Bullous Pemphigoid-Associated Mortality Rate in a Canadian Tertiary Referral Centre.

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disorder in adults. Most individuals with BP are over the age of 60. Its worldwide incidence has been increasing owing to population aging. Observational studies published over the last 2 decades highlight the non-negligible, albeit variable overall mortality of BP patients, with reported 12-month mortality rates of 10.8% to 40.8%, and 24-month mortality rates of 20.1% to 51.0%. Data in the Canadian population are lacking. OBJECTIVES: We aimed to estimate the 12- and 24-month overall mortality rate of Canadian patients diagnosed with BP, and to identify independent risk factors adversely impacting overall survival. METHODS: A retrospective cohort study of 166 patients with a diagnosis of BP between 2010 and 2020 was carried out at Centre hospitalier de l'Université de Montréal (CHUM), a tertiary referral center in Montréal, Québec, Canada. Cumulative mortality was calculated using the Kaplan-Meier estimator, and independent prognostic factors were identified using a Cox proportional hazards regression model. RESULTS: Eighty-five patients (51.2%) in our study were female. The median age was 79.1 years old, and 80 patients (48.2%) were 80 years old or older. Mortality at 12 and 24 months in our study cohort was 16.2% (CI95% = 10.5 - 21.8) and 27.6% (CI95% = 20.5 - 34.7), respectively. In a multivariate analysis, patients who were male, 80 years old or older, and/or had a diagnosis of a major neurocognitive disorder had a poorer overall survival. CONCLUSIONS: The all-cause mortality of patients with BP in our study population compared favorably with international data reported in the literature.

Primary cicatricial alopecia: Lymphocytic primary cicatricial alopecias, including chronic cutaneous lupus erythematosus, lichen planopilaris, frontal fibrosing alopecia, and Graham-Little syndrome.

Both primary and secondary forms of cicatricial alopecia have been described. The hair follicles are the specific target of inflammation in primary cicatricial alopecias. Hair follicles are destroyed randomly with surrounding structures in secondary cicatricial alopecia. This 2-part continuing medical education article will review primary cicatricial alopecias according to the working classification suggested by the North American Hair Research Society. In this classification, the different entities are classified into 3 different groups according to their prominent inflammatory infiltrate (ie, lymphocytic, neutrophilic, and mixed). Part I discusses the following lymphocytic primary cicatricial alopecias: chronic cutaneous lupus erythematosus, lichen planopilaris, frontal fibrosing alopecia, and Graham-Little syndrome.

Primary cicatricial alopecia: Other lymphocytic primary cicatricial alopecias and neutrophilic and mixed primary cicatricial alopecias.

Primary cicatricial alopecias can be frustrating for both patients and physicians. Proper diagnosis guides more successful management of these challenging conditions. Part II will cover the remaining lymphocytic primary cicatricial alopecias, which include pseudopelade of Brocq, central centrifugal cicatricial alopecia, alopecia mucinosa, and keratosis follicularis spinulosa decalvans. It will also discuss the neutrophilic and mixed primary cicatricial alopecias, namely folliculitis decalvans, dissecting cellulitis, folliculitis keloidalis, folliculitis (acne) necrotica, and erosive pustular dermatosis.

Influence of the quantity of sunscreen applied on the ability to protect against ultraviolet-induced polymorphous light eruption.

BACKGROUND/PURPOSE: Despite the fact that most people apply less sunscreen than the 2 mg/cm(2) required to measure sun protection factor (SPF), there is a lack of clinical data on the protection afforded from lower applied quantities. The aim of this study was to compare the ability of sunscreens to protect against UV-induced polymorphous light eruption (PLE) when applied at 2 mg/cm(2) and 1 mg/cm(2) . METHODS: Two SPF 45 sunscreens (one with a high level and one with a low level of UVA protection) were applied at 2 mg/cm(2) and 1 mg/cm(2) to four randomized 6 × 6 cm areas on the upper thorax of 15 female patients with a typical history of PLE. The areas were exposed daily to increasing UVA-UVB radiation until a PLE reaction was detected or a maximum of five consecutive days. RESULTS: The proportion of patients who developed a PLE reaction with the high UVA-protection sunscreen was significantly lower (0%) than with the low UVA-protection sunscreen (73%) when both sunscreens were applied at 2 mg/cm(2) (P = 0.004). At 1 mg/cm(2) , 33% and 80% of patients presented a PLE reaction with the high and low UVA-protection sunscreen, respectively (P = 0.064). CONCLUSION: A high SPF and high UVA-protection broad spectrum sunscreen was able to protect the majority of patients from the development of UV-induced PLE reaction even at 1 mg/cm(2) .

