CASE REPORT

洪嘉蔚 醫師 / 吳維峰 主任 台北市立仁愛醫院 小兒科

General Data

       Name: 李 小弟 Birth day: 85/04/24 Age: 6 y/o Chart number: 15213493 Admission day: 91/05/03 Discharge day: 91/05/20 BW: 22 Kg

Chief Complaint

 Fever off and on for 8 days

Present Illness

 A 6 year-old boy suffered from fever off and on for 8 days. He also complained of cough, rhinorrhea and difficult to expectorate sputum. He was taken to LMD twice and our OPD on 91/04/30, but the symptoms persisted in spite of drugs use. So he was taken to our OPD again on 91/05/03. Physical examination revealed decreased breathing sound on right chest. CXR showed lobar pneumonia.

Brief history

        Birth Hx: GA: 39 Wks, BBW:3050 gm, NSD Previous admission: Denied Vaccination: As schedule Allergy Hx: Denied Food exposure: Denied Drug exposure: Denied Recent travel: Denied Family Hx: Non-contributory

Physical Examination:

    Vital sign: BT 39.9, PR:120 bpm, RR 32/min General appearance: Acute-ill looking HEENT: No gross anomaly Conjunctiva: not injected Throat: mild injection Chest: Symmetric expansion Retraction: no decreased breathing sound: right lung, fine moist rales(+) percussion: dullness of right chest

WBC Hgb Hct MCV PLT Neut Lym Mono Eos

CBC/DC

5/3 9100 11.9

32.9

72.6

190000 92.3

3.3% 2.3% 0.3% 5/7 10110 10.6

29.7

75.2

206000 89.5

5.5% 1.6% 0.5%

Appearance SP. Gr.

PH Protein Glucose OB Bilirubin Nitrate RBC WBC Bacteria

Urinalysis

5/3 5/4 Y-CLEAR 1.010

6.0

1+ 0-2 4-6 + Y-CLEAR 1.015

6.0

1+ 8-10 40-50 +

Biochemistry

5/3 5/4 5/7 Glu 94 BUN 6.0

Cr 0.5

93 3.0

0.5

AST 117 85 ALT 39 179 Na 125 129 137 K 4.5

4.0

Blood culture

  5/3 NO GROWTH 5/7 NO GROWTH

Urine culture

 5/5 NO GROWTH

Serology

CRP  5/4 163 mg/l  5/7 126 mg/l Mycoplasma Pneumoniae Antibody  5/4 NEGATIVE

Hospital Course (I)

  Initially (5/3), empiric antibiotics with Cefuroxime 500mg IV q6h and Erythromycin 250mg PO q6h were used, but intermittent high fever up to 39C was still noted.

Gentamicin was added on 5/4 due to pyuria of urinalysis and suspected UTI

Hospital Course (II)

 On 5/5, multiple fine, discrete, rubella-like skin rashes developed on the face, trunk and extremities with itchy sensation. Vena infusion and Sinbaby lotion were used for symptom relief.

Serology

 5/7 IgA 126 (70-400) IgM 105 (40-230) IgG 778 (700-1600)  5/8 Measles IgM (-) Rubella IgM (-)

Hospital Course (III)

 On 5/7, followed CXR showed massive amount of pleural effusion, right lung. So we do chest CT, and erythromycin was changed to 220mg IV q6h  On 5/8, thoracocentasis was done and showed exudate effusion. So we do chest tube insertion. About 200ml of yellow reddish fluid was drained.

Chest CT

  Date 91/05/07 Impression: Consolidation of right lower lobe and medial segment of middle lobe, pneumonia is likely. Moderate amount of right pleural effusion and scanty amount of left pleural effusion.

Abdominal echo

  Date 91/05/07 Ultrasonic Impression: Negative finding of abdominal ultrasonography

Pleural Effusion Study (I)

5/8 Pleural fluid  Appearance cloudy  Color reddish-yellow     Bloody (+) Chylous (-) Coagulation (+) Sp. Gr. 1.025

Pleural Effusion Study (II)

   WBC 630 cumm Polynuclear cells 55.0% Mononuclear cells 45.0% Abnormal cells (-) Pleural, Acid-Fast Stain: Not Found Pleural, Gram ’ s Stain: Not Found

Pleural Effusion Study (III)

 Pleural Effusion Glucose 71 mg/dl   LDH 3149 IU/L (H) Protein 3.30 g/dl (L)

Pleural Effusion Study (IV)

 Pleural effusion culture on 5/8 no growth on 5/13 no growth

Pleural Effusion Study (V)

  5/8 Pleural effusion cytology: No evidence of malignancy 5/14 Pleural PCR assay for mycobacteria result: Negative

Hospital Course (IV)

  On 5/10, followed CBC/DC showed leukocytosis with left shift (WBC 19570, Neu 92.9%). Persistent high fever was noted. So Cefuroxime was changed to Ceftriaxone 1g IV q12h High fever up to 40C persisted in spite of Ceftriaxone + Gentamicin + Erythromycin combined use

CBC/DC

WBC Hgb Hct MCV PLT Neut Lym 5/3 9100 10110 19570 26450 12270 11.9

32.9

72.6

5/7 10.6

29.7

75.2

5/10 8.8

25.2

85.7

5/13 8.4

24.2

76.2

5/15 8.9

25.1

74.1

190000 206000 378000 551000 707000 92.3

89.5

92.9

92.8

87.1

3.3% 5.5% 4.2% 3.5% 6.9% Mono 2.3% 1.6% 2.2% 1.9% 2.6% Eos 0.3% 0.5% 0.4% 0.8% 1.8%

Appearance SP. Gr.

