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Year : 2019  |  Volume : 10  |  Issue : 3  |  Page : 154-157

Herpes simplex virus: A seed or sequelae to pemphigus?

Department of Oral and Maxillofacial Pathology, DA Pandu Memorial RV Dental College and Hospital, Bengaluru, Karnataka, India

Date of Submission24-Apr-2019
Date of Acceptance20-Jun-2019
Date of Web Publication15-Oct-2019

Correspondence Address:
Dr. Sarita Yanduri
Department of Oral and Maxillofacial Pathology, DA Pandu Memorial RV Dental College and Hospital, Bengaluru, CA 37, JP Nagar 1st Phase, Bengaluru - 560 078, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/srmjrds.srmjrds_33_19

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Pemphigus vulgaris is a vesiculobullous lesion in which autoantibodies are produced against desmoglein-3 antigens. Despite having an autoimmune etiology, herpes simplex virus (HSV) is found to be an additional aggravating factor for this disease. Sometimes, there can be a coexistence between the two entities. Here, a unique case of a 65-year-old female patient who presented with the chief complaint of ulcers in the oral cavity for the past 2–3 months is discussed. Histopathologic and immunofluorescence investigations were suggestive of pemphigus, but the cytopathologic smears manifested characteristics indicative of HSV infection. The existence of a viral infection with the known case of pemphigus poses a potential difficulty in the classical treatment of the latter. This case report throws light on the interesting coexistence of these two disease processes, thus highlighting the pathogenesis and treatment plan which may have to be considered in such controversial cases.

Keywords: Herpes simplex virus, oral, pemphigus

How to cite this article:
Yanduri S, Gokuldas A, Kumar B V, Suma S, Madhura M G. Herpes simplex virus: A seed or sequelae to pemphigus?. SRM J Res Dent Sci 2019;10:154-7

How to cite this URL:
Yanduri S, Gokuldas A, Kumar B V, Suma S, Madhura M G. Herpes simplex virus: A seed or sequelae to pemphigus?. SRM J Res Dent Sci [serial online] 2019 [cited 2022 Jul 5];10:154-7. Available from:

  Introduction Top

Pemphigus vulgaris (PV) is an autoimmune disorder in which autoantibodies are directed against desmoglein-3 antigens. It is an intraepithelial blistering disease and affects the skin and mucous membranes. The destruction of keratinocytes leads to the formation of vesicles or bullae just above the basal layer, causing a suprabasilar split.[1],[2]

Herpes simplex virus (HSV) is a DNA virus that can infect and cause fever and cutaneous and intraoral vesicles in humans. The viral-induced keratinocytes also undergo changes and are known as “Tzanck” cells as in pemphigus, but vary in their microscopic appearance.[3]

The present case is unique as there is an interesting coexistence between these two entities which otherwise usually occur separately and are different clinically and histopathologically.

  Case Report Top

A 65-year-old female patient visited the Department of Oral Medicine and Radiology of D. A. Pandu Memorial R. V Dental College and Hospital with the chief complaint of ulcers in the oral cavity for the past 2–3 months. She reported a history of fluid-filled vesicles on the buccal mucosa that ruptured within a few hours to form ulcers. These were associated with pain and burning sensation which had aggravated with spicy food. Topical steroids (details not known) were applied as suggested by a private practitioner but with no relief. The ulcers had progressed to involve the labial mucosa, floor of the mouth, and the soft palate [Figure 1].
Figure 1: Labial and buccal mucosa presented with ulcers

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On enquiry, she had genital lesions, with pain and itching, and a history of weight loss. She was on insulin for diabetes for 10 years and also on medication for hypertension (details not known) for 5 years.

On cutaneous examination, multiple intact vesicles and shallow ulcers were noted in the lower back region. On intraoral examination, there was extensive sloughing of the labial and buccal mucosa, palate, dorsal aspect of the tongue, and floor of the mouth. The lesions were tender on palpation and elicited a positive Nikolsky's sign.

Based on the patient's chief complaint and the clinical findings, a provisional diagnosis of PV and a differential diagnosis of bullous pemphigoid and mucous membrane pemphigoid were arrived at.

Cytological smears were taken from the lower labial mucosa, buccal mucosa, and the tongue which revealed many “Tzanck cells,” exhibiting nuclear clearing and ballooning degeneration. A few of the Tzanck cells showed viral-induced changes such as multinucleation, margination of chromatin, and molding of nuclei, suggestive of herpetic infection [Figure 2].
Figure 2: The cytological smear revealing cells with multinucleation, molding of nuclei, and margination of chromatin (H and E, ×40)

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An incisional biopsy specimen was taken from the right buccal mucosa and was sent for routine histopathological and immunofluorescence examination. The sections stained with hematoxylin and eosin revealed a suprabasilar split. Many acantholytic or Tzanck cells were also present suggestive of PV [Figure 3].
Figure 3: The histopathologic section revealing suprabasilar split with Tzanck cells (H and E, ×10)

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A direct immunofluorescence examination of the oral mucosa done at a private laboratory revealed that the epithelium was positive for intercellular deposits of IgG and C3c with the characteristic “fishnet pattern” of binding of immunoglobins in the intercellular spaces [Figure 4]. This had confirmed the diagnosis of PV.
Figure 4: Direct immunofluorescence of oral epithelium showing characteristic fishnet pattern

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On clinicopathological correlation and in view of histopathological and cytopathological reports, a final diagnosis of PV superimposed with herpetic infection was made. The patient was referred to the dermatopathology department of a general medical hospital in view of her medical status, where she was put on systemic corticosteroid therapy.

