4. Epidemiology
• Prevalence of SLE in children and adolescents (1-
6/100,000)
• Childhood onset of SLE : approximately 20% of all
cases
• predominantly affects females
• 2-5 : 1 ratio prior to puberty
• 9 : 1 ratio during reproductive years
• median age at diagnosis of 11-12 yr
20. Investigations
• ANA
• Serum C3 and C4 level : decreased
• ESR & CRP : raised
• complete blood cell count : decreased
• Platelet count : decreased
• prothrombin and partial thromboplastin time :
prolonged
• Coombs test : positive
21. Investigations
• Baseline renal function testing
– Urinalysis
– urea, creatinine
– albumin levels
– 24-hour urine collection to determine total protein
and creatinine clearance
• Renal biopsy
– Performed if evidence of renal disease
– safe in the absence of severe thrombocytopenia,
hypertension, on uremia
26. Systemic Lupus International Collaborating
Clinics (SLICC) Classification Criteria for SLE 2012
presence of 4 criteria
(including at least 1 clinical and 1 immunologic
criterion)
28. Course of disease
• Several activity indices developed : BILAG, SLEDAI, LAI, SLAM
• Renal disease and infection are leading cause of morbidity
29. Course of disease
• Characterized by exacerbations and remissions that vary in
severity
• Lupus flare
– Clinically : Increasing fatigue, Arthralgias and myalgias,
New or worsening rash, Persistent headache, Fever,
Abdominal pain
– blood : anaemia, raised ESR and thrombocytosis
– Urine examination : proteinuria, leucocyturia, haematuria,
casts
– Complement levels fall and dsDNA level rises
• 5 yr survival rate for pediatric SLE is ~95%, though the 10 yr
survival rate remains ~80-90%.
30. Neonatal Lupus
• passive transfer of maternal immunoglobulin G
autoantibodies to the fetus
• associated with maternal anti-Ro and anti-La
antibodies
• characteristic annular or macular rash
typically affecting the face
(especially the periorbital area),
trunk, and scalp
• appears within the 1st 6 wk of life
after exposure to ultraviolet light
and lasts 3-4 mo
31. Neonatal Lupus
• Conduction system abnormalities
– prolongation of the PR interval, complete heart block,
cardiomyopathy
– Detected in utero by fetal echocardiogram beginning at
16 wk of gestational age
• cytopenias and hepatitis : reversible
• fluorinated corticosteroids, intravenous immunoglobulin,
plasmapheresis, hydroxychloroquine, and terbutaline have
been used in pregnant women with anti-Ro or anti-La
antibodies
• Significant conduction system abnormalities after birth:
cardiac pacing, intravenous immunoglobulin and steroids
• severe cardiomyopathy : cardiac transplantation.
32. Drug induced lupus
• triggered by exposure to specific medications,
including minocycline, many anticonvulsants,
sulfonamides, antiarrhythmic agents, and other
drugs
• If prone to SLE, may act as a trigger for true SLE
• In others, provoke a reversible lupus-like syndrome.
• affects males and females equally
• genetic predisposition toward slow drug acetylation
• Circulating antihistone antibodies seen in serum
33. Treatment
• Goals
– educate the patient about the nature of the illness
– to control symptoms
– To prevent organ damage
• Avoid sun exposure
– Sunscreen with minimum SPF-24
– avoidance of prolonged periods in the sun
– Use of long-sleeved clothing, hats and sun glasses
34. Medical management
• Immunosuppressive treatment regimens consist of a period of
intensive induction therapy over 6–12 months to achieve
disease quiescence followed by a period of long-term
maintenance therapy to control disease and prevent
subsequent flares.
• Induction treatment
– depends on the severity of disease activity
– use of intravenous corticosteroids (eg, intravenous
methylprednisolone for 3–5 daily doses) as broad
suppressants of the immune response
– followed by longer term high-dose oral corticosteroids (eg,
prednisolone 1–2 mg/kg/day)
35. Medical management
• Induction treatment
– together with disease-modifying agents selected on
the severity of disease activity
– Weaning of corticosteroid dose must be gradual and
supervised carefully
• Maintainance treatment
– disease-modifying agents, such as AZA or MMF, in
combination with a weaning regime of oral
corticosteroids
• Management of flares
– High dose corticosteroid
37. Treatment
• Hydroxychloroquine
– (5-7 mg/kg/day up to 400 mg/day)
– For mild SLE manifestations
– prevents SLE flares, improves lipid profiles, and
beneficial impact on mortality and renal outcomes
– ophthalmology exams every 6-12 mo
• NSAIDs
– arthralgias and arthritis
• Corticosteroids
– improve acute deterioration
– optimal dosing of corticosteroids in children and
adolescents remains unknown
38. Treatment
• Corticosteroids
– severe disease : high doses of intravenous
methylprednisolone (e.g.,30 mg/kg/day for 3 days,
followed by weekly pulses) or high doses of oral
prednisone (1-2 mg/kg/day)
– gradually tapered over months
• Steroid-sparing immunosuppressive agents
– Methotrexate, leflunomide, and azathioprine for
persistent moderate disease : arthritis, significant
cutaneous or hematologic involvement, pleural disease
– Intravenous or oral cyclophosphamide reserved for the
severe, potentially lifethreatening SLE manifestations,
such as renal, neurologic, and cardiopulmonary
disease.
