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SYSTEMIC AUTOIMMUNE DISEASE IN CHILDREN

Dr Sumadiono,SpAK
Dr Cahya Dewi Satria, SpA,Mkes
Departmen Ilmu Kesehatan Anak,
RSUP Dr Sardjito, FK UGM
CASE I
• A girl, 10 years old.
• Fever for 2 months
• Hair fall easily
• Inflammation in the knee joint
• Seizure (-)
• GA: malaise, fever, malnutrition
• Malar rash, painless mouth ulceration
• Anemia, trombocytopenia
• Proteinuria, hematuria

1. What’s the diagnosis and differential diagnosis in this case?


2. What’s investigation you need in this case?
3. What’s the management of this case?
4. What’s the complication of this case?
SLE (Systemic Lupus Erythematosus)
EPIDEMIOLOGY
 SLE incidence in children ± 15 – 17 %
 Rare happen in children younger than 5 yo
 Girl > Boy

• Fye KH, Sack KE. Rheumatic diseases. Dalam: Stites DP, Terr AI, penyunting. Basic and clinical immunology; Edisi ke-7. Norwalk:
Appleton & Lange, 1991; 438-63.
• Soepriadi, M; Setiabudiawan B. Lupus eritematosus sistemik. Dalam: Garna H, Nataprawira HMD, penyunting. Pedoman diagnosis dan
terapi Ilmu Kesehatan Anak. Edisi ke-3. Bandung: Bagian IKA FK Universitas Padjadjaran, 2005;133-42
ETIOLOGY
 Its not certain
 Interaction among genetic factor, acquired factor, and
environmental factor.
 Immune disorder  Persistence of autoreactive B and T
lymphocytes.
 AutoAb – AutoAg binding  immune complex 
complement activation  inflammatory reaction  lesion
(Type 3 Hypersensitivity)
Sign and Symptoms
 Systemic
malaise, anorexia, fever, fatigue,
weight loss, sometimes
accompained by alopecia.

Alopecia

• Petty RE, Laxer RM. Systemic lupus erythematosus. Dalam: Cassidy JT, Petty RE, Laxer RM, dkk, penyunting. Textbook of pediatrics rheumatology. Edisi ke-5.
Philadelphia: Elsevier Saunders, 2005; 342-83.
Sign and Symptoms
Malar rash
 Skin
Malar rash (butterfly rash),
photosensitivity, purpura, discoid rash,
alopecia, Raynaud’s phenomenon, and
or mucous ulceration.
 Muskuloskeletal
Polyarthralgia, arthritis, tenosynovitis,
myopathy, aseptic necrosis
 Vascular Discoid lupus
Raynaud’s phenomenon, retikularis
livedo, thrombosis, erythromelalgia,
lupus profundus.

Reticularis livedo
Raynaud’s phenomenon

• Petty RE, Laxer RM. Systemic lupus erythematosus. Dalam: Cassidy JT, Petty RE, Laxer RM, dkk, penyunting. Textbook of pediatrics rheumatology. Edisi ke-5.
Philadelphia: Elsevier Saunders, 2005; 342-83.
Sign and Symptoms
 Heart
Pericarditis, pericardial effusion, myocarditis, Libman Sacks endocarditis
 Lung
Pleuritis, basilar pneumonitis, atelectasis, hemorrhage
 Gastrointestinal
Peritonitis, esophageal dysfunction, lymphadenopathy, hepatomegaly,
splenomegaly.
 Nerve
Seizure, psychosis, polyneuritis, peripheral neuropathy.
 Eye
exudate, papilledema, retinopathy.
 Ren
Glomerulonephritis, nephrotic syndrome, hypertension, acute renal failure.

