.5,6 It is on these symp- increased risk of depression, mania, delirium and
toms that we will focus. panic disorder, as well as a 7-fold increase in the
risk of attempted or completed suicide.7 These
Correspondence to: Mary-Ellen Lynall, Department of Psychiatry, psychological adverse effects are somewhat
University of Cambridge, Herchel Smith Building for Brain and dose-related, but can occur during initiation,
Mind Sciences, Robinson Way, Cambridge Biomedical Campus,
Cambridge, CB2 0SZ, UK.
maintenance or weaning of corticosteroid
Email: [email protected] therapy.
! The Author(s), 2018. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav 10.1177/0961203318801672
 Lupus neuropsychiatry
M Lynall
19

Table 1 The American College of Rheumatology nomencla- with neuropsychiatric symptoms would respond
ture for neuropsychiatric lupus syndromes best to immunosuppression, treatment with psy-
Central Peripheral
chotropics, psychological therapy, or combinations
of the three. Specialists, general practitioners (GPs)
 Aseptic meningitis  Acute inflammatory demyelinating and patients alike struggle with this uncertainty.
 Cerebrovascular disease polyradiculoneuropathy The commonest psychiatric presentation which
 Demyelinating syndrome (Guillain-Barré syndrome)
 Headache  Autonomic disorder
GPs will manage in SLE is depression: current
 Movement disorder  Mononeuropathy best practice for treatment of low mood (without
 Myelopathy  Myasthenia gravis history of mania) involves standard treatment with
 Seizure disorders  Neuropathy, cranial antidepressants and psychological therapy as for
 Acute confusional state  Plexopathy patients without lupus (see Clinical vignette). The
 Anxiety disorder  Polyneuropathy
 Cognitive dysfunction
rheumatology team may also consider changes to
 Mood disorder immunosuppressive therapy. If mood alterations
 Psychosis are associated with an overall increase in disease
activity, immunosuppression may need to be
increased. But if psychological symptoms seem to
. Many patients with SLE experience frequent relate to corticosteroid use, the aim is to minimize
infections, which increase the risk of mood epi- corticosteroid burden where possible, balanced
sodes. The risk of mood disorder is particularly against the need to treat other aspects of the con-
high in the year following discharge from hos- dition. Fatigue is more challenging to manage:
pital with an infectious episode.1 there are no lupus-specific treatments for fatigue
. For reasons that are unclear, autoimmune dis- at present and new therapeutics are urgently
eases are associated with childhood trauma.8 needed. Best current management involves exercise,
Many patients with lupus have a history of treatment of any underlying mood disorder and
adverse childhood experiences which contribute treatment of insomnia.
to the burden of mental health symptoms. It can be difficult for patients with lupus to
. The mechanisms by which inflammation contrib- access secondary psychiatric services. Current
utes to neuropsychiatric symptoms are unclear. budgetary constraints mean that secondary care
Some lupus autoantibodies cross-react with the psychiatric triage predominantly focuses on risk,
N-methyl-D-aspartate (NMDA) receptor, a so it is helpful to make explicit the particular
brain glutamate receptor. These antibodies are risks to your patient, for example the elevated
increased in acute confusional states in lupus, risk of harm to lupus patients on warfarin who
but there are no clear correlations between can self-harm or the risk of deterioration in a patient’s
cause mood alterations and fatigue and autoan- renal function (and consequent risk to life) if neuro-
tibodies in SLE.9 Experimental studies in psychiatric symptoms contribute to medication
humans show that inflammatory cytokines non-adherence. Patients frequently feel that the
released by the immune system can cause mood psychological burden of lupus is underrecognized.
disorder and fatigue, and animal studies show Do not be hesitant to ask about psychological
that these cytokines can alter behaviour by symptoms, and to highlight the benefits of treat-
acting directly on the brain and brain endothe- ment even where there are apparently ‘good rea-
lium.10 However, it is unclear to what extent sons’ for symptoms.
immune activation and cytokine release contrib-
ute to altered mood and fatigue in SLE.
. Around 80% of patients with lupus report prob-
lematic fatigue, but fatigue has an unclear rela- Clinical vignette: the pitfalls of subtherapeutic
tionship with disease activity and is often prescribing
prominent in patients without active disease.11
Angela is 30 years old and has had a diagnosis of
In summary, the causes of neuropsychiatric
SLE for the last 2 years. She had experienced a
symptoms in lupus are poorly understood.
short episode of depression as a teenager from
Outside of frank neurological presentations (e.g.
which she recovered without treatment. She became
stroke), there are no blood, brain or cerebrospinal depressed again following discharge from hospital
fluid biomarkers indicating whether an individual’s where she received a diagnosis of SLE after she pre-
symptoms have an inflammatory basis or not. sented with rapidly progressive end-stage renal dis-
Thus, it is often unclear whether a given patient ease following a year of non-specific symptoms. Her

Lupus
 Lupus neuropsychiatry
M Lynall
20

GP noticed her low mood and started 10 mg citalo- Declaration of conflicting interests
pram. She felt a little better on citalopram, and con-
tinued it for the next year, but remained low, gave up The author declared no potential conflicts of inter-
her job and became socially withdrawn. She did not est with respect to the research, authorship, and/or
raise her ongoing low mood with either her GP or her publication of this article.
hospital team because she thought it was natural that
she was depressed, given her diagnosis. She eventu-
ally presented to A&E having taken an overdose. Funding
Citalopram was increased to 20 mg, then to 40 mg
(with electrocardiogram monitoring) and she took a The author received no financial support for the
course of cognitive behavioural therapy via the research, authorship, and/or publication of this
Improving Access to Psychological Therapies ser- article.
vices. Her mood improved significantly, and she
returned to part-time work, but fatigue remains a
significant problem. References
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Not applicable.

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