Higher Serum Ferritin Levels Correlate with an Increased Risk of Cutaneous Morbidity in Adult Patients with ß-Thalassemia: A Single-Center Retrospective Study.

Disturbed iron homeostasis characterizes ß-thalassemia and increases its morbidity. Our aim was to retrospectively associate ß-thalassemia disease characteristics with treatment-requiring skin conditions. The files of adult ß-thalassemia (including sickle ß-thalassemia) patients were screened over a 10-year period for treatment-requiring skin disease episodes and their correlation with hematologic diagnoses and epidemiological and serological characteristics. Seventy-eight patients were identified, and 7 (9%) developed at least one relevant episode including cutaneous small-vessel vasculitis (CSVV), urticaria, and leg ulcers. Average ferritin serum level correlated significantly with development of a dermatosis (2,034 ± 799 µg/l in cases vs. 920 ± 907 µg/l in the overall population; p = 0.001, ANOVA). This difference relied exclusively on the high ferritin levels observed in patients with 'generalized' dermatoses (urticaria and CSVV: 3,860 ± 1,220 µg/l) as opposed to values within the normal range in the case of 'localized' ones (leg ulcers: 662 ± 167 µg/l). The employed iron chelation treatment influenced ferritin levels (p = 0.002, Kruskal-Wallis test) since chelation with a single agent seems to increase the risk of a skin disease (p = 0.013, likelihood ratio method). Conclusively, serum ferritin can be evaluated as risk factor for generalized dermatoses, but not for leg ulcers, in patients with the ß-thalassemia genotype. This risk can be efficiently controlled with adequate chelation.

Paraneoplastic Syndromes in Patients with Keratinocyte Skin Cancer.

A variety of well-characterized cutaneous paraneoplastic syndromes (PNS) are diagnosed during internal malignancies; however, the spectrum of keratinocyte skin neoplasms (KSC) related to PNS is still obscure. The aim of the present review is to compile and evaluate the literature data on PNS associated with a keratinocyte skin neoplasm (KSC). Employing Pubmed, MEDLINE was searched for KSC-associated PNS reports. Forty relevant entries were assembled, reporting a total of 41 PNS cases associated with a KSC (34 male). No review paper compiling this topic was found. Six distinct PNS entities were identified, and malignancy associated hypercalcemia (MAH; 78%), anemia (10%) and Bazex syndrome (5%) were the most frequently reported among them. 85% of the PNS were reported in association with SCC, 10% with BCC, and the rest with adnexal tumors. The median age of the patients at the time of PNS diagnosis was 58 years (range: five-83 years). In most cases the PNS was diagnosed either concurrently or after the KSC diagnosis. KSC predisposing conditions, as scars (22%) or hidradenitis suppurativa (20%), were reported in >70% of the PNS cases. Most PNS resolved after KSC treatment. In conclusion, PNS of a rather limited spectrum of entities are reported in association with KSC. They also seem to be rare, possibly reflecting a limited capacity of KSC to provoke overt PNS.

Psoriasis and inflammatory bowel disease: links and risks.

Psoriasis and the spectrum of inflammatory bowel diseases (IBD) are chronic, inflammatory, organotropic conditions. The epidemiologic coexistence of these diseases is corroborated by findings at the level of disease, biogeography, and intrafamilial and intrapatient coincidence. The identification of shared susceptibility loci and DNA polymorphisms has confirmed this correlation at a genetic level. The pathogenesis of both diseases implicates the innate and adaptive segments of the immune system. Increased permeability of the epidermal barrier in skin and intestine underlies the augmented interaction of allergens and pathogens with inflammatory receptors of immune cells. The immune response between psoriasis and IBD is similar and comprises phagocytic, dendritic, and natural killer cell, along with a milieu of cytokines and antimicrobial peptides that stimulate T-cells. The interplay between dendritic cells and Th17 cells appears to be the core dysregulated immune pathway in all these conditions. The distinct similarities in the pathogenesis are also reflected in the wide overlapping of their therapeutic approaches. Small-molecule pharmacologic immunomodulators have been applied, and more recently, biologic treatments that target proinflammatory interleukins have been introduced or are currently being evaluated. However, the fact that some treatments are quite selective for either skin or gut conditions also highlights their crucial pathophysiologic differences. In the present review, a comprehensive comparison of risk factors, pathogenesis links, and therapeutic strategies for psoriasis and IBD is presented. Specific emphasis is placed on the role of the immune cell species and inflammatory mediators participating in the pathogenesis of these diseases.