GUIDELINES ■

Management of systemic lupus

erythematosus in adults
STEVE CHAPLIN

Earlier this year, the

Clinical criteria Acute cutaneous lupus
British Society for Chronic cutaneous lupus
Rheumatology (BSR) Oral ulcers
published the first Non-scarring alopecia
Synovitis (≥2 joints)
UK guideline on the Serositis
management of systemic Proteinuria
lupus erythematosus Neurological signs and symptoms
(SLE) in adults. This Haemolytic anaemia
Leukopenia or lymphopenia
article summarises its Thrombocytopenia
recommendations on
diagnosis, monitoring and Immunological criteria Anti-nuclear antibodies raised
treatment. Anti-double stranded DNA antibodies raised
Anti-Smith antibodies
Antiphospholipid antibody

S ystemic lupus erythematosus (SLE)

is a challenging disorder for clini-
cians and those affected. It is rare:
Low complement
Direct Coombs’ test (in the absence of haemolytic
anaemia)
the age-standardised prevalence in
the UK is 8.3/100,000 for women and See full guideline for definitions. Patients can be classified as having SLE if
1.4/100,000 for men, but among people they satisfy four of the clinical and immunological criteria, including at least one
of African Caribbean descent the figure clinical criterion and one immunological criterion, OR if they have biopsy-proven
is 31.4/100,000. It is a multisystem nephritis compatible with SLE in the presence of anti-nuclear antibodies or anti-
autoimmune disease that can occur at double stranded DNA antibodies
any age and, though it is most frequent
Table 1. Clinical and immunological criteria for the classification of systemic lupus
among women of reproductive age, the
erythematosus (SLE)1
mean age at diagnosis is 49 years.
SLE is characterised by relapses and vival data over the last 40 years, lupus
remissions. Flares cause considerable patients still die on average 25 years ear-
morbidity and organ damage accumu- lier than the mean for women and men
lates, increasing the risk of premature in the UK. The disease can present with
death due to infection or cardiovascular slowly or rapidly progressive active dis-
disease. One-third of people with SLE ease at any age and can be associated
develop nephritis, further reducing the with the rapid accumulation of damage
mean age at death from 54 to 40 years, if not promptly diagnosed, appropriately
with an average of only seven to eight treated and regularly monitored.” This is
years between the onset of nephritis and the first UK guideline on the overall man-
death. agement of SLE, updating the 2008 guid-
ance published by the European League
The first UK guideline on SLE Against Rheumatism (EULAR).
management The aim of the guideline is to “pro-
The British Society for Rheumatology duce recommendations for the manage-
(BSR) has published a guideline on the ment of adult lupus patients in the UK
management of SLE in adults1 because that cover the diagnosis, assessment
“Despite some improvement in sur- and monitoring of lupus and the treat-

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■ GUIDELINES l Systemic lupus erythematosus

