This document summarizes the case of a 7-year-old Filipino girl who presented with fever, cough, periorbital and neck swelling, and weight gain for 2-3 weeks. Her examination found edema, arthritis, a facial rash, hemolytic anemia, thrombocytopenia, proteinuria, and low complement levels. Her hospital course involved worsening edema, ascites, oliguria, and gastrointestinal bleeding. Testing found positive antinuclear antibodies, anti-DNA antibodies, and low complement levels consistent with systemic lupus erythematosus. The document provides background information on SLE including definitions, epidemiology, clinical manifestations, diagnostic criteria, and laboratory findings.

1. Practice Based Learning
[ GRAND ROUND ]
PREPARED BY
Dr. Jafar Alsaggaf

2. 
7 yrs old Filippino girl presented at 22-11-2014 through
OPD with hx of
 fever and cough * 3 wks
 weight gain
 Periorbital and neck swelling
History
Case presentation

3. 
 The fever was on/off, responding partially to
antipyretics for 2-3 weeks
 The cough is productive for 2-3 wks
 weight gain is subjective
 No hx of SOB or sore throat, no hx of lower limbs
swelling or abdominal distension, no change in urine
color or amount
History of Presenting
Illness

4. 
 She was suspected to have ?mumps (parotitis) 2wks
back (came with same persentation but still in the
beginning)
 Otherwise previously healthy
 No previous admissions
 she underwent dental extraction safely
Past history

5. 
 No hx of dyspnea, orthopnea or PND
 No vomiting, diarrhea, jaundice or steatorrhea. She’s c/o
abdominal pain (not specified) with decreased oral intake
 No chest pain or night sweats
 There’s hx of Lt knee and Rt. Shoulder pain with
limitation in movement with no swelling of several days
duration
 Hx of facial rash over cheeks ?malar area for 1-2 days only
prior to presentation
 Many episodes of epistaxis (recent and by history)
Systemic Review

6. 
 Fhx : unremarkable
 Vaccination hx: she didn’t receive mumps vaccine
(4-6yrs of age) since she was in Philippine that time but
she received (MR)
 Perinatal hx : FT, NVD
Cont. History

7. 
In Summary:
6yrs 10m old girl , presented with fever, cough,
periorbital and neck swelling and wt. gain for
2-3 wks, with hx of facial rash and joints pain
Cont. History

8. 
 VITALS: were stable
 ANTHROPOMETRIC MEASUREMENT:
wt 19.25kg .. Ht 116.5 cm .. BMI 14.2 .. 18.9 percintile
 She’s conscious, alert, oriented, not in pain, not in
RD, pale, average body built, lying flat on bed,
anxious, connected to IV line
Physical Examination

9. 
 hands: no clubbing, no Osler nodes, no Janeway
lesions
 Face: bilateral periorbital edema with no redness, no
central cyanosis
 Neck: bilateral neck edema (submandibular) left
more than rt side, soft with no redness, no scars, no
clear edges, no LN enlargement
 CHEST: no scars, normal abdominal breathing
symmetrical, no deformity, resonant in percussion,
EAE, vesicular, no added sounds
Physical Examination

10. 
 CVS: S1 + S2 + 0
 Abdomen: no distention, no scars, soft, lax, not
palpable spleen, liver 2 cm BCM span: 6-7 cm
 MSK: Lt knee swelling, redness, tenderness, with
Limitation of movement
 Lower limb: no edema
Physical Examination

11. 
 WBC 22.4 (90% NE)
 HB 7.2 (MCV, MCH  NORMAL) RETIC >3
 PLT 69 (WAS 100 the day before)
 CRP 64.6 ESR 140
 NA 122 K 4.5 Ca 7.1
 BUN 26 Crea .83 SERUM ALB 1.77
 TOTAL PROTEIN 6 URIC ACID 9.6
 C3 .19 C4 .03 ASO TITER < 49.9
 URINE ANALYSIS: PROTEIN >300 , ERYTHROCYTE
NUMEROUS ,, BACT NUMEROUS
 ALB/CREA RATIO 226 = MICROALBUMINURIA (30-300)
 BLOOD,THROAT AND URINE C/S were taken
Admission investigation

