Current Treatments for Generalized Pustular Psoriasis: A Narrative Summary of a Systematic Literature Search.

Generalized pustular psoriasis (GPP) is a rare, chronic and potentially life-threatening autoinflammatory skin disease characterized by widespread eruption of sterile pustules, with or without systemic inflammation. GPP can significantly reduce patients' quality of life (QoL). Several therapeutic approaches have been described in the literature, but there is no consensus on optimal treatment. In this review, we summarize published literature on efficacy, safety and QoL outcomes associated with current treatment of GPP with both approved and non-approved products. Embase and MEDLINE databases were searched (1980-September 2023). A search protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on the PROSPERO database (CRD42021215437). Details on publication, population, intervention, efficacy, safety and QoL were captured and checked by independent reviewers. In total, 118 publications were included, with only 19% of publications reporting on the results of clinical trials. Treatment modalities reported for GPP included non-biologic systemic therapies such as retinoids, cyclosporine and methotrexate, topical agents, biologics and small molecules, among others. Results were highly heterogeneous and methodological quality was very low, with only the interleukin-36R inhibitor spesolimab reporting results from placebo-controlled randomized trials; based on this, spesolimab is now approved for GPP treatment in regions including the USA, Japan, China, the EU and several other countries. Some other biologics are approved exclusively in Japan and Taiwan for the treatment of GPP based on open-label studies with small patient numbers in lieu of double-blind studies. Non-standardization of clinical outcomes across studies remains a major hurdle in reaching a consensus on optimal treatment. However, recently trials have been conducted using well-defined, disease-specific endpoints to evaluate GPP-targeted treatments, which will hopefully advance patient care. In conclusion, this review highlights the need for prospective randomized studies with GPP-specific endpoints to determine the optimal treatment strategy.

Generalized pustular psoriasis (GPP) is a rare, chronic skin condition characterized by painful, sterile pustules that can occur all over the body. These pustules may also be accompanied by systemic inflammation, which can lead to serious health complications. GPP significantly impacts patients' quality of life and can even be life-threatening. Because the disease is so rare, treatment guidelines have typically been based on those for plaque psoriasis. However, these guidelines do not specifically address the unique needs of GPP. In this review, we analysed the published literature on GPP management, focussing on treatment efficacy, safety and quality of life outcomes. We searched the literature databases Embase and MEDLINE for articles published between 1980 and September 2023. In total, we identified 118 publications on this topic, covering a wide range of therapies; only one of these therapies, spesolimab, reported results from placebo-controlled randomized trials. Based on these trials, spesolimab is now approved for GPP treatment in the USA, Japan, China, the EU and several other countries. Some other therapies are approved exclusively in Japan and Taiwan based on small, open-label studies in the absence of higher-quality data. To date, comparing treatments has been challenging because of different clinical outcomes used to measure effectiveness. However, well-defined endpoints specific to GPP have recently been developed and used in trials. In conclusion, our review highlights the need for prospective randomized studies with GPP-specific endpoints to determine the best treatment strategy.

A cross-sectional study of noninfectious - nonvenereal genital dermatoses among adult males at tertiary care hospital in South Gujarat.

Background: A number of dermatoses affect the genitalia in a unique and distinct manner. Nonvenereal dermatoses may not be restricted to genitalia alone; it may affect other body sites and mucous membranes as well. Dermatoses involving genital areas are not necessarily sexually transmitted. Skin lesions of the genitalia may be physiological, venereal, or nonvenereal in origin. Studies on genital dermatoses of only nonvenereal and noninfectious origin among adults are not commonly documented in India. Objectives: The objectives of this study were to determine the clinical pattern and frequency of noninfectious nonvenereal genital dermatoses. Materials and Methods: A total of 261 patients with noninfectious nonvenereal genital dermatoses attending tertiary care hospital were enrolled from August 2019-July 2020. Cases of more than 18 years of age who had given informed valid consent were included in the study, whereas venereal or infectious dermatoses were excluded from this study. The diagnosis was established based on a detailed history, examination, biopsy, and relevant investigations. Data collection was done using predesigned pro forma, and analysis was perfomed using MS Excel. Results: Maximum participants were middle aged with a mean age of 43.38 ± 9.45 years. The most common nonvenereal genital dermatoses were vitiligo (23.37%), followed by physiological conditions (19%-92%), papulosquamous dermatosis (18.77%), lichen simplex chronicus (16.48%), premalignant conditions (6.51%), vesiculobullous conditions and benign conditions (4.98%) each, adverse cutaneous drug reactions (4.21%), and malignant conditions (0.77%). About 78.54% of participants had dermatosis over genitalia only. Focal vitiligo was the most common dermatosis involving only genitalia. Conclusions: This study is novel as participants enrolled only of noninfectious, nonvenereal genital dermatoses among males.

