European guideline (EuroGuiDerm) on atopic eczema - part II: non-systemic treatments and treatment recommendations for special AE patient populations.

The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti-inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for paediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology.

European guideline (EuroGuiDerm) on atopic eczema: part I - systemic therapy.

The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for paediatric, adolescent, pregnant and breastfeeding patients.

A systematic review of treatments for pityriasis lichenoides.

Pityriasis lichenoides (PL) represents a spectrum of inflammatory skin diseases comprising pityriasis lichenoides et varioliformis acuta (PLEVA) and pityriasis lichenoides chronica (PLC). This study aimed to provide a summary of effective treatments for PL. A systematic review was performed according to PRISMA guidelines for studies investigating PL treatment including ≥3 subjects and published in English between 1 January 1970 and 15 April 2019. A total of 441 papers were screened, and 37 original manuscripts meeting the inclusion and exclusion criteria were found, including 12 case series, 18 reviews, four prospective studies, two comparative studies and a single randomized controlled study. In most studies, ultraviolet (UV) phototherapy (narrow-band UVB, broadband UVB, UVA1 or PUVA) was used. Clearance rates with the different modalities are hardly comparable between different studies, ranging approximately between 70% and 100%. Narrow-band UVB showed an efficacy similar to PUVA as such as the combination of UVA and UVB vs. PUVA. Oral erythromycin showed clearance rates ranging between 66% and 83%, whereas methotrexate up to 100% but in small and dated studies. Evidence for other treatments is scarce. There is a lack of high level of evidence studies on PL treatment. The interpretation of the results is biased by the possible auto-resolution of the disease, the sample heterogeneity between children and adults and the short follow-up period of the studies. Only some studies investigated how results were durable after cessation of therapy. Quality of life and the impact of treatment were never assessed. According to the results of this review, we suggest narrow-band UVB phototherapy as first-line treatment. Oral erythromycin with or without topical corticosteroids and low-dose methotrexate as second-line therapies. High-powered studies and randomized controlled trials are needed to establish the optimal treatment for PL.

Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II.

This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus-based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This second part of the guideline covers antimicrobial therapy, systemic treatment, allergen-specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions, whereas the first part covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy. Management of AE must consider the individual clinical variability of the disease. Systemic immunosuppressive treatment with cyclosporine, methotrexate, azathioprine and mycophenolic acid is established option for severe refractory cases, and widely available. Biologicals targeting the T helper 2 pathway such as dupilumab may be a safe and effective, disease-modifying alternative when available. Oral drugs such as JAK inhibitors and histamine 4 receptor antagonists are in development. Microbial colonization and superinfection may cause disease exacerbation and can require additional antimicrobial treatment. Allergen-specific immunotherapy with aeroallergens may be considered in selected cases. Psychosomatic counselling is recommended especially in stress-induced exacerbations. Therapeutic patient education ('Eczema school') is recommended for children and adult patients. General measures, basic emollient treatment, bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy have been addressed in the first part of the guideline.

Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I.

This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus-based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This first part of the guideline covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy, whereas the second part covers antimicrobial therapy, systemic treatment, allergen-specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions. Management of AE must consider the individual clinical variability of the disease; highly standardized treatment rules are not recommended. Basic therapy is focused on treatment of disturbed barrier function by hydrating and lubricating topical treatment, besides further avoidance of specific and unspecific provocation factors. Topical anti-inflammatory treatment based on glucocorticosteroids and calcineurin inhibitors is used for flare management and for proactive therapy for long-term control. Topical corticosteroids remain the mainstay of therapy, whereas tacrolimus and pimecrolimus are preferred in sensitive skin areas and for long-term use. Topical phosphodiesterase inhibitors may be a treatment alternative when available. Adjuvant therapy includes UV irradiation, preferably with UVB 311 nm or UVA1. Pruritus is targeted with the majority of the recommended therapies, but some patients may need additional antipruritic therapy. Antimicrobial therapy, systemic anti-inflammatory treatment, immunotherapy, complementary medicine and educational intervention will be addressed in part II of the guideline.

