Effectiveness and safety of secukinumab updosing in patients with moderate to severe plaque psoriasis: data from the PURE registry.

Secukinumab is a fully human IgG1 antibody that selectively binds to and neutralizes the proinflammatory cytokine interleukin-17A. Secukinumab is an effective and well-tolerated treatment for plaque psoriasis. There is a limited real-word evidence for dose optimisation of secukinumab based on clinical response. PURE is a multi-national, prospective, observational study in patients with moderate to severe chronic plaque psoriasis in Canada and Latin America, assessing the real-world safety and effectiveness of secukinumab and other indicated therapies. The aim of the current snapshot analysis was to evaluate the effectiveness and safety of on-label dose and updosed secukinumab in patients with plaque psoriasis enrolled in the PURE study. At the time of analysis, 676 patients received secukinumab, of which 84.6% (n = 572) remained on the on-label dose, while 15.4% (n = 104) were updosed. With on-label secukinumab, the absolute Psoriasis Area and Severity Index (PASI) score was reduced from 13.6 at baseline to 1.2 over 36 months, with treatment persistence of 73% at 40 months. At Month 36, 73.2% of the patients receiving on-label secukinumab achieved Investigator's Global Assessment (IGA) 0/1. With updosed secukinumab (300 mg every 2 weeks, 300 mg every 3 weeks, 450 mg every 4 weeks, or 450 mg every 3 weeks), 57.9% of the patients showed improvement in the absolute PASI score at the first visit after updosing, with treatment persistence of 50% at 12 months after updosing. At Month 15, 40% of patients receiving updosed secukinumab achieved IGA 0/1. Patients with previous biologic exposure (odds ratio [OR]: 3.25; 95% confidence interval [CI]: 2.03, 5.18, p < 0.0001) were more likely to be updosed while those with a body weight < 90 kg (OR: 0.49; 95% CI [0.31, 0.77], p = 0.0019) were less likely to be updosed. Previous biologic exposure (HR [hazard ratio]: 1.47; 95% CI [1.24, 1.75], p < 0.0001) and current biologic exposure (secukinumab vs. other indicated therapies: HR 0.57; 95% CI [0.43, 0.75], p = 0.0001) were significantly associated with time to secukinumab updosing. No new or unexpected safety signals were observed with updosed secukinumab. Secukinumab updosing was efficacious and well-tolerated in patients with psoriasis who failed to respond to the approved on-label regimen, suggesting that updosing may be a useful therapeutic option for approved dose non-responders.

Pemphigus herpetiformis: a case series and review of the literature.

BACKGROUND: Pemphigus herpetiformis (PH) is a rare subtype of pemphigus that presents challenges in diagnosis. OBJECTIVE: To review the presentation, diagnosis, and management of PH. METHODS: We reviewed the charts of all patients diagnosed and treated for PH in an immunobullous referral center between September 2007 and June 2013. RESULTS: Eight patients were identified with a diagnosis of PH. All presented initially with pruritus. Clinical disease was manifest as either urticated erythematous plaques or a vesiculobullous eruption. Histological evaluation demonstrated eosinophilic spongiosis in all patients with acantholysis in half of cases (n = 4/8). Peripheral eosinophilia was noted in three of eight (37.5%) patients. In all cases, direct immunofluorescence showed intercellular deposition of immunoglobulin G in the epidermis. All patients required high-dose corticosteroid initially. All patients treated with dapsone or sulfasalazine (n = 4) achieved at least partial control. Other effective treatments included intravenous immunoglobulin (n = 2), azathioprine (n = 2), and leflunomide (n = 1). Rituximab was ineffective in two patients. CONCLUSION: The clinical and histological features of PH develop over time and with treatment, making distinction between pemphigus subtypes challenging and delay in diagnosis common. Diagnosis of PH requires a high index of suspicion and is made on clinical grounds (urticated erythema) in the context of compatible histology and immunofluorescence findings. Treatment may be challenging, although efficacy of sulfonamide derivatives appears to offer a therapeutic effect.

