Matteo Megna

Educational and motivational support service: a pilot study for mobile‐phone‐based interventions in patients with psoriasis

Background  Psoriasis is a chronic disease which requires long‐term therapy. Therefore, adherence to therapy and patient motivation are key points in controlling the disease. Mobile‐phone‐based interventions, and in particular text messages (TM), have already been used effectively to motivate patients and improve treatment adherence in many different chronic diseases such as diabetes, cardiovascular disease and asthma.

Insulin Resistance and Skin Diseases

In medical practice, almost every clinician may encounter patients with skin disease. However, it is not always easy for physicians of all specialties to face the daily task of determining the nature and clinical implication of dermatologic manifestations. Are they confined to the skin, representing a pure dermatologic event? Or are they also markers of internal conditions relating to the patients overall health? In this review, we will discuss the principal cutaneous conditions which have been linked to metabolic alterations. Particularly, since insulin has an important role in homeostasis and physiology of the skin, we will focus on the relationships between insulin resistance (IR) and skin diseases, analyzing strongly IR-associated conditions such as acanthosis nigricans, acne, and psoriasis, without neglecting emerging and potential scenarios as the ones represented by hidradenitis suppurativa, androgenetic alopecia, and hirsutism.

Vitamin D and its role in psoriasis: An overview of the dermatologist and nutritionist

Psoriasis is a chronic immune-mediated inflammatory skin disease. Psoriasis lesions are characterized by hyper-proliferation of epidermal keratinocytes associated with inflammatory cellular infiltrate in both dermis and epidermis. The epidermis is the natural source of vitamin D synthesis by sunlight action. Recently, a role for vitamin D in the pathogenesis of different skin diseases, including psoriasis, has been reported. Indeed, significant associations between low vitamin D status and psoriasis have been systematically observed. Due to its role in proliferation and maturation of keratinocytes, vitamin D has become an important local therapeutic option in the treatment of psoriasis. To date, the successful treatment based on adequate dietary intake of vitamin D or oral vitamin D supplementation in psoriasis represent an unmet clinical need and the evidence of its beneficial effects remains still controversial. This information is important either for Dermatologists and Nutritionists to increases the knowledge on the possible bi-directional relationships between low vitamin D status and psoriasis and on the potential usefulness of vitamin D in psoriasis with the aim not only to reduce its clinical severity, but also for delineating the risk profile for co-morbidities cardiac risk factors that may result from psoriasis. In the current review, we analyzed the possible bi-directional links between psoriatic disease and vitamin D.

Efficacy and safety of ustekinumab in a group of 22 elderly patients with psoriasis over a 2‐year period

Oral isotretinoin is known to cause ocular side effects, most commonly dry eyes and very rarely, corneal opacity and keratitis. We describe what we believe is the first case of recurrent corneal epithelial erosion (RCES) precipitated by the commencement of isotretinoin therapy for acne vulgaris. A 38-year-old woman presented to her optometrist with severe, spontaneous, sudden-onset pain, along with photophobia, watering and redness of her left eye. She had persistent excoriated acne, which had been treated successfully over the previous 18 months with oral isotretinoin 20 mg daily. On physical examination, an area of corneal epithelial loss was detected, and standard treatment with topical antibiotic ointment was commenced. One month later, the patient re-presented to the ophthalmology clinic with the same symptoms in the same eye. Corneal examination revealed epithelial microcysts, typical of recurrent corneal erosion syndrome, as well as a corneal epithelial defect. Long-term prophylactic ocular lubrication was prescribed. On further enquiry, the patient described minor trauma to her left eye 2 years previously, for which she had received treatment at a different centre. It was deemed probable that the isotretinoin was having an exacerbating effect on the ocular surface environment, and thus the dose was reduced. The patient continued to use regular lubrication and had no further episodes of recurrent corneal erosion over a follow-up period of 6 months. Recurrent corneal epithelial erosion is an acutely painful relapsing ocular condition caused by defective attachment of the basal cells of the corneal epithelium to their basement membrane, and is typically associated with a history of previous traumatic corneal abrasion. In the months/years following an abrasion, episodes of corneal epithelial breakdown (erosions) are experienced by an affected individual, usually overnight or on waking, when the ocular surface is less well lubricated by the blink mechanism. Salient clinical features include pain, photophobia and epiphora. Long-term ocular lubrication is the mainstay of prophylaxis in order to maintain tear film stability and ensure corneal protection. A stable tear film is essential for normal vision, ocular comfort and maintenance of a healthy ocular surface environment. The meibomian glands secrete the lipid layer of the tears, and are essential to reduce tear evaporation and maintain tear film stability. Isotretinoin has a direct effect on the function of these glands, causing atrophy and hypoplasia. In a study of 1741 adverse drug reactions related to isotretinoin, there were no reports of RCES. Any cause of tear film instability or meibomian gland dysfunction could precipitate or exacerbate RCES in vulnerable patients, and we believe that isotretinoin should be considered a risk factor for RCES in such cases. We advise that clinicians commencing patients on isotretinoin should ask about previous ocular conditions, including previous trauma and corneal abrasions. For patients with such conditions, the low-risk prophylactic intervention of commencing ocular lubricants should be suggested, as well as making the patient aware of the symptoms of RCES.