Use of systemic corticosteroids for atopic dermatitis: International Eczema Council consensus statement.

BACKGROUND: Guidelines discourage the use of systemic corticosteroids for atopic dermatitis (AD), but their use remains widespread. OBJECTIVES: To reach consensus among an international group of AD experts on the use of systemic corticosteroids for AD. METHODS: A survey consisting of statements accompanied by visual analogue scales ranging from 'strongly disagree' to 'neutral' to 'strongly agree' was distributed to the International Eczema Council (IEC). Consensus was reached in agreement on a statement if < 30% of respondents marked to the left of 'neutral' towards 'strongly disagree'. RESULTS: Sixty of 77 (78%) IEC members participated. Consensus was reached on 12 statements, including that systemic corticosteroids should generally be avoided but can be used rarely for severe AD under certain circumstances, including a lack of other treatment options, as a bridge to other systemic therapies or phototherapy, during acute flares in need of immediate relief, in anticipation of a major life event or in the most severe cases. If used, treatment should be limited to the short term. Most respondents agreed that systemic corticosteroids should never be used in children, but consensus was not reached on that statement. The conclusions of our expert group are limited by a dearth of high-quality published evidence. If more stringent consensus criteria were applied (e.g. requiring < 20% of respondents marking towards 'strongly disagree'), consensus would have been reached on fewer statements. CONCLUSIONS: Based on expert opinion from the IEC, routine use of systemic corticosteroids for AD is generally discouraged and should be reserved for special circumstances.

Prevalence of alexithymia in patients with psoriasis and its association with disease burden: a multicentre observational study.

BACKGROUND: Single-centre studies show that alexithymia, defined as difficulty in recognizing and describing emotions, is more prevalent among patients with psoriasis than in the general population. However, its prevalence and the consequences of the association between alexithymia and psoriasis are unclear. OBJECTIVES: The primary objective of this study was to determine the prevalence of alexithymia, as defined by a score ≥ 61 in the 20-item Toronto Alexithymia Scale, in a large sample of patients who had plaque psoriasis for ≤ 10 years and were eligible for phototherapy or systemic treatment. The secondary objectives were to investigate the relationship between alexithymia and the clinical and psychological aspects of psoriasis. METHODS: Data were collected in the framework of an observational, multicentre, international study, the EPidemiological Study In Patients With Recently DiagnosEd PSOriasis (EPIDEPSO), aiming at investigating the prevalence of alexithymia and other psychosocial comorbidities in patients with psoriasis of ≤ 10 years' disease duration. RESULTS: The prevalence of alexithymia within a cohort of 670 patients was 24·8% (95% confidence interval 21·7-28·2). Patients with alexithymia had a higher burden of psoriasis, including significant impairment of quality of life, higher levels of anxiety and depression, a higher risk of alcohol dependency and impairment of work productivity, compared with patients without alexithymia. CONCLUSIONS: It is important to identify alexithymic patients with psoriasis in clinical practice as they experience a higher disease burden and have a lower ability to express their feelings.

Scleredema. A multicentre study of characteristics, comorbidities, course and therapy in 44 patients.

BACKGROUND: The prognostic and therapeutic features of scleredema are poorly documented. OBJECTIVES: To describe the characteristics of patients with scleredema regarding demographics, clinical characteristics, comorbidities, therapeutic interventions and course. METHODS: We conducted a retrospective multicentre study. RESULTS: We identified 44 patients (26 men).The mean age at diagnosis was 53.8 years. The most common associated disorders were endocrine/metabolic diseases including 30 patients suffering from diabetes, mostly type 2 diabetes. Monoclonal gammopathies were confirmed in five cases. A preceding respiratory tract infection was not a feature. Treatments with different combination or sequential modalities were used with variable results. Phototherapy (UVA1 or PUVA) was the treatment associated with higher, although partial response. Systemic corticosteroids and immunosuppressive drugs were reserved to patients with severe disease in whom phototherapy had failed or for patients with multiple myeloma. Forty-one patients were followed up (mean period: 32.2 months).Thirty-nine patients are alive, 30 with and 9 without skin disease. Two patients died of cardiovascular complications due to myeloma and severe diabetes. CONCLUSIONS: Scleredema is a chronic debilitating disease associated with diabetes and metabolic syndrome, unresponsive to various treatments but not necessarily a life-threatening condition. Although there is no definitive treatment, phototherapy should be attempted first. Treatment of primary disease including strict glycaemic control combined with physical therapy should be also employed.

