Pemphigus vulgaris and pregnancy

The management and counseling of patients with pemphigus vulgaris during pregnancy is a challenge. The frequency of the association is very low and the current knowledge is based only on case reports or small series. The authors report 2 cases ofpemphigus vulgaris and pregnancy that differed from each other in the time of occurrence and clinical course but had similar favorable outcomes. Based on a literature review and their personal observations, the authors discuss the characteristics of this association, the therapeutic behavior, patients' followup, and fetal prognosis.     

Autoimmune blistering dermatoses as systemic diseases

Autoimmune blistering dermatoses are examples of skin-specific autoimmune disorders that can sometimes represent the cutaneous manifestation of a multiorgan disease due to potential common pathogenic mechanisms. As soon as a distinct autoimmune blistering dermatosis is diagnosed, it is imperative to consider its potential systemic involvement, as well as the autoimmune and inflammatory conditions that are frequently associated with it. In paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome, the internal organs (particularly the lungs) are affected by the autoimmune injury. Pemphigus erythematosus may manifest with overlapping serologic and immunohistologic features of lupus erythematosus. In patients with bullous pemphigoid, there is a greater prevalence of neurologic disease, possibly caused by cross-reactivity of the autoantibodies with isoforms of bullous pemphigoid antigens expressed in the skin and brain. Anti-laminin 332 pemphigoid shows an increased risk for adenocarcinomas. Patients with anti-p200 pemphigoid often suffer from psoriasis. A rare form of pemphigoid with antibodies against the α5 chain of type IV collagen is characterized by underlying nephropathia. Particularly interesting is the association of linear IgA disease or epidermolysis bullosa acquisita with inflammatory bowel disease. Dermatitis herpetiformis is currently regarded as the skin manifestation of gluten sensitivity. Bullous systemic lupus erythematosus is part of the clinical spectrum of systemic lupus erythematosus, a prototypic autoimmune disease with multisystem involvement.     

Pemphigus vulgaris: environmental factors. Occupational, behavioral, medical, and qualitative food frequency questionnaire

BACKGROUND: There have been reports suggesting the involvement of environmental factors in the disease process of pemphigus. Factors suggested include exposure to pesticides or certain drugs. OBJECTIVE: To analyze the association of pemphigus with environmental exposure to various agents, including smoking, recreational and occupational insults, drugs, and food. DESIGN AND SETTING: In-person interviews of pemphigus patients and control subjects were conducted by trained medical investigators using a structured questionnaire. Questions included occupational, behavioral, medical, and qualitative food frequency details. The multicenter study was conducted at outpatient services of teaching hospitals in Bulgaria, Brazil, India, Israel, Italy, Spain, and the USA. PARTICIPANTS: A total of 126 pemphigus patients (55 men, 71 women; age, 54 +/- 17 years) and 173 healthy controls (87 men, 86 women; age 50 +/- 19 years) were interviewed in the period between October 1, 1999 and March 31, 2000. The diagnosis of pemphigus was based on clinical, histologic, immunohistologic, and immunohistochemical criteria. The disease duration was 2-27 years (8.4 +/- 7.2 years). Individuals with skin diseases other than pemphigus were selected as control subjects. MAIN OUTCOME MEASURE: Information on drugs, foods, and occupational, environmental, constitutional, and other possible risk factors was analyzed by t-tests and chi-squared tests as applicable. A multivariate logistic regression model was applied to the data to study simultaneously the independent relationship between each risk factor and pemphigus vulgaris. RESULTS: The risk for pemphigus vulgaris was lower for ex-smokers and current smokers than for patients who had never smoked. Exposure to pesticides and occupational exposure to metal vapor were associated with an increased risk of pemphigus. Pemphigus patients had more pregnancies than controls. There were differences in environmental factors between countries, with exposure to gardening materials and pesticides being highest among patients from Bulgaria, followed by Israel. Disease characteristics also exhibited differences between countries. Bulgarian patients less frequently had oral mucous membrane lesions: 66% compared to 92% for Israeli patients and 83% for Italians. The distribution of the disease in skin and mucous membranes was similar among patients from all countries. Exclusive skin involvement was seen in 50% of patients, mucous membranes alone in 23% of patients, and both skin and mucous membranes in 27% of patients. CONCLUSIONS: The beneficial effect of smoking on pemphigus might be explained by its effect on the immune system. In addition, smoking has an antiestrogenic effect, while pesticides have an estrogenic effect. The lower numbers of smokers among patients, the higher exposure rates to pesticides, and the higher number of female patients who had been pregnant may point to the contribution of estrogens to the disease process. It remains to be determined whether measures, such as avoiding exposure to pesticides or metal vapor, may be beneficial in the clinical context. As the present study was a survey, more definitive studies should be conducted to validate the results.     

Covid-19 pandemic and the skin

In the beginning of the COVID-19 outbreak, skin manifestations, if present, were not paid enough attention. Then, the focus moved toward the impact of the prolonged use of personal protective measures in both healthcare workers and patients. In the meantime, attention is increasingly paid to dermatology as a result of the concern for certain groups of dermatologic patients, including those whose condition may worsen by the thorough disinfection measures and those treated with immunosuppressants or immunomodulators. Following patients with psoriasis on biological therapy, as well as other inflammatory and autoimmune cutaneous disorders such as atopic dermatitis, pemphigus, pemphigoid diseases, and skin cancer provoked the interest of dermatologists. Finally, an intriguing question to the dermatologic society was whether skin changes during COVID-19 infection exist and what could be their diagnostic or prognostic value. Here, we summarize skin conditions during the COVID-19 pandemic, patient information, and expert recommendations and give an overview about the registries launched to document skin changes during COVID-19, as well as details about certain patient groups infected with SARS-CoV-2, for example, psoriasis, atopic dermatitis, and autoimmune bullous diseases.     

Detection and characterization of anti-envoplakin linker autoantibodies in paraneoplastic pemphigus using specific bead-based assay

Paraneoplastic pemphigus (PNP) is characterized by an autoantibody response directed against desmosomal antigens, desmogleins and plakin's proteins, i.e., periplakin and envoplakin. Notably, PNP antibodies were shown to recognize major epitopes located in the linker subdomain of human envoplakin and thus, may constitute a diagnostic marker of PNP. In this study, a recombinant envoplakin-linker subdomain (rENV-L) was produced and used to develop a specific bead-based assay to determine the prevalence and titers of anti-rENV-L antibodies in patients with different types of autoimmune bullous skin diseases. Sera from 33 PNP, 41 pemphigus vulgaris, 46 pemphigus foliaceus, 24 bullous pemphigoid and 74 normal subjects were analyzed by rENV-L bead-based assay: 23/33 (69.7%) PNP, 2/24 (8.3%) bullous pemphigoid and 4/74 (5.4%) healthy control sera showed IgG reactivity against rENV-L. For PNP, the sensitivity and specificity of the assay were 69.7% and 94.6%, respectively. Among the PNP sera reacting with envoplakin and periplakin by immunoblot analysis, 80.8% contained anti-rENV-L antibodies. Finally, we showed that an anti-rENV-L mAb that recognizes both envoplakin and periplakin gave the same fluorescence pattern on rat bladder sections than PNP sera. Thus, anti-rENV-L antibodies constitute a useful diagnostic marker of PNP and our bead-based assay, notably combined with other epidermal autoantigens, a useful tool to diagnose PNP.