Prevalence and management of chronic hepatitis B in pemphigus and pemphigoid patients: New evidence for the safety of rituximab.

Although the treatments of pemphigus and pemphigoid patients have tended toward safer options, patients with chronic infections seem to be still at the risk of infection reactivation when they are exposed to any of immunosuppressive treatments. A retrospective study on 1646 registered pemphigus and pemphigoid patients was conducted between January 2017 and February 2019 and the prevalence of HBV, the association between the treatments, mainly prednisolone and rituximab with HBV reactivation as well as outcomes of patients after management with antiviral therapies were evaluated. From 1646 reviewed patients, 10 (0.60%) patients with chronic HBV were identified. We found a negative correlation between the ALT (p-value<0.001), AST (p-value = 0.090), and Pemphigus Disease Area Index (PDAI) (p-value = 0.034) and age of patients. At the time points that prednisolone dosage was higher, higher levels of ALT, but no difference in AST levels was noted. The portion of patients with normal ALT was significantly higher (p-value = 0.036; OR = 2.22) in those who had received rituximab within the previous 6 months (38 of 49; 77.6%) as compared to those who did not (81 of 133; 60.9%). We concluded that avoidance (high dose) systemic corticosteroids in patients with chronic HBV, and using rituximab instead in severe cases benefit this group of patients.

Assessment of Diagnostic Strategy for Mucous Membrane Pemphigoid.

IMPORTANCE: An accurate diagnosis of mucous membrane pemphigoid (MMP) is essential to reduce diagnostic and therapeutic delay. OBJECTIVE: To assess the diagnostic accuracy of direct immunofluorescence microscopy on mucosal biopsy specimens and immunoserology in a large cohort of patients with suspected MMP. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was carried out in a single tertiary care center for blistering diseases between January 2002 and March 2019. Eligible participants were patients with suspected MMP and paired data on at least a mucosal biopsy specimen for direct immunofluorescence microscopy (DIF) and indirect immunofluorescence microscopy (IIF) on a human salt-split skin substrate (SSS). In addition, an optional DIF test on a skin biopsy specimen and one or more performed routine immunoserologic tests were analyzed. Data analysis was conducted from April 2019, to June 2020. MAIN OUTCOMES AND MEASURES: Diagnostic accuracy of DIF, IIF SSS, and immunoblot for BP180 and BP230. RESULTS: Of the 787 participants, 121 (15.4%) received the diagnosis of MMP (50 men [41.3%], 71 women [58.7%]; mean [SD] age at diagnosis, 60.1 [17.7] years). Sixty-seven of the patients with MMP (55.4%) had monosite involvement, of which oral site was the most frequently affected (51 [42.1%]). No significant difference was found between the sensitivity of DIF on a perilesional buccal biopsy and a normal buccal biopsy (89.3% vs 76.7%). Three patients with solitary ocular involvement showed a positive DIF of only the oral mucosa. In 6 patients with a negative mucosal DIF, a skin biopsy confirmed diagnosis of MMP. Overall, IIF SSS was less sensitive (44.6%), but highly specific (98.9%). The sensitivity of immunoblot (66.1%) was higher compared to SSS, but with lower specificity (91.3%). CONCLUSIONS AND RELEVANCE: This comparative diagnostic accuracy study of a cohort of 787 patients found a high sensitivity of a mucosal DIF biopsy for diagnosis of MMP, and lower sensitivity of serologic analysis. A biopsy can be taken from either perilesional or normal buccal mucosa. An additional DIF biopsy of another mucosal site or of affected or unaffected skin may increase the diagnostic yield and is recommended in patients with negative DIF results and high clinical suspicion.

Assessment of the Characteristics and Associated Factors of Infectious Complications in Bullous Pemphigoid.

Objectives: The clinical outcome of bullous pemphigoid appears worse in patients with infectious complications, and assessment of the prevalence and risk factors of infectious complications could be necessary to plan preventative strategies and to instruct the treatment plans. We sought to determine the risk factors of infection and compare associated factors in inpatients and outpatients with different system infections. Design: This is a single-centered retrospective study on the medical records of 252 patients from 2010 to 2018 at the dermatology department, Peking Union Medical College. Medical profiles of medical history, diagnosis, infectious complications, and treatment plans were analyzed. The associated factors were compared between the subgroups, including inpatients and outpatients, different body sites of infection. Results: Of the total 252 patients with bullous pemphigoid (BP), 81 patients (81/252, 32.1%) had infectious complications. Forty-eight patients died from pulmonary infections (11/48, 22.9%), cardiovascular diseases (6/48, 12.5%), and other diseases. Infections were most frequently found in skin/mucosa (44/252, 17.5%), respiratory system (32/252, 12.7%), and blood (10/252, 4.0%). On multivariate analysis, risk factors of infections in BP were maximal control dose of corticosteroids (OR 2.539, 95% CI 1.456-4.430, p = 0.001), low serum albumin level (OR 2.557, 95% CI 1.283, 5.092, p = 0.007), hospitalization (OR 4.025, 95% CI 2.289, 7.079, p < 0.001), comorbidities including respiratory disease (OR 4.060, 95% CI, 1.861, 8.858, p < 0.001), eye disease (OR 4.431, 95% CI 1.864, 10.532, p < 0.001), and diabetes (OR 2.667, 95% CI 1.437, 4.949, p = 0.002). The rate of infection was significantly higher in inpatients compared to that in outpatients (54.0 vs. 20.6%, p < 0.001), with diverse risk factors. Mucocutaneous infections were associated with a maximal control dose of corticosteroid and other dermatoses. Respiratory infections were related to respiratory disease and old age, and hematologic infection was associated with low serum hemoglobin levels and mucosal involvement of BP. Both of them were associated with mucosal involvement of BP and high titer anti-BP180 antibody. Conclusions: Infectious complications of bullous pemphigoid are common and are associated with mucosal involvement of BP, more comorbidities, the higher dose of corticosteroids, and the lower level of serum albumin.

