Monica Salvi

Importance of Regulatory T Cells in the Pathogenesis of Psoriasis: Review of the Literature

Psoriasis is a common chronic relapsing inflammatory cutaneous disease; the main role in the inflammation of this condition is played by lymphocyte Th1, Th17 and their cytokines. The activity of these cells is modulated by a particular kind of T cells recently described: the T regulatory cells (Treg). These are able to inhibit the immunological response and to maintain the cutaneous immunological homeostasis, thus preventing autoimmunity against self antigens. Few data are available in the literature as to Treg in psoriasis; several studies demonstrate that the function of these cells is impaired in this condition and treatments for psoriasis may increase the number and activity of Treg. The role of these cells in the pathogenesis of psoriasis is very important to understand how they may contribute to the development of this cutaneous disorder. In the near future it would be possible to target therapies at these defects, improving the activity of these cells and maintaining cutaneous homeostasis, preventing psoriasis or other inflammatory cutaneous conditions.

CD4+ CD25+ T-regulatory cells in psoriasis. Correlation between their numbers and biologics-induced clinical improvement

BACKGROUND Regulatory T-cells (T-reg) play a central role in the immunopathogenesis of psoriasis. T-reg cells are both functionally and numerically impaired in psoriasis and they are up-regulated by drug therapy. OBJECTIVE To analyse the circulating CD4+CD25 bright FOXP3+ subset in 14 patients with vulgaris/arthropathic psoriasis treated with biological drugs and to investigate their relationship with the clinical response. METHODS The CD4+ CD25 bright FOXP3+ expression was determined in peripheral blood by flow cytometry at baseline and during treatment. RESULTS A response was obtained in 10/14 patients with increased CD4+ CD25 bright FOXP3+ (T-reg) in peripheral blood after the first month and then 4 months after therapy with biological drugs. This increase is associated with the achievement of a clinical response and with a reduction in the Psoriasis Activity and Severity Index (PASI) score. 2/14 patients showed a decrease in T-reg after drug therapy and this decrease correlated with a worsening of the clinical skin. CONCLUSION Biological drugs induce circulating T-reg up-regulation in psoriatic patients; such an increase is an early predictive marker of clinical response.

Psoriasis and bone mineral density: Implications for long‐term patients

Psoriasis is a chronic inflammatory disease associated with several comorbidities. Osteoporosis is defined as a reduction in bone mineral density with impaired bone microarchitecture. Several mechanisms may be implicated as a possible cause for the association between psoriasis and osteoporosis, such as systemic inflammation, anti‐psoriatic drug intake and joint dysfunction for psoriatic arthritis (PsA). The aim of the present study was to assess bone mineral density (BMD) in patients with psoriasis, correlating the prevalence of osteopenia/osteoporosis with Psoriasis Area and Severity Index (PASI) score, mean duration of psoriatic disease, PsA and previous treatments for psoriasis. Forty‐three consecutive patients with psoriasis, 19 of whom were affected by the arthropathic form, were enrolled. We evaluated the severity of psoriasis as measured by PASI score, the CASPAR criteria and ultrasounds of the joints to verify the diagnosis of PsA and the age of psoriasis onset to estimate mean disease duration. Patients underwent a bone density scan of the lumbar spine and femoral neck by dual‐energy X‐ray absorptiometry to measure BMD. Patients with osteopenia/osteoporosis showed a statistically significant longer average duration of psoriatic disease (17 years), compared to patients affected by psoriasis with normal T‐score (8.8 years) (P = 0.04). The linear logistic regression confirms a significant relation between mean psoriatic disease duration and BMD alterations (P = 0.04). Our results suggest the necessity of an early diagnostic evaluation of bone metabolism in patients with psoriasis, especially if characterized by longer disease duration.

Safety and efficacy of anti-tumor necrosis factors α in patients with psoriasis and chronic hepatitis C

Up to date, in literature, it is still debated the role of anti-tumor necrosis factors (TNF)-α treatments in hepatitis C virus (HCV) patients. TNF-α performs a lot of functions, it is an important pro-inflammatory cytokine and it is involved in the hosts immunity. Since TNF-α is implicated in the apoptotic signaling pathway of hepatocytes infected by HCV, anti TNF-α therapy may increase the risk of viral replication or their reactivation. However the treatment of anti TNF-α could have a healthful role because TNF-α appears to be engaged in the pathogenesis of liver fibrosis, inducing apoptotic pathways. We describe the case of a patient with plaque-type psoriasis and concomitant chronic HCV, who was treated successfully with anti-TNF agents simultaneously to cyclosporine without sign of reactivation of HCV and increase of liver enzymes. Our personal experience shows that anti-TNF-α agents are not only effective but also safe. Furthermore the combination therapy of cyclosporine and anti-TNF-α appears to be well-tolerated and able to reduce the amount of liver enzymes as well as HCV-viral-load. However systematic, large-scale studies with long follow-ups will be needed to confirm our results, in association with close liver function monitoring.