• Petty RE, Laxer RM. Systemic lupus erythematosus. Dalam: Cassidy JT, Petty RE, Laxer RM, dkk, penyunting. Textbook of pediatrics rheumatology. Edisi ke-5.
Philadelphia: Elsevier Saunders, 2005; 342-83.
DIAGNOSIS
 Consensus  Based on American College of Rheumatology (ACR)
Criteria (1997)
 At least 4 of 11 ACR criteria (sensitivity 86% dan specificity
93% )
 The Systemic Lupus International Collaborating Clinics (SLICC)
Classification 2012 is used to revise ACR Criteria 1997
(sensitivity 94% dan specificity 92%)

• Petty RE, Laxer RM. Systemic lupus erythematosus. Dalam: Cassidy JT, Petty RE, Laxer RM, dkk, penyunting. Textbook of pediatrics
rheumatology. Edisi ke-5. Philadelphia: Elsevier Saunders, 2005; 342-83.
• Abbreviations: ACR, American College of Rheumatology; SLICC, Systemic Lupus International Collaborating Clinics Classification
Kriteria ACR & SLICC
ACR 1997 (Sn 85.6%; Sp 91.5%) SLICC 2011 (Sn 93.2%; Sp 93%)
Cutaneous 4 items (malar rash, discoid rash, 4 items (ACLE/SCLE, CCLE, Oral ulcers,
manifestation photosensitivity, oral ulcers) nonscarring alopecia)

Joints 1 item (non erosive arthtitis ≥ 2 peripheral joints) 1 item (nonerosive arthritis ≥ 2 peripheral joints)

Serositis 1 item (pleuritis rub, pleural effusion or pericarditis) 1 item (pleuritis, typical pleurisy, rub, pleural effusion,
pericarditis, typical pericardial pain, pericardial fusion)

Renal disorder 1 item (proteinuria > 0.5 g/day or cellular 1 item (urine protein/creatinine ratio or urinary
cast) protein concentration of 0.5 g of protein/24 h or red
blood cell cast)

Neurologic 1 item (seizure or psychosis) 1 item (seizure or psychosis)


Hematologic 1 item (hemolytic anemia with elevated 3 items (hemolytic anemia, leukopenia or
disorder reticulocytes, leukopenia, lymphopenia or lymphopenia, thrombocytopenia)
thrombocytopenia)

Immunologic 2 items (positive anti-dsDNA/anti- 6 items (positive ANA. Positive anti ds-DNA,
abnormal Sm/antiphospholipid antibodies , anti-Sm, antiphospholipid antibody, low
DIAGNOSIS
 Other conditions to be considered in the differential diagnosis of SLE:
 Infection
 Malignancy
 Toxin exposure
 Other multisystem disorder
 Investigation of SLE:
 Complete blood count: anemia, leucopenia, thrombocytopenia*,
reticulocyte.
 Coomb test, ESR*, CRP, ureum and creatine serum*, SGOT and SGPT
 Electrolite, random blood sugar, coagulogram, complement: C3, C4, and
CH50*
 ANA Test*,anti-dsDNA*, anti-Smith, antiphospholipid antibody,
anticoagulant lupus, siphylis serology (VDRL)
 Urinalysis*, protein urine (quantitative and or semi quantitative)*, urine
culture;
 Imaging: Thorax and Joint X-ray, Renal USG, Head MRI (by indication)
 ECG
 Not all investigation must to be examined, but the investigation with (*)
sign are better to do early.
MANAGEMENT
NSAID (non steroid anti inflammatory drug)
Given if there are skin and joint impairment only. It can be as a
single or combination with hydroxychloroquine.
Naproxen *
10 - 20 mg/kgBW/day, po, divided into 2 - 3 dose
Sodium Tolmetin (Tolectin) *
20 - 30 mg/kgBW/day, po, divided into 3 - 4 dose
Salicylate
durante cunam
<20 kg : 80–90 mg/kgBW/day, po, divided into 3 - 4 dose
>20 kg : 60–80 mg/kgBW/day, po, divided into 3 - 4 dose

