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 Table of Contents  
Year : 2022  |  Volume : 6  |  Issue : 2  |  Page : 154

Pemphigus herpetiformis with atypical features

Department of Dermatology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India

Date of Submission24-Feb-2021
Date of Decision20-Apr-2021
Date of Acceptance27-May-2021
Date of Web Publication26-Aug-2022

Correspondence Address:
Raghavendra Rao
Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/cdr.cdr_14_21

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Pemphigus herpetiformis (PH) is considered as an uncommon and mild variant of pemphigus. Here, we report the case of a 34-year-old woman who presented with intensely pruritic, annular crusted lesions with vesicles arranged in the periphery over the abdomen, back, and scalp. Cutaneous features were consistent with the clinical diagnosis of PH. However, she had certain unusual clinicoimmunopathological features. She also had oral erosions, which is a rare finding in this variant of pemphigus. The results of histopathological examination and enzyme-linked immunosorbent assay were also in line with the diagnosis of pemphigus vulgaris. She responded well to dapsone with significant objective and subjective improvement in 1-week follow-up.

Keywords: Desmoglein 1 and 3 enzyme-linked immunosorbent assay, pemphigus herpetiformis, suprabasal cleft

How to cite this article:
Arora S, Rao R. Pemphigus herpetiformis with atypical features. Clin Dermatol Rev 2022;6:154

How to cite this URL:
Arora S, Rao R. Pemphigus herpetiformis with atypical features. Clin Dermatol Rev [serial online] 2022 [cited 2023 Jan 30];6:154. Available from: https://www.cdriadvlkn.org/text.asp?2022/6/2/154/354743

  Introduction Top

Pemphigus herpetiformis (PH) is a rare, atypical variant of pemphigus.[1] It is generally considered as a mild disease with a benign course.[2] Skin lesions of PH are characterized clinically by pruritic, erythematous vesicular lesions that show a tendency for grouping, thus masquerading as dermatitis herpetiformis (DH).[3] Here, we report a case of PH with unusual features.

  Case Synopsis Top

A 34-year-old female presented with an itchy, blistering eruption of 6 months' duration. The lesions started initially as flaccid vesicles over the abdomen which evolved to form erosions. Over the next few weeks, she observed similar lesions on the back and the scalp. This was associated with intense itching; the blister eventually healed with hyperpigmentation in a weeks' time. She had deformity of the right leg due to poliomyelitis; general physical examination was otherwise unremarkable. She had been treated by her family physician with oral prednisolone (5 mg per day) for 2 months with partial improvement.

Cutaneous examination revealed crusted papules distributed over the trunk and scalp; some of these lesions were surrounded by vesicles in a “string of pearl” appearance [Figure 1] and [Figure 2]. Examination of the oral cavity revealed small erosions on the left buccal mucosa and right retro molar area. Nikolsky sign was negative. A provisional diagnosis of PH was considered, and she was investigated. Her routine biochemical and hematological parameters were within the normal limits. Tzanck smear of the fresh vesicle demonstrated presence of acantholytic cells. Histopathological examinations revealed suprabasal, intraepidermal blister composed of rounded acantholytic keratinocytes, neutrophils, and a few eosinophils [Figure 3]. Direct immunofluorescence microscopy (DIF) of the perilesional skin biopsy showed IgG and C3 staining on the surface of keratinocytes [Figure 4]. Indirect immunofluorescence (IIF) microscopy using normal human skin substrate (NHS) revealed circulating IgG class of antibodies in 1:100 titre. Enzyme-linked immunosorbent assay (ELISA) revealed high titer of IgG anti Desmoglein 1 (Dsg 1) antibodies (>200 RU/mL) and anti Dsg 3 titers (134 RU/mL). She was treated with dapsone 100 mg per day; at 1 week follow-up, she reported significant alleviation of her symptoms. Most the lesions have subsided with postinflammatory hyperpigmentation [Figure 5]; oral erosions also had healed completely. She was advised to continue dapsone.
Figure 1: Multiple vesicles on an erythematous base arranged in an annular fashion over the back

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Figure 2: Arciform arrangement of vesicles with central crusting

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Figure 3: Acantholysis and suprabasal cleft with neutrohilic and eosinophilic infiltrate H and E, ×100

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Figure 4: Intercellular staining of epidermis with IgG suggestive of Pemphigus

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Figure 5: Most of the lesions healed with post-inflammatory hyperpigmentation at 1 week follow-up

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  Case Discussion Top

PH is an uncommon type of pemphigus accounting for about 7% of all cases of pemphigus.[2] It was originally described by Jablonska et al. in a patient who presented with clinical features compatible with the diagnosis of DH but immunopathology revealed pemphigus-like pattern with intercellular staining (ICS) of the epidermis with IgG.[1] It usually presents in the fifth or sixth decades of life. Skin lesions of PH are characterized by the presence of erythematous, papulovesicle or bullae often showing tendency for grouping or annular configuration mimicking those of other autoimmune bullous diseases, especially DH, linear IgA dermatosis and IgA pemphigus.[3] Another hallmark of PH is the presence of severe pruritus. Lesions are predominantly distributed over the trunk and proximal extremities. In contrast to pemphigus vulgaris (PV), mucosal involvement is rare in PH and when present, tends to be mild and heals faster.[4] In a series of 15 patients, only four patients had occasional mucosal lesions.[2]

