Keratinocytes in inflammatory skin diseases.

Although in the past, keratinocytes were considered simply as passive targets of immunological attack from infiltrating T lymphocytes, a number of studies have definitively demonstrated that keratinocytes actively participate in the cutaneous immune responses. Upon activation, keratinocytes express a plethora of cytokines, chemokines and accessory molecules, which can transmit both positive and negative signals to cells of innate and adaptive immunity. Dysregulation and abnormal expression of inflammatory mediators or their receptors in keratinocytes are relevant to the pathogenesis of chronic inflammatory skin diseases such as psoriasis, atopic dermatitis and allergic contact dermatitis.

Prevalence of psoriatic arthritis and joint complaints in a large population of Italian patients hospitalised for psoriasis.

We investigated the prevalence of psoriatic arthritis and joint complaints in a large population of Italian patients hospitalised for psoriasis. A total of 936 patients were evaluated for psoriatic arthritis according to the European Spondyloarthropathy Study Group (ESSG) criteria. They were visited by a dermatologist who evaluated specific joint signs and symptoms (i.

Pimecrolimus in dermatology: atopic dermatitis and beyond.

Pimecrolimus is a calcineurin inhibitor developed for the topical therapy of inflammatory skin diseases, particularly atopic dermatitis (AD). Pimecrolimus selectively targets T cells and mast cells. Pimecrolimus inhibits T-cell proliferation, as well as production and release of interleukin-2 (IL-2), IL-4, interferon-gamma and tumour necrosis factor-alpha.

Severe impairment of quality of life in Hailey-Hailey disease.

Hailey-Hailey disease (a skin fragility disorder) runs a chronic course and may cause important disability. However, little has been formally investigated concerning the quality of life (QoL) of patients affected by this disorder. We studied the impact of Hailey-Hailey disease on the QoL of 22 consecutive patients seen at our dermatological clinic.

ERK1/2 regulates epidermal chemokine expression and skin inflammation.

Resident cell populations of the skin contribute to the inflammatory response by producing an array of chemokines, which attract leukocytes from the circulation. TNF-alpha is a major inducer of proinflammatory mediators in keratinocytes. We have recently observed that epidermal growth factor receptor (EGFR) signaling affects TNF-alpha-driven chemokine expression in epidermal keratinocytes, and its functional impairment increases the levels of crucial chemoattractants such as CCL2/MCP-1, CCL5/RANTES, and CXCL10/IFN-gamma-inducible protein-10.

Leukocyte extravasation as a target for anti-inflammatory therapy - Which molecule to choose?

In view of the central pathogenic importance of leukocyte extravasation in inflammatory skin diseases, therapeutic interference with this - surprisingly complex - process is clearly a promising new approach for treating these dermatoses. Despite some disappointments during the clinical use of these agents and despite their crippling price tag, the recent incorporation of biologicals that target defined molecular controls of leukocyte extravasation into dermatological and rheumatological practise, consequently, has greatly enriched our therapeutic options for battling major, chronic, inflammatory dermatoses such as psoriasis. However, the - as yet unresolved and still rather controversially discussed - critical question is: Which of the multiple steps that control leukocyte extravasation in the human system really offer the most promising, most pragmatic, and safest molecular targets for therapeutic intervention for which disease entity? The current debate intends to stimulate public and rational debate of this crucial issue, beyond the evident commercial interests that are touched by whatever stand one takes.

Persistent unilateral orbital and eyelid oedema as a manifestation of Melkersson-Rosenthal syndrome.

Melkersson-Rosenthal syndrome (MRS) is a complex neuromucocutaneous disorder characterized by localized orofacial oedema and cranial nerve dysfunction, frequently associated with minor signs, including furrowed tongue. Complete forms are rare whereas mono- and oligosymptomatic variants are more common. A 71-year-old man presented with a 2-year history of relapsing and progressively persistent oedema of the right eyelids and periorbital region.

An itchy vesiculobullous eruption in a patient with chronic lymphocytic leukaemia.

Exaggerated reactions to insect bites are characteristic of patients with haemoproliferative disorders, particularly chronic lymphocytic leukaemia (CLL). Skin lesions usually appear after the diagnosis of leukaemia and seem unrelated to laboratory findings, disease course or therapy. Rarely, the eruption may precede the diagnosis of the haematologic malignancy.

Identification of the keratin K9 R162W mutation in patients of Italian origin with epidermolytic palmoplantar keratoderma.

Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant skin disorder characterized by hyperkeratosis of the palms and soles associated with histologic findings of hyperkeratosis and epidermolysis. Ultrastructurally, there is vacuolization of the cytoplasm and abnormal keratin filament network with tonofilament clumping. EPPK is caused by mutations in the keratin 9 gene (KRT9), which is expressed exclusively in suprabasal keratinocytes of palmoplantar epidermis.

H1 histamine receptor mediates inflammatory responses in human keratinocytes.

Background: Keratinocytes participate in initiation and amplification of T-cell-mediated skin diseases. During these disorders, histamine can be released from both residents skin cells and immigrating leukocytes, and can affect the functions of dendritic cells, monocytes, and lymphocytes. Little information is available on the effects of histamine on keratinocytes.

Prevalence of symptoms experienced by patients with different clinical types of psoriasis.

Background: The main dermatology textbooks describe only in passing pruritus in psoriasis and rarely mention other symptoms. A quantification of the presence of symptoms is not available for clinical subgroups of psoriasis.

Objectives: To investigate the prevalence of symptoms experienced by patients with different clinical types of psoriasis.

Characterization of the biological activities of uridine diphosphate in human dendritic cells: Influence on chemotaxis and CXCL8 release.

