Clinical Course of Bacillus Calmette-Guerin Lymphadenitis

Round 1

Reviewer 1 Report

1. The authors assume that BCG lymphadenitis is not associated with inborn errors of immunity, which is incorrect. The type of outcome of BCG lymphadenitis depends on whether there is an inborn error of immunity. For example, chronic granulomatous disease may be the first manifestation and not evolve to a systemic form.
2. The authors describe, "Disseminated BCG infection requires consultation with pediatric immunology and infectious diseases specialists." It is not like that; a patient with BCG lymphadenitis is a warning sign to detect an inborn error of immunity.
3. Which strain of vaccine was administered to the patients? Some strains are associated with more significant adverse effects.
4. Is there any study in Korea with similar data, comment in the discussion.
5. The values ​​in the tables are average, but it is noteworthy that the SD gives negative values, for example, 320.3±465.7
6. I do not understand what the concept "Symptom on fluctuation" refers to in the table
7. The item "Symptom on fluctuation" 6 (15.2%) eliminates the percentage sign.
8. In the discussion, it is only a bibliographic description, but they do not compare their results with those of the literature.
9.  Add as limitations of the study that it is unknown whether these patients suffer from inborn errors of immunity.

Author Response

1. The authors assume that BCG lymphadenitis is not associated with inborn errors of immunity, which is incorrect. The type of outcome of BCG lymphadenitis depends on whether there is an inborn error of immunity. For example, chronic granulomatous disease may be the first manifestation and not evolve to a systemic form.
   Answer: We agree with your opinion. In this study, we only excluded patients who were diagnosed with CGD. We added exclusion information in material and method section. (page 2)

 

2. The authors describe, "Disseminated BCG infection requires consultation with pediatric immunology and infectious diseases specialists." It is not like that; a patient with BCG lymphadenitis is a warning sign to detect an inborn error of immunity.
   Answer: If the patients visited for BCG lymphadenitis, we consulted pediatricians. (page 6, line 60-64). We excluded the patients diagnosed with innate immunodeficiency diseases such as chronic granulomatous disease and severe combined immunodeficiency.

 

3. Which strain of vaccine was administered to the patients? Some strains are associated with more significant adverse effects.
   Answer: In Korea, Danish 1331 strain is used for percutaneous vaccine and Tokyo 172 strain is used for intradermal vaccination. We added information about vaccination in manuscript. (page 2, highlighted)
   
   
4. Is there any study in Korea with similar data, comment in the discussion.
   Answer: We added previous Korean data in the discussion section. (page 6, highlighted)
   Regarding the incidence of BCG lymphadenitis, Kim et al. reported a retrospective multicenter study. They reported incidence of lymphadenitis after BCG vaccination was 0.20% in Tokyo strain intradermal and 0.69% in Danish percutaneous administration. During the two-week survey period, ten patients' parents complained of lymphadenitis as a result of immunization.
5. The values ​​in the tables are average, but it is noteworthy that the SD gives negative values, for example, 320.3±465.7
   Answer: We corrected the error in the results. (pages 4-6)
6. I do not understand what the concept "Symptom on fluctuation" refers to in the table
   Answer: We intended the wax and wane pattern of inflammation as a “symptom of fluctuation”
7. The item "Symptom on fluctuation" 6 (15.2%) eliminates the percentage sign.
   Answer: We corrected as you commented. (page 3)
8. In the discussion, it is only a bibliographic description, but they do not compare their results with those of the literature.
   Answer: In each paragraph, we explained our findings and compared them to those found in the literature. (highlighted on page 6)
9. Add as limitations of the study that it is unknown whether these patients suffer from inborn errors of immunity.
   Answer: We added the limitation of this study as you commented. (“ We did not include patients who suffer from inborn errors of immunity such as chronic granulomatous disease. “ page 7, line 101-102)

Author Response File: Author Response.docx

Reviewer 2 Report

In their manuscript, Ko et al. present an original and interesting study about the description of lymphadenitis as a complication on BCG injection. They also present results of three methods of treatment : observationnal, surgical excision and incision/drainage (I/D). Their approach is based on retrospective study and long time follow up of children. Discussion is well-written; references to clinical studies and/or case reports are relevant.

Therefore, these results have bias due to retrospective collection of data on medical chart review and unequal patients repartition between the three groups with a statistically larger size of lymphadenitis in  I/D group  but  these bias are well detailled et discussed.

One element could have been relevant on the study at the time of the study especially for the surgical group: presence or absence of esthetic sequels  and need to consider further surgery for scars. If this data is available, could you add this point to the study ?

I also have specific comments.

Specific comments

Material and methods : 

Could the authors bring details on review board approval of data collection and the word [anonymized] could be relevant after "aquired retrospectively]

Results

Table 2: Legend do not partially match with table 2 but also with Table 3 on the manuscript

Figure 2 : presentation could be more readable with a unique figure instead of four charts.

 

Author Response

Reviewer 2

In their manuscript, Ko et al. present an original and interesting study about the description of lymphadenitis as a complication of BCG injection. They also present results of three methods of treatment: observational, surgical excision, and incision/drainage (I/D). Their approach is based on retrospective study and longtime follow up of children. Discussion is well-written; references to clinical studies and/or case reports are relevant.

Therefore, these results have bias due to retrospective collection of data on medical chart review and unequal patients repartition between the three groups with a statistically larger size of lymphadenitis in I/D group but these biases are well detailed et discussed.

• One element could have been relevant on the study at the time of the study especially for the surgical group: presence or absence of esthetic sequels and need to consider further surgery for scars. If this data is available, could you add this point to the study?

Answer: As you mentioned, there were several cases of patients with esthetic sequelae such as a hypertrophic scar. Unfortunately, in this study, we did not investigate the esthetic result in BCG-related lymphadenitis due to the limitation of retrospective review. In case of further study, we will include esthetic results. However, no patient needs for corrective surgery regarding hypertrophic scar.

I also have specific comments.

Specific comments

Material and methods: 

• Could the authors bring details on review board approval of data collection and the word [anonymized] could be relevant after "acquired retrospectively

Answer: Yes, the IRB approval date was included in the manuscript. (page 7, line 132)

Results

• Table 2: Legend does not partially match with table 2 but also with Table 3 on the manuscript
  Answer: we corrected the legend of Table 2 and Table 3. (Page 4-6)
• Figure 2: presentation could be more readable with a unique figure instead of four charts.(??)

Answer: Actually, we attempted to present clearly whether or not symptoms recurred after treatment in each group. After many trials, we separate diagrams A to D as shown in Figure 2.

 

 

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Your answer 6: You explained what you meant but it will be confusing to readers, replace this one (symptom on fluctuation).

Author Response

Thank you for your comments. In previous other reports, some authors described repeated symptoms as recurrence. We replaced the term “symptom on fluctuation” with “recurrent symptom”. 

Author Response File: Author Response.docx