The risk of herpes zoster in the anti-TNF-α era: a case report and review of the literature

BACKGROUND Tumor necrosis factor-α (TNF-α) inhibitors represent efficacious therapeutic agents in many chronic inflammatory diseases such as psoriasis and rheumatoid arthritis. However they have been connected with increased risk of infection and reactivation of a variety of infectious agents, such as viruses. The reactivation of varicella zoster virus infection causes herpes zoster (HZ), a self-limiting, dermatomally localized, vesicular rash that can be accompanied by postherpetic neuralgia and severe neurological complications. MAIN OBSERVATIONS Limited information has been published regarding HZ during therapy with TNF-α inhibitors especially for the occurrence of HZ during adalimumab treatment. We report the case of a 58-year-old immunocompetent man with a 18-year history of plaque psoriasis who develops ophthalmic HZ during treatment with adalimumab. CONCLUSION We report this case to enrich the literature and to highlight the increased risk of HZ infections in patient on anti-TNF-α therapy (incidence of HZ is about 3-fold increased respect to general population). Clinically, these infections often have atypical presentations that may hamper prompt diagnosis. Therefore, it is very important to identify early signs and symptoms of herpes zoster in patients on biologic therapy in order to start prompt efficient antiviral treatment to prevent the development of severe complications.

Hidradenitis suppurativa: from pathogenesis to diagnosis and treatment

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease primarily affecting apocrine gland-rich areas of the body and presenting with painful nodules, abscesses, sinus tracts, and scarring. HS is a multifactorial disease in which genetic and environmental factors play a key role. The primary defect in HS pathophysiology involves follicular occlusion of the folliculopilosebaceous unit, followed by follicular rupture, and immune responses (perifollicular lympho-histiocytic inflammation), finally leading to the development of clinical HS lesions. HS has a destructive impact on the patient’s quality of life, being a very challenging disease. Available treatments are limited, mostly off-label and with high variability in the reported efficacy. Fortunately, a monoclonal antibody against tumor necrosis factor alpha has been recently approved for treatment of moderate to severe HS, offering patients a promising new option. This review focuses on the main features of HS, including epidemiology, clinical aspects, pathogenesis, severity classifications, comorbidities, and currently available treatments.

Nonalcoholic fatty liver disease, spleen and psoriasis: New aspects of low-grade chronic inflammation.

AIM To investigate spleen status in psoriasis and its relationship with hepatic steatosis, Psoriasis Area and Severity Index, and insulin resistance. METHODS Seventy-nine psoriatic patients who were not suffering from any chronic inflammatory disease were retrospectively selected for inclusion in this study, and their complete medical records were accessed. An age- and sex-matched group of 80 non-psoriatic, obese patients was included as a control. The following relevant data were collected: age, sex, weight, height, body mass index, waist circumference, blood pressure, insulin resistance status, age at psoriasis onset, and severity of psoriasis. Abdominal ultrasonography was performed to determine spleen longitudinal diameter (SLD), and hepatic steatosis grade. RESULTS The SLD of control obese patients was greater than that of psoriatic subjects (P = 0.013), but body mass index predicted the size of the spleen in psoriatic patients (P < 0.001). The SLD of psoriatic patients with normal weight was significantly reduced with respect to the overweight/obese psoriatic patients (P = 0.002). A multiple regression analysis revealed that body mass index was a unique predictor of the spleen size (P < 0.001). Finally, the disease duration predicted the spleen size in psoriatic subjects (P = 0.038). CONCLUSION This study shows a correlation between the SLD and the duration of psoriasis.