12. 
 7 yrs old girl with edema, arthritis, ? Malar rash,
hemolytic anemia, thrombocytopenia, proteinuria,
hypoalbuminemia, uremia, low C3 and low C4
 ? HUS
 ? SLE
 ? PIGN
 ? MALARIA
 ? Henoch-Schonlein purpura
Differential diagnosis

13. 
While hospitalized on the Floor:
 Clinically: she developed Ascitis, lower limb edema,
oliguria, hematuria (tea colored)
 vitally: no hypertension, normal RR, normal PR, with
spikes of fever
 by u/s  anasarca (pleural effusion & mild pericardial
effusion + ascitis) Her BUN was gradually rising and
crea was up to 1.2-1.3 range ? ARF
 she was receiving IV diuretics and IV albumin along
with fluids restriction
HOSPITAL COURSE

14. 
 Bl c/s taken 3 times: showed S.pneumonia twice and last
one was –ve but pt was already on Abx since admission
 so she had Bacteremia + fever + GN+ hemolytic anemia
with conjunctival hemorrhage and positive RF ?IE so
Echo was done: normal
 although she is on Abx, Still she's Febrile and there's no
clear source of this bacteremia +left knee arthritis though
improved but still not completely back to
normal ?osteomylitis – bone scan done  not diagnostic
for osteomyelitis
HOSPITAL COURSE

15. 
 She also had melena (occult blood in stool analysis)
then she vomited blood that’s why she was
transferred to PICU ?GI bleeding
HOSPITAL COURSE

16. 
 In PICU:
 She was receiving blood products FFP, PLTS and PRBC along
with IV Steroids, Diuretics and oral and IV antihypertensive
medications.
 She had 12 hrs of oliguria then UO improved on Lasix drip
with 1-2ml/kg/hr. She developed 4-5 days later gradual
oxygen requirements with evidence of pulmonary hemorrhage
by bronchoscopy IV cytoxan was added along with Novo 7.
She was on high vent settings for 1 week// BAL positive for
ESBL Klebsiella. She received 3 hemodialysis sessions for
uremia, fluid overload and to decrease bleeding tendency.
 She developed worsening severe subcutaneous emphysema on
her last day of life.
HOSPITAL COURSE

17.  ANA: negative
 ANA: 1:320
 ANA: 1:320
 Anti DNA DS: -ve
 Anti DNA DS: 1:40
 Anti DNA DS: -ve
 CH50 : LOW <13 (31-60)
 Factor VIII associated antigen: 260 (50-217) high
 Anti DNASE (SO)  normal
 Anti smith (SO) 8 (<1) high
 Beta 2 glycoprotein Igg, Igm, IgA  normal
 Coombs test 1-indirect –ve 2-direct weak +ve
 +ve RF
 Low c3, c4
 ANCA and PANCA both negative
 Anti-GBM ?
Autoantibodies labs

19. 
 Is a multisystem disorder of unknown etiology characterized by
a production of large amount of circulating autoantibodies
 Many of the clinical manifestations are mediated directly or
indirectly by antibody formation and the creation of immune
complexes.
 It mostly affects skin, joints, kidney, blood forming cells, blood
vessels and CNS
 SLE in children is fundamentally the same disease as in adults,
with similar etiology, pathogenesis, clinical manifestations, and
laboratory findings. However, the care of children and
adolescents with SLE is different from that of adults because of
the impact of the disease and its therapy on physical and
psychologic growth and development
Definition SLE

20. 
 Childhood SLE affects girls more often than boys
(8:1)
 In retrospective reviews from France, Canada, and
the United Kingdom, the median age of onset of
juvenile SLE was 12 to 13 years, with the disease
developing in the majority of patients after eight
years of age
epidemiology

