Osteopontin: A New Facilitating Factor in Alopecia Areata Pathogenesis?

Osteopontin (OPN) is a multifunctional glycophosphoprotein secreted by many cell types, including osteoblasts, lymphocites, macrophages, epithelial cells, and vascular smooth muscle cells. It has been implicated in many physiological and pathological processes, such as cell-mediated immunity, inflammation, cell survival, and tumor invasion and metastasis. Osteopontin has multiple emerging roles in cutaneous biology and pathology and OPN involvement has been emphasized in Th1-mediated diseases such as psoriasis. Alopecia areata (AA) is a form of non-scarring hair loss affecting anagen stage hair follicles with a multifactorial autoimmune pathogenesis characterized by a prevalent Th1 cytokine profile. Given the role of osteopontin in Th1-mediated inflammation, we have postulated that OPN may be involved in AA pathogenesis. The aim of our study was to investigate plasma OPN level in alopecia areata before and after DPCP treatment. Our results showed that OPN plasma levels in patients with alopecia areata were higher than in healthy controls, but patients achieving complete recovery after DPCP treatment did not show a statistically significant reduction of OPN plasma levels.</p

Aspetti biomolecolari dei linfomi cutanei

La micosi fungoide (MF) è la forma più comune di linfoma cutaneo a cellule T (CTCL). La patogenesi della MF è in gran parte sconosciuta, ma sono state implicate la stimolazione persistente dell'antigene, l'espressione aberrante delle chinasi SRC, la regolazione anormale della segnalazione dei recettori delle citochine, la disregolazione delle vie apoptotiche e le alterazioni epigenetiche. Più recentemente, è stato anche suggerito un ruolo centrale per l'espressione aberrante dei microRNA (miRNA). I miRNA sono piccoli RNA non codificanti che regolano l'espressione proteica a livello post-trascrizionale mediante degradazione dell'mRNA. I miR sono fondamentali per il normale sviluppo e il mantenimento dell'omeostasi nei tessuti adulti e numerose indagini hanno dimostrato che profili alterati di miRNA sono coinvolti nella patogenesi sia dei linfomi sia dei tumori solidi. Inoltre, studi indipendenti hanno dimostrato che alcuni miRNA sono up-regolati (miR-155, miR-21, miR-199/214) o down-regulation (miR-223, miR-150) nei CTCL e agiscono come onco- miR o miR soppressori del tumore per promuovere la proliferazione, ridurre l'apoptosi o migliorare l'invasione. I miRNA sembrano anche avere un potenziale come strumento diagnostico nei CTCL. Nel nostro studio abbiamo preso in esame i miR-155, miR-146a, miR-21, miR-126, i quali, sono stati valutati nel plasma, nei PBMC e nelle CAC in 10 pazienti e in 10 controlli. Si è osservato che i valori di miRNA nel plasma e nelle PBMC risultavano tutti più alti nei pazienti rispetto ai controlli, in modo statisticamente significativo solo per il plasma e per il miR-146a nelle PBMC. Un andamento opposto si è osservato invece nelle CAC dove abbiamo ottenuto valori più bassi nei pazienti rispetto ai controlli anche se in modo non statisticamente significativo. I miRNA presi in esame nel nostro studio sono probabilmente implicati nel meccanismo patogenetico e nelle alterazioni infiammatorie e vascolari della MF testimoniato dal comune trend di modificazione di tali miRNA nel plasma, nei PBMC e nelle CAC tra malato e controllo.Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL). The neoplastic cells presumably originate from mature, skin-homing memory T cells and the disease is histologically-characterized by the presence of epidermal and dermal infiltrates of atypical Tcells with irregular (cerebriform) nuclei. The early stages are characterized by persistent patches or plaques, but the disease can progress to tumor lesions and can transform to large T-cell lymphomas and disseminate to lymph nodes and internal organs. The pathogenesis of MF is largely unknown, but persistent antigen stimulation, aberrant expression of SRC kinases, abnormal regulation of cytokine receptor signaling, dysregulation of apoptotic pathways and epigenetic alterations have been implicated. More recently, a central role for aberrant microRNA (miR) expression has also been suggested. miRs are small non-coding RNAs that regulate protein expression at the post-transcriptional level by mRNA degradation or translational repression. miRs are central to normal development and maintenance of homeostasis in adult tissues, and numerous investigations have shown that altered miR profiles are involved in the pathogenesis of both lymphomas and solid tumors. Furthermore, independent studies have shown that certain miRs are consistently differentially up-regulated (miR-155, miR-21, miR-199/214) or down-regulated (miR-223, miR-150) in CTCL and act as onco-miRs or tumor-suppressor miRs to promote proliferation, reduce apoptosis or enhance invasion. miRs also appear to have potential as a diagnostic tool in CTCL. miR studies in CTCL have, with very few exceptions, exclusively focused on advanced MF or SS (Sézary Syndrome). No knowledge is available about the global miR expression pattern in early MF. In our study miR-155, miR-146a, miR-21, miR-126 were evaluated in plasma, PBMC (Peripheral blood mononuclear cell) and CAC (circulating angiogenetic cell) in 10 patients and in 10 controls. It was observed that miRNA values in plasma and PBMC were all higher in patients than controls, statistically significant only for plasma and for miR-146a in PBMCs. On the contrary, the opposite trend was observed in the CAC where we obtained lower values in the patients compared to the controls, even if not statistically significant. The miRNAs examined in our study are probably implicated in the pathogenetic mechanism and in the inflammatory and vascular alterations of MF testified by the common trend of modification of such miRNAs in plasma, in PBMC and in CAC between patient and control. It would be useful to investigate miRNAs in relation to the stage of disease progression to identify predictive factors of progression or less of MF, suggesting a role for dysregulated miRNAs both in early malignant transformation and in disease progression. It would also be interesting to evaluate how systemic treatments can modify the levels of both circulating and intracellular miRNAs and whether these phenomena are specific to the various cell types

Hidradenitis suppurativa in Crohn's disease during adalimumab therapy: a paradox?

