The vulvovaginal gingival syndrome: a severe subgroup of lichen planus with characteristic clinical features and a novel association with the class II HLA DQB1*0201 allele.

BACKGROUND: The vulvovaginal gingival syndrome is an uncommon and severe variant of lichen planus characterized by erosions or desquamation of vulval, vaginal, and gingival mucosae with a predilection for scarring and stricture formation. OBJECTIVE: We sought to define the clinical, immunopathologic, and human leukocyte antigen findings in a large cohort of patients. METHODS: The clinical presentation and outcome during long-term follow-up were documented in 40 patients. In addition, human leukocyte antigen typing for class II by polymerase chain reaction and sequence-specific primers was performed. RESULTS: During a mean follow-up period of 8.7 (SD +/- 6.8) years, long-term sequelae included strictures of the esophagus, lachrymal ducts, and external auditory canal; loss of vulval architecture; vaginal stenosis; and buccal mucosal fibrosis. The DQB1( *)0201 allele was present in 80% of patients versus 41.8% of control subjects (P

The specific dermatoses of pregnancy revisited and reclassified: results of a retrospective two-center study on 505 pregnant patients.

OBJECTIVES: We sought to evaluate the frequency and clinical characteristics of pruritic dermatoses in pregnancy and to assess a rationalized classification. METHODS: Data of 505 pregnant patients seen at two university-based dermatologic hospitals (1994-2004) were retrospectively studied. RESULTS: Diagnoses included eczema in pregnancy (49.7%), polymorphic eruption of pregnancy (PEP) (21.6%), pemphigoid gestationis (PG) (4.2%), intrahepatic cholestasis of pregnancy (ICP) (3%), prurigo of pregnancy (0.8%), pruritic folliculitis of pregnancy (0.2%), and miscellaneous dermatoses (20.6%). Eczema in pregnancy, prurigo of pregnancy, and pruritic folliculitis of pregnancy showed considerable overlap and were summarized as atopic eruption of pregnancy (AEP). While PEP, PG, and ICP presented in late pregnancy, AEP started significantly earlier. Primigravidae and multiple gestations were characteristic for PEP, abdominal involvement for PEP and PG, and a history of affected pregnancies for ICP. LIMITATIONS: This was a retrospective study. CONCLUSION: We propose classifying the dermatoses of pregnancy as PG, PEP, AEP, and ICP. Stereotypic immunofluorescence and laboratory findings are diagnostic of PG and ICP, whereas distinct clinical characteristics facilitate discrimination between PEP and AEP.

Usefulness of BP180 NC16a enzyme-linked immunosorbent assay in the serodiagnosis of pemphigoid gestationis and in differentiating between pemphigoid gestationis and pruritic urticarial papules and plaques of pregnancy.

BACKGROUND: Pemphigoid gestationis (PG) is a rare pregnancy-associated subepidermal immunobullous disease that targets hemidesmosomal proteins, particularly BP180. Clinically, PG can resemble the eruption known as polymorphic urticarial papules and plaques of pregnancy (PUPPP), and accurate differentiation between these 2 pruritic pregnancy dermatoses has important implications for fetal and maternal prognoses. Results of epitope mapping studies show that IgG autoantibodies in up to 90% of PG serum samples target the well-defined membrane-proximal NC16a domain of BP180. OBJECTIVE: To examine the usefulness of a commercially available NC16a domain enzyme-linked immunosorbent assay in the serodiagnosis of PG and in the differentiation of PG from PUPPP. PARTICIPANTS: A total of 412 women consisting of pretreatment patients with PG (n = 82), patients with PUPPP (n = 164), and age- and sex-matched controls (n = 166). METHODS: All serum samples were assayed in duplicate. Receiver operating characteristic analyses were performed to determine a cutoff value for the diagnosis of PG and for differentiation from PUPPP and controls. RESULTS: A cutoff value of 10 enzyme-linked immunosorbent assay units was associated with specificity and sensitivity of 96%. CONCLUSIONS: The NC16a enzyme-linked immunosorbent assay is highly sensitive and highly specific in differentiating PG from PUPPP, and it is potentially a valuable tool in the serodiagnosis of PG.

Paraneoplastic pemphigus: a brief update.

First described in 1990, paraneoplastic pemphigus is an autoimmune condition that causes considerable morbidity, is resistant to therapy and is frequently fatal. Clinical heterogeneity is being recognized as more cases are reported and the documented auto-antigen profile is also increasing. Target antigens are now known to be not restricted to the skin, suggesting that this condition is part of a paraneoplastic autoimmune multiorgan syndrome.

Atypical presentation of erythema elevatum diutinum.

A 47-year-old man presented with two red-brown plaques on his back. The histology was consistent with erythema elevatum diutinum. The case was unusual in the site of presentation and in the paucity of lesions. Investigations were aimed at screening for associations such as infections, malignancies and inflammatory diseases. Dapsone remained an effective treatment.

Case of the Brooke-Spiegler syndrome.

