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Lymphomas of the eye and ocular adnexa are rare lymphoproliferative diseases of the ocular and ocular adnexal tissue. The incidence of these diseases has been rapidly increasing over the past few decades. The exact pathogenesis remains unknown, but it is postulated to be multifactorial and includes genetic aberrations, epigenetic and environmental factors, infectious agents, and chronic antigenic stimulation. The majority of ocular and ocular adnexal lymphomas are of B-cell origin, except for eyelid lymphomas, which are more often of T-cell type. Lymphoproliferative diseases of ocular and ocular adnexal structures are either primary, when they arise in the eye, orbit, lacrimal gland, eyelid, and/or conjunctiva, or secondary extranodal manifestation of systemic lymphoma. Diagnosis is challenging and requires a multidisciplinary approach involving ophthalmologists, dermatologists, oncologists, and radiation oncologists., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Nutrition and dietary supplements have been used to promote a youthful appearance for millennia. Despite high public demand for these products, evidence supporting their efficacy is limited and often inconsistent. We discuss the structural and functional changes that occur in the skin during the aging process. We also review evidence supporting the use of nutritional supplements commonly used to promote a youthful appearance, including essential fatty acids, coenzyme Q, collagen peptides, curcumin, polyphenols, flavonoids, probiotics, silymarin, and vitamins A, C, D, and E. We also consider the role of advanced glycosylated end products, antiinflammatory diets, and caloric restriction in delaying premature skin aging. Although evidence supporting the use of some dietary interventions is promising, further long-term studies in humans are required to fully understand their effects on the promotion of a youthful appearance., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The microbiome plays a significant role in human health, homeostasis, immune system, and disease pathogenesis. Disrupted communication between the microbiome and host has been extensively studied in gastrointestinal diseases. To a lesser extent, there is emerging research on the skin microbiome and its connection with the gut, referred to as the gut-skin axis and its effects on dermatologic conditions. A basic overview will be provided of the gut and skin microbiome with a focus on the impact of this connection on cutaneous diseases, such as psoriasis, atopic dermatitis, rosacea, acne vulgaris, photoaging, and cutaneous wounds. In addition, we shall discuss nutrition-based approaches mediated through the gut-skin axis and topical treatments that could serve as potential adjunctive management by manipulation of the microbiome. In particular, there is a growing body of research on oral probiotics, prebiotics, and dietary modifications that may help improve symptoms for a variety of dermatologic conditions in select demographic groups., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Granulomatous diseases represent a heterogeneous group of conditions characterized by histiocytic inflammation that affect patients of any age. These diseases differ widely in their pathogenesis and include infectious and noninfectious conditions. This review focuses on noninfectious granulomatous conditions, with particular emphasis on age-related differences in the onset, epidemiology, clinical manifestations, prognosis, and age-specific management of specific granulomatous disorders. Knowledge of age-specific aspects of granulomatous conditions in adults and children improves both the extent of the diagnostic workup and the management of these patients., (Copyright © 2017. Published by Elsevier Inc.)

Cutaneous T-cell lymphomas (CTCLs) are non-Hodgkin lymphomas that predominantly affect older patients. Onset of cutaneous lymphoma in childhood is rare, but it can present as early as the first decade of life. In both adults and children, the diagnosis of cutaneous lymphoma can be challenging because inflammatory dermatoses can mimic CTCL both clinically and histologically. The clinicopathologic manifestations can be similar in adults and younger individuals; however, differences in the prevalence of certain CTCL variants among age groups exist. Whereas the classic Alibert-Bazin-type mycosis fungoides (MF) and Sézary syndrome represent the overwhelming majority of adult cutaneous T-cell lymphomas, in younger individuals, certain mycosis fungoides variants, such as hypopigmented MF, are over-represented and Sézary syndrome is extremely rare. CD30 + lymphoproliferative diseases, which include lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (ALCL), represent the second most common subtype of CTCL in both adults and children; however, in the pediatric population, most of these are represented by LyP, and primary cutaneous ALCL is very rare. The prognosis is stage dependent, and the most significant prognostic factor in MF is the extent of skin involvement and the presence or absence of extracutaneous disease. The overwhelming majority of pediatric patients present with early-stage disease, and progression to more advanced stages, such as tumor stage, erythrodermic MF, and large cell transformation, which can be seen in adults, is very rare. The choice of treatment, regardless of age, is dependent on the extent of skin involvement and the presence or absence of extracutaneous disease., (Published by Elsevier Inc.)