Efficacy and safety of adalimumab in patients with plaque psoriasis who have shown an unsatisfactory response to etanercept.

BACKGROUND: The safety and efficacy of adalimumab in patients who have shown an unsatisfactory response to etanercept are unknown. OBJECTIVE: We sought to evaluate the safety and efficacy of adalimumab in patients who failed to show a satisfactory response or lost their satisfactory response to etanercept. METHODS: This multicenter study enrolled patients who either failed to reach a physician global assessment (PGA) score of 0 or 1 after 12 weeks of etanercept (group A; 50 patients) or who lost their PGA score of 0 or 1 at any time after etanercept dose decrease from 50 mg twice a week to 50 mg every week (group B; 35 patients). Patients received adalimumab 40 mg every other week without loading dose for 12 weeks followed by 40 mg every week for an additional 12 weeks if they did not reach a PGA score of 0 or 1. RESULTS: After 12 weeks of adalimumab, 34.0% (n = 17; 95% confidence interval [CI] 20.4-47.6) and 31.4% (n = 11; 95% CI 15.2-47.6) of patients from groups A and B, respectively, reached a PGA score of 0 or 1. A total of 46.0% (n = 23; 95% CI 31.7-60.3) and 45.7% (n = 16; 95% CI 28.4-63.1) of patients from group A and B, respectively, achieved a PGA score of 0 or 1 after 24 weeks of adalimumab. Adalimumab was well tolerated and no serious adverse events were reported. LIMITATIONS: This was an open-label uncontrolled study. CONCLUSIONS: Adalimumab should be considered as an alternative in patients with psoriasis who have not shown an adequate response or who lost their response to etanercept after a dose decrease.

Photodynamic therapy with methylaminolevulinate 80 mg/g without occlusion improves acne vulgaris.

BACKGROUND: Photodynamic therapy (PDT) with methylaminolevulinate (MAL) under occlusion is effective for the treatment of acne vulgaris but is associated with significant phototoxic side effects. OBJECTIVE: To evaluate the safety and efficacy of topical MAL with or without occlusion followed by red light exposure in patients with facial acne vulgaris. PATIENTS/METHODS: Forty-four patients with facial acne vulgaris were randomized to receive four MAL applications (80 mg/g) at two-week intervals with occlusion on either the right or left side followed 90 minutes later by either 25 or 37 J/cm2 of red light. RESULTS: At 18 weeks after the first MAL-PDT treatment, the percentage of inflammatory lesions was reduced by a median of 31.7, 59.4, 58.1 and 55.8 percent for patients randomized to 25 J/cm2 without occlusion, 25 J/cm2 with occlusion, 37 J/cm2 without occlusion and 37 J/cm2 with occlusion respectively. MAL-PDT was, in general, well tolerated and only two patients discontinued their participation due to adverse events. CONCLUSION: PDT with MAL at 80 mg/g without occlusion reduces the number of inflammatory lesions in patients with facial acne vulgaris.

Multifocal cocaine-induced pyoderma gangrenosum: A report of two cases and review of literature.

Pyoderma gangrenosum is often associated with a systemic disease. Cocaine-induced pyoderma gangrenosum, most probably caused by levamisole, has been described recently and typically presents as multiple, large cribriform ulcers. Peri-nuclear antineutrophil cytoplasmic antibody is the most common serological finding. A strong counseling for cocaine cessation, combined with wound care and immunosuppressive therapy, is the mainstay of treatment. We present two cases of cocaine-induced pyoderma gangrenosum and correlate their findings with the typical clinical, histological and serological presentation.

Protection afforded by sunscreens containing inorganic sunscreening agents against blue light sensitivity induced by aminolevulinic acid.

