“Prolonged fever”

Supervised byProf. Achra Sumboonnanonda MD

Rattanavalai Chantorn MDPaisarn Parichatiganond MD

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 excessive hair 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 hospitalPE: erythematous rash on malar

area The rash became worse and she

developed painful ulcer on her lips andoral mucosa, She also had erythematousmacules on her soles and swelling of her face

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-UA : WNL-Urine culture: > 105 Streptococcus 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

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 eyeballs , 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

Round shape erythematous macule with central hyperpigmentation

single erythematous patch with peripheral hyperpigmentation on scalp

Painful shallow ulcer at hard palate with oral thrush

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

CBC 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 pictureUrinalysis 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 bacteria

Investigation

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

CXR WNLU/C, H/C : pending

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

Fever in this patient can be defined as fever of unknown origin (FUO)

The Petersdorf and Beeson criteria for FUO, definitionin1 9 6 1 are:      ▪ a body temp ≥ 38.3°C for at least 3weeks;and      ▪ 1failure to establish a diagnosis after weekoo oooooooooooooo

Differential diagnosis of FUO

Infection Autoimmune disease Neoplasm Miscellaneous (drug-related fever,

factitious fever, etc.)

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 Salmonellosis Tuberculosis Rickettsial disease Bacterial endocarditis Infectious mononucleosis

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 Non-shaking fever Manifestation of active SLE: such

as Acute cutaneous LE Arthritis Hypertension, Edema Leukopenia with lymphopenia,

Thrombocytopenia

“Active SLE disease”

Study from department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University

* **Suroj Supavekin MD ,Wanida Chatchomchuan MD , Anirut Pattaraga

* * *rn MD , Vibul Suntornpoch MD , Achra Sumboonnanonda MD *

-2005 88 8 11523J Med Assoc Thai ; (Suppl ): S From July 1985 to March 2003, 101 patients

The major clinical presentation of pediatric SLE are

- Renal (86.2%)- S kin and mucocutaneous (76.3%)

- hematological involvement (73.4%)

Pediatric Systemic Lupus Erythematosus in SirirajHospital

* **Suroj Supavekin MD ,Wanida Chatchomchuan MD ooooooooooo o o o o , * , * ,

*AchraSumboonnanonda MD *

-2005 88 8 115J Med Assoc Thai ; (Suppl ): S23

Signs and Symptoms at Diagnosis

The Results of Renal Biopsies

-2005 88 8 115J Med Assoc Thai ; (Suppl ): S23

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

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 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 investigationAutoimmune 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 investigation

Total protein 5.4 g/dl, Albumin 1.7 g/dl Urine Creatinine 28.3 mg/dl Urine Micro-TP148 mg/dl Urine protein/creatinine ratio 5 Urine protein 24 hr 55 mg/kg/d

“Nephrotic range proteinuria” Renal 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

TREATMENT

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 nephritisBase 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

Progression

-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

MedicationPrednisolone (2mg/kg/d)Hydroxychloroquine ( 5mg/kg/d)0.02%TA cream apply to lesions at face0.1% TA cream apply to lesions on scalp

Progression

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 18/4/2550pH 7.0, sp.gr 1.010, protein neg, WBC 0-1,RBC neg, occult blood neg, others neg

RENAL PATHOLOGY

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)

References• Suroj Supavekin MD,Wanida Chatchomchuan MD, Anirut

Pattaragarn MD, Vibul Suntornpoch MD, Achra Sumboon nanonda 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

Thank you