Dr Theresa Raju, Dr Sathyajith Nair, Dr Sajith Kesavan, Dr C Jayakumar,
Amrita Institute of Medical Sciences, Kochi
Ten year old female child presented with h intermittent fever with a Tmax of 104degree F and dry cough of 7 and breathing difficulty days duration and breathing difficulty of 3 days duration. CXR taken showed left upper lobe consolidation. USG Chest showed consolidation of left lung with minimal pleural effusion on left side.
Irrespective of antibiotics and supportive breathing difficulty increased and xray was repeated which showed worsening.
Since symptoms persisted and CXR showed worsening, child was referred to AIMS
First child of non-consanguineous marriage born term with birth weight of 1.450kg and cried immediately after birth.
Child was shifted to NICU for low birth weight care.
She is developmentally normal and immunized for age according to NIS schedule
Auxology: Weight:21kg(between -2 and -3SD), Height:132cm(between 0 and -1SD), BMI:12.1kg/m2(below -3SD)
At admission, child was febrile, sick looking and tachypneic
Vitals: Temp:100.2F, PR:120/min, RR:43/min, Spo2:90% in room air and 99% with 2L oxygen, GRBS:72mg/dl
Systemic examination showed decreased air entry on left side with bilateral crepitations and stony dull note on percussion on left side with subcostal and intercostal retractions. Other systems were within normal limits
Chest xray was taken which showed left side homogeneous opacification.
Initial labs done showed: TC:8.51K/Ul, N:79.8%, L:16.6% with elevated CRP of 220.4mg/l. RFT, LFT, Serum electrolytes and URE were within normal limits.
The child was admitted to paediatric HDU and was started on Inj Piptaz, Clarithromycin, Inj Clindamycin, oral oseltamivir, nebulized bronchodilators. USG chest done showed gross left pleural effusion with floating echogenic particles within.
Complete collapse consolidation of left upper lobe and near complete collapse of left lower lobe. Effusion appears free. No loculations/septations/significant pleural thickening. Trace right pleural effusion.
Paediatric surgery consultation was availed and ICD drainage was did undera septic condition on day 3 of admission. Pleural fluid analysis showed exudative pattern (pleural fluid glucose:106.90, LDH:1330, Protein:4.74 and TC:150cells/mm3).
Repeat CXR after ICD drainage showed mild improvement.
Repeat USG chest showed minimal left pleural effusion persists with no echogenic particles and partial collapse consolidation of left upper lobe and near collapse consolidation of left lower lobe. No loculations/septations.Trace right pleural effusion with basal consolidation collapse.
Gene xpert was negative. Pleural fluid Gram smear, smear AFB, gene xpert, cytology and culture were negative. Virus/pathogen detection assay- negative for streptococcus pneumonia.
Respiratory viral panel done was positive for influenza B virus . In view of persistent fever spikes, respiratory distress and chest pain, paediatric pulmonology consultation was availed and advised HRCT chest and antibiotics were hiked to Inj vancomycin and Meropenem.
HRCT chest showed pulmonary thromboembolism in segmental branches of right upper lobe, right middle lobe, left lower lobe branches. Pulmonary infarct in right lower lobe. Left upper lobe consolidation with homogeneous enhancement and few areas of necrosis within. Small left pleural effusion.
USG doppler of bilateral lower limb done showed deep vein thrombosis involving left posterior, tibial and soleal vein.
Hence following work up was done – ANA-IF, DCT, Complement levels, Lupus anticoagulant, beta 2 glycoprotein IgG, IgM, Anticardiolipinantibody IgG and IgM, MPN reflex panel, Hb electrophoresis HPLC. Child was started on enoxaparin subcutaneously and factor Xa levels were monitored. Meanwhile, mycoplasma IgM which was sent earlier was positive (>27) and the child was started on Azithromycin orally.
Work up done was positive for anticardiolipin antibodies and HPLC showed no abnormal peak. DCT- 2+. Hematologyreview was given and advised to bridge to oral Warfarin. ANA IFA showed 3+, pattern: mixed (cytoplasmic + fine speckled). Rheumatology consultation was availed and wasadvised to start oral steroids suspecting SLE with secondary APLA positivity and NA blot was sent. Daily INR levels were monitored and enoxaparin was stopped once target levels were achieved.
Repeat labs and CXR prior to discharge showed improvement.
Child improved with the treatment given with no further fever spikes and was discharged with stable vitals with an advice to follow up pending reports .
On review, pending reports were negative for ANA blot, lupus anticoagulant, beta 2 glycoprotein. Positivity of ANA, Anti cardiolipin antibodies and DCT can also occurs secondary to Mycoplasma pneumonia infection. Hence, possibility of SLE was low.
DISCUSSION:
MYCOPLASMA PNEUMONIA:
Most common organism causing respiratory tract infections inschool going children and young adults. Like other mycoplasmas, M. pneumoniae is distinguished the complete absence of cell wall, resulting in, 1) Dependence on host cells for nutrients, 2) Intrinsic resistance to Beta lactam agents, 3) Their pleomorphic shape and lack of visibility on gram staining. It is a frequent cause of community acquired pneumonia in children more than 5 years of ageand adults. Accounts for approx. 20% of all CAP in middle school and high school children.
