The severity of cutaneous and oral pemphigus is related to desmoglein 1 and 3 antibody levels

BACKGROUND: Pemphigus vulgaris (PV) and foliaceus (PF) are characterized by antibodies to the desmosomal proteins desmoglein 3 (Dsg3) and desmoglein 1 (Dsg1), respectively. Past studies using indirect immunofluorescence (IIF) as a measure of pemphigus antibody levels have failed to demonstrate consistently a relationship between disease severity and IIF titres. However, IIF is not able to measure separately Dsg1 and 3 antibodies, unlike enzyme-linked immunosorbent assays (ELISA), which utilize recombinant proteins. OBJECTIVES: To compare independently Dsg1 and 3 antibody levels with the severity of both cutaneous and oral involvement in PV and PF. Patients and methods Four hundred and twenty-four serum samples were analysed from 80 subjects with PV and 24 with PF. IgG antibodies to Dsg1 and 3 were measured by ELISA. For every sample analysed, the associated severity of skin and oral disease were graded from 0 to 3; quiescent, mild, moderate and severe. RESULTS: A relationship between Dsg1 antibodies and skin severity was demonstrated such that a 10-unit increase in Dsg1 ELISA value was associated with a 34% chance of having a higher severity score [95% confidence interval (CI), 25-45%, P < 0.0005]. This was observed in both PV and PF. Oral severity was associated with Dsg3 antibody levels and a 10-unit increase in the Dsg3 ELISA value was associated with a 25% chance of a higher oral severity score (CI 17-33%, P < 0.0005). We were unable to demonstrate a relationship between Dsg1 antibodies and oral severity, even after adjusting for the effect of Dsg3 antibodies. Similarly, there was no relationship between Dsg3 antibodies and skin severity. CONCLUSIONS: This study suggests that the clinical phenotype of pemphigus, in particular the balance of skin and oral disease, is determined principally by the quantities of Dsg1 and 3 autoantibodies, respectively.     

The clinical transition between pemphigus foliaceus and pemphigus vulgaris correlates well with the changes in autoantibody profile assessed by an enzyme-linked immunosorbent assay

BACKGROUND: There are a number of reports of pemphigus with clinical shifting between pemphigus foliaceus (PF) and pemphigus vulgaris (PV). On the other hand, a novel enzyme-linked immunosorbent assay (ELISA) against recombinant baculoproteins of desmoglein 1 (Dsg1) (PF antigen) and Dsg3 (PV antigen) has been established and found to be extremely sensitive and specific. OBJECTIVES: To characterize the change in the antibody profiles in a series of pemphigus cases with mixed features of PF and PV by various methods, including the novel ELISA. Patients/methods Sera were obtained from eight cases undergoing a shift between PF and PV and three cases of coexistent PF and PV. The autoantigens were analysed by ELISA, as well as by immunofluorescence using normal human skin sections and immunoblotting using normal human epidermal extracts. RESULTS: The results of the ELISA, immunofluorescence and immunoblotting studies showed that the transition between PF and PV correlates well with the changes of autoantibodies against either Dsg1 or Dsg3. CONCLUSIONS: The clinical phenotype at each stage is defined by the anti-Dsg antibody profile in the serum of these pemphigus patients showing mixed features of PF and PV. In addition, ELISA using recombinant baculoproteins was particularly useful in distinguishing PF and PV.     

Low pathogenicity of anti‐desmoglein 3 immunoglobulin G autoantibodies contributes to the atypical clinical phenotypes in pemphigus

