Search Results (11)

(1) Background: The IL-36 cytokines have been identified as key contributors to pustular psoriasis, and their inhibitor is already in clinical use. However, few studies have explored them in atopic dermatitis. (2) Methods: The role of IL-36α was investigated in various atopic dermatitis models using wild-type, keratin 14-specific IL-33 transgenic, IL-18 transgenic, caspase-1 transgenic, and caspase-1 transgenic mice with IL-17AF deletion, reflecting diverse aspects of human skin inflammation. IL-36α was administered subcutaneously in five doses on alternate days across the five strains to examine cellular infiltration patterns and cytokine expression levels. (3) Results: The skin phenotype was exacerbated, accompanied by worsening edema and skin thickness in all mouse groups upon IL-36α administration. An increase in infiltrating cells was observed among innate immune cells, while lymphocyte counts, including T cells and innate lymphoid cells, did not rise. Additionally, anti-inflammatory cytokines were induced simultaneously with inflammatory cytokines and downstream cytokines of IL-36α as well. Infiltrating lymphocytes in the skin displayed a distinct Type 2 cytokine-dominant profile for innate lymphoid cells and a Type 3 cytokine-dominant profile for T helper cells and γδ T cells, contrasting with the Type 1-dominant cell profile in draining lymph nodes. Type 1, Type 2, and Type 3 cytokine dominance patterns were not affected by the administration of IL-36α. (4) Conclusions: IL-36α triggers inflammatory responses in atopic dermatitis by activating innate immunity. The infiltrating lymphocytes in the skin have different cytokine production profiles between innate lymphoid cells and T cells, as well as different patterns of cytokine production in their draining lymph nodes. Full article

The sebaceous gland (SG) is an integral part of the pilosebaceous unit and is a very active and dynamic organ that contributes significantly to the maintenance of skin homeostasis. In addition to its primary role in sebum production, the SG is involved in the maintenance of skin barrier function, local endocrine/neuroendocrine function, the innate immune response, and the regulation of skin bacterial colonization. Structural and functional alterations of SGs leading to the dysregulation of sebum production/composition and immune response may contribute to the pathogenesis of inflammatory dermatoses. This review summarises the current knowledge on the contribution of SGs to the pathogenesis of common inflammatory skin diseases. These findings are crucial for the development of more effective therapeutic strategies for the treatment of inflammatory dermatoses. Full article

Acute and recurrent pustulosis (ARP), previously known as actinic folliculitis, superficial actinic folliculitis, or even acne aestivalis, is a rare, underdiagnosed dermatological condition characterized by the sudden onset of monomorphic pustular eruptions on an erythematous background localized predominantly on the upper body. While typically associated with sun exposure, ARP can also be triggered by other factors, such as heat or sweating, underscoring its multifactorial etiology. We report the case of a 40-year-old woman with ARP, presenting diagnostic challenges due to overlapping clinical features and the coexistence of atopic dermatitis (AD), an association not previously documented in the literature. The patient exhibited recurrent pustular episodes localized on sun-exposed and non-exposed areas, unresponsive to conventional therapies. Comprehensive microbiological, histopathological, and clinical assessments excluded infectious, drug-induced, and other inflammatory pustular dermatoses, confirming the diagnosis of ARP. Importantly, treatment with Baricitinib, a Janus kinase (JAK) inhibitor primarily prescribed for AD, resulted in marked improvement in both conditions, suggesting shared inflammatory pathways. This therapeutic response highlights the potential role of JAK inhibitors in ARP management, particularly in cases resistant to standard interventions. This report also proposes the inclusion of heat- and sweat-induced ARP as a distinct subtype, expanding the understanding of its diverse triggers beyond UV radiation. Furthermore, it underscores the need for standardized diagnostic criteria and a structured approach to differential diagnosis, given the condition’s underdiagnosed and often misinterpreted nature. By shedding light on the clinical and therapeutic aspects of ARP, this case contributes to a more nuanced understanding of this rare entity and its potential interplay with inflammatory skin disorders such as AD. Full article