Follmann balanitis in secondary syphilis.

Syphilitic balanitis is an uncommon rather underreported manifestation of primary syphilis initially described by Eugene Follmann and subsequently named after him. It is characterized by balanitis with or without a primary chancre and inguinal lymphadenopathy. Given its rarity, Follmann balanitis may be misdiagnosed with other causes of balanitis. Therefore, a strong clinical suspicion and awareness are crucial, particularly in the current resurgence of syphilis. With this background, we hereby report a case of Follmann balanitis in secondary syphilis, diagnosed based on clinical features, positive syphilis serology, and response to benzathine penicillin treatment.

Nevus comedonicus of glans with unusual morphology due to manipulation.

Nevus comedonicus, an uncommon skin condition, was originally termed "comedo nevus" by Kofmann in 1895. It is characterized by the clusters of pits-containing black keratinous plugs resembling blackheads. Conventionally, nevus comedonicus manifests at birth (in 50% of cases) or during the first decade of life. The commonly affected areas include the head, neck, chest, upper, and lower limbs, with patterns ranging from unilateral, bilateral, linear, interrupted, segmental, to blaschkoid. While genital nevus comedonicus is rare, some cases have been reported. In this report, we present a case of nevus comedonicus on the glans, underscoring the importance of considering nonsexually transmitted disease-related causes for genital lesions.

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.

UVB-induced TRPS1 regulates MITF transcription activity to promote skin pigmentation.

Hyperpigmented dermatoses are characterized by increased skin pigmentation caused by genetic, environmental factors and inflammation, which lasts a long time and is difficult to treat. Ultraviolet (UV), especially ultraviolet B (UVB), is the primary external factor inducing skin pigmentation. However, the specific regulatory mechanisms are not fully understood. Through analysis of GEO datasets from four UV-exposed skin cell/tissue samples, we found that TRPS1 is the only gene differentially expressed in multiple datasets (GSE22083, GSE67098 and GSE70280) and highly positively correlated with the expression of key melanogenesis genes. Consistently, we observed that TRPS1 is highly expressed in sun-exposed skin tissues compared to non-exposed skin. Additionally, the expression of TRPS1 was also significantly upregulated after UVB irradiation in isolated skin tissues and melanocytes, while knockdown of TRPS1 expression inhibited the UVB-induced melanogenesis. Further research revealed that overexpression of TRPS1 increased melanin content and tyrosinase activity in MNT1 cells, as well as upregulated the expression levels of key melanogenesis genes (MITF, TYR, TYRP1, DCT). In contrast, inhibition of TRPS1 expression showed the opposite effect. Moreover, we found that TRPS1 can bind to the promoter region of MITF, inhibiting the expression of MITF can antagonize the melanogenesis induced by TRPS1. In conclusion, UVB-induced TRPS1 promotes melanogenesis by activating the transcriptional activity of MITF.

Coencapsulation of Immunosuppressive Drug with Anti-Inflammatory Molecule in Pickering Emulsions as an Innovative Therapeutic Approach for Inflammatory Dermatoses.

Psoriasis is an inflammatory skin disease characterized by epidermal and immune dysfunctions. Although efficient, current topical treatments display adverse effects, including skin atrophy and burning sensation, leading to poor patient adherence. To overcome these downsides, pickering emulsions were formulated in which the calcitriol-containing dispersed phase was stabilized with either cyclosporin A- or tacrolimus-loaded poly(lactic-co-glycolic) acid nanoparticles. This study aimed to investigate their biological effects on lymphocytes and epidermal cells and their effectiveness in an imiquimod-induced psoriasis-like mouse model. Results showed that both emulsions significantly inhibited nuclear factor of activated T cell translocation in T lymphocytes as well as their IL-2 production, cell activation, and proliferation. In keratinocytes, inhibition of nuclear factor of activated T cell translocation decreased the production of IL-8 and TNF-α. Topical application of emulsions over skin biopsies ex vivo showed accumulation of rhodamin B-coupled poly(lactic-co-glycolic) acid nanoparticles throughout the epidermis by immunofluorescence and significantly decreased the antigen-presenting capacity of Langerhans cells in relation to a reduced expression of activation markers CD40, CD86, and HLA-DR. Using an imiquimod-induced psoriasis model in vivo, pickering emulsions significantly alleviated psoriasiform lesions potentially attributed to the decreased cutaneous expression of T-cell markers, proinflammatory cytokines, chemokines, and specific epidermal cell genes. Altogether, pickering emulsion might be a very efficient formulation for treating inflammatory dermatoses.