• Klippel JH, Weyand CM, Wortman RL. Primer on Rheumatic Disease. Edisi ke-11. Atlanta:Arthritis Foundation,1997.
• Carreno L, Longo FJL, Gonzalez CM, Monteagudo I. Treatment option for juvenile onset systemic lupus erythematosus. Pediatr Drugs 2002;4(4):241-256.
MANAGEMENT
Antimalarial
Given if skin or mucosa disorder are found dominantly with or without
arthritis.
 Hydroxychlroquine (steroid-sparing agent)
Initial dose: 6-7 mg/kg BW/day divided into 1-2 dose for 2 months
Continued: 5 mg/kgBW/day p.o. (max.300 mg/day)
 Chloroquine HCl
Adult: 250 mg/day
Child: 6-8 mg/kg/day divided into 2 dose
Indication: Severe discoid LE that not response to maximal dose of hydroxychloroquine.
Side effect: Retinopathy (higher than hydroxychloroquine)

• Klein-Gitelman MS, Miller ML. Systemic Lupus Erythematosus. Dalam: Nelson Textbook of Pediatrics. Behrman RE, Kliegman RM, Jenson HB, penyunting.
Edisi ke-17. Philadelphia:Saunders. 2004:809-813.
• Cassidy JT, Petty RE. Textbook of pediatric rheumatology. Edisi ke-2. NewYork: Churchill Livingstone, 1990.
• Hanh, B et al. American College of Rheumatology Guidelines for Screening, Treatment, and Management of Lupus Nephritis. Arthritis Care & Research. 2012;
Vol. 64, 797–808
Management
 Prednisone (oral)
Low dose <0,5 mg/kgBW/day divided into 3-4 dose.
Indication: severe symptoms like prolonged fever, skin disorder, pleuritis,
combined with intravenous high dose intermittent methylprednisolone.
High dose 1-2 mg/kgBW/day (max. 60–80 mg/day) p.o, divided into 3-4
dose for 3-6 weeks until anti-dsDNA (-) and normal complement level,
continue with tapering-off for 1-2 weekss.
Indication: acute fulminant lupus, severe SLE

 Methyl prednisolone (parenteral)


Dose: 30 mg/kgBW/day i.v. (max. 1 g), for 90’, in 3 days continue with
intermittent MP (every week), combine with low dose prednisone every day.
Indication: Severe SLE that not controlled with high dose CS oral, very severe
active recurrency.
Because of its significant toxic effect, high dose CS medication is limited.

• Klein-Gitelman MS, Miller ML. Systemic Lupus Erythematosus. Dalam: Nelson Textbook of Pediatrics. Behrman RE, Kliegman RM, Jenson HB, penyunting.
Edisi ke-17. Philadelphia:Saunders. 2004:809-813.
• Cassidy JT, Petty RE. Textbook of pediatric rheumatology. Edisi ke-2. NewYork: Churchill Livingstone, 1990.
MANAGEMENT
Immunosuppresant / Cytotoxic / Immunomodulator
If there is unresponsive CS medication or have severe side effect of CS medication.
Cyclophosphamide
 Oral: 1–3 mg/kgBW/day
 Parenteral: Initial dose 500 – 750 mg/m2, max 1 g/m2/hr bolus per IV (lowest dose for
leucopenia, trombositopenis, and creatine > 2 gr/dl) in 150 ml Dextrose 5% for 1 hour.
 Indication: severe nephritis lupus or neuropsychiatric disorder.
 Give intravenous mesna to prevent cyclophosphamide induced hemorrhagic cystitis
Mycophenolate mofetil (MMF)
 ACR guideline for the treatment of Nephritis Lupus recommended to use MMF (total 2-3 gram
po) or intravenous combined with glucocorticoid (level A).
 Induction fase: 6 months
 Maintenance fase: 3 years
• Klein-Gitelman MS, Miller ML. Systemic Lupus Erythematosus. Dalam: Nelson Textbook of Pediatrics. Behrman RE, Kliegman RM, Jenson HB, penyunting.
Edisi ke-17. Philadelphia:Saunders. 2004:809-813.
• Cassidy JT, Petty RE. Textbook of pediatric rheumatology. Edisi ke-2. NewYork: Churchill Livingstone, 1990.
• Darmstadt GL, Sidbury R. The Skin. Dalam: Nelson Textbook of Pediatrics. Behrman RE, Kliegman RM, Jenson HB, penyunting. Edisi ke-17.
Philadelphia:Saunders. 2004:2156
MANAGEMENT
Adjuvant therapy:
 Betamethasone 0,05%, Fluosinosid 0,05%  2 weeks, then
Hydrocortisone.
 Sun Block.
 Long term CS medication low natrium diet, sugar, fluid restriction,
Ca and Vit D supplememtation.
Vitamin D: BB < 30 kg: 20 mcg p.o. 3 times/week, BB > 30 kg: 50
mcg p.o. 3 times/ week.
Calcium carbonate (Caltrate) : < 6 mo: 360 mg/day, 6-12 mo: 540
mg/day, 1-10 yo: 800 mg/day, 11-18 yo: 1.200 mg/day
 Physiotherapy.

