Symposium: bone & connective tissue

Diagnosis and management Lupus is a chronic disease and has unpredictable flares and
remissions. The condition impacts on the whole family and the

of systemic lupus child’s care requires a multidisciplinary approach to help them

cope with the disease. Despite relatively little new understand-

erythematosus in children ing of the pathogenesis and no ‘cure’, the long term outcome for
children with SLE is fairly good if they are followed closely by a
medical team with suitable expertise.1–3
Pete Malleson

Jenny Tekano Definition

Abstract
Systemic lupus erythematosus in children is uncommon, but not rare. It
should be considered in any child (particularly an older child) who has
been unwell for more than 1 week with multisystem clinical features
without a diagnosis. The most common presentation is a febrile child
with fatigue, an erythematosus malar rash and arthritis. Leukopenia,
thrombocytopenia and a raised ESR is suggestive, as is a urinalysis
indicative of nephritis. The presence of anti-DNA antibodies confirms the
diagnosis, but its absence does not exclude this possibility.
Although a life-long and serious disease with a high morbidity and
substantial mortality, the prognosis has dramatically improved ­recently,
largely because of the aggressive use of high-dose corticosteroids at ­onset
and with disease flares, combined with other potent anti-­inflammatory
agents. The early empirical use of antibiotics for possible sepsis is
­essential. Early referral and frequent follow-up by a team ­specialized in
the management of the condition has probably been critical in ­improving
outcome.
SLE is best defined as an episodic, multisystem, autoimmune dis-
ease characterized by widespread inflammation of blood vessels
and connective tissues, and by the presence of antinuclear anti-
bodies (ANAs), especially antibodies to double-stranded DNA
(dsDNA).4
Diagnosis versus classification
A distinction should be made between the classification and the
diagnosis of SLE. The diagnosis is made on the basis of a com-
bination of clinical features and laboratory findings and may not
fulfil the American College of Rheumatology (ACR) classifica-
tion criteria (Table 1),5 which were defined and validated for the
American College of Rheumatology 1997
classification criteria for systemic lupus
erythematosus.5 A person is classified with lupus
if (s)he has four or more of the 11 criteria, either
simultaneously or over time

Keywords autoimmune disease; child; prognosis; systemic lupus Malar rash

­erythematosus; treatment Discoid rash
Photosensitivity
Oral or nasal ulcerations
Introduction Non-erosive arthritis
Nephritis
Systemic lupus erythematosus (SLE) is the prototypic autoim- Proteinuria > 0.5 g/day
mune disease. It can vary widely in its severity, both at onset and Cellular casts
during its course; some children may have very mild disease with Encephalopathy
few symptoms and no serious organ involvement, while others Seizures
may be very ill with a number of organs affected. Psychosis
Diagnosing SLE in children is not always easy. Most children Pleuritis or pericarditis
present with fever, arthralgia, arthritis, rashes, myalgia, fatigue Cytopenia
and weight loss. These symptoms are fairly non-specific, so a Positive immunoserology
high level of suspicion for the diagnosis is required and appropri- Antibodies to dsDNA
ate laboratory tests performed to confirm or refute the diagnosis. Antibodies to Sm nuclear antigen*
Early diagnosis is crucial in ensuring prompt treatment to mini- Positive findings of antiphospholipid
mize life-threatening complications. Children generally have a Antibodies based on:
more severe disease onset and progression than in adults, with a • IgG or IgM anticardiolipin antibodies, or
greater disease burden over their lifetime. • Lupus anticoagulant, or
• False positive serological test for syphilis for at least
6 months, confirmed by Treponema palidum immobilization
Pete Malleson MBBS MRCP(UK) FRCPC is Professor of Pediatrics, Division of or fluorescent treponemal antibody absorption test
Pediatric Rheumatology, University of British Columbia, Rheumatology Positive antinuclear antibody test
Service, BC Children’s Hospital, Vancouver, Canada.
*Sm is Smith, not smooth muscle.

Jenny Tekano RN is a Clinical Nurse, Rheumatology Service, BC

Children’s Hospital, Vancouver, Canada. Table 1

PAEDIATRICS AND CHILD HEALTH 18:2 61 © 2007 Published by Elsevier Ltd.