Clinical manifestations:
RESPIRATORY: Bronchitis and atypical pneumonia are themost commonly associated clinical syndrome associated withM. pneumonia. Onset is characterized gradual development of headache, malaise, fever and sore throat followed progression of lower respiratory symptoms, including hoarseness and nonproductive cough. Chest examination may have no auscultative or percussive findings or only minimal dry rales. Radiographic findings are variable and non specific. It may show bilateral diffuse infiltrates, lobar pneumonia or hilar lymphadenopathy which occur in 30% patients. WBC and DC are usually normal.
EXTRAPULMONARY DISEASE:
1)CNS disease: Occurs in 0.1% of all patients with M. pneumonia and in 7% of those requiring hospitalization. Manifestation includes: encephalitis, GBS, Transverse myelitis, cerebellar ataxia, Bells palsy. CNS manifestation occurs 3-23 days after onset of respiratory infection in up to 20% cases. Studies suggest that 2 pathogenic mechanisms for M. pneumoniae- associated neurological disease.
1st pattern: characterised almost absent or no prodromal respiratory symptoms(<7 days) and non reactive IgM response.
2nd pattern – presence of respiratory symptoms ( mc:cough) for >7 days + reactive IgM in active serum.
Studies suggest that encephalitis occurring more than 7 days after onset of prodromal symptoms are more likely to be caused auto immune response to M. pneumoniae. Involvement in brainstem results in severe dystonia and movement disorders. CSF maybe normal or have mild mononuclear pleocytosis and/or increased CSF protein concwith normal glucose. Diagnosis is positive CSF PCR, positive PCR from throat swab. MRI findings – focal ischemic changes, venticulomegaly, diffuse edema
2) MUCOCUTANEOUS: Mostly mucopapular rashes, urticaria, mycoplasma induced rash and mucositis syndrome or SJS. Usually develop 3-21 days after initial respiratory symptoms
3)HEMATOLOGICAL: Mild degree of hemolysis with a positive DCT and minor reticulocytosis 2-3 weeks after illness onset.
DIAGNOSIS:
No specific clinical, epidemiologic or lab findings – allow for specific diagnosis
1)Best method of diagnosis – Combination of PCR and Serology
2) Cultures on special media (SP4 agar media) – demonstrate classic M. pneumonia mulberry colonies 3) Serological tests: To detect IgG, IgM, IgA antibodies against M. pneumoniae
IgM antibodies – have high false positive and false negative results. Fourfold or greater increase in IgG antibody titre against M. pneumoniae between acute and convalescent sera obtained 2-4 weeks apart– diagnostic
4) Cold hemagglutinins – non specific
5)Nucleic acid amplification tests: More rapid diagnosis in acutely ill patients. Can be positive earlier in course of infection rather than serological tests.
TREATMENT:
They are sensitive to macrolides, tetracyclines, quinolones. Preferred in children lesser than 8 years of age. Recommended treatment in clarithromycin (15mg/kg/day divided into 2 doses PO for 10 days, Azithromycin –10mg/kg on day 1 followed 5mg/kg OD for 4 days, Doxycycline (2-4mg/kg/day BD for 7 days) and fluroquinolones such as levofloxacin (10mg/kg/per dose twice daily in children <5 years and 10mg/kg/day OD >5 years) – effective but have higher minimum inhibitory concentrations compared with macrolides– currently no recommended as first line therapy.
Thromboembolism is relatively rare in children and is mainly associated with critical illness, the presence of central venous line, congenital heart or vascular malformation. However, recent reports have confirmed the correlation between infection and thromboembolism. Infection of different pathogen can cause thromboembolism. Mycoplasma pneumoniae is an important pathogen of respiratory tract infection in children. From various case reports it was demonstrated that Mycoplasma pneumoniae is an important risk factor for thromboembolism, especially in pulmonary vascular, but less in extrapulmonary. Mechanism proposed for extra-pulmonary manifestations of MPP include direct invasion, cytotoxicity and inflammation through the activation of immune system cells for cytokine production and immune response with the production of cross-reactive antibodies molecular mimicry. The majority of pulmonary artery embolism cases were in situ pulmonary artery thrombosis (ISPAT), not classis thromboembolic PE (which often had co existing thrombosis in the veins of either the lower extremity or at non extremity sites,). Antiphospholipid antibodies, as commonly found in SLE, are associated with an increased risk of arterial and venous thrombosis. Case reports of patients have indicated that anti cardiolipin antibodies, lupus anticoagulant, and beta 2 glycoprotein can occur after infection with clinical consequences, not just as a transient non-pathogenic process. In a study conducted Flateau et al. it was described how immune mediation might also play a part in the hypercoagulability seen in Mycoplasma pneumoniae infection: antiphospholipid antibodies react with proteins that binds to phospholipid on plasma membrane contributing to thrombosis. A previous study reported that mycoplasma pneumonia infection induces positive antiphospholipid antibodies without thrombosis. In a study conducted in Beijing children hospital, it was concluded that pulmonary arteriovenous thromboembolism is the most common thromboembolism complicated in Mycoplasma pneumonia, and cerebral artery embolism and cardiac thrombosis are common in extra pulmonary thromboembolism. In the case of MPP with thromboembolic complications, pulmonary consolidation with pleural effusion in the main characteristic. About 2/3rd of the cases waspositive for antiphospholipid antibodies.