[CIS PIDD] 3 month old Pneumocystis pneumonia, normal labs

[Karin Chen]

Dear All,

I am interested in hearing your thoughts on this 3 month old girl with history of Pneumocystis jirovecii pneumonia (PJP) and what appears to be normal immunologic workup thus far:

_____________________

2.5 months old - Upper respiratory infection that gradually worsened over 10 days, admitted for hypoxemia, fever  and cough with bilateral opacities on chest x-ray. Extensive sepsis workup completed (see below). + Rhinovirus,

+ Pneumocystis jirovecii on PCR of bronchoalveolar lavage fluid, but no Pneumocystis organisms seen. She has NORMAL lymphocyte enumeration, NORMAL lymphocyte mitogen proliferation, ELEVATED IgG/IgM/IgA.  She was followed by our infectious disease service, and they are fairly convinced that this was PJP pneumonia.



Summary of hospitalization:

A rule out sepsis workup including lumbar puncture and extensive testing for pulmonary infections was initiated. She was initially rhinovirus positive, with other studies negative. In the hospital, she developed fevers and had continued oxygen requirement despite antibiotics including ampicillin, gentamicin and ceftriaxone. Due to continued illness, she was switched to high-dose ampicillin, and azithromycin was added. A chest CT was obtained which showed extensive bilateral opacities/interstitial lung disease. Bronchoscopy on 8/13/12 demonstrated moderate right bronchomalacia and cloudy bronchoalveolar lavage fluid (BAL). BAL pathology results included  lipid laden macrophages, no cellular evidence of Pneumocystis/viral inclusions/fungal elements.  Pneumocystis PCR was positive and PO Trimethoprim/sulfamethoxazole (Bactrim) and prednisone was started.  Within 2 days after starting Bactrim, CRP decreased and she was weaned off oxygen. She was discharged home 2 days after with a 3 week course of Bactrim.



Past Medical History: born term, nonconsanguineous.

-2 weeks old- blistering lesion on dorsum of foot at site of bandage (applied after heelstick for newborn screening). The lesion ulcerated enough that she was seen by dermatology x2.  The lesion healed after application of Biafine emulsion cream x 1 week.

-1.5 months old -mild viral upper respiratory infection that gradually improved but never completely went away



Exam: Healthy appearing, no dysmorphic features, developmentally appropriate. 5-10% for weight.



PERTINENT LABS:
Respiratory virus panel by PCR: + Rhinovirus

8/4/12 (day of admission) 2.5 months old
WBC 31.3 (ANC 18500, lymphs 9100, monos 3400, eosinophils 300)  Hg 10.5, Plt unable to calculate MPV 7.3



8/5/12 CRP 17.6

8/8/12
Pertussis Ab IgM 1.6 high, Pertusis IgG/IgA normal, pertussis IgM immunoblot negative

8/9/12
HIV 1/2 Ab nonreactive
IgG 1040 (206-581) IgM 569 (17-105)  IgA 79 (3-47)

Lymphocyte enumeration (absolute counts)
CD3 T cells 5250
CD4 T cells 4033
CD4+ CD45RA+ naive T cells 3353
CD4+ CD45RO+ memory T cells 445
CD8+ T cells 1104
CD19+ B cells 2157
NK cells 595

8/12/12
Quantiferon Gold TB : indeterminate either due to T cell anergy or specimen mishandling

8/13/12
Sweat test: normal
LFTs normal
Respiratory virus panel by PCR: + Rhinovirus in BAL

Bronchoalveolar lavage: Oil-Red-O stain poaitive in 75% of macrophages. Moderate acute and chronic inflammation. Cellular pattern consistent with but not diagnostic of lipid aspiration or lipid pneumonia. No cellular evidence of Pneumocystis, viral inclusions or fungal elements identified by Pap stain. PAS stain is also negative for organisms. Cell differential: 75% macrophages, 3% bronchial lining cells, 15% neutrophils, 12% lymphocytes.

By report PJP DFA or PCR was positive but I have not personally seen the record of the result.

8/14/12
HIV RNA not detected

CRP 29.1



8/16/12 (Bactrim/steroids started)

CRP 3.8



8/17/12

Lymphocyte Mitogen Proliferation
                       Patient        Control 1   Control2
                       CPM     SI*       CPM     SI*       CPM     SI*
Media alone     2796       1          147       1          278     1

PHA 1:20       625187   224     504662 3433   293475 1056
PHA 1:50       725830   260     581172  3954      422990  1522

CON A 1:40     412868  148     283437  1928    174111  626
CON A 1:200   483651  173     296690  2018    169166  609

Media alone         3030     1          353      1          329     1

PWM 1:40          492744  163   161412  457     201283  612
PWM 1:200        505916  167     146529  415     284449  865
Interpretation:
Normal Lymphocyte responses to PHA.
Normal Lymphocyte responses to Con A.
Normal Lymphocyte responses to Pokeweed Mitogen.



Additional infectious disease workup: ALL NEGATIVE: includes chlamydia  pneumoniae PCR, mycoplasma PCR, chlamydia trachomatis DFA, enterovirus PCR,  blood cultures, CSF culture, respiratory cultures, urine culture.



Genetic testing for SFTPC mutation (ABCA3-related surfactant deficiency): no mutation detected on full gene sequencing.



IMAGING:

Chest x-ray: coalescent patchy opacities in both lungs, predominantly in the lower lobes but also the right upper lobe.

Chest CT: Extensive bilateral patchy and confluent airspace opacities, atypical/viral pneumonia favored over bilateral bacterial or fungal infection.



_____________________

My thoughts are to consider CD40 or TLR defect, but the pieces are not quite fitting. She is still young to obtain specific antibody testing, but perhaps I should obtain anyways? The IgG/IgA/IgM levels suggest to me that humoral immunity is also intact and she developed an appropriate inflammatory response.



This infant is petite, but  NOT malnourished and does NOT have diarrhea. My infectious disease colleagues feel fairly certain her illness was due to pneumocystis, and there is almost no likelihood that the PJP PCR was a false positive.



Anything else to consider? Is it possible for a "normal" 3 month old to develop PJP?



Best regards,

Karin





Karin Chen, MD
Department of Pediatrics
Division of Allergy, Immunology & Rheumatology
University of Utah
karin.chen at hsc.utah.edu
-------------- next part --------------
An HTML attachment was scrubbed...
URL: <http://seven.pairlist.net/pipermail/pagid/attachments/20120905/dade15be/attachment.htm>