Relationship Between Pemphigus Vulgaris Severity and PCR-positive Herpes Simplex Virus

Authors

  • Sharon Baum Department of Dermatology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
  • Itai Atar
  • Dan Coster
  • Sara Dovrat
  • Michal Solomon
  • Eli Sprecher
  • Tal Zeeli
  • Aviv Barzilai

DOI:

https://doi.org/10.2340/actadv.v102.917

Keywords:

pemphigus vulgaris, herpes simplex, disease exacerbation, acyclovir

Abstract

Pemphigus vulgaris is a rare autoimmune skin disease. Although herpes simplex virus has been associated with autoimmune diseases, evidence regarding its association with pemphigus vulgaris exacerbations is scarce. This retrospective cohort study aimed to characterize the epidemiological and clinical features of patients with pemphigus vulgaris who were herpes simplex-positive, compared with those who were herpes simplex-negative, during disease onset. Of 62 patients with pemphigus vulgaris who underwent PCR testing for herpes simplex virus, 25 (40.3%) were positive, with a mean age of 56.1 ± 15.5 years; 35.5% were male. The herpes-positive group had significantly elevated levels of C-reactive protein, Pemphigus Disease Activity Index score, and shorter time to relapse. The time to remission, number of exacerbations per year, and remission status were non-significantly elevated in the herpes-positive group. Thus, routine testing lesions from patients with pemphigus for herpes simplex virus should be performed. If positive, antiviral treatment should be initiated; and preventive antiviral treatment should be considered in severe cases.

Downloads

Download data is not yet available.

References

Kridin K. Pemphigus group: overview, epidemiology, mortality, and comorbidities. Immunol Res 2018; 66: 255-270.

https://doi.org/10.1007/s12026-018-8986-7 DOI: https://doi.org/10.1007/s12026-018-8986-7

Kayani M, Aslam AM. Bullous pemphigoid and pemphigus vulgaris. BMJ 2017; 357.

https://doi.org/10.1136/bmj.j2169 DOI: https://doi.org/10.1136/bmj.j2169

Bystryn JC, Rudolph JL. Pemphigus. Lancet 2005; 366: 61-73.

https://doi.org/10.1016/S0140-6736(05)66829-8 DOI: https://doi.org/10.1016/S0140-6736(05)66829-8

Lever WF, Hashimoto K. The etiology and treatment of pemphigus and pemphigoid. J Invest Dermatol 1969; 53: 373-389.

https://doi.org/10.1038/jid.1969.165 DOI: https://doi.org/10.1038/jid.1969.165

Hammers CM, Stanley JR. Mechanisms of disease: pemphigus and bullous pemphigoid. Annu Rev Pathol 2016; 11: 175-197.

https://doi.org/10.1146/annurev-pathol-012615-044313 DOI: https://doi.org/10.1146/annurev-pathol-012615-044313

Stanley JR, Amagai M. Pemphigus, bullous impetigo, and the staphylococcal scalded-skin syndrome. N Engl J Med 2006; 355: 1800-1810.

https://doi.org/10.1056/NEJMra061111 DOI: https://doi.org/10.1056/NEJMra061111

Brenner S, Sasson A, Sharon O. Pemphigus and infections. Clin Dermatol 2002; 20: 114-118.

https://doi.org/10.1016/S0738-081X(01)00254-1 DOI: https://doi.org/10.1016/S0738-081X(01)00254-1

Ruocco E, Ruocco V, Lo Schiavo A, Brunetti G, Wolf R. Viruses and pemphigus: an intriguing never-ending story. Dermatology 2014; 229: 310-315.

https://doi.org/10.1159/000365845 DOI: https://doi.org/10.1159/000365845

Brandão ML, Fernandes NC, Batista DP, Santos N. Refractory pemphigus vulgaris associated with herpes infection: case report and review. Rev Inst Med Trop Sao Paulo 2011; 53: 113-117.

https://doi.org/10.1590/S0036-46652011000200010 DOI: https://doi.org/10.1590/S0036-46652011000200010

Armangue T, Moris G, Cantarín-Extremera V, Conde CE, Rostasy K, Erro ME, et al. Autoimmune post-herpes simplex encephalitis of adults and teenagers. Neurology 2015; 85: 1736-1743.

