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“Prolonged fever”. Extern conference. Supervised by Prof. Achra Sumboonnanonda MD Rattanavalai Chantorn MD Paisarn Parichatiganond MD. Patient profile. 12 years old Thai girl CC: Low grade fever for 1 month PTA

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prolonged fever
“Prolonged fever”

Extern conference

Supervised by

Prof. Achra Sumboonnanonda MD

Rattanavalai Chantorn MD

Paisarn Parichatiganond MD

patient profile
Patient profile
  • 12 years old Thai girl
  • CC: Low grade fever for 1 month PTA
  • Hx: 4 mo PTA She had persistent erythematous rash on both cheeks and active hair loss.She came to a local hospital and was diagnosed as dermatitis.
  • 1Mo PTA. She had low grade fever relieved by antipyretic drug.

She had no other symptoms except rash on her face that sometimes aggravated by sun exposure and increase excessivehair loss

  • 3 wk PTA she became more malaise, pallor and went to private clinic. She received parenteral fluid and oral medications, the symptoms were partial improved.
  • 2 wk PTA she still had persistent fever then she went to a local hospital.

At the hospital

PE: erythematous rash on malar area

The rash became worse and she

developed painful ulcer on her lips and

oral mucosa,She also had erythematous

macules on her soles and swelling of her



Investigation at the hospital

-BUN/Cr 22/0.7 mg/dl

-CBC: Hb 8 g/l, Hct 27 %, WBC 4,470 /mm3

(N75%, L20 %) Plt 196,000/mm3

-Stool exam : WNL


-Urine culture: > 105Streptococcus Gr. D,

Enterococci spp


Rx :Ceftriaxone 2 gm OD x 9 d then

Cefotaxime 1 gm IV q 6 hrs x 3d

Doxycycline x 7d

Gentamycin 100mg IV OD x 7d

Symptoms persisted then the patient

was referred to “Siriraj hospital”

  • Past history : healthy
  • Family history : no family history of atopy
  • Drug history: analgesic drug allergy
physical examination
Physical examination
  • V/S: T 38.3 oC, P110/min, R20/min,

BP118/60 mmHg

  • BW 37.5 kg(P25-50), HT 155 cm(P50-75)
  • GA: Irritable, look weak, not cooperative,

mildly pale, no jaundice, no dyspnea,

dry lips, good skin turgor, no sunken eye

balls , capillary refill <2 sec, no eschar

  • HEENT: findings as figures

Bilateral scaly erythematous to brownish patches at malar eminence, nasal ridge and nasolabial folds,scaly edematous erythematous painful lips


RS: normal

  • CVS: normal
  • ABDOMEN: normal
  • Extremities: Bilateral symmetrical partially blanchable erythematous to purplish macules and papules on both palms and soles, no sign of joints inflammation
  • NS: normal
  • No lymphadenopathy

Hb 8.6 g/dl, Hct 26.9 %, MCV 71.7 fl, RDW

14.9 %, WBC 2,840 /mm3 (N 72.2, L 20.1),

Platelets 198,000/mm3

HCMC RBC, no hemolytic blood picture


pH 7.0, Sp.Gr. 1.015, Protein +++, Occult

blood +, Bilirubin neg, Acetone neg,

WBC 0-1/HF, RBC 1-2/HF, no cast and



Blood chemistry

BUN 13.0 mg/dl, Cr 0.5 mg/dl

Na 135 mEq/dl, K 4.5 mEq/dl,

Cl 95 mEq/dl, HCO3- 19 mEq/dl


U/C, H/C : pending

problem list
Problem list
  • Prolonged fever for 4 weeks
  • Active hair loss for 4 months
  • Abnormal skin manifestation on scalp, face, ears, lips, mouth and extremities
  • Oral thrush
  • Anemia: Hypochromic,microcytic
  • Leukopenia and lymphopenia
  • Proteinuria
children with prolonged fever
Children withprolonged fever
  • Fever in this patient can be defined as fever of unknown origin(FUO)
  • The Petersdorf and Beeson criteria for FUO, definition in 1961are:   ▪  a body temp ≥ 38.3°C for at least 3weeks; and  ▪  failure to establish a diagnosis after 1week of investigation.
differential diagnosis of fuo
Differential diagnosisof FUO
  • Infection
  • Autoimmune disease
  • Neoplasm
  • Miscellaneous (drug-related fever, factitious fever, etc.)
relation between infection and autoimmune disease
Relation between infection and autoimmune disease
  • Clinical symptoms of infection may be indistinguishable from those of autoimmune disease
  • Immunosuppressive therapy for autoimmune disease may lead to increased susceptibility to infection
infectious cause of fuo in children
Infectious cause of FUO in children
  • Salmonellosis
  • Tuberculosis
  • Rickettsial disease
  • Bacterial endocarditis
  • Infectious mononucleosis
criteria of sle
Criteria of SLE
  • Malar rash
  • Discoid rash
  • Photosensitivity
  • Oral ulcer
  • Arthritis
  • Serositis
  • Renal disorder: persistent proteinuria
  • Neurologic disorder: seizure, psychosis
  • Hematologic disorder: hemolytic anemia, leukopenia, lymphopenia, thrombocytopenia
  • Immunologic disorder: anti-dsDNA, anti-Sm, antiphospholipid antibody
  • ANA positive

ACR 1982, updating classification criteria 1997

characteristic of fever in active sle disease
Characteristic of fever in active SLE disease
  • Non-shaking fever
  • Manifestation of active SLE: such as
    • Acute cutaneous LE
    • Arthritis
    • Hypertension, Edema
    • Leukopenia with lymphopenia, Thrombocytopenia
the most likely diagnosis

