Submited on: 11 Dec 2012 12:16:16 PM GMT
Published on: 11 Dec 2012 01:42:20 PM GMT

  • What are the main claims of the paper and how important are they?

    See below

  • Are these claims novel? If not, please specify papers that weaken the claims to the originality of this one.

    See below

  • Are the claims properly placed in the context of the previous literature?

    See below

  • Do the results support the claims? If not, what other evidence is required?

    See below

  • If a protocol is provided, for example for a randomized controlled trial, are there any important deviations from it? If so, have the authors explained adequately why the deviations occurred?

    See below

  • Is the methodology valid? Does the paper offer enough details of its methodology that its experiments or its analyses could be reproduced?

    See below

  • Would any other experiments or additional information improve the paper? How much better would the paper be if this extra work was done, and how difficult would such work be to do, or to provide?

    See below

  • Is this paper outstanding in its discipline? (For example, would you like to see this work presented in a seminar at your hospital or university? Do you feel these results need to be incorporated in your next general lecture on the subject?) If yes, what makes it outstanding? If not, why not?

    See below

  • Other Comments:

    This is a highly interesting case report and worth publishing as it directly concerns the treatment of a difficult to diagnose and potentially dangerous complication of Darier’s disease.

    General remark. The case reports are too extensive and can be summarized. The discussion should be more to the point. The lengthy explanation of what DD is could be skipped entirely.

    You should really focus on HSV infection in DD and the importance of the smear and the antiviral treatment.

    Furthermore, there are a lot of wording and phrasing problems.



    The Tzanck test is a diagnostic test but cannot be used to determine the degree of infections. Please rectify

    How can you be sure that the infection was HSV-1. As far as I have read you did not perform IHC staining nor PCR to differentiate with VZV and HSV2? Please clarify

    The second sentence has nothing to do with “methods” please change


    Usually antiviral treatment offers solace of the viral infection after 1 week. So how can you incriminate a positive effect of antiviral treatment on the course of DD after three months.? Please clarify.



    Last sentence:

    Again, you say that you can follow the severity with a Tzanck test. Please reword as this is not true.


    Case 1:

    In the Tzanck smear one is not able to detect follicular keratinocytes as the scraping of cellular material is not going deep enough?  Please explain

    NB UVB treatment for DD?? Especially infected with HSV?? It is usually considered as an absolute contraindication for DD. Please explain.

    Why was the HSV serologic status regularly checked. It is well known that the evolution of the IgG level does not reflect clinical activity. Please explain?

    Case 2:

    After a 5 day antiviral cure, there was still signs of HSV infection on the Smear.?? Was antiviral resistance tested.? Please explain.


    References are adequate

    Pictures are of good quality but 15 images are too much to illustrate the purpose of the paper

  • Competing interests:
  • Invited by the author to review this article? :
  • Have you previously published on this or a similar topic?:
  • References:

    See references of the article

  • Experience and credentials in the specific area of science:
  • How to cite:  Nikkels A .Considerable Remission after Continuous Oral Antiviral Therapy in Darier's Disease: Two Sisters[Review of the article 'Considerable Remission after Continuous Oral Antiviral Therapy in Darier's Disease: Two Sisters ' by Hsiao L].WebmedCentral 2013;4(1):WMCRW002427
1 2 3 4 5 6 7 8 9
Report abuse
Dear Professor Nikkels: Thank you very much for reviewing my article about Darier’s Disease. I have also learned a great deal from your papers on HSV infection. Because the HSV is DNA virus and is replicated and assembled in the nucleus, viral replication results in cytopathic changes in the cells. “Nuclei have ground glass appearance due to accumulation of viral particles, which causes peripheral margination of chromatin” (). This observation is consistent with my opinion that the cytologic changes may reflect the severity of the HSV infection. I do not have the equipment to do IHC or PCR, so I did not specify whether the infection was HSV type 1 or 2. The antiviral agents used are effective for both types. The differential diagnosis with herpes zoster was made because the lesions were extensive, symmetrical, and bilateral. Treatment guidelines for primary and recurrent orolabial and genital HSV infections are established; however, treatment options for atypical cutaneous HSV infections, traumatic herpes, and eczema herpeticum are not firmly established and should be monitored using complementary viral identification techniques (Nikkels AF, Pierard GE. Treatment of muco-cutaneous presentation of herpes simplex virus infections. Am J Clin Dermatol 2002;3(7):475-487). In my case, the presence of the viral cytopathic changes detected using the QTT helped in deciding the necessity of continuous antiviral therapy. Compared with previous treatment without any improvement for nearly 10 years, the patients were happy with the improvement 3 months after it had been initiated. As the sample materials, including the epidermal sheet and vesicular content, are removed, cytologic changes in the follicular epithelium and dermis were seen. The case reported in DermAtlas demonstrated the changes in the follicular epithelium better. There is limitation of tissue removed by the QTT, but is not limited only in epidermis. Please find more information about this case, which is available at: . Ultraviolet B (UVB) was effective in treating a patient with psoriasis and refractory Hailey-Hailey disease (HHD) (Hayakawa K, Shiohara T. Coexistence of psoriasis and familial benign chronic pemphigus: efficacy of ultraviolet B treatment. Br J Dermatol 1999;140(2):374-375). The clinical and histological features of DD overlap with those of HHD. Because phototherapy is contraindicated for DD, I checked carefully on whether there was deterioration of the symptoms. The patients claimed that narrow-band UVB (NBUVB) therapy decreased itching, so it was continued. Hamada reported that another patient with refractory HHD was treated by NBUVB successfully (Hamada T, Umemura H, Aoyama Y, Iwatsuki K. Successful therapeutic use of targeted narrow-band ultraviolet B therapy for refractory Hailey-Hailey disease. Acta Derm Venereol 2012;93(1):110-111. doi: 10.2340/00015555-1390). There are reports of drug resistance after long-term use of antiviral agents. The symptoms and signs gradually subsided whenever acyclovir or valacyclovir was prescribed. Because the antiviral therapy was clinically effective, a drug resistance test was not done. Sincerely yours, Lily Hsiao, MD
Responded by Dr. Lily Hsiao on 03 Feb 2013 12:30:08 AM