Latent tuberculosis infection in patients with chronic plaque psoriasis: evidence from the Italian Psocare Registry.

BACKGROUND: The nationwide prevalence of latent tuberculosis infection (LTBI) in Italian patients with psoriasis has never been investigated. OBJECTIVES: To estimate the nationwide prevalence of LTBI in Italian patients with psoriasis who are candidates for systemic treatment. METHODS: Data were obtained from the Psocare Registry on those patients (n = 4946) with age > 18 years, systemic treatment at entry specified and tuberculin skin test (TST) performed according to the Mantoux method. LTBI diagnosis was based on a positive TST result in the absence of any clinical, radiological or microbiological evidence of active tuberculosis. RESULTS: Latent tuberculosis infection was diagnosed in 8·3% of patients with psoriasis (409 of 4946). The prevalence of LTBI was lower in patients on biologics than in those on conventional systemic treatments, ranging from 4·3% (19 of 444) of patients on adalimumab to 31% (eight of 26) of those on psoralen-ultraviolet A (P < 0·05). Independent factors associated with LTBI were male sex [odds ratio (OR) 1·30, 95% confidence interval (CI) 1·04-1·62; P = 0·02], age over 55 years (OR 2·93, 95% CI 2·18-3·93; P < 0·001) and being entered into a conventional treatment (OR 3·83, 95% CI 3·10-4·74; P < 0·001). Positive history of tuberculosis was seen in 1% of patients (n = 49). CONCLUSIONS: The nationwide prevalence of LTBI in Italian patients with psoriasis candidate to systemic treatment is high, and screening is recommended prior to biological treatment.

Consensus on the use of the fixed combination calcipotriol/betamethasone dipropionate in the treatment of plaque psoriasis.

Calcipotriol, a vitamin D analogue, and betamethasone dipropionate, a high potency corticosteroid, are complementary agents for the topical treatment of psoriasis vulgaris. Robust evidence on the efficacy and safety of their fixed combination has been provided by randomized, double-blind, controlled clinical trials involving more than 7000 patients with the ointment formulation in psoriasis of the body and more than 4000 patients with the gel formulation in scalp psoriasis. These trials have shown that the fixed combination ointment is more effective and better tolerated, not only than placebo, but also than calcipotriol and tacalcitol monotherapies. In addition, it has proved, in most instances, to be more effective than betamethasone and at least as well tolerated. The same applies to the gel for scalp and body psoriasis. Safety studies have excluded that repeated courses of treatment with the fixed combination for up to one year produce systemic effects. Studies have also shown that the fixed combination treatment improves quality of life to a significantly greater extent than calcipotriol, with the once daily regimen most appreciated by patients, in both active disease and recurrency. Because of the extensive evidence, American and European guidelines recommend the calcipotriol/betamethasone dipropionate fixed combination as first line topical treatment for mild to moderate plaque psoriasis of the body and scalp.

Attitude to treatment of patients with psoriasis attending spa center.

AIM: The aim of this paper was to investigate beliefs and preferences towards treatment of patients with psoriasis attending Comano SPA (Trentino, Italy) in comparison to patients referring to the University Hospital of Verona. METHODS: Patient with psoriasis referring to Comano SPA and to the University Hospital of Verona were visited, their clinical data were collected and they were administered a questionnaire investigating their knowledge about psoriasis, as well as their attitude and preferences towards conventional therapies and SPA treatments. RESULTS: [Corrected] A total of 288 patients with chronic plaque psoriasis were recruited, 169 from Comano SPA and 119 from Verona Hospital. There were no differences regarding demographic data, severity of psoriasis, impact on quality of life and prevalence of cardio-metabolic comorbidities between the two groups. SPA patients more rarely believed that pharmacological treatments are safe and effective (6.5% vs. 21.8% P=0.001), had less trust in physician (32.5% vs. 67.2%; P=0.001) and preferred alternative therapies like balneotherapy compared to hospital patients (55.6% vs. 30.3%; P=0.0001), because they assumed they were more safe and effective than systemic drugs (37.3% vs. 1.7%; P=0.001). SPA patients preferred living with psoriasis rather than taking drugs to treat it more commonly than hospital patients (26.6% vs. 5%; P=0.001). CONCLUSION: Patients attending a SPA centre tend to trust conventional drug treatments less often than those attending a hospital clinic, and prefer balneotherapy as a dedicated alternative therapy. Fear of adverse events is a major concern among patients with psoriasis, especially those attending a SPA center.

