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.

Case Report of a 21-Year-Old Man With Epidermolysis Bullosa Acquisita.

Epidermolysis bullosa acquisita (EBA) is a rare acquired type of mechanobullous disease affecting the dermal-epidermal junction (DEJ) of trauma prone acral surfaces. It manifests as tense vesicles, bullae, and milia and typically heals as atrophic hypo- or hyperpigmented scars. Classic noninflammatory mechanobullous EBA typically presents at a mean age of 48 years. A 21-year-old man presented with a 2-year history of nonpainful papular-vesicular lesions on his hands, knees, and toes after minor trauma to these areas. Physical exam revealed postinflammatory hypopigmented scarring and milia to the bilateral dorsal hands and bilateral extensor elbows and knees, with tense blisters on the dorsal hand and patella regions. Direct immunofluorescence revealed strong linear IgG and IgM with weak focal positivity for IgA and C3 at the DEJ. Blood work revealed an increased diffuse gamma region of 71 g/L (6-13 g/L) on serum protein electrophoresis. Pathology showed a fibrotic underlying dermis, with subepidermal bullae and separation and no significant inflammation. The patient was started on colchicine. This case showcases an unusual early age of presentation for mechanobullous EBA and illustrates the importance of interpreting pathology in the context of clinical findings and maintaining a high index of suspicion for EBA in younger patients who present with classic findings. This case is unique as it is the first report of an association between EBA and polyclonal gammopathy and could be suggestive of chronic inflammation, which would fit with our patient's chronic history of EBA.

Cutaneous Strongyloides Infection Postchemotherapy.

BACKGROUND AND OBJECTIVE: While clinical symptoms of strongyloidiasis are often nonspecific, larva currens (with erythematous, serpiginous, and pruritic papules and plaques) should prompt investigation including stool microscopy, serology, and skin biopsy of the lesion. Appropriate diagnosis and treatment with ivermectin is necessary, especially in the immunocompromised patient who is at increased risk for hyperinfection syndrome and disseminated disease. CONCLUSION: We present a 61-year-old immunocompromised man with presentation of larva currens of cutaneous strongyloides infection without symptoms of hyperinfection or disseminated disease.

Dysplastic Nevus: Management by Canadian Dermatologists.

BACKGROUND: The management of dysplastic nevi is controversial. No studies have collected data regarding management of the lesion amongst Canadian dermatologists. OBJECTIVE: To provide a comprehensive review of what the prevailing opinions are, regarding treatment and terminology of dysplastic nevi, amongst Canadian dermatologists. METHODS: An online survey of 25 questions was e-mailed to 613 members of the Canadian Dermatology Association, in French and English. RESULTS: A total of 179 responses were received. Varying numbers of participants completed each question. The majority of participants think that the term dysplastic nevus should not be abandoned, and they indicated that they never reexcise lesions with mild to moderate atypia even when the margins are positive. CONCLUSIONS: The majority of Canadian dermatologists retain the use of the term dysplastic nevus and do not reexcise lesions with mild to moderate atypia even when the margins are positive.

Cutaneous polyarteritis nodosa sine nodosa.

BACKGROUND AND OBJECTIVE: Cutaneous polyarteritis nodosa, a form of vasculitis affecting the small to medium sized arteries, most commonly presents as tender subcutaneous nodules over the lower legs and feet. Other features include livedo reticularis, skin ulcers and tender indurated plaques. CONCLUSION: We report a 51-year old woman with a primarily livedo reticularis presentation of cutaneous polyarteritis nodosa without a nodular component.

Vitiligo and associated autoimmune disease: retrospective review of 300 patients.

BACKGROUND: Vitiligo, the most common cutaneous depigmentation disorder, has reported associations with other autoimmune diseases. However, literature on the strengths of the associations is conflicting, and no data on the subject exist from a Canadian population. OBJECTIVE: To determine autoimmune disease associations with vitiligo and which, if any, screening bloodwork is appropriate in vitiligo patients. METHODS: A retrospective review of vitiligo patients admitted to the Toronto Western Hospital phototherapy unit was conducted from January 1, 2000, to August 30, 2009. Data regarding patient characteristics, vitiligo clinical features (family history, age at onset, type, extent), associated diseases in the patient and family, and admission bloodwork (hemoglobin, vitamin B12, thyroid-stimulating hormone [TSH], antinuclear antibody) were recorded and compared, using the Fisher exact test where applicable. RESULTS: A total of 300 patient charts were reviewed (average age 41.5 ± 15.5 years; 47% male, 53% female). Hypothyroidism was present in 12.0% and pernicious anemia in 1.3% of patients-significant increases over the population prevalence. No other differences in prevalence were seen compared to the general population. TSH was increased in 3.7% of patients without a history of hypothyroidism. Hemoglobin and vitamin B12 were decreased in 0.3% of vitiligo patients without a history of pernicious anemia. CONCLUSION: We found a significantly higher prevalence of hypothyroidism and pernicious anemia in vitiligo patients.

Linear arrangement of neutrophils along the Basal layer in bullous pemphigoid: a unique histological finding.

Bullous pemphigoid is an inflammatory autoimmune subepidermal bullous disease with distinct immunohistological features. We report an unusual case of a 59-year-old woman with a bullous eruption whose lesional skin biopsy showed a subepidermal blister with a linear arrangement of neutrophils, mimicking linear IgA bullous dermatosis. However, direct immunofluorescence studies demonstrated IgG and C3 linear deposition along the basement membrane zone, compatible with bullous pemphigoid. We suggest that bullous pemphigoid should therefore be considered in the differential diagnosis of neutrophil-rich subepidermal bullous diseases along with dermatitis herpetiformis and linear IgA.

Figurate erythema: an unusual presentation of the nonbullous phase of bullous pemphigoid.

BACKGROUND AND OBJECTIVE: Bullous pemphigoid, an autoimmune disorder, most commonly presents as a bullous eruption in patients over the age of 60. There may be a prodromal urticarial or papular eruption that evolves to bullae. CONCLUSION: We report a 46-year-old woman with a figurate erythema presentation of bullous pemphigoid.

Cutaneous penile and perianal Crohn's disease treated with a combination of medical and surgical interventions.

A 73-year-old man presented with fistulizing cutaneous Crohn's disease of the penis and perianal area without involvement of the gastrointestinal tract. The disease failed to respond to topical clobetasol propionate and oral cyclosporin and methotrexate. A combination treatment of minocycline, thalidomide and prednisolone brought the disease under control and induced remission. Surgery with excision and skin grafting were required to produce cure.