Calcified Granulomatous Pneumocystis Jirovecii Pneumonia in a Toddler with Severe Combined Immunodeficiency—A Case Report
Round 1
Reviewer 1 Report
Page 1 line 33: "typical infections" should change to "common infections". In the same sentence the word "typical" is used twice.
Despite the fact that the title is "Calcified Granulomatous Pneumocystis Jirovecii Pneumonia in a Toddler With Severe Combined Immunodeficiency. A Case Report." in the Case Report section the clinical presentation and the course of the pneumonia are not presented.
The Discussion section is too small. You could add a paragraph regarding the IL2RG mutations (https://www.ncbi.nlm.nih.gov/gene/3561). Apart from that, I suggest that you remove from the Introduction the section that refers to similar cases descibed in the literature (page 2 lines 41-44) and put it in the Discussion section, where you can compare these cases and give more information about granulomatous PJP.
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Author Response
Page 1 line 33: "typical infections" should change to "common infections". In the same sentence the word "typical" is used twice.
Thank you for the suggestion. We made this change (line 33).
Despite the fact that the title is "Calcified Granulomatous Pneumocystis Jirovecii Pneumonia in a Toddler With Severe Combined Immunodeficiency. A Case Report." in the Case Report section the clinical presentation and the course of the pneumonia are not presented.
We agree with the reviewer and we added the paragraph with the clinical presentation description in the Case Report section (lines 46-48, 52-69, 72-74).
The Discussion section is too small. You could add a paragraph regarding the IL2RG mutations (https://www.ncbi.nlm.nih.gov/gene/3561). Apart from that, I suggest that you remove from the Introduction the section that refers to similar cases descibed in the literature (page 2 lines 41-44) and put it in the Discussion section, where you can compare these cases and give more information about granulomatous PJP.
We thank the reviewer for the advice. We added a paragraph regarding the IL2RG mutations (lines 127-138).
Also, we moved the phrase from page 2 (old lines 41-44) to the discussion section (lines 110-113).
Author Response File: 
Author Response.doc
Reviewer 2 Report
The authors diagnosed that calcified lesion occured by PJ, However, the evidence of PJ does not showed in this paper.
Other pathogens might form calcified lesion.
The authors must add the evidence supported the diagnose of PJ.
Author Response
The authors diagnosed that calcified lesion occurred by PJ, However, the evidence of PJ does not showed in this paper.
Other pathogens might form calcified lesion.
The authors must add the evidence supported the diagnose of PJ.
We agree with the reviewer. Many pathogens can cause calcification during the healing of a primary infectious lesion. However, the clinical course from ICU to Bone Marrow Transplant Centre of our patient, being severely immunodeficient, has been closely monitored.
The diagnosis of PJP was found with polymerase chain reaction analysis revealed Pneumocystis DNA from the BAL fluid during admission of the child to the ICU. Other bacterial, viral, and fungal causes have been excluded by culture and direct polymerase chain reaction (PCR) on both peripheral blood and BAL fluid. The patient remained in the ICU for one month. After his discharge, he was immediately transferred to the BMT Unit in the positive pressure isolation room. He received only sterilized food and water and never stopped anti-infectious prophylaxis. Throughout the pre-transplant phase, he never had any clinical or laboratory signs of an infection and was subjected to microbiological and virological surveillance weekly.
Also, calcified lesions detected on the pre-transplant CT were present in the same areas as the primary granulomas, particularly the larger ones. We modified this sentence for a better description (lines 86-88).
Author Response File: Author Response.doc
Round 2
Reviewer 1 Report
Dear authors,
Thank you for your replies to my comments.
I enjoyed reading your revised manuscript.
I have no further recommendations to make.
I approve it to be published as it is.
Author Response
Thank you!
Reviewer 2 Report
The author seems to have judged from the clinical course that the lesions after Pneumocystis treatment became calcified, but since this has not been proven histologically or bacteriologically, I think that this is an overstatement. I would like to see histological and bacteriological evidence.
Author Response
As for the absence of histological evidence, the reviewer is right. We want to point out that calcified lesions were diagnosed in a child who was completely cured of pneumonia. Therefore, doing a lung biopsy, exclusively for "scientific" reasons, of an infant who must undergo a rescue transplant a few days seemed inappropriate.
Regarding microbiological confirmation: "Diagnosis of PJP was documented with polymerase chain reaction analysis revealed Pneumocystis DNA from the broncho-alveolar lavage fluid." (lines 67-69 of the manuscript). And precisely, the absence of further microbiological findings (BALs, blood cultures, and swabs performed weekly in the ICU) confirms that our diagnosis is the only possible.
This child underwent HSCT 5 years ago; he is completely cured. The last CT scan performed four months ago shows the unchanged persistence of the same calcified lesions, devoid of any clinical significance. We intended to help physicians manage a similar clinical situation without necessarily subjecting already fragile patients to examinations that are not without risk.
Round 3
Reviewer 2 Report
I interpreted this paper as a message that if calcification was observed in the lungs before transplantation, it would be better to consider PjP as well. However, we usually pay attention developing PjP after transplantation, I don't think this article is worth much.
