Pemphigus vulgaris of the pompholyx type

ARTICLE

Auteur(s) : Vassiliki Bekou¹, Ralf Müller², Daniela Goeppner¹, Ingolf Franke¹, Michael Hertl², Harald Gollnick¹, Martin Leverkus¹

¹Department of Dermatology and Venerology, Otto-von-Guericke-University Magdeburg, Leipziger-Street 44, 39120 Magdeburg
²Department of Dermatology and Allergy, Philipps University Marburg, Germany

Pemphigus may present with a striking variety of clinical phenotypes. Here we report an 86-year old man who complained for six months about extensive blisters, dyshidrotic bullae and pustules limited to both plantae, and intense pruritus (figures 1A, B). Histopathology revealed eosinophilic and neutrophilic spongiosis (figures 1C, D). Direct immunofluorescence microscopy of perilesional skin showed intercellular deposition of IgG (figure 1E). Indirect immunofluorescence analysis on monkey oesophagus showed a positive intercellular staining pattern (figure 1F) and was negative on rat bladder. ELISA showed IgG against Dsg3, consistent with PV, while IgG autoantibodies against Dsg1, bullous pemphigoid (BP)180, BP230 and collagen type VII were not detectable. Moreover, an allergy work-up showed a positive patch test with fragrance mix (++), and parabene mix (+). In light of the limited involvement of PV, treatment with dapsone and topical steroids was initiated and relevant contact allergens, i.e. fragrance and parabene mix, were avoided, leading to complete remission within 3 weeks. When dapsone was tapered, a severe unilateral relapse occurred despite continued contact allergen avoidance. We thus started immunosuppressive treatment with azathioprine, dapsone, and systemic corticosteroids which led to complete remission for a total of 42 months despite the persistence of serum autoantibodies. Allergy patch tests performed 40 months after the initial presentation confirmed contact allergy to fragrances and parabene mix.

IgG reactivity of the patient's serum against distinct Dsg3 subdomains was further studied during the course of the disease by immunoblot analysis and ELISA [1]. ELISA analyses with baculovirus-derived recombinant Dsg3 (entire ectodomain) and recombinant Dsg3 subdomains were performed as previously described [1]. For immunoblot analyses with the identical Dsg3 proteins, the recombinants were fractionated by 12.5% SDS-PAGE, transferred to nitrocellulose and reacted with patient's sera. The correct size of the purified recombinant proteins was visualized by anti E-Tag antibody (figure 1H, left panel). Immunoreactivity of the patient's sera with the Dsg3 recombinants was visualized by HRP-labelled anti-human IgG as previously described [1]. The levels of IgG autoantibodies against all subregions of the Dsg3 ectodomain correlated with clinical disease activity, as measured by “Autoimmune Bullous Skin Disorder Intensity Score” (ABSIS) [2] (figure 1G). Noteworthy, serum IgG titers against distinct subdomains of Dsg3 by ELISA, i.e. EC1, EC2, EC3, EC4, and EC5 subdomains and the entire extracellular domain of Dsg3, initially correlated with the clinical disease activity, but persisted at lower levels despite clinical remission (figures 1G, H).

Among autoimmune bullous diseases, the manifestation of bullous pemphigoid with a dyshidrotic phenotype has been described [3, 4] Thus far, only two cases of dyshidrosiform pemphigus have been documented [5, 6]. In contrast to our case report, Milgraum et al. reported a female patient with an initial manifestation of pemphigus as podopompholyx which later on also involved the palms as cheiropompholyx before it eventually showed a more generalized skin involvement [5]. Another patient reported by Borradori et al. suffered from PV with typical mucocutaneous manifestation for 8 years. Noteworthy, 7 years after remission, he had a relapse with plantar manifestation following a dermatophyte infection that was suggested to act as a potential trigger [6]. The PV patient presented here had not only intercellular deposits of IgG in lesional/perilesional skin, but also a contact allergy to fragrances and parabene mix which was considered to be relevant for the initial podopompholyx-like PV. However disease relapse occurred independent of allergen exposure and subsequently upon tapering of immunosuppressive medication, further supporting the clinical relevance of PV autoantibodies for this localized manifestation of PV of pompholyx type.

In summary, only a few reports have described the clinical manifestation of PV in a dyshidrosiform manner such as cheiro- or podopompholyx. Therefore, clinicians should consider autoimmune bullous diseases when the more common causes of vesiculopustular lesions on palms and soles have been excluded. In addition, our observation suggests that contact allergens may trigger limited variants of autoimmune bullous skin disorders such as PV.

Acknowledgments

References

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5 Milgraum SS, Friedman DJ, Ellis CN, Waldinger TP. Pemphigus vulgaris masquerading as dyshidrotic eczema. Cutis 1985; 35: 445-6.

6 Borradori L, Harms M. Podopompholyx due to pemphigus vulgaris and Trichophyton rubrum infection. Report of an unusual case. Mycoses 1994; 37: 137-9.

  Vassiliki Bekou and Ralf Müller contributed equally to this manuscript