The challenge of unravelling the molecular basis of multifactorial disorders nowadays cannot rely just on association studies searching for potential causative variants shared by groups of patients and not present in healthy individuals; indeed, association studies have as a main limitation the lack of information on the interactions between the disease-causing variants. Thus, new genomic analysis tools focusing on disrupted pathways rather than associated gene variants are required to better understand the complexity of a disease. Therefore, we developed the Variant Enrichment Analysis (VEA) workflow, a tool applicable for whole exome sequencing data, able to find differences between the numbers of genetic variants in a given pathway in comparison with a reference dataset. In this study, we applied VEA to discover novel pathways altered in patients with complex autoinflammatory skin disorders, namely PASH (n = 9), 3 of whom are overlapping with SAPHO) and PAPASH (n = 3). With this approach we have been able to identify pathways related to neutrophil and endothelial cells homeostasis/activations, as disrupted in our patients. We hypothesized that unregulated neutrophil transendothelial migration could elicit increased neutrophil infiltration and tissue damage. Based on our findings, VEA, in our experimental dataset, allowed us to predict novel pathways impaired in subjects with autoinflammatory skin disorders.

Syndromic hidradenitis suppurativa (HS) is a form of symptom constellations, which differs from the familial and genetic form and comprises predominantly osteoarticular manifestations. Many forms include pyoderma gangrenosum and acne (PASH), pyogenic arthritis (PAPASH), spondyloarthritis (PASS) and psoriatic arthritis (PsAPASH) and are categorized in the autoinflammatory syndromes. Anti-TNF-α and anti-IL-1a blockade are between the therapeutic approaches that improve skin symptoms and prevent permanent osteoarticular damage. This case report refers to the successful treatment of a mixed phenotype of the aforementioned symptoms using the IL-17A inhibitor secukinumab after initial treatment with adalimumab. The therapy improved both cutaneous and reported osteoarticular symptoms. Different approaches for these recalcitrant HS syndromes are essential in order to achieve long-term remission for those patients.

BACKGROUND: Hidradenitis suppurativa (HS) and pyoderma gangrenosum (PG) are reported to coexist, although the prevalence of PG among patients with HS has not been systematically evaluated.
OBJECTIVE: To evaluate PG prevalence among patients with HS.
METHODS: Cross-sectional analysis of adults with PG among patients with HS and patients without HS through use of electronic health records data from a population-based sample of 55 million patients.
RESULTS: The prevalence of PG among 68,232 patients with HS was 0.18% (125 of 68,232), compared with 0.01% (1835 of 31,435,166) among those without HS (P < .0001). Prevalence was markedly higher among patients with HS and Crohn\'s disease (CD) (3.68%) than among patients with HS but without CD (0.12%). The odds of having PG were 21.14 (95% confidence interval [CI], 17.51-25.51) times greater among patients with HS than among those without HS. Patients with HS with CD had 12.38 (95% CI, 9.15-16.74) times the odds of having PG than did patients without HS but with CD. Among patients without CD, compared with patients without HS, those with HS had 26.51 (95% CI, 21.07-33.36) times the odds of having PG.
CONCLUSIONS: We could not establish HS phenotype among those having coexistent PG, nor could we distinguish syndromic from nonsyndromic cases.
CONCLUSIONS: Patients with HS have an increased prevalence of PG, regardless of CD status. Painful ulcerations among patients with HS warrant additional evaluation for PG.

Pyoderma gangrenosum (PG) is a complex neutrophilic dermatosis that can occur as an idiopathic disease, in association with systemic conditions such as inflammatory bowel disease, as part of an inherited inflammatory syndrome. It can be challenging to treat, as it occurs in a wide variety of clinical settings and there is a lack of a standardized treatment approach. The main limitations to treatment have been an incomplete understanding of the pathogenesis. However, recent advances have been made in understanding the pathogenesis of this condition, and PG is now considered an autoinflammatory disease process. Areas covered: This review discusses the newest studies that further define our understanding of this disease and the relevant literature on treatment options for pyoderma gangrenosum. Expert commentary: The presence of abnormal neutrophils and T-cells lead to immune dysregulation, leading to lesions of PG. Increased levels of inflammatory mediators including IL-1β, IL-8, IL-17, and TNF-α contribute to the development of the disease but there are still several unknown factors, including the trigger for immune dysregulation and additional contributory components of the immune system. We provide our approach to the management of PG lesions, which involves a multi-faceted approach including wound care, topical therapy, and systemic medications in most cases.

BACKGROUND: Acne fulminans (AF) is a severe variant of inflammatory acne. It typically manifests as an explosive worsening and ulceration of skin lesions, and can be associated with systemic symptoms. However, there is a paucity of evidence-based information and no clear guidelines concerning the classification and treatment of AF.
OBJECTIVE: To better define the spectrum of AF and its variants, devise optimal therapeutic approaches, and identify areas of future research.
METHODS: A panel of physicians with expertise in severe acne vulgaris was convened after a comprehensive literature review of severe acne variants. Priority topics were reviewed and presented by each panelist at a 5-hour conference. Following review of the audiotape and scribed notes from the conference, surveys were utilized to address points of controversy and to clarify consensus recommendations.
RESULTS: Appropriate clinical case presentations and consensus survey questions were utilized to create final recommendations based on both the literature and the expert consensus.
CONCLUSIONS: Limited evidenced-based data and prospective studies in the literature concerning the treatment of AF is available.
CONCLUSIONS: These guidelines better characterize AF and provide health care practitioners approaches to the classification, treatment, and prevention of AF and its variants.