BACKGROUND: Application of aminolevulinic acid (ALA) for photodynamic therapy induces significant sensitivity to visible light. OBJECTIVE: To determine whether sunscreens containing inorganic agents are effective against sensitivity to blue light induced by ALA application. METHODS & MATERIALS: Twenty subjects received application of ALA on the arm. Thirty minutes before blue light exposure, two sun protection factor 50 inorganic-based sunscreens containing iron oxide 3.2% and 0.2% were applied on separate areas where ALA was applied; a third area received no sunscreen. Small areas of skin were exposed to increasing fluences of blue light 3 or 18 hours later, and the minimal phototoxic dose (MPD) was noted. RESULTS: Three hours after ALA application MPD was 29.2 and 22.6 J/cm(2) for skin protected with sunscreen containing iron oxide 3.2% and 0.2%, respectively, and 10.6 J/cm(2) for unprotected skin (p=.003 and .0497 respectively). At 18 hours after ALA application, MPD for sunscreen containing iron oxide 3.2% was 5.78, compared with 0.33 for unprotected skin (p<.001) with a blue light protection factor of 21. CONCLUSION: The sunscreen containing iron oxide 3.2% afforded significant protection against blue light sensitivity induced by ALA application.

Palmoplantar pustular psoriasis (PPPP) is characterized by activation of the IL-17A pathway.

BACKGROUND: Palmoplantar pustular psoriasis (PPPP) is a variant of psoriasis, which has significant negative impact on quality of life. The cellular and molecular inflammatory pathways involved in PPPP have not been well studied. OBJECTIVE: Study the expression of cytokines and chemokines involved in the IL-17/IL-23 axis in palmoplantar pustular psoriasis and other difficult to treat psoriasis areas (palms, scalp, elbows and lower legs). METHODS: Skin biopsies were performed on a total of 80 patients with PPPP, non-pustular palmoplantar psoriasis (NPPPP), or psoriasis located on elbows, knees and scalp as well as 10 healthy subjects. RT-PCR, immunohistochemistry and flow cytometry on cells extracted from skin biopsies were used to compare PPPP to other forms of psoriasis. RESULTS: There was a significant (p<0.05) increase in the expression of IL-1ß, IL-6, LL-37, IL-19, IL-17A, CXCL1 and CXCL2 in PPPP as compared to NPPPP. However, there was no significant difference in expression of IL-23 in PPPP as compared to NPPPP and other forms of psoriasis. The proportion of IL-22+ but not IL-17A+ mast cells was higher in PPPP as compared to NPPPP (p<0.05). CONCLUSION: These results suggest that the IL-17A pathway may play a more important role in PPPP than in NPPPP.

Open-label exploratory study of acitretin for the treatment of severe chronic hand dermatitis.

INTRODUCTION: Acitretin is a retinoid approved for the treatment of psoriasis that has good efficacy for palmoplantar psoriasis. The safety and efficacy of acitretin in severe chronic hand dermatitis (CHD) is unknown. METHODS: A total of nine patients with severe CHD were enrolled and treated with acitretin 10 mg once daily which could be increased to 30 mg daily if well-tolerated. Patients were treated for up to 24 or 12 weeks if the physician global assessment (PGA) was clear or almost clear at that time. CHD severity was evaluated using a 5-grade PGA scale and the modified total lesion symptom score (mTLSS). RESULTS: The proportion of patients achieving PGA of clear or almost clear was 33.3% (95% CI: 9-69%) and the proportion achieving PGA of clear, almost clear or mild was 44% (95% CI: 15-77%). The mTLSS decreased by 45% (-6.3 ± 4.7; p = 0.02). Three patients did not complete the study: one due to an increase in facial dermatitis, one due to lack of efficacy and one who withdrew consent. CONCLUSIONS: This pilot study suggests that acitretin could improve severe CHD. Further studies are needed to better assess the efficacy and safety of acitretin in patients with severe CHD.

Effect of adalimumab on sleep parameters in patients with psoriasis and obstructive sleep apnea: a randomized controlled trial.

INTRODUCTION: Obstructive sleep apnea (OSA) is frequently seen in patients with psoriasis vulgaris. The effect of adalimumab, a TNF-α antagonist, on OSA is unknown. METHODS: Patients with at least 5% of their body surface area covered with psoriasis and a sleep apnea defined as an apnea/hypopnea index (AHI) of at least 15 were recruited. They were randomized to either adalimumab 80 mg followed by adalimumab 40 mg every other week for 7 weeks or placebo. Patients were evaluated by polysomnography at baseline and day 56. The objective of this trial was to study the efficacy of adalimumab on sleep parameters in patients with psoriasis and OSA. The primary end point of this double-blind study was the change in AHI between baseline and day 56. RESULTS: A total of 20 patients who were randomized completed the trial. There was no significant difference (p = 0.485) (95% CI = -21.07-42.73) at day 56 in the change from baseline in AHI between groups. CONCLUSIONS: Adalimumab used for 8 weeks at 40 mg every other week for the treatment of psoriasis did not improve OSA in this 20-patient study.