 Symposium: bone & connective tissue
purposes of clinical trials. They are therefore more stringent than
those needed to diagnose lupus. This is important since occa-
sionally treatment would be inappropriately delayed by waiting
for the classification criteria to be fulfilled.
An oddity of the classification system is that the presence of
an ANA and the presence of anti-DNA antibodies count as two
criteria, when technically it is not really possible to have anti-
DNA antibodies without also having a positive ANA test. Fur-
thermore, the ANA test has very poor specificity, being found in
a large percentage of children who do not have lupus, and who
in fact have no rheumatic disease whatsoever.6
Pathogenesis
Lupus is characterized by chronic or recurrent inflammation
affecting one or more tissues in association with multiple auto-
antibodies. Some of these, such as anti-red cell and antiplatelet
antibodies, are clearly pathogenic, whilst others may be merely
markers of the breakdown of tolerance. The aetiology remains a
mystery, but as in many chronic diseases, it seems probable that
the disease is triggered by environmental agents in a predisposed
individual.
Endogenous factors
Many of the autoantibodies (particularly the ANAs) are directed
against intracellular antigens normally ‘invisible’ to the immune
system. This suggests that autoimmunity is developing, at least
in some cases, as a consequence of abnormal or dysregulated cell
death including programmed cell death (apoptosis). In favour of
this concept has been the recognition that the animal model of
lupus in the MLR/lpr mouse is due to a genetic mutation of FAS.7
Activation of FAS leads to apoptosis; abnormal FAS prevents nor-
mal apoptosis leading to uncontrolled lymphocytic proliferation
and the production of autoantibodies. A human homologue of
this animal model is autoimmune lymphoproliferative syndrome
(ALPS) in which, due to a mutation of FAS, young children
develop massive lymphadenopathy and splenomegaly with auto-
antibody production.8
Another example of a mutation of an intracellular signalling
protein predisposing to autoimmunity is protein tyrosine phos-
phatase non receptor 22 (PTPN22). This protein appears to act by
setting thresholds for T-cell receptor signalling; a polymorphism
in the PTPN22 gene is associated with several autoimmune dis-
eases.9 This polymorphism has been shown to be associated with
childhood lupus in Mexicans with an odds ratio more than 3.10
The fact that diseases similar to lupus can be due to mutations
in proteins important in intracellular signalling lends strength
to the concept that several minor genetic variations (polymor-
phisms), any one of which may be unimportant by itself, may
in combination lead to a disease state, either spontaneously, or
more likely, following some environmental trigger.
Tolerance is induced and maintained by central (thymic) and
peripheral (lymphnode/splenic) mechanisms. Breakdown in
­tolerance due to gene mutations in both these areas can cause
specific (albeit rare) autoimmune diseases in children.
The role of ‘disturbances’ in both the acquired and the innate
immune system as a contributor to SLE has been recognized
for many years; e.g. mutations in the proteins of the comple-
ment system, particularly the early complement components,
PAEDIATRICS AND CHILD HEALTH 18:2
predispose to the development of lupus particularly in young
children.11
Toll-like receptors recognize various common motifs found
on bacteria, triggering an innate inflammatory response to the
bacteria. Abnormalities of these receptors are associated with
abnormal immune function including autoimmunity.12
These, and other examples not discussed here, demonstrate
that lupus or lupus-like conditions occur due to genetic abnor-
malities in a variety of pathways involving both innate and
acquired immunity. Which genes are truly important in ‘com-
mon or garden’ lupus remains unclear.
Exogenous factors
Even less is known about the triggers responsible for most forms
of lupus. Drugs such as the anticonvulsants and antibiotics (par-
ticularly minocycline) can cause lupus.13,14 Sunlight may trigger
both the cutaneous and systemic manifestations of lupus (and
neonatal lupus).15,16 The ingestion of very large amounts of
alfalfa sprouts may also cause lupus; the active trigger appears
to be L-canvanine.17
The role, if any, of viruses and bacteria in triggering lupus
remains obscure despite considerable research. There is no
convincing evidence that any specific infection is important in
causing lupus. Interestingly, there is an increase of rheumatic
diseases in people with HIV infection, and autoimmune disease
including lupus seems to be more common when there is res-
toration of immune competence with the use of highly active
antiretroviral therapy.18
Some people have ANAs for many years before developing
disease manifestations.19 This again suggests that one or more
triggers, either sequentially or in combination, are essential to the
onset of lupus. The increasing female predominance after puberty
suggests that hormonal influences may also be important.
In summary, the evidence suggests that SLE occurs after a
triggering event in a child with some perturbation of the innate
and/or acquired immune system, probably due to a number of
functionally important polymorphisms in immune regulating
cell-signalling pathways.
Specific autoantibodies and disease manifestations
Although children with lupus make a large number of differ-
ent autoantibodies, almost all of them make antibodies to
double-stranded DNA and/or to a small group of nuclear anti-
gens known collectively as extractable nuclear antigens (ENA).
These antibodies include anti-Smith (Sm), anti-RNP, anti-Ro
(SSA), and anti-La (SSB). The ‘pattern’ of production of these
antibodies (as well as anti-red cell, antiplatelet and antiphos-
pholipid antibodies, among others) tends to be consistent in any
individual. Some ethnic groups also seem to have idiosyncratic
‘patterns’. The reason for this consistency in an individual, and
occasionally in ethnic groups, but variability between individu-
als is unclear.
The ‘pattern’ of autoantibodies produced is often associated
with a ‘pattern’ of clinical manifestations, such that children with
these ‘patterns’ are considered to have a distinct disease. Chil-
dren producing anti-RNP in high titre, often without any other
ANAs, are labelled as having mixed connective tissue disease
as the clinical manifestations often seem to overlap between
­dermatomyositis, scleroderma and juvenile idiopathic arthritis.20
62 © 2007 Published by Elsevier Ltd.
 Symposium: bone & connective tissue