21. 
 The most common initial symptoms are the gradual
onset of fever, weight loss, and malaise with general
deterioration over several months, although some
children have acute or even life-threatening
symptoms
Clinical manifistation

22. 
 In retrospective reviews from France and Canada, the most common
presenting manifestations were as follows :
 Hematologic – Anemia, lymphopenia,
leukopenia, and/or thrombocytopenia
 Mucocutaneous – Malar rash and/or oral ulcers
 Musculoskeletal – Arthritis or arthralgia
 Fever
 Renal abnormalities – Nephritis and nephrotic syndrome
 These manifestations, in addition to seizures and lymphadenopathy,
are more common in childhood-onset lupus than adult-onset lupus,
whereas Raynaud phenomenon and pleuritis are more common
manifestations in patients who are adults at disease onset
Clinical manifistation

23. 
 hematologic abnormalities: will be discussed
 presence of autoantibodies: will be discussed
 markers of inflammation : high ESR, CRP
 vitamin D deficiency:
 Avoidance of sun exposure and renal disease playing a
role in that.
 Some studies shows that hypovitaminosis D may have
contributed to the development of active disease
 Hypocomplementemia: Low C3, low C4 and, decreased
complement function (CH50)
C3 and C4 are used to moniter therapy effectiveness
Muscle enzymes
laboratory findings

24. 
 The Systemic Lupus International Collaborating
Clinics (SLICC) group classification criteria for SLE is
a revised and validated version of the American
College of Rheumatology (ACR) criteria used for
adults
diagnosis

25. 

26. 
 A patient is classified as having SLE if four or more
of the SLICC criteria, including at least one clinical
and one immunologic criterion, are present either
serially or simultaneously, during any interval of
observations, in the absence of another explanation
for the findings.
 An alternative requirement is positive antinuclear
antibodies (ANA) or anti-double-stranded DNA
antibodies (anti-dsDNA) in conjunction with biopsy-
proven lupus nephritis.
DIAGNOSIS
SLICC CRITERIA

27. 
 Children with two or three classification criteria may
go on to develop a fourth over time. The key to
proper care is to appropriately treat the
manifestations present when the child is first seen
and to carefully follow those who present with fewer
than four criteria for the development of additional
findings over time. Such progression may occur over
a period of three to five years or longer
DIAGNOSIS
SLICC CRITERIA

28. 

29. 
DIAGNOSTIC CRITERION (1) Acute Cutaneous Lupus OR
Subacute Cutaneous Lupus
Acute cutaneous lupus: lupus malar rash (do not count if malar
discoid), bullous lupus, toxic epidermal necrolysis variant of SLE,
maculopapular lupus rash, photosensitive lupus rash (in the absence
of dermatomyositis)
Subacute cutaneous lupus: nonindurated psoriaform and/or
annular polycyclic lesions that resolve without scarring, although
occasionally with postinflammatory dyspigmentation or
telangiectasias)
DIAGNOSTIC CRITERION (2) Chronic Cutaneous Lupus
Classic discoid rash localized (above the neck) or generalized (above
and below the neck), hypertrophic (verrucous) lupus, lupus
panniculitis (profundus), mucosal lupus, lupus erythematosus
tumidus, chillblains lupus, discoid lupus/lichen planus overlap
CLINICAL CRITERIA
(MUCOCUTANEOUS)

30. 
DIAGNOSTIC CRITERION (3) Oral Ulcers OR Nasal
Ulcers
Oral: palate, buccal, tongue
Nasal ulcers
In the absence of other causes, such as vasculitis, Behcet’s
disease, infection (herpesvirus), inflammatory bowel
disease, reactive arthritis, and acidic foods
DIAGNOSTIC CRITERION (4) Nonscarring alopecia
Diffuse thinning or hair fragility with visible broken hairs,
in the absence of other causes such as alopecia areata,
drugs, iron deficiency, and androgenic alopecia
CLINICAL CRITERIA
(MUCOCUTANEOUS)

31. 
EPIDEMIOLOGY:
maculopapular rash, discoid lesions, nonscarring
alopecia, cutaneous vasculitis, and Raynaud
phenomenon are less common findings of skin
involvement in children
CLINICAL CRITERIA
(MUCOCUTANEOUS)

32. 

