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7/M, A case of late-diagnosed Mycobacteria tuberculosis due to combined infection with Mycoplasma pneumoniae / fever(onset: 6 days ago), intermittent right chest pain (onset: 20 days ago)
Chief complaint
or Title
A case of late-diagnosed Mycobacteria tuberculosis due to combined infection with Mycoplasma pneumoniae / fever(onset: 6 days ago), intermittent right chest pain (onset: 20 days ago)
Difficulty For student/For resident
Hyun-Joo Jeoung, MD, Joon Hu, MD, Eon-Jin Kim, MD, Soo-Young Lee, MD[jsjs87@madang.ajou.ac.kr],
Department of Pediatrics, Ajou University School of Medicine
* History
Date of Admission; 2001.2.10
Present illness; A 7 year-old previously healthy boy was admitted to our hospital via emergency room because of fever and intermittent right chest pain. Because of fever and chest pain he took a chest radiograph in a private clinic. The chest radiograph revealed pleural effusion, and he was transferred to out hospital for the diagnosis and management.
  Past history : He was born by NSVD at IUP 40 wks and birth weight was 3.60kg.
He completed vaccines as routine vaccination schedule including BCG.
Family history : He was born as a second baby of two siblings. There were no medical histories of cardiovascular, autoimmune, or pulmonary disease in his family.
* R.O.S.& P/Ex
Review of system : general malaise(-), chronic fatigue(-), weight loss(-),
fever/chilling(+/-), respiratory distress on walking(+), right chest pain(+), cough/sputum/rhinorrhea(/-/-), nausea/vomiting/diarrhea(-/-/-)
Physical examination :  
Vital sign : blood pressure: 100/60mmHg, pulse rate: 98/min, respiratory rate: 22/min,  body temperature: 36.8?.
He was alert and not so ill looking. No chest retraction was found, but breath sound was decreased without rale or wheezing on right lung field. There was no digital clubbing nor cyanosis
* Lab
1) Hematologic values
first hospital daythird hospital dayeight hospital daydischarge day10days after discharge15months after discharge
white-cell count(/mm3)7,7005,3005,4008,6006,80011,290
band forms
platelet count(/mm3)334x103333x103438x103659x103384x103395x103

2) Biochemical findings
AST 32 U/L, ALT 15 U/L, Ca 9.4 mg/dL, P 4.2 mg/dL, BUN 12.4mg/dL, Cr 0.5 mg/dL, LDH 329 U/L, total protein 7.0 g/dL, albumin 3.9 g/dL, Na 136 mmol/L, K 3.8 mmol/L, Cl 100 mmol/L

3) Mycoplasma antibody titer
On admission : =1:1280
12th hospital day : 1:640
6 weeks after intial examination : 1:320  
15 months after initial examination : 1:640

4) Mantoux tuberculin skin test
on admission : negative
12 month after discharge : 20 mm of induration

5) pleural fluid evaluation
1st hospital day3rd hospital day
appearanceyellow and hazyreddish and cloudy
PF : serum ratio0.80.77
LDH (U/L)1200750
PF : serum ratio3.652.54
ADA (U/L)143.8108.1
red-cell count(/uL)52503360
white-cell count(/uL)7250210
atypical lymphocytes2%

Gram stain: (-) (first hospital day) ? (-) (third hospital day)
bacterial culture : no growth (first hospital day) ? no growth (third hospital day)
AFB stain: (-) (first hospital day) ? (-) (third hospital day)
Culture for M. tuberculosis complex
  *  no growth after 8 wks (specimen from first hospital day)
  * Mycobacterium tuberculosis complex 10 CFU/medium (specimen from third hospital day, but we could not confirm this till 1 year after the result because the patient did not visit hospital for 1 year)
* Clinical Course
On the 1st hospital day, body temperature was over 38?. Initially he was treated with intravenous antibiotics (ampicillin/sulbactam, ceftriaxone), oral antibiotics (roxithromycin). The chest radiographs showed massive pleural effusion in the right lung and collapse of right middle lobe (Fig.1).  Diagnostic thoracentesis was done and the data from pleural fluid examination was described as above. A closed chest tube thoracostomy was performed which yielded large amount of yellowish and hazy fluid. On the 5th hospital day, the closed chest tube was removed because there was no drainage of pleural fluid collection. Mycoplasmal antibody titer was =1:1280, which was positive. The patient gradually recovered with oral roxithromycin without progression of pleural fluid collection. On the 10th hospital day, fever subsided. On the 12th hospital day, the intravenous dexamethasone was started because the chest radiographs showed remained pleural effusion and adhesive pleural thickening and the chest ultrasonogram revealed complicated pleural effusion which had adhesive irregular pleural surface. On 7th hospital day, the chest radiograph  showed the remarkable improvement of pleural effusion and nearly clear lung. He was discharged with roxithromycin at the 18th hospital day(Fig. 2).