Uridine nucleotides are endogenous nucleotides which are released into the extracellular space from mechanical stressed endothelial and epithelial cells as well as lipopolysaccharide (lps)-stimulated monocytes. Here, we studied the biological activity of the selective purinoreceptor P2Y6 (P2YR6) agonist Uridine 5'diphosphate (UDP) as well as the P2YR2- and P2YR4-activating uridine 5'triphosphate (UTP) on human dendritic cells (DC). These cells in their immature state have the ability to migrate from blood to peripheral target sites where they sense dangerous signals and capture potential antigens.

Chemokine networks in inflammatory skin diseases.

The superfamily of chemokines comprises numerous small, cytokine-like chemotactic proteins, which have a fundamental role in the regulation of leukocyte trafficking. The chemokine-chemokine receptor system is highly redundant and promiscuous, and forms a complex network relevantly involved in the expression of chronic inflammatory skin diseases, including allergic contact dermatitis, atopic dermatitis and psoriasis. The pattern of chemokine expression shows overlapping features but also important differences in these diseases due to distinct sources and types of pro-inflammatory signals involved in chemokine induction, and the inherent capacity of resident skin cells to produce chemokines.

Treatment of recalcitrant scleromyxedema with thalidomide in 3 patients.

Scleromyxedema is a generalized, papular, and sclerodermoid form of lichen myxedematosus associated with monoclonal gammopathy and systemic changes. Despite anecdotal reports of success with various agents, no satisfactory treatments are currently available. We report 3 adult patients with recalcitrant scleromyxedema associated with paraproteinemia who were treated with thalidomide.

Immunoregulation of allergic contact dermatitis.

Allergic contact dermatitis (ACD) to haptens can serve as a valuable paradigm for understanding the physiopathology of T cell mediated immune responses. In sensitized individuals, exposure to the relevant hapten initiates clinical expression of ACD, which depends on the rapid activation of specific T cells. Mechanisms of tissue damage include direct cytotoxicity against keratinocytes, mostly mediated by CD8+ T cells, and T cell release of cytokines, which amplify the inflammatory response by targeting resident skin cells.

Targeting tumor necrosis factor-alpha in the therapy of psoriasis.

Tumor necrosis factor-alpha (TNF-alpha) plays a fundamental role in the initiation and persistence of skin inflammation in psoriasis. The best evidence of the essential activity of this cytokine in the pathogenesis of psoriasis came from the observation that selective TNF-alpha blockers are dramatically effective in the therapy of this disease. The TNF-alpha inhibitors, infliximab and etanercept, have been employed with success in moderate to severe psoriasis and in psoriatic arthritis in randomized controlled trials.

Inosine stimulates chemotaxis, Ca2+-transients and actin polymerization in immature human dendritic cells via a pertussis toxin-sensitive mechanism independent of adenosine receptors.

Inosine is an endogenous purine nucleoside, which is formed by adenosine deaminidase during adenosine breakdown and is released into the extracellular space from the sympathetic nervous system or injured cells. Here, we studied the biological activity of inosine on human dendritic cells (DC), which are specialized antigen presenting cells characterized by their ability to migrate from the blood to peripheral tissues, and then to secondary lymphoid organs where they initiate adaptive immune responses. In immature DC, inosine concentration-dependently stimulated Ca(2+)-transients, actin polymerization, and chemotaxis.

Disseminated lupus vulgaris.

Lupus vulgaris is the most common form of cutaneous tuberculosis, and usually presents as a solitary lesion on the face. We report two patients with multiple lesions on different skin areas. The first patient presented a diffuse involvement of the right foot, and reddish-brown plaques on the right leg, the back and the face.

Annular lichenoid dermatitis of youth.

Background: Lichenoid dermatoses are composed of a wide spectrum of disorders with a common histopathologic interface pattern but diverse causes and pathophysiology.

Objective: We describe a series of young patients with a peculiar annular lichenoid dermatitis, the clinical appearance of which initially suggested diagnoses of morphea, mycosis fungoides, or annular erythema.

Results: The study involved 23 patients (median age 10 years; age range 5-22 years).

Human CD25+ regulatory T cells maintain immune tolerance to nickel in healthy, nonallergic individuals.

We investigated the capacity of CD25(+) T regulatory cells (Treg) to modulate T cell responses to nickel, a common cause of allergic contact dermatitis. CD4(+) T cells isolated from the peripheral blood of six healthy, nonallergic individuals showed a limited capacity to proliferate in response to nickel in vitro, but responsiveness was strongly augmented (mean increment +/- SD, 240 +/- 60%) when cells were depleted of CD25(+) Treg. Although CD25(+) Treg were anergic to nickel, a small percentage up-regulated membrane CTLA-4 upon nickel exposure.

Papular neutrophilic dermatosis and erythema elevatum diutinum following erythropoietin therapy in a patient with myelodysplastic syndrome.

A 65-year-old man with refractory anaemia with an excess of blasts developed an erythematous papular eruption symmetrically distributed on the legs and trunk 3 months after initiation of erythropoietin therapy. The lesions showed a dense neutrophilic infiltrate in the absence of leucocytoclastic vasculitis, and did not fit the criteria of a well-defined neutrophilic dermatosis. Concomitant with the rapid resolution of these skin lesions following erythropoietin discontinuation, typical lesions of erythema elevatum diutinum arose on the extensor surface of the fingers, knees and elbows, which responded to a brief course of dapsone treatment.

Epidermodysplasia verruciformis with multiple mucosal carcinomas treated with pegylated interferon alfa and acitretin.

Epidermodysplasia verruciformis (EV) is characterized by abnormal genetically-determined susceptibility to widespread and persistent infection of the skin with human papillomaviruses (HPV). The infection results in disseminated pityriasis versicolor-like lesions and flat warts. Skin malignant changes are very common and occur on sun-exposed areas.