Whipple Disease Presenting as Isolated Transverse Myelitis with Permanent Neurological Damage in a Patient with Systemic Lupus Erythematosus: A Case Report of a Difficult Diagnosis with a Literature Review

Round 1

Reviewer 1 Report

Interesting case and certainly demonstrated that Whipple disease is very difficult to diagnose clinically especially with the manifestation of transverse myelitis. 

The author and team had done extensive review of the literature on the epidemiology, clinical manifestation, diagnostic and therapeutic options. 

Line 63-65, please be specific what microbiological examination method and PCR for which organism were negative. For PCR method, not detected will be a more appropriate description of the nature of the test, whereas for serological testing reactivity on initial and convalescent sample should be commented. 

Line 92-94 Microbiological tests and PCR hardly reached 100% analytical sensitivity and specificity, thus rather than the word exclude certain infections, replacement with some infective etiologies as listed were less likely would be more appropriate. 

Line 289-290 - Please revise the sentence, the hypothesis for WD at this stage, most people would have exposure to sewage, but WD might only manifest in genetically predisposed individual. Seroprevalence for different age groups and country may vary. 

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

This is a relatively well written, novel, and very educational case that was a quite challenging for diagnosis. Unfortunately, it led to permanent paralysis. I would like to ask authors to edit the paper in the following aspects: 

Title should also include wording permanent paralysis or permanent neurological damage.

Introduction is rather short; it should include one paragraph describing SLE and its neurologic manifestation as well as other etiologies of acute transverse myelitis (infectious and non-infectious). Please see the following:

Frontiers | Neurological Disease in Lupus: Toward a Personalized Medicine Approach (frontiersin.org)

Acute transverse myelitis – A rare clinical manifestation of Lyme neuroborreliosis - PMC (nih.gov)

Line 45- please mention the doses of immunosuppressive medications used to treat lupus. 

Line 60- CFF " limpid"? I am not sure I understand.

Line 66- have you tested for any tick-borne infection present in your region of Italy? For example, Lyme disease can cause transverse myelitis.

 Line 68, 69- please report doses of these medications. 

Line 149- " comments " should be replaced with discussion. 

Discussion should focus more on acute transverse myelitis rather than broadly on CNS involvement. Additionally, how use of immunosuppressive medication affected WD progression should be elaborated, and clinical course compared to immunocompromised vs immunocompetent individuals.

some grammatical mistakes and sentence structure 

Author Response

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Author Response File: Author Response.pdf

Reviewer 3 Report

In this case study, the authors depict an unusual instance of Whipple disease affecting the spinal cord in a 14-year-old patient with systemic lupus erythematosus (SLE) undergoing immunosuppressive therapy. The rarity of Whipple disease in conjunction with spinal cord involvement makes this case study particularly intriguing. Please see my comments below:

1. There are very few cases documented in which WD has been observed to impact the spinal cord (PMID 15804244). Are there any similarities noted among these cases? Specifically, have these patients undergone comparable types of immunosuppressive treatment?

2. Please include information about the treatment the patient received for systemic lupus erythematosus (SLE) before the diagnosis of Whipple disease (WD). While I acknowledge the mention of low-dose steroids, please provide additional details, if available, such as the specific steroid name and dosage.

3. The authors mention an elevated ANA titer. Could you kindly specify the exact titre measured?

4.Was there evidence of monoclonal gammopathies in the patient?

5. Please cite the documented cases of Whipple disease (WD) and systemic lupus erythematosus (SLE) found in the literature, as presented in the case studies (PMID: 31096758 and 6198977).

Minor:

Line 94, please shift ")" after Bartonella instead of after therapy.

Line 243, please write "Authors" in lower-case

Author Response

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Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

I would like to thank the authors for detailed revision. I have no further comments and would recommend the acceptance. 

minor edits