33. 
DIAGNOSTIC CRITERION (5) Synovitis involving 2 or more
joints
Characterized by swelling or effusion
OR tenderness in 2 or more joints and at least 30 minutes of
morning stiffness.
EPIDEMIOLOGY:
the most common musculoskeletal findings in children with
SLE are:
 arthritis and arthralgias.
 Bone abnormalities include osteopenia and osteonecrosis.
These findings are primarily due to glucocorticoid toxicity.
CLINICAL CRITERIA
MUSCULOSKELETAL

34. 
DIAGNOSTIC CRITERION (6) SEROSITIS
Typical pleurisy for more than 1 day OR pleural effusions OR
pleural rub
Typical pericardial pain (pain with recumbency improved by
sitting forward) for more than 1 day OR pericardial effusion OR
pericardial rub OR pericarditis by electrocardiography
In the absence of other causes, such as infection, uremia, and
Dressler’s pericarditis
CLINICAL CRITERIA
SEROSITIS

35. 
EPIDEMIOLOGY (CARDIAC ABNORMALITIES):
 Pericarditis is the most common cardiac abnormality in
children with SLE, but other problems, such as
myocarditis, valvular disease (eg, endocarditis), and
coronary artery disease (CAD), can occur.
 Cardiac abnormalities in children with SLE are often
silent
 The prevalence of clinical heart disease among children
with SLE ranges in various studies from 12 to 54 percent.
CLINICAL CRITERIA
SEROSITIS

36. 
EPIDEMIOLOGY (PULMONARY INVOLVEMENT):
 Most reviews of childhood lupus report respiratory
findings in 30 to 50 percent of cases, with pleuritis which
is inflammation of the parietal and visceral pleura being
the most common finding
 Acute pulmonary hemorrhage and pulmonary
hypertension are the most severe forms of lupus-
associated pulmonary involvement, although they occur
infrequently in children with SLE.
 Other pulmonary manifestations of SLE in children
include pneumonia, shrinking lung syndrome,
pneumonitis, and pneumothorax.
CLINICAL CRITERIA
SEROSITIS

37. 
DIAGNOSTIC CRITERION (7) Renal diagnostic criteria
Urine protein–to-creatinine ratio (or 24-hour urine protein)
representing 500 mg protein/24 hours OR red blood cell
casts
EPIDEMIOLOGY:
 Renal involvement in SLE may vary from the detection of
hematuria and proteinuria on routine examination to the
presence of nephrotic syndrome or acute renal failure.
 SLE nephritis occur in 50-70% of children with SLE
CLINICAL CRITERIA
RENAL

38. 
DIAGNOSTIC CRITERION (8) Neurologic diagnostic criteria
Seizures, psychosis, mononeuritis multiplex(in the absence of other
known causes such as primary vasculitis), myelitis, peripheral or
cranial neuropathy (in the absence of other known causes such as
primary vasculitis, infection, and diabetes mellitus), acute confusional
state (in the absence of other causes, including toxic/metabolic, uremia,
drugs)
EPIDEMIOLOGY:
 Headache is a frequent complaint.
 Adolescents commonly present with progressive deterioration in
academic performance, withdrawal, depression, and social isolation.
 More dramatic neurologic presentations of SLE include seizures,
chorea, stroke, dementia, and coma.
CLINICAL CRITERIA
NEUROLOGICAL

