Tetracyclines and photosensitive skin reactions: A narrative review.

Tetracyclines are a group of broad-spectrum antibiotics largely employed in infectious, dermatological and surgical fields. Some adverse events may occur during treatment, including photosensitivity reactions, which are divided in phototoxic or photoallergic. We performed a systematic search on Pubmed, Cochrane and Embase from database inception to August 9, 2020 aim to summarize all available papers on photosensitive reactions related to tetracyclines in all clinical settings where they are used on human being. On the basis of our inclusion criteria, we selected only randomized controlled trials, open comparative trials and prospective cohort studies performed on both volunteers and patients, moreover we included a pharmacovigilance register. Thirty-eight articles met inclusion criteria, describing photo-sensitive effects due to doxycycline, minocycline, tetracycline, lymecycline, sarecycline, demethylchlortetracycline, chlortetracycline and metacycline, across six diagnoses (acne, Lyme disease, Gulf Veteran Illness, adbominal aortic aneurysms, traveler's diarrhea and pterygium) and several volunteers who were deliberately exposed to natural or artificial light sources. Not all drugs belonging to tetracyclines class are available to date, moreover the studies included lacked a homogeneous design and most of them involved a scarce number of patients, including reactions induced in volunteers during photo-testing. Available data on incidence, severity and clinical relevance of tetracyclines-related photo-sensitive reactions are scarce, heterogeneous and weak. What we can extrapolate is that some tetracyclines are more often related to phototoxic skin reactions than others and some of those seem to have a very low risk of phototoxicity.

A Critical Reappraisal of Off-Label Use of Photodynamic Therapy for the Treatment of Non-Neoplastic Skin Conditions.

BACKGROUND: In the past 30 years, topical photodynamic therapy (PDT) has been investigated for the treatment of a broad spectrum of cosmetic, inflammatory, and infectious skin conditions with variable, and often contrasting, results. However, the non-expert clinician may be in difficulty evaluating these results because different sensitizers, concentrations, formulations, light sources, and irradiation protocols have been used. In addition, many of these studies have poor quality design being case reports and uncontrolled studies of few cases. SUMMARY: With the aim to clarify the potential usefulness of PDT for the treatment of infectious and inflammatory skin diseases as well as selected cosmetic indications, we searched for randomized controlled clinical trials, non-randomized comparative studies, retrospective studies, and case series studies with a number of at least 10 patients, published since 1990. Later, we reappraised the results in order to give a simple critical overview. Key Messages: Evidence from the literature seems to strongly support the use of ALA- and MAL-PDT for the treatment of common skin diseases such as acne, warts, condylomata, and Leishmania skin infection and for photorejuvenation, i.e., the correction of selected cosmetic changes of aging and photoaging. For other disorders, the level of evidence and strength of recommendation are lower, and controlled randomized studies with prolonged follow-ups are necessary in order to assess the clinical usefulness and other potential advantages over current treatment options.

Italian expert-based recommendations on the use of photo(chemo)therapy in the management of mycosis fungoides: Results of an e-Delphi consensus.

BACKGROUND: Phototherapy is a mainstay for the treatment of MF. However, there is scarce evidence for its use, mostly due to the lack of a unified schedule. AIMS: The primary aim of this study was to establish the first structured, expert-based consensus regarding the indications and technical schedules of NB-UVB and PUVA for MF. The secondary aim was to determine the consensus level for each specific item. MATERIALS & METHODS: E-delphi study. Item-specific expert consensus was defined as the number of "Totally Agree" results to ≥80% of the panelists. Cronbach alpha index ≥0.7 was used as a measure of homogeneity in the responses among questions related to the same topic. RESULTS: Overall, there was a high homogeneity among responders (0.78). On specific topics, the highest grade was observed for technical items (0.8) followed by indications for early (0.73) and advanced stages (0.7). CONCLUSIONS: Items related to the most canonical indications of phototherapy and to treatment schedules showed the highest agreements rates. There is consensus about the use of standardized treatment schedules for the induction and consolidation phases for NB-UVB and PUVA in MF.

Psoriatic cutaneous inflammation promotes human monocyte differentiation into active osteoclasts, facilitating bone damage.

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy that can be associated with focal bone erosions. Psoriasis usually precedes the psoriatic arthritis onset by an average of 10 years, but this relation is not yet fully elucidated. Pro-inflammatory cytokines, such as IL-33, OPN, IL-17, and TNF-α are involved in both psoriasis and PsA pathogenesis as well as in bone homeostasis. In this study, we have demonstrated that IL-33, OPN, IL-17, and TNF-α induced the release of a wide range of pro-osteoclastogenic factors from the skin, such as RANKL, that promote monocyte differentiation in osteoclasts. The addition of osteoprotegerin, a RANKL inhibitor, to monocyte cultures treated with supernatant from stimulated skin did not completely deplete osteoclast formation, suggesting that skin produced several additional pro-osteoclastogenic mediators, which could act in a RANKL-independent manner. Moreover, we have found that RANKL serum levels as well as osteoclast number and activity in psoriatic patients with and without arthritis, was influenced by severity of cutaneous disease. Our data demonstrate that psoriatic cutaneous inflammation contributes to bone damage.

