Blood T Helper Memory Cells: A Tool for Studying Skin Inflammation in HS?

Hidradenitis suppurativa (HS) is an inflammatory skin disease characterized by painful lesions on intertriginous body areas such as the axillary, inguinal, and perianal sites. Given the limited treatment options for HS, expanding our knowledge of its pathogenetic mechanisms is a prerequisite for novel therapeutic developments. T cells are assumed to play a crucial role in HS pathogenesis. However, it is currently unknown whether blood T cells show specific molecular alterations in HS. To address this, we studied the molecular profile of CD4+ memory T (Thmem) cells purified from the blood of patients with HS and matched healthy participants. About 2.0% and 1.9% of protein-coding transcripts were found to be up- and down-regulated in blood HS Thmem cells, respectively. These differentially expressed transcripts (DETs) are known to be involved in nucleoside triphosphate/nucleotide metabolic processes, mitochondrion organization, and oxidative phosphorylation. The detected down-regulation of transcripts involved in oxidative phosphorylation suggest a metabolic shift of HS Thmem cells towards glycolysis. The inclusion of transcriptome data from skin from HS patients and healthy participants in the analyses revealed that in HS skin lesions, the expression pattern of transcripts identified as DETs in blood HS Thmem cells was very similar to the expression pattern of the totality of protein-coding transcripts. Furthermore, there was no significant association between the extent of the expressional changes in the DETs of blood HS Thmem cells and the extent of the expressional changes in these transcripts in HS skin lesions compared to healthy donor skin. Additionally, a gene ontology enrichment analysis did not demonstrate any association of the DETs of blood HS Thmem cells with skin disorders. Instead, there were associations with different neurological diseases, non-alcoholic fatty liver disease, and thermogenesis. The levels of most DETs linked to neurological diseases showed a positive correlation to each other, suggesting common regulatory mechanisms. In summary, the transcriptomic changes in blood Thmem cells observed in patients with manifest cutaneous HS lesions do not appear to be characteristic of the molecular changes in the skin. Instead, they could be useful for studying comorbidities and identifying corresponding blood biomarkers in these patients.

Interleukin-19 Levels Are Increased in Palmoplantar Pustulosis and Reduced following Apremilast Treatment.

Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease characterised by neutrophilic granulocyte (neutrophil)-filled pustules on the palms and soles. The pathogenesis of PPP is poorly understood. This study conducted an identification of the immune mediators associated with PPP and an exploration of apremilast treatment effects on them. We screened for immune mediators elevated in blood taken from 68 patients with PPP versus control participants and included the most promising parameters in the protocol of phase the 2, multicentre study of apremilast (PDE4 inhibitor) in 21 patients with moderate-to-severe PPP (APLANTUS; EudraCT 2016-005122-11) for respective analysis of blood and skin samples of study patients. We investigated stimulated neutrophils and three-dimensional reconstituted epidermis cultures. Interleukin (IL)-19 was found to be the most upregulated immune mediator in the blood of PPP patients. IL-19 serum levels were independent of patients' age, gender, and BMI but were associated with strongly upregulated cutaneous IL-19 expression and correlated with the number of palmoplantar pustules. In patients participating in the APLANTUS study, apremilast reduced pustules more effectively than erythema and scaling. Moreover, this treatment significantly reduced IL-19 blood and skin levels. The reduction in IL-19 blood levels at week 4 correlated with the reduction in pustule counts at week 20 (end of treatment). IL-19 was expressed by neutrophils activated in vitro and induced CXCL6, a neutrophil-attracting chemokine, in epidermis models. This work demonstrates elevated IL-19 levels in the blood and skin of PPP patients and suggests a relevant role of this cytokine in the appearance of pustules in this disorder. It also suggests the suitability of IL-19 blood levels as a predictive biomarker for the treatment response of PPP patients, which should be validated in further studies.

Efficacy and Safety of Methotrexate in Psoriasis Vulgaris Long-Term Treatment: A Real-World Observation Study.

