Lupus

PRIMER
a
b
c
Although evidence for their efficacy in renal lupus
is stronger, agents including azathioprine (a purine
analogue that blocks immune cell proliferation) or
mycophenolate mofetil (an inhibitor of purine synthesis
that blocks immune cell proliferation) are often coprescribed
with antimalarials in non-renal SLE. However,
because immunosuppression can cause adverse effects,
including bone marrow suppression or liver test abnormalities,
blood tests must be monitored during use for
these changes.
Figure 4 | Multifocal osteonecrosis in a patient with SLE Nature following Reviews long-term | Disease Primers
corticosteroid treatment. MRI scans showing typical serpiginous osteonecrosis in the
left knee (part a; arrow), right knee (part b; arrows) and shoulder (part c; arrow).
Osteonecrosis in young patients with systemic lupus erythematosus (SLE) is an important
comorbidity as MRI is needed to confirm diagnosis in early stages and joint replacements
might be required in advanced stages. The management of SLE-associated bone disease
is to try to reduce glucocorticoid exposure while ensuring adequate control of SLE.
Intravenous iloprost (a vasodilator) and bisphosphonates (bone resorption inhibitors)
have successfully been used in early osteonecrosis.
immunosuppressive action) are used if problems persist.
Mild-to-moderate arthritis or pleurisy that causes chest
pains are usually treated with NSAIDs 121 .
More-severe SLE disease activity often requires systemic
glucocorticoids as initiation therapy with the
addition of maintenance immunosuppressive therapy in
the longer term to permit glucocorticoid dose tapering.
The optimal dose of glucocorticoids as initiation therapy
varies in practice. Minimizing total dosage is vital
to prevent signifi cant steroid-induced comorbidities,
yet undertreatment can lead to insufficient immunosuppression
and tissue damage accrual. More-persistent
or severe joint or skin involvement often involves using
oral prednisolone (<0.5 mg per kg) while intravenous
methyl prednisolone can be used for more-aggressive
neuropsychiatric or skin manifestations.
Maintenance treatment of non-renal SLE
To permit steroid tapering over the following weeks or
months (dependent on response) and to prevent the
high risk of relapse, immunosuppressive therapy is
initiated in the early stages of glucocorticoid treatment.
This is because, unlike glucocorticoids, many immunosuppressive
agents require weeks to become effective.
Antimalarials that are used for their immunosuppressive
actions, for example, hydroxychloroquine or, less commonly,
quinacrine (also known as mepacrine) or chloroquine,
are commenced immediately. The LUMINA study
suggested that hydroxychloroquine is well tolerated and
is associated with prolonged lifespan 122 , effects that are
potentially mediated by reducing flares 123 , and damage
accrual. Hydroxychloroquine may also reduce the risk of
incident diabetes mellitus in a dose-dependent manner 124 .
Hydroxychloroquine is effective against cutaneous lupus
and might have other clinical benefits, such as improvement
of arthralgias and fatigue. Some experts recommend
that antimalarials should be used for all patients with
SLE unless there are contraindications. Potential retinal
toxicity, albeit rare, requires ophthalmological monitoring
with long-term use.
Refractory non-renal SLE
Belimumab — a humanized recombinant IgG monoclonal
antibody directed against BAFF — is licensed
for the treatment of patients with ‘active SLE despite
conventional therapy’ (REF. 125). Current SLE activity
indices might be inappropriate to monitor the efficacy
of belimumab, as the drug is effective but has a slow
onset of action. Although the exact role of belimumab in
SLE management remains to be determined, subgroup
analyses of the belimumab trials (BLISS I and BLISS II)
showed that the drug has greater therapeutic benefit in
patients with higher disease activity, anti-dsDNA positivity
and low complement levels than in patients with SLE
with lower levels of these markers 125 . One concern is that,
although licensed for SLE, belimumab has not received
approval from funding bodies in some countries, which
might limit its use. Although well tolerated with no
significant adverse events over conventional therapy,
prescription requires tailored assessment of the overall
course of the disease, including past degree of activity,
recent flare frequency, the dose of glucocorticoids
that is required to control the disease and the degree of
response to conventional agents. A subcutaneous version
of belimumab is undergoing phase III testing 126 .
Management of specific features of SLE
Several other drugs have been used in the management of
additional SLE features, with limited evidence supporting
their use. Treatment of patients with SLE with DHEA,
a corticosteroid intermediate in the biosynthesis of androgens
and oestrogens, can improve overall disease activity
and enable reduction in glucocorticoid dosage with
minor adverse effects of hirsutism (excessive hairiness)
or acne 127 . However, this drug is not licensed for SLE.
Haematological SLE manifestations including refractory
thrombocytopaenia or haemolytic anaemia can improve
with the semi-synthetic androgen analogue danazol 128 .
Thalidomide (an immunomodulatory drug) has successfully
been used in the treatment of cutaneous lupus 129 , but
shows toxicity (especially peripheral neuropathy) and is
contraindicated in women of childbearing age.
While fatigue, joint pains, muscle aches and cognitive
symptoms are common in patients with SLE, they do
not always represent disease activity. These symptoms are
similar to fibromyalgia, which may coexist with SLE 130 .
Complicating the clinical picture, thyroid dysfunction 131 ,
headaches and depression are all over-represented in
patients with SLE and require differentiation from SLE
disease activity before treatment is tailored. Treatments
aimed at controlling SLE activity do not always act against
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