Histological feature is variable and may not be able to clinch the diagnosis of PH. Laws et al. observed eosinophilic spongiosis to be the most common feature followed by neutrophilic spongiosis and acantholysis in their series of eight patients.[5] The acantholysis may be localized either in suprabasal or subcorneal location. DIF microscopy clinches the diagnosis of PH; it uniformly demonstrates the ICS with IgG and C3 in the epidermis. Most cases show a pemphigus foliaceus (PF) type of DIF pattern with intercellular IgG and C3 staining in the superficial epidermis. Less frequently, these immunoreactants can be localized to the lower layers of the epidermis mimicking the typical PV pattern. IIF microscopy using monkey/guinea pig esophagus or human skin substrates shows ICS with IgG. By ELISA, reactivity is primarily directed against desmoglein1 (Dsg1) and less often against Dsg3, further implicating the predominant autoimmunity similar to PF rather than PV.[6] Unlike in PV, presence of circulating antibodies against Dsg3 in PH may not correlate with the mucosal lesions.[7] It is also not documented in the literature whether there is any correlation between the burden of circulating autoantibodies and the clinical activity of the disease in PH patients. Occasionally, patient's sera may fail to reveal antibodies against Dsg1 and 3. Tateishi et al. reported a case of PH with antibodies to Desmocollin 1 and with absence of reactivity to Dsg1 and 3.[8] Recently, a case of PH with antibodies to nondesmosomal sites and intracellular regions of Dsg 1 have been described in a patient where both anti-Dsg and anti-Dsc ELISA were negative [Table 1].[9]
Table 1: Summary of clinical, histopathological and direct immunofluorescence findings in various types of pemphigus and bullous pemphigoid

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Costa et al. recently proposed diagnostic criteria [Table 2].[10] Clinical phenotype in our patient was consistent with PH but histopathological and immunopathological features were suggestive of PV. Presence of autoantibodies to both major desmosomal proteins (Dsg 1 and Dsg3) is not common in PH. Ishii et al. demonstrated that 16 out of 20 PH patients in their series had only anti-Dsg 1 autoantibodies while the other 4 had antibodies to only Dsg 3. None of the patients in their study had autoantibodies against both Dsg 1 and 3.[11] Our patient had circulating antibodies to both Dsg 1 and 3; this type of antibody profile was documented in only one patient out of eight in a previous series.[5]
Table 2: Diagnostic criteria for pemphigus herpetiformis proposed by costa et al.

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Dapsone is considered the drug of choice for PH with most patients responding well to dapsone monotherapy (100–200 mg daily). A low dose systemic corticosteroids therapy may be added to patients who fails to respond to dapsone monotherapy.[6] Immunosuppressants such as azathioprine, cyclophosphamide, and mycophenolate mofetil are rarely required in the management of PH.[3]

  Conclusion Top

A diagnosis of PH has to be considered in a patient presenting with itchy, blistering eruption. Although the histopathology is often inconclusive, DIF microscopy often clinches the diagnosis. Advanced diagnostic tests such as ELISA and immunoblotting should be considered in every patient to identify the target antigen.

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.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Jablonska S, Chorzelski TP, Beutner EH, Chorzelska J. Herpetiform pemphigus, a variable pattern of pemphigus. Int J Dermatol 1975;14:353-9.  Back to cited text no. 1
Maciejowska E, Jablonska S, Chorzelski T. Is pemphigus herpetiformis an entity? Int J Dermatol 1987;26:571-7.  Back to cited text no. 2
Kasperkiewicz M, Kowalewski C, Jabłońska S. Pemphigus herpetiformis: from first description until now. J Am Acad Dermatol 2014;70:780-7.  Back to cited text no. 3
Mangold AR, Costello CM, Pittelkow MR, DiCaudo DJ. Concomitant pemphigus herpetiformis and sarcoidosis. JAAD Case Rep 2016;2:436-8.  Back to cited text no. 4
Laws PM, Heelan K, Al-Mohammedi F, Walsh S, Shear NH. Pemphigus herpetiformis: A case series and review of the literature. Int J Dermatol 2015;54:1014-22.  Back to cited text no. 5
Robinson ND, Hashimoto T, Amagai M, Chan LS. The new pemphigus variants. J Am Acad Dermatol 1999;40:649-71.  Back to cited text no. 6
Lebeau S, Müller R, Masouyé I, Hertl M, Borradori L. Pemphigus herpetiformis: Analysis of the autoantibody profile during the disease course with changes in the clinical phenotype. Clin Exp Dermatol 2010;35:366-72.  Back to cited text no. 7
Tateishi C, Tsuruta D, Nakanishi T, Uehara S, Kobayashi H, Ishii M, et al. Antidesmocollin-1 antibody-positive, antidesmoglein antibody-negative pemphigus herpetiformis. J Am Acad Dermatol 2010;63:e8-10.  Back to cited text no. 8
Ishiura N, Tamura-Nakano M, Okochi H, Tateishi C, Maki M, Shimoda Y, et al. Herpetiform pemphigus with characteristic transmission electron microscopic findings of various-sized ballooning vacuoles in keratinocytes without acantholysis. Br J Dermatol 2019;180:187-92.  Back to cited text no. 9
Costa LM, Cappel MA, Keeling JH. Clinical, pathologic, and immunologic features of pemphigus herpetiformis: a literature review and proposed diagnostic criteria. Int J Dermatol 2019;58:997-1007.  Back to cited text no. 10
Ishii K, Amagai M, Komai A, Ebihara T, Chorzelski TP, Jablonska S, et al. Desmoglein 1 and desmoglein 3 are the target autoantigens in herpetiform pemphigus. Arch Dermatol 1999;135:943-7.  Back to cited text no. 11


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

  [Table 1], [Table 2]


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