A Case of Paraneoplastic Anti-TIF1-γ Antibody-Positive Dermatomyositis Presenting with Generalized Edema and Associated with Aortic Aneurysm

Round 1

Reviewer 1 Report

This is an interesting case report. However, I have comments as follows:

1. Dermatomyositis belongs to the diseases which may mimic angioedema - please briefly discuss this point and cite: Andersen, M.F.; Longhurst, H.J.; Rasmussen, E.R.; Bygum, A. How Not to Be Misled by Disorders Mimicking Angioedema: A Review of Pseudoangioedema. Int. Arch. Allergy Immunol. 2016, 169, 163–170.

2. Together, the discussion is too concise and may be written more in detail.

Author Response

We thank the reviewer for taking the time to review our manuscript and making these very valuable suggestions and comments. Please see our responses below.

1. Dermatomyositis belongs to the diseases which may mimic angioedema - please briefly discuss this point and cite: Andersen, M.F.; Longhurst, H.J.; Rasmussen, E.R.; Bygum, A. How Not to Be Misled by Disorders Mimicking Angioedema: A Review of Pseudoangioedema.  Arch. Allergy Immunol.2016, 169, 163–170.

Response: We thank the reviewer for drawing our attention to this important point and further assisting us with providing a very useful article.

A paragraph was added to the discussion to explain the differential diagnosis, lines 95 to 105

2. Together, the discussion is too concise and may be written more in detail.

Response: We thank the reviewer for this suggestion that resulted in more reading and expansion of our awareness of very interesting possible etiopathogenesis links.

We enriched the discussion with the following:

1. Expanding on the following ideas:
2. How vascular involvement in DM can contribute to both the aortic aneurysm and the edematous phenotype of our patient’s DM (lines 119 to 164).
3. The role of myositis specific antibodies and anti–TIF1-γ in dermatomyositis (Lines 165 to 206).

1. Exploring and adding the following discussion

1. Paraneoplastic vasculitis and how it could possibly explain most of our patient’s findings (Lines 207 to 216).
2. The importance of understanding to the underlying pathology to guide therapeutic decisions (217 to 233).
3. Treatment options of edematous DM given the known more aggressive course and poor prognosis (234 to 240).

Reviewer 2 Report

This is an interesting CR, of a female DM patient, expressing anti-TNF abs. I would prefer that the authors elaborate further in their discussion on the plausible role of fibrous tissue damage, its relation to aortic aneurysm and malignancy, chemotaxis, macrophage migration etc.

Author Response

We thank the reviewer for taking the time to review our manuscript and making these very valuable suggestions and comments. Please see our responses below

Comment: This is an interesting CR, of a female DM patient, expressing anti-TNF abs. I would prefer that the authors elaborate further in their discussion on the plausible role of fibrous tissue damage, its relation to aortic aneurysm and malignancy, chemotaxis, macrophage migration etc.

Response: Thank you for drawing our attention to this very valuable point.

We included four paragraphs to make these connections as follow:

1. Expanding on the following ideas:
2. How vascular involvement in DM can contribute to both the aortic aneurysm and the edematous phenotype of our patient’s DM (lines 119 to 164).
3. The role of myositis specific antibodies and anti–TIF1-γ in dermatomyositis (Lines 165 to 206) with and without associated malignancy.

1. Exploring and adding the following discussion

1. Paraneoplastic vasculitis and how it could possibly explain most of our patient’s findings (Lines 207 to 216).

Additionally, we added two follow up points to explain the importance of understanding the underlying pathogenesis.

1. The importance of understanding to the underlying pathology to guide therapeutic decisions (217 to 233).

2. Treatment options of edematous DM given the known more aggressive course and poor prognosis (234 to 240).