ment of mild, moderate and severe active

lupus disease”. It is a mammoth task to Activity Definition Typical SLE manifestations
provide succinct advice about such a Mild Clinically stable disease with Fatigue, malar rash, diffuse
complex disorder – and the 400 refer- no life-threatening organ alopecia, mouth ulcers,
ences culled from a literature search up involvement and that is not arthralgia, myalgia, platelets
to June 2015 that are cited in support likely to cause significant 50–149 x 109/L
of the recommendations is testament scarring or damage
to the work that has gone into the docu-
ment (there is an executive summary for Moderate More serious manifestations, Fever, lupus-related rash up
quick reference). which if left untreated would to 2/9 body surface area,
But even this has only been possi- cause significant chronic cutaneous vasculitis, alopecia
ble by limiting the guideline’s scope. The scarring with scalp inflammation,
management of renal disease is cov- arthritis, pleurisy, pericarditis,
ered by other guidance.2 The BSR does hepatitis, platelets 25–49 x
not include isolated cutaneous lupus, it 109/L
directs the reader elsewhere for advice
on management during pregnancy, and Severe Organ or life threatening Rash involving >2/9 body
does not address complications such as and reflects the most surface area, myositis, severe
chronic fatigue, osteoporosis, infection serious form of systemic pleurisy and/or pericarditis
and the risk of cardiovascular disease disease that requires potent with effusion, ascites, enteritis,
and cancer because their management immunosuppression myelopathy, psychosis, acute
is not unique to lupus patients. confusion, optic neuritis,
People with SLE, of whom 80% report platelets <25 x 109/L
fatigue3 and 50% report severe fatigue,4
might not endorse such a separation. Table 2. Definitions of mild, moderate and severe systemic lupus erythematosus (SLE)
The guideline’s focus is made clear in a activity1
table listing the incidence of SLE mani- are common. The guideline’s table of tis compatible with SLE is present with
festations in published reports: though SLE manifestations illustrates the wide antinuclear antibodies or anti-double
superficially exhaustive, it does not variety of signs and symptoms, but the stranded DNA antibodies. However, SLE
mention fatigue. An otherwise positive causes of major morbidity are renal and may also be diagnosed in people who do
commentary published alongside the neurological complications, and one- to not meet these criteria but have appropri-
guideline notes that only the role of the two-thirds of patients have gastrointes- ate serology.
specialist is defined and “active patient tinal and hepatic features that are often
involvement, shared decision-making and unrecognised as being due to SLE. Assessment
patient empowerment are excluded in the In acute SLE, inflammation is trig- The diversity and complexity of SLE
BSR management recommendations, as gered by the formation of immune com- means a systematic approach to assess-
unfortunately is patient education”.5 This plexes involving autoantibodies and ment is essential but categorising SLE
is not the NICE style of guideline with complement consumption and, in some disease activity has, in the past, seemed
which we’ve become familiar. people, thrombosis due to antiphos- a convoluted process. To make planning
The guideline has six sections cov- pholipid antibodies. For patients with treatment more straightforward, this
ering recommendations for clinical and a strong clinical likelihood of SLE, the guideline greatly simplifies the issue by
serological features prompting diagno- presence of anti-double stranded DNA defining categories for mild, moderate
sis; patient assessment; monitoring; antibodies, low complement C3 and C4, and severe SLE (see Table 2), but also
and the management of mild, moderate and anti-Smith antibodies is highly pre- correlates these with the more traditional
and severe SLE. Each section includes a dictive of a diagnosis. The presence of assessment instrument scores.
detailed description of the evidence base antiphospholipid antibodies predicts an The guideline stresses the importance
underpinning the recommendations. increased risk of thrombosis and adverse of taking a detailed history and carrying
pregnancy outcomes. Levels of other out a full physical examination, then carry-
Diagnosis autoantibodies may be raised but they ing out the appropriate laboratory investi-
Diagnosis requires a combination of are not specific for lupus. gations. Treatment for a flare, categorised
clinical features and the presence of at The guideline adopts a classification in the same way, depends on ascertaining
least one relevant immunological abnor- system for SLE that requires the pres- its timing and possible triggers.
mality. SLE is clinically heterogeneous ence of four clinical and immunological
and should be considered in the differ- criteria, including at least one of each Monitoring
ential diagnosis of many acute and sub- (see Table 1). Alternatively, the diagno- People with active SLE should be
acute presentations; delays in diagnosis sis can be made if biopsy-proven nephri- reviewed every month initially then every

