Pathological and Therapeutical Implications of Pyroptosis in Psoriasis and Hidradenitis Suppurativa: A Narrative Review.

This manuscript explores the role of pyroptosis, an inflammatory programmed cell death, in the pathogenesis of two chronic dermatoses, psoriasis and hidradenitis suppurativa (HS). The diseases, though clinically diverse, share common pathogenetic pathways involving the unbalanced interaction between the adaptive and innate immune systems. This review focuses on the molecular changes in psoriatic and HS skin, emphasizing the activation of dendritic cells, secretion of interleukins (IL-17, IL-22, and TNF-α), and the involvement of inflammasomes, particularly NLRP3. This manuscript discusses the role of caspases, especially caspase-1, in driving pyroptosis and highlights the family of gasdermins (GSDMs) as key players in the formation of pores leading to cell rupture and the release of proinflammatory signals. This study delves into the potential therapeutic implications of targeting pyroptosis in psoriasis and HS, examining existing medications like biologics and Janus kinase inhibitors. It also reviews the current limitations and challenges in developing therapies that selectively target pyroptosis. Additionally, the manuscript explores the role of pyroptosis in various inflammatory disorders associated with psoriasis and HS, such as inflammatory bowel disease, diabetes mellitus, and cardiovascular disorders. The review concludes by emphasizing the need for further research to fully elucidate the pathomechanisms of these dermatoses and develop effective, targeted therapies.

Illuminating characteristic patterns of inflammatory dermatoses: A comprehensive dual-imaging approach using Optical coherence tomography and Line-field confocal optical coherence tomography.

BACKGROUND: Inflammatory skin diseases, such as psoriasis, atopic eczema, and contact dermatitis pose diagnostic challenges due to their diverse clinical presentations and the need for rapid and precise diagnostic assessment. OBJECTIVE: While recent studies described non-invasive imaging devices such as Optical coherence tomography and Line-field confocal OCT (LC-OCT) as possible techniques to enable real-time visualization of pathological features, a standardized analysis and validation has not yet been performed. METHODS: One hundred forty lesions from patients diagnosed with atopic eczema (57), psoriasis (50), and contact dermatitis (33) were imaged using OCT and LC-OCT. Statistical analysis was employed to assess the significance of their characteristic morphologic features. Additionally, a decision tree algorithm based on Gini's coefficient calculations was developed to identify key attributes and criteria for accurately classifying the disease groups. RESULTS: Descriptive statistics revealed distinct morphologic features in eczema, psoriasis, and contact dermatitis lesions. Multivariate logistic regression demonstrated the significance of these features, providing a robust differentiation between the three inflammatory conditions. The decision tree algorithm further enhanced classification accuracy by identifying optimal attributes for disease discrimination, highlighting specific morphologic criteria as crucial for rapid diagnosis in the clinical setting. CONCLUSION: The combined approach of descriptive statistics, multivariate logistic regression, and a decision tree algorithm provides a thorough understanding of the unique aspects associated with each inflammatory skin disease. This research offers a practical framework for lesion classification, enhancing the interpretability of imaging results for clinicians.

Compression Therapy in Dermatology. / Terapia compresiva en Dermatología.

The benefit of lower limb compression therapy is not limited to chronic venous insufficiency or/and lymphoedema. Thanks to its anti-edema and anti-inflammatory effects, compression therapy is considered a beneficial adjuvant therapy to treat atypical wounds, inflammatory dermatoses, cellulitis, and traumatic wounds in the absence of contraindications. Strict contraindications are limited to severe peripheral arterial disease and decompensated heart failure. The variability of commercially available compression materials and systems, such as short-stretch bandages, multi-component systems, zinc oxide bandages, medical adaptive compression systems, ulcer compression stockings or medical compression stockings, facilitates the adaptation of compression therapy to the individual needs of each patient. Compared to venous leg ulcers, low pressures of 20mmHg are often sufficient to treat dermatological disorders, with higher patient tolerance and compliance.