Double blind clinical trial in a series of 115 patients with seborrheic dermatitis: prevention of relapses using a topical modulator of Toll like receptor 2.

AIM: Seborrheic dermatitis is a chronic inflammatory disease aggravated by Malassezia species. Toll-like receptors (TLR) are part of innate immune system that can be activated by yeasts. Previous studies showed that an association of Umbelliferae extract with a lipid (TLR2-Regul™) decreases the IL-8 expression in human skin in contact with M. furfur. The aim of this study was to assess the activity of a topical formulated with TLR2-Regul™ in the prevention of seborrheic dermatitis (SD) relapses. METHODS: Immune-competent SD adult patients were treated for SD (topical imidazoles or steroids). Cleared patients were randomized and received a topical containing TLR2-Regul™ (A) or its vehicle (B). Erythema, scales and pruritus were assessed during two months. RESULTS: The study included 115 patients, mean age 43.4, sex ratio m/f 1.5. At week 4 the relapse rate was 26% (N.=15) in group A and 43% (N.=25) in group B. At W8 the relapse rate was 21% (N.=12) in group A and 40% (N.=23) (P=0.0309). CONCLUSION: In this series of 115 adults with seborrheic dermatitis, patients treated with a topical containing TLR-Regul™ showed a significantly less relapse rate compared with the excipient group (P<0.05). TLR modulation could represent a new therapeutic approach in the prevention of seborrheic dermatitis relapses.

European S3-guidelines on the systemic treatment of psoriasis vulgaris.

Of the 131 studies on monotherapy or combination therapy assessed, 56 studies on the different forms of phototherapy fulfilled the criteria for inclusion in the guidelines. Approximately three-quarters of all patients treated with phototherapy attained at least a PASI 75 response after 4 to 6 weeks, and clearance was frequently achieved (levels of evidence 2 and 3). Phototherapy represents a safe and very effective treatment option for moderate to severe forms of psoriasis vulgaris. The onset of clinical effects occurs within 2 weeks. Of the unwanted side effects, UV erythema from overexposure is by far the most common and is observed frequently. With repeated or long-term use, the consequences of high, cumulative UV doses (such as premature aging of the skin) must be taken into consideration. In addition, carcinogenic risk is associated with oral PUVA and is probable for local PUVA and UVB. The practicability of the therapy is limited by spatial, financial, human, and time constraints on the part of the physician, as well as by the amount of time required by the patient. From the perspective of the cost-bearing institution, phototherapy has a good cost-benefit ratio. However, the potentially significant costs for, and time required of, the patient must be considered.

Italian position paper on urticaria. Italian Board on Urticaria.

The Italian Board on Urticaria has prepared a document focusing on the definition and classification of urticaria, taking into account the recent progress in identifying the causes, eliciting factors, and pathomechanisms of this disease. As urticaria has a profound impact on the quality of life, effective treatment is important. Therefore, specific treatment options for the management of urticaria are evaluated on the basis of the recent literature. Non-sedating H(1) antihistamines are recommended as the first-line treatment as they have proven effective in several randomized double-blind controlled studies. Dosages higher than those recommended may be necessary in some cases. However, additional or alternative therapies may be required for different urticaria subtypes and in view of individual variations in the course of the disease and response to treatment. Immunosuppressive drugs such as corticosteroids are not recommended for long-term treatment due to unavoidable, severe adverse effects.

