Lucia Gallo

Osteopontin: a new emerging role in psoriasis.

Osteopontin (OPN) is a phosphorylated acidic glycoprotein produced by cells of the immune system, epithelial tissue, smooth muscle cells, osteoblasts, and tumor cells. OPN interacts with integrins and CD44 to enhance Th1 and inhibit Th2 cytokine expression. The involvement of this molecule in the onset of psoriasis has not previously been studied. Here, we demonstrate that OPN is expressed in peripheral blood mononuclear cells and in skin biopsies of psoriatic patients. The study was conducted on 30 patients affected with plaque psoriasis, and on 11 healthy donors. Two blood samples and two skin samples from patients affected with atopic dermatitis were used as control for Th2 typical inflammatory skin disease. The analysis of IL-1β, IFN-γ, ΤΝF-α, IL-8, and ICAM-1 showed the characteristic Th1 pattern in all the psoriatic blood and skin samples analyzed. This study offers an opportunity for understanding inflammation in psoriasis and supports the hypothesis that OPN could represent a potential target for therapeutic intervention in psoriatic patients.

Cutaneous alternariosis in a kidney transplantation recipient: Report of a case

Phaeohyphomycoses are induced by dematiaceous or darkly pigmented fungi. Alternaria species are the most important causative agents. Factors such as immunosuppression, local wounds or systemic disease are generally present. We report a case of phaeohyphomycosis induced by Alternaria alternata in an immunocompromised patient. The main interest in this case is the rareness of the cutaneous alternariosis and of its clinical aspects and the good response to therapy. Recognition of Alternaria spp. as potential opportunistic pathogens is important for the differential diagnosis of dermatological lesions, such as granulomatous or ulcerative lesions in immunocompromised patients.

Visceral leishmaniasis infection in a patient with psoriasis treated with efalizumab.

LDS751/SSC revealed: 4% lymphocytes, 2% monocytes, 66% granulocytes, 6% immature blast cells, 18% erythroblasts and other CD45– cells, confirming the diagnosis of pancytopenia. Physical examination revealed splenomegaly and hepatomegaly, confirmed by ultrasonography too. Serology for typhoid fever and brucellosis was negative. The examination of a Giemsastained smear from a bone marrow aspirate detected Leishmania amastigotes, and indirect immunofluorescence antibody test (ELISA) serology was positive at the titre of 1/640. The IgM + IgG ELISA test detected an IgM antiLeishmania concentration of 1.6 ! 10 –7 M , indicating a primary infection. A polymerase chain reaction for the amplification of Leishmania genomic sequences in peripheral blood and in bone marrow samples confirmed the diagnosis. The patient was treated intravenously with teicoplanin, ciprofloxacin, furosemide, albumin and folic acid and intramuscularly with vitamin B 12 . Despite the initial treatment, the patient remained febrile in a markedly fluctuant manner so that a combination of piperacillin sodium and tazobactam was added to his intravenous treatment. He was not started on a course of any antiparasitic treatments. After 6 weeks, the bone marrow examination did not detect any Leishmania parasites. Leishmaniasis is a parasitic (protozoan) disease, caused by various species of Leishmania . Humans, wild animals and domestic animals are known to act as reservoir hosts. In Italy the domestic and wild canines are the reservoir of the parasite Leishmania infantum . Our patient was living in Campania, southwest Italy, which has long been known to be endemic for VL [1] . A consistent principle is that healing and resistance to reinfection are associated with expanding numbers of Leishmania -specific Th1 cells, production of -interferon and activation of macrophages to kill intracellular amastigotes. Efalizumab (Raptiva ) is a humanized monoclonal immunoglobulin G1 antibody that binds with high specificity and affinity to the -subunit of leucocyte function-associated antigen 1 on the surface of T cells. Efalizumab is one of several biological therapies used for the treatment of psoriasis. Its efficacy in clinical trials has ranged from 24 to 38% of patients achieving a 75% or better improvement from baseline in PASI score at 12 weeks, increasing to 44% at 24 weeks in one trial [2, 3] . The most common adverse events seen are fever, chills, headache, nausea and myalgias, usually occurring within 48 h of the initial conditioning dose [4] . More serious adverse effects are rare but include reports of psoriasis flares during and after discontinuation of treatment, infection and malignancy [5] . Malignancies occur more frequently in populations that are immunosuppressed or immunodeficient, and the development of biological therapies for psoriasis that target the immune system has focused attention on the risk. From an analysis of 2,980 psoriasis patients treated with efalizumab, the incidence of malignancy over the relatively short duration of the clinical trials (aver