Achieving consensus on patient-reported outcome measures in clinical practice for inflammatory skin disorders.

BACKGROUND: International Dermatology Outcome Measures and the American Academy of Dermatology recently agreed on a physician-reported global severity measure to demonstrate quality of care in inflammatory dermatoses. OBJECTIVE: Because patient-reported outcome measures are also important, we aimed to achieve consensus on 1 of these measures for clinical practice. METHODS: Patients and providers participated in a consensus-building study involving a modified-Delphi technique. Voting was focused on identifying a minimal set of assessments for clinical practice, patient global assessments (PtGAs), Skindex instruments, and final instrument selection for quality improvement. RESULTS: Among 53 stakeholders, >70% agreed that identification of patient goals, assessment of treatment harm, and assessment of the adequacy of treatment response were the minimal assessments needed for clinical practice. The most preferred PtGA was a 5-point PtGA (scale 0-4; 0 = clear, 4 = severe) having an optional check-box for worst ever. A new metric to assess change since treatment initiation, which we called a trajectory measure, was proposed. Stakeholders preferred Skindex instruments over PtGAs and a trajectory measure for clinical practice. LIMITATIONS: A small number of patients and caregivers were involved and a consensus was not reached on all items. CONCLUSION: PtGAs as standalone measures do not adequately capture the patient's assessment of disease severity or the effect of care. The combination of a PtGA with a Skindex instrument or another measure of health-related quality of life might provide a more comprehensive evaluation of patients in clinical practice.

Dermatoscopy of nodular/plaque-type primary cutaneous T- and B-cell lymphomas: A retrospective comparative study with pseudolymphomas and tumoral/inflammatory mimickers by the International Dermoscopy Society.

BACKGROUND: Limited data on dermatoscopy of nodular/plaque-type T-/B-cell primary cutaneous lymphomas (PCLs) is available. OBJECTIVE: To describe dermatoscopic features of nodular/plaque-type PCLs, comparing them with those of clinical mimickers (pseudolymphomas, tumors, and inflammatory lesions) and investigating possible differences according to histologic subtypes. METHODS: Participants were invited to join this retrospective, multicenter case-control study by submitting histologically/immunohistochemically confirmed instances of nodular/plaque-type PCLs and controls. Standardized assessments of the dermatoscopic images and comparative analyses were performed. RESULTS: A total of 261 lesions were included (121 PCLs and 140 controls). Orange structureless areas were the strongest PCL dermatoscopic predictor on multivariate analysis compared with tumors and noninfiltrative inflammatory dermatoses. On the other hand, a positive association was found between PCLs and either unfocused linear vessels with branches or focal white structureless areas compared with infiltrative inflammatory dermatoses, whereas white lines were predictive of PCLs over pseudolymphomas. Differences in the vascular pattern were also seen between B- and T-cell PCLs and among B-cell PCL subtypes. LIMITATIONS: Retrospective design and the lack of a dermatoscopic-pathologic correlation analysis. CONCLUSION: Nodular/plaque-type PCLs display dermatoscopic clues, which may partially vary according to histologic subtype and whose diagnostic relevance depends on the considered clinical differential diagnoses.

Bullous Pemphigoid-Associated Mortality Rate in a Canadian Tertiary Referral Centre.

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disorder in adults. Most individuals with BP are over the age of 60. Its worldwide incidence has been increasing owing to population aging. Observational studies published over the last 2 decades highlight the non-negligible, albeit variable overall mortality of BP patients, with reported 12-month mortality rates of 10.8% to 40.8%, and 24-month mortality rates of 20.1% to 51.0%. Data in the Canadian population are lacking. OBJECTIVES: We aimed to estimate the 12- and 24-month overall mortality rate of Canadian patients diagnosed with BP, and to identify independent risk factors adversely impacting overall survival. METHODS: A retrospective cohort study of 166 patients with a diagnosis of BP between 2010 and 2020 was carried out at Centre hospitalier de l'Université de Montréal (CHUM), a tertiary referral center in Montréal, Québec, Canada. Cumulative mortality was calculated using the Kaplan-Meier estimator, and independent prognostic factors were identified using a Cox proportional hazards regression model. RESULTS: Eighty-five patients (51.2%) in our study were female. The median age was 79.1 years old, and 80 patients (48.2%) were 80 years old or older. Mortality at 12 and 24 months in our study cohort was 16.2% (CI95% = 10.5 - 21.8) and 27.6% (CI95% = 20.5 - 34.7), respectively. In a multivariate analysis, patients who were male, 80 years old or older, and/or had a diagnosis of a major neurocognitive disorder had a poorer overall survival. CONCLUSIONS: The all-cause mortality of patients with BP in our study population compared favorably with international data reported in the literature.

