Matteo Bordignon

Immunosuppression and melanocyte proliferation.

Melanocytes are pigmented cells derived from the neural crest; their proliferation is restrained by immune system. The eruption of nevi after an immunosuppressive condition is a peculiar phenomenon indicating that the immune system may play a major role in limiting proliferation of melanocytes. In this review, we analyze the role of immunosuppressive regimens on melanocyte proliferation. In particular, we discuss the eruptive nevi phenomenon, which is determined by the inability of the immune system to inhibit melanocyte proliferation. These clinical observations indicate that the immune system has a pivotal role in restraining melanocyte proliferation. However, although the role of the immune system in the development of nonmelanoma skin cancer has been shown clearly in several studies involving organ transplant patients, the role of immunosuppression in melanoma genesis has not yet been established. Further investigations are required to establish the real immunogenicity of melanoma, particularly in the light of the dichotomy between the eruptive nevi phenomenon in immunosuppressed patients and the low incidence of melanoma in transplanted patients.

Detection of autoantibodies against recombinant desmoglein 1 and 3 molecules in patients with pemphigus vulgaris: correlation with disease extent at the time of diagnosis and during follow-up.

The recent availability of cDNA clones for pemphigus antigens has allowed the production of recombinant desmoglein 1 and desmoglein 3 molecules and the development of an ELISA approach in order to determine levels of antibodies to them. The aim of the study was to determine the relationship between autoantibodies levels and the extent of both mucosal and skin lesions in 20 patients with pemphigus vulgaris at the time of diagnosis and during follow-up. For the detection of autoantibodies by ELISA we used the recombinant proteins expressing overlapping sequences with the entire extracellular desmoglein 1 and desmoglein 3 domains. We showed that in presence of mucosal lesions there was a correlation between extension of mucosal involvement and autoantiboidies titres against both desmoglein 1 and desmoglein 3, whereas in presence of skin lesions there was a statistically significant correlation between extension of skin lesions and autoantibodies titres against desmoglein 3, but not against desmoglein 1. A not negligible number of patients showed variations of the desmoglein 3 autoantibodies titre which did not correlate with the severity of both cutaneous and mucosal involvement. Similar results were obtained analyzing autoantibodies titres against desmoglein 1. In conclusion, we believe that the utilization of recombinant desmoglein 1 and desmoglein 3 proteins by ELISA should be used with caution to monitor disease severity and response to therapy, although it remains a high specific test for the initial diagnosis of pemphigus and the identification of a change in the clinical phenotype of this condition.

Primary Cutaneous CD30+ Anaplastic Large Cell Lymphoma in a Heart Transplant Patient: Case Report and Literature Review

Solid organ transplant recipients are at risk of developing a wide range of viral-associated malignancies, including skin tumours and lymphoproliferative disorders. The risk of a post-transplant lymphoproliferative disorder is 28-49 times the risk of a lymphoproliferative disorder in the normal population. Most cases are of B-cell phenotype and are associated with Epstein-Barr virus infection. Post-transplant lymphoproliferative disorders presenting clinically in the skin are rare and usually of B-cell phenotype. Only rare cases of cutaneous T-cell post-transplant lymphoproliferative disorder have been reported previously, mostly mycosis fungoides type. We describe here a rare primary cutaneous T-cell lymphoma CD30+ arising in a heart transplant patient who had a nodule on the right leg, several years after heart transplantation. The morphology and immunohistochemical findings were consistent with a CD30+ anaplastic large cell lymphoma with a T-cell phenotype. Excisional biopsy and radiotherapy of the affected area were performed. In this patient, the presence of a solitary lesion and the lack of systemic involvement represented the main factors taken into account in choosing the therapy and the patient was therefore treated using a non-aggressive approach, although with systemic immunosuppression. In conclusion, the diagnosis of a CD30+ anaplastic large cell lymphoma in transplant recipients does not imply aggressive clinical behaviour by the lymphoma.

Successful treatment of a 9-year-old boy affected by acrodermatitis continua of Hallopeau with targeted ultraviolet B narrow-band phototherapy

Acrodermatitis continua of Hallopeau (ACH) consists of a relapsing pustular eruption of the distal portions of hands and feet. We described a case of a 9‐year‐old boy affected by ACH, successfully treated with targeted ultraviolet B 311 nm phototherapy, which seems to be an effective and safe therapy for this condition.

Subcorneal Pustular Dermatosis (Sneddon-Wilkinson Disease) with Absence of Desmoglein 1 and 3 Antibodies : Case Report and Literature Review

Subcorneal pustular dermatosis (SPD) [Sneddon-Wilkinson disease] is a benign and uncommon disorder characterized by a chronic, relapsing vesiculopustular eruption of unknown etiology. We present a case of SPD in a young Black woman in whom ELISA was performed to test for desmoglein 1 and 3 antigens (the first reported case of evaluation for these antigens in a patient with SPD). The test revealed the absence of both antibodies. The patient was successfully treated with topical corticosteroids and narrow-band UVB phototherapy. In this report, we review both the pathophysiology of SPD, which has yet to be clarified, and its treatment. Data obtained from our case report add further support to the hypothesis that a non-antibody-mediated mechanism is operative in SPD. The treatment of choice for SPD is dapsone. However, the combination of corticosteroids and UVB phototherapy should be considered a valid therapeutic option in patients who are not appropriate candidates for dapsone therapy.