The clinical phenotypes of pemphigus can be explained by the desmoglein (Dsg) compensation theory. However, some atypical cases such as cutaneous pemphigus vulgaris (cPV), in which patients have anti‐Dsg3 antibodies without oral erosions, do not conform to this theory. To explain the discrepancy between clinical phenotypes and anti‐Dsg antibody profiles, the pathogenic strength of immunoglobulin (Ig)G autoantibodies against Dsg3 must be taken into consideration. We analyzed the epitopes and blister‐inducing pathogenic strength of the sera from three patients having IgG against Dsg3 without oral erosions with domain‐swapped recombinant proteins and dissociation assay using cultured normal human epidermal keratinocytes. The results showed that all sera contained IgG directed against the amino terminal EC1 domain of Dsg3, as is found in most PV sera. However, dissociation assays revealed that the pathogenic strength of the anti‐Dsg3 antibodies in all three cases was extremely lower than that of typical PV cases with mucosal involvement. In conclusion, when anti‐Dsg3 IgG antibodies are not sufficient to inhibit the expression of Dsg3 in the oral mucosa, but can inhibit the expression in the skin, skin blisters can result. Therefore, the pathogenicity of anti‐Dsg3 antibodies should be regarded as a key factor contributing to the clinical phenotype in pemphigus patients with conflicting antibody profiles.     

Neonatal pemphigus vulgaris with extensive mucocutaneous lesions from a mother with oral pemphigus vulgaris

The clinical phenotype of pemphigus is well explained by the combination of desmoglein (Dsg) 1 and Dsg3 distribution pattern and antiDsg autoantibody profile (Dsg compensation theory). It has been reported that neonatal skin has a similar Dsg distribution pattern to adult mucosal epithelia. We describe a newborn girl with mucocutaneous pemphigus vulgaris (PV) from a mother with mucosal dominant PV. The mother had had painful oral erosions for at least 7 months. Histopathological examination and direct and indirect immunofluorescence studies confirmed the diagnosis of PV and neonatal PV in the mother and daughter, respectively. The mother had a high titre of anti-Dsg3 IgG and a low titre of antiDsg1 IgG, while the neonate had only a high titre of anti-Dsg3 IgG, but no detectable antiDsg1 IgG. AntiDsg3 IgG, which caused the oral dominant phenotype in the mother, induced extensive oral as well as cutaneous lesions in the neonate. Our case provides clinical evidence for the Dsg compensation theory in neonatal PV.     

Cutaneous type pemphigus vulgaris: a rare clinical phenotype of pemphigus

Pemphigus is an autoimmune blistering disease of the skin, mucous membranes, or both. There are two main categories of pemphigus: pemphigus foliaceus (PF) and pemphigus vulgaris (PV). PV is further subdivided into mucosal dominant and mucocutaneous types, according to the extent of cutaneous lesions. These classes of pemphigus have distinct histopathologic and serologic findings, with most cases falling into these subtypes. We report 4 cases that clinically showed blisters and erosions in the skin only, without mucosal involvement. Histologic examination of cutaneous lesions demonstrated suprabasilar acantholysis, a typical finding for PV. These patients had predominant anti-desmoglein 1 (Dsg1) IgG autoantibodies as well as anti-Dsg3 IgG autoantibodies, as determined by enzyme-linked immunosorbent assay. The desmoglein compensation theory posits that this rare phenotype can be produced by pathogenically weak anti-Dsg3 IgG in the presence of potent anti-Dsg1 IgG autoantibodies. Thus, cutaneous type PV without apparent mucosal involvement is observed as a rare clinical and histologic expression of pemphigus. This expression can be a transient phenotype that may develop from, or evolve into, other subtypes of pemphigus.     

A study of desmoglein 1 autoantibodies in pemphigus vulgaris: racial differences in frequency and the association with a more severe phenotype

