Pitfall: Pemphigus herpeticatus should not be ...

Journal of Dermatological Treatment. 2010; 21:311–313

CASE REPORT

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Pitfall: Pemphigus herpeticatus should not be confounded with resistant pemphigus vulgaris

LAURENCE FELDMEYER, RALPH M. TRÜEB, LARS E. FRENCH & JÜRG HAFNER Department of Dermatology, University Hospital of Zurich, Switzerland

Abstract Human herpes simplex virus (HSV) infections are well-recognized complications of various dermatoses and have also been reported in both hereditary and acquired acantholytic diseases such as dyskeratosis follicularis (Darier’s disease), familial benign chronic pemphigus (Hailey-Hailey disease) and pemphigus vulgaris, respectively. The possibility of HSV infection should be considered in pemphigus patients with lack of improvement under adequate immunosuppressive therapy. This has therapeutic implications, since antiviral treatment instantly clears the HSV-induced chronic erosions. Instead, augmentation or change of immune suppression for assumed refractory pemphigus will obviously not improve the condition. We suggest using the diagnostic term pemphigus herpeticatus to describe HSV-superinfected pemphigus, alluding to the pathophysiologic analogies with eczema herpeticatum.

Key words: eczema herpeticatum, herpes simplex virus, pemphigus foliaceus, pemphigus herpeticatus, pemphigus vulgaris

Introduction Human herpes simplex virus (HSV) infections are well-recognized complications of various dermatoses. The possibility of HSV infection should be considered in pemphigus patients with lack of improvement under adequate immunosuppressive therapy. This has therapeutic implications, since antiviral treatment instantly clears the HSV-induced chronic erosions. Instead, augmentation or change of immune suppression for assumed refractory pemphigus will obviously not improve the condition. We suggest using the diagnostic term pemphigus herpeticatus to describe HSV-superinfected pemphigus, alluding to the pathophysiologic analogies with eczema herpeticatum. We report on three cases of HSV superinfection of pemphigus vulgaris (PV) and pemphigus foliaceus (PF). In two instances, the diagnosis was delayed by more than 2 months; only in the third case was suspicion high enough to promptly establish the diagnosis of HSV superinfection. The apparently

refractory skin lesions improve rapidly as soon as antiviral therapy is installed.

Case reports Patient 1 A 42-year-old man was referred with a 3-month history of progressive, erosive and scaly skin lesions of the head and trunk. Histology and direct immunofluorescence (DIF) studies confirmed the suspected clinical diagnosis of PF. Serum antibodies to desmoglein 1 were detectable by ELISA. Remission was established with oral prednisone (initial dose 0.5 mg/kg daily), azathioprine (1.25 mg/kg daily) and topical corticosteroids. Prednisone was tapered and the patient remained in remission with azathioprine monotherapy, while the topical corticosteroids were switched to topical tacrolimus.

Correspondence: Laurence Feldmeyer, Department of Dermatology, University Hospital of Zurich, CH-8091 Zurich, Switzerland. Fax: 41 33 255 89 88. E-mail: [email protected] (Received 10 June 2009; accepted 5 August 2009) ISSN 0954-6634 print/ISSN 1471-1753 online Ó 2010 Informa UK, Ltd. DOI: 10.3109/09546630903287452


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Later, apparent recurrence occurred with skin lesions resembling the clinical presentation of Kaposi’s varicelliform eruption or eczema herpeticatum. Virological swabs were obtained, which confirmed the presence of HSV1 by direct immunostaining (MicroTrakÒ HSV Culture Identification Kit; Trinity Biotech, Product Code: 8H349UL). The patient was started on oral valaciclovir 500 mg twice daily for 10 days and topical tacrolimus was stopped. Under this regimen, the skin lesions healed completely within 10 days. Further treatment of PF was continued with azathioprine monotherapy (1.25 mg/kg daily) and weak topical corticosteroids. Two weeks later, new erosions arose on the neck and right cheek. The presence of HSV1 was again confirmed by direct immunostaining and culture. A new course with oral valaciclovir was once more successfully performed for 10 days.

culture remained negative. The patient was put on oral valaciclovir (500 mg twice daily for 10 days), with almost complete remission. A further course remained uneventful under medication with prednisone (0.2 mg/kg daily), azathioprine (1.25 mg/kg daily) and cyclosporine (2.5 mg/kg daily). More recently, the patient was successfully switched to a combination of 5 mg oral prednisone, 100 mg azathioprine, and 100 mg dapsone, and currently remains in full remission (Figure 1: right).