Comparison of p53 immunohistochemical staining in differentiated vulvar intraepithelial neoplasia (dVIN) with that in inflammatory dermatoses and benign squamous lesions in the vulva.

AIMS: Differentiated vulvar intraepithelial neoplasia (dVIN), the precursor lesion to human papillomavirus-independent vulvar squamous cell carcinoma (VSCC), can be difficult to distinguish from vulvar inflammatory dermatoses. Our goal was to determine if p53 could be a useful biomarker for dVIN, by characterizing p53 percentage, intensity and patterns of staining in dVIN and its histological mimics. METHODS AND RESULTS: We studied p53 immunohistochemical staining patterns in 16 dVIN cases and 46 vulvar non-neoplastic squamous lesions [12 lichen sclerosus (LS); seven lichen simplex chronicus; three lichen planus (LP); six psoriasis; 13 spongiotic dermatitis (SPO); and five candidiasis]. dVIN cases were adjacent to a p16-negative invasive VSCC in resection specimens. All dVIN cases showed null-type or moderate to strong uniform p53 staining in >70% of basal cells, with moderate to strong continuous parabasal staining extending to two-thirds of the epidermis. This was in contrast to weak or weak to moderate patchy p53 staining in the majority of other lesions. Moderate to strong and increased basal p53 staining (≥70%) was also observed in a subset of LS cases (5/12, 42%), LP cases (1/3, 33%), and SPO cases (36%, 4/11); however, in all categories, this was limited to the basal layer, and any staining in the parabasal layers was patchy. CONCLUSION: Strong and uniform p53 staining of basal cells, extending into the parabasal layers, and a complete absence of staining (null type) is useful in distinguishing dVIN from other mimics in the vulva. p53 staining of lesser intensity or quantity, particularly basal overexpression only, overlaps with that in vulvar inflammatory lesions.

Can intermittent, time-restricted circadian fasting modulate cutaneous severity of dermatological disorders? Insights from a multicenter, observational, prospective study.

The impact of intermittent circadian fasting (ICF) on skin disorders is far to be plenty deciphered. However, the circadian rhythm seems to exert a modulation on dermatoses severity, drug-response, and drug-related side effects. We aimed to evaluate ICF effect in the daily management of dermatological diseases. In this multicenter, prospective observational study we enrolled patients willing to undergo the 2018 ICF (from May 16 to June 14). Dermatoses severity were evaluated at the beginning of ICF (T0) and at the end of ICF (T1) by two independent board-certified dermatologists. Seventy-two patients suffering from different dermatoses volunteered to take part into the study. They displayed a mean age of 40.38 ± 12.46 years (median 41.0 years), 25 subjects were males (34.7% of the entire sample). The median weight change was 0 kg. The overall ICF effect size was -0.58 ([95% CI -0.83 to -0.33], P < .0001, medium effect size). Since in the present investigation no weight loss occurred, we could speculate that the impact of fasting in terms of improvements in the clinical symptoms could be rather due to the perturbation of the human biological clock. Despite our data remain preliminary, a chronobiological approach should be incorporated in the dermatological armamentarium.

Tetracyclines in COVID-19 patients quarantined at home: Literature evidence supporting real-world data from a multicenter observational study targeting inflammatory and infectious dermatoses.