Acrodermatitis continua of Hallopeau responding to efalizumab therapy

mesenchymal tissue of the nail. Recently, we proposed a new term for mesenchymal cells, onychofibroblasts, because they can be distinguished from the dermal fibroblasts by their CD10 expression. Versican is a large chondroitin sulphate proteoglycan molecule. It is expressed in the dermal papilla of human hair follicles. Because the nail shares some features with the hair follicle, we examined the immunohistochemical localization of versican in the nail unit. The distal fingers with nail unit were obtained during polydactyly operations and frozen tissues were longitudinally sectioned. The monoclonal antibody to versican (1 : 100; Seikagaku Corporation, Tokyo, Japan) was applied. Interestingly, versican was expressed diffusely in well-defined areas, the mesenchymal cells and the surrounding extracellular matrix beneath the nail matrix and proximal nail bed (Fig. 1). In addition, versican was expressed in the nail matrix. However, in the proximal nail fold, versican was expressed only in some areas, including around blood vessels and eccrine structures. Here, we found that versican was localized to mesenchyme beneath the nail matrix and the proximal nail bed within the nail unit. This finding supports the existence of specialized nail mesenchyme containing onychofibroblasts and the need of the terminology named onychofibroblasts in nail histology.

Erythema multiforme-like eruption because of para-phenylenediamine.

A 29-year-old woman was admitted, in October 2006, with an acute dermatitis involving the scalp, ears, and limbs; physical examination showed EM-like lesions, target-like appearance at the periphery of the sharply delineated lesions. The onset of the rash began with multiple, erythematous, itching papules and vesicles on her scalp and behind the ears; subsequently an eruption of erythemato-papular patches with a target-like appearance on the trunk and limbs developed (Fig. 1); manifestations on lower limbs were milder than the ones on upper limbs. There were no oral, ocular, or genital lesions; reactive retroauricolar lymphadenopathy was also present. The patient was affected by alopecia areata totalis since she was 10, and she was used to wear a wig, made of natural hair, and to dye it with black colour. She had had her false hair dyed 1 day before the onset of the rash. She had no personal or familiar history of atopy, no history of infection, and no history of drug assumption for more than 6 weeks prior to the eruption. She was obese, but she was otherwise in good health. In addition, the growth of hair in eczematous areas of the scalp was noticed after 1 month. Patch testing with standard Società ItalianadiDermatologiaAllergologica Professionale e Ambientale (SIDAPA) series gave positive reactions to PPD (þþ) and nickel sulfate (þ). She was treated with topical and systemic corticosteroids and systemic antihistamines; the rash cleared after 2 weeks of treatment.

Trichophyton violaceum infection in an adult black patient in Europe.

References 1 Morelli JG. Cutaneous viral infections. In: Kliegman RM, Behrman RE, Jenson HB, eds. Nelson Textbook of Pediatrics, 18th edn. Philadelphia: WB Saunders, 2007: 2751–2754. 2 Drake LA, Ceilley RI, Cornelison RL, et al. Guidelines of care for warts: human papillomavirus. J Am Acad Dermatol 1995; 32: 98–103. 3 Kuwahara RT, Craig SR, Amonette RA. Forceps and cotton applicator method of freezing benign lesions. Dermatol Surg 2001; 27: 183–184. 4 Ahmed I, Agarwal S, Ilchyshyn A, et al. Liquid nitrogen cryotherapy of common warts: cryo-spray vs. cotton wool bud. Br J Dermatol 2001; 144: 1006–1009. 5 James WD, Berger TG, Elston DM. Andrew’s Diseases of the Skin, 10th edn. Philadelphia: WB Saunders, 2006: 874–876.

Excess granulation tissue and hair loss following acitretin

Retinoids are routinely used in dermatology for various clinical entities including acne vulgaris, rosacea, hypertrophic scars, strie distensae, psoriasis, disorders of dyskeratinization, cancer prevention and other chronic hyperkeratotic disorders. Oral acitretin therapy is effective in the treatment of psoriasis normalizing cellular differentiation and maturation but clinical side-effects are reported. We describe the occurrence of excess granulation tissue in the nails sulcus and noncicatricial universal alopecia in a psoriatic patient receiving oral acitretin.

