IgA Vasculitis Complicated by Both CMV Reactivation and Tuberculosis
Round 1
Reviewer 1 Report
This case reports underline an occurrence that should be taken always into account when managing a child with IgA vasculitis. The final message “Our case demonstrates that an attempt to eliminate and prevent infections may contribute to the improvement of the prognosis of the underlying disease. The treatment of nephropathy associated with IgA vasculitis includes immunosuppression, which may predispose to reactivation of latent infections. Special attention should be paid to the early detection of such infections. Their presence should always be taken into consideration in cases when, despite properly applied treatment, the renal function improvement is unsatisfactory and proteinuria is rising. It is important to keep in mind that symptoms may not be specific and therefore, the diagnosis may be difficult. Delay in diagnosis, especially in the course of active immunosuppressive treatment, can result in worsening of the course of infection.” In my opinion is very important for the clinicians.
The Figure is very explicative but I would suggest to add more details about anti-TBC treatment as you did for CMV treatment. In the top of figure in the top you indicated MMF as treatment but you did not show the anti-TBC drugs.
Line 50, please add 24h proteinuria value at admission to the Nephrology Department and before the start of the treatment.
Author Response
Dear Reviewer
At the outset, we would like to thank you for the time devoted to familiarize yourself with the work and its thorough analysis. We fully agree with the submitted comments and will take each of them into account, treating them as an important guideline. Below is our reference to each of the comments in the review.
The added and changed sentences are marked in green in the text.
POINT 1
Line 50, please add 24h proteinuria value at admission to the Nephrology Department and before the start of the treatment.
ANSWER 1
We added proteinuria value in the text. The same value is presented in Table 1. We started treatment with prednisone at exactly the same time.
POINT 2
The Figure is very explicative but I would suggest to add more details about anti-TBC treatment as you did for CMV treatment. In the top of figure in the top you indicated MMF as treatment but you did not show the anti-TBC drugs.
ANSWER 2
We added anti-TBC treatment. Line 80-81 and 115-117.
Reviewer 2 Report
Please find attached my comments and suggestions
IgA vasculitis complicated by both CMV reactivation and tuberculosis
Thank you for giving me the opportunity to review you case report. Below are some few suggestions for the authors
Line 44
The authors need to describe in detail whether the patient in this case report has an established IgA vasculitis and also what relationship existed between the appendicitis and the Ig A vasculitis .
Did the infection – appendicitis and the surgery - appendectomy triggered a stress response leading to activation of Ig A vasculitis???? The authors need to establish a cause-and-effect relationship between the appendicitis and Ig A vasculitis. This was not reflected in the opening statement of the case report.
Line 45 and 46
The lesion that the patient developed. Is this a new diagnosis of Ig A vasculitis or the patient has this diagnosis from the beginning? If this is a new diagnosis, then is the skin lesion alone sufficient to give the clinical diagnosis of Ig A vasculitis?
The authors need to describe the lesion in more details- papular, macular, purpura???
Please can the author include a picture of the initial lesion. A picture speaks better than a thousand word.
I will suggest to the authors to write “that the characteristics of the lesion raises the suspicion for Ig A vasculitis” Further workup confirmed the diagnosis.
Line 55
The authors have to describe in better details the laboratory findings of nephrotic syndrome. It seems that the patient in this report has both nephritic and nephrotic syndrome.
Please mention that the cholesterol level was not elevated in this patient.
Line 63-85
The description of the management plan is too wordy and lengthy. This needs to be condensed and made more succinct.
Line 78-79
“the presence of an infection and a positive result of the QuantiFERON test was obtained.”
The authors have to state that prior to the diagnosis the patient did not have any significant risk factor for TB - Did not come contact with anybody with active tuberculosis; Does not live in an area endemic for tuberculosis etc., etc.
Line 118-119.
Statement is not very clear. The authors should elucidate their thought processes better.
Discussion
The discussion and conclusion should be under different sub heading. The conclusion should not have any references and only reflect the opinion of the authors.
Finally I urge the authors to argue in their conclusion why the CMV and TB infection is not due solely to immunosuppressive therapy with steroids, azathioprine, and, cyclophosphamide and MMF for the Ig A nephritis.
Comments for author File: 
Comments.pdf
Author Response
Dear Reviewer,
At the outset, we would like to thank you for the time devoted to familiarize yourself with the work and its thorough analysis. We fully agree with the submitted comments.
All the revisions are marked in blue.
Please see the attachment with a corrected case report.
Point 1
Line 44
The authors need to describe in detail whether the patient in this case report has an established IgA vasculitis and also what relationship existed between the appendicitis and the Ig A vasculitis .
Did the infection – appendicitis and the surgery - appendectomy triggered a stress response leading to activation of Ig A vasculitis???? The authors need to establish a cause-and-effect relationship between the appendicitis and Ig A vasculitis. This was not reflected in the opening statement of the case report.