Primary cutaneous mantle cell lymphoma.

© 2011 The Authors. doi: 10.2340/00015555-1084 Journal Compilation

Adaptive Immune Responses in Primary Cutaneous Sarcoidosis

Sarcoidosis is a multisystemic inflammatory disorder with cutaneous lesions present in about one-quarter of the patients. Cutaneous lesions have been classified as specific and nonspecific, depending on the presence of nonnecrotizing epithelial cell granulomas on histologic studies. The development and progression of specific cutaneous sarcoidosis involves a complex interaction between cells of the adaptive immune systems, notably T-lymphocytes and dendritic cells. In this paper, we will discuss the role of T-cells and skin dendritic cells in the development of primary cutaneous sarcoidosis and comment on the potential antigenic stimuli that may account for the development of the immunological response. We will further explore the contributions of selected cytokines to the immunopathological process. The knowledge of the adaptive immunological mechanisms operative in cutaneous sarcoidosis may subsequently be useful for identifying prevention and treatment strategies of systemic sarcoidosis.

Non-alcoholic fatty liver disease, alcohol intake and psoriasis

Haemostatic changes following surgery. Thromb Res 1983;32:223–227. [5] Bezeaud A, Denninger MH, Dondero F, Saada V, Venisse L, Huisse MG, et al. Hypercoagulability after partial liver resection. Thromb Haemost 2007;98:1252–1256. [6] Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ. American College of Chest Physicians. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians EvidenceBased Clinical Practice Guidelines (8th edition). Chest 2008;133: 454S–545S. [7] Bauer KA. New anticoagulants. Hematology Am Soc Hematol Educ Program 2006:450–456. [8] Tripodi A, van den Besselaar AMHP. Laboratory monitoring of anticoagulation: where do we stand? Semin Thromb Hemost 2009;35:34–41. [9] Tripodi A. Monitoring oral anticoagulant therapy. In: Kitchen S, Olson JD, Preston FE, editors. Quality in laboratory hemostasis and thrombosis. Oxford: Wiley–Blackwell; 2009. p. 179–189. Armando Tripodi* Massimo Primignani Veena Chantarangkul Pier Mannuccio Mannucci Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine and Medical Specialties, Italy Third Division of Gastroenterology, IRCCS Cà Granda Ospedale Maggiore Policlinico Foundation and Università degli Studi di Milano, Milano, Italy * Address: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine and Medical Specialties, Via Pace 9, 20122 Milano, Italy. Tel.: +39 02 503 20725; fax: +39 02 503 20723. E-mail address: armando.tripodi@unimi.it (A. Tripodi) JOURNAL OF HEPATOLOGY

Primary Subcutaneous B-cell Lymphoma : Case Report and Literature Review

Primary cutaneous B-cell lymphomas are defined as malignant B-cell proliferations presenting with cutaneous involvement alone and no evidence of extracutaneous manifestations when complete staging has been performed. It has been shown that the infiltrate in some cases could involve the underlying subcutaneous tissues, but primary localization in this compartment has been rarely reported. We describe here the case of a 53-year-old woman who noticed a nodular lesion on the left shoulder that rapidly enlarged in a few months. The histological and immunophenotypical features were compatible with a subcutaneous B-cell lymphoma. The tumoural mass was confined predominantly to the subcutaneous compartment, as confirmed by computed tomography. No other tumour localizations were found. Thus, primary B-cell lymphoma of the subcutis was diagnosed. We report a review of the literature indicating that B-cell lymphomas that are primarily localized to the subcutaneous tissues represent a very rare modality of presentation with a biological behaviour different from conventional cutaneous B-cell lymphoma.

The role of immunohistochemical analysis in the diagnosis of parapsoriasis.

Parapsoriasis is a chronic dermatosis whose biological distinction from early mycosis fungoides, the most frequent form of cutaneous T-cell lymphoma, is still not clearly defined. Two types of parapsoriasis have been delineated: large-plaque parapsoriasis and small-plaque parapsoriasis. The lack of clinical and histological features, which may allow distinguishing parapsoriasis from early mycosis fungoides has prompted several investigations to assess the role of immunohistochemistry in establishing a conclusive diagnosis of these conditions. However, the additional data obtained by immunohistochemical analysis concerning the CD4/CD8 ratio, the aberrant expression of T-cell antigens and the expression of proliferation markers has not generally helped establish a more definitive diagnosis. This review critically discusses these immunohistochemical markers and their use in diagnosis of parapsoriasis.