39. Treatment
• Lupus dermatitis
–Topical glucocorticoids and antimalarials
(such as hydroxychloroquine)
–Systemic treatment with retinoic acid is a
useful strategy in patients with inadequate
improvement
–therapy-resistant lupus dermatitis topical
tacrolimus, systemic dapsone or thalidomide
40. Treatment of lupus nephritis
• for the treatment of severe and refractory SLE
Childhood Arthritis Rheumatology Research Alliance
(2012) consensus treatment plan induction therapy of
newly diagnosed proliferative lupus nephritis
– 6 mo of therapy with either cyclophosphamide or MMF ,
used in combination with a standardized glucocorticoid
regimen
– For patients who fail to achieve a partial response in 6 mo it
is appropriate to switch agents
– maintenance therapy of lupus nephritis recommend use of
mycophenolate mofetil, every 3 mo IV cyclophosphamide
or azathioprine for 12 mo after completing induction
therapy
• ESRD : dialysis and renal transplant
42. Treatment
• Patient Education
– natural history of their disease
– potential complications of treatment
– Issues of compliance must be discussed to prevent children
from being tempted to discontinue steroids because of
undesired changes in body image or fear of serious side
effects
– danger of suddenly stopping high-dose steroids
• Social worker trained to deal with chronically ill adolescents /
psychologist consultation
– Dealing with problems of self image and self-esteem
43. Preventive approach
• Vaccinations : influenza and pneumococcal
• Osteoporosis : calcium and vitamin D
supplements, bisphosphonates
• management of hyperglycemia
• management of obesity
44. Newer modalities in treatment
• Belimumab (FDA approved)
– monoclonal antibody against BLyS (B-cell
activating factor)
– reduces the number of SLE flares& decreases the
dose of prednisone
• Biologic agents in early phase investigation:
– Tabalumab, Rigerimod, Epratuzumab
• Rituximab : unsatisfactory results
• Transplantation of autologous hematopoietic stem
cells in severe refractory SLE
45. References
• Nelson textbook of Paediatrics, 20e
• Harrison’s Principles of Internal Medcine, 19e
• OP Ghai textbook of Paediatrics,
• Pediatrics in Review Vol. 14 No. 5
• EULAR Textbook on Rheumatic Diseases
• 2015 ACR/SLICC Revised Criteria for Diagnosis of
Systemic Lupus Erythematosus : Autoimmune
Diseases and Therapeutic Approaches 2015
46. References
• Lupus flare : how to diagnose and treat ?; medicine
update 2011; www.apiindia.org
• Juvenile SLE- review of clinical features and
management; Indian Paediatrics , Volume 48;
november 17, 2011
• New insights into the pathogenesis and management
of lupus in children; Midgley A, et al. Arch Dis Child
2014;99:563–567
• ACR guidelines for lupus nephritis; Hahn et al. 2012
Compared with adults, children and adolescents with SLE have more severe disease and more widespread organ involvement
Up to 20% of all cases of SLE are diagnosed prior to age 16 yr
Rarely onset prior to the age of 5 Years.
Lupus dermatitis can be classified as acute, subacute, or chronic
DLE : ) roughly circular with slightly raised, scaly hyperpigmented erythematous rims and depigmented, atrophic centers with follicular plugging in which all dermal appendages are permanently destroyed.