Psoriatic disease treatment nowadays: unmet needs among the “jungle of biologic drugs and small molecules”

Rheumatology is the branch of medicine dealing with the diagnosis and treatment of articular and connective tissue diseases. Outstanding progresses have been done in the last few decades regarding diseases pathogenesis and new diagnostic processes as well as innovative therapies [1]. Indubitably, the evolution in psoriatic arthritis (PsA) knowledge represents an emblematic example [2]. Indeed, fundamental advances in understanding PsA pathogenesis and natural history have deeply changed its perception by both patients and physicians [3]. In the past, psoriasis was considered just a mere esthetic concern due to a primary defect in keratinocytes, leading to their hyper-proliferation. Nowadays, it is well known that psoriasis and PsA have to be considered a systemic disease, not limited to the skin and joints, but linked to increased cardiovascular risk, obesity, and metabolic syndrome through a shared chronic pro-inflammatory background, establishing the concept of psoriatic disease (PsD) [4]. PsD often requires a multidisciplinary approach through the collaboration of dermatologist, rheumatologist, immunologist, etc. [5]. In addition, being a chronic inflammatory multifactorial disease and dysregulation of immune cells (Th1 and Th17 above all) have been reported as key features of PsD pathogenesis [6]. In this context, a major role is played by inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)17, IL-22, and IL-23 [6, 7]. Advances in PsD pathogenesis have put the basis for the development of new effective drugs for its treatment. Particularly, monoclonal antibody and fusion protein able to inhibit the effects of pro-inflammatory cytokines involved in PsD development, the so-called biologic drugs, have completely revolutionized disease management [8]. It is relevant, for example, that 40 years ago topical treatments such as corticosteroid, salicylic acid, and coal tar represented the main stay of psoriasis therapies, whereas nowadays different new systemic drugs are available such as biologics like anti-TNF-α (adalimumab, etanercept, golimumab, certolizumab, infliximab), anti-IL-12–23 (ustekinumab), and anti-IL-17 (ixekizumab, secukinumab) [8–10]. Moreover, literature is constantly enriching of clinical trials and surveys regarding newer biologic drugs which will be soon available for psoriasis and PsA treatment such as anti-IL-17 receptor (brodalumab) [11], anti-IL-23 (guselkumab, tildrakizumab) [12, 13], and anti-CD6 (itolizumab) [14]. However, PsD treatment scenario is going to becomemore andmore complex and wide apart from the development of biologic drugs. A new era will be introduced by the so-called small molecules which are able to act at the basis of the pro-inflammatory cascade which dominates PsD pathogenesis, preventing the production of inflammatory cytokines. This is the case of molecules such as phosphodiesterase 4 (PDE4) inhibitor (apremilast) and Janus kinase (JAK) inhibitor (tofacitinib) [15]. The intracellular enzyme, PDE4, hydrolyzes cyclic adenosine monophosphate (cAMP) into the intracellular second messenger AMP and activates protein kinase A, leading to regulation of anti-inflammatory and pro-inflammatory cytokines, chemokines, and leukotriene B4 [16]. Further, in PsD, a coordinate involvement of the JAKSTAT phosphoproteins pathway has been found [17]. Apremilast and tofacitinib, targeting respectively PDE4 and JAK molecules, have been showed efficacious on psoriasis and PsA [18–21]. Therefore, insights into the pathogenesis of PsD increasing the understanding of the action of cytokines and their * Raffaele Scarpa rscarpa@unina.it

Blastic Plasmacytoid Dendritic Cell Neoplasm: Report Of A Case

Blastic plasmacytoid dendritic cell neoplasm (BPDCN), also known as CD4+/CD56+ hematodermic neoplasm, is a rare, highly aggressive hematopoietic malignancy characterized by cutaneous, lymph node and bone marrow involvement, high risk of a leukemic dissemination, and a poor prognosis. It has been recognized as an independent entity in the World Health Organization (WHO) 2008 classification for cutaneous lymphomas and is thought to be derived from the precursors of plasmacytoid dendritic cells. This neoplasm most commonly affects middle-aged or elderly patients with predominant skin or soft tissue involvement. We report a case of a 87-year-old man with a purplered plaque on his face and multiple purple-red nodules on his trunk. Histopathology and immunohistological staining confirmed the diagnosis of blastic plasmacytoid dendritic cell neoplasm.