Pathophysiology of moderate to severe plaque psoriasis: anti-IL-17 towards disease modification.

Psoriasis is a chronic inflammatory disease that can be triggered by injury, trauma, infection and medications. Genetic and immunologic studies have highlighted the importance of the interleukin (IL)-23/T-helper 17 (Th17) pathway in systemic psoriasis pathogenesis. Main IL-23 is an upstream regulatory cytokine with direct effects on epidermal keratinocytes and other resident skin cells while IL-17, a downstream molecule, can activate inflammatory responses in different cells across a diversity of organs. Disease modification could be achieved with drugs that can slow down the biological processes that cause the persistent inflammation in moderate to severe psoriasis. Early intervention with anti-IL-17 and anti-IL-23 agents in new-onset moderate to severe plaque psoriasis might modify the natural course of the disease. Perhaps we are not simply seeing a pharmacologic and mechanistic effect of new-generation biologics but eventually a disease modification process. In this short report we underline the main available data which supports an important role for IL-17 blockade and address whether these new drugs targeting the IL-23/IL-17 axis could be disease-modifying agents in plaque psoriasis. This type of data gains more relevance in the current pandemic era, where chronic patients undergoing earlier treatment may have better outcomes and consequently avoid constant hospital visits.

Anti-Tumor Necrosis Factor-α-Induced Dermatological Complications in a Large Cohort of Inflammatory Bowel Disease Patients.

BACKGROUND/AIMS: The broader use of anti-tumor necrosis factor (TNF) agents in inflammatory bowel disease (IBD) has been associated with a high rate of adverse reactions. Dermatological complications are among the most common adverse events. We assessed the incidence, risk factors, management, and outcome of anti-TNF-induced dermatological complications in a large cohort of IBD patients. METHODS: This was an observational retrospective study at a single tertiary referral center. All consecutive adult IBD patients treated with anti-TNF agents between 2005 and 2015 were identified. Patients who developed at least one dermatological complication while on anti-TNF therapy were included. RESULTS: From the 732 patients treated with anti-TNF agents, 211 (29%) developed at least one dermatological complication: 52% women (mean age of 42 ± 13 years), 85% with Crohn's disease, 67% were under infliximab. Median follow-up time under anti-TNF therapy was 53 (27-77) months. Dermatological complications recorded were: infections (13.5%), psoriasiform lesions (5.3%), injection/infusion reactions (3.8%), skin cancer (0.5%), and miscellaneous (5.6%). Overall, female gender (OR = 1.658, p = 0.029), smoking (OR = 2.021, p = 0.003), and treatment with an infliximab dose of 10 mg/kg (OR = 2.012, p = 0.007) were independent risk factors for dermatological complications in multivariable analysis. Female gender (OR = 3.63, p = 0.017), smoking (OR = 2.846, p = 0.041), and treatment with adalimumab (OR = 8.894, p < 0.001) were independently associated with development of psoriasiform lesions. Three (3%) patients with infectious complications and 12 (31%) patients with psoriasiform lesions discontinued anti-TNF therapy definitively. CONCLUSIONS: Dermatological manifestations occurred in almost one-third of our population. Infections were the most common complication, but anti-TNF-induced psoriasiform lesions were the most common cause for anti-TNF therapy definitive discontinuation.

Reformulations of well-known active ingredients in the topical treatment of psoriasis vulgaris can improve clinical outcomes for patients.

