Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic hidradenitis suppurativa treated with the IL-17A inhibitor secukinumab

Nikolakis, Georgios; Kreibich, Katja; Vaiopoulos, Aristeidis G.; Kaleta, Katarzyna; Talas, Joud; Becker, Markus; Zouboulis, Christos C.

doi:10.12688/f1000research.52100.2

Cited by 14 publications

(6 citation statements)

References 20 publications

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“…VEA Applied to Inflammatory Skin Disorders: PAPASH, PASH, and PASH/SAPHO Hidradenitis suppurativa is a common feature of PASH, PAPASH, and PASH/SAPHO; these syndromes are elicited by a sterile and recurrent autoinflammation leading to several dermatological manifestations [10]. It is a well-known fact that the three conditions share an ethological pattern, including the molecular signature of IL-1b and TNF-a [10]; however other key molecular players could be involved in these disorders. Our VEA analysis allowed us to identify novel molecular pathways characterizing PASH, PAPASH, and PASH/SAPHO syndromes.…”

Section: Discussionmentioning

confidence: 99%

Variant Enrichment Analysis to Explore Pathways Functionality in Complex Autoinflammatory Skin Disorders through Whole Exome Sequencing Analysis

Brandão

Moura

Marzano

et al. 2022

IJMS

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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.

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Section: Discussionmentioning

confidence: 99%

Variant Enrichment Analysis to Explore Pathways Functionality in Complex Autoinflammatory Skin Disorders through Whole Exome Sequencing Analysis

Brandão

Moura

Marzano

et al. 2022

IJMS

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“…For example, HS lesions affected predominantly flexural sites, while PASH, PAPASH 114,116,[119][120][121][122][123][124][125][126] and PASS 120,[127][128][129][130] also exhibited atypical localisations (neck/nape, back, chest, scalp, extremities). Lesions were most frequently abscesses, nodules, fistulae, sinus tracts and scars in PASH and PsAPA-SH, 120,[131][132][133] with no specific patterns for PASS or PAPASH. PG was mainly pustular in PASS and ulcerative in PASH and PAPASH, generally involving the lower extremities and trunk, with sporadic reports in the upper extremities, back, anogenital, face/mandible, peristomal or mammary sites.…”

Section: Syndromic Hidradenitis Suppurativa: a Conundrum In Phenotypi...mentioning

confidence: 94%

Hidradenitis suppurativa: Detangling phenotypes and identifying common denominators

Vișan,

Căruntu,

Costache

et al. 2023

Acad Dermatol Venereol

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Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a severe impact on patients' quality of life through its recurrent and painful nature, as well as its comorbidity burden. The shift in the pathogenic paradigm from a condition of the apocrine glands to an autoinflammatory disease associated with follicular destruction has rendered its understanding difficult, as there are still large gaps in pinpointing the underlying mechanisms, which cannot currently explain the existing clinical variation and as a result, translate into suboptimal therapy. Multifactorial involvement is hypothesized, with an implication of genetic mutations, microbiome dysbiosis, cytokine upregulation and environmental factors. Clinical observation is fundamental for diagnosis, however, the marked heterogeneity in presentation leads to delays in detection and challenges in treatment selection, showcasing clear limits in defining the link between genetic aspects of HS, the role of epigenetic factors and its pathogenic pathways. There have been attempts to formulate phenotypes that could aid in prognostication and management, however, current classification schemata show significant overlap and no validation through longitudinal studies. In this context, nomenclature poses a great challenge due to the lack of global agreement in the definition of lesions, which should be addressed by future research to enable simplified recognition and allow for more precise severity scoring. This could be complemented by the addition of extra dermatologic findings or paraclinical assessment in constructing phenotypes. The development of valid, predictive and reliable classifications of HS may lead to an improvement in comprehending its pathophysiology, favouring a more personalized approach in management. This could be achieved through consensus in the characterization of clinical features and data gathering, as well as validation attempts for described phenotypes. Ultimately, the genotype‐endotype‐phenotype correlation in HS requires targeted, systematic inquiries and should be addressed more largely to broaden the perspective on this debilitating entity.

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“…Nikolakis et al [ 4 ] described 1 patient treated with secukinumab 300 mg subcutaneously weekly for the first month and then monthly for 4 months. A 50-year-old woman presented with confluent erythematous pustules on the palms and soles with psoriasis-like scaling of the lesions, followed by intermittent pain and swelling of the shoulders and knees.…”

Section: Literature Searchmentioning

confidence: 99%

Exceptional response of skin symptoms to secukinumab treatment in a patient with SAPHO syndrome: Case report and literature review

Wang

Pan

et al. 2022

Medicine

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Rationale: SAPHO syndrome is a rare clinical entity characterized by a wide range of dermatological and musculoskeletal manifestations. Treatment strategies are not standardized. Palmoplantar pustulosis (PPP) is the most common rash in patients with SAPHO syndrome.Patient concerns: A 24-year-old Chinese woman with no relevant medical or familial history had a 1-year history of cutaneous lesions with PPP and pain in the sternoclavicular joint.Diagnosis: Based on the diagnostic criteria for SAPHO syndrome proposed by Nguyen et al in 2012, we diagnosed SAPHO syndrome with severe PPP as the predominant manifestation.Interventions: Due to the limited therapeutic efficacy of methotrexate and cyclosporin, we started therapy with subcutaneous secukinumab 150 mg weekly for the first month, then 150 mg monthly thereafter.Outcomes: After 4 weeks of secukinumab administration, the patient showed significant remission of pustular skin lesions, with almost no joint pain and no adverse reaction. Complete remission of skin symptoms was achieved after 3 months. Joint pain and adverse events have not reoccurred in follow-up thus far.Conclusions: In patients with SAPHO syndrome, we recommend personalized treatment, which may have excellent therapeutic efficacy in those with PPP or severe skin symptoms. Although data related to the use of IL-17 blockers for SAPHO syndrome are very limited, secukinumab provides a novel therapeutic option, especially for patients with PPP and severe skin lesions. Further prospective studies are needed to support our findings.

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Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic hidradenitis suppurativa treated with the IL-17A inhibitor secukinumab

Cited by 14 publications

References 20 publications

Variant Enrichment Analysis to Explore Pathways Functionality in Complex Autoinflammatory Skin Disorders through Whole Exome Sequencing Analysis

Variant Enrichment Analysis to Explore Pathways Functionality in Complex Autoinflammatory Skin Disorders through Whole Exome Sequencing Analysis

Hidradenitis suppurativa: Detangling phenotypes and identifying common denominators

Exceptional response of skin symptoms to secukinumab treatment in a patient with SAPHO syndrome: Case report and literature review

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