Patient 3

A 71-year-old man had suffered from PV for 6 years that was well controlled with oral prednisone 0.15–1 mg/kg daily and azathioprine 1.25 mg/kg daily. At that time, he additionally developed refractory vegetating skin lesions, especially of the centrofacial area (Figure 1: left). Therefore, systemic immunosuppression was rotated from azathioprine to mycophenolate mofetil, cyclosporine, cyclophosphamide, and eventually cyclosporine in combination with intravenous immunoglobulin. The latter regimen finally showed a good effect on the lesions on the head and trunk, but no improvement of the vegetating lesions around the nose. A nasal smear was positive for HSV2 by direct immunostaining, but the virus

A 58-year-old man was recently diagnosed as suffering from PF on the trunk with confluent, oozing and scaly lesions, confirmed by histology, DIF and ELISA to desmoglein 1. The PF was treated with prednisone (2 mg/kg) and azathioprine (1.8 mg/kg) and the skin lesions stabilized quickly at first so that prednisone could be tapered by 0.3 mg/kg per week. However, 3 weeks later, a relapse with more generalized erosions at the head, trunk and upper extremities occurred, and the immunosuppression was adapted. Prednisone was augmented to 2 mg/kg daily, azathioprine was switched to mycophenolate mofetil 2 g daily and topical corticosteroids were added to the local therapy. Under this regimen, the generalized skin lesions improved again rapidly, with the exception of some confluent oozing erosions on the neck (Figure 2: left). A superinfection by HSV was suspected and the swabs proved to be positive for HSV1 by direct immunostaining, polymerase chain reaction (PCR) and culture. A course of valaciclovir 250 mg twice daily for 10 days was introduced and the persistent skin lesions around the neck cleared completely (Figure 2: right).

Figure 1. Patient 2 before (left) and after (right) valaciclovir therapy.

Figure 2. Patient 3 before (left) and after (right) valaciclovir therapy.

Patient 2

Pemphigus herpeticatus


Discussion HSV superinfection of PV or PF has some common traits with HSV superinfection in atopic dermatitis (eczema herpeticatum). In both conditions, an attenuated immune response and an impaired skin barrier constitute two underlying factors that may favor the occurrence of HSV superinfection. Patients with PV or PF are commonly under systemic and/or local immune suppression and have a lesional skin surface. Therefore, we suggest using the diagnostic term pemphigus herpeticatus for HSV-superinfected PV or PF in analogy with the well-established diagnostic concept of eczema herpeticatum. The diagnostic challenge of viral superinfection in PV and PF, particularly with HSV, has been recognized and published in at least six instances since 1977 (1–6). The risk of atypical manifestations of herpes infections, including erythema exsudativum multiforme (EEM)-like presentations, is occasionally stressed in the literature (7). When the treating clinicians are not aware of the possibility of pemphigus herpeticatus, the oozing erosions may be confused with refractory pemphigus and can mislead them to increase the immunosuppression instead of testing for HSV and treating accordingly. The timely recognition of pemphigus herpeticatus helps to avoid unnecessary changes of immunosuppressive

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treatment and to start an effective antiviral treatment without delay. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. References 1. Suter L, Bilek I, Vakilzadeh F. [Kaposi’s herpes eczema in pemphigus foliaceus.] Z. Hautkr. 1977;52:151–154. 2. Brown P, Taylor B. Herpes simplex infection associated with pemphigus vulgaris. Case report and literature review. J Am Acad Dermatol. 1989;21:1126–1128. 3. Schlupen EM, Wollenberg A, Hanel S, Stumpenhausen G, Volkenandt M. Detection of herpes simplex virus in exacerbated pemphigus vulgaris by polymerase chain reaction. Dermatology. 1996;192:312–316. 4. Takahashi I, Kobayashi TK, Suzuki H, Nakamura S, Tezuka F. Coexistence of pemphigus vulgaris and herpes simplex virus infection in oral mucosa diagnosed by cytology, immunohistochemistry, and polymerase chain reaction. Diagn Cytopathol. 1998;19:446–450. 5. Zouhair K, el Ouazzani T, Azzouzi S, Sqalli S, Lakhdar H. [Herpetic superinfection of pemphigus: 6 cases.] Ann Dermatol. Venereol. 1999;126:699–702. 6. Kalajian AH, Callen JP. Atypical herpes simplex infection masquerading as recalcitrant pemphigus vulgaris. Australas J Dermatol. 2007;48:242–247. 7. Wollina U, Gemmeke A. Herpes zoster-associated erythema multiforme. Journal of Dermatological Case Reports. 2009;3:11–13.