Although the majority of patients with psoriasis vulgaris are treated exclusively with topical therapies, research to develop more effective topical therapies that are associated with higher patient satisfaction has lagged behind the development of systemic agents. The aim of this literature review was to determine whether there is documented evidence that applying an innovative approach to improving the formulation of active ingredients commonly used in the topical treatment of psoriasis can have a positive effect on clinical outcomes and patient-reported outcomes (PROs). The Embase and PubMed databases were searched for articles published between 2001 and 2016 that made direct head-to-head comparisons of different formulations of an active pharmaceutical ingredient (API), focusing on clinical outcomes and PROs. In total, 22 publications on APIs or API combinations met the eligibility criteria (19 head-to-head clinical trials, one pooled analysis, one health-economic modelling study and one systematic review). Significant clinical benefit associated with the use of a reformulated API over an older formulation was reported in three trials of clobetasol propionate, one trial of calcipotriol, three trials of betamethasone and five trials/pooled analyses of calcipotriol/calcipotriene + betamethasone dipropionate (Cal/BD) formulations. Significantly improved PROs associated with the use of a reformulated API over an older formulation were reported in three trials of clobetasol propionate, one trial of betamethasone valerate and two trials of Cal/BD formulations. These results demonstrate that the innovative reformulation of APIs used in the treatment of psoriasis can produce therapies that attain significantly improved clinical outcomes and PROs. This suggests that improvement in topical therapy for psoriasis need not only to be achieved by the identification of new targets and the development of new APIs, but that improvement in the vehicle used to deliver existing APIs has the potential to result in significant clinical and patient benefits.

Generalized Bullous Fixed Drug Eruption due to Bromhexine.

We describe a patient with a generalized bullous form of Fixed Drug Eruption (FDE) induced by bromhexine, a commonly used drug for respiratory symptoms. This is a rare association and generalized bullous FDE is also very rare. We emphasize the importance of patch tests in identifying the culprit drug.

Anti-TNF-alpha induced psoriasiform eruptions with severe scalp involvement and alopecia: report of five cases and review of the literature.

We describe 5 cases of anti-tumor necrosis factor-alpha (anti-TNF-α) induced psoriasiform eruptions with severe scalp involvement inducing inflammatory alopecia and review the literature on this subject. All our 5 patients were provided topical therapy, with good results in only 1 case. The remaining 4 were provided systemic therapy (methotrexate ± cyclosporine): 3 concomitantly suspended the anti-TNF-α treatment (2 are currently clear/almost clear but 1 has so far only observed mild improvement) and 1 switched anti-TNF-α (recurrent flare-ups of the disease continue). So far, no patient has developed scarring alopecia. To our knowledge, a total of 15 cases of anti-TNF-α induced psoriatic alopecia have been described. Anti-TNF-α was discontinued in 9 of the 15 patients and systemic therapy was provided to 9 of the 15 patients. Nonetheless, 2 patients developed scarring alopecia. We conclude that in anti-TNF-α induced psoriasiform eruptions some patients may respond to topical treatment, however in cases of severe scalp involvement anti-TNF-α suspension and systemic treatment should be considered in order to avoid scarring alopecia.

Salt sensitivity of blood pressure in patients with psoriasis on ciclosporin therapy.

BACKGROUND: Hypertension is one of the main side-effects of long-term therapy with ciclosporin. However, the influence of salt intake on the 24-h mean blood pressure of patients with psoriasis treated with ciclosporin is not known. OBJECTIVES: To evaluate, in patients with psoriasis, the sodium sensitivity of the ciclosporin-induced rise in blood pressure. METHODS: The 24-h ambulatory blood pressure was evaluated in 13 patients with psoriasis (age range 20-57 years) in two phases, before (phase I) and after the completion of 4 months of therapy with ciclosporin 3 mg kg(-1) daily (phase II). In both phases, the patients were studied in conditions of low sodium (LS) intake followed by a high sodium (HS) diet. RESULTS: Twenty-four-hour mean +/- SD blood pressure during LS and HS intake was, respectively, 86.3 +/- 1.6 mmHg and 85.5 +/- 1.8 mmHg during phase I, and 88.5 +/- 1.5 mmHg and 91.8 +/- 2.2 mmHg (P < 0.001 vs. phase I, HS; P < 0.05 vs. phase II, LS) during phase II. The median (interquartile range) sodium sensitivity index was greater during phase II than during phase I: - 0.0028 (- 0.0071 to 0.0009) vs. 0.0065 (- 0.0055 to 0.0258) (P < 0.02). The plasma levels and the daily urinary excretion of noradrenaline did not differ between phases I and II. CONCLUSIONS: The ciclosporin-induced rise in blood pressure is sodium sensitive. It is also suggested that sympathetic activation is not involved in the pathogenesis of ciclosporin-induced rise in blood pressure.