Background: Methotrexate (MTX) in the therapy of psoriasis vulgaris (PV) is a well and long-established treatment option. Aims: To assess the long-term experience of individual patients in the real world with regard to the efficacy and safety of MTX in PV therapy. Patients and Methods: In a retrospective study, MTX as a weekly used monotherapy in PV was examined. Clinical data including the Psoriasis Area Severity Index (PASI), prevalence of psoriatic-arthritis (PsA), Investigator Global Assessment (IGA), laboratory parameters, occurrence of adverse events (AEs), dosing of MTX and characteristics of patients treated for at least 24 months were collected. Results: A total of 55 patients with 247 patient-years under MTX therapy were included. The mean PASI reduction was 51.2% with a significant (P < 0.001) improvement in the skin condition in the first 6 months of treatment, remaining stable thereafter. The mean MTX dose increased from 11.8 ± 3.7 mg to 12.9 ± 3.8 mg in the first year of therapy, with a constant mean dose in the following years. In 247 patient-years, no serious AE was documented. Gastrointestinal side effects or fatigue were commonly detected. The liver parameter alanine aminotransferase/ glutamate-pyruvate transaminase (ALT/GPT) (baseline 35.8 ± 22.0 U/L) increased after 3 years of therapy (42.0 ± 22.4 U/L; P = 0.013) without clinical significance. Conclusion: In this patient collective, MTX in low doses was effective and safe in long-term therapy. The improved skin condition was steady and reached by an unvarying dose. New data showed a better efficacy of MTX in higher doses; however, additional data must be collected on the long-term efficacy and safety of MTX with a higher dose regime.

Patient Preferences in Hidradenitis Suppurativa (APProach-HS): a discrete choice experiment.

BACKGROUND AND OBJECTIVES: Treatment options for moderate-to-severe hidradenitis suppurativa (HS) comprise antibiotics, biologics, and different surgical methods. These approaches differ substantially regarding the treatment process, success rates, and adverse events. However, information on patient preferences for HS therapies is hitherto scarce. Our aim was to assess patient preferences for medicamentous and surgical treatment of HS with conjoint analysis. PATIENTS AND METHODS: In this cross-section study, computerized discrete choice experiments were used to quantify patient preferences for HS therapies decomposed into treatment modality (tablets, subcutaneous injections, surgery with secondary-intention healing or primary closure), probability of sustained therapeutic success, probability of mild or severe adverse events, and duration of treatment or wound healing. RESULTS: Averaged over the cohort (n  =  216 patients with HS), sustained therapeutic success was considered as most important (Relative Importance Score [RIS]: 36.2), followed by the treatment modality (RIS: 24.0), and duration of treatment/wound healing (RIS: 19.9), whereas mild or severe adverse events (RIS: 10.7 or 9.3) were regarded as less relevant. Patients preferred tablets, followed by subcutaneous injections, and disliked surgery with primary closure. Preferences differed significantly dependent on age and affected body regions. CONCLUSIONS: Awareness of patient preferences is essential for patient-centered care in HS.

Low Pneumococcal Vaccination among Patients with Psoriasis in Germany: Results from Vac-Pso.

While suboptimal pneumococcal vaccination rates have been reported in immunosuppressed patients with rheumatic diseases, data for patients with psoriasis (PsO) or atopic dermatitis (AD) are scarce. Pneumococcal vaccination in Germany is recommended in patients with certain comorbidities, immunosuppression, and/or aged 60 years or above. The aim of this multicenter cross-sectional study was to investigate the pneumococcal vaccination rate in patients with PsO compared to patients with AD and to evaluate patient perceptions. All patients completed a questionnaire on vaccination status and perceptions, patient and disease characteristics, as well as comorbidity. Medical records and vaccination certificates were reviewed. Over the whole cohort (n = 327 PsO (41.9% female), n = 98 AD (42.9% female)), 83.8% and 42.9% of PsO and AD patients, respectively, had an indication for pneumococcal vaccination due to immunosuppressive treatment. The pneumococcal vaccination rate was 14.4% and 10.2% in PsO and AD patients, respectively. The vaccination rate depended significantly on age, working status and presence of psoriatic arthritis. The most common reason for nonvaccination was lacking recommendation by physicians. Higher awareness, particularly for vaccination indication due to immunosuppression among dermatologists, general physicians, and patients, is warranted.

Generalized pustular psoriasis: overview of the status quo and results of a panel discussion.

Generalized pustular psoriasis (GPP) is a rare, severe, potentially life-threatening, autoinflammatory, neutrophilic skin disease that may be accompanied by fever and leukocytosis. This paper describes the current state of knowledge on GPP in terms of classification, (differential) diagnosis and prevalence. We present a comparison of the genetics and pathoimmunology of GPP and psoriasis vulgaris with the central mechanisms of autoimmunology and autoinflammation. The currently available therapeutic options, expert recommendations for therapy, and data from early clinical trials investigating targeted therapies will be summarized. We present the results of our discussion with 13 experts for psoriasis vulgaris and GPP and give an integrated overview of indication and therapy based on our personal experience and present an outlook on further research questions. Collectively, this article highlights the high unmet need in GPP, as there exists no satisfactory method of diagnosis or treatment to date and new treatment options will be of great therapeutic benefit to those affected.