Francesco Loconsole

Immunogenicity of anti-TNFα therapy in psoriasis: a clinical issue?

Introduction: Immunogenicity of antitumor necrosis factor-alpha (TNFα) agents has been proven to play a significant role in the variability of clinical responses among patients with chronic inflammatory diseases. However, its clinical impact on the outcome of patients with psoriasis and psoriatic arthritis receiving anti-TNFα treatment is not yet fully clear. Despite the high rates of efficacy of anti-TNFα agents in psoriasis, a substantial proportion of patients remain who experience a primary or secondary failure or significant side effects, which are potentially ascribable to immunogenicity. Areas covered: Topics include immunologic response elicited by anti-TNFα agents, the impact of immunogenicity on treatment response to anti-TNFα and the role played by immunogenicity in the lack of efficacy of anti-TNFα agents (infliximab, adalimumab and etanercept) in psoriasis. Expert opinion: Based on data available in the literature and the clinical experience of the authors, this article suggests the optimal approach to drug monitoring and antidrug antibody assay and the most effective use of biologic immunotherapies in this setting. Immunogenicity should be taken into account in the adoption of therapeutic choices in psoriatic patients, such as anti-TNFα agent intensification, or switching to another anti-TNFα agent or a drug with a different mechanism of action.

Infliximab in recalcitrant severe atopic eczema associated with contact allergy.

Infliximab is an anti-tumour necrosis factor (TNF)-alpha chimeric monoclonal antibody which is effective in diseases associated with a T-helper (Th) 1 response, such as rheumatoid arthritis, Crohns disease and psoriasis. There are sporadic case reports of atopic dermatitis (AD) induced or precipitated by anti-TNF-alpha therapy, which have been attributed to the switch towards Th2-mediated reactions. We report the case of a 30-year-old man with long-standing severe AD associated with contact allergy and poorly responding to conventional treatments. The use of infliximab resulted in a dramatic amelioration of AD lesions and pruritus, persisting at follow-up examinations over a 3-year period. Probably, the unexpected response to infliximab therapy in this case might be due to some peculiar features of AD in our patient (i.e. chronic-continuous course and concomitant contact allergy) which could have been responsible for a more preponderant recruitment of Th1 cells as compared to common forms of AD.

Classical Kaposi’s Sarcoma: A Survey of 163 Cases Observed in Bari, South Italy

BACKGROUND Classical Kaposis sarcoma (KS) is a sporadic disease that is particularly prevalent in Mediterranean countries. OBJECTIVE The aim of the study was to update clinical information about this rare condition. METHODS A survey of 163 cases observed in the period 1971-1990 in Bari, South Italy, was carried out. All records were reviewed and, when lost to follow-up for more than 6 months, patients were called back to update personal and family histories. The age at onset averaged 64 years (range 18-85). The male-to-female ratio was 3:1. No familiar occurrence was identified, and no significant association was found with other conditions (i.e. second primary malignancies and diabetes mellitus). Death from KS occurred in 16 cases, at the mean age of 71 years, an average of 5.7 years after the onset of the disease. To assess whether the different clinical patterns of the disease in its earlier stages may give any indication of its subsequent clinical course, all cases were re-classified into three groups (low-, moderate- and high-eruptivity group) on the basis of both the extent and the rate of spread of the disease before first admission; group-stratified survival function was evaluated using Kaplan-Meiers life table method. RESULTS Highly significant (p < 0.0001) differences were found in survival profiles of the three study groups, also when only deaths due to KS were computed. CONCLUSION These findings provide some support to the hypothesis that three subsets of classical KS exist that have different prognoses and, consequently, need different therapeutic approaches.

Role of Th2 cytokines, RANTES and eotaxin in AIDS-associated eosinophilic folliculitis.

The pathogenesis of AIDS-associated eosinophilic folliculitis is still unknown. The expression of chemokines and Th2-type cytokines is increased in other conditions associated with tissue eosinophilia and in allergic reactions. We evaluated the mRNA expression by reverse transcriptase polymerase chain reaction of two Th2 cytokines (interleukin-4 and interleukin-5) and of two chemokines (RANTES and eotaxin) in the skin of 6 patients with AIDS-associated eosinophilic folliculitis; the tissue localization of eotaxin was shown by immunohistochemistry. We demonstrated the increased expression of interleukin-4, interleukin-5, RANTES and eotaxin in lesional skin of the patients compared to normal skin of HIV+ individuals. We concluded that a Th2 pattern is present in AIDS-associated eosinophilic folliculitis. The cytokine milieu in this disease may favour a Th2 immune response to an unknown antigen, whereby RANTES and eotaxin act in synergy with interleukin-4 and interleukin-5 to mediate tissue inflammation.

Cutaneous sporotrichosis in the period 1978–1992 in the province of Bari, Apulia, Southern Italy

Summary. The authors report 16 cases of cutaneous sporotrichosis observed in the province of Bari, southern Italy, since 1978. While no more than 55 cases have been documented in other European countries in the last 30 years, in Italy 58 cases (present series included) have been recorded in the same time period. Furthermore, 42 of them (73.7%) originated from Apulia. This unexpectedly high incidence rate in Italy, and in Apulia in particular, provides evidence of the important role played by this area in the eco‐epidemiology of sporotrichosis in Europe.