Scalp tumour as a sign of systemic B-cell lymphoma.

An 86-year-old man presented with a painful reddish tumour on the scalp with a 3-month history, mental confusion with recent onset and lymphadenopathies. Histological examination of the lymph node and cutaneous lesion revealed a dense infiltrate of atypical and large B cells. There was no evidence of bone marrow invasion. According to REAL (Revised European-American Classification of Lymphoid Neoplasms), this lymphoma was considered as a diffuse large B-cell lymphoma with concurrent cutaneous and nodal involvement. Cerebral computerized tomography (CT) scan showed bone and dura mater invasion in the right parieto-occipital region with collapse of lateral ventricle. The patient was submitted to systemic chemotherapy with cyclophosphamide, vincristine and prednisolone (CVP). There was a good response with regression of the cutaneous lesion, but the patient died after the third cycle. We point out the unusual clinical presentation and aggressive behaviour of this lymphoma.

Tuberculosis in a child presenting as asymptomatic oropharyngeal and laryngeal lesions.

We describe an 11-year-old boy who had several, asymptomatic, erythematous papules in the oropharynx and larynx with recent onset, two cervical lymphadenopathies, and a painless, erythematous plaque on the right wrist with a 2.5-year history of slow growth. Histologic examination of the mucocutaneous lesions revealed a submucous infiltrate of lymphocytes and Langhans giant cells in the papules and granulomatous dermatitis in the plaque. The cervical lymph node was biopsied and on the surgical scar, an erythematous, nodular lesion developed. A biopsy specimen of this lesion showed tuberculoid granulomas with prominent caseation necrosis, and culture was positive for Mycobacterium tuberculosis. The Mantoux test was strongly positive with a vesicular response. A diagnosis of mucocutaneous lupus vulgaris and scrofuloderma secondary to cervical tuberculous lymphadenitis was made. Two months after initiation of antituberculosis therapy there was a complete resolution of mucous lesions and healing with atrophic scars on the neck and wrist. This is a rare presentation in the literature and reminds clinicians that tuberculosis should be kept in mind in the differential diagnosis of oral cavity lesions.

Dermatological and ophthalmological sequels in toxic epidermal necrolysis.

BACKGROUND: Toxic epidermal necrolysis (TEN) is a rare, drug-induced disease characterized by epidermal detachment and mucosal involvement. After an acute period, potentially disabling cutaneous and ocular sequels may appear. Although long-term complications are not rare, only few outcome studies are published. OBJECTIVE: To evaluate the incidence of dermatological and ophthalmological sequels following TEN, to describe its clinical aspects and correlation with acute involvement. PATIENTS AND METHODS: Eight patients surviving to TEN were submitted to dermatological and ophthalmological observation ranging from 0.5 to 8 years after hospitalization. Cutaneous and ocular involvement, during the acute phase, was retrospectively analysed. RESULTS: Dermatological sequels were observed in 6 patients (75%) corresponding to those with more extensive skin involvement in the acute phase. The most frequent complications were cutaneous dyschromia (62.5%) and nail dystrophies (37.5%). Six patients (75%) had ocular complications with tarsal conjunctiva keratinization in 5 (62.5%) and keratoconjunctivitis sicca in 4 of them (50%). Trichiasis, corneal neovascularization and symblepharon were observed in 1 case. There was no correlation between the severity of acute ocular involvement and long-term complications. CONCLUSION: Following TEN, most patients have dermatological and ophthalmological sequels that persist for several years.