Children with antibodies to Ro and/or La alone may present with

recurrent parotitis, later develop sicca (dry mouth and eyes) Clinical findings and investigations suggestive of
and are considered to have Sjögren syndrome. The syndrome of systemic lupus erythematosus in childhood
­neonatal lupus is almost always due to transplacental transfer of
anti-Ro antibodies.21 Findings Comments
Antibodies to ENA tend to vary relatively little, whether or
not the child’s disease appears active. However, antibodies to Rashes Erythematosus malar rash sparing
DNA may vary significantly and reflect disease activity. This phe- nasal folds, punctuate palmar
nomenon is perhaps seen most commonly in children presenting erythema, erythematous ulcerated
with idiopathic thrombocytopenia who are anti-DNA negative hard palate are very suggestive
initially, but later develop these antibodies and clinical manifes- Systemic symptoms Fevers and fatigue are common,
tations of ‘full-blown’ lupus. but non-specific. Headache and
Rheumatoid factor is an IgM antibody against IgG. It is found mild cognitive difficulties at school
in about one-third of children with lupus; unlike in children suggestive of CNS involvement, but
with juvenile idiopathic arthritis, its presence does not correlate may simply be due to ill-health
with the development of erosive joint disease. Very high titres Arthritis Polyarthritis of small and large joints.
of rheumatoid factor are often found in children with Sjögren Findings often less than symptoms
syndrome. Investigations