"Fifty Shades" of Black and Red or How Carboxyl Groups Fine Tune Eumelanin and Pheomelanin Properties.

Recent advances in the chemistry of melanins have begun to disclose a number of important structure-property-function relationships of crucial relevance to the biological role of human pigments, including skin (photo) protection and UV-susceptibility. Even slight variations in the monomer composition of black eumelanins and red pheomelanins have been shown to determine significant differences in light absorption, antioxidant, paramagnetic and redox behavior, particle morphology, surface properties, metal chelation and resistance to photo-oxidative wear-and-tear. These variations are primarily governed by the extent of decarboxylation at critical branching points of the eumelanin and pheomelanin pathways, namely the rearrangement of dopachrome to 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA), and the rearrangement of 5-S-cysteinyldopa o-quinoneimine to 1,4-benzothiazine (BTZ) and its 3-carboxylic acid (BTZCA). In eumelanins, the DHICA-to-DHI ratio markedly affects the overall antioxidant and paramagnetic properties of the resulting pigments. In particular, a higher content in DHICA decreases visible light absorption and paramagnetic response relative to DHI-based melanins, but markedly enhances antioxidant properties. In pheomelanins, likewise, BTZCA-related units, prevalently formed in the presence of zinc ions, appear to confer pronounced visible and ultraviolet A (UVA) absorption features, accounting for light-dependent reactive oxygen species (ROS) production, whereas non-carboxylated benzothiazine intermediates seem to be more effective in inducing ROS production by redox cycling mechanisms in the dark. The possible biological and functional significance of carboxyl retention in the eumelanin and pheomelanin pathways is discussed.

Assessment of the Combined Efficacy of Needling and the Use of Silicone Gel in the Treatment of C-Section and Other Surgical Hypertrophic Scars and Keloids.

OBJECTIVE: To evaluate the individual effectiveness of needling therapy using the Dermapen (Dermapen, Salt Lake City, Utah) and topical therapy with silicone gel (Kelo-cote, Sinclair Pharma, London, England), and their combined effectiveness for the treatment of linear surgical scars, hypertrophic scars, and keloids. MATERIALS AND METHODS: Twenty patients were randomly selected and equally divided into 2 groups (A and B), with each group of 10 including 6 patients with keloids and 4 with hypertrophic scars. Treatment assignments were random. In group A, the entire scar was treated by skin needling, with silicone gel applied to half of the scar. Patients in group B were treated with silicone gel on the whole scar, with only half of the scar also treated with skin needling. During follow-up visits, clinical photographs, evaluation of the scars' thickness, skin ultrasound, and modified Vancouver Scar Scale were performed. RESULTS: Group A showed an average improvement of 68% (P < .01) on the half of the scar with the combination treatment (skin needling plus silicone gel) compared with a 52% improvement on the half of the scar that was treated with only skin needling. Group B showed an average improvement of 63% (P < .01) where the combination treatment was performed, compared with 47% improvement on the area treated with only the silicone gel. CONCLUSIONS: In conclusion, the combination of these 2 treatments is safe and effective for the treatment of hypertrophic scars and keloids. These modalities achieved favorable results with each patient adhering to the study paramenters.

Anti-inflammatory properties of low and high doxycycline doses: an in vitro study.

Doxycycline is used to treat infective diseases because of its broadspectrum efficacy. High dose administration (100 or 200 mg/day) is often responsible for development of bacterial resistances and endogenous flora alterations, whereas low doses (20-40 mg/day) do not alter bacteria susceptibility to antibiotics and exert anti-inflammatory activities. In this study, we wanted to assess the efficacy of both low and high doxycycline doses in modulating IL-8, TNF-α, and IL-6 gene expression in HaCaT cells stimulated with LPS. Three experimental settings were used, differing in the timing of doxycycline treatment in respect to the insult induced by LPS: pretreatment, concomitant, and posttreatment. Low doses were more effective than high doses in modulating gene expression of LPS-induced proinflammatory cytokines (IL-8, TNF-α, and IL-6), when added before (pretreatment) or after (posttreatment) LPS stimulation. This effect was not appreciated when LPS and doxycycline were simultaneously added to cell cultures: in this case high doses were more effective. In conclusion, our in vitro study suggests that low doxycycline doses could be safely used in chronic or acute skin diseases in which the inflammatory process, either constantly in progress or periodically recurring, has to be prevented or controlled.

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 patient's 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.

Acne smart club: an educational program for patients with acne.

OBJECTIVE: To evaluate adherence to therapy in acne patients using mobile phones and Short Message Service (SMS) to communicate. METHODS: 160 patients were randomly assigned to two groups: the SMS group received 2 text messages twice a day for a period of 12 weeks; the control group did not receive any messages. Before and after 12 weeks, the following evaluations were performed in all patients: digital photographs, the Global Acne Grading System, the Dermatology Life Quality Index, the Cardiff Acne Disability Index, the doctor-patient relationship evaluated through the Patient-Doctor Depth-of-Relationship Scale, and the adherence to treatment evaluated by asking patients how many days a week they had followed the therapy. For statistical analysis we used Student's t test. RESULTS: The SMS group had a better improvement of all parameters compared to the control group. CONCLUSION: Adherence and compliance are higher for patients who are included in a strategy of control.

