D'Epiro S

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.

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.

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.

Folgoration as an Example of Pathergy in a Patient Affected by Pyoderma Gangrenosum and Takayasu's Arteritis

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unknown aetiology. Clinical manifestations of PG are characterized by destructive, necrotizing, and noninfective ulceration of the skin. 20–30% of cases are initiated and aggravated by minor trauma or surgery, a phenomenon named pathergy. PG is related to several autoimmune diseases including ulcerative colitis, Crohns disease, rheumatoid arthritis, and monoclonal gammopathy. The association with Takayasus arteritis (TA), a chronic inflammatory and stenotic disease of large and medium-sized arteries, is instead less common. We report a case of PG associated with TA that was induced by an accident with folgoration of the skin; in this case the folgoration can be considered as an exemple of Pathergy, that is, a characteristic feature of PG.

Mutational profiling in melanocytic tumors: multiple somatic mutations and clinical implications.

In this study, we analyzed multiple somatic mutations in 10 genes relevant in melanoma tumorigenesis and targeted therapies. Overall, 45% of the tumors showed mutations and, in particular, 33% had multiple mutations. Based on our results, we conclude that the assessment of mutation status of multiple genes, including CDKN2A, could provide a genetic profile that can be useful as a prognostic and therapeutic marker in melanocytic tumors.

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.

Use of biological drugs in patients with psoriasis and psoriatic arthritis in Italy: Results from the PSONG survey

This Italian multicenter retrospective study compared the drug survival and efficacy of different anti‐TNF agents in psoriasis (PsO) and psoriatic arthritis (PsA) patients. A database of PsO/PsA patients treated with adalimumab, etanercept, and infliximab from May 2013 to May 2014 was analyzed. PASI 75, 90, and 100 was calculated at each time point to evaluate efficacy. Drug survival rate and probability of maintaining PASI response were evaluated. The impact of dependent variables on probability of PASI 75 loss was evaluated by logistic regression. 1,235 patients were included, 577 with PsO and 658 with PsA. Highest survival rates were observed with adalimumab followed by etanercept and infliximab in PsO and PsA patients. The probability of maintaining PASI response was significantly higher for adalimumab followed by infliximab. For PsO patients, the odds of losing PASI 75 was higher in etanercept‐treated patients (OR: 8.1; 95% CI: 4.2–15.6, p < .001) or infliximab (OR: 6.6; 95% CI: 2.6–16.3, p < .001) vs. adalimumab. Likewise, for PsA patients the odds of losing PASI 75 was higher in etanercept‐treated patients (OR: 2.3; 95% CI: 1.4–3.8, p = .01) or infliximab (OR: 2.2; 95% CI: 1.1–4.1, p = .018) vs. adalimumab. Adalimumab could be the best therapeutic option over other anti‐TNF agents for the treatment of PsO and PsA patients.

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.

Bosentan Treatment of Digital Ulcers Related to Autoimmune Disorders

Endothelin 1, a powerful endogenous vasoconstrictor and mitogen, may be causal to pulmonary hypertension. Evidence also suggests that endothelin (ET) may have a fundamental role in scleroderma pathogenesis, including pulmonary arterial hypertension (PAH), a leading cause of death in patients with scleroderma. The development of a new class of drug, ET receptor antagonists, provides an improved outlook for patients with scleroderma and related diseases. Increasing vigilance toward early detection of PAH in scleroderma and a multidisciplinary approach to diagnosis and treatment may improve the clinical outcome for these patients. We describe the efficacy and safety of bosentan, an orally active dual ET‐receptor antagonist, in patients with digital ulcers. Bosentan increases exercise capacity and improves hemodynamics in patients with pulmonary hypertension, suggesting that ET has an important role in pulmonary hypertension but in our experience also for refractory skin ulcers. Drug Dev Res 72:750–755, 2011.