Practice Based Learning[ GRAND ROUND ]

PREPARED BYDr. Jafar Alsaggaf

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

HistoryCase presentation

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

SLE

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

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

 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

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

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 effectivenessMuscle enzymes

laboratory findings

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

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.

DIAGNOSISSLICC CRITERIA

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

DIAGNOSISSLICC CRITERIA

DIAGNOSTIC CRITERION (1) Acute Cutaneous Lupus OR Subacute

Cutaneous LupusAcute 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 LupusClassic 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)

DIAGNOSTIC CRITERION (3) Oral Ulcers OR Nasal Ulcers

Oral: palate, buccal, tongueNasal ulcersIn 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 alopeciaDiffuse 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)

EPIDEMIOLOGY:

maculopapular rash, discoid lesions, nonscarring alopecia, cutaneous vasculitis, and Raynaud phenomenon are less common findings of skin involvement in children

CLINICAL CRITERIA(MUCOCUTANEOUS)

DIAGNOSTIC CRITERION (5) Synovitis involving 2 or more

jointsCharacterized by swelling or effusionOR 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 CRITERIAMUSCULOSKELETAL

DIAGNOSTIC CRITERION (6) SEROSITIS

Typical pleurisy for more than 1 day OR pleural effusions OR pleural rubTypical pericardial pain (pain with recumbency improved by sitting forward) for more than 1 day OR pericardial effusion OR pericardial rub OR pericarditis by electrocardiographyIn the absence of other causes, such as infection, uremia, and Dressler’s pericarditis

CLINICAL CRITERIASEROSITIS

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 CRITERIASEROSITIS

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 CRITERIASEROSITIS

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 CRITERIARENAL

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 CRITERIANEUROLOGICAL

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 CRITERIAANEMIA

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 CRITERIALEUKOPENIA

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 CRITERIATHROMBOCYTOPENIA

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

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

DIAGNOSTIC CRITERION (5) Low complement (C3, C4,

or CH50)

DIAGNOSTIC CRITERION (6) Direct Coombs’ test (in the absence of hemolytic anemia)

IMMUNOLOGIC CRITERIA

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

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

Thanks for: Dr. May Salem Dr.Husam Althagafi Dr.Abdulkarim Akila

Thank you