Spontaneous regression of primary cutaneous diffuse large B-cell lymphoma, leg type: A case series and review of the literature.

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT) is a subtype of cutaneous B-cell lymphoma with unfavorable prognosis usually requiring aggressive polychemotherapy for disease control. Only single cases of spontaneous regression of PCDLBCL, LT are reported in the literature, peaking 3 months post-biopsy following a clinical history of no longer than 1 year. Here, we report the first case of a spontaneously relapsing and remitting PCDLBCL, LT with complete regression after a clinical history of more than 9 years and thus an atypically indolent clinical course. The female patient presented with recurrent erythematous, non-ulcerated, non-raised plaques of the right lower leg for 6 years. Pathological workup and exclusion of a systemic disease confirmed the diagnosis of PCDLBCL, LT. Due to the history of repeated spontaneous remission, no therapy was initiated. Nine years after first occurrence the patient presented with complete clinical remission lasting for 64 months. We retrospectively identified four additional PCDLBCL, LT patients with spontaneous remission lasting up to 53 months. Our data provide evidence for a distinct PCDLBCL, LT patient subgroup that clinicians should be aware of and warrants a watch-and-wait treatment regime.

Current challenges in diagnosing and treating infectious skin diseases - a case series. / Choroby zakazne skóry jako wciaz aktualny problem diagnostyczny i terapeutyczny ­ przeglad nietypowych przypadków klinicznych.

Infectious skin diseases constitute a significant public health problem. Despite the systematic development of many modern diagnostic and therapeutic tools, they still pose a serious challenge for clinicians. Due to their prevalence and mild course in most cases, they are often marginalized, which can delay their diagnosis and treatment initiation. Such an approach in more clinically advanced cases can have serious consequences, sometimes leading to tragic outcomes. This work presents a series of four cases of common infectious skin diseases with an unusually atypical clinical picture: the history of a 49-year-old female patient with recurrent erysipelas of the right lower leg co-occurring with a SARS-CoV-2 infection, a 75-year-old male patient with a generalized form of herpes zoster, a 38-year-old female patient with a complicated severe course of head lice, and a 34-year-old male patient with a severe form of post-steroid mycosis. In each of these cases, difficulties in making the correct diagnosis were highlighted, even though they represent some of the most common bacterial, viral, parasitic, and fungal dermatoses. The paper discusses the risk factors for these diseases, the pathophysiology of their atypical course, the effects and challenges in the therapeutic approach conducted. Infectious skin dermatoses require aggressive treatment and should never be underestimated.

Isolated Neutrophilic Urticarial Dermatosis in a Previously Healthy Male: A Case Report.

Neutrophilic urticarial dermatosis (NUD), a variant falling under the larger umbrella of neutrophilic dermatoses (NDs), is characterized by distinctive clinical and histopathological attributes often associated with systemic conditions. This report presents a case of a 45-year-old male with no prior health issues who exhibits both clinical and pathological hallmarks of NUD without any concurrent systemic illness. This singular case illuminates the intricate aspects of NUD, emphasizing the necessity for accurate diagnostic methods and effective treatment strategies.

Adjunctive hyperbaric oxygen treatment for challenging pyoderma gangrenosum cases.

INTRODUCTION: Pyoderma gangrenosum (PG) is a rare, difficult-to-treat neutrophilic ulcerative cutaneous condition that severely impacts those affected. Treatment options for PG are limited, and disease remission is not guaranteed. Hyperbaric oxygen treatment is a potential therapeutic option for treating various ulcerative conditions not frequently utilized for PG. CASE REPORT: We present a case of a patient with treatment-resistant PG who achieved remission with adjunctive HBOT, and then later had difficulty achieving remission without HBOT during a future flare. DISCUSSION: HBOT should be more readily considered as a treatment option for those with PG.