CBC, ESR and CRP Leukopenia, thrombocytopenia

Epidemiology
common. Unusual to have a normal
Lupus is uncommon, but not rare. It occurs rarely in early child- ESR. A raised CRP may suggest
hood but increases in frequency throughout adolescence, with superimposed infection
the peak incidence of about 5 in 100 000 per year in young adult Urinalysis Red cells and proteinuria suggestive
women.22,23 By contrast, in children the overall incidence is of lupus nephritis
about 0.5 in 100 000 per year.24,25 In young children, the sex dis- ANA test A negative test makes lupus very
tribution is only slightly skewed towards females, but in adoles- unlikely. A positive test has very low
cents and young adults the female to male ratio is about 10:1.26,27 specificity
Lupus is increased in families and may also be increased in unre- Specific antinuclear Anti-DNA and/or anti-ENA antibodies
lated household contacts, suggesting that not all the familial antibodies almost diagnostic (few false positives)
aggregation is genetic in origin.28 There are also significant eth- Other autoantibodies Antiglobulin test (Coombs’ test) and
nic differences, with lupus being much more common in people rheumatoid factor are quite commonly
of African, Native American, Hispanic and Asian origins than in found. Antiphospholipid antibodies
caucasians.27,29,30 and lupus anticoagulant may be
suggestive thrombotic predisposition
Complement Low complement levels indicate
Diagnosis immune complex disease, but also
Clinical manifestations may suggest contributing complement
Lupus may present in many ways – ‘the greater mimicker’. How- component deficiency. Useful in
ever, typical clinical manifestations include a malar rash that monitoring disease activity
spares the nasal folds, excessive hair loss, polyarthritis, often
with pain and stiffness being more overt than actual joint swell- Table 2
ing, and constitutional symptoms of fever and fatigue.
Extreme sun sensitivity and other kinds of rashes (usually,
but not always, in association with a malar rash), including other chronic inflammatory diseases (e.g. Crohn disease or a
­punctuate erythema of the palms and erythema of the hard systemic vasculitis) may also present in a similar non-specific
palate, are fairly common. Renal disease is common, but will manner.
often not be obvious unless a urinalysis is performed. Renal Another fairly common presentation is with petechiae and
­disease may present with nephrotic syndrome, but usually there bleeding due to thrombocytopenia. The child may have no other
are other features pointing to non-minimal change nephrotic systemic manifestation and be correctly diagnosed as having
­syndrome (Table 2). idiopathic thrombocytopenic purpura, and only considerably
It is reasonable to consider the diagnosis in any child who is later develops other clinical manifestations. Somewhat less often
unwell for more than a week and in whom no other cause can children may present with neurological features, although the
be found. The most common initial diagnosis in a child later majority with established lupus have evidence of neuropsychiat-
found to have lupus is ‘probable viral infection’. However, very ric involvement.31 Headache is quite common, but is diagnosti-
few viral infections have symptoms that persist for more than a cally non-specific. Nowadays in the developed world, chorea is
week and most other infections (at least in the developed world) probably a more common manifestation of lupus than of rheu-
have declared themselves before then. In a child presenting with matic fever. Lupus may also rarely present with an encephalo­
fever and weight loss, malignancy is a diagnostic possibility and pathy, transverse myelitis or polyneuropathy.

PAEDIATRICS AND CHILD HEALTH 18:2 63 © 2007 Published by Elsevier Ltd.

