Elena Campione

Involvement of interleukin-21 in the epidermal hyperplasia of psoriasis

T cells are crucial mediators of the skin damage in psoriasis. We here show that interleukin-21 (IL-21), a T cell–derived cytokine, is highly expressed in the skin of individuals with psoriasis, stimulates human keratinocytes to proliferate and causes epidermal hyperplasia when injected intradermally into mice. In the human psoriasis xenograft mouse model, blockade of IL-21 activity resolves inflammation and reduces keratinocyte proliferation. Blocking IL-21 may represent a new therapeutic strategy in psoriasis.

Topical treatment of basal cell carcinoma with tazarotene: a clinicopathological study on a large series of cases.

Background  Basal cell carcinoma (BCC) is the most common cancer in humans. Medical treatment modalities offer cost reductions and clinical advantages in selected cases such as low‐risk areas, surgically inaccessible sites, patients with multiple neoplasms, and older, infirm or anticoagulated subjects. Tazarotene has been proposed for the treatment of BCC; however, data on its efficacy are lacking.

Diagnosis of pigmented skin lesions by dermoscopy: web-based training improves diagnostic performance of non-experts

Summary Background Dermoscopy has been shown to enhance the diagnosis of melanoma. However, use of dermoscopy requires training and expertise to be effective.

Bilateral Thoracoscopic T2 to T3 Sympathectomy Versus Botulinum Injection in Palmar Hyperhidrosis

BACKGROUND Bilateral T2 to T3 thoracoscopic sympathectomy and injection of botulinum toxin-A are presently the most effective modalities in the treatment of primary palmar hyperhidrosis. In this study we evaluated comparative merits of the two therapies. METHODS Patients suffering primary palmar hyperhidrosis were treated by either bilateral T2 to T3 thoracoscopic sympathectomy (n = 68) or by injection of botulinum toxin-A (n = 86). The groups were homogeneous for relevant demographic, physiologic, and clinical data. Quantification of sweat production was performed by Minors iodine starch and glove tests. Subjective changes were assessed by quality of life questionnaires (Hyperhidrosis, Dermatology Life Quality Index, Short Form-36, Nottinghams Health Profile) and patients satisfaction self-assessment. A cost comparison between groups was also carried out. RESULTS No operative mortality or major morbidity was recorded in either group. Minors test showed a more significant reduction in the surgical group: +94% versus +63% at 6 months and +94% versus +30% at 12 months. Compensatory sweating was significantly greater and long-lasting in the surgical group. All subjective tests improved rapidly and significantly in both groups. After 6 months, results mildly worsened in the surgical group and more significantly in the botulinum group. Patients satisfaction was initially greater in the botulinum group (p = 0.03), but after 6 months it significantly reversed (p = 0.04). Surgical treatment cost approximately as much as four botulinum treatments. CONCLUSIONS Thoracoscopic sympathectomy is superior to botulinum toxin-A injection. The greater initial costs and discomfort are offset by a greater reduction in compensatory sweating.

The use of high-dose immunoglobulin in the treatment of pyoderma gangrenosum.

BACKGROUND: Immunosuppressive medications such as corticosteroids and cyclosporin are the most commonly employed therapies in pyoderma gangrenosum. We describe a patient with multiple ulcers of pyoderma gangrenosum on the lower extremities in whom immunosuppressive therapy caused serious side effects and had to be discontinued but who was subsequently treated successfully with high dose intravenous immunoglobulin (IVIG). METHODS: IVIG was given intravenously at a dose of 400 mg/kg per day for 5 consecutive days. After 1 week there was an arrest in the progression of the ulcers and a marked reduction in pain. Two weeks later clinical improvement of the ulcers was observed. Subsequently, IVIG was given at a dose of 1 g/kg per day for 2 consecutive days. RESULTS: The treatment induced a dramatic clinical improvement of one ulcer and healing of the others. Side effects were minimal and well tolerated, and consisted of chills and a slight fever, which resolved with the administration of acetaminophen. CONCLUSION: We feel that IVIG can be used in patients with pyoderma gangrenosum in whom conventional therapies are ineffective or produce serious side effects. ( J Dermatol Treat (2000) 12: 19-22)

IL-21 Promotes Skin Recruitment of CD4+ Cells and Drives IFN-γ–Dependent Epidermal Hyperplasia

