IgM-Associated Cryoglobulinaemia

Round 1

Reviewer 1 Report

see my attached PDF

Comments for author File: Comments.pdf

Author Response

Many thanks to the reviewer for your helpful and thorough points raised.

 

Response to reviewer 1:

My remarks:

1) Your title reads

IgM Associated Cryoglobulinaemia, but in the introduction you
write management approach of monoclonal IgM associated cryoglobulinaemia.
May be monoclonal can be deleted ?

 

Response: Many thanks we have amended the text as suggested, for clarity.

2) Bing Neel syndrome is characterized by the involvement of the central nervous

system in Waldenström’s Macroglobulinemia. I would not use the eponym, but state
the condition.

Response: Many thanks. For clarity we have amended the text and put the eponym in brackets.

 

3) What do you mean by

therapy related neuropathy

Response: We have amended the text to clarify that we are referring to ‘treatment emergent neuropathy’, referring to potential toxicity from therapies such as bortezomib, thalidomide, vinca alkaloids and cisplatin.

 

4)

In those with rapidly progressing axonal and demyelinating peripheral neuropathy
cryoglobulinaemia should be considered after AL amyloidosis is excluded (19).
It is not clear to which patients those refer to. The reference is from a WM paper. Is
this group of patients considered? If this so, it should be stated. In otherwise rapidly
progressing axonal and demyelinating peripheral neuropathies such as CIDP, GBS or
AMAN a screening for cryo is not indicated.

Response:

Many thanks. The reference refers to IWMM-8 consensus panel for patients with IgM related disorders (including IgM MGUS and WM) and neuropathy. For clarity, we have amended the statement to say:

In those with a IgM monoclonal protein alongside rapidly progressing axonal and demyelinating peripheral neuropathy, cryoglobulinaemia should be considered after AL amyloidosis is excluded

 

5)

A biopsy may be required, particularly in establishing renal or nerve involvement
This sentence gives the impression that nerve biopsy is required for the diagnosis of
nerve involvement, which is of course wrong. Could be rephrased as follow: If
indicated a renal or nerve biopsy may be considered.

Response: Many thanks. We agree that this should be rephrased to say:

A biopsy may be required, particularly in establishing renal or nerve involvement, if indicated, to distinguish from other causes, however there are no standardised diagnostic criteria.

6) Given the neurotoxicity of bortezomib I am less enthusiastic about its proposed

used as suggested by the authors

Response: We agree that there is potential associated neurotoxicity with bortezomib and have outlined in the text that:

weekly, subcutaneous administration and close monitoring may ameliorate the risk and has been shown to be efficacious in WM.

7) Make sure that all abbreviations are explained

Response: Many thanks. We have amended abbreviations.

Reviewer 2 Report

The review is well written and easy to read. In this reviewer's opinion, it adds relevant information in the field and may be clinically useful. A greater attention is only suggested in the deepening of the bibliographic references and in the field of virus-related mixed cryoglobulinemia, which in the present version is only mentioned.

Author Response

Dear reviewer,

Many thanks for your helpful comments.

We have amended the text to address the references and virus-related mixed cryoglobulinaemia and have attached the revised manuscript.

Kind regards,

Jahanzaib