 Symposium: bone & connective tissue
Raynaud phenomenon may be a presenting feature. Indeed,
it was one of the clinical manifestations listed in the original
ACR classification criteria, but was dropped due to poor speci-
ficity and sensitivity. Many normal adolescents have vasomotor
changes in the periphery with or without the triphasic pattern
of colour change seen in true Raynaud disease. The finding of
capillary loop abnormalities at the pre-nail skin in a child with
­Raynaud phenomenon is suggestive that the child has lupus or
mixed connective tissue disease. However, most children with
Raynaud phenomenon who later develop lupus do not have
­significantly abnormal capillary loops.32
Investigations at diagnosis
A complete blood count and differential, ESR and urinalysis, stud-
ies performed on most unwell children, may provide results that
strongly suggest lupus. Most newly diagnosed children will have a
normochromic normocytic anaemia, a lymphopaenia and a low or
low–normal platelet count in the face of a high ESR. A leukocytosis
or thrombocytosis would be distinctly unusual unless there was a
concomitant infection. A high ESR with a normal or low platelet
count should always raise the suspicion of lupus or leukaemia. It
is relatively unusual for a child with SLE to have a normal ESR.
Microscopic haematuria and/or proteinuria indicates probable
nephritis. A plasma creatinine will help assess its severity.
The sine qua non of SLE is the finding of autoantibodies
including ANAs. Although the presence of ANAs is one of the
classification criteria for SLE and a negative test makes lupus
very unlikely, a positive ANA test occurs so commonly in chil-
dren without lupus or any serious illness that its presence (even
in quite high titres) is of minimal diagnostic value.6 A strong
argument can therefore be made in favour of ordering an anti-
DNA and anti-ENA test immediately in any child in whom the
diagnosis is seriously considered. Other autoantibodies worth
seeking in the evaluation of a child with possible lupus is the
indirect antiglobulin test (Coombs’ test) and the rheumatoid fac-
tor test, both of which are found in about one-third of children
with lupus, and which have quite high specificity for the disease.
Hypocomplementemia (low C3 and C4) is common in lupus and
raised complement levels are strong evidence against the diagno-
sis. With the combination of above tests, the diagnosis of lupus
can usually be established.
Investigations to further assess and to monitor the disease
Anticardiolipin or other antiphospholipid antibodies, and par-
ticularly the presence of a lupus anticoagulant, may indicate that
the child is at risk of a thrombotic event. However, many chil-
dren with lupus have antiphospholipid antibodies but never have
a thrombosis, so the value of these tests is limited. Nevertheless,
a thrombotic risk is much greater for children with lupus than for
an age-matched population, and this possibility becomes greatly
increased in pregnancy.
A kidney biopsy adds relatively little information to help ini-
tial management, even when the urinalysis is abnormal.33 How-
ever, a renal biopsy certainly helps determine management if
the urinalyses remain abnormal for even a few weeks despite
appropriate treatment, and would certainly be appropriate if
renal function is abnormal.
Although some centres do routine echocardiograms and pul-
monary function tests initially and at yearly or 2-yearly ­intervals,
PAEDIATRICS AND CHILD HEALTH 18:2
there is little evidence that these investigations are very help-
ful, although they may help detect otherwise unexpected organ
involvement. A complete blood count, urinalysis, plasma creati-
nine, anti-DNA, C3 and C4 levels at regular intervals are help-
ful in monitoring the disease and modifying therapy. At disease
onset these tests need to be repeated frequently (every few days),
but as the disease improves the frequency can be reduced to
monthly and then 3-monthly or even less often if the child is
on minimal therapy and the disease is clinically quiescent. It is
valuable every few months to ask a haematologist specifically to
look for Howell–Jolly bodies as they can be easily overlooked by
technicians in a busy service laboratory. They are indicators of
splenic hypofunction, which occurs occasionally in lupus and is
associated with overwhelming pneumococcal infection.34
Management
Management of SLE in children is challenging. The unpredict-
ability of the disease, with remissions and relapses, can make it
difficult for the family and child to cope and adversely affects the
quality of life.35 All treatment must be tailored to the individual
child and the choice of medications often depends on the extent of
organ involvement. Although the disease itself may result in sig-
nificant morbidity and mortality, unfortunately many of the medi-
cations themselves are also associated with morbidity. To provide
the best care for the child and family often takes the involvement
of many subspecialties and allied healthcare professionals. The
paediatrician is often a key player, ensuring coordination of care
and being the primary communicator between subspecialties.
The choice of medications depends on the severity of disease
and extent of organ damage. All children with SLE will require
some medication in the course of their disease (Table 3). Corticoste-
roids are the mainstay of treatment. Most children will also require
additional medications depending on organ involvement. Hydroxy-
chloroquine is almost always started at diagnosis and continued for
many years after corticosteroid therapy has been stopped.
Corticosteroids
Prednisone is nearly always required at some stage. Very often the
doses are high and associated with serious side effects (Table 4)
so careful judgement is needed in weighing up the pros and cons
of treatment. It is not uncommon for children to feel that the
side effects of prednisone are worse than the disease itself and
consequently they may be non-adherent to the therapy without
the treatment team being aware of this. It is important during this
difficult time that children are seen frequently.
Because of the serious side effects of corticosteroids, they are
usually the first drug to be reduced once improvement is noted in
the clinical picture and laboratory parameters. At disease onset
children are usually put on a three times a day schedule of pred-
nisone. The midday dose is usually tapered and discontinued
first. Once the child is on twice daily prednisone, the evening
dose is decreased. It is tempting to decrease prednisone quickly
because of the significant side effects, but experience has shown
that a steady cautious decrease results in fewer children flaring
and having to go back on high-dose corticosteroids.
Initially corticosteroids are started at high doses (approximately
2 mg/kg/day). Often megadoses of intravenous methylpred-
nisolone for 3 consecutive days followed by oral ­corticosteroids
64 © 2007 Published by Elsevier Ltd.
 Symposium: bone & connective tissue

Medications used in the treatment of systemic lupus erythematosus

Drug Indications for use Dosage and comments

Hydroxychloroquine As single treatment for mild disease 5 mg/kg/day

As an adjunct therapy with corticosteroids for moderate or
severe disease
Recent studies have shown more generalized benefits,
including a decrease in disease flares36
May have a lipid lowering affect37
Annual ophthalmology visit for colour and visual
field monitoring - though risk of retinal damage at
this dose appears to be negligible

