Khalaf Kridin

Mortality and Cause of Death in Israeli Patients with Pemphigus.

All-cause and cause-specific mortality among patients with pemphigus compared with the general population is yet to be established. This study investigated overall mortality and cause-specific mortality in a large immunopathologically validated cohort of patients with pemphigus. Mortality of patients with pemphigus was compared with age- and gender-matched control subjects in the general population. All-cause and cause-specific standardized mortality ratios (SMRs) were estimated. The study cohort included 245 patients newly-diagnosed with pemphigus between January 1990 and June 2016, contributing 2,679.4 person-years of follow-up. Overall, 48 deaths were observed during a mean follow-up period of 10.9 ± 8.1 years, which was more than twice the number expected (SMR 2.4; 95% confidence interval (95% CI) 1.82-3.20). The SMRs for death due to infections (22.6; 95% CI 13.6-35.3), namely pneumonia (25.7; 95% CI 11.7-48.8) and septicaemia (8.6; 95% CI 1.7-25.0), and due to cardiovascular diseases (2.8; 95% CI 1.0-6.0) were significantly higher than expected. Overall mortality among patients with pemphigus is 2.4-times greater than for the general population, mainly due to infections.

Pemphigus Vulgaris and Pemphigus Foliaceus: Differences in Epidemiology and Mortality

Little is known about differences in epidemiological features and prognosis between pemphigus vulgaris (PV) and pemphigus foliaceus (PF). The objective of this study was to compare PV and PF patients regarding ethnic variations and mortality rates. Mortality of PV and PF patients was compared with age- and sex-matched control subjects in the general population. The study cohort comprised 207 patients with PV and 30 with PF diagnosed during the period 2000 to 2015. The incidence rate of PV among Jews was 3.6-fold higher than among Arabs (p<0.001), whereas no ethnic predisposition to PF was noted (p = 0.379). The risk of death for patients with PV was almost 3-fold higher than in the general population (standardized mortality ratio (SMR) 2.6). For patients with PF, the risk of mortality was not significantly increased relative to the general population (SMR 1.4). There is a racial predisposition to PV, whereas PF is sporadic. Mortality among patients with PV is higher compared with PF and the general population.

Pemphigus group: overview, epidemiology, mortality, and comorbidities

Pemphigus forms a group of rare autoimmune bullous diseases that affect the skin and mucous membranes. This group has a chronic course leading to high morbidity and mortality. It is characterized by the production of pathogenic autoantibodies directed against different proteins of the desmosome, leading histologically to intraepidermal cleavage, and clinically to vesicles and erosions on the epithelium of the mucous membranes and/or the skin. The diagnosis of the subtype of pemphigus is based on clinical features, the level of histologic cleavage, and the identification of the antigens recognized by circulating autoantibodies by immunoserological analyses. The epidemiological features of pemphigus vary considerably in different regions of the world. Observational studies examining comorbidities and associations among patients with pemphigus are scarce and sometimes inconclusive. The prognosis, mortality, and clinical outcomes in pemphigus have undergone dramatic change throughout the years. This review provides a brief overview about the different subtypes of pemphigus: pemphigus vulgaris, pemphigus foliaceus, paraneoplastic pemphigus, pemphigus herpetiformis, and IgA pemphigus. In addition, it summarizes the most recent understanding of the epidemiology, mortality data, and comorbidities of this group of organ-specific autoimmune diseases.

Association between bullous pemphigoid and psoriasis: A case-control study

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Association Between Pemphigus and Neurologic Diseases

Importance The association between pemphigus and neurologic diseases was not evaluated systematically in the past. In a recent uncontrolled cross-sectional study, Parkinson disease was found to be significantly associated with pemphigus; in the same study, epilepsy had a nonsignificant association with pemphigus. Several case reports have suggested that pemphigus coexists with multiple sclerosis and dementia. Objective To estimate the association between pemphigus and 4 neurologic conditions (dementia, epilepsy, Parkinson disease, and multiple sclerosis), using one of the largest cohorts of patients with pemphigus. Design, Setting, and Participants A retrospective population-based cross-sectional study was performed between January 1, 2004, and December 31, 2014, using the database of Clalit Health Services, the largest public health care organization in Israel, in the setting of general community clinics, primary care and referral centers, and ambulatory and hospitalized care. A total of 1985 patients with a new diagnosis of pemphigus and 9874 controls were included in the study. Main Outcomes and Measures The proportion of dementia, epilepsy, Parkinson disease, and multiple sclerosis was compared between patients diagnosed with pemphigus and age-, sex-, and ethnicity-matched control participants. Logistic regression was used to calculate odds ratios (ORs) for dementia, epilepsy, Parkinson disease, and multiple sclerosis. The association was examined after a sensitivity analysis that included only patients treated with long-term, pemphigus-specific medications (corticosteroids, immunosuppressants, or rituximab) and after adjustment for several confounding factors. Results When comparing the 1985 cases (1188 women and 797 men; mean [SD] age, 72.1 [18.5] years) with the 9874 controls (5912 women and 3962 men; mean [SD] age, 72.1 [18.5] years), dementia was seen in 622 cases (31.3%) vs 1856 controls (18.8%), with an OR of 1.97 (95% CI, 1.77-2.20). Epilepsy was present in 74 cases (3.7%) vs 210 controls (2.1%), with an OR of 1.78 (95% CI, 1.36-2.33). Parkinson disease was seen in 175 cases (8.8%) vs 437 controls (4.4%), with an OR of 2.09 (95% CI, 1.74-2.51). Multiple sclerosis was present in 2 cases (0.1%) vs 6 controls (0.01%), with an OR of 1.65 (95% CI, 0.34-8.22). Study findings were robust to sensitivity analysis that included patients receiving pemphigus-specific treatments. Estimates were not altered significantly after controlling for comorbidities and overuse of health care. Conclusions and Relevance An association was observed between pemphigus and specific neurologic diseases, including dementia, Parkinson disease, and epilepsy. Physicians treating patients with pemphigus should be aware of this possible association. Patients with pemphigus should be carefully assessed for comorbid neurologic disorders and receive appropriate treatment.

