Cardiovascular and Lung Involvement in Patients with Autoimmune Pancreatitis

Round 1

Reviewer 1 Report

The authors analyzed 127 AIP patients experienced in a single institute in this study. They reported the frequence and clinicopathological information of AIP cases with cardiovascular involvement by reporting type of lung diseases (nodular, pleural thickenings, type of artery involved, and so on), other OOI, smoking status, and the period between the diagnosis of AIP and cardiovascular lesions. They compared their data with previously reported literatures. They found 11 and 10 cases which had lung and cardiovascular involvement respectively and reported some information of each case. 

Althouhg the clinicopathological features of IgG4-related cardiovascular lesions are important to know and the number of studied cases are relatively big, I have several concerns for this manuscript. First, as autors menthioned (from Line 221), the  cardivascular lesions they included are heterogeneous and might be lesions unrelated to IgG4-systemic disease, such as Wegeners or some infectious disease, since no pathological evaluation were done. From the introduction part and the paper it seems as if  the authors were reporting IgG4-related cardiovascular lesions, which is confusing. Second, the presentation of the type of lung involvement (nodular, pleural thickenings, and so on)  are poor and should be improved. Table 2 is not good. They should make separate columns for the onset, relapse, and radiological features of lung lesions. Simiarly Table 3-5 must be improved. 

There are some misleading writings and ambiguous presentation in this manuscript. Since scientific papers must clearly present what you can conclude from your study, it seems the big problem for this manuscript. 

Author Response

Dear Reviewer!

 

Thank you very much for your time and valuable comments related to our manuscript!

 

Please find enclosed answers:

 

The authors analyzed 127 AIP patients experienced in a single institute in this study. They reported the frequence and clinicopathological information of AIP cases with cardiovascular involvement by reporting type of lung diseases (nodular, pleural thickenings, type of artery involved, and so on), other OOI, smoking status, and the period between the diagnosis of AIP and cardiovascular lesions. They compared their data with previously reported literatures. They found 11 and 10 cases which had lung and cardiovascular involvement respectively and reported some information of each case.

 

Althouhg the clinicopathological features of IgG4-related cardiovascular lesions are important to know and the number of studied cases are relatively big, I have several concerns for this manuscript.

First, as autors menthioned (from Line 221), the cardivascular lesions they included are heterogeneous and might be lesions unrelated to IgG4-systemic disease, such as Wegeners or some infectious disease, since no pathological evaluation were done. From the introduction part and the paper it seems as if the authors were reporting IgG4-related cardiovascular lesions, which is confusing.

Authors’ answer: We agree. Introduction part was corrected accordantly.

Second, the presentation of the type of lung involvement (nodular, pleural thickenings, and so on) are poor and should be improved. Table 2 is not good. They should make separate columns for the onset, relapse, and radiological features of lung lesions. Similarly Table 3-5 must be improved.

Authors’ answer: Before the start of manuscript writing we had a long discussion with the various specialist and we decided to use the same terminology as in previous publications, in first hand from Japanese authors. In that way the results are comparable and can be performed in all other centers in the world. The same worth for tables. In contacts with the colleagues from other centers at European congresses we received feedback regarding their patients and considering heterogenicity and differences between individual patients we decided to use the tables that will include type of AIP, onset of other organ involvement, treatment and smoking status.

There are some misleading writings and ambiguous presentation in this manuscript. Since scientific papers must clearly present what you can conclude from your study, it seems the big problem for this manuscript.

Authors answer: It will be much easier to answer if the reviewer should be more detailed regarding “misleading writings and ambiguous presentation” that is quite strong accusation in the academical world, if we may notice. We just reported other organ involvement in one of the biggest cohorts of AIP in the Europe and wanted to increase awareness among all types of clinicians that may meet these patients. We strongly believe that presenting manuscript will help to fill some knowledge gaps in this field.

 

With kind regards!

 

Miroslav Vujasinovic, MD, PhD

Senior Consultant

Department for Digestive Diseases

Karolinska University Hospital

SE-141 86 Stockholm

Sweden

Tel: +46 (0) 8-123 943 20

Cell: +46 (0) 72-469 49 38

E-mail: [email protected]

 

Reviewer 2 Report

Type 1 autoimmune pancreatitis (AIP) is a kind of IgG4 related disease, which characterized by lymphoplasmacytic infiltrations affecting multiple organs. The exact prevalence of IgG4-related disease (IgG4-RD) in worldwide is unknown. As mentioned by this manuscript, the most epidemiological data on IgG4-RD are from Japan. This study filled with a piece of data from Sweden patients. They found 15% of type 1 AIP had lung and/or cardiovascular involvement, which can also be alleviated by corticosteroid treatment. This is a nice designed and presented study. the conclusion of this manuscript promotes our knowledge of AIP and IgG4-RD.