[Palmoplantar dermatoses: Diagnostic approach in primary care]. / Dermatosis palmoplantares: aproximación diagnóstica en atención primaria.

This article addresses the diagnostic challenges of palmoplantar dermatoses (PPD) within the scope of Primary Health Care (PHC). These common skin conditions, encountered in daily practice, exhibit a diverse range of symptoms and morphologies, complicating their diagnosis. They are etiologically classified into infectious inflammatory, non-infectious inflammatory, and hereditary keratodermas. While various dermatoses may affect the palms and soles, few are specific to this area. Notable examples include palmoplantar pustulosis, dyshidrosis, erythema pernio, and Bazex syndrome. Given the high prevalence of dermatological consultations in PHC, this article underscores the significance of PHC professionals' knowledge regarding these conditions. It proposes a diagnostic algorithm to facilitate their management and timely referral.

A Review of the Use of Intravenous Immunoglobulin Therapy in Dermatology.

Intravenous immune globulin (IVIG) is a manufactured blood product commonly used to treat immunodeficiency syndromes, inflammatory disorders, and autoimmune diseases of the skin. The use of IVIG in dermatology has evolved and expanded over time, serving as a useful therapeutic intervention for several inflammatory skin disorders. In addition to demonstrating efficacy in treating several cutaneous pathologies, IVIG also mitigates the need for steroids or other immunosuppressant medications in many dermatologic diseases. This review highlights the evidence for IVIG use across several dermatologic conditions, emphasizing the dosing regimens and safety considerations.

Pharmacology of drugs used in autoimmune dermatopathies in cats and dogs: A narrative review.

Immunosuppressive drugs are the mainstay of treatment for many feline and canine autoimmune skin diseases, either as monotherapy or in combination with other drugs. Treatment with these drugs is often lifelong and may have long-term consequences on the affected animal's overall quality-of-life. Clinicians need to understand the pharmacology of immunosuppressants in planning and executing the treatment regimen for the best possible clinical outcome, as well as reducing the risk of adverse effects. This review paper will focus on the mechanism of action, pharmacokinetics and pharmacodynamics, clinical uses and adverse effects of immunosuppressive drugs used to treat autoimmune dermatoses in cats and dogs. These include glucocorticoids, ciclosporin A, azathioprine, chlorambucil, mycophenolate mofetil, oclacitinib and Bruton's tyrosine kinase inhibitors.

Les médicaments immunosuppresseurs constituent la base de la thérapeutique de nombreuses dermatoses auto­immunes félines et canines, soit en monothérapie, soit en association avec d'autres médicaments. Le traitement par ces médicaments dure souvent toute la vie et peut avoir des conséquences à long terme sur la qualité de vie globale de l'animal affecté. Les cliniciens doivent comprendre la pharmacologie des immunosuppresseurs afin de planifier et de mettre en place le plan thérapeutique, afin d'obtenir le meilleur résultat clinique possible et de réduire le risque d'effets indésirables. Cet article de synthèse cible le mécanisme d'action, la pharmacocinétique et la pharmacodynamie, les utilisations cliniques et les effets indésirables des médicaments immunosuppresseurs utilisés pour traiter les dermatoses auto­immunes chez les chats et les chiens. Ces médicaments comprennent les glucocorticoïdes, la ciclosporine A, l'azathioprine, le chlorambucil, le mycophénolate mofétil, l'oclacitinib et les inhibiteurs de la tyrosine kinase de Bruton.

Os medicamentos imunossupressores são a base do tratamento para muitas doenças de pele autoimunes felinas e caninas, seja em monoterapia ou em combinação com outros medicamentos. O tratamento com esses medicamentos costuma durar toda a vida e pode ter consequências a longo prazo na qualidade de vida geral do animal afetado. Os clínicos precisam compreender a farmacologia dos imunossupressores para planejar e executar o protocolo de tratamento para se obter o melhor resultado clínico possível, assim como reduzir o risco de efeitos adversos. Este artigo de revisão será focado no mecanismo de ação, farmacocinética e farmacodinâmica, indicações clínicas e efeitos adversos de medicamentos imunossupressores usados para tratar dermatoses autoimunes em cães e gatos. Estes incluem glucocorticóides, ciclosporina A, azatioprina, clorambucil, micofenolato de mofetila, oclacitinib e inibidores da tirosina quinase de Bruton.