Answer 1
We added a paragraph in the discussion
Line 104-111
The patient first presented with symptoms of appendicitis and underwent an appendectomy. It raises the question whether the appendicitis triggered a stress response leading to activation of IgA vasculitis or if it was its first manifestation. At the moment of surgery the patient did not show symptoms raising suspicion for IgA vasculitis. The patient underwent surgery at another hospital where appendicitis simplex was diagnosed. The inflammatory process in the appendix may have caused autoimmune vasculitis.
However, there are known cases where IgA vasculitis first manifested as appendicitis. In that case IgA immune complexes deposit in the appendix, which is not typical for acute appendicitis [10]. Appendicitis itself can be also a very rare complication of the underlying vascular disease [11].
Point 2
Line 45 and 46
The lesion that the patient developed. Is this a new diagnosis of Ig A vasculitis or the patient has this diagnosis from the beginning? If this is a new diagnosis, then is the skin lesion alone sufficient to give the clinical diagnosis of Ig A vasculitis?
The authors need to describe the lesion in more details- papular, macular, purpura???
Please can the author include a picture of the initial lesion. A picture speaks better than a thousand word.
I will suggest to the authors to write “that the characteristics of the lesion raises the suspicion for Ig A vasculitis” Further workup confirmed the diagnosis.
Answer 2
We added line 45-47.
Point 3
Line 55
The authors have to describe in better details the laboratory findings of nephrotic syndrome. It seems that the patient in this report has both nephritic and nephrotic syndrome.
Please mention that the cholesterol level was not elevated in this patient.
Answer 3
We added the information that the cholesterol level was not elevated in this patient at admission, however after a few days the cholesterol lever went up and we also added the value. Line 54, Line 61
Point 4
Line 63-85
The description of the management plan is too wordy and lengthy. This needs to be condensed and made more succinct.
Answer 4
We removed excessive information from the management plan.
Point 5
Line 78-79
“the presence of an infection and a positive result of the QuantiFERON test was obtained.”
The authors have to state that prior to the diagnosis the patient did not have any significant risk factor for TB - Did not come contact with anybody with active tuberculosis; Does not live in an area endemic for tuberculosis etc., etc.
Answer 5
Added Line 80
Point 6
Line 118-119.
Statement is not very clear. The authors should elucidate their thought processes better.
Point 7
Discussion
The discussion and conclusion should be under different sub heading. The conclusion should not have any references and only reflect the opinion of the authors.
Finally I urge the authors to argue in their conclusion why the CMV and TB infection is not due solely to immunosuppressive therapy with steroids, azathioprine, and, cyclophosphamide and MMF for the Ig A nephritis.
Answer 6 and 7
We divided conclusions from the discussion and elaborated on why the CMV and TB infection is not only a result of immunosuppressive therapy. Line 135-137
Reviewer 3 Report
Authors have presented a rare case of CMV and TB following Ig A vasculitis. Authors to make following changes before re-submission.
Line 51: and albumin.
Line 60.: also observed
Line 80: The patient was treated. Remove 'Boy'
Line 91: and genetic
Line 94: Remove coma after hypertension. 'Hypertension and extensive changes'
Line 103: Remove ' Nowadays'
Line 104: duration is long and in pulmonary
Author Response
Dear Reviewer,
At the outset, we would like to thank you for the time devoted to familiarize yourself with the work and its thorough analysis. We fully agree with the submitted comments.
All the revisions are marked in yellow. Changes regarded line 53, 64, 80, 93, 114, 115.
Please see the attachment with a corrected case report.
Round 2
Reviewer 2 Report
Line 120
Therefore, anti-tuberculosis treatment also improves kidney function.
I will suggest rephrasing this sentence
Therefore treatment with antituberculosis medication will help to improve impaired kidney functions.
Line 133-134
Our case demonstrates that an attempt to eliminate and prevent infections may improve the control and prognosis in IgA vasculitis nephritis.
This statement is not very clear, please reword or rephrase the sentence. What message are the authors trying to convey here?
Line 139
...and proteinuria is rising
I will suggest
..with worsening proteinuria
Author Response
We fully agree with the submitted comments. Below is our reference to each of the comments in the review. The added and changed sentences from round one are marked in green, yellow and blue in the text. Now, the changed sentences are marked in pink in the text.
POINT 1
Therefore, anti-tuberculosis treatment also improves kidney function.
I will suggest rephrasing this sentence
ANSWER 1
We rephrased the sentence. Line 120.
POINT 2
Our case demonstrates that an attempt to eliminate and prevent infections may improve the control and prognosis in IgA vasculitis nephritis.
This statement is not very clear, please reword or rephrase the sentence. What message are the authors trying to convey here?
ANSWER 2
We changed the sentence. Line 133-134.
POINT 3
I will suggest
..with worsening proteinuria
ANSWER 3
We changed the sentence. Line 139.
We added two words. Line 142.
Author Response File: Author Response.pdf