The research aimed to investigate the perinatal pathology of Alpine ibex (Capra ibex) through the study of four young subjects (at the age of 3 to 4 months) found dead in Valle d’Aosta, a region of northwestern Italy. The carcasses were submitted to necropsy followed by an examination of ecto- and endoparasites (ECP and ENP); samples from the gross lesions (in summary, cutaneous papilloma and crusts, ocular discharge, lobular haemorrhagic areas in the lungs, catarrhal–haemorrhagic enterocolitis) were analysed by bacteriological, histopathological, and biomolecular methods to define the etiological agent. The subjects, with various co-infection patterns, were affected by contagious ecthyma virus (ORFV) (agent of a highly diffusive pustular dermatitis transmissible to small ruminants and humans), Enteropathogenic Escherichia coli (EPEC) (major etiological agent of infantile diarrhoea especially in developing countries), Mycoplasma conjunctivae (MC) (cause of an ocular infection common to goats and sheep), various ECP (ticks and keds) and ENP (lung and intestinal nematodes, and coccidia). This study emphasises the potential role of the Alpine ibex in the transmission of infectious diseases to other animals such as to humans and, secondly, the need to apply diversified analytical approaches, with the commitment of various specialistic skills, in order to define, in detail, the various and frequently overlapping causes that led a free-ranging animal to the death. Full article

Background: Orf is a highly contagious zoonosis caused by Orf virus (ORFV), which is endemic in sheep and goats worldwide. Human Orf is usually a self-limiting disease, but potential complications, including immune-mediated reactions, may occur. Methods: We included all articles regarding Orf-associated immunological complications published in peer-reviewed medical journals. We conducted a literature search of the United States National Library of Medicine, PubMed, MEDLINE, PubMed Central, PMC, and the Cochrane Controlled Trials. Results: A total of 16 articles and 44 patients were included, prevalently Caucasian (22, 95.7%) and female (22, 57.9%). The prevailing immunological reaction was erythema multiforme (26, 59.1%), followed by bullous pemphigoid (7, 15.9%). In most cases, the diagnosis was made on the basis of clinical and epidemiological history (29, 65.9%), while a biopsy of secondary lesions was performed in 15 patients (34.1%). A total of 12 (27.3%) patients received a local or systemic treatment for primary lesions. Surgical removal of primary lesion was described in two cases (4.5%). Orf-immune-mediated reactions were treated in 22 cases (50.0%), mostly with topical corticosteroids (12, 70.6%). Clinical improvement was reported for all cases. Conclusions: Orf-related immune reactions can have a varied clinical presentation, and it is important for clinicians to be aware of this in order to make a prompt diagnosis. The main highlight of our work is the presentation of complicated Orf from an infectious diseases specialist’s point of view. A better understanding of the disease and its complications is essential to achieve the correct management of cases. Full article

Orf is an important zoonotic disease caused by the Orf virus (ORFV) which can cause contagious pustular dermatitis in goats and sheep. Orf is widespread in most sheep-raising countries in the world, causing huge economic losses. Although diagnostic methods for ORFV infection already exist, it is still necessary to develop a time-saving, labor-saving, specific, low-cost and visual diagnostic method for rapid detection of ORFV in the field and application in grassroots laboratories. This study establishes a DNA extraction–free, real-time, visual recombinase–aided amplification (RAA) method for the rapid detection of ORFV. This method is specific to ORFV and does not cross-react with other common DNA viruses. The detection limits of the real-time RAA and visual judgment of the RAA assay at 95% probability were 13 and 21 copies per reaction for ORFV, respectively. Compared with qPCR, the sensitivity and specificity of the real-time RAA assay were 100%, and those of the visual RAA assay were 92.31% and 100.0%, respectively. The DNA extraction–free visual detection method of RAA established in this study can meet the needs of rapid onsite detection and grassroots laboratories and has important reference value and significance for the early diagnosis of diseased animals. Full article

The growing human and livestock populations in the world today and increased international transport of livestock is increasing the risk of both emerging and endemic zoonotic diseases. This review focuses on the potential for the live export trade to transmit zoonotic diseases. Both cattle and sheep are exposed to major stresses during the transport process, which are described, together with the impact of these stresses on the immune function of transported animals. Heat stress, overcrowding, inanition, ship and vehicle motion and accumulation of noxious gases are analysed for their ability to potentiate infectious diseases. The major zoonoses are described: pustular dermatitis, pneumonia, salmonellosis, as well as some common conditions, such as conjunctivitis, with specific reference to stressors associated with each disorder. Historical precedents exist for restriction of the trade based on disease risks. Finally, the economic and regulatory frameworks are considered to evaluate ways in which the spread of zoonotic diseases can be controlled. Full article

