Pemphigus and bullous pemphigoid in the United States: a 21-year analysis of patient characteristics, treatment patterns, and comorbidities

Bullous dermatoses are autoimmune blistering skin diseases that can be potentially life-threatening. The incidences for bullous pemphigoid (BP) and pemphigus are 2.4–4 per 100,000 and 0.1–0.68 per 100,000, respectively (1,2). There is a dearth of epidemiological studies examining bullous dermatoses in the United States (U.S.). These data help inform decisions on health policy, resource utilization, and approaches to improve care for patients with bullous diseases. This epidemiologic study aims to examine visits trends, patient demographics and comorbidities, and medication prescribing patterns for bullous dermatoses from 1995 to 2015 across the U.S. We conducted a cross-sectional, population-based analysis from 1995 to 2015 using the National Ambulatory Medical Care Survey (NAMCS), which was conducted annually. NAMCS provides nationally representative data regarding the use of ambulatory medical care services in the U.S by reporting data per outpatient visit. Estimation procedures for data generation in NAMCS follow four elements: inflation of weekly estimates to derive annual estimates, adjusting for nonresponse, ratio adjustment within specialties, and weight smoothing to account for extremes in final weights (3). Visit weights were used to generate nationally representative visit estimates. We included the two bullous dermatoses with the highest visit counts during this period: ‘pemphigus’ (694.4) and ‘bullous pemphigoid’ (694.5) as defined in the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9). We also evaluated comorbidities associated with bullous diseases by examining diagnoses that were made concomitant to pemphigus or pemphigoid, where both the bullous dermatosis and the associated diagnoses need to be among the top five diagnoses made during the visit. From a 21-year period (1995–2015), a total of 453,348 pemphigus visits (weighted) were recorded (Table 1). The majority of the pemphigus visits were for females (61%). Overall, older patients comprised the largest proportion of outpatient visits, with those between the ages of 60–69 years accounting for 33% of the visits. Pemphigus visits were also associated with diagnoses such as urinary tract infections (15%), diabetes (15%), and gastroesophageal reflux disease (12%). Pemphigus treatment included prednisone (44%), topical corticosteroids (27%), trimethoprim/sulfamethoxazole (13%), and tetracycline (2%) (Table 2). Dermatologists conducted 92% of pemphigus visits, as compared to primary care physicians (PCP) conducting 6%. From 1995 to 2015, a total of 1,020,457 (weighted) BP visits occurred (Table 1). The majority of the BP visits were for females (68%). Overall, older patients comprised the largest proportion of outpatient visits, with those individuals 70 and older accounting for 68% of the visits. Hypertension (5%) was the most commonly reported condition associated with BP. The most commonly reported treatments for BP included prednisone (32%), topical corticosteroids (22%), methotrexate (6%), minocycline (6%), and doxycycline (5%) (Table 2). For BP visits, dermatologists conducted 96% of visits, and PCP did not conduct any visits. This study demonstrates that both BP and pemphigus predominantly affect an older population. These findings are congruent with prior studies that reported advancing age contributing to the rising BP incidence (4,5). While the mean age for pemphigus is lower than that of BP, the substantial proportion of older patients with pemphigus and multiple comorbidities reveals the need for skilled dermatologists caring for this medically complex population. Females accounted for a majority of patient visits for pemphigus and BP. Because the unit of analysis for NAMCS is visits, the predominance of females may be attributable to factors such as better patient follow up or longer life expectancy than males. Of note, a limitation of the NAMCS dataset is that it does not allow for the assessment of disease incidence or prevalence. Regarding treatments for pemphigus, oral prednisone was the most commonly prescribed treatment, followed by topical corticosteroids and oral antibiotics. For BP, oral prednisone and topical corticosteroids were the two most commonly used treatments. Because oral prednisone has been associated with increased mortality in BP patients, efforts to minimize their use are important (6). These prescription preferences for systemic corticosteroids highlight the need for non-steroid-based systemic therapies for BP patients. For pemphigus, rituximab was approved in 2018, which postdated the most recently available NAMCS data (7). We anticipate that more effective and safe systemic agents will emerge to treat our aging population of patients with bullous diseases and multiple comorbidities.