PH Protein Glucose OB Bilirubin Nitrate RBC WBC Bacteria

Urinalysis

5/3 Y-CLEAR 1.010

6.0

1+ 0-2 4-6 + 5/4 Y-CLEAR 1.015

6.0

1+ 8-10 40-50 + 5/11 Y-CLEAR 1.010

5.0

0-2 0-2 - 5/14 Y-CLEAR 1.020

6.5

0-1 8-10 --

Biochemistry

5/3 5/4 5/7 5/9 5/11 5/14 5/16 Glu 94 BUN 6.0

Cr 0.5

93 3.0

5.0

11.2

0.5

0.4

0.4

AST 117 85 46 ALT 39 179 99 Na 125 129 137 131 136 85 71 175 146 K 4.5

4.0

5.2

Alb 3.0

3.5

Blood culture

   5/3 NO GROWTH 5/7 NO GROWTH 5/11 NO GROWTH

Urine culture

   5/5 NO GROWTH 5/10 NO GROWTH 5/12 NO GROWTH

Serology (I)

CRP  5/4 163 mg/l   5/7 126 mg/l 5/14 113 mg/l

Serology (II)

5/13 Direct Coombs ’ test: positive Indirect Coombs ’ test: positive 5/14 RA< 10.2 IU/ML (<40.0) C3 166.0 mg/dl (90.0-180.0) C4 21.4 mg/dl (10.0- 40.0)

Serology (III)

  5/14 Heterophil Ab: Negative ANA Negative 5/14 Legionella Ab: Negative Chlamydia Ab: Negative

Ga-67 Inflammation Survey

   Date 91/05/15 A patch of abnormal tracer uptake at the right lower lung field, may be inflammatory focus.

Diffusely increase uptake of liver. This phenomenon can be found in iron deficiency anemia

Serology (I)

Mycoplasma Pneumoniae Antibody  5/4 Negative  5/7 160X  5/14 320X

Pleural Effusion Study (II)

 5/8 Pleural fluid for Mycoplasmal pneumonia antibody: 80X

Serology (III)

 5/16 Cold hemaglutination: 512 X (<32X)

Hospital Course (V)

    Chest tube was removed on 5/13 We used prednisolone (2mg/kg/day in 4 divided doses) on 5/14. Fever subsided on the night of 5/14.

Steroid was tapered gradually On 5/20, patient was discharged under stable condition.

CBC/DC

WBC Hgb Hct MCV PLT Neut Lym 5/3 11.9

32.9

72.6

5/7 9100 10110 19570 26450 12270 9780 10.6

29.7

75.2

5/10 8.8

25.2

85.7

5/13 8.4

24.2

76.2

5/15 8.9

25.1

74.1

92.3

89.5

92.9

92.8

87.1

3.3% 5.5% 4.2% 3.5% 6.9% Mono 2.3% 1.6% 2.2% 1.9% 2.6% Eos 0.3% 0.5% 0.4% 0.8% 1.8% 5/23 10.1

30.2

78.9

190000 206000 378000 551000 707000 377000 66.1

22.3

10.0

1.0

Biochemistry

5/3 5/4 5/7 5/9 5/11 5/14 5/16 5/23 Glu 94 BUN 6.0

Cr 0.5

93 3.0

5.0

11.2

0.5

0.4

0.4

AST 117 85 46 ALT 39 179 99 Na 125 129 137 131 136 85 71 21 175 146 30 K 4.5

4.0

5.2

Alb 3.0

3.5

Serology (I)

CRP  5/4 163 mg/l    5/7 126 mg/l 5/14 113 mg/l 5/30 5.2 mg/l

Final Diagnosis

 Mycoplasmal lobar pneumonia, complicated with prolonged fever, skin rashes, right lung pleural effusion, and hemolytic anemia

DISCUSSION

Mycoplasma Pneumoniae

 In 1944, M. pneumoniae was reported by Monroe Eaton, originally called the Eaton agent.

 Smallest free-living microorganism, belongs to the class Mollicutes.

 Mycoplasmas lack a cell wall, so tend to be pleomorphic .

Clinical Manifestations

 M. pneumoniae causes approximately 20% of all cases of pneumonia.

 Peak incidence at 6-21 years of age.

 Incubation period of 2-3 weeks.

 Transmission by inhalation of infected droplet aerosols.

 Pneumonia is the most important clinical manifestation of M. pneumoniae infection.

* Bronchopneumonia pattern mostly.

Lobar pneumonia and large amount pleural fluid are unusual.