Tetracyclines (TetraC) are widely used in dermatology for both inflammatory and infectious dermatoses; recently both in vivo and in vitro studies started to suggest also a potential antiviral effect. During COVID-19 outbreak, several dermatological patients contracted SARS-CoV-2 experiencing only mild symptoms, but no protocol were approved. A multicenter prospective observational study that enrolled COVID-19 patients visited with teledermatology and undergoing TetraC was performed. About 38 adult outpatients (M/F: 20/18, age 42.6 years [21-67]) were enrolled. During the TetraC treatment, symptoms resolved in all patients within 10 days. Remarkably, ageusia and anosmia disappeared in the first week of TetraC treatment. TetraC seem a promising drug to treat COVID-19 outpatients with mild symptoms.

Coexistence of Hidradenitis Suppurativa and Steatocystoma Multiplex: Is It a New Variant of Hidradenitis Suppurativa?

Hidradenitis suppurativa and steatocystoma multiplex may coexist in the same patient. The overlap of these 2 conditions could be suggestive of an unrecognized defect in follicular proliferation mutual in the pathogenesis of both conditions. Here we present 5 patients with both hidradenitis suppurativa and steatocystoma multiplex. Recognizing the overlap between these 2 conditions is important for accurate diagnosis, management, and identification of potential surgical candidates, as well as future basic science research.

Photodynamic therapy in dermatology: Beyond current indications.

Photodynamic therapy (PDT) has long been used in dermatology as a therapeutic strategy for several malignant and premalignant conditions. Currently, it is approved in Europe for the treatment of actinic keratosis, squamous cell carcinoma in situ, and some forms of basal cell carcinoma, with favorable clearance rates associated with satisfying aesthetic results. Nonetheless, in the past few years, PDT has also demonstrated efficacy in many other conditions, including inflammatory and infectious dermatoses. These results, probably explained by its immunomodulatory, anti-inflammatory, and bactericidal effects, may lead to an expansion of PDT indications in the upcoming years. In this article, conditions where PDT may be useful are reviewed, thus highlighting the potential of this therapeutic modality for the dermatologist.

Pearls in Mitigating Application Pain of Topical Nonsteroidal Agents.

BACKGROUND: Topical steroid-sparing agents (SSA), such as tacrolimus, pimecrolimus, and crisaborole, represent an important therapeutic option in the treatment of inflammatory dermatoses such as atopic dermatitis. While these agents lack the common side effects associated with topical corticosteroids, they all share application site pain as an important adverse effect. SUMMARY: Based on the available evidence and our experience, we suggest the following 7 practical strategies for decreasing the pain associated with SSA use. (1) Use a topical corticosteroid for a few days to reduce inflammation before starting the SSA treatment. (2) Use SSAs strategically. (3) Apply moisturizer before applying SSAs. (4) Store moisturizers in the refrigerator. (5) Ask the patient to apply the SSA on a small test area before broader application. (6) Apply the SSA on dry rather than on damp skin. (7) Consider using aspirin when appropriate for the patient.

Impact of the COVID-19 Pandemic on Chronic Inflammatory Dermatoses: Mixed Messages Regarding the Dermatologist's Point of View and the Patient's Concerns.

is missing (Short communication).

Off-Label Therapeutic Potential of Crisaborole.

Crisaborole, a topical phosphodiesterase-4 inhibitor, was recently approved in 2016 for the treatment of mild to moderate atopic dermatitis in adults and children greater than 2 years of age. Since that time, several case reports and a small randomized controlled trial have been published regarding the off-label use of crisaborole for the treatment of other inflammatory dermatologic disorders. This paper reviews the current, albeit limited, evidence for off-label use of crisaborole for psoriasis, seborrheic dermatitis, vitiligo, and inflammatory linear verrucous epidermal nevus. Additional potential therapeutic uses for crisaborole are also postulated, based on its mechanism of action. Future studies are required to elucidate the full therapeutic potential of crisaborole; however, it is a welcome addition to the current nonsteroid topical treatments for inflammatory dermatologic disease.