Effects of the tumor necrosis factor-α antagonist adalimumab on arterial inflammation assessed by positron emission tomography in patients with psoriasis: results of a randomized controlled trial.

BACKGROUND: Psoriasis is a chronic inflammatory disease associated with increased risks of myocardial infarction and stroke. Systemic treatments for moderate to severe psoriasis can reduce skin and joint inflammation; however, their effects on vascular inflammation are unknown. METHODS AND RESULTS: This randomized, controlled trial included 30 patients with moderate to severe psoriasis and a history, or multiple risk factors, of coronary atherosclerosis. Patients were randomized (2:1) to receive either adalimumab subcutaneously for 4 months or to control nonsystemic treatment (topical therapies or phototherapy). Vascular inflammation was measured in the carotid artery and ascending aorta at baseline and week 15, by (18)F-fluorodeoxyglucose uptake on positron emission tomography. The change in target: BACKGROUND: =0.004) but not for the control group (-0.10 [95% CI, -0.32 to 0.12]; P=0.35). The difference between study arms for this primary end point did not reach statistical significance (-0.13 [95% CI, -0.01 to 0.14]; P=0.32). The change in target: BACKGROUND: =0.021) and in carotid arteries (-0.32±0.15, P=0.037) when analyzed separately (secondary end points). Changes in other positron emission tomography indices also improved significantly with adalimumab compared with controls in the ascending aorta and carotids. High-sensitivity C-reactive protein decreased by 51% at week 16 with adalimumab compared with 5% in controls (P=0·002). CONCLUSIONS: The study did not meet its primary end point because the change in target:background ratio in patients randomized to adalimumab was not different from controls. Although adalimumab may reduce vascular inflammation in patients with moderate to severe psoriasis, this effect is not large enough to be demonstrated in a study with a small sample size. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00940862.

Safety and efficacy of adalimumab for the treatment of severe alopecia areata: case series of three patients.

BACKGROUND: Current therapeutic options for extensive alopecia areata (AA) often lead to disappointing results. OBJECTIVE: To study the efficacy and safety of adalimumab in patients with severe AA. METHODS: This was a prospective, open-label, single-center, pilot study. Three subjects of the planned 10 were enrolled and received two weekly subcutaneous (SC) loading doses of adalimumab 80 mg followed by 40 mg SC every week for 6 months. Patients were evaluated for efficacy and safety on a monthly basis. RESULTS: Enrolment in this trial was stopped following publication of studies showing no improvement in patients with AA treated with tumor necrosis factor α antagonists. One patient had a favorable response to adalimumab, whereas the two other patients had no benefit from the therapy. Adalimumab was well tolerated by patients with AA. CONCLUSION: Adalimumab was well tolerated in patients with AA but did not induce clinically significant hair regrowth.

A double-blind study of tolerance and efficacy of a new urea-containing moisturizer in patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis patients almost all use moisturizers to prevent and treat their skin disease. However, the safety and efficacy of moisturizers are rarely studied in this patient population. Aims To evaluate the efficacy and tolerability of urea-containing moisturizers in subjects with atopic dermatitis. METHODS: One hundred subjects with atopic dermatitis were randomized to apply either a new 5% urea moisturizer or a commercially available 10% urea lotion twice a day for 42 days. Scoring Atopic Dermatitis severity index (SCORAD) was performed at Day 0 and Day 42. Cosmetic acceptability questionnaires, adverse events, and a 5-point tolerance evaluation were administered or performed at Day 42. RESULTS: Both study products were very well tolerated by subjects and only three subjects discontinued their participation in the study due to adverse events. Mean SCORAD significantly decreased between Day 0 and Day 42 by 19.76% and 19.23%, respectively, for subjects treated with the new 5% urea moisturizer or the 10% urea lotion (P < 0.001). There was no difference between the two products in SCORAD reduction; however, significantly more subjects preferred using the new 5% urea moisturizer as compared with the 10% urea lotion. CONCLUSIONS: Both the new 5% urea moisturizer and the 10% urea lotion improved atopic dermatitis and were very well tolerated. However, the cosmetic acceptability questionnaire showed that subjects preferred using the new 5% urea moisturizer over the 10% urea lotion.