The most likely diagnosis

“Active SLE disease”


Study from department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol UniversitySuroj Supavekin MD*,Wanida Chatchomchuan MD**, Anirut Pattaragarn MD*, Vibul Suntornpoch MD*, Achra Sumboonnanonda MD**J Med Assoc Thai 2005; 88(Suppl 8): S115-23

  • From July 1985to March 2003,101 patients
  • The major clinical presentation of pediatric SLE are

- Renal (86.2%)

- Skin and mucocutaneous (76.3%)

- hematological involvement (73.4%)


Pediatric Systemic Lupus Erythematosus in Siriraj HospitalSuroj Supavekin MD*,Wanida Chatchomchuan MD**, Anirut Pattaragarn MD*, Vibul Suntornpoch MD*, Achra Sumboonnanonda MD**

Signs and Symptoms at Diagnosis

J Med Assoc Thai 2005; 88(Suppl 8): S115-23

the results of renal biopsies
The Results of Renal Biopsies

J Med Assoc Thai 2005; 88(Suppl 8): S115-23

classification of lupus nephritis
Classification of lupus nephritis

Class I: Minimal mesangial LN

Class II: Mesangial proliferative LN

Class III: Focal LN

Class IV: Diffused LN

Class V: Membranous LN

Class VI: Advanced sclerosis LN

International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003

further investigation
Further investigation

Work up for source of infection

  • KOH for oral thrush: Pseudohyphae with budding yeast
  • Stool concentration for parasite x 3days negative
  • Urine culture (10/4/50) No growth
  • Hemoculture (10/4/50) No growth
  • PPD skin test: Negative at 48, 72 hr
  • Consult dentist: No dental caries
further investigation1
Further Investigation
  • peripheral blood smear (14/4/2550):

hypochromic microcytic RBC, no

anisopoikilocytosis, Plt 10-15/HPF

  • Reticulocyte count 0.61%
  • Direct coomb’s test: negative
  • Serum ferritin (17/4/2550): 1,537 (13-50)

“Iron deficiency anemia”

further investigation2
Further investigation

Autoimmune profile

  • ANA Positive

Positive with Fine-speckled pattern titer >1:2,560

Positive with Coarse-speckled pattern

Positive with Homogeneous pattern

Positive with Peripheral pattern

Positive with Anti-Cytoplasmic Ab

  • Anti-ds DNA Positive titer > 1:160
  • C3 level 36.8 (N 83-177)
  • C4 level 6.56 (N 15-45)
further investigation3
Further investigation

Total protein 5.4 g/dl, Albumin 1.7 g/dl

Urine Creatinine 28.3 mg/dl

Urine Micro-TP 148 mg/dl

Urine protein/creatinine ratio 5

Urine protein 24 hr 55 mg/kg/d

“Nephrotic range proteinuria”

Renal biopsy

indication for kidney biopsy
Indication for kidney biopsy

All patient who correlate with criteria of LN

Nephrotic patient with undetermined diagnosed of Diffuse proliferative GN or Membranous GN

Patient whose renal function get worse despite of receiving high dose steroid

patient education
Patient education

Avoid sunlight

Avoid physical and mental stress

Drug compliance

Fever and malaise:

Low dose NSAIDs with antimalarial drug or low dose oral corticosteroid

Cutaneous lesion:

Sunblock cream with topical steroid and antimalarial drug

Treatment of lupus nephritis

Base on renal pathology

Class I: no treatment required

Class II: short course treatment of low

dose steroid (prednisolone 0.5-1 MKD)

Class III: prednisolone 1-2 MKD(max60mg/d) +immunosuppressive drug(Azathioprine 2MKD)

Class IV: prednisolone 2 MKD+pulse cyclophosphamide

Class Ⅴ: prednisolone 1-2 MKD

Class Ⅵ:slow renal progression,aggressive immunosuppressive drug not required


-Continue cefotaxime until 7days(10-13/4/50)

-Cotrimazole troche to treat oral candiasis

- Septic work up: all negative

so non-infectious cause is most likely


Prednisolone (2mg/kg/d)

Hydroxychloroquine (5mg/kg/d)

0.02%TA cream apply to lesions at face

0.1% TA cream apply to lesions on scalp

  • Anemia:FeSO4 (200mg) 1 tab PO tid pc

(5.6 mg/kg/day) (start 17/4/2550)

  • New onset HT:BP 128/86(16/4/2550)

max135/73 mmHg (P95 124/81mmHg)

- Enalapril (5mg) 1 tab PO OD pc

  • Follow up urinalysis 18/4/2550

pH 7.0, 1.010, protein neg,

WBC 0-1,RBC neg, occult blood neg,

others neg

renal pathology1
Renal pathology
  • Mesangial hypercellularity and matrix expansion
  • No endocapillary proliferation
  • No crescent
  • Microthrombi in 1 arteriole

Imp: Lupus nephritis class II with

thrombotic microangiopathy(TMA)

  • Suroj Supavekin MD,Wanida Chatchomchuan MD, Anirut Pattaragarn MD, Vibul Suntornpoch MD, Achra Sumboonnanonda MD Study from department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University J Med Assoc Thai 2005; 88(Suppl 8): S115-23
  • The Subcommittee for Systemic Lupus Erythematosus Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982;25:1271-7
  • Wallco DJ, Halm BH, eds. Dubois’ lupus erythematosus. 5th edn. Baltimore: Williams and Wilkins, 1997