• Bertsias G, Ioannidis JP, Boletis J, et al. EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task
Force of the EULAR Standing Committee for International Clinical Studies Including T erapeutics. Ann Rheum Dis 2008;67:195–205
Case 2
 a boy, 12 years old
Inflammation in knee and hand fingers since 6 weeks ago
Fever (-), nausea vomiting (-)
GA: looked in pain, VS normal.
Limited movement in knee and fingers.
CBC normal
Knee X-Ray : osteoporosis, narrow joint space, soft tissue
swelling

1.What’s the diagnosis and differential diagnosis in this case?


2.What’s the classification of this case?
3.What’s the clinical manifestation?
4.What’s investigation you need in this case?
5. What’s the management of this case?
6.When the patient need to give IA injection?
7. What’s the complication of this case?
Case 2
P-GALS examnination:
1. Pain? yes
2. Difficult to wearing clothes? No
3. Difficult to walk? Yes

Appearance Movement
Gait √ x
Arm √ √
Leg x x
Spine √ √

Right knee joint: swelling, redness, warm, crepitation (+)


JIA(Juvenile Idiopatic Arthritis)

 (JIA) is the most common type of arthritis in


children. It cause limited functionale and
decrease quality of life.
 JIA is new term of chronic arthritis ILAR (
International Laegue Against Rheumatism)
1997

Cassidy & Petty, Chronic Arthritis in Childhood in Textbook of Pediatric Rheumatology, 5th Ed. Elsevier Saunders
Cimaz, Lehman. 2008.Pediatrics in Systemic Autoimmune Diseases in Asherson, Handbook of Systemic Autoimmune Disease Vol 6
DEFINITION
(AMERICAN COLLEGE OF RHEUMATOLOGY REVISED CRITERIA)

 onset < 16 yo
 Monoarthritis or more
 Arthritis lasting at least > 6 weeks
 Exclude the others cause of arthritis in child:
infection, non infection, hematology and
malignancy, vasculitis and other
autoimmune disease.
Cassidy & Petty, Chronic Arthritis in Childhood in Textbook of Pediatric Rheumatology, 5th Ed. Elsevier Saunders

Cimaz, Lehman, 2008,Pediatrics in Systemic Autoimmune Diseases in Asherson,


Handbook of Systemic Autoimmune Disease Vol 6
DIFFERENTIAL DIAGNOSIS OF JIA
Khubchandani,2002
Peter & Richard, 2001
(Kim et al,
2010)
OLIGOARTHRITIS JIA
 40-60% of JIA case
 Onset : early life, peak 1-2 yo
 Male : Female = 1 : 5
 Systemic symptoms (-)
 Joint impairment ≤ 4 , big joint and asymmetric.
 Uveitis 20%
 Type:
 Persistent ( just impaired ≤ 4 joints) and
 Extended ( additional impaired ≥ 5 joint) after the first
6 months of the disease
Makalah Lengkap Penanganan Komprehensif Artritis Anak, UKK Alergi dan Imunologi IDAI, Bandung Juli 2009
UVEITIS
Cassidy & Petty, Chronic Arthritis in Childhood in Textbook of Pediatric Rheumatology, 5th Ed. Elsevier Saunders
OLIGOARTHRITIS