Los tratamientos inmunosupresores son la línea de tratamiento principal en muchas enfermedades autoinmunes de la piel de perros y gatos, bien como monoterapia o en combinación con otros fármacos. El tratamiento con estos fármacos es a menudo de larga duración o de por vida y puede tener consecuencias adversas de larga duración en la calidad de vida de los animales. Los veterinarios clínicos tienen que entender la farmacología de los inmunosupresores durante la planificación y ejecución de los tratamientos para obtener los resultados más beneficiosos y reducir los efectos adversos. Este artículo de revisión está enfocado en los mecanismos de acción, farmacocinética, farmacodinámica, usos clínicos y efectos adversos de tratamientos inmunosupresores utilizados en perros y gatos para tratar dermatopatías inmunomediadas de la piel. Se incluyen glucocorticoides, ciclosporina A, azatioprina, clorambucilo, mofetil micofenolato, oclacitinib e inhibidores de la tirosina quinasa de Bruton.

Mimicry unveiled: The challenging diagnosis of pigmented purpura-like mycosis fungoides initially misdiagnosed as pigmented purpura.

Key Clinical Message: Unlike most cases, the lesions were localized to the dorsum of the hand, lacked pruritus (itching), and did not exhibit "sperm-like blood vessels," which are typically pathognomonic to classical MF. Abstract: The study presents a rare case involving a 44-year-old woman who developed a skin condition on the base of her left thumb. Initially misdiagnosed as pigmented purpura, the need for further investigation arose to determine the nature of the condition accurately. The medical evaluation encompassed a comprehensive analysis of the patient's skin ailment. A series of diagnostic examinations were conducted to ascertain the underlying cause. Although routine blood tests yielded unremarkable results, the distinct characteristics of the rash prompted a more thorough investigation. Subsequent assessment revealed that the skin condition was not pigmented purpura, as initially presumed, but rather a manifestation of cutaneous T-cell lymphoma (CTCL) known as mycosis fungoides (MF). MF is an infrequent lymphoma predominantly affecting individuals aged 45-65, exhibiting a male-to-female sex ratio of 2:1. The annual incidence of MF ranges from 0.3 to 0.96 cases per 100,000 individuals. The woman's skin exhibited discrete patches adorned with colored dots, progressively thickening and pigmentation. Notably, the absence of pruritus did not dispel suspicion. This case underscores the significance of accurately diagnosing uncommon dermatological disorders to facilitate appropriate medical intervention. The unique appearance of the rash and its distinctive features, despite normal blood results, enabled the identification of MF. The patient's treatment encompassed a combination of steroids and narrowband UV therapy. Vigilance, continued research, and heightened awareness are paramount for early intervention and improved patient outcomes. Such efforts contribute to an enhanced understanding of the complexities of this condition.

Eosinophilic Dermatoses: Cause of Non-Infectious Erythema after Volume Replacement with Diced Acellular Dermal Matrix in Breast Cancer?

INTRODUCTION: Non-infectious erythema, or Red Breast Syndrome (RBS), has been observed on the skin where acellular dermal matrix was implanted, although the exact cause is yet to be determined. PATIENTS AND METHODS: A total of 214 female patients underwent breast-conserving surgery (BCS) and volume replacement using diced acellular dermal matrix (dADM) for breast cancer between December 2017 and December 2018. After collecting and evaluating relevant clinical data, inflammation markers, along with NK cell status presented by IFN-γ secretion assay, were measured using ELISA. RESULTS: Nineteen patients (8.88%) presented with RBS after BCS and dADM use. A significant increase of platelet-to-lymphocyte ratio was noted in the non-RBS group (p = 0.02). Compared to the RBS group (p = 0.042), the WBC level of the non-RBS group showed significant decrease over time. Eosinophil counts increased significantly at follow-up but went up higher in the RBS group. Multivariate analysis showed preoperative chemotherapy significantly increased the hazard of RBS (OR 3.274, p = 0.047 and OR 17.098, p < 0.001, respectively). DISCUSSION: Though no causal relationship between RBS and immune status was proven, the results suggest an association between preoperative chemotherapy and RBS in addition to the possible role of eosinophilia in leading to eosinophilic dermatoses, which warrants further exploration and elucidation.