,malar rash : slightly raised erythema, occasionally scaly, on the face (particularly the cheeks and nose—the “butterfly” rash), ears, chin, V region of the neck and chest, upper back, and extensor surfaces of the arms
SCLE : Subacute cutaneous lupus erythematosus (SCLE) consists of scaly red patches similar to psoriasis, or circular flat red-rimmed lesions
AVN: mostly femoral heads, but also may affect knees, shoulders, elbows, or wrists. Risk in steroids, vasculitis and Raynaud phenomenon
Arthritis : : symmetrical polyarthritis affecting large and small joints, most commonly the hands, wrists, and knees and less commonly the hips and ankles
70% of children who have SLE
Leading cause of morbidity & mortality
careful monitoring of blood pressure and urinalyses
High white cell count
unusual
unless there is an associated infection or the patient is in corticosteroid therapy
Leukopenia : lymphopenia (predominantly) and neutropenia
Platelet :
Thrombocytopenia : due to peripheral platelet destruction
Antiplatelet antibodies without thrombocytopenia
Idiopathic thrombocytopenic purpura
thrombocytopenic thrombotic microangiopathy
a prolonged APTT : circulating anticoagulant that blocks activation of the prothrombin activaton complex in vitro by reacting with the phospholipid portion of the complex
crossreacts with anticardiolipin antibodies and is responsible for the false-positive serologic test for syphilis (VDRL) in SLE patients.
These patients may be at increased risk of bleeding in patients with prothrombin deficiency due to prolonged prothrombin time as a result of specific inhibitors of the coagulation cascade factors
occurs in 15% to 45% of children who have SLE and is second only to renal disease as a cause of morbidity and mortality.
Before a diagnosis of primary CNS lupus is, other causes of CNS dysfunction must be excluded, including CNS infection, hypertensive encephalopathy, metabolic disturbance, intracranial hemorrhage or thrombosis, and steroid- induced psychosis.
Headache : ; severe, unremitting “lupus headache” that reflects active disease
Transverse myelitis
Cerebellar ataxia
Papilledema
Guillan-Barr like syndrome
Premature atherosclerosis and myocardial infarction
Predisposing factors appear to include prolonged steroid use, vasculitis, hyperlipidemia, hypertension, the presence of a Lupus anticoagulant, diabetes mellitus, and a strong family history of MI
Interstitial lung disease : insidious onset of cough or dyspnea in patients who have long-standing SLE
Restrictive defects and diffusion abnormalities can be detected on pulmonary function tests
Noncardiogenic pulmonary edema (such as sepsis, uremia, and pancreatitis)
Pancreatitis : spontaneously or secondary to steroid or azathioprine treatment
Mild, transient elevations of liver function studies occur in up to 25% of patients and typically are exacerbated by aspirin treatment. If marked abnormalities of liver function are detected on tests, one should consider
other diagnoses, particularly autoimmune chronic active hepatitis, which shares many clinical and serologic findings with SLE Occasionally, esophageal dysmotility similar to that seen in scleroderma may occur
MCTD is characterized by overlapping features of SLE, systemic sclerosis (SSc), and polymyositis (PM), and by the presence of high titers of antibodies against U1 ribonucleoprotein (RNP)
UCTD have signs and symptoms suggestive of a systemic autoimmune disease but do not satisfy the classification criteria for a defined connective tissue disease such as SLE or MCTD
Overlap syndrome : rhupus
Patients with Sjögren’s syndrome may have extraglandular manifestations that can be observed in SLE, such as neurologic and pulmonary abnormalities, express antibodies to Ro and La antigens
Systemic sclerosis coexistence of Raynaud phenomenon and gastroesophageal reflux is typically observed in SSc; however, these findings are nonspecific and may be seen in patients with SLE or healthy individuals. By contrast, sclerodactyly, telangiectasias, calcinosis, and malignant hypertension with acute renal failure are more consistent with SSc rather than SLE. Further, a positive ANA is present in most patients with SSc, while other serologies such as anti-double-stranded DNA (dsDNA) and anti-Smith (Sm) antibodies which are more specific for SLE, are not commonly observed in SSc
Behçet’s syndrome – Oral aphthae are present in almost all patients with Behçet’s syndrome, and may be observed in patients with SLE. Other overlapping features include inflammatory eye disease, neurologic disease, vascular disease, and arthritis. However, patients with Behçet’s are more commonly male and ANA-negative.