BACKGROUND: Pemphigus vulgaris (PV) is characterized by pathogenic autoantibodies to desmoglein (Dsg) 3, but additional antibodies to Dsg1, the pemphigus foliaceus antigen, are detectable in some cases. OBJECTIVES: To investigate the clinical significance of the presence of both Dsg 1 and 3 antibodies. METHODS: In 79 subjects with PV, enzyme-linked immunosorbent assays were used to detect IgG autoantibodies reactive with the ectodomain of Dsg1 and Dsg3. RESULTS: There was a clear association between the clinical phenotype and the Dsg antibody profile. All subjects had Dsg3 autoantibodies and 61% had coexisting Dsg1 antibodies (Dsg3+/Dsg1+). PV limited entirely to the mucosal surfaces was seen only in Dsg3+/Dsg1- patients, while additional Dsg1 antibodies (Dsg3+/Dsg1+) predicted cutaneous in addition to mucosal involvement. Although minor cutaneous involvement was observed in most Dsg3+/Dsg1- patients, severe cutaneous involvement was seen only in Dsg3+/Dsg1+ patients. Dsg1 antibodies were detectable early in the course of disease and their appearance did not relate to the use of systemic therapy. The proportion of Dsg1+ patients was higher in those of Indian origin compared with white northern Europeans (P < 0.05). CONCLUSIONS: These data suggest that the presence of Dsg1 antibodies is predictive of a potentially more severe disease and that genetic factors may determine the Dsg antibody profile.     

Three cases of transition from pemphigus vulgaris to pemphigus foliaceus confirmed by desmoglein ELISA

We report 3 cases of pemphigus vulgaris (PV) confirmed by histology and direct and indirect immunofluorescence that showed transition to pemphigus foliaceus (PF) 2-4 years from the time of disease onset. Desmoglein (Dsg) ELISA testing of the sera from these 3 patients in the later stages of their disease showed the presence of anti-Dsg1 antibodies and the absence of anti-Dsg3 antibodies. These patients were on prednisolone and immunosuppressives at the time the sera were tested, and it is unclear if the transition from PV to PF is a permanent one or whether it is due to preferential suppression of Dsg3 antibodies below a certain threshold. Previously reported cases of transition from PV to PF and PF to PV are summarized.     

Study of desmoglein 1 and 3 antibody levels in relation to disease severity in Indian patients with pemphigus

OBJECTIVES: To conduct a cross-sectional study to compare Dsg1 and Dsg3 antibody levels independently with severity of disease activity in pemphigus vulgaris (PV) and pemphigus foliaceus (PF). METHODS: Blood samples from 44 patients with pemphigus (PV-38, PF-6) were analyzed using ELISA. The severity of skin and mucosal disease was graded using a score from 0 to 3. RESULTS: A statistically significant correlation between increase in Dsg 3 antibody titres with severity of oral involvement and Dsg 1 titres with severity of skin involvement was found in both PV and PF patients (p < 0.01). However, we were unable to demonstrate a relationship between increased titres of Dsg1 and Dsg 3 antibodies with oral and skin involvement respectively. CONCLUSION: This study suggests that the severity of skin and oral disease in pemphigus is determined by the quantities of Dsg1 and Dsg3 antibodies respectively.     

Serum and salivary desmoglein 1 and 3 enzyme‐linked immunosorbent assay in pemphigus vulgaris: correlation with phenotype and severity

Background To the best of our knowledge there is only one report about salivary desmoglein (Dsg) 1 and 3 enzyme‐linked immunosorbent assay (ELISA) in pemphigus vulgaris (PV), whereas several studies have been performed on serum. Aims To find the sensitivity of serum and salivary anti‐Dsg1 and 3 antibodies in the diagnosis of PV, and to determine the relationship between disease severity and phenotype with antibody levels. Methods Fifty new patients with PV were included in this study. The diagnosis of PV was confirmed by histopathology and direct immunofluorescence. Demographical data, disease severity and phenotypes were recorded on questionnaire sheets. Dsg1 and Dsg3 ELISA were performed on serum and salivary samples of patients and controls. Results Thirty‐seven patients had mucocutaneous phenotype; whereas mucosal dominant and cutaneous dominant phenotypes were seen in 11 and 2 patients respectively. The sensitivities of serum anti‐Dsg3 and anti‐Dsg1 were 94% and 72% respectively. The sensitivities of salivary anti‐Dsg3 and anti‐Dsg1 antibodies were accordingly 94% and 70%. Compared with mucosal phenotype, serum and salivary anti‐Dsg1 antibodies were significantly higher in the patients with mucocutaneous phenotype. Serum Dsg1 antibodies were related with cutaneous and serum Dsg3 antibodies with mucosal severity scores. Salivary Dsg1 antibodies were significantly correlated with mucosal severity (P = 0.00); however there was no correlation between this antibody and cutaneous severity (P = 0.07). Salivary Dsg3 antibodies were not correlated with mucosal severity (P = 0.16). Conclusion Saliva Dsg ELISA could be used for diagnosis of PV. Salivary Dsg1 antibodies had a significant correlation with mucosal severity.     

