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.

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.

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.

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.

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) .

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.

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.

Efficacy and tolerability of topical tacrolimus ointment for the treatment of male genital psoriasis.

BACKGROUND: Genital psoriasis is difficult to treat and has a significant psychological impact on affected patients. OBJECTIVE: To study the safety and efficacy of topical tacrolimus ointment in male patients with genital psoriasis. METHODS: This was an open-label study in 12 male patients with genital psoriasis. Patients received topical tacrolimus 0.1% ointment twice daily for 8 weeks followed by a 4-week observational period. Efficacy was assessed by a modification of the Psoriasis Area and Severity Index (PASI) scale adapted for genital psoriasis (male genital PASI). Severity was also evaluated individually for the glans, shaft of the penis, and scrotum. RESULTS: Male genital PASI decreased from a mean score of 15.8 at baseline to 1.2 at week 8 (p < .001). Psoriasis severity also improved significantly for the glans, shaft of the penis, and scrotum evaluated individually. Tacrolimus 0.1% ointment was very well tolerated, with only mild pruritus or burning sensation of limited duration reported. CONCLUSIONS: Topical tacrolimus ointment appears very efficacious and well tolerated in male patients with genital psoriasis.

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.

The expression of insulin-like growth factor 1 in follicular dermal papillae correlates with therapeutic efficacy of finasteride in androgenetic alopecia.

BACKGROUND: It is generally believed that dihydrotestosterone is one of the pivotal mediators of hair loss in androgenetic alopecia (AGA). Finasteride, which blocks the conversion of testosterone to dihydrotestosterone, has now become an integral part of the current treatment approaches for male AGA. Several lines of evidence support the notion that dermal papilla (DP) cells represent the androgen target within the hair follicle. The specific molecular regulators modulated by androgens within hair follicles in the balding scalp are unknown. OBJECTIVE: The purpose of this study was to identify and quantify changes in expression of specific molecular hair growth regulators in DP of men with AGA treated with finasteride and correlate these findings to clinical efficacy. METHODS: Biopsy specimens were collected from 9 male patients from both the balding area and nonbalding occipital area before and after 4 months of finasteride therapy. DP were microdissected and total RNA was extracted from an equal number of DP from each biopsy specimen. The expression of various cytokines, including insulin-like growth factor (IGF)-1, was determined by reverse transcription polymerase chain reaction. The signals were detected by autoradiography. All 9 patients were given finasteride for 1 year and evaluated for efficacy at month 12. Efficacy was graded on a 7-point scale on the basis of comparison with initial baseline photography. RESULTS: IGF-1 was up-regulated by finasteride treatment in 4 of 9 patients. Among the patients with increased IGF-1 expression, 3 of them showed moderate clinical improvement after 12 months of treatment and another patient remained unchanged. In contrast, 3 patients with decreased IGF-1 expression in the balding scalp showed clinical worsening after 12 months. The other 2 patients without noticeable change in IGF-1 expression showed either slight improvement or no change in their hair condition. CONCLUSION: In a small uncontrolled study of 9 patients with AGA, an increased expression of IGF-1 messenger RNA levels in the DP was associated with patient response to finasteride.