Psoriasis is a chronic inflammatory disorder of the skin characterized by epidermal hyperplasia and infiltration of leukocytes into the dermis and epidermis. T cell-derived cytokines, such as IFN-γ and IL-17A, play a major role in the psoriasis-associated epidermal hyperplasia, even though factors/mechanisms that regulate the production of these cytokines are not fully understood. We have recently shown that IL-21 is synthesized in excess in psoriatic skin lesions and causes epidermal hyperplasia when injected intradermally in mice. Moreover, in the human psoriasis SCID mouse model, neutralization of IL-21 reduces both skin thickening and expression of inflammatory molecules, thus supporting the pathogenic role of IL-21 in psoriasis. However, the basic mechanism by which IL-21 promotes skin pathology remains unknown. In this study, we show that CD4+ cells accumulate early in the dermis of IL-21–treated mice and mediate the development of epidermal hyperplasia. Indeed, IL-21 fails to induce skin damage in RAG1-deficient mice and CD4+ cell-depleted wild-type mice. The majority of CD4+ cells infiltrating the dermis of IL-21–treated mice express IFN-γ and, to a lesser extent, IL-17A. Studies in cytokine knockout mice show that IFN-γ, but not IL-17A, is necessary for IL-21–induced epidermal hyperplasia. Finally, we demonstrate that IFN-γ–producing CD4+ cells infiltrating the human psoriatic plaque express IL-21R, and abrogation of IL-21 signals reduces IFN-γ expression in cultures of psoriatic CD4+ cells. Data indicate that IL-21 induces an IFN-γ–dependent pathogenic response in vivo, thus contributing to elucidate a mechanism by which IL-21 sustains skin-damaging inflammation.

Severe acne successfully treated with etanercept

Effective systemic treatments for severe acne vulgaris, such as oral antibiotics, oral isotretinoin and anti-andro-gens, are often associated with undesirable side-effects or are limited to a selected patient population. Furthermore, some patients with severe acne fail to respond to these therapies (1).Etanercept, a dimeric fusion protein linking part of the human p75 tumour necrosis factor (TNF) receptor extracellular domain with the Fc region of IgG

Localized morphea treated with imiquimod 5% and dermoscopic assessment of effectiveness

The cases are reported of two women patients presenting asymptomatic solitary lesions: one in the anterior tibial region of the right leg, the other on the right arm. The first patients lesion was 3 cm in diameter and had appeared 2 years earlier as a translucent oval atrophic patch with a definite border. The second patient presented a whitish area with a lilac ring, 2.5 cm in diameter, which had appeared nearly a year earlier. Both patients had no other similar cutaneous lesions, and their family histories for cutaneous disease were negative. The lesions underwent punch biopsy, and the histopathological findings confirmed the diagnosis of morphea. Laboratory investigations showed no abnormalities. Imiquimod 5% cream was prescribed for 5 consecutive days a week for 16 weeks. Clinical and dermoscopic assessment of the lesions was performed before treatment, during follow-up and at treatment end point. No local or systemic side effects were observed during treatment. Following treatment, both patients achieved complete clinical remission of the lesions, with a definitive improvement in the lesions’ initial disfiguring features.

Pyoderma vegetans and ulcerative colitis

Pyoderma vegetans (PV) is a chronic, vegetating pustular disorder characterized clinically by erythematous vesiculopustular vegetating cutaneous plaques. Marked epidermal hyperplasia, intraepidermal and subepidermal neutrophilic microabscesses and a dermal inflammatory infiltrate are the prominent histopathological findings. We describe a patient with PV associated with ulcerative colitis and mammary Paget’s disease. Pustular eruptions associated with ulcerative colitis are reviewed.

Connexin 26 (GJB2) mutations, causing KID Syndrome, are associated with cell death due to calcium gating deregulation.

The autosomic dominant KID Syndrome (MIM 148210), due to mutations in GJB2 (connexin 26, Cx26), is an ectodermal dysplasia with erythematous scaly skin lesions, keratitis and severe bilateral sensorineural deafness. The Cx26 protein is a component of gap junction channels in epithelia, including the cochlea, which coordinates the exchange of molecules and ions. Here, we demonstrate that different Cx26 mutants (Cx26D50N and Cx26G11E) cause cell death in vitro by the alteration of intra-cellular calcium concentrations. These results help to explain the pathogenesis of both the hearing and skin phenotypes, since calcium is also a potent regulator of the epidermal differentiation process.