Salicylic acid for the treatment of melasma: new acquisitions for monitoring the clinical improvement.

OBJECTIVE: The Melasma Area and Severity Index (MASI) and the Melasma Severity Score (MSS) are calculated on the basis of only a subjective clinical assessment. This raises the need to have an objective score, uniform in the evaluation by different clinicians. The purpose of this study was to establish if the images by Canfield Reveal Imager can be correlated to MASI score to better evaluate the clinical efficacy of salicylic acid 33% peeling in the treatment of melasma respect to the clinical observation. METHODS: The study was a voluntary observational study. Twenty female patients affected with melasma, aged between 30 and 60 years, were included in the study. Treatment with salicylic acid 33% was performed once a month, for a total of four times. The dermatologist (Doc A) examined each patient's melasma areas using MASI score, at the face-to-face observation and at Reveal images evaluation during the first (T0) and the end point time (T4). Digital photographs were also evaluated by another experienced dermatologist (Doc B), who has never seen clinically the patients before and who evaluated MASI score by Reveal images at time T0 and T4. RESULTS: Student's t-test and linear regression test were performed, showing statistically significant values comparing MASI score obtained by digital photo and MASI score obtained clinically. CONCLUSION: The monitoring of the improvement by Reveal images can optimize the treatment approach and the efficacy of same dermocosmetics procedures can be revised following standard criteria.

Efficacy and safety of biologics and small molecules for psoriasis in pediatric and geriatric populations. Part II: focus on elderly patients.

INTRODUCTION: The management of moderate-to-severe forms of psoriasis is becoming a frequent concern in geriatric age due to the higher risk to develop treatment adverse events, logistic issues, vulnerability to immune-related diseases and cancer, presence of comorbidities and the risk of drug interactions. In this context, traditional systemic treatments are often contraindicated, and biologic drugs and small molecules seem to be a valuable option. However, data on their effectiveness and safety in elderly patients are scant. AREAS COVERED: The aim of this review is to analyze the current literature in order to point out data on the efficacy and safety of biologic drugs and small molecules for the management of psoriasis in elderly patients in order to put the basis for universally shared treatment algorithm following available evidence. Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were used for the literature research. EXPERT OPINION/COMMENTARY: Our review suggests biologics and small molecules as an effective and safe option for the management of moderate-to-severe forms of psoriasis in elderly patients.

Efficacy and safety of biologics and small molecules for psoriasis in pediatric and geriatric populations. Part I: focus on pediatric patients.

INTRODUCTION: Psoriasis management is challenging, especially in pediatric age for different factors. The introduction of biologic drugs and oral small molecules (OSM) revolutionized the armamentarium of available weapons in psoriasis treatment. Despite the use of these drugs in adult patients has been widely investigated, pediatric patients have often been unconsidered in clinical trials and real-life studies. However, the high efficacy and speed of action, the safety profile and the ease-to-use administration make these innovative drugs an invaluable therapeutic opportunity. AREAS COVERED: The aim of this manuscript is to perform a review of the current literature examining data on the effectiveness and safety of biologic drugs and OSM for the management of psoriasis in pediatric patients in order to put the basis for universally shared treatment algorithm following available evidence. PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines were used for the literature research. EXPERT OPINION/COMMENTARY: Our review based on currently available evidence suggests biologics and OSM as an ideal treatment option for pediatric patients, with an excellent profile in terms of efficacy and safety as compared to traditional systemic drugs.

In vitro ultraviolet A irradiation decreases both release ability and gene-expression of vascular endothelial growth factor-A from mast cells.

Ultraviolet A (UVA) rays penetrate the dermis, influencing the function of different cells, including mast cells, able to produce angiogenic factors. We investigated vascular endothelial growth factor (VEGF) release and gene-expression from mast cells (MCs), after UVA irradiation in vitro. The release of VEGF-A by Human MCs-1 (HMC-1) was induced by calcium ionophore A23187 and phorbol 12 myristate 13 acetate (PMA). Half of the cells received increasing doses of UVA (5, 25 and 50 J/cm(2)), the unirradiated HMC-1 served as controls. VEGF release and VEGF's messenger ribonucleic acid (mRNA) were detected respectively by enzyme-linked immunoabsorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR) analysis. Results showed a UVA dose-dependent inhibitory effect on VEGF-A release from HMC-1. In particular, the release ability was reduced by 71.2% with 5 J/cm(2); 85% with 25 J/cm(2) and 86.3% with 50 J/cm(2). The VEGF-A RNA expression was reduced after UVA irradiation with 5 J/cm(2). We speculated that, at least in vitro and at our experimental conditions, UVA irradiation decreases mast cells-VEGF release and gene-expression.