A sporadic association between hidradenitis suppurativa and other diseases is reported in the literature, but few authors have described the association with Crohn's disease. Adalimumab is a fully human monoclonal antibody targeted at tumor necrosis factor alpha approved for the treatment of Crohn's disease and, recently, for active moderate to severe hidradenitis suppurativa in adult patients that do not respond adequately to systemic conventional treatment. We report an unusual case of a paradoxical effect of adalimumab in the onset of hidradenitis suppurativa in a 40-year-old woman during the treatment of Crohn's disease

Coexistence of systemic lupus erythematosus, Hashimoto's thyroiditis, and bilateral breast cancer in the same patient: a random association?

Estrogens influence many physiological processes and play a crucial role in the development of several diseases, including autoimmune disorders and hormone-sensitive cancers. Systemic lupus erythematosus is one of the most common systemic autoimmune rheumatic diseases affecting young and middle-aged females. The coexistence of multiple autoimmune disorders is well recognized, whereas the association between systemic lupus erythematosus and malignancies, especially hormone-sensitive cancers, remains enigmatic. We report the unusual case of a middle-aged woman that presented with concomitance of lupus erythematosus, Hashimoto's thyroiditis, and bilateral breast cancer

Efficacy, safety and tolerability of field treatment of actinic keratosis with ingenol mebutate 0.015 % gel: a single center case series

INTRODUCTION: Actinic keratosis (AK) is a cutaneous intraepithelial neoplasm appearing within areas referred as ‘fields of cancerization’. AK can progress to invasive squamous cell carcinoma. Treatments that target both clinically visible and subclinical AKs in cancerization fields are able to reduce the risk of malignant progression. Ingenol mebutate gel is a new effective topical therapy for AK, used once daily for 2 or 3 days depending on the location of lesions. CASE DESCRIPTION: Three elderly patients with multiple non-hypertrophic AKs within a contiguous 25-cm(2) treatment area on the face or scalp were treated with ingenol mebutate 0.015 % gel once daily for three consecutive days and followed up over a period of 57 days. DISCUSSION AND EVALUATION: Although individual local responses to treatment varied, all patients had total clearance of AK lesions without any sign of recurrence. In addition, all patients said that they were satisfied with the effectiveness of ingenol mebutate treatment and the aesthetic outcome, and would be prepared to use this agent again to treat AK in the future, if necessary. CONCLUSIONS: These three cases demonstrate that ingenol mebutate 0.015 % gel is effective and well tolerated in a clinical setting, with effective clearance of AK lesions present on the face and scalp, and good patient acceptability

Lifelong widespread warts associated with human papillomavirus type 70/85: a new diagnostic entity?

We present a patient with HPV 70/85-positive widespread cutaneous warts characterized by clinical and histological features atypical for classic generalized verrucosis or epidermodysplasia verruciformis. The cutaneous HPV infection is characterized by verrucous papules or plaques variable in size, number, and distribution depending on the genotype of HPV involved and the immune status of the patient. Human papillomaviruses comprise five genera (alpha, beta, gamma, mu, and nu papillomavirus) with different life-cycle characteristics, epithelial tropisms, and disease associations. Epidermodysplasia verruciformis (EV) is a rare, lifelong, autosomal recessive skin disease characterized by persistent cutaneous human papillomavirus infection not necessarily associated with immune system defects. The disease results from an unusual genetic susceptibility to infections with various types of HPVs (especially β-HPV), some of which cause malignant transformation. Conversely, generalized verrucosis has been more typically associated with generalized warts, which are associated with immunocompromised conditions

Botulinum Toxin Off-Label Use in Dermatology: A Review

Botulinum toxin is a neurotoxin produced by the bacterium Clostridium botulinum which causes a flaccid muscle paralysis. It is currently used for aesthetic treatments and in the focal hyperhidrosis. Recently, botulinum toxin has also been used experimentally in many other dermatological conditions with good results

Elastosis perforans serpiginosa: a case successfully treated with intralesional steroids and topical allium cepa-allantoin-pentaglycan gel

Elastosis perforans serpiginosa is a rare skin disease in which abnormal elastic fibers, other connective tissue elements, and cellular debris are expelled from the papillary dermis through the epidermis. Three clinical variants of EPS can be detected: idiopathic, reactive, and drug-induced. Clinically it consists of small horny or umbilicated papules arranged in a linear, arciform, circular, or serpiginous pattern. It usually occurs in young adults and shows a predilection for the head and neck. The lesions are generally asymptomatic or slightly itching. Several treatments have been reported with poor long-term success; these include intralesional and topical corticosteroids, tazarotene, imiquimod, and cryotherapy. We report a case of 40-year-old black woman affected by elastosis perforans serpiginosa that was referred to our department and treated with intralesional injections of triamcinolone acetonide and topical application of allium cepa-allantoin-pentaglycan gel