[Psoriasis in dupilumab-treated atopic dermatitis]. / Psoriasis bei Dupilumab-behandeltem atopischem Ekzem.

Dupilumab is a monoclonal antibody that binds to the common alpha chain of the IL­4 and IL-13 receptor and blocks the Th2 signaling pathway, which plays a key role in the development of atopic dermatitis. We report on the case of a 40-year-old man, who developed histologically confirmed psoriasis after 6 weeks of dupilumab therapy. The arbitrary, abrupt stopping of the unusual, not guideline-based oral steroid therapy, together with the blockade of the Th2 signaling pathway by dupilumab were apparently the relevant trigger factors for the newly developed psoriasis in our patient.

A provider global assessment quality measure for clinical practice for inflammatory skin disorders.

In our evolving health care system, dermatologists are increasingly being asked to prove the value of care they provide to patients with severe skin diseases. Current quality measures for inflammatory dermatoses have limited validity and feasibility. Through collaboration and a modified Delphi process, International Dermatology Outcome Measures and the American Academy of Dermatology sought to reach consensus on a valid and feasible provider-assessed global disease severity metric to be incorporated into a quality measure for inflammatory dermatoses. To inform the modified Delphi process, a review of the literature was performed, and data were collected on current provider-assessed global disease severity metrics. After literature review, 36 members of International Dermatology Outcome Measures and the American Academy of Dermatology participated in the modified Delphi process to reach consensus on features of the metric. Psoriasis, atopic dermatitis, and acne achieved overwhelming consensus for inflammatory dermatoses that could be measured in a global disease severity metric. Consensus was also reached on the use of a 5-point ordinal scale with descriptors provided through referenced electronic platforms. Expert development of quality measures incorporating this metric and its inclusion in data collection platforms are critical to enabling dermatologists to prove the value of care provided to patients with severe inflammatory dermatoses.

Mycosis fungoides with spongiosis: A potential diagnostic pitfall.

BACKGROUND: Mycosis fungoides (MF) is characterized by epidermotropic atypical lymphocytes in the absence of spongiosis. However, we describe an unusual presentation of MF with spongiosis, mimicking benign inflammatory dermatoses and highlight the importance of pathologic interpretation for diagnostic confirmation. METHODS: A cross-sectional study of consecutive patients diagnosed with MF with spongiosis was conducted. The clinical, histopathologic, immunophenotypic, and molecular genetic features of cases were reviewed. RESULTS: We identified nine cases of MF (age range 34-82 years; mean 75 years), with an initial diagnosis of dermatitis (6/9), psoriasis (4/9), or other inflammatory dermatoses (2/9). Pruritus, pain, and blisters were common clinical manifestations. The most common areas of involvement were the extremities (8/9). Epidermotropism with spongiosis was a central histopathological feature in all cases. CONCLUSION: These cases highlight prominent spongiosis in MF and overlap with common benign inflammatory dermatoses. We present these cases to show the diagnostic pitfalls associated with spongiotic presentations of MF. Dermatitis, psoriasis, and other inflammatory skin conditions not responsive to standard therapy warrant further work-up including biopsy to rule out MF. Multiple skin biopsies and review by a dermatopathologist with expertise in the diagnosis of cutaneous lymphoma is highly recommended.

A Pilot Study Characterizing Factors in Adherence to Cutaneous Lupus Treatment.

Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease that manifests as scarring, dyspigmentation, erythema, and pain. Topical corticosteroids are a mainstay of treatment. Irritation, messiness, and tediousness may deter use. Thus, nonadherence, rather than nonresponse, can result in treatment failure. Prior adherence studies were limited to systemic lupus erythematosus. We performed a single-center, open-label pilot study to assess adherence to topical medication in patients with CLE. CLE adherence to topical medications is suboptimal and declines over time. Shorter treatment duration and greater patient perception of disease severity may contribute to higher adherence. Improving adherence to existing treatments could be as or more valuable than new therapies for the disease.