32 ❚ Prescriber September 2018 prescriber.co.uk

 Systemic lupus erythematosus l GUIDELINES ■

three months; those who are in remission taking hydroxychloroquine should have get B cells by different mechanisms)
or have stable low activity disease should normal renal and liver function. Although are further options but should only be
be seen every 6–12 months. Monitoring treatment is usually well tolerated, the prescribed at specialist centres. NHS
should cover SLE manifestations, risks risk of retinopathy increases with dura- England has a commissioning policy for
associated with pregnancy, drug toxicity tion of use and cumulative dose. In prac- rituximab for this indication. NICE has
(eg due to immunosuppressants) and tice, the average duration of treatment recommended belimumab as add-on
co-morbidities such as atherosclerotic is about six years and retinal damage, therapy for patients with SLE towards the
disease, osteoporosis, avascular necro- though unpredictable, is unlikely within more severe end of moderate activity.6
sis, malignancy and infection. There seven years. Optician eye tests should Patients prescribed either drug must
is always a risk of flare contributing to be carried out at baseline and annually, be enrolled in the British Isles Lupus
cumulative damage and patients should with more detailed ophthalmological Assessment Group Biologics Register.
be advised to report new or significant examinations after five years.
worsening of clinical manifestations. Methotrexate is not licensed for the Managing severe SLE
For all patients, monitoring should be treatment of SLE but is used to control Other aetiologies, such as infection,
more frequent if there is renal involve- inflammatory arthritis and rash. It may be should be excluded in patients present-
ment or if treatment is being withdrawn co-prescribed with hydroxychloroquine to ing with severe SLE, including renal
or stopped, even during remission. The minimise steroid use. Caution is needed and neuropsychiatric manifestations.
guideline provides detailed advice on in patients with nephritis, who are at The evidence base is strongest for the
interpreting laboratory tests and on the increased risk of toxicity, and it is terato- management of nephritis, less so for
value of monitoring autoantibody levels genic. neuro­psychiatric disease and weakest
for disease activity, predicting flares and NSAIDs are useful in the short term for other organ-specific manifestations.
adjusting treatment. to treat inflammatory arthralgia, myalgia, The underlying aetiology may be inflam-
chest pain and fever when paracetamol matory, thrombotic or both and this
Managing mild SLE is not sufficient. Patients with nephritis determines the choice of treatment with
Treatment of mild SLE relieves patients are at increased risk of renal toxicity and an immunosuppressant and/or antico-
of troubling symptoms and may prevent SLE generally is associated with greater agulant. Regimens for immunosuppres-
progression to more severe forms. There susceptibility to allergic reactions, asep- sion include a high-dose steroid, usually
are five options: corticosteroids, hydroxy­ tic meningitis, cutaneous reactions and with a second immunosuppressant, to
chloroquine (or the less well-tolerated hepatotoxicity. induce remission; and mycophenolate
chloroquine), methotrexate, NSAIDs and People with SLE have an abnor- mofetil or ciclosporin for lupus nephritis
sunscreens. mal reaction to UV light, and both UVA and refractory, severe non-renal disease.
Topical steroids are recommended and UVB can induce cutaneous lupus. If such strategies are ineffective or not
for skin manifestations and, via intra- Patients should be informed about tolerated, rituximab or belimumab are
articular or intramuscular injections, for sources of UV radiation and advised further options.
arthritis. When local treatment is not to cover up in the sun. High-factor sun- Patients with refractory cytopenias,
possible or ineffective, a short course of screens (five stars for UVA protection; thrombotic thrombocytopenic purpura,
oral prednisolone can induce remission SPF factor 30–50 for UVB) can be pre- rapidly deteriorating acute confusional
and may also be offered to women who scribed on the NHS. state or the catastrophic variant of
are trying to conceive, are pregnant or antiphospholipid syndrome may be con-
are breast-feeding. Doses should be the Managing moderate SLE sidered for treatment with IV immuno-
lowest possible due to adverse effects Immunosuppressants should be pre- globulin G and plasmapheresis.
and the risk of contributing to chronic scribed in addition to hydroxychloroquine
damage. to reduce disease activity, prevent the The guideline in practice
Hydroxychloroquine, one of the few risk of flares, reduce the risk of damage The authors repeat that the diagnosis
drugs licensed specifically for SLE (the accumulation and to minimise exposure and assessment of SLE “can be diffi-
others are steroids and belimumab), to steroids. Options include lefluno- cult due to multisystem involvement and
has anti-inflammatory and anti-throm- mide and, in patients with non-renal variable laboratory and serological test
botic activity. It is the most frequently disease, methotrexate, azathioprine, results”. They acknowledge that relatively
prescribed drug for SLE and it should mycophenolate mofetil, ciclosporin and few of the developments in management
be given to all patients with mild lupus tacrolimus. Steroids remain an option. emerging in the past 10 years come from
to prevent flares and the development The dose and choice of drug should be high-quality randomised controlled trials
of damage, and to improve survival. It altered if the response to treatment (and given the rarity of SLE that is not sur-
can improve skin and joint symptoms, is weaker than anticipated within the prising) but they believe the new guide-
myalgia, fever, fatigue and pleurisy and expected time frame. line “will increase knowledge and raise
reduces the development of renal dis- If SLE is refractory to these drugs, the standard of care for patients with
ease; it is also steroid-sparing. Patients rituximab or belimumab (which tar- lupus”. They foresee no barriers to imple-