  Discussion Top

Pemphigus (derived from the Greek word “blister”) is a group of bullous diseases of autoimmune etiology which are characterized by the loss of cell-to-cell adhesion within the epidermis and/or mucosal surfaces. The immunological basis is very well established, with the main pathogenesis being the presence of autoantibodies targeted against desmoglein 1 and 3, the two components of the desmosomal apparatus.[4]

However, there is a lot of speculation regarding the triggering factors of this debilitating illness, with suggestions being made regarding interactions between endogenous (genetic predisposition) and exogenous factors.[5] The latter include ultraviolet radiation, X-rays, drugs, neoplasm, and emotional stress to name a few, but it is interesting to note that infectious agents such as HSV have also been implicated.[4],[5]

The present case report is an interesting example, where there is evidence of coexistence of the two disease processes that are pemphigus and HSV infection. When such a situation arises, it is difficult to assess whether the HSV infection is a triggering factor or it has developed as a consequence of the autoimmune disease.

Krain was the first to report this association between HSV and pemphigus when two out of 59 cases of pemphigus were antedated by severe HSV infection.[6] Brandao described several ways in which infectious agents can trigger PV.[5] They can generate an immune response in genetically susceptible individuals, producing an excess of interleukins (ILs) and interferons.[5],[7] High levels of interferon gamma induce the expression of HLA type 2 in the membranes of keratinocytes, making the structural site of PV antigen immunologically active. It was suggested that chronic viral infections may also generate an excessive production of IL-4 and IL-10 which can shift the TH1 response to a TH2 type and thus increase the antibody production. They can also directly infect T and B lymphocytes, contributing to the production of autoreactive B lymphocytes and autoimmune antibodies. When infected, the keratinocytes can pass through structural changes which favor the exposure of antigens.[5]

Other than being a triggering factor, the HSV infection may be a secondary infection in a person suffering from PV. It is important to observe that most PV patients when treated with immunosuppressive therapy are highly prone to oppurtunistic infections by viruses.[5] However, in the present case, the patient was not on any prior immunosuppressive medication, and hence, the trigger may perhaps be pointed to a preceding HSV infection. HSV in PV patients is also reported to have no mutual correlation.[8]

The coexistence of these two diseases comes with several complications. Studies by Grunwald et al. have revealed that in such cases, the oral lesions were refractory to treatment by corticosteroids, and only the use of a combination of antiviral drugs such as acyclovir and corticosteroids was able to provide relief to the patients.[9]

Although these two entities have different etiologies and clinical features, both are characterized by acantholysis and thus can be diagnosed by the Tzanck test. The pattern of acantholysis is, however, different in both the cases. In pemphigus, it is primary in nature due to the direct injury to the desmosomes, with the cells exhibiting ballooning degeneration and hyperchromatic staining of the nucleus. The viral-induced Tzanck cells, in addition, may show multinucleation, molding of nuclei, and margination of chromatin, features not seen in pemphigus. This type of acantholysis is considered secondary in nature.[10]

In the present case, although pemphigus was confirmed by histopathology and immunofluorescence, the simultaneous cytology report revealed the presence of a coexisting herpetic infection. This is a case wherein a chance diagnosis of coexistence of the two diseases was made by cytology and biopsy. Therefore, we suggest that, especially in lesions of PV cases refractory to treatment, secondary HSV infection must be considered and laboratory diagnosis has to be carried out with the help of not only cytological smears, but sometimes also by polymerase chain reaction, viral isolation, and immunohistochemistry.

  Conclusion Top

This report highlights the coexistence between PV and HSV infection. It is noteworthy that in such coexistences, there may be alterations in the clinical course, cytological features, treatment modality, and follow-up, as compared to PV without HSV infection.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Baroni A, Lanza A, Cirillo N, Brunetti G, Ruocco E, Ruocco V. Vesicular and bullous disorders: Pemphigus. Dermatol Clin 2007;25:597-603.  Back to cited text no. 1
Tamgadge S, Tamgadge A, Bhatt DM, Bhalerao S, Pereira T. Pemphigus vulgaris. Contemp Clin Dent 2011;2:134-7.  Back to cited text no. 2
[PUBMED]  [Full text]  
Gupta LK, Singhi MK. Tzanck smear: A useful diagnostic tool. Indian J Dermatol Venereol Leprol 2005;71:295-9.  Back to cited text no. 3
[PUBMED]  [Full text]  
Sagi L, Sherer Y, Trau H, Shoenfeld Y. Pemphigus and infectious agents. Autoimmun Rev 2008;8:33-5.  Back to cited text no. 4
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;53:113-7.  Back to cited text no. 5
Krain LS. Pemphigus: Epidemiologic and survival characteristics of 59 patients, 1955-1973. Arch Dermatol 1974;110:862-5.  Back to cited text no. 6
Iraji F, Faghihi G, Siadat AH. The efficacy of acyclovir in treatment of the pemphigus vulgaris. J Res Med Sci 2013;18:976-8.  Back to cited text no. 7
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.  Back to cited text no. 8
Grunwald MH, Katz I, Friedman-Birnbaum R. Association of pemphigus vulgaris and herpes simplex virus infection. Int J Dermatol 1986;25:392-3.  Back to cited text no. 9
Seshadri D, Kumaran MS, Kanwar AJ. Acantholysis revisited: Back to basics. Indian J Dermatol Venereol Leprol 2013;79:120-6.  Back to cited text no. 10
[PUBMED]  [Full text]  


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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