The interleukin-1 (IL-1) family is involved in the correct functioning and regulation of the innate immune system, linking innate and adaptative immune responses. This complex family is composed by several cytokines, receptors, and co-receptors, all working in a balanced way to maintain homeostasis. Dysregulation of these processes results in tissue inflammation and is involved in the pathogenesis of common inflammatory dermatoses such as psoriasis, hidradenitis suppurativa, and atopic dermatitis. Therefore, therapeutic targeting of IL-1 pathways has been studied, and several monoclonal antibodies are currently being assessed in clinical trials. So far, promising results have been obtained with anti-IL-36R spesolimab and imsidolimab in pustular psoriasis, and their efficacy is being tested in other conditions. Full article

The similarity between pustular psoriasis (PP) and acute generalized exanthematous pustulosis (AGEP) poses problems in the diagnosis and treatment of these two conditions. Significant clinical and histopathologic overlap exists between PP and AGEP. PP is an inflammatory disorder that has numerous clinical subtypes, but all with sterile pustules composed of neutrophils. AGEP is a severe cutaneous adverse reaction that is also characterized by non-follicular sterile pustules. Clinical features that suggest a diagnosis of PP over AGEP include a history of psoriasis and the presence of scaling plaques. Histologically, eosinophilic spongiosis, vacuolar interface dermatitis, and dermal eosinophilia favor a diagnosis of AGEP over PP. Importantly, PP and AGEP vary in clinical course and treatment. PP treatment involves topical steroids, oral retinoids, and systemic immunosuppressants. Newer therapies targeting IL-36, IL-23, IL-1, and PDE-4 have been investigated. The removal of the offending agent is a crucial part of the treatment of AGEP. Full article

Autoinflammation is defined by aberrant, antigen-independent activation of the innate immune signaling pathways. This leads to increased, pro-inflammatory cytokine expression and subsequent inflammation. In contrast, autoimmune and allergic diseases are antigen-directed immune responses from activation of the adaptive immune system. The innate and adaptive immune signaling pathways are closely interconnected. The group of ‘complex multigenic diseases’ are a result of mutual dysregulation of both the autoinflammatory and autoimmune physiologic components. In contrast, monogenic autoinflammatory syndromes (MAIS) result from single mutations and are exclusively autoinflammatory in their pathogenesis. Studying the clinical and histopathological findings for the various MAIS explains the phenotypical correlates of their specific mutations. This review aims to group the histopathologic clues for autoinflammation into three recognizable patterns. The presence of these histologic patterns in a pediatric patient with recurrent fevers and systemic inflammation should raise suspicion of an autoinflammatory component in MAIS, or, more frequently, in a complex multigenic disease. The three major histopathological patterns seen in autoinflammation are as follows: (i) the ‘neutrophilic’ pattern, seen in urticarial neutrophilic dermatosis, pustular psoriasis, aseptic neutrophilic folliculitis, and Sweet’s syndrome; (ii) the ‘vasculitic’ pattern seen in small vessel-vasculitis (including hypersensitivity/leukocytoclastic vasculitis, thrombosing microangiopathy and lymphocytic vasculitis), and intermediate-sized vessel vasculitis, mimicking polyarteritis nodosa; and (iii) the ‘granulomatous’ pattern. Beyond these three patterns, there are additional histopathologic clues, which are detailed below. It is important for a dermatopathologist to recognize the patterns of autoinflammation, so that a diagnosis of MAIS or complex multigenic diseases may be obtained. Finally, careful histopathologic analyses could contribute to a better understanding of the various clinical manifestations of autoinflammation. Full article

Photodynamic Therapy (PDT) is a non-invasive treatment successfully used for neoplastic, inflammatory and infectious skin diseases. One of its strengths is represented by the high safety profile, even in elderly and/or immuno-depressed subjects. PDT, however, may induce early and late onset side effects. Erythema, pain, burns, edema, itching, desquamation, and pustular formation, often in association with each other, are frequently observed in course of exposure to the light source and in the hours/days immediately after the therapy. In particular, pain is a clinically relevant short-term complication that also reduces long-term patient satisfaction. Rare complications are urticaria, contact dermatitis at the site of application of the photosensitizer, and erosive pustular dermatosis. Debated is the relationship between PDT and carcinogenesis: the eruptive appearance of squamous cell carcinoma (SCC) in previously treated areas has been correlated to a condition of local and/or systemic immunosuppression or to the selection of PDT-resistant SCC. Here we review the literature, with particular emphasis to the pathogenic hypotheses underlying these observations. Full article