After discharge, the pleural thickening was remained, but the patient stop to visit hospital for a ling time without confirm the complete resolution of the chest radiograph. During 12 month after discharge, he has experienced 2 episodes of skin infection on the right chest wall, but the lesions were healed spontaneously. On the day of visit with 3rd skin infection, we found the skin lesion was related with previous chest tube insertion and on the same day we could confirm the positive culture data from the specimen yield on 3rd hospital day. And the follow up chest radiograph showed residual pleural thickening and newly developed parenchymal consolidation on the pleural side of right mid-lung field(Fig.3). At the time he took the Mantoux tuberculin skin test again. The test conversed to positive while the first test had shown negative on the admission (12 month ago). According to the previous culture result( Mycobacterium tuberculosis complex (10 CFU/medium, isolated from his pleural fluid which was yielded at 3rd hospital day, 12 month ago), oral anti-TB therapy was started. After 12 months' chemotherapy (2 months of INH, RIF, PZA/10 month with INH and RIF), the chest radiograph showed marked improvement and the skin lesion was healed completely after 2 month of anti-TB medication.

* If you click the image you able to see original image

Figure 1. Initial chest radiographs

Figure 1. Initial chest radiographs

Figure 2. Chest radiographs on discharge

Figure 3. Chest radiograph at12month after discharge(no anti-TB medication)

Figure 4. Chest radiograph after 10 months of anti-TB medication

Discussion points for differential diagnosis of pleural effusion due to M. tuberculosis and M. pneumoniae in this case.

Question 1. Can we suspect M. tuberculosis infection in this case from clinical manifestation and initial laboratory findings ?

Family history of tuberculosis : no
Clinical manifestation : non specific
PPD skin test : negative
Chest radiograph : unilateral massive pleural effusion with shifting
Mycoplasmal antibody : 1:1280 on admission day
PCR for M. tuberculosis : not done
Pleural fluid examination :
case patientreference patient
appearanceyellow and hazyyellow and hazy
protein (mg/dL)56005400
PF : serum ratio0.80.77
g1ucose (mg/dL)9526
LDH (U/L)1200848
PF : serum ratio3.653.39
ADA (U/L)143.8133.9
red-cell count(/uL)52502950
white-cell count(/uL)72502240
atypical lymphocytes3

Question 2. Are there any specific clinical manifestations which are favorable to the diagnosis of Mycobacterium tuberculosis ?

Chronically ill looking : no
Weight loss : no
More severe respiratory symptoms : not specific
Long lasting fever : no

Question 3. Are there any clues in personal or familial histories ?

BCG vaccination : done
Family history of pulmonary tuberculosis : no
History of immunodeficiency : no
Poor socioeconomic state : yes

Question 4. Is there any special finding of chest X-ray ?

Unilateral pleural effusion with shifting : non specific for any kinds of pleural effusion
Incomplete resolution of chest  X-ray : it may suspect that antibiotic therapy is not proper in this case, however, many cases of mycoplasmal pneumonia would show radiological abnormalities more than 4 weeks after initial proper management.

Question 5. Are there any solid parameters for initial diagnosis of Mycobacterium tuberculosis before culture proof ?

It is not always clear, however, several clinical and laboratory tests could be the  indicative parameters which suggest Mycobacterium tuberculosis infection :

1. Family history of tuberculosis.
2. Contact history with tuberculosis patient.
3. Positive skin test for PPD.
4. Clinical symptoms and radiographic findings resist on going antibiotic therapy.
5. Positive result of PCR for Mycobacterium tuberculosis.
6. Positive AFB staining from pleural fluid or biopsy specimen.
7. Typical features of pleural fluid examination  
8. Positive culture for Mycobacterium tuberculsosis (however, the confirmation of result needs more than 4-6 weeks after inoculation)

Cf. Comparison of initial pleural fluid examination in 4 cases of culture-proven tuberculosis combined with mycoplsmal infection diagnosed by anti-mycoplasmal antibody titer.

casesex/ageFHxmycoplasmal AbADAWBCneutlymmonoLDH
UKSM, 15-1:16053.2320504551786
SWDM, 4+1:640133.9224038014848
PJMM, 6-1:1280143.872503849131200
PJWM, 14+1:64074.62106893790

Question 6. Is there any problem with the delayed initial anti-TB medication ?

Question 7. Dose a mycoplasmal infection decrease host cellular immunity and could it possible that coincidental mycoplasmal infection induce the reactivation of tuberculosis, or increase the susceptibility to mycobacterial infection ?
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