Pathogenesis of Psoriasis: The Role of Pro-Inflammatory Cytokines Produced by Keratinocytes

Psoriasis is a chronic, inflammatory skin disease affecting 2 to 3% of the white population (Gudjonsson & Elder, 2007). It is a multifactorial disease since its development depends on a complex interplay of genetic and environmental factors. As no pathogen has been consistently identified within psoriatic plaques (indeed skin infections are rare in lesions because of antimicrobial peptides) (Nomura et al., 2003), an autoimmune basis for the chronic inflammation is the dogma for this complex disorder. Psoriasis is characterized by macroscopic (clinical) and corresponding microscopic (histological) skin alterations and leads to considerable impairment of the quality of life of the affected patients. Special forms of psoriasis (e.g. arthropathic form) can be accompanied by severe extra-cutaneous changes.

Effects of climate changes on skin diseases

Global climate is changing at an extraordinary rate. Climate change (CC) can be caused by several factors including variations in solar radiation, oceanic processes, and also human activities. The degree of this change and its impact on ecological, social, and economical systems have become important matters of debate worldwide, representing CC as one of the greatest challenges of the modern age. Moreover, studies based on observations and predictive models show how CC could affect human health. On the other hand, only a few studies focus on how this change may affect human skin. However, the skin is the most exposed organ to environment; therefore, it is not surprising that cutaneous diseases are inclined to have a high sensitivity to climate. The current review focuses on the effects of CC on skin diseases showing the numerous factors that are contributing to modify the incidence, clinical pattern and natural course of some dermatoses.

Mammalian target of rapamycin in inflammatory skin conditions

The conserved serine/threonine kinase mammalian target of rapamycin (mTOR) is a major regulator of survival growth, proliferation and motility, in response to mitogens, energy and nutrient levels. Dysregulation of mTOR pathway has been observed in various inflammatory or neoplastic human diseases. To assess the potential involvement of mTOR in some of the most common inflammatory skin diseases, and its interaction with other inflammatory mediators, we investigated mTOR expression in psoriasis, allergic contact dermatitis (ACD) and atopic dermatitis (AD). mTOR gene expression was assessed in the following conditions: i) skin biopsies from 15 patients affected by psoriasis, 5 patients with ACD, 5 patients with AD and 3 patients with EGFR-inhibitor-induced skin rash; ii) in immortalized keratinocytes HaCaT, primary human keratinocytes (KCs) and full thickness skin organ cultures, incubated with tumor necrosis factor (TNF)-α, interleukin (IL) 17A or their combination; iii) in HaCaT cells stimulated with ultraviolet (UV)B; iv) in skin biopsies from 5 psoriatic patients before and after 16 weeks of anti-TNF-α therapy; mTOR expression was also evaluated through immunohistochemistry in lesional and non-lesional skin samples from 5 psoriatic patients. Moreover, mTOR major up-stream and down-stream regulator gene expression was assessed in skin biopsies from 15 patients affected by psoriasis, 5 patients with ACD, 5 patients with AD and 3 patients with EGFR-inhibitor-induced skin rash. All analyzed skin diseases showed an increase of mTOR gene expression whereas mTOR up-stream negative regulators were reduced or not enhanced in all of them. mTOR was strongly expressed in all epidermal layers of lesional and non-lesional psoriatic skin. Conversely, pro-inflammatory conditions, in vitro, were not able to increase mTOR levels, except for UVB. Similarly, anti-TNF-α therapy was not able to reduce mTOR gene expression in patients with psoriasis. Our study provides evidence that mTOR is involved in cutaneous inflammatory process, but through a signalling not directly dependent from Th1-Th17 pathway.