Assessment of Diagnostic Strategy for Early Recognition of Bullous and Nonbullous Variants of Pemphigoid.

Importance: A substantial number of patients with bullous pemphigoid do not develop skin blisters and may not have received the correct diagnosis. Diagnostic criteria and an optimal diagnostic strategy are needed for early recognition and trials. Objectives: To assess the minimal requirements for diagnosis of bullous and nonbullous forms of pemphigoid and to evaluate the optimal diagnostic strategy. Design, Setting, and Participants: This paired, multivariable, diagnostic accuracy study analyzed data from 1125 consecutive patients with suspected pemphigoid who were referred to the Groningen Center for Blistering Diseases from secondary and tertiary care hospitals throughout the Netherlands. Eligible participants were patients with paired data on at least (1) a skin biopsy specimen for the direct immunofluorescence (DIF) microscopy test; (2) indirect immunofluorescence on a human salt-split skin substrate (IIF SSS) test; and (3) 1 or more routine immunoserologic tests administered between January 1, 2002, and May 1, 2015. Samples were taken from patients at the time of first diagnosis, before introduction of immunosuppressive therapy, and within an inclusion window of a maximum of 4 weeks. Data analysis was conducted from October 1, 2015, to December 1, 2017. Main Outcomes and Measures: Pairwise DIF, IIF SSS, IIF on monkey esophagus, BP180 and BP230 enzyme-linked immunosorbent assays, and immunoblot for BP180 and BP230 tests were performed. The results were reported in accordance with 2015 version of the Standards for Reporting Diagnostic Accuracy. Results: Of the 1125 patients analyzed, 653 (58.0%) were women and 472 (42.0%) were men, with a mean (SD) age of 63.2 (19.9) years. In total, 343 participants received a pemphigoid diagnosis, with 782 controls. Of the 343 patients, 74 (21.6%, or 1 in 5) presented with nonbullous pemphigoid. The DIF microscopy was the most sensitive diagnostic test (88.3% [n = 303]; 95% CI, 84.5%-91.3%), whereas IIF SSS was less sensitive (77.0% [n = 263]; 95% CI, 72.2%-81.1%) but was highly specific (99.9%; 95% CI, 99.3%-100%) and complemented most cases with negative DIF findings. Results of the BP180 NC16A enzyme-linked immunosorbent assay did not add diagnostic value for initial diagnosis in multivariable logistic regression analysis of combined tests. These findings lead to the proposed minimal criteria for diagnosing pemphigoid: (1) pruritus and/or predominant cutaneous blisters, (2) linear IgG and/or C3c deposits (in an n-serrated pattern) by DIF on a skin biopsy specimen, and (3) positive epidermal side staining of IgG by IIF SSS on a serum sample; this proposal extends bullous pemphigoid with the unrecognized nonbullous form. Conclusions and Relevance: Both DIF and IIF SSS tests should be performed for diagnosis of the bullous and nonbullous variants of pemphigoid, and the BP180 NC16A enzyme-linked immunosorbent assay is recommended as an add-on test for disease activity monitoring.

Assessment of bullous pemphigoid disease area index during treatment: a prospective study of 30 patients.

BACKGROUND: Recently, a consensus Bullous Pemphigoid Disease Area Index (BPDAI) was proposed to measure therapeutic outcomes in bullous pemphigoid (BP). OBJECTIVE: To compare BPDAI with other clinical parameters of disease activity at baseline and to describe the variations of BPDAI during the initial phase of treatment. METHODS: Thirty BP patients were included and followed for 1 year. BPDAI was assessed at baseline and on days 30, 90 and 360 by the same investigator. Concomitantly, the number of daily new blisters, the skin surface area of erythematous/eczematous/urticarial plaques and blisters/erosions, total lesion area (TLA), pruritus score and mucosal involvement were recorded. RESULTS: At baseline, BPDAI was 46.7 ± 25 (mean ± SD); it was well correlated with erythematous/eczematous/urticarial skin surface (r = 0.63), TLA (r = 0.83), number of daily new blisters (r = 0.7; p ≤ 0.0002) and anti-BP180 autoantibodies (r = 0.49; p = 0.006), but not with anti-BP230 autoantibodies. For the 8 patients with severe BP at baseline, the mean BPDAI was 76.5, versus 35.9 for moderate BP (p = 0.0007). A value of 56 was proposed as a cut-off value for severe BP. BPDAI decreased to 11.9 ± 8.7, 10.7 ± 12.7 and 2.5 ± 4.1 on days 30, 90 and 360, respectively. CONCLUSION: BPDAI rapidly decreased during the early treatment stage of BP with variations almost totally conditioned by the skin activity component.

Bullous autoimmune skin disease in the dog: (1) clinical and pathological assessment.

The clinical and pathological findings of two cases of pemphigus vulgaris and four cases of bullous pemphigoid in the dog are reported. Clinically these cases were typified by ulcerative lesions of the oral mucous membranes, mucocutaneous junctions and skin. Pathologically there were intraepithelial separation and bulla formation in one of the cases of pemphigus and subepithelial separation and bulla formation in all cases of pemphigoid.