A 36-year-old woman presented with lesions on her scalp, face and trunk. Histopathological examination of these lesions demonstrated facial trichoepithelioma, and scalp cylindroma. A solitary nodule on the trunk had features of cylindroma, spiradenoma and trichoepithelioma, a previously unreported occurrence. Based on the clinical picture, the diagnosis of Brooke-Spiegler syndrome was established. Genetic studies confirmed the diagnosis, demonstrating a splice site mutation, designated 1518+2T>C, on the CYLD1 gene of chromosome 16q12-q13.

Development of antigen-specific ELISA for circulating autoantibodies to extracellular matrix protein 1 in lichen sclerosus.

Lichen sclerosus is a common, acquired chronic inflammatory skin disease of unknown etiology, although circulating autoantibodies to the glycoprotein extracellular matrix protein 1 (ECM1) have been detected in most patients' sera. We have examined the nature of ECM1 epitopes in lichen sclerosus sera, developed an ELISA system for serologic diagnosis, and assessed clinicopathological correlation between ELISA titer and disease. Epitope-mapping studies revealed that lichen sclerosus sera most frequently recognized the distal second tandem repeat domain and carboxyl-terminus of ECM1. We analyzed serum autoantibody reactivity against this immunodominant epitope in 413 individuals (95 subjects with lichen sclerosus, 161 normal control subjects, and 157 subjects with other autoimmune basement membrane or sclerosing diseases). The ELISA assay was highly sensitive; 76 of 95 lichen sclerosus patients (80.0%) exhibited IgG reactivity. It was also highly specific (93.7%) in discriminating between lichen sclerosus and other disease/control sera. Higher anti-ECM1 titers also correlated with more longstanding and refractory disease and cases complicated by squamous cell carcinoma. Furthermore, passive transfer of affinity-purified patient IgG reproduced some histologic and immunopathologic features of lichen sclerosus skin. This new ELISA is valuable for the accurate detection and quantification of anti-ECM1 autoantibodies. Moreover, the values may have clinical significance in patients with lichen sclerosus.

Treating immunobullous diseases: an update.

Autoimmune bullous diseases are often associated with significant morbidity and some can even cause mortality, if left untreated. Multiple therapies are now available to treat these blistering conditions. However, few have been evaluated objectively.

Autoantibodies to extracellular matrix protein 1 in lichen sclerosus.

BACKGROUND: Lichen sclerosus is a common acquired inflammatory disorder of skin and mucous membranes. The aetiology is unknown, although HLA-subtype susceptibility and high rates of other autoimmune disorders suggest that autoantibodies to specific mucocutaneous antigens are involved. The clinicopathological similarities between lichen sclerosus and lipoid proteinosis, which results from mutations in extracellular matrix protein 1 (ECM1), suggest this protein as an autoantigen. METHODS: We analysed serum autoantibody profiles in 171 individuals (86 with lichen sclerosus, 85 healthy controls) by immunoblotting of extracts from normal human skin and lipoid proteinosis skin (lacking ECM1). We generated a full-length glutathione-S-transferase fusion protein for ECM1 to confirm specific immunoreactivity. We affinity-purified serum from patients with lichen sclerosus and did indirect immunofluorescence microscopy on normal skin with or without preabsorption with recombinant ECM1. FINDINGS: By immunoblotting, IgG autoantibodies were found in 20 (67% [95% CI 45-84]) of 30 lichen sclerosus serum samples. The highest titre was 1 in 20. The bands were not detected in ECM1-deficient substrate. These samples, and those from 56 other patients with lichen sclerosus, showed immunoreactivity to the recombinant ECM1 protein (64 of 86 positive; 74% [65-84]). Only six (7% [2-13]) of 85 control serum samples were positive. Affinity-purified IgG from serum of patients with lichen sclerosus labelled skin similarly to a polyclonal antibody to ECM1. The positive staining was blocked by preabsorption with excess recombinant ECM1 protein. INTERPRETATION: These findings provide evidence for a specific humoral immune response to ECM1 in lichen sclerosus and offer insight into disease diagnosis, monitoring, and approaches to treatment.

Oral and genital lichenoid reactions associated with circulating autoantibodies to desmoplakins I and II: a novel target antigen or example of epitope spreading?

We describe the first reported case of persistent oral and genital lichenoid reactions associated with circulating antibodies to 250- and 215-kd proteins, compatible with desmoplakin I and II, respectively. We discuss the potential role of epitope spreading, leading to the novel development of specific autoantibodies to desmoplakin.

Dermatoses específicas da gravidez / Specific pregnancy dermatoses

A gravidez é um estado em que ocorrem profundas mudanças endocrinológicas e metabólicas que säo toleradas pelo organismo por um curto período de tempo. A maioria das dermatoses específicas da gravidez säo de patogenia desconhecida, o que dificulta sua classificaçäo. A terminologia destas dermatoses é confusa, havendo vários nomes para designar condiçöes clínicas semelhantes. Em 1982 Black e Holmes propuseram uma nova classificaçäo mais simplificada e composta por quatro entidades: penfigóide gestacional, erupçäo polimórfica da gravidez, prurigo da gravidez, e foliculite pruriginosa da gravidez. A presente revisäo baseia-se nesta classificaçäo e apresenta cada dermatose separadamente