Desmoglein 1 and 3 enzyme-linked immunosorbent assay in Iranian patients with pemphigus vulgaris: correlation with phenotype, severity, and disease activity

BACKGROUND: Pemphigus vulgaris (PV) is a chronic autoimmune blistering disorder of the skin and mucosa characterized by the presence of autoantibodies against desmoglein3 (Dsg3). Some patients also have antibodies against desmoglein1 (Dsg1). The aims of this study were to evaluate the diagnostic value of Dsg enzyme-linked immunosorbent assay (ELISA) in Iranian PV patients, to assess its correlation with the clinical phenotype and severity of disease and to investigate the changes of these antibodies after treatment. METHODS: Seventy-three patients with PV (29 men, 44 women) presenting to the Pemphigus Research Unit at Razi Hospital, Tehran, Iran were enrolled. ELISAs were used to detect IgG autoantibodies reactive with the ectodomains of Dsg1 and Dsg3, and the correlation of antibodies with the clinical phenotype as well as oral and skin disease severity was assessed. In addition, the tests were repeated in 18 patients after treatment and the resulting remission. RESULTS: Anti-Dsg1 and anti-Dsg3 were detected in 56 (76.7%) and 69 (94.5%) patients, respectively. Anti-Dsg1 and anti-Dsg3 antibodies were present in 48 (94.1%) and 50 (98%) patients with mucocutaneous type, in 2 (12.5%) and 15 (93.7%) patients with mucosal type, and in 6 (100%) and 4 (66.7%) patients with cutaneous PV, respectively. The mean anti-Dsg1 index values were significantly higher in cutaneous and mucocutaneous phenotypes than mucosal PV (P < 0.001). The mean anti-Dsg3 index values were significantly lower in cutaneous and mucosal phenotypes than mucocutaneous PV (P < 0.01). The severity of skin lesions (but not oral lesions) was correlated with anti-Dsg1 antibody level (P < 0.001); on the other hand, the severity of oral lesions (P < 0.01) as well as skin lesions (P < 0.001) was significantly correlated with anti-Dsg3 antibody levels. Both anti-Dsg1 and anti-Dsg3 levels were significantly reduced after treatment and clinical remission (P < 0.001). CONCLUSION: Dsg ELISA is not only a sensitive tool for the diagnosis of PV, it can also serve as a predictive means for assessing the severity as well as for monitoring the disease activity. Although, in general, the clinical phenotype is related to the antibody profile, there are occasional cases with discordant phenotype and antibody profile. These discrepancies might be explained by genetic variations or the presence of possible minor antigens involved in the pathogenesis of pemphigus.     

Case of pemphigus foliaceus that shifted into pemphigus vulgaris after adrenal tumor resection

A 79-year-old Japanese woman visited our hospital on 6 May 2003, who had suffered from erythema and crusted vesicles located on the head, face and trunk. The eruptions first appeared in February 2003. Histopathological findings included blister formation spreading from just below the horny layers to the upper squamous layers, where acantholytic cells were observed. Direct immunofluorescence disclosed immunoglobulin G depositions in the epidermal intercellular spaces. Enzyme-linked immunosorbent assay showed an elevated titer of anti-desmoglein (Dsg)1 autoantibodies (154 index value), but almost normal levels of anti-Dsg3 autoantibodies (8 index value in serum). The diagnosis at first was made as pemphigus foliaceus (PF). Topical use of corticosteroids alone could control the eruptions well. Systemic examinations on admission revealed a right adrenal tumor that had caused Cushing's syndrome. Its resection was performed on 24 July 2003. Histopathological diagnosis of the removed tumor was a functional adrenal adenoma. The symptoms had worsened after the resection. Topical use of corticosteroids alone could no longer control the symptoms. Additional p.o. medications of minocycline hydrochloride and nicotinic acid amides improved the symptoms to some extent. However, oral cavity erosions appeared in December 2004, and the titer of anti-Dsg3 autoantibodies in serum elevated, suggesting a transition from PF to pemphigus vulgaris (PV). p.o. administration of corticosteroids started, which improved the symptoms significantly. To date, there have been no reports of pemphigus complicated with an adrenal tumor that caused Cushing's syndrome in Japan. The present case is particularly interesting in that the symptoms became worse after the tumor resection and that the first diagnosis of PF shifted into PV after the operation.     