Author Response

Type 1 autoimmune pancreatitis (AIP) is a kind of IgG4 related disease, which characterized by lymphoplasmacytic infiltrations affecting multiple organs. The exact prevalence of IgG4-related disease (IgG4-RD) in worldwide is unknown. As mentioned by this manuscript, the most epidemiological data on IgG4-RD are from Japan. This study filled with a piece of data from Sweden patients. They found 15% of type 1 AIP had lung and/or cardiovascular involvement, which can also be alleviated by corticosteroid treatment. This is a nice designed and presented study. the conclusion of this manuscript promotes our knowledge of AIP and IgG4-RD.

 

Dear Reviewer!

 

Thank you very much for your time and positive opinion!

 

With kind regards!

 

Miroslav Vujasinovic, MD, PhD

Senior Consultant

Department for Digestive Diseases

Karolinska University Hospital

SE-141 86 Stockholm

Sweden

Tel: +46 (0) 8-123 943 20

Cell: +46 (0) 72-469 49 38

E-mail: [email protected]

 

Reviewer 3 Report

Reformat Table 1. It is difficult to read as data does not align with patient or treatment characteristics.  Re Table 1. P value for comparing treatment modalities between the two cohorts should be independent for each modality, not a grouped statistical analysis. Similarly for smoking history.  Was the diagnosis of AIP confirmed and how? Would address this in the methods section. Were other diagnoses that cause IgG4 elevation like Churg Strauss, sarcoid, etc evaluated and were patients with those diagnoses excluded?  Patients who developed cholangitis, were other causes excluded ie choledocholithiasis, etc? Would address this in the methods section There are figures and tables in the paper that are not referenced to in the text of the paper - figure 3 and 4, table 5 Did any patients with OOI have biopsies to confirm IgG4 mediated disease? Did the patients with pulm or vascular involvement improve with treatment?  Figure 2 does not make sense. Why are individual patient AIP diagnosis time points connected. Each individual patient is an independent variable 

Author Response

Dear Reviewer!

 

Thank you very much for your time and valuable comments!

 

Please find enclosed answers:

 

Reformat Table 1. It is difficult to read as data does not align with patient or treatment characteristics.  Re Table 1. P value for comparing treatment modalities between the two cohorts should be independent for each modality, not a grouped statistical analysis. Similarly for smoking history.

Authors’ answer: We agree. We made corrections accordantly.

Was the diagnosis of AIP confirmed and how? Would address this in the methods section.

Authors’ answer: The diagnoses of AIP was confirmed according to ICDC criteria – please see lines 76 and 77. It was already included in the method section.

Were other diagnoses that cause IgG4 elevation like Churg Strauss, sarcoid, etc evaluated and were patients with those diagnoses excluded? 

Authors answer: Patients with Churg Strauss are mentioned in the manuscript (table 2, table 3, line 168). Complete work up of these patients was performed (via rheumatologists).

Patients who developed cholangitis, were other causes excluded ie choledocholithiasis, etc?

Authors’ answer: Yes. Other causes were excluded, and all the patients were followed.

Would address this in the methods section There are figures and tables in the paper that are not referenced to in the text of the paper - figure 3 and 4, table 5 Did any patients with OOI have biopsies to confirm IgG4 mediated disease? Did the patients with pulm or vascular involvement improve with treatment? 

Authors’ answer: We agree. Text was corrected accordantly. Figures 3 and 4 are important for the manus and were mentioned (please see line 210) Tables 4 and 5 are mentioned in line 176 now. Majority of patients with OOI (small lung changes or aortitis were not biopsed). Minority (cardiac involvement and some large vessel involvement were biopsied). Imaging and clinical symptoms, as well as good response on steroid treatment were in used for diagnosis.

Figure 2 does not make sense. Why are individual patient AIP diagnosis time points connected. Each individual patient is an independent variable.

Authors’ answer: We agree. Figure 2 was removed and the changes in the text were performed accordingly.

 

With kind regards!

 

Miroslav Vujasinovic, MD, PhD

Senior Consultant

Department for Digestive Diseases

Karolinska University Hospital

SE-141 86 Stockholm

Sweden

Tel: +46 (0) 8-123 943 20

Cell: +46 (0) 72-469 49 38

E-mail: [email protected]

 

Round 2

Reviewer 3 Report

Reviews accepted. Agree with comments from other reviewer that characterization of cardiovascular and pulmonary disease in greater detail would be vastly beneficial for the reader