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formed of erythematous papulovesicular lesions of 1-2<span class="elsevierStyleHsp" style=""></span>mm diameter&#44; with a herpetiform distribution on the patient&#39;s back &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; There was no mucosal involvement and the Nikolsky sign was negative&#46; Histology of a lesion showed neutrophilic spongiosis&#46; Direct immunofluorescence revealed intercellular deposits of immunoglobulin &#40;Ig&#41; G and was negative for C3 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Additional tests&#44; including complete blood count&#44; routine biochemistry with liver and kidney profiles&#44; serology for hepatitis B&#44; hepatitis C&#44; and human immunodeficiency virus&#44; were normal or negative&#46; The study of autoimmunity by enzyme-linked immunosorbent assay &#40;ELISA&#41; was positive for antidesmoglein 1 antibodies at a titer of 1&#58;80 &#40;normal value&#44; &#60; 1&#58;10&#41; and for antidesmoglein 3 antibodies at a titer of 1&#58;30 &#40;normal value&#44; &#60; 1&#58;10&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Correlating the clinical manifestations&#44; histology&#44; and autoimmunity pattern&#44; we were able to make a diagnosis of PH&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">After the detection of normal levels of glucose-6-phosphate dehydrogenase&#44; treatment was started with oral dapsone&#44; 100<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#44; combined with prednisone&#44; 60<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#46; The skin lesions and pruritus resolved within a few days&#46; Tapering of the dose of prednisone was then initiated&#44; with complete withdrawal 6 months after starting the treatment&#46; After a year of follow-up&#44; the patient remains asymptomatic and is only receiving treatment with dapsone&#44; 100<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The clinical manifestations of PH are similar to those of DH&#46; It is characterized by papulovesicular lesions on an erythematous base with a predominantly annular morphology&#46; The lesions occur mainly on the trunk and proximal regions of the limbs and they are highly pruritic&#46; In contrast to pemphigus vulgaris&#44; mucosal involvement is very rare&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1&#44;2</span></a> An important finding on histology is the presence of spongiosis with subcorneal microabscesses without acantholysis&#46; Neutrophils predominate in the inflammatory infiltrate in 20&#37; of cases&#44; eosinophils in another 20&#37;&#44; and a mixed infiltrate of neutrophils and eosinophils is seen in 60&#37;&#46; Neutrophilic spongiosis is an early finding in PH&#44; but when acantholysis is present&#44; it indicates a late phase&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1&#44;3</span></a> Direct immunofluorescence in PH reveals intercellular deposits of IgG and&#44; less frequently&#44; of C3&#46; The antibody profile against desmosomal proteins detected by ELISA shows mainly antidesmoglein 1 and&#44; less commonly&#44; antidesmoglein 3&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> Interestingly&#44; in the study by Ishii et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> with 20 samples from patients with PH&#44; 16 were positive for antidesmoglein 1 and 4 for antidesmoglein 3&#44; but none was positive for both antibodies&#46; In the literature reviewed&#44; our case stands out for being the first to be positive for antibodies to both antidesmoglein 1 and 3&#46; The antibodies in pemphigus vulgaris and pemphigus foliaceous are pathogenic and comply with the desmoglein compensation theory&#44; but this theory is not satisfied in PH&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">5&#44;6</span></a> This is because the antibodies in PH recognize a less important segment of the protein and thus have a lower potential to induce acantholysis&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> As described in previous cases&#44; the absence of mucosal involvement in our patient despite the presence of antidesmoglein 3 antibodies may also indicate that the antibodies in PH are less pathogenic&#46; However&#44; we cannot rule out that the absence of mucosal involvement was due to the low titers of antidesmoglein 3&#46; Recently&#44; new cases of PH with a different immunological profile have been published&#44; with detection of antidesmocollin antibodies&#44; with or without antidesmoglein antibodies&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">2&#44;7</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The differential diagnosis of PH includes DH&#44; pemphigus foliaceous&#44; IgA pemphigus&#44; bullous pemphigoid&#44; and linear IgA dermatosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1&#44;5</span></a> Associations have been reported between PH and malignant tumors and autoimmune diseases&#44; but this association is rare and no firm relationship has been demonstrated&#46; PH is a disease with a good prognosis and usually responds to the use of dapsone at a dose of 100-300<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#46; Dapsone is therefore considered first-line therapy in PH&#44; sometimes combined with a systemic corticosteroid&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In conclusion&#44; we would like to stress that knowledge of PH is important as it has a different treatment and prognosis from pemphigus vulgaris&#46; Our case is the first in the literature we consulted to show positivity for both antidesmoglein 1 and 3 antibodies&#46; The absence of mucosal involvement despite the presence of antidesmoglein 3 antibodies can be explained by the lower pathogenicity of the antibodies in PH&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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Case and Research Letters
Pemphigus Herpetiformis With Autoantibodies to Desmoglein 1 and 3
Pénfigo herpetiforme con anticuerpos anti-desmogleína 1 y 3
J.I. Galvañ-Pérez del Pulgara,d,
Corresponding author
galvanderma@telefonica.net

Corresponding author.
, J. Tercedor-Sánchezb,d, D. Jiménez-Galloc,d, M. Linares-Barriosc,d
a Centro Privado de Dermatología Dr. Galvañ, Málaga, Spain
b Unidad de Gestión Clínica de Dermatología Médico-Quirúrgica y Venereología, Hospital Universitario Virgen de las Nieves, Granada, Spain
c Unidad de Gestión Clínica de Dermatología Médico-Quirúrgica y Venereología, Hospital Universitario Puerta del Mar, Cádiz, Spain
d DERMACHAT (Grupo Español de Consenso on-line en Dermatología)
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Pemphigus herpetiformis &#40;PH&#41; is a rare variant of pemphigus&#44; with an incidence of 6&#37; to 7&#46;3&#37; within the pemphigus population&#46; Jablonkska et al&#46; established the diagnostic criteria for PH in 1975&#44; although similar cases had been described in 1955 under the name of dermatitis herpetiformis &#40;DH&#41;&#46; PH is characterized clinically by similarity with DH with an autoimmunity pattern that is similar to pemphigus&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A 43-year-old woman with no personal or family history of interest was seen in dermatology outpatients for highly pruritic skin lesions localized mainly on her back&#46; Physical examination revealed annular plaques of up to 3<span class="elsevierStyleHsp" style=""></span>cm in diameter&#44; formed of erythematous papulovesicular lesions of 1-2<span class="elsevierStyleHsp" style=""></span>mm diameter&#44; with a herpetiform distribution on the patient&#39;s back &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; There was no mucosal involvement and the Nikolsky sign was negative&#46; Histology of a lesion showed neutrophilic spongiosis&#46; Direct immunofluorescence revealed intercellular deposits of immunoglobulin &#40;Ig&#41; G and was negative for C3 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Additional tests&#44; including complete blood count&#44; routine biochemistry with liver and kidney profiles&#44; serology for hepatitis B&#44; hepatitis C&#44; and human immunodeficiency virus&#44; were normal or negative&#46; The study of autoimmunity by enzyme-linked immunosorbent assay &#40;ELISA&#41; was positive for antidesmoglein 1 antibodies at a titer of 1&#58;80 &#40;normal value&#44; &#60; 1&#58;10&#41; and for antidesmoglein 3 antibodies at a titer of 1&#58;30 &#40;normal value&#44; &#60; 1&#58;10&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Correlating the clinical manifestations&#44; histology&#44; and autoimmunity pattern&#44; we were able to make a diagnosis of PH&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">After the detection of normal levels of glucose-6-phosphate dehydrogenase&#44; treatment was started with oral dapsone&#44; 100<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#44; combined with prednisone&#44; 60<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#46; The skin lesions and pruritus resolved within a few days&#46; Tapering of the dose of prednisone was then initiated&#44; with complete withdrawal 6 months after starting the treatment&#46; After a year of follow-up&#44; the patient remains asymptomatic and is only receiving treatment with dapsone&#44; 100<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The clinical manifestations of PH are similar to those of DH&#46; It is characterized by papulovesicular lesions on an erythematous base with a predominantly annular morphology&#46; The lesions occur mainly on the trunk and proximal regions of the limbs and they are highly pruritic&#46; In contrast to pemphigus vulgaris&#44; mucosal involvement is very rare&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1&#44;2</span></a> An important finding on histology is the presence of spongiosis with subcorneal microabscesses without acantholysis&#46; Neutrophils predominate in the inflammatory infiltrate in 20&#37; of cases&#44; eosinophils in another 20&#37;&#44; and a mixed infiltrate of neutrophils and eosinophils is seen in 60&#37;&#46; Neutrophilic spongiosis is an early finding in PH&#44; but when acantholysis is present&#44; it indicates a late phase&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1&#44;3</span></a> Direct immunofluorescence in PH reveals intercellular deposits of IgG and&#44; less frequently&#44; of C3&#46; The antibody profile against desmosomal proteins detected by ELISA shows mainly antidesmoglein 1 and&#44; less commonly&#44; antidesmoglein 3&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> Interestingly&#44; in the study by Ishii et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> with 20 samples from patients with PH&#44; 16 were positive for antidesmoglein 1 and 4 for antidesmoglein 3&#44; but none was positive for both antibodies&#46; In the literature reviewed&#44; our case stands out for being the first to be positive for antibodies to both antidesmoglein 1 and 3&#46; The antibodies in pemphigus vulgaris and pemphigus foliaceous are pathogenic and comply with the desmoglein compensation theory&#44; but this theory is not satisfied in PH&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">5&#44;6</span></a> This is because the antibodies in PH recognize a less important segment of the protein and thus have a lower potential to induce acantholysis&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> As described in previous cases&#44; the absence of mucosal involvement in our patient despite the presence of antidesmoglein 3 antibodies may also indicate that the antibodies in PH are less pathogenic&#46; However&#44; we cannot rule out that the absence of mucosal involvement was due to the low titers of antidesmoglein 3&#46; Recently&#44; new cases of PH with a different immunological profile have been published&#44; with detection of antidesmocollin antibodies&#44; with or without antidesmoglein antibodies&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">2&#44;7</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The differential diagnosis of PH includes DH&#44; pemphigus foliaceous&#44; IgA pemphigus&#44; bullous pemphigoid&#44; and linear IgA dermatosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1&#44;5</span></a> Associations have been reported between PH and malignant tumors and autoimmune diseases&#44; but this association is rare and no firm relationship has been demonstrated&#46; PH is a disease with a good prognosis and usually responds to the use of dapsone at a dose of 100-300<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#46; Dapsone is therefore considered first-line therapy in PH&#44; sometimes combined with a systemic corticosteroid&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In conclusion&#44; we would like to stress that knowledge of PH is important as it has a different treatment and prognosis from pemphigus vulgaris&#46; Our case is the first in the literature we consulted to show positivity for both antidesmoglein 1 and 3 antibodies&#46; The absence of mucosal involvement despite the presence of antidesmoglein 3 antibodies can be explained by the lower pathogenicity of the antibodies in PH&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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Article information
ISSN: 15782190
Original language: English
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