Review for 10.1186/s12876-021-01664-1 (2021)

Reviewer’s report
Title: 
Whipple's Disease: the great masquerader. A high level of suspicion is the
key to diagnosis
Version: 
0 
Date: 
10 Nov 2020
Reviewer: 
Ian Beales
Reviewer's report:
The authors present three cases with relatively classic presentations in the
modern world of preceeding non-specific or rheumatolocgical feaures, failure to
repond to potent anti-inflammatory medicaton and eventual diagnosis of
Whipples's disease. There is nothing really new here. Although the authors
points about needing to consider what is always a rare diseease with protean
manifestation are important. Whipple's diease presenting as a treatment resistant
arthropathy is well documented and several studies have already highlighted that
many patients have been treated with anti-TNF or other biologics before a
diagnosis of Whipple's disease is made. Hence, although these cases are
generally well characterised, they are in no way unique. That does not mean that
publication to emphasize these issues with delayted diagnosis would not be
unreasonable.
Major points:
1. The paper is really too long for what amounts to 3 not unique case reports. In
their efforts to be inclusive of as much information as possible, the authors have
probably dilauted out their own message. Much of the detail of the exact details
within each patients timeline can be omitted without loss of clarity over the
overall points. For instance the details of which service the patient was admitted
under at any particualr time is really unnecessary. The cases have beed described
almost as they would be for a Grand Round presentaion but for the purposes of
publication a lot of extraneous information can be stripped out. For example, pn
page 11, any discussions about whether/how to perform a lymph node biopsy are
irrevelent. It is suffice to say that lymph nocde biopsy was performed.
2. The description of both cases 1 and 2 can be easily trimmed by at least 30 %.
3. 
Page 6 Line 14..he was in bad condition....is very poor English. It would be
suffice to say "his condition deteriorated"
4. Page 6, line 46. I do not understand what is meant by "fibres" in the
duodenum. The associated figure does ot clarify either, is this fibrin?
5. Was there any follow up on pateint 1?
6. What PCR assay was used for the diagnosis. Commercial or in house? Which
primers?
7. Page 10, line 54, TTE is used as an abbreviation without prior explanation?
8. It is interesting that the authors cite treatment recommendations from 2004
and have used treatments no longer recommended in more modern Europea
guidelines, with apparent good success, although we must accept that the
evidence base for such guidelines is poor. I agree with the authors statment about
the utility of early in therapy duodenal biopsy
8. It is not explicity stated but the assumption is that none of the patients had any
neurological or dermatological signs?
9. The figure legends need more detail. What is the magnification of the
histology pictures?
10. Table 1 is unnecessary, the point has already be sufficiently made that the
patient did not respond to potent immune modulators. Suggest this is removed.
11.Table 2 merely seems to have been lifted from another review paper. It is
irrelvent in this manuscript, suggst this is removed.
12. Figures 6 & are unnecessary and can be removed
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Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
No
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Yes
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Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes