Effectiveness and Safety of Secukinumab for Psoriasis in a Real-World Clinical Setting in the Asia-Pacific and Middle East Regions: Results from the REALIA Study.

INTRODUCTION: Secukinumab has demonstrated sustained long-term efficacy with a favourable safety profile in various manifestations of psoriatic disease. We investigated effectiveness and safety of secukinumab, other biologics and conventional systemic therapies in patients with chronic plaque psoriasis in a real-world setting. METHODS: REALIA was a non-interventional, multicentre, prospective, parallel group study. Eligible patients were ≥ 18 years old with chronic plaque psoriasis commencing a new treatment with a biologic agent or conventional systemic therapies. RESULTS: At baseline, 541 patients were divided into three cohorts based on treatment initiated: conventional systemics (173), secukinumab (184) and other biologics (184). A significantly higher proportion of patients achieved almost clear to clear skin based on physician's judgement in secukinumab versus conventional systemics at month 3 (64.7% versus 22.8%, P < 0.001) and month 6 (61.8% versus 20.8%, P < 0.001). At month 12, clear to almost clear skin was achieved by 52.1% of the patients in secukinumab versus 35.8% in conventional systemics (P = 0.066). The proportion of patients achieving Psoriasis Area Severity Index (PASI) 90 on conventional systemics, secukinumab and other biologics was 18.8%, 59.7% and 40.0% at month 3 and 35.3%, 60.8% and 50.0% at month 12, respectively. Secukinumab patients showed significantly higher change in PASI total score from baseline versus conventional systemics at month 3 {least squares [LS] mean [standard error (SE)]: -14.49 [0.648] versus -8.48 [1.149], P < 0.001} and numerically higher [LS mean (SE): -13.60 (0.475) versus -10.84 (1.733), P = 0.122] at month 12. The proportion of patients with Dermatology Life Quality Index 0/1 score on conventional systemics, secukinumab and other biologics was 22.6%, 65.0% and 41.6% at month 3 and 32.0%, 63.5% and 41.3% at month 12, respectively. Safety profile was comparable across cohorts. CONCLUSIONS: Secukinumab is effective and well tolerated in patients with chronic plaque psoriasis in a real-world setting in an Asia-Pacific and Middle East population, and these results are in agreement with clinical outcomes of secukinumab reported in randomised clinical trials. TRIAL REGISTRATION NUMBER: 170803-001645.

Improving diagnostic accuracy of skin biopsies

BACKGROUND: The skin biopsy is a simple but essential clinical skill of the general practitioner. Performed properly, it can be quick and comfortable for the patient, and yield a very high level of diagnostic information. Performed incorrectly, it can lead to delays in diagnosis and treatment for the patient. OBJECTIVE: This article reviews some simple but effective steps the clinician can take to ensure proper technique and maximise the diagnostic accuracy of their skin biopsies. DISCUSSION: Diagnostic accuracy can be improved through optimal selection of biopsy site, correct biopsy technique, requesting ancillary tests where appropriate, proper handling of specimens, and providing detailed clinical information for the dermatopathologist.

Erythema nodosum - a review of an uncommon panniculitis.

Panniculitis, inflammation of the subcutaneous fat, is a relatively uncommon condition that usually presents with inflammatory nodules or plaques. Erythema nodosum (EN) is clinically the most frequent form of panniculitis and is considered a reactive process that may be triggered by a wide variety of stimuli. Whilst up to 55% of EN is considered idiopathic, the most common causes include infections, drugs, systemic illnesses such as sarcoidosis and inflammatory bowel disease, pregnancy, and malignancy. EN typically presents in the teens and 20s, and is seen more commonly in females. It is often preceded by a non-specific prodrome of one to three weeks, which may include fever, malaise, and symptoms of an upper respiratory tract infection. Cutaneous lesions then follow, typically localized on the extensor aspect of the limbs. The lesions are painful rounded or oval, slightly raised, non-ulcerative red nodules. The exact pathogenesis of EN is not understood, although is thought to result from deposition of immune complexes in the venules of the septae in subcutaneous fat, causing a neutrophilic panniculitis. The classical histopathological picture is of a septal panniculitis without vasculitis. However, the pathological features vary with the chronology of the lesions. Even without specific therapy for a causative condition, EN typically resolves without treatment. Therefore, symptomatic support is adequate for the majority of patients.

Cutaneous Crohn's disease treated with infliximab and 4 years of follow up.

Metastatic Crohn's disease (MCD) is a rare, non-contiguous cutaneous manifestation of Crohn's disease. To date, there have been only four reports in the literature of an effective treatment of this condition with infliximab and there are no long-term follow-up studies on adult MCD patients treated with infliximab. We present a case of MCD treated with infliximab with 4.5 years of follow up.

Hydroxyurea induced dermatomyositis-like eruption.

Medication-induced dermatomyositis (DM) is rare, but a recent review highlighted hydroxyurea (HU) as the most common inciting agent. To aid diagnosis, HU-induced DM-like eruption (HU DM-LE) forms a distinct dermopathy where the typical cutaneous features of DM are without systemic involvement and co-exist with other HU-induced cutaneous findings such as severe xerosis, atrophy, stomatitis, cutaneous and mucosal ulceration and melanonychia. On cessation of HU the DM-LE clears avoiding unnecessary immunosuppression and demonstrating the importance of consideration of medication aetiology in DM presentations. We present a case report and review of the literature.

Hybrid follicular cyst (pilomatrical and infundibular) arising within a sebaceous nevus.

A 7-year-old girl presented with a 3-month history of a small blue-brown papule arising within a large sebaceous nevus on her temporal scalp. A punch excision was performed that demonstrated a hybrid follicular cyst. The majority of the cyst wall displayed pilomatrical differentiation consisting of basaloid matrical-type cells with luminal shadow cell keratinization. The matrical epithelium displayed strong membranous, cytoplasmic, and nuclear staining for ß-catenin. Only a small component of the wall displayed infundibular differentiation. These findings were consistent with a hybrid follicular cyst predominantly displaying pilomatrical differentiation with only a small component of infundibular lining. The most common tumors arising within sebaceous nevi are the syringocystadenoma papilliferum and trichoblastoma. Follicular cysts with infundibular (sebaceous cyst) and trichilemmal (pilar cyst) differentiation are exceedingly common, although their development within sebaceous nevi appears to be rare. We report a rare case of a hybrid follicular cyst with matrical differentiation occurring within a sebaceous nevus.

Pyogenic granuloma, port-wine stain and pregnancy.

We present a novel case of pyogenic granuloma occurring within a port-wine stain in two sequential pregnancies at different sites. There was no history of precipitating events such as trauma. We discuss why a pyogenic granuloma may occur within a port-wine stain and how pregnancy may increase the likelihood of this occurring.

Early melanoma with halo eczema (Meyerson's phenomenon).

We present a case of a 49-year-old man who presented with a solitary atypical pigmented lesion with a surrounding halo of dermatitis. Dermoscopy showed a pigment network at the periphery with areas of scar-like depigmentation, negative pigment network and erythema. The lesion was treated preoperatively with a potent topical corticosteroid resulting in a reduction of inflammation. Histology showed an early Clark level 1 melanoma arising within a severely dysplastic compound melanocytic naevus. There was an adjacent perivascular chronic inflammatory cell infiltrate with occasional eosinophils. Minimal, though definite spongiosis with parakeratosis was also present. The scar was subsequently re-excised achieving appropriate excision margins for melanoma in situ. Six months later, there was recurrence of dermatitis at the scar with no evidence of recurrent melanoma. To our knowledge, melanoma with Meyerson phenomenon has not been reported in the literature. This case highlights that all lesions should be evaluated on clinical and dermoscopic grounds regardless of the presence or absence of eczema. Our case adds yet another entity that may display Meyerson phenomenon and consequently a halo of eczema cannot be considered a reassuring sign when evaluating melanocytic lesions.

Tumor size and survival in multicentric and multifocal breast cancer.