https://doi.org/10.1212/WNL.0000000000002125 DOI: https://doi.org/10.1212/WNL.0000000000002125

Mohammadi F, Khalili Z, Mahdi Marashi S, Ehsani A, Daneshpazhooh M, Teymoori-Rad M, et al. The potential roles of herpesvirus and cytomegalovirus in the exacerbation of pemphigus vulgaris. Dermatol Pract Concept 2018; 8: 262-271.

https://doi.org/10.5826/dpc.0804a03 DOI: https://doi.org/10.5826/dpc.0804a03

Machado AR da SR, La Serra L, Turatti A, Machado AM, Roselino AM. Herpes simplex virus 1 and cytomegalovirus are associated with pemphigus vulgaris but not with pemphigus foliaceus disease. Exp Dermatol 2017; 26: 966-968.

https://doi.org/10.1111/exd.13342 DOI: https://doi.org/10.1111/exd.13342

Grover S. Scoring systems in pemphigus. Ind J Dermatol 2011; 56: 145-149.

https://doi.org/10.4103/0019-5154.80403 DOI: https://doi.org/10.4103/0019-5154.80403

Murrell DF, Peña S, Joly P, Marinovic B, Hashimoto T, Diaz LA, et al. Diagnosis and management of pemphigus: recommendations of an international panel of experts. J Am Acad Dermatol 2020; 82: 575-585.

https://doi.org/10.1016/j.jaad.2018.02.021 DOI: https://doi.org/10.1016/j.jaad.2018.02.021

Murrell DF, Dick S, Ahmed AR, Amagai M, Barnadas MA, Borradori L, et al. Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus. J Am Acad Dermatol 2008; 58: 1043-1046.

https://doi.org/10.1016/j.jaad.2008.01.012 DOI: https://doi.org/10.1016/j.jaad.2008.01.012

Filén F, Strand A, Allard A, Blomberg J, Herrmann B. Duplex real-time polymerase chain reaction assay for detection and quantification of herpes simplex virus type 1 and herpes simplex virus type 2 in genital and cutaneous lesions. Sex Transm Dis 2004; 31: 331-336.

https://doi.org/10.1097/00007435-200406000-00002 DOI: https://doi.org/10.1097/00007435-200406000-00002

Centers for Disease Control and Prevention. Sexually transmitted infections treatement guidelines, 2021. Available from: https://www.cdc.gov/std/treatment-guidelines/herpes.htm.

Ercolini AM, Miller SD. The role of infections in autoimmune disease. Clin Exp Immunol 2009; 155: 1-15.

https://doi.org/10.1111/j.1365-2249.2008.03834.x DOI: https://doi.org/10.1111/j.1365-2249.2008.03834.x

Vega-Memíje ME, García-Vázquez FJ, Cuevas-González JC, Rodríguez-Lobato E, Aguilar-Urbano MA. Is there a causal relationship between HSV-1 and pemphigus vulgaris? Springerplus 2015; 4: 811.

https://doi.org/10.1186/s40064-015-1414-8 DOI: https://doi.org/10.1186/s40064-015-1414-8

Lucchese A. From HSV infection to erythema multiforme through autoimmune crossreactivity. Autoimmun Rev 2018; 17: 576-581.

https://doi.org/10.1016/j.autrev.2017.12.009 DOI: https://doi.org/10.1016/j.autrev.2017.12.009

Esmaili N, Hallaji Z, Abedini R, Soori T, Mortazavi H, Chams-Davatchi C. Pemphigus vulgaris and herpesviruses: Is there any relationship? Int J Dermatol 2010; 49: 1261-1265.

https://doi.org/10.1111/j.1365-4632.2010.04515.x DOI: https://doi.org/10.1111/j.1365-4632.2010.04515.x

Konda D, Chandrashekar L, Dhodapkar R, Ganesh RN, Thappa DM. Clinical markers of herpes simplex virus infection in patients with pemphigus vulgaris. J Am Acad Dermatol (accessed 2019 Jun 10). Available from: https://doi.org/10.1016/j.jaad.2019.06.002.