Antibodies to the amino-terminal domain of desmoglein 1 are retained during transition from pemphigus vulgaris to pemphigus foliaceus

Background

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are two blistering skin diseases mediated by antibodies to desmoglein 3 (Dsg3) and/or Dsg1. Phenotypic transition from PV to PF is rarely reported.

Objectives

To determine the immune response to extracellular (EC) domains of Dsgs during this transition.

Materials and Methods

We report two PV patients who subsequently developed a PF phenotype. To map the conformational epitopes in these cases, we examined the reactivity of the sera of two patients by immunoprecipitation-immunoblotting analysis, using five Dsg1/Dsg3 domain-swapped molecules on a backbone of Dsg2.

Results

Reactivity exclusively with the EC1 domain of Dsg1 was maintained in both PV and PF stages. No reactivity to Dsg3 in the PF stage was found in patient 1. Various changes in immunoreactivity to Dsg3 were found and the EC1 and EC2 domains of Dsg3 reacted weakly to serum taken at remission and PF stages in patient 2.

Conclusions

Our findings suggest that amino-terminal pathogenic antibodies to the EC domain of Dsg1 were retained, while considerable epitope changes occurred in response to Dsg3 during the shift from PV to PF, with an absolute or significant decrease in pathogenic antibodies to the EC1 domain of Dsg3.

     

Clinical and immunological profile of umbilical involvement in pemphigus vulgaris and pemphigus foliaceus

Background. Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune vesicobullous disorders with IgG autoantibodies directed against desmoglein (Dsg)1 and 3, which lead to intraepidermal acantholysis. Aim. To characterize the clinical and immunological profile of patients with PF or PV with umbilical involvement. Methods. In total, 10 patients (7 women, 3 men; age range 24–70 years, disease duration 3–16 years) diagnosed with either PV (n = 5) or mucocutaneous PF (n = 5) were assessed according to their clinical features, histopathology and immunological findings [direct and indirect immunofluorescence (DIF and IIF) and ELISA with recombinant Dsg1 and Dsg3]. Results. Erythema, erosions, crusts and vegetating skin lesions were the main clinical features of the umbilical region. DIF of the umbilical region gave positive results for intercellular epidermal IgG and C3 deposits in eight patients and for IgG alone in the other two. Indirect immunofluorescence with IgG conjugate showing the typical pemphigus pattern was positive in all 10 patients, with titres varying from 1 : 160 to 1 : 2560. ELISA with recombinant Dsg1 gave scores of 24–266 in PF and 0–270 in PV. Reactivity to recombinant Dsg3 was positive in all five patients with PV (ELISA 22–98) and was negative in all PF sera. Conclusions. All 10 patients with pemphigus with umbilical presentation had the clinical and immunopathological features of either PF or PV. This peculiar presentation, not yet completely elucidated, has rarely been reported in the literature. A possible explanation for this unique presentation may be the presence of either novel epitopes or an association with embryonic or scar tissue located in the umbilical‐cord region.     