Subepidermal autoimmune bullous diseases: overview, epidemiology, and associations

Subepidermal autoimmune bullous diseases of the skin and mucosae comprise a large group of chronic diseases, including bullous pemphigoid, pemphigoid gestationis, mucous membrane pemphigoid, linear IgA bullous dermatosis, epidermolysis bullosa acquisita, and anti-p200 pemphigoid. These diseases are characterized by an antibody response toward structural components of the basement membrane zone, resulting in subepidermal blistering. The epidemiological features of these diseases vary substantially in different regions of the world. Observational studies investigating comorbidities and associations among patients with these diseases are inconsistent and sometimes inconclusive. This review provides a brief overview regarding each one of the subepidermal autoimmune bullous diseases. In addition, it summarizes the most recent understanding of the epidemiological features and associations of this group of organ-specific autoimmune diseases.

Ethnic variations in the epidemiology of bullous pemphigoid in Israel

No ethnic or geographic predisposition to bullous pemphigoid (BP) was reported so far.

Ulcerative colitis associated with pemphigus: a population-based large-scale study

Abstract Background: The coexistence of pemphigus and ulcerative colitis (UC) has been described, but the association between the two entities was not examined in the past. The primary endpoint of this study was to investigate the association between pemphigus and UC. Materials and methods: Patients with pemphigus were compared to age-, sex- and ethnicity-matched control subjects regarding the prevalence of UC in a cross-sectional study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was conducted utilizing the computerized database of Clalit Health Services. Results: The study enrolled 1985 pemphigus patients and 9874 controls. The prevalence rate of UC was greater in patients with pemphigus than in controls (0.9% vs. 0.4%, respectively; p = .004). In a multivariate analysis pemphigus was independently associated with UC (odds ratio 1.9, 95% confidence interval 1.1–3.3, p = .034). This association was stronger among younger patients, and persisted after performing a sensitivity-analysis including only patients who were prescribed pemphigus-specific medications. Conclusions: Pemphigus is significantly associated with UC. Thus, physicians treating patients with pemphigus should be aware of this possible association. Further research is warranted to better understand the mechanism underlying this association.

Association between pemphigus and psoriasis: A population-based large-scale study

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Pemphigus and hematologic malignancies: A population-based study of 11,859 patients

Background: The association of nonparaneoplastic pemphigus with comorbid hematologic malignancies has yet to be established. Objective: To estimate the association between pemphigus and the common types of hematologic malignancies. Methods: A cross‐sectional study was conducted comparing pemphigus patients with age‐, sex‐ and ethnicity‐matched control subjects regarding the prevalence of 6 comorbid hematologic malignancies. The study was performed using the computerized database of Clalit Health Services ensuring the availability of 4.5 million patients. Results: The study included 1985 pemphigus patients and 9874 control subjects. The prevalence of chronic leukemia (0.9% vs 0.4%, odds ratio [OR] 2.1, 95% confidence interval [CI] 1.2–3.6), multiple myeloma (0.8% vs 0.4%, OR 2.2, 95% CI 1.2–3.9), and non‐Hodgkin lymphoma (1.8% vs 1.2%, OR 1.5, 95% CI 1.0–2.2) was greater in patients with pemphigus than in controls. The association with chronic leukemia remained significant following the adjustment for immunosuppressive therapy (adjusted OR 2.0, 95% CI 1.1–3.7). No significant associations were observed between pemphigus and acute leukemia, Hodgkin lymphoma, myelodysplastic syndrome, and polycythemia vera. Limitations: Lack of immunopathologic validation of the diagnosis of pemphigus. Conclusion: A significant association was observed between pemphigus and chronic leukemia, multiple myeloma, and non‐Hodgkin lymphoma. Further research is warranted to establish this observation in other cohorts.