Immunome Research
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Pemphigus Herpetiformis with Only Positive Anti-Envoplakin Antibodies: A Case Report

Cristina Sousa^*, Manuel Campos, Jorge Lopes, Armando Baptista and Ana Oliveira ^*Correspondence: Cristina Sousa, Department of Dermatology, Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal, Tel: +351916568715, Email:

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Introduction

Pemphigus herpetiformis (PH), first described in 1975 by Jablonska et al, is a rare subtype of bullous autoimmune disease that associates clinical manifestations of dermatitis herpetiformis with immunological features of pemphigus [1]. The diagnosis is based on clinical, histopathological and direct immunofluorescence findings. PH exhibits IgG autoantibodies against desmoglein 1 in most of the cases, rarely IgG autoantibodies against desmoglein [2]. There are some cases with negative anti-desmoglein and positive anti-desmocollin antibodies [3-6].

Case Synopsis

A 48-years-old woman, previously healthy, presented with a 6- year history of pruritic lesions located mainly in the upper limbs and trunk. Physical examination revealed erythematous papules, some excoriated and translucent vesicles distributed over patient’s arms, trunk and neck. The mucous membranes were unaffected (Figures 1 and 2).

Figure 1. Erythematous papules and plaques on the face and neck.

Figure 2. Erythematous papules, some of them excoriated, on the upper limb.

A skin biopsy specimen revealed the presence of sub epidermal vesicles associated with necrosis of the epidermis and perivascular lymphocytic infiltrate in the papillary and reticular dermis (Figure 3). Serum indirect immunofluorescence (IIF) to human skin revealed IgG antikeratinocyte cell surface antibodies with titers 1/160 (normal<1/10). Enzyme-linked immunosorbent assay (ELISA) was negative for desmoglein (Dsg) 1, Dsg 2, bullous pemphigoid (BP) 180, BP230, desmocollin (Dsc) 1, Dsc 2, Dsc 3 and positive for envoplakin.

Figure 3. H&E 20x: Intraepidermal vesicle with necrosis of the underlying epidermis.

The positivity of the anti-envoplaquine antibody is often associated with paraneoplastic pemphigus, so a cancer screening was performed which was negative. Based on the clinical, histopathological and immunological findings, a PH with exclusive anti-envoplaquine antibodies was diagnosed.

Oral prednisolone (20 mg/day) and dapsone (50 mg/day) were introduced, with complete resolution of the lesions after 3 weeks, and then tapered off over 2 months without relapse. The patient remains in complete remission after 24 months of follow-up.

Discussion

Pemphigus herpetiformis is a rare subtype of pemphigus [7]. This can occur at any age, more commonly between the 5th and 6th decade of life [8]. Of the few cases described, the clinical presentation varies between urticariform plaques to pruritic vesicle or blisters. The mucous membrane is usually intact. Histologically, the most common characteristic is an eosinophilic or neutrophilic spongiosis with variable acantholysis [5]. Direct immunofluorescence shows intercellular IgG and C3 in the epidermis, in 100% and 65% of the cases respectively [8]. The most frequent antibody is anti-desmoglein 1, although cases with negative anti-desmoglein and positive anti-desmocollin are reported [3-6]. As far as we know, our case is the first clinical case of pemphigus herpetiformis with high titers IgG antikeratinocyte cell surface antibodies, negative antidesmoglein and only positive anti-envoplakin.

Systemic corticosteroids alone or in combination with dapsone are described as effective in controlling lesions and pruritus. However, the evidence for the treatment of PH is limited, based only on case reports and series [4-8].

The prognosis is favorable, with an indolent course although there are cases described with progression to pemphigus vulgaris or pemphigus foliaceus [9-11].

Conclusion

To our knowledge this is the first clinical case of pemphigus herpetiformis with only positive anti-envoplakin antibodies. This rare and often overlooked entity has a wider variability in terms of the autoimmune response. It is important to recognise this disease since it was a good prognosis, and responses well to dapsone and/or low doses of steroids.

Potential Conflicts of Interest

The authors declare no conflicts of interests.

References

1. Jablonska S, Chorzelski TP, Beutner EH, Chorzelska J. Herpetiform pemphigus, a variable pattern of pemphigus. Int J Dermatol. 1975;14:353-359.
2. Kasperkiewicz M, Kowalewski C, Jabłońska S. Pemphigus herpetiformis: from first description until now. J Am Acad Dermatol. 2014;70:780-787.
3. Ishii N, Teye K, Uehara R, Hachiya T, Koga H. Antidesmocollin autoantibodies in nonclassical pemphigus. Br J Dermatol. 2015;173:59-68.
4. Rafei D, Muller R, Ishii N, Llamazares M, Hashimoto T, Hertl M, et al. IgG autoantibodies against desmocollin 3 in pemphigus sera induce loss of keratinocyte adhesion. Am J Pathol. 2011;178:718-23.
5. Ansai O, Shimomura Y, Fujimoto A, Sakai A, Tsuchida Y, Hayashi R, et al. Case of pemphigus herpetiformis with immunoglobulin G autoantibodies against desmocollin-3. J Dermatol. 2017; 44:104-5.
6. Costa LMC, 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.
7. Maciejowska E, Jablonska S, Chorzelski T. Is pemphigus herpetiformis na entity. Int J Dermatol. 1987;26:571-577.
8. 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;54:1014-1022.
9. Miyagawa S, Amagai M, Lida T, Yamamoto Y, Nishikawa T, Shirai T, et al. Late development of antidesmoglein 1 antibodies in pemphigus vulgaris: Correlation with disease progression. Br J Dermatol. 1999;141:1084-1087.
10. Lebeau S, Muller 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;35:366-372.
11. Muramatsu T, Iida T, Honoki K, Nakatani C, Hatoko M, Shirai T, et al. Pemphigus vulgaris preceded by herpetiform-like skin lesions wit negative immunofluorescence findings. J Dermatol. 1999;26:154-159.