Randomized controlled trial comparing the effectiveness of 308-nm excimer laser alone or in combination with topical hydrocortisone 17-butyrate cream in the treatment of vitiligo of the face and neck.

BACKGROUND: Vitiligo is a pigmentary disorder which may have disfiguring consequences. Its treatment remains a challenge. OBJECTIVES: We designed a parallel-group randomized controlled trial to compare the effectiveness of 308-nm excimer laser alone or in combination with topical hydrocortisone 17-butyrate cream in patients with vitiligo unresponsive to previous treatment with topical steroids or narrow-band ultraviolet (UV) B phototherapy. METHODS: Consecutive patients aged 18-75 years with nonsegmental vitiligo localized on the face and/or neck lacking response to previous conventional treatment were eligible. In total, 84 patients (44 women and 40 men, mean age 44 years) were randomized to 308-nm excimer laser phototherapy twice weekly alone or in combination with topical hydrocortisone 17-butyrate cream twice daily for three periods of 3 weeks followed by a 1-week steroid-free interval. The primary outcome was a reduction of at least 75% of the overall lesional areas as judged by automatic image analysis on reflected UV photographs, conducted blind to treatment assignment, at 12 weeks compared with baseline. Secondary outcomes were clearance, and improvements on Physician's Global Assessment (PGA) and Skindex-29 scores. RESULTS: A total of 76 (90%) patients completed the study. In an intention-to-treat analysis, seven [16.6%; 95% confidence interval (CI) 5.3-27.8%] patients in the excimer monotherapy arm and 18 (42.8%; 95% CI 27.8-57.8%) in the combination arm showed > or = 75% reduction of vitiligo lesions at 12 weeks (chi(2) test 6.89, P = 0.0087). Clearance was observed in two (4.7%; 95% CI 1.6-11.2%) and nine (21.4%; 95% CI 9.0-33.8%) patients, respectively (Fisher's exact test P = 0.04). A significant difference also emerged for PGA scores, while no difference was documented for Skindex-29. CONCLUSIONS: Recalcitrant vitiligo of the face and neck may benefit from the combination of excimer laser phototherapy with topical hydrocortisone 17-butyrate cream.

IL-4 enhances keratinocyte expression of CXCR3 agonistic chemokines.

IFN-induced protein of 10 kDa (IP-10), monokine induced by IFN-gamma (Mig), and IFN-inducible T-cell alpha-chemoattractant (I-TAC) belong to the non-glutamate-leucine-arginine motif CXC chemokine family and act solely through the CXCR3 receptor for potent attraction of T lymphocytes. In this study, we evaluated the capacity of the T cell-derived cytokines IL-4, IL-10, and IL-17 to modulate IP-10, Mig, and I-TAC in cultured human keratinocytes and CXCR3 expression in T cells from allergic contact dermatitis (ACD). IL-4, but not IL-10 or IL-17, significantly up-regulated IFN-gamma- or TNF-alpha-induced IP-10, Mig, and I-TAC mRNA accumulation in keratinocytes and increased the levels of IP-10 and Mig in keratinocyte supernatants. Immunohistochemistry of skin affected by ACD revealed that >70% of infiltrating cells were reactive for CXCR3 and that CXCR3 staining colocalized in CD4+ and CD8+ T cells. Nickel-specific CD4+ and CD8+ T cell lines established from ACD skin produced IFN-gamma and IL-4 and expressed moderate to high levels of CXCR3. Finally, CXCR3 agonistic chemokines released by stimulated keratinocytes triggered calcium mobilization in skin-derived nickel-specific CD4+ T cells and promoted their migration, with supernatant from keratinocyte cultures stimulated with IFN-gamma and IL-4 attracting more efficaciously than supernatant from keratinocytes activated with IFN-gamma alone. In conclusion, IL-4 exerts a proinflammatory function on keratinocytes by potentiating IFN-gamma and TNF-alpha induction of IP-10, Mig, and I-TAC, which in turn may determine a prominent recruitment of CXCR3+ T lymphocytes at inflammatory reaction sites.