Late development of antidesmoglein 1 antibodies in pemphigus vulgaris: correlation with disease progression

The coexistence of antidesmoglein 3 (Dsg3) and antidesmoglein 1 (Dsg1) autoantibodies is well described in patients with pemphigus vulgaris (PV); however, there is little evidence of sequential development of these two autoantibodies. Autoantibody responses to Dsg3 and Dsg1 were studied in seven PV patients over time by enzyme-linked immunosorbent assay, using baculovirus expressed recombinant fusion proteins. All patients had anti-Dsg3 IgG antibodies at presentation. Two patients developed anti-Dsg1 later in the course of the disease. The transition in autoantibody profile was associated with disease progression to generalized PV involving mucous membranes and skin in both patients; one patient initially presented with a predominantly mucosal phenotype, the other with herpetiform pemphigus-like features. These findings demonstrate that there is an extension of autoimmune response from anti-Dsg3 only to both anti-Dsg3 and anti-Dsg1 in some patients, which is associated with an alteration in clinical expression in PV.     

Four mild but refractory cases of pemphigus foliaceus successfully treated with intravenous immunoglobulin

Intravenous immunoglobulin (IVIG) is a potential second line of therapy for pemphigus, with increasing evidence of its effectiveness and safety, although oral corticosteroids remain the first treatment for pemphigus. IVIG is usually applied in severe cases of pemphigus, particularly pemphigus vulgaris (PV). Pemphigus foliaceus (PF) caused by immunoglobulin PF autoantibodies to desmoglein 1 (Dsg1) is usually milder than PV. However, PF cases are occasionally resistant to corticosteroids and require long‐term treatment to control the disease, leading to various adverse effects. IVIG was used in patients with relatively mild PF, who were resistant to therapies with corticosteroids and dapsone. We assessed the disease severity by Pemphigus Disease Area Index (PDAI) and measured anti‐Dsg1 antibody indices by enzyme‐linked immunosorbent assay, before and 4 months after IVIG. Four Japanese female PF patients (57.3 ± 8.6 years) were treated with a single cycle of IVIG (400 mg/kg per day for five consecutive days) in combination with the previous therapies. Within 1–2 months of addition of IVIG, all PF cases showed remarkable improvement of skin lesions, and PDAI also markedly decreased. For 2 years after IVIG, no apparent exacerbation was observed. Anti‐Dsg1 antibody indices decreased in all cases during the 2 years. IVIG could be a potential treatment for not only severe cases of PV but also mild and refractory cases of PF. IVIG may trigger the shift from intractable condition to remission via non‐pathogenic anti‐Dsg1 antibodies or some mechanisms excluding anti‐Dsg1 antibody.     

Human leukocyte antigen genotypes and antibody profiles associated with familial pemphigus in Japanese

Previous population-based, genetic studies have shown that human leukocyte antigen (HLA) class II loci such as HLA-DR4 (DRB1*04) and HLA-DR14 (DRB1*14) alleles are consistently associated with the occurrence of pemphigus vulgaris (PV) in Japanese as well as other ethnic populations. Among PV-related HLA-DRB1 alleles (*0406, *1401, *1405, *1406) in Japan, HLA DRB1*1405 and DRB1*0406 were found to be associated with both PV and pemphigus foliaceus (PF) phenotypes. We report four familial cases of pemphigus in two unrelated families, together with analysis of their HLA-DR and -DQ alleles, and their antibody profiles. One family comprised a woman with PF and her mother with PV: both patients shared a HLA haplotype of A31(19), B54(22), CW1 and DRB1*1405. Another family included two sisters with PF and PV, respectively: both of these patients shared a DRB1*1405-DQA1*0104-DQB1*0503 haplotype. Clinicopathological and serological monitoring revealed that the elder sister with PF presented with a PV phenotype later, and gained anti-desmoglein (Dsg)3 antibodies in addition to having a low titer of anti-Dsg1 antibodies. Conversely, the younger sister with PV developed PF with only anti-Dsg1 antibody detected. These results indicate that an HLA-DRB1*1405 (DQB1*0503) haplotype may confer susceptibility to both PV and PF, and that genetic susceptibility alone is not always responsible for the clinical phenotype and autoantibody profile.     