Hashkes (2005)
POLIARTHRITIS JIA
 30-40 % of JIA case
 Onset : all children lifetime, peak 1 - 3 yo
 Male : Female = 1 : 3
 Systemic Symptoms: mild - moderate
 Joint impairment ≥ 5 , small joint included cervical spine and
symmetric.
 Uveitis 5%
 2 type :
 Rheumatoid Factor positive (in 2 or more test for RF at least
3 month apart during the first 6 months of disease are
positive)
 Rheumatoid Factor negative (negative IgM RF during the
first 6 monts of disease
Makalah Lengkap Penanganan Komprehensif Artritis Anak, UKK Alergi dan Imunologi IDAI, Bandung Juli 2009
 CBC: WBC , Hgb , platelets WNL
to 
 ESR : 
 ANA : +/-
 RF: +/-
 synovial fluid: class II (inflammatory)
 x-ray findings: soft tissue swelling,
periarticular osteoporosis, joint space
narrowing, erosions
Makalah Lengkap Penanganan Komprehensif Artritis Anak, UKK Alergi dan Imunologi IDAI, Bandung Juli 2009
POLIARTHRITIS

Hashkes (2005)
SISTEMIK JIA
 10-20 % of JIA case
 Onset : all children lifetime, no peak onset
 Male:Female= 1 : 1
 Systemic symptoms: fever, rash, lymphadenopathy,
hepatosplenomegaly, pericarditis, pleuritis
 Joint impairment : variative, symmetric , polyarticular
 Uveitis : rarely
 CBC : WBC , Hb , platelets to ,
 LED : to
 ANA and RF (-) commonly
 x-rays : soft tissue swelling

Makalah Lengkap Penanganan Komprehensif Artritis Anak, UKK Alergi dan Imunologi IDAI, Bandung Juli
2009
RHEUMATOID RASH
SYSTEMIC
ARTHRITIS

Hashkes (2005)
MANAGEMENT

 Nonsteroidal anti-inflammarory drugs (NSAIDs)


 Disease Modifying Antirheumatoid Drug (DMARDs)
 Corticosterois (systemic, intra-articular)
 Biological modifying agents
CASE 3
 A boy, 9 years old
 Abdominal pain intermittent
 Spots in leg and bottom
 Arthralgia
 Fever (-), nausea (-), vomiting (-)
 GA: good, VS: normal, hepatosplenomegaly (-),
orchitis (-)
 Palpable purpura in lower extremity
 CBC: normal

1.What’s the diagnosis and differential diagnosis


in this case?
2.What’s investigation you need in this case?
3. What’s the management of this case?
4.What’s the complication of this case?
HSP (Henoch Schonlein Purpura)
Epidemiology
 According to a population-based survey, the estimated annual
incidence of childhood HSP is 20.4/100 000
 the figure is highest in children between 4 to 6 years
(70.3/100.000 per year). 90% are less than 10 years.
 Boys are affected slightly more often than girls
 Seasonal peak is in the autumn, winter and spring months,
evidently related to infections.

Ronkainen, Jaana. Henoch-schönlein purpura in children: long-term


outcome and treatment,, Oulu University Press, 2005
Diagnostic Criteria

the presence of any 2 or more criteria yields


 sensitivity of 87.1% and specificityof 87.7%

Sohagia et al. Henoch-schönlein purpura. Gastroenterology Research and practice, 2010


Patophysiology

Sohagia et al. Henoch-schönlein purpura. Gastroenterology Research and practice, 2010


Major clinical manifestation

Ronkainen, Jaana. Henoch-schönlein purpura in children:


long-term outcome and treatment,, Oulu University Press,
2005
Treatment

Sohagia et al. Henoch-schönlein purpura. Gastroenterology Research and practice, 2010


Prognostic Factor
• Age
• Presenting
symptoms
• Histology
• Pregnancy

Rai A, et al. Henoch-


schönlein purpura
Nephritis. J Am Soc
Nephrol 10: 2637–2644,
1999 Sohagia et al. Henoch-schönlein purpura.
Gastroenterology Research and practice, 2010
THANK YOU