Non-steroidal anti- For musculoskeletal signs and symptoms Naproxen 15 mg/kg/day (divided BID)
inflammatory drugs For pericarditis or pleuritis Ibuprofen 30–50 mg/kg/day (divided TID)
Indomethacin 1–3 mg/kg/day (divided TID)

ASA For significantly elevated anticardiolipin antibodies and/or 81 mg/day (a baby aspirin)
lupus anticoagulant

Corticosteroids Required in all children except those with mild disease who Prednisone 1-2 mg/kg/day (in divided doses)
may only need hydroxychloroquine tapered as improvement occurs. Consolidated into
BID and then single daily dose as dose decreased
or
IV methylprednisolone 30 mg/kg/day for 3 days
followed by prednisone 0.5–2 mg/kg/day (higher
dose for more severe disease)

Azathioprine For disease not controlled adequately with corticosteroids 1–3 mg/kg/day as single daily dose
and hydroxychloroquine

Cyclophosphamide Severe organ involvement, particularly lupus nephritis and 500–1000 mg/m2/monh IV × seven doses followed
CNS disease by 3 monthly × eight doses

Mycophenolate mofetil Some forms of lupus nephritis (membranous) 500 mg BID increasing to 3 g/day depending on
(MMF)* Possible maintenance therapy after a course of intravenous child’s size and tolerance
cyclophosphamide

Rituximab** Monoclonal antibody that targets CD20 on B cells 375 mg/m2 IV once weekly for 4–8 doses or
In severe SLE, especially in those with autoimmune 750 mg/m2 in two doses 2 weeks apart
cytopenia or lupus nephritis who fail or are intolerant of
cyclophosphamide.
Not well established therapy and effectiveness is anecdotal

*Relatively little experience in its use.

**Should be considered experimental at present.

Table 3

are used. This may allow oral therapy to be started at a rather
lower dose while getting a quicker symptomatic and laboratory
response. Intravenous methylprednisolone may also be used
for disease exacerbations, allowing a smaller increase in oral
­corticosteroids.
Adherence to corticosteroid therapy, especially in an adoles-
cent, is challenging. The side effects of prednisone can be quite
devastating. The consequences of not taking treatment must be
emphasized and the benefit of corticosteroids stressed. The most
upsetting side effect to the adolescent is weight gain. As part of
the treatment team, a dietician who can counsel these adoles-
cents is very helpful. A recent study found that restrictions in
dietary fat and salt can significantly decrease the weight gained
by adolescents on high-dose corticosteroids.38
Hydroxychloroquine
Hydroxychloroquine has recently become a standard therapy,
being used in mild lupus or in combination with other drugs in
more severe disease. There is convincing evidence that its ­regular
use decreases the risk of disease exacerbations.36 It also has an
effect on plasma lipids and may lower the long term risk of car-
diovascular complications.37 Although chronic hydroxychlo-
roquine therapy has been associated with retinopathy, the risk
seems to be minimal or non-existent if the daily dose is kept at
6 mg/kg/day or less.39
Acetylsalicylic acid and non-steroidal anti-inflammatory drugs
Low dose acetylsalicyclic acid (ASA) (3–5 mg/kg/day) may be
used as prophylaxis against thrombotic events. Generally it is

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 Symposium: bone & connective tissue

Experimental or ‘desperation’ therapies

Corticosteroid side effects
Side effects
Increase in appetite and
weight gain, cushingoid
facies
Acne
Recommendations
Restrict salt and fat intake in diet,
nutritional counselling if available
Topical antiacne creams
Rituximab
There has been some recent interest in the role of B-cell depletion
using a monoclonal antibody to a B-cell marker, CD 20, in the
management of lupus, particularly thrombocytopenia. The early
data are promising, but it does not appear to be effective in all
children. Its use should probably be restricted to children with
severe disease refractory to cyclophosphamide and perhaps also
to plasmapharesis.43

Mood swings Discuss openly and let child and

family know that some of these
behaviours are difficult to control
Stretch marks There is no effective cream;
reinforce that the redness will fade
Plasmapharesis
This has been used for many years in refractory lupus. It is some-
times beneficial, particularly when combined with high-dose
corticosteroids and cyclophosphamide. It is not a consistently
effective therapy.