Cutaneous T-cell lymphoma (CTCL) is a malignancy of skin-homing T cells. A major feature of CTCL is profound immunosuppression, such that patients with advanced mycosis fungoides or Sézary syndrome have been compared with patients with advanced HIV disease and are susceptible to opportunistic infection. The etiology of this immunosuppression is unclear. We analyzed peripheral blood T cells of patients with CTCL with stage I to IV disease, using a sensitive beta-variable complementarity-determining region 3 spectratyping approach. Our data revealed a profound disruption of the complexity of the T-cell repertoire, which was universally observed in patients with advanced disease (stages III and IV), and present in up to 50% of patients with early-stage disease (stages I and II). In most patients, multiple monoclonal and oligoclonal complementarity-determining region 3 (CDR3) spectratype patterns in many different beta-variable families were seen. Equally striking was a reduction of normal T cells (as judged by absolute CD4 counts) across multiple beta-variable families. In general, CTCL spectratypes were reminiscent of advanced HIV spectratypes published elsewhere. Taken together, these data are most consistent with a global assault on the T-cell repertoire in patients with CTCL, a process that can be observed even in early-stage disease.

Hairy cell leukemia (HCL) is a chronic lymphoproliferative disease, the cause of which is unknown. Diagnostic of HCL is abnormal expression of the gene that encodes the beta2 integrin CD11c. In order to determine the cause of CD11c gene expression in HCL the CD11c gene promoter was characterized. Transfection of the CD11c promoter linked to a luciferase reporter gene indicated that it is sufficient to direct expression in hairy cells. Mutation analysis demonstrated that of predominant importance to the activity of the CD11c promoter is its interaction with the activator protein-1 (AP-1) family of transcription factors. Comparison of nuclear extracts prepared from hairy cells with those prepared from other cell types indicated that hairy cells exhibit abnormal constitutive expression of an AP-1 complex containing JunD. Functional inhibition of AP-1 expressed by hairy cells reduced CD11c promoter activity by 80%. Inhibition of Ras, which represents an upstream activator of AP-1, also significantly inhibited the CD11c promoter. Furthermore, in the hairy cell line EH, inhibition of Ras signaling through mitogen-activated protein kinase/extracellular signal-regulated kinase kinases 1 and 2 (MEK1/2) reduced not only CD11c promoter activity but also reduced both CD11c surface expression and proliferation. Expression in nonhairy cells of a dominant-positive Ras mutant activated the CD11c promoter to levels equivalent to those in hairy cells. Together, these data indicate that the abnormal expression of the CD11c gene characteristic of HCL is dependent upon activation of the proto-oncogenes ras and junD.

Chemokines are critical molecules in leukocyte trafficking, promoting site-specific migration to various tissues. The chemokine receptor CCR4 has recently been associated with skin-homing T cells. In view of the potential importance of CCR4 in skin homing of T cells, we investigated the expression pattern of CCR4 and its ligands TARC/CCL17 and MDC/CCL22 in the peripheral blood and skin of patients with cutaneous T cell lymphoma, a putative malignancy of the skin-homing T cells. In this study we analyzed the pattern of coexpression of the skin-homing molecules cutaneous lymphocyte antigen (CLA) and CCR4 in the blood and skin of patients with cutaneous T cell lymphoma. In the blood of cutaneous T cell lymphoma patients with peripheral blood involvement we found significantly increased percentages of T cells displaying the skin-homing phenotype (CLA+CCR4+) compared with healthy individuals. T cells expressing CLA and CCR4 were also found at high levels in cutaneous T cell lymphoma lesions along with abundant expression of the two CCR4 ligands TARC/CCL17 and MDC/CCL22. These data may explain, in part, why these T cells accumulate in the skin, a diagnostic feature of cutaneous T cell lymphomas.