Internalization of constitutive desmogleins with the subsequent induction of desmoglein 2 in pemphigus lesions

Acantholytic blisters in pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are caused by a dissociation of desmosomes mediated by autoantibodies against desmoglein (Dsg) 3 and Dsg 1, respectively. The blistering occurs at the suprabasilar level in PV and at the subcorneal level in PF, which corresponds to the distribution of target antigens in the epidermis: there is a more prominent expression of Dsg 1 in the upper layer, whereas Dsg 3 is more prominent in the lower layer. To elucidate the histogenesis of acantholysis, we studied the alterations of the desmosomal components and the expression pattern of Dsg isoforms in the lesional and perilesional epidermis of pemphigus patients. The results demonstrated an internalization of the desmosomes in the lower epidermis of PV, PF and pemphigus vegetans. A similar phenomenon was induced in monolayers of keratinocytes cultured with PV sera. However, little change was observed in E-cadherin expression until acantholysis became manifest. This internalization occurred prior to overt acantholysis, and was frequently associated with the induction of Dsg 2 expression in the basilar or lower layers of the epidermis. These findings indicate an alteration of Dsg isoform expression in subclinical pemphigus lesions, which might be related to the characteristic acantholytic patterns: the suprabasilar layer in PV and the upper epidermis in PF.     

Cutaneous pemphigus vulgaris with absence of desmoglein 1 autoantibodies. An example of the extended desmoglein compensation theory

A 79 year‐old male patient presented clinically as a typical case of pemphigus foliaceus. He displayed a seborrhoeic pattern of crusting and erosions with an absence of oral involvement. Surprisingly, a biopsy showed suprabasilar acantholysis and direct immunofluorescence consistent with pemphigus vulgaris. Indirect pemphigus antibodies were positive for desmoglein 3 (DSG‐3) but negative for DSG‐1 antibodies. Most cases of cutaneous pemphigus are reported to have both DSG‐1 and DSG‐3 antibodies. A rare cutaneous subtype of pemphigus vulgaris is reported in the literature that may present clinically as seen in our patient. Our patient is clinically similar to these previous reported cases but with a negative DSG‐1 antibody titre. The extended DSG compensation theory explains the differences of clinical expression in pemphigus based on the variable pathogenicity of DSG antibodies as well as the distribution of DSG‐1 and DSG‐3. We discuss this case, highlighting the theories of the pathogenesis of pemphigus and, in particular, the cutaneous pemphigus subtype.     

Mucocutaneous pemphigus vulgaris carrying high-titre antidesmoglein 1 antibodies with skin lesions resembling pemphigus erythematosus

Patients with pemphigus vulgaris (PV) who have both antidesmoglein (Dsg)1 and anti-Dsg3 antibodies usually develop flaccid blisters on skin and mucous membranes. We report a case of PV with crusting skin lesions resembling pemphigus erythematosus, the localized variant of pemphigus foliaceus (PF). Notably, the patient had high titres of anti-Dsg1 IgG, as assessed by ELISA. We then established an in vitro model of pemphigus, and found that patient's serum was able to induce suprabasilar acantholysis in mouse skin culture. However, epidermal splitting also occurred within the granular layer, suggesting that the pathogenic potential of such a high-titre anti-Dsg1 serum was intermediate between PV and PF. Thus, the levels of anti-Dsg1 antibodies could play a role in determining the clinical phenotype of pemphigus.     

Neonatal pemphigus vulgaris

A male newborn with skin erosions was born to a 32-year-old woman who was under treatment for pemphigus vulgaris that had been diagnosed 16 months earlier. Antibodies to desmoglein (Dsg)1 and Dsg3 were analyzed by enzyme-linked immunosorbent assay. Index values of antibodies to Dsg1 and Dsg3 were 49 (normal index values, <14) and 121 (normal index values, <7), respectively. Those findings concluded a diagnosis of neonatal pemphigus vulgaris. No new vesicles or bullae appeared in the newborn after the birth. Non-corticosteroid ointments produced prompt epithelialization on the erosive lesions. All the eruptions disappeared in 3 weeks. The level of serum anti-Dsg3 autoantibodies when measured at the 76th day was negative (<5).