Homocysteine plasmatic status in patients with psoriasis

ejd.2011.1455 Auteur(s) : Antonio Giovanni Richetta1 antoniorichetta@hotmail.com, Carlo Mattozzi1, Laura Macaluso1, Carmen Cantisani1, Simona Giancristoforo1, Sara D’epiro1, Monica Salvi1, Marco Scarno2, Stefano Calvieri1 1 Department of Dermatology, Policlinico “Umberto I” University of Rome “La Sapienza”, Viale del Policlinico, 155, 00133 Rome, Italy 2 CASPUR Department of medical statistics, Italy Hyperhomocysteinaemia represents an independent risk factor for atherosclerotic cardiovascular [...]

Serum levels of functional T-regs in vitiligo: our experience and mini-review of the literature

Vitiligo is an acquired depigmentary skin disorder due to the loss of cutaneous melanocytes or alteration in melanocyte function, affecting over 0.5% of the world population. The exact cause of melanocyte loss in non-segmental vitiligo is still debatable, but many observations have pointed to the main role of cellular immunity. Earlier evidence has shown that depigmenting vitiligo skin is accompanied by CD8+ T cytotoxic lymphocytes infiltrates at the dermal-epidermal junction. Dysregulation of Tregs may be one of the factors that can break tolerance to melanocyte self-antigens and contribute to the pathogenesis of vitiligo. The objectives of the present study were to provide evidence of the presence of a functional defect and decrease of peripheral regulatory T cells in patients affected by vitiligo, supporting the hypothesis of their involvement in the pathogenesis of the disease, opening new possibilities to advance therapeutic approaches.

Downregulation of circulating CD4+ CD25(bright) Foxp3+ T cells by cyclosporine therapy and correlation with clinical response in psoriasis patients: report of three cases.

of KS because the main lesion was soft, unilateral, and involved the inguinal region, a localization that, to the best of our knowledge, has never been described. Furthermore, as in the patient reported by Caminiti et al., in whom KS was initially misdiagnosed as a diabetic plantar foot ulcer, the ulcer on the sole of the left foot in our patient could be considered as a manifestation of the disease. However, in the absence of histological examination, this is only a hypothesis. In this case, AIDS-related KS displayed unusual cutaneous features that we were able to diagnose correctly only by biopsy. Awareness that KS can occur with atypical manifestations, particularly in HIV-positive patients, is important to avoid misdiagnosis and to enable treatment to be started as soon as possible.

Gemcitabine-Induced Extensive Skin Necrosis

An 82-year-old woman presented with oedema and extensive necrotic ulcerative lesions on the back side of her lower limbs, emerging after the second cycle of chemotherapy consisting of Gemcitabine for metastatic pancreatic cancer. The absence of any convincing argument in favor of cardiovascular or autoimmune disease led us to attribute the onset of skin necrosis to chemotherapy administration. Although skin ischemia has also been described as a paraneoplastic syndrome, in this case we could observe a temporal and causal relationship to Gemcitabine infusion. Recently, this drug has been associated with important vascular side effects; its vascular toxicity is in fact higher than previously estimated. To our knowledge, careful attention should be reserved to neoplastic patients candidated to Gemcitabine administration, especially if previously affected by arterial vascular disease, venous thromboembolism, or collagenoses.

Facial superficial granulomatous pyoderma.

Dear Editors, We describe the case of a 16-year-old woman who developed ulcerative lesions on the face and in the genital area. She presented with a 5-month history of ulcerative indolent lesions in both zygomatic regions that were sharply demarcated from normal skin. The patient developed new lesions beginning as pustules and then progressing to superficial ulceration with a relatively clean wound bed and vegetative borders. Surrounding skin was erythematous and violaceous. Pustules were also located on the chin area and cheeks (Figure 1A,B). Similar lesions developed in the genital area (Figure 1C). The patient had generally been in good health and she had no history of acne vulgaris. Laboratory test results, including autoimmunity, were in the normal range. No clinical and instrumental evidences of malignancy or inflammatory bowel disease were detected. A culture swab from the ulcerative lesions did not reveal bacterial or fungal infections. Skin biopsy of a lesion in the genital area showed a dense inflammatory infiltrate with neutrophils, lymphocytes, histiocytes, giant cells, focal granuloma formation and granulation tissue. No histological signs of mycobacterium and fungal infections were detected. The diagnosis of superficial granulomatous pyoderma (SGP) was subsequently supported by the clinical and histopathological characteristics.

Drug cutaneous side effect: Focus on skin ulceration

Skin ulcers are defined as tissue loss interesting the deeper layers of the dermis and hypodermis, with low tendency to spontaneous healing. They cause disability related to pain, risk of infection and amputation, chronic management, requiring working absence with notably economic burden. The major cause is often related to underlying vascular disease, infections, tumors, autoimmunity, trauma, even if literature occasionally reported several cases of drug inducing skin ulceration. Most of drugs involved are chemotherapy agents and more recently molecular target therapies. Evidences supporting these drugs as the major cause of skin ulcers include delay of onset after therapy initiation, improvement after withdrawal of the drug, recurrence after its reintroduction and, sometimes, simultaneous occurrence of other skin lesions that have previously been reported to be associated with these agents. Attention should be reserved to patients undergoing antineoplastic agents, especially if previously affected by predisposing comorbidities, considering such side effect as possible differential diagnosis for skin ulceration in neoplastic patients.