Slower growth Emphasize to child and family that

Splenectomy
most children catch up to their
For children with severe refractory cytopenias unresponsive to
predetermined height
the standard therapies for idiopathic thrombocytopenia, splenec-
Osteopenia Calcium and vitamin D supplements tomy is occasionally effective. It does, however, greatly increase
the risk of overwhelming sepsis, particularly with ­salmonella and
Avascular necrosis (AVN) If AVN is suspected, X-ray and/ or
pneumococcus.
MRI, and if present refer to
orthopaedics
Bone marrow or stem cell transplants
Increased susceptibility Yearly flu shot, pneumovax vaccine, Autologous or allogeneic bone marrow or stem cell transplants
to infection varicella vaccine if child has not have been effective in some adults.44 Data in children with lupus
had chicken pox are extremely limited. There is significant morbidity and mortal-
ity with this approach and it should only be used as a last resort.
High blood pressure Monitor regularly and start
It is unclear if the reconstitution with autologous or allogeneic
antihypertensive drugs if necessary
cells has a specific effect or merely improves recovery time after
Cataracts These cataracts generally do not immune ablation.
affect vision. Regular monitoring by
ophthalmologist
Monitoring of disease activity
Increased risk of Lipid profile before corticosteroid
Monitoring SLE activity is not always easy. There are numer-
atherosclerosis treatment. Hydroxychloroquine
ous factors which must be looked at and all should be taken
into account before any treatment changes are made. Laboratory
Table 4
investigations are important and must be done on a regular basis.
Laboratory tests include: haematology, ESR, C3, C4, anti-DNA
used in children with high levels of antiphospholipid antibod- (quantitative), AST, ALT, LDH, albumin, U&E, creatinine and
ies and/or those with a lupus anticoagulant. Whether or not urinalysis. It is crucial in monitoring a child with SLE that they
the presence of raised homocysteine levels warrants the use of are seen by a physician on a frequent basis. This can be as often
chronic ASA therapy is also unknown. as every 2–4 weeks at diagnosis, to every 2 months or less when
Non-steroidal anti-inflammatory drugs (NSAIDs) are used the disease is under control.
for musculoskeletal symptoms and signs, which surprisingly can There are a number of well validated disease activity scores
­sometimes be severe even in children on moderate or high-dose that can be helpful in monitoring SLE. The more commonly used
corticosteroids. These agents are also valuable for treating serositis. in children are: SLE Disease Activity Index (SLEDAI), Lupus
Activity Index (LAI), the European Consensus Lupus Activ-
Immunosuppressive agents ity Measurement (ECLAM), Systemic Lupus Activity Measure
Azathioprine and cyclophosphamide are the most commonly (SLAM) and the British Isles Lupus Assessment Group (BILAG).
used immunosuppressive agents in lupus. There seems fairly All of these are sensitive to change.45
convincing evidence that early use of these agents helps lessen
corticosteroid toxicity and improves the outcome of lupus, but
Assessing disease damage
there remains controversy about which agent is preferable in
the management of renal disease.40,41 Recently, mycophenolate A related but separate issue in a chronic relapsing disease like
mofetil has been increasingly used in children with lupus, with lupus is how to evaluate the cumulative disease damage. This
some evidence of benefit, particularly in class V (membranous) is perhaps more important for clinical studies than day-to-day
glomerulonephritis. Also, it may be less toxic than cyclophospha- patient management, but is of importance as we look to improve
mide.42 However, its exact role remains to be determined. the long term outcomes. Such damage (e.g. endstage renal