Treatment of Psoriasis Vulgaris with the Two-Compound Product Calcipotriol/Betamethasone Dipropionate followed by Different Formulations of Calcipotriol

AbstractBackground: A calcipotriol (calcipotriene)/betamethasone dipropionate two-compound product has been shown to be efficacious for the treatment of psoriasis vulgaris. It is usually administered once daily for up to 4 weeks followed by treatment with corticosteroid-free conventional products (e.g. calcipotriol). The aim of this study was to evaluate the efficacy and tolerability of a 4-week treatment with the two-compound product in psoriasis vulgaris and the effects of sequential 8-week maintenance treatment with different calcipotriol formulations. Methods: After an initial 4-week phase with the once-daily calcipotriol/betamethasone dipropionate two-compound product, adult patients with stable psoriasis vulgaris entered an 8-week maintenance phase and were allocated to one of the following treatments: calcipotriol ointment twice daily, calcipotriol cream twice daily, or calcipotriol cream once daily in the morning and calcipotriol ointment once daily in the evening. Clinical assessment was performed at baseline, after 4 weeks and after 12 weeks, and employed evaluation of the severity of pruritus using a scale from zero to four and the Psoriasis Area and Severity Index (PASI). Results: After 4 weeks’ treatment with the calcipotriol/betamethasone dipropionate two-compound product, a significant improvement in the severity of psoriasis was observed in all groups, with a mean reduction in the PASI of 71.3% (p < 0.001 vs baseline). A significant improvement in pruritus was also obtained after 4 weeks. These results were maintained after 8 weeks of treatment with calcipotriol, regardless of the formulation used. Treatment was very well tolerated and accepted by patients. On a scale ranging from poor to excellent, more patients treated with calcipotriol cream (49%) rated the acceptability of the treatment as excellent when compared with patients treated with the calcipotriol ointment (33%) or both calcipotriol formulations (36%). Conclusion: This study shows that the calcipotriol/betamethasone dipropionate two-compound product causes a rapid and marked improvement in both psoriasis lesions and pruritus. Our preliminary results suggest that the three calcipotriol-based regimens are equally effective in maintaining the therapeutic results obtained with the calcipotriol/betamethasone dipropionate two-compound product and that the use of calcipotriol cream was the best accepted maintenance treatment.

Topical finasteride in the treatment of androgenic alopecia. Preliminary evaluations after a 16-month therapy course

The enzyme 5α-reductase (5AR), which catalyzes reduction of testosterone to the more potent metabolite dihydrotestosterone, has been assumed to play a key role in a variety of skin disorders, including acne, seborrhea, hirsutism, and androgenic alopecia (AA). Also, evidences have been provided supporting the pathogenetic relevance of higher rates of testosterone reduction at lesional level. The azasteroid finasteride, a 5AR inhibitor, is widely employed in the treatment of benign prostatic hyperplasia; by contrast, its potential role in other androgen-related conditions have been, so far, only poorly evaluated.We present herein the results of a single-blind, placebo-controlled, 16-month trial carried out in 52 patients with AA using a 0.005% finasteride solution. The clinical outcome, in terms of both hair regrowth and balding areas reduction, seems to be encouraging, in the absence of either any evidence of percutaneous absorption of finasteride, or local/systemic untoward effects.We also briefly review ...

Treatment of psoriasis with different dosage regimens of etanercept: preliminary results from the Tαranta Plastic Study Group.

This pilot open-label study is aimed to assess clinical response in psoriasis patients receiving diverse dose regimens of etanercept, consisting of the same global cumulative dose of etanercept administered over different treatment periods. Eligible patients were assigned sequentially in a 1:1 ratio to receive: etanercept 50 mg once weekly (QW) or 50 mg twice weekly (BIW) for 12 weeks. The final analysis included a total of 72 patients. At week 12 the Psoriasis Area and Severity Index (PASI) and Skindex-29 scores notably improved in both treatment arms, without significant differences between the two groups. The rate of patients attaining a PASI improvement ≥ 50% (PASI 50) at week 12 was 92% in the high-dose group. In these patients, etanercept dosage was decreased to 50 mg QW from week 13, with persistence of the PASI 50 response at week 24 in all cases. Thereafter, treatment was discontinued up to week 36 and almost 30% of patients experienced a gradual relapse of their psoriasis within this period. In the low-dose group, the PASI 50 response was observed in 75% of patients. These responders continued to be treated with etanercept 50 mg QW up to week 36 with persistence of the PASI 50 in 100% of cases at week 24 and 93% at week 36. In the low-dose regimen, 8 patients who did not respond at week 12 underwent dose escalation to 50 mg BIW for a further 12 weeks. At week 24, six of these patients gained the PASI 50 response, 4 of whom maintained the response up to week 36, after treatment discontinuation from week 24. Our results confirm that etanercept is very effective and well-tolerated in psoriasis and that the drug dosages and treatment duration may be modulated and adapted to clinical needs in a flexible way.

Late paradoxical development of pyoderma gangrenosum in a psoriasis patient treated with infliximab

In July 2013 a 43-year-old Caucasian man presented to our outpatient Dermatology clinic with multiple extensive ulcerative lesions on the posterior aspects of both legs, which reportedly appeared some weeks before and had since rapidly extended. The lesions, which were very painful, had first developed as multiple erythemato-violaceous plaques which later became deeply ulcerated, showing irregular margins and a seropurulent bed. The patient suffered from severe psoriasis, for which he had been under [...]

Therapeutic hotline: Re-induction may be useful to manage psoriasis relapse during long-term maintenance treatment with infliximab: a retrospective analysis.

Infliximab is an anti‐tumor necrosis factor‐alpha monoclonal antibody that is highly effective for the treatment of psoriatic disease. During maintenance treatment, some patients may experience a disease relapse, and, in such circumstances, dose intensification is frequently used to regain efficacy. We report our cumulative experience on the use of infliximab re‐induction in patients whose psoriasis relapsed during long‐term maintenance treatment with infliximab. From September 2005 to January 2009, 22 patients required re‐induction because of a relapse of their psoriasis. Re‐induction was effective in restoring response in most patients and was well tolerated in all cases, without occurrence of serious or unexpected adverse events.