Patients with medium and small vessel vasculitides such as polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA) (Wegener’s), or microscopic polyangiitis (MPA) may present with overlapping features of SLE including constitutional symptoms, skin lesions, neuropathy and renal dysfunction
malignancies – Leukemia or myelodysplastic syndromes may present with hematologic and constitutional symptoms similar to those observed in SLE. However, monoclonal expansion of B and T cells (as assessed by immunophenotyping), monocytosis, or macrocytosis can distinguish these malignancies from SLE
MS : Although rare, patients with SLE can present with cranial neuropathies that must be distinguished from MS
Several viral infections can produce signs and symptoms present in SLE, including cytomegalovirus (CMV) and Epstein-Barr virus (EBV). In addition, EBV infection may lead to a positive ANa
Diseases where ANA is useful in diagnosis
Systemic lupus erythematosus 100%
Systemic sclerosis 60–80%
Sjögren’s syndrome 40–70%
Dermatomyositis or polymyositis 30–80%
Mixed connective tissue disease 100%
Autoimmune hepatitis 100%
A closed renal biopsy is contraindicated in the presence of a prolonged bleeding time.
C3 and C4 levels, together with antidouble-
stranded DNA titers and close
monitoring of renal function and dinical
disease, can guide therapy in patients
who have active lupus
Nephritis.
Skin biopsy : the patient suspected of having ANAnegative
SLE; lupus band test detects
immunoglobulin and complement
deposition at the dermal-epidermal
junction, which while not specific, does suggest SLE
cerebrospinal fluid studies may be normal or show a mild lymphocytic pbeocytosis and elevated protein levels.
computed tomographic scan : evidence of brain edema on atrophy and may suggest sites of vasculitis
Plain radiographs and bone scans
diagnosis of avascular necrosis and compression fractures
Developed for long term observational studies and have been shown to be strong predictors of damage and mortality, and reflect change in disease activity
British Isles Lupus Assessment
Group Scale (BILAG), t
European Consensus Lupus Activity Measure (ECLAM)
the SLE Disease Activity Index (SLEDAI)
the Lupus Activity Index (LAI)
The National Institutes of Health SLE Index Score (SIS)
The Systemic Lupus Activity Measure (SLAM)
Sunscreens and clothing covering the extremities can be helpful. Abruptly stopping medications, especially corticosteroids, can also cause flares and should be avoided.
severity of disease in pediatric SLE is notably worse than the
typical course for most adult-onset SLE
Rx : fluorinated corticosteroids (dexamethasone or betamethasone), intravenous immunoglobulin, plasmapheresis, hydroxychloroquine, and terbutaline (combined with steroids) have been used in pregnant women with anti-Ro or anti-La antibodies to prevent occurrence or progression
Most encouraging are retrospective cohort studies suggesting maternal treatment with hydroxychloroquine may provide effective prophylaxis
Antiphospholipid antibody present in 40% of patients with SLE
More risk of arterial or venous thromboses so require long term warfarin therapy.. Sle with aps has more risk of fetal loss than sle only
important predictor of the development of irreversible organ damage
and avoidance of prolonged direct sun exposure and other ultraviolet light may help control disease and should be reinforced at every visit with the patient.
cyclosporine and infliximab or biologic therapies available
through clinical trials. Autologous haematopoietic stem cell transplant are reserved for the rare cases of refractory cSLE
HCQ : treating mild SLE manifestations such as rash and mild arthritis,
Potential toxicities include retinal pigmentation and color
NSAIDS : Use naproxen , ibuprofen causes aseptic meningitis
vision impairment
Potential consequences
of corticosteroid therapy include growth disturbance, weight
gain, striae, acne, hyperglycemia, hypertension, cataracts, avascular
necrosis, and osteoporosis.
cyclophosphamide is highly effective in
controlling disease, the potential toxicities are significant, including
cytopenias, infection, hemorrhagic cystitis, premature gonadal failure,
and increased risk of future malignancy. Attention to adequate hydration
can attenuate the risk of hemorrhagic cystitis. Use mesna as antidote for urothelial toxicity.
Fortunately, young
girls are at much lower risk of gonadal failure than older women, and
the use of gonadotropin-releasing hormone agonists, such as leuprolide
acetate, may help prevent gonadal failure.
patients with renal transplants show mixed
results: some series show a twofold increase in graft rejection compared
to patients with other causes of ESRD, whereas others show no
differences. Overall patient survival is comparable (85% at 2 years).
Lupus nephritis occurs in approximately 10% of transplanted kidneys
Grade 3 & 4 : 2 regimens with IV CYC : 1. low dose euro lupuS cyc followed by oral AZA or MMF
2. high dose CYC followed by maintaince with AZA or MMF
Pulse therapy with IV glucocorticoid with immunosupressive for induction then taper to minimal amount to control disease
Suddenly stopping steroids : emphasized which may cause life threatening adrenal insufficiency may be life-threatening.
Multidisciplinary team approach
A medical alert bracelet is recommended