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 Symposium: bone & connective tissue
f­ailure, atherosclerotic cardiovascular disease and osteoporosis)
may occur as a consequence of the disease itself and/or its treat-
ment. The validated SLICC/ACR damage index provides useful
prognostic information about individuals with lupus.3,46 In chil-
dren cumulative disease activity and long term high-dose corti-
costeroid use have been shown to be risk ­factors for increased
damage; immunosuppressive therapy may be ­protective.3
Immunizations
Children with SLE are at increased risk for bacterial and viral
infections. They should have their recommended childhood
­immunizations but those on any corticosteroids who are immuno­
compromised should not have live vaccines.
• Varicella vaccine (Varivax) is recommended to all children
who have not had varicella zoster virus. This is a live vaccine
and must be given before corticosteroid therapy is started.
• Pneumococcal vaccine is recommended for all children at
­diagnosis and every 5 years. Invasive pneumococcal infections
are more common in children with SLE.
• Influenza vaccine is recommended on a yearly basis. Studies
have shown that children who receive it have a protective anti-
body response, although the antibodies tended to be lower then
in the healthy control groups.47,48
• Haemophilus influenza (Hib) and meningococcal vaccines are
also recommended for all children with SLE.
Sun protection
Exposure to ultraviolet (UV) light can result in exacerbations of
the lupus rash and also systemic symptoms such as joint pains
and fatigue. There have been reports that patients who regularly
use sunscreen (SPF 15 or greater) have significantly lower renal
involvement, thrombocytopenia and hospitalizations, and require
less cyclophosphamide treatment.49 All children with SLE must be
advised to wear sunscreen daily to all exposed skin (including ears),
not just on sunny days as clouds do not eliminate UV exposure.
Diet and exercise
There are no special dietary requirements but because of cor-
ticosteroid-induced weight gain, foods high in calories and in
salt should be avoided. Exercise should be encouraged. Most
children participate in full time school, except during periods of
severe active disease. Failure to attend school should alert the
healthcare team to possible psychosocial issues. Communication
with school teachers is left to the discretion of the family, with
the involvement of the clinical team if requested.
Fatigue and sleep
Fatigue is one of the most common symptoms. It will generally
improve as the disease improves. Some parents find it difficult
during this time to allow their children to participate in activities.
Occupational and physical therapists can be very helpful in help-
ing to develop better activity and sleep behaviours.
Some children’s sleep pattern can change at the onset of SLE.
This is usually related to corticosteroids. Some children become
hyperactive and moody, and have difficulty falling asleep. This
PAEDIATRICS AND CHILD HEALTH 18:2
can be improved by taking the evening dose of corticosteroids
earlier. Some children on high-dose corticosteroids need to uri-
nate several times at night and can find it difficult to fall back
to sleep. This is dose related and once the corticosteroids are
reduced it becomes less problematical.
Impact of systemic lupus erythematosus on the child
and their family
Once the diagnosis has been made, for many families it feels like
a rollercoaster ride. A family that has a good support network
and resources and is able to seek this support when they feel
they need it will cope better.
Education is often a first step in helping a family feel that they
have some control. It is important to remember not to overload
families at the first couple of visits following diagnosis. The nurse
can play a key role in assisting them with learning about the dis-
ease by frequent follow-up telephone calls and visits. Written
information and frequent reviews of the disease and medication
side effects are necessary.
Teenagers often provide a unique challenge as they may use
denial as a coping mechanism. This is not necessarily a bad
mechanism, but it can be frustrating for family members. Most
children are able to attend school full time. Many choose not to
tell friends or teachers about their disease. Often teenagers will
continue with all their previous activities as they do not want to
be different.
Often the chronicity of SLE is not fully understood by a fam-
ily or the child until well into the second or third year after
diagnosis. It is at this time, even though the disease may be
well controlled and few medications are needed, that sup-
port and further education is required. The unpredictability of
SLE, where a child can be well for a number of years and then
have a flare of their disease, is extremely stressful. This again
reinforces the chronicity of SLE and families may have a more
difficult time coping with a disease flare than at the original
diagnosis. A trusting relationship with the medical care team
is crucial with open and honest communication with both the
child and parents.
Children with SLE and their families require a team of health
professionals to assist them through to adulthood. As children
grow older it is important that the healthcare team encourages
the family to give increasing control of the disease management
to the child. This transition of the disease management from the
parents to the child may be helped by having a specific transi-
tion clinic for adolescents run jointly by paediatric and adult
physicians. The unpredictability of lupus with its flares and
remissions means that close monitoring will always be required,
but many children adapt to these challenges and do not let their
disease interfere excessively with their lives. It can be very
rewarding to watch these individuals grow into healthy success-
ful adults. ◆
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Practice points
• The diagnosis can usually be made quite easily once the
possibility is considered
• A positive antinuclear antibody test has very low specificity.
Positive anti-DNA antibodies are almost diagnostic
• Early aggressive treatment with high-dose corticosteroids is
almost always required
• The disease is serious and life-long
• Regular clinic visits with a team specializing in the rheumatic
diseases of childhood has helped improve outcome
Acknowledgements
We would like to acknowledge the thoughtful and helpful
­comments of our colleague Dr Lori Tucker.
69 © 2007 Published by Elsevier Ltd.