Biopsies of facial dermatoses made simple.

CONTEXT: Biopsy of the face is rarely done for inflammatory skin diseases, unless the entire process is confined to the face. OBJECTIVE: We hypothesized that facial dermatitis has a differential diagnosis that is more limited than the differential diagnosis of inflammatory skin diseases that affect other parts of the body. To our knowledge, the classification of inflammatory skin diseases occurring on the face has never been conducted before in the English literature. DESIGN: The most-recent 100 facial biopsies of inflammatory skin conditions were retrieved from our files, and the cases were categorized into the main inflammatory skin patterns. RESULTS: Forty-seven cases (47%) were categorized as interface dermatitis, 2 cases (2%) as psoriasiform dermatitis, 11 cases (11%) as spongiotic dermatitis, 16 cases (16%) as diffuse and nodular dermatitis, 8 cases (8%) as perivascular dermatitis, 14 cases (14%) as folliculitis and perifolliculitis, 1 case (1%) as panniculitis, and 1 case (1%) as fibrosing dermatitis. The number of diagnostic entities represented within each of these patterns was small. CONCLUSIONS: We believe that facial dermatitis should have its own more-circumscribed differential diagnosis. From a practical viewpoint, many of the inflammatory skin diseases that affect other parts of the body should be excluded from the differential diagnosis after the tissue is determined to be from a facial skin biopsy, and others should not be considered unless the biopsy is from the face.

Durable remission of pemphigus with a fixed-dose rituximab protocol.

IMPORTANCE: Rituximab induces B-lymphocyte apoptosis by targeting CD20 antigen and has shown efficacy in antibody-mediated autoimmune disease. Rituximab is increasingly being acknowledged as an effective and safe treatment option for pemphigus. OBJECTIVE: To assess the clinical response of patients with pemphigus to rituximab using a modified fixed-dose rheumatoid arthritis protocol (1 g intravenously on days 1 and 15, followed by 500 mg intravenously if clinically warranted at 6-month intervals or repeated full dosing). DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted using records from a tertiary referral center for autoimmune bullous disorders. Participants included 92 patients (pemphigus vulgaris, 84 [91%], and pemphigus foliaceus, 8 [9%]) who received rituximab treatment between May 1, 2006, and August 30, 2012. MAIN OUTCOMES AND MEASURES: The primary outcomes were time to relapse and achievement of a complete response with or without treatment at the end of the study. RESULTS: Median time to relapse after the first treatment cycle was 15 months (95% CI, 10.3-19.7). All patients experienced improvement. Complete remission rates with or without adjuvant treatment at final follow-up were 89% (56 patients [61%] were in complete remission without treatment and 26 patients [28%] were in complete remission during adjuvant treatment). No serious infectious adverse events occurred. CONCLUSIONS AND RELEVANCE: The fixed-dose, modified rheumatoid arthritis protocol for rituximab was efficacious and well tolerated in patients with pemphigus. Patients who do not achieve remission after 1 cycle or patients who experience relapse benefit from further cycles of rituximab. Our results need to be confirmed in larger and controlled trials.

Friction-induced pagetoid dyskeratosis.

BACKGROUND: Pagetoid dyskeratosis (PD) is characterized by pale cells within the epidermis resembling those of Paget disease. These cells have been seen as an incidental finding in a variety of benign papules most commonly located in intertriginous areas. The lesion is considered a reactive process in which a small proportion of the normal population of keratinocytes is altered. Among the triggers for this lesion, friction has been suggested; however, a direct cause-and-effect relationship has not yet been reported. RESULTS: We confirmed the relationship between PD and friction in a biopsy taken from a 19-year-old woman who presented with clinical features indicating exogenously induced bullae and erosions and consented to a biopsy of a lesion immediately after its induction, demonstrating combined features of PD and friction bulla.