Secukinumab in multi-failure psoriatic patients: the last hope?

Psoriasis is a multi-systemic chronic inflammatory disease that affects about 1.5-3% of the general population, of which almost 20% suffer from a moderate-severe form. Those patients can be treated with a systemic agent and in case of scarce response or contraindications, they may require a biologic therapy, such as tumor necrosis factor or interleukin-12/23 inhibitors. When also these agents fail, clinicians face a true therapeutic challenge. We report a case series of multi-failure 16 patients, successfully treated with secukinumab, a human monoclonal antibody that selectively neutralizes interleukin-17 A and is recently approved for the treatment of plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis.

Increased IL-18 in patients with systemic lupus erythematosus: relations with Th-1, Th-2, pro-inflammatory cytokines and disease activity. IL-18 is a marker of disease activity but does not correlate with pro-inflammatory cytokines.

OBJECTIVE: The aim of this study was to investigate the imbalance between Th-1 and Th-2 cytokines in systemic lupus erythematosus patients (SLE) and to asses if any of these cytokines could be related to disease activity. METHODS: Twenty SLE patients and 20 healthy individuals were investigated. Blood samples were collected to evaluate, using ELISA method, serum levels of a wide array of cytokines including: Th-1 type cytokines (Interleukin (IL)-12, Interferon (IFN)-gamma), Th-2 cytokines (IL-4, IL-10), pro-inflammatory cytokines (tumor necrosis factor (TNF)-alpha, IL-1beta and IL-18). Disease activity was assessed using the SLE Disease Activity Index (SLEDAI). Data were evaluated using the Mann-Whitney and Spearman's rank tests. RESULTS: The SLE patients group had a higher IL-4, IL-10, IL-12 and IL-18 serum concentration compared to the normal control group. IL-18 was negatively correlated with IL-4 and positively correlated with IFN-gamma. No serum cytokine level was correlated with disease activity except for IL-18, which was found strongly correlated with "active disease", defined as SLEDAI > 8 points. IL-18 showed no correlation with pro-inflammatory cytokines. CONCLUSIONS: Our results show that Th-1 as well Th-2 cytokines can be elevated in SLE patients suggesting that lupus is a complex disease that may be supported by different cytokine patterns in different time-points. Only IL-18 has been found to be disease-activity related. The role of IL-18 in the pathogenesis of SLE might be important through apoptosis-mediating properties.

What proportion of dermatological patients receive evidence-based treatment?

OBJECTIVE: To determine the proportion of dermatological patients who are offered evidence-based therapy in the routine dermatological practice. METHODS: For every patient seen for the first time at one of our tertiary hospital setting clinics between April and May 1999, the primary diagnosis and the primary intervention were recorded. For each primary diagnosis-primary intervention combination, evidence was searched for in electronic databases from January 1966 to December 1999. The proportion of patients who were offered evidence-based interventions was calculated as the main outcome measure. RESULTS: With a study sample of 136 patients, 61 different diagnosis-treatment couples were generated and 94 queries on electronic databases were performed (to account for "primary interventions" including more than 1 drug or treatment modality). Eighty-seven (64%) of 136 patients received evidence-based interventions. Evidence from randomized controlled trials was found for 69 patients (50.7% of the sample). Controlled studies lacking randomization or double blinding or including fewer than 20 patients per treatment group dealt with treatments offered to 14 patients (10.3%). The treatments offered to 4 patients (2.9%) were judged to have self-evident validity (ie, trials unanimously judged unnecessary). Symptomatic and supportive measures accounted for most interventions lacking substantial evidence (36% of the patients), but we had to include in this class other important treatment regimens, mainly for rare conditions. CONCLUSIONS: Most of the study patients received evidence-based care. However, published trials should be carefully appraised, and relevance of clinical end points should be evaluated together with methodological issues. More accessible, clinically oriented, evidence-based information sources are needed.

Occupational generalised urticaria and allergic airborne asthma due to anisakis simplex.

Anisakis simplex (AS), a fish and cephalopodes parasite, may cause allergic reactions in humans on eating and/or handling contaminated fish. We present a case of occupational hypersensitivity to AS in a woman employed in a frozen-fish factory. She showed both generalised urticarial rash and asthmatic symptoms after work place exposure. All these symptoms immediately disappeared after work place exposure was ceased. The presence of a positive skin prick test and high specific IgE values confirmed a hypersensitivity to anisakis. This is the first case reported of both occupational generalised urticaria and allergic airborne asthma due to AS in the same patient. We suggest that AS could be an important cause of occupational asthma and/or urticaria in the fish industry.

Skewed expression of activation, differentiation and homing-related antigens in circulating cells from patients with cutaneous T cell lymphoma associated with CD7- T helper lymphocytes expansion.

Mycosis fungoides and Sézary syndrome represent the most frequent forms of cutaneous T cell lymphoma. Both are characterized by skin infiltrating and/or circulating malignant cells displaying a CD4+CD7- phenotype in the majority of cases. Because an expansion of CD4+CD7- cells may also be found in inflammatory dermatoses or in the aging process, we evaluated, by flow cytometry, the relationship between CD7 expression and the distribution of differentiation/activation or homing antigens on peripheral blood lymphocytes from 36 cutaneous T cell lymphoma patients and from healthy donors. CD4+CD7- cells were increased in all patients with cutaneous T cell lymphoma. As a consequence, the CD7+/- ratio was reduced in stage I-II mycosis fungoides (3.96 vs 6.55 in healthy donors), and inverted in stage III-IV MF and Sézary syndrome (0.28 and 0.12 respectively). In the late stage of disease, the CD7+/- inverted ratio was strictly related to the expression of CD15s, CD60, and CD45R0, and the lack of expression of CD26 and CD49d. Interestingly, in leukemic patients, this phenotype was also associated with peculiar morphologic (large size) or phenotypical (CD3dim expression) characteristics. Furthermore, a progressive reduction of circulating CD8+ cells was also seen throughout all stages of disease. The presence of these populations in cutaneous T cell lymphoma at late phases of disease and Sézary syndrome suggests that all of these molecules may play an important part in the activation pathway and skin homing of circulating T cells in lymphoproliferative disorders. Therefore, this may constitute a distinctive feature in cutaneous T cell lymphoma patients with more aggressive characteristics.

Unilateral demodicidosis.

A 45-year-old man presented with a unilateral, papulopustular, rosacealike, chronic dermatitis which involved the left portion of the forehead and the eyelids unilaterally. Many Demodex mites were found in the follicles of the affected area. Topical crotamiton cleared the lesions after an unsuccessful trial with oral metronidazole. This observation provides further evidence that demodicidosis is a condition distinct from common rosacea.

Schnitzler's syndrome: report of a new case and a review of the literature.

Schnitzler syndrome is a rare condition characterized by chronic non-pruritic urticaria, recurrent fever, bone pain, osteocondensation, and monoclonal IgM gammopathy without features of lymphoproliferative disease. We describe the case of a 44-year-old man with an 8-year history of bone pain with hyperostosis and a 5-year history of chronic non-pruritic urticaria, associated with fever, hyperleukocytosis, hepatomegaly, serum monoclonal IgM-kappa. Systemic treatment with steroids was effective against bone pain but was ineffective in controlling the urticaria. We also review 35 cases. No adequate treatment has yet been found. The pathogenesis is unclear and the role of the IgM component in the induction of urticaria has not been established.