A Review of Atypical Cutaneous Histological Manifestations of Herpes Zoster

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript reviews the histopathology of varicella-zoster virus (VZV) herpes zoster lesions that are atypical compared the more common histological presentations of this disease.

The importance of this paper is based upon the problems associated with appropriate diagnosis of these atypical manifestations of herpes zoster.

The authors have conducted an extensive literature review of papers describing unusual histological features of herpes zoster.

The article appropriately initially describes and shows the more typical histological aspects of herpes zoster skin lesions (Figure 1). The paper then goes on to describe and illustrate the histopathology of more atypical manifestations of herpes zoster associated folliculitis, pseudolymphoma, syringitis, and verrucous lesions. These unusual histologic features of herpes zoster are generally seen in immunosuppressed patients, such as AIDS patients.

Confirming a diagnosis of herpes zoster based upon these histological features is not sufficient. As pointed out by the authors, PCR and immunohistochemical approaches are needed to confirm VZV infection.   

The manuscript is well-written. The histological presentation of these atypical VZV infections is adequately discussed and shown in the figures.  

Author Response

Comments n'1: 

This manuscript reviews the histopathology of varicella-zoster virus (VZV) herpes zoster lesions that are atypical compared the more common histological presentations of this disease.

The importance of this paper is based upon the problems associated with appropriate diagnosis of these atypical manifestations of herpes zoster.

The authors have conducted an extensive literature review of papers describing unusual histological features of herpes zoster.

The article appropriately initially describes and shows the more typical histological aspects of herpes zoster skin lesions (Figure 1). The paper then goes on to describe and illustrate the histopathology of more atypical manifestations of herpes zoster associated folliculitis, pseudolymphoma, syringitis, and verrucous lesions. These unusual histologic features of herpes zoster are generally seen in immunosuppressed patients, such as AIDS patients.

Confirming a diagnosis of herpes zoster based upon these histological features is not sufficient. As pointed out by the authors, PCR and immunohistochemical approaches are needed to confirm VZV infection.   

The manuscript is well-written. The histological presentation of these atypical VZV infections is adequately discussed and shown in the figures.  

Answer n'1: Thank you very much for this wonderful words.

Reviewer 2 Report

Comments and Suggestions for Authors

This Perspective describes atypical herpes zoster manifestations on skin.  The report is well written with good illustrations.  The report will be of interest to many readers of this journal.  See comments below about one error and two suggested new references.

1.  Error in manuscript (lines 131-132).

Herpes zoster causes vasculitis in certain locations but not in the temporal arteries.  Therefore, giant cell arteritis is not caused by HZ.  See reference 31 for list of articles that disproved original paper.  Remove the 3 words (giant cell arteritis) from the article.  Here is a suggested replacement: “linking VZV reactivation to cerebral vasculitis and stroke, the classic example being herpes zoster ophthalmicus followed by ipsilateral cerebral artery infarction and contralateral hemiparesis.

The next sentence about small vessel vasculitis is acceptable (lines 133-135).

2.  Line 170.

Failure to cite an interesting HZ paper.  The authors do not cite a similar report to their report, which describes odd cutaneous features of HZ.  Please cite this report and describe what the report says in a new section of manuscript.

            See report by J. Kroth, Journal of Dermatology, “Isotopic response, Kobner phenomenon and Renbok phenomenon after HZ.”  (volume 38, pages 1058-61, 2011).

3.  Line 170.

            The authors also should mention keloid formation after HZ.  See article by J. Wang and H. Shen.  Keloids after HZ, in the journal called Clinical, Cosmetic and Investigational Dermatology 16:2129-33, 2023. In this Reviewer’s clinic, keloids appear to occur after HZ more commonly in people of African descent than in people of Caucasian descent. Is there a racial difference in keloid formation?

4. References. Add 2 new references

Author Response

Comments 1: 

1. Error in manuscript (lines 131-132).

Herpes zoster causes vasculitis in certain locations but not in the temporal arteries.  Therefore, giant cell arteritis is not caused by HZ.  See reference 31 for list of articles that disproved original paper.  Remove the 3 words (giant cell arteritis) from the article.  Here is a suggested replacement: “linking VZV reactivation to cerebral vasculitis and stroke, the classic example being herpes zoster ophthalmicus followed by ipsilateral cerebral artery infarction and contralateral hemiparesis.

The next sentence about small vessel vasculitis is acceptable (lines 133-135).

Answer n'1: Dear Reviewer n'2, thank you very much for this useful tip. We corrected the sentence and, also, removed the three words "giant cell arteritis". Thank you very much.

Comments 2: 

2. Line 170.

Failure to cite an interesting HZ paper.  The authors do not cite a similar report to their report, which describes odd cutaneous features of HZ.  Please cite this report and describe what the report says in a new section of manuscript.

            See report by J. Kroth, Journal of Dermatology, “Isotopic response, Kobner phenomenon and Renbok phenomenon after HZ.”  (volume 38, pages 1058-61, 2011).

Answer n'2: Thank you very much. We have added this interesting paper and discussed it in a new paragraph.

Reviewer n'2: 

3. Line 170.

            The authors also should mention keloid formation after HZ.  See article by J. Wang and H. Shen.  Keloids after HZ, in the journal called Clinical, Cosmetic and Investigational Dermatology 16:2129-33, 2023. In this Reviewer’s clinic, keloids appear to occur after HZ more commonly in people of African descent than in people of Caucasian descent. Is there a racial difference in keloid formation?

Answer n'3: Dear Reviewer, thank you again. Unfortunately, we can't add this reference because we specifically say that the paper covers only the activa phase and not post-HZ. we will happy to add and discuss this paper in a future work. Thank you.