https://doi.org/10.1016/j.jaad.2019.06.002 DOI: https://doi.org/10.1016/j.jaad.2019.06.002

Kridin K, Zelber-Sagi S, Bergman R. Pemphigus vulgaris and pemphigus foliaceus: differences in epidemiology and mortality. Acta Derm Venereol 2017; 97: 1095-1099.

https://doi.org/10.2340/00015555-2706 DOI: https://doi.org/10.2340/00015555-2706

Kurata M, Mizukawa Y, Aoyama Y, Shiohara T. Herpes simplex virus reactivation as a trigger of mucous lesions in pemphigus vulgaris. Br J Dermatol 2014; 171: 554-560.

https://doi.org/10.1111/bjd.12961 DOI: https://doi.org/10.1111/bjd.12961

Sacks SL, Griffiths PD, Corey L, Cohen C, Cunningham A, Dusheiko GM, et al. HSV shedding. Antiviral Res 2004; 63: S19-S26.

https://doi.org/10.1016/j.antiviral.2004.06.004 DOI: https://doi.org/10.1016/j.antiviral.2004.06.004

Miller CS, Danaher RJ. Asymptomatic shedding of herpes simplex virus (HSV) in the oral cavity. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008; 105: 43-50.

https://doi.org/10.1016/j.tripleo.2007.06.011 DOI: https://doi.org/10.1016/j.tripleo.2007.06.011

Mertz GJ. Asymptomatic shedding of herpes simplex virus 1 and 2: implications for prevention of transmission. J Infect Dis 2008; 198: 1098-1100.

https://doi.org/10.1086/591914 DOI: https://doi.org/10.1086/591914

Chiu HY, Chang CY, Hsiao CH, Wang LF. Concurrent cytomegalovirus and herpes simplex virus infection in pemphigus vulgaris treated with rituximab and prednisolone. Acta Derm Venereol 2013; 93: 200-201.

https://doi.org/10.2340/00015555-1429 DOI: https://doi.org/10.2340/00015555-1429

Atzmony L, Hodak E, Leshem YA, Rosenbaum O, Gdalevich M, Anhalt GJ, et al. The role of adjuvant therapy in pemphigus: a systematic review and meta-analysis. J Am Acad Dermatol 2015; 73: 264-271.

https://doi.org/10.1016/j.jaad.2015.04.038 DOI: https://doi.org/10.1016/j.jaad.2015.04.038

Didona D, Maglie R, Eming R, Hertl M. Pemphigus: current and future therapeutic strategies. Front Immunol 2019; 10: 1418.

https://doi.org/10.3389/fimmu.2019.01418 DOI: https://doi.org/10.3389/fimmu.2019.01418

Joly P, Maho-Vaillant M, Prost-Squarcioni C, Hebert V, Houivet E, Calbo S, et al. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial. Lancet 2017; 389: 2031-2040.

https://doi.org/10.1016/S0140-6736(17)30070-3 DOI: https://doi.org/10.1016/S0140-6736(17)30070-3

Kumar S, De D, Handa S, Ratho RK, Bhandari S, Pal A, et al. Identification of factors associated with treatment refractoriness of oral lesions in pemphigus vulgaris. Br J Dermatol 2017; 177: 1583-1589.

https://doi.org/10.1111/bjd.15658 DOI: https://doi.org/10.1111/bjd.15658

Kalra A, Ratho RK, Kaur I, Kumar B. Role of herpes simplex and cytomegalo viruses in recalcitrant oral lesions of pemphigus vulgaris. Int J Dermatol 2005; 44: 259-260.

https://doi.org/10.1111/j.1365-4632.2004.02370.x DOI: https://doi.org/10.1111/j.1365-4632.2004.02370.x

Published

2022-05-04

How to Cite

Baum, S., Atar, I., Coster, D., Dovrat, S., Solomon, M., Sprecher, E., … Barzilai, A. (2022). Relationship Between Pemphigus Vulgaris Severity and PCR-positive Herpes Simplex Virus. Acta Dermato-Venereologica, 102, adv00703. https://doi.org/10.2340/actadv.v102.917