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■ GUIDELINES l Systemic lupus erythematosus

mentation other than funding limitations tion and pregnancy planning are heavily https://academic.oup.com/rheumatology/
for rituximab and belimumab. A form to dependent on personal motivation, so article/57/1/e1/4318863.
facilitate audit of the guideline is avail- the patient’s role (and the professional’s 2. Bertsias GK, et al. Joint European League
able from the BSR (www.rheumatology. role in fostering it) might usefully have Against Rheumatism and European Renal
org.uk). received greater prominence. Association European Dialysis and Transplant
People with suspected or known SLE Association (EULAR/ERA-EDTA) recommen-
should be referred to a clinician expe- Summary dations for the management of adult and
rienced in SLE care and managed by The first UK guideline on the manage- paediatric lupus nephritis. Ann Rheum Dis
2012;71:1771–82.
a multidisciplinary team that includes ment of SLE provides a comprehensive,
3. Tench CM, et al. The prevalence and
nurse specialists and physiotherapists. evidence-based structure for a disorder
associations of fatigue in systemic lupus
The team should be able to call on a that crosses the boundaries of many spe-
er ythematosus. Rheumatology (Oxford)
wide range of specialties within a col- cialties and presents diagnostic and ther-
2000;39:1249–54.
laborative clinical network that involves apeutic challenges. Though the details
4. Overman CL, et al. The prevalence of severe
regional specialist centres, local hospi- are of interest primarily to specialists, fatigue in rheumatic diseases: an international
tals and GPs. everyone involved in providing or commis- study. Clin Rheumatol 2016;35:409–15.
The aim of drug treatment is to sioning services for people with SLE will 5. Schneider M. Guidelines for the manage-
reduce disease activity to a low level benefit from a greater understanding of ment of systemic lupus erythematosus: great
(which is not defined) or remission to the need for careful and thorough investi- synthesis of evidence and eminence with lim-
reduce cumulative damage from the dis- gation, and the limitations and potential ited focus on patient’s needs. Rheumatology
ease, and to minimise the use of ster- benefits of treatment. While implement- 2018;57:12–3.
oids. If drug treatment is not working as ing this advice, clinicians need to remem- 6. National Institute for Health and Care
expected, the possibility of non-adher- ber the many relevant guidelines that Excellence. Belimumab for treating active
ence should be considered. contribute to overall management but autoantibody-positive systemic lupus erythe-
The guideline recommends patients fall outside the immediate remit of rheu- matosus. TA397. June 2016. Available from:
are given personalised advice, written matology. https://www.nice.org.uk/guidance/ta397.
information and education about SLE
and its treatment. Measures such as sun References Declaration of interests
avoidance, adequate vitamin D intake, 1. Gordon C, et al. The British Society for None to declare.
lifestyle change (weight control, exercise, Rheumatology guideline for the management
not smoking), reducing atherosclerotic of systemic lupus erythematosus in adults. Steve Chaplin is a medical writer
risk factors, cancer screening, contracep- Rheumatology 2018;57:e1–45. Available from: specialising in therapeutics

34 ❚ Prescriber September 2018 prescriber.co.uk