39. 
DIAGNOSTIC CRITERION (9) Hemolytic anemia
EPIDEMIOLOGY:
 The most common types of anemia in children with
SLE are anemia of chronic disease, iron deficiency
anemia, and autoimmune hemolytic anemia (AIHA)
CLINICAL CRITERIA
ANEMIA

40. 
DIAGNOSTIC CRITERION (10) Leukopenia (<4000/mm3)
OR Lymphopenia (<1000/mm3)
Leucopenia at least once: In the absence of other known
causes such as Felty’s syndrome, drugs, and portal
hypertension.
Lymphopenia at least once: in the absence of other known
causes such as corticosteroids, drugs, and infection
EPIDEMIOLOGY:
 Leukopenia occurs in nearly two-thirds of children at
some point during the course of illness (in form of
lymphopenia)
CLINICAL CRITERIA
LEUKOPENIA

41. 
DIAGNOSTIC CRITERION (11) Thrombocytopenia
(<100,000/mm3)
At least once in the absence of other known causes such
as drugs, portal hypertension, and thrombotic
thrombocytopenic purpura
EPIDEMIOLOGY:
 Thrombocytopenia: (ITP), usually a disease sui generis,
may be the first manifestation of SLE. This evolution
occurs in up to 15 percent of patients with ITP. Thus, it is
important that the clinician caring for a child with a
positive ANA and ITP periodically look for evidence of
SLE manifestations in other organ systems
CLINICAL CRITERIA
THROMBOCYTOPENIA

42. DIAGNOSTIC CRITERION (1) ANA level above laboratory reference range
EPIDEMIOLOGY:
 ANA: is positive in > 97% of SLE pt.  -ve ANA has a high negative predictive value
for SLE
DIAGNOSTIC CRITERION(2) Anti-dsDNA antibody level above laboratory reference
range (or 2-fold the reference range if tested by ELISA)
EPIDEMIOLOGY:
 Anti DS DNA is almost exclusively in SLE, vary with disease activity.
DIAGNOSTIC CRITERION (3) Anti-Sm: presence of antibody to Sm nuclear antigen
EPIDEMIOLOGY:
 Anti smith abs found in 30% of the cases and it’s specific
IMMUNOLOGIC CRITERIA

43. 
DIAGNOSTIC CRITERION (4) Antiphospholipid
antibody positivity, as determined by
 Positive test for lupus anticoagulant
 False-positive test result for rapid plasma reagin
 Medium- or high-titer anticardiolipin antibody level (IgA, IgG, or
IgM)
 Positive test result for anti–2-glycoprotein I (IgA, IgG, or IgM)
EPIDEMIOLOGY:
 These are found with varying frequency and are less strongly
associated with SLE
 Children and adolescents with SLE who have aPL should be
presumed to have the same increased risk of developing a clotting
disorder as adults with aPL
IMMUNOLOGIC CRITERIA

44. 
DIAGNOSTIC CRITERION (5) Low complement (C3, C4,
or CH50)
DIAGNOSTIC CRITERION (6) Direct Coombs’ test (in the
absence of hemolytic anemia)
IMMUNOLOGIC CRITERIA

45. 

46. 
 Corticosteroid
 NSAIDs for arthritis
 Hydroxychloroquine as maintenance and for lupus
skin dz
 These are not sufficient for SLE nephritis or cerebritis
 Cyclophosphamide is effective for the worst form of
SLE nephritis. Also CNS lupus resonds to it
 Steroid sparing agents – azathioprine, methotrexate
may be indicated for pt. not able to tolerate steroid
tapering
TREATMENT

47. 
 Avoid sun exposure  flaring of the dz
 Ca and Vit D (prolonged corticosteroid use) to
prevent osteopenia
 Early treatment of hyperlipidemia to prevent long-
term CVS complications
PREVENTION

48. 
 Thanks for:
 Dr. May Salem
 Dr.Husam Althagafi
 Dr.Abdulkarim Akila
Thank you