PURPOSE: Current AJCC/UICC staging of early breast cancer defines tumor stage using the largest focus, adding the suffix "(m)" to indicate multiplicity. This method may underestimate the total tumor burden in multifocal and multicentric breast cancer (MMBC). This study examines other measures of tumor size in MMBC to determine which provides the best fit in a multivariate model for survival outcomes. PATIENTS AND METHODS: This prospective cohort study used data from the Australian Capital Territory and New South Wales Breast Cancer Treatment Group database to identify 812 women with ipsilateral invasive breast cancer; 141 of these women had MMBC. The pathology slides of all women with MMBC were reviewed and all foci of invasive breast cancer were re-measured. The measures of interest were the diameter of the largest deposit, the aggregate diameter and the aggregate volume. These measures of tumor size were included with other clinicopathological features of MMBC in a multivariate analysis to assess their relationship with progression-free survival (PFS) and overall survival (OS). RESULTS: Tumor size was associated with PFS and OS in MMBC using any of the three measures; however, the diameter of the largest deposit provided the best fit in the multivariate model for OS. CONCLUSION: Tumor size is an important prognostic factor for MMBC, and the diameter of the largest deposit provides a better fit in a multivariate model for OS than aggregate diameter and aggregate volume. Therefore, tumor size in MMBC should continue to be measured using the diameter of the largest deposit.

Minichromosome maintenance protein 2 expression in normal kidney and renal cell carcinomas: relationship to tumor dormancy and potential clinical utility.

PURPOSE: A major problem in the management of patients with renal cell carcinoma is predicting tumor behavior. In the search for more accurate markers of prognosis, tumor cell proliferation has been investigated. These studies have mostly used antibodies directed against Ki-67 or proliferating cell nuclear antigen and have given conflicting results, findings that are likely because of a combination of specificity and methodological differences. Minichromosome maintenance (Mcm) proteins are a series of closely related proteins that are components of the prereplicative complex. The Mcm proteins are essential for initiating eukaryotic DNA replication and serve as useful markers of proliferating cells. EXPERIMENTAL DESIGN: The aims of this study were to determine the frequency and pattern of Mcm2 expression by immunohistochemistry in normal kidney (n = 10) and renal tumors [n = 56; clear cell n = 36; chromophil (papillary) n = 7; oncocytoma n = 5; and transitional cell carcinoma n = 8], compare its sensitivity to the established proliferation marker Ki-67, examine for differences in tumors derived from stable and labile epithelial cell populations in the kidney, and assess the relationship of Mcm2 proliferation to clinicopathological characteristics of kidney tumors. In addition, to additionally investigate the issue of tumor dormancy we wished to assess the relationship between Mcm2 labeling index (LI) and the angiogenic factors angiopoietin-1 (Ang) and Ang-2. RESULTS: In normal tissues, Mcm2 nuclear labeling was identified in both glomeruli (LI median 0.35%; range 0-1.7) and renal tubules (LI median 0.3%; range 0.1-2.9%). In tumors Mcm2 labeling was predominantly at the periphery with LIs ranging from 0.2-91.5%, which was significantly greater than Ki-67 LI (0.2-40.5%; P < 0.001). Mcm2 LI was also significantly higher in tumors derived from a labile epithelium (transitional cell carcinomas) than a stable epithelium (renal cell carcinomas; P = 0.013). A significant association was also demonstrated between Mcm2 LI and tumor grade (P = 0.0006), and angiogenic phenotype (defined by Ang expression; P = 0.03) but not with patient age (P = 0.84), patient sex (P = 0.25), tumor size (P = 0.74), or stage (P = 0.33). Furthermore, although not significant, a survival analysis demonstrated that 100% of patients with a low Mcm2 LI survived compared with 84% of those with a high Mcm2 LI over the follow-up period (up to 53.2 months; P = 0.14). CONCLUSIONS: This is the first study examining Mcm2 protein in normal and tumor kidney samples, and the first to perform histological subgroup analysis. It shows that Mcm2 is a superior marker to Ki-67 in the assessment of cell cycle entry in histological archival material and that normal kidney has a subset of cells within the glomerular and tubular compartments that are in cycle. It demonstrates that the frequency of cells in cycle in tumors formed from stable or labile epithelial populations mirrors that in the nonneoplastic epithelium. This study additionally demonstrates that the number of cells in cycle in tumors is limited by the angiogenic phenotype and supports animal models that show angiogenesis determines the likelihood of tumor dormancy. Additional study to confirm the clinical utility of Mcm2 as a prognostic marker is now indicated.