Pediat Radiol 1989;19(8):499-503 * Respiratory disease other than pneumonia: unspecific URI, pharyngitis, AOM, croup, sinusitis, bronchitis, bronchiolitis, asthma.

 Cutaneous manifestations : common.

* Exanthem and enanthem of Mycoplasma pneumoniae infection are observed in 5 to 24% of cases AAP, Report of Committee on Infectious Diseases, 1994:333-5 * Most common with an erythematous maculopapular rash on the trunk and back; discrete (rubelliform) or confluent (morbilliform).

* Most serious presentation: Erythema multiforme and Stevens-Johnson syndrome .

Clini Pediatrics 1991:30(1),42-9

 Hematologic manifestations: * Hemolytic anemia: usually mild, however, it may become severe and result in 50% reduction in hemoglobin concentration.

Pediat Infec Dis J 1998;17(2):173-7 * Direct Coombs test usually positive.

* Steroid administration may be beneficial.

South Med J 1990;83(9):1106-8

Hemolytic anemia is presumably related to the presence of cold agglutinins in serum which at high concentration, may agglutinate erythrocytes at 37 ℃ Rev Pneumol Clin 1990,46(2),83-4

 Gastrointestinal findings are nonspecific with nausea, vomiting, abdominal pain, and/or diarrhea.

 Neurologic disease association was reported 2.6-4.8%.

* Encephalitis, meningitis, transverse myelitis, psychosis, Bell palsy and Guillain-Barre` syndrome.

 Arthritis in association with M.pneumoniae

infection have not been established.

 Hepatitis was once thought to be unusual, but recent studies suggest that liver dysfunction may be present in up to 30% of M. pneumoniae infection.

Pediatr Pulmonol 1990;8:182-7

 Liver dysfunction was observed more frequently in patients with pleuropneumonia than in simple pneumonia cases.

Pediatr Pulmonol 1990;8:182-7

Radiographic Manifestation (I)

Interstitial infiltration was more commonly seen in pediatric than adult patients (46% vs 20%) Unilateral lesions 80% Single lobe lesions 77% Lower lobe predominant 69% Pleural effusion 7% 高雄醫學科學雜誌 1993;9(4):204-11

Radiographic Manifestation (II)

     Unilateral infiltration 84% Lower lobe predominance 60% Confluent consolidation 56% Patchy consolidation 33% Pleural effusion 24% 長庚醫學雜誌 1991;14(3):156-62

Diagnosis (I)

    WBC, CRP, ESR are non-specific, may be normal or elevated.

Growth of the organism takes weeks, generally only in expertise laboratories.

PCR is sensitive and specific.

Serologic testing : Cold agglutinins, titer of >1:64 is suggestive of infection; Anti mycoplasmal Ab detection, fourfold or greater rise are considered diagnostic.

Diagnosis (II)

 Imaging : Interstitial infiltrate or bronchopneumonia pattern. Lobar consolidation and pleural effusion are uncommon but may occur.

Treatment

• Erythromycin is the drug of choice.

(40-50mg/kg/24hr q6h for 10-14 days).

• Newer macrolides: Azithromycin (10mg/kg on day 1, and 5mg/kg/24hr on days 2-5) or Clarithromycin (15mg/kg/24hr given in two divided doses for 10 days).

Empiric Therapy for Lobar Pneumonia  Clinically moderate to severely toxic, treat empirically for S. pneumonia, S. pyogens ( and H. influenzae type b in unimmunized children)  In toxic children, tests for Mycoplasma should be considered because focal pneumonia is a rare presentation

   Cefuroxime intravenously, ceftriaxone or cefotaxime intravenously For anti-staphylococcal coverage, add to the above, either: nafcillin, oxacillin, or clindamycin For Mycoplasma: intravenous erythromycin or azithromycin; or oral erythromycin, azithromycin, or clarithromycin.

Pneumonia, with pleural fluid or empyema  Treat empirically for S. pneumonia, S. pyogenes, and S. aureus ( and H. influenzae type b in unimmunized children)  Consider aspiration pneumonia with anaerobic oral flora as pathogens; needle or catheter aspiration of pleural fluid, with drainage, is often required for clinical cure.

 Ceftriaxone or cefotaxime  For antistaphylococcal covarage, add to the above either: nafcillin, oxacillin, or clindamycin (also covers anaerobes found in aspiration pneumonia as well as most pneumoncocci)  Single agent therapy with meropenem, or ticarcillin/clavulanate (Timentin) both of which cover both aerobic and anaerobic pathogens

CONCLUSION

 Presence of pleuropneumonia appears to be associated with more severe and prolonged course of illness Pediatr Pulmonol 1990;8:182-7

 Even in patients with clinically mild pneumonia, Mycoplasma pneumoniae may be the cause of severe anemia Ann of Hematol 2001;80(3):180-2

 Association of exanthem and pneumonia or of hemolytic anemia and pneumonia are considered to be strongly suggestive for the diagnosis of M. pneumonia infection Clin Infec Dis 1993;17(Suppl 1):S47-51

THANKS FOR YOUR ATTENTION !

THE END