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.

Clinical, histological and high-frequency ultrasonographic evaluation (50 MHz) of morphoea treated with ultraviolet A1 phototherapy.

BACKGROUND: There are few studies in the literature correlating the ultrasonographic findings, clinical scoring systems or histological findings in morphoea after ultraviolet (UV)A1 phototherapy. AIMS: To evaluate the quantitative and morphological aspects of high-frequency ultrasonography in the treatment of plaque morphoea in response to UVA1 phototherapy, and to correlate these with clinical and histological scores. METHODS: In total, 17 patients with morphoea were studied. Initially and at study end, high-frequency ultrasonography (50 MHz) was performed on the edge of a morphoea lesion treated with UVA1 phototherapy. A quantitative and qualitative analysis of dermal features was performed and compared with the features of healthy skin. Skin biopsy specimens were obtained from lesions analysed at the beginning and end of the study, assessing dermal sclerosis and dermal inflammatory infiltrate and their distribution. RESULTS: All affected skin showed a statistically significant increase in dermal thickness and hypoechogenicity, corresponding to a reduction in dermal density by ultrasonography compared with healthy skin. Morphological evaluation identified undulations of the dermis in 11 of 17 lesions (64.7%) and in 5 healthy skin areas (29.4%) (P = 0.08), while 'yoyo' figures were identified in 8 lesions (47%) but only 1 healthy skin area (5.9%) (P = 0.02). Ultrasonographic morphological analysis highlighted an improvement in dermal hyperechogenic bands and disappearance of yoyo figures after UVA1 treatment. Histology revealed a reduction in dermal sclerosis and inflammation, although this was not statistically significant. CONCLUSIONS: Ultrasonographic pattern analysis of morphoea is a suitable technique for monitoring UVA1 phototherapy response.

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.

Synergism between narrowband ultraviolet B phototherapy and etanercept for the treatment of plaque-type psoriasis.

BACKGROUND: Previous investigations have demonstrated that a combination of etanercept (ETN) and narrowband ultraviolet B (NB-UVB) phototherapy is more effective than ETN alone. However, it is unclear if this combination is more effective than NB-UVB phototherapy alone. OBJECTIVES: To evaluate whether the combination of NB-UVB phototherapy with ETN improves the efficacy of ETN alone in the treatment of moderate-to-severe psoriasis. METHODS: We enrolled 322 consecutive patients with moderate-to-severe plaque-type psoriasis, who were treated with NB-UVB phototherapy as the first-line treatment option. Patients who did not achieve a 75% improvement in Psoriasis Area and Severity Index (PASI 75) were treated with conventional systemic therapies for psoriasis. If they were ineligible for these, they were treated with ETN 50 mg twice weekly. If they did not achieve PASI 75 within 12 weeks, NB-UVB phototherapy was added. RESULTS: PASI 75 was achieved in 262 patients (81.4%) treated with NB-UVB phototherapy. Sixteen patients (5.0%) dropped out for personal reasons and 24 (7.5%) were treated with at least one of the conventional systemic treatments for psoriasis. Twenty patients (6.2%) were treated with ETN. The combination regimen was needed in eight patients (2.5%) with poor response to both phototherapy and ETN alone. All of these patients achieved PASI 75 and three of them had a complete remission after 14.6 ± 3.3 NB-UVB exposures. The combined treatment was well tolerated without acute adverse events. Unfortunately, all of these patients relapsed, with PASI > 10 within 2.8 ± 1.7 months. CONCLUSIONS: The combined treatment has a synergistic effect for clearing plaque-type psoriasis previously unresponsive to ETN and NB-UVB phototherapy alone. The clearance rate is very high in a very short time without short-term adverse effects. However, concerns regarding potential cocarcinogenicity remain. Therefore the number of patients who require, and could benefit from, the combined treatment is likely to be small.

Italian guidelines and therapeutic algorithm for actinic keratoses.

The prevalence of actinic keratosis (AK) continues to rise among white people throughout the world and it is necessary to increase the level of attention paid to it from a diagnostic and a preventive point of view. Today, AK must be considered an in situ squamous cell carcinoma and as such, must be managed using one of the available approved therapeutic alternatives. However, when multiple AKs develop on severely photodamaged skin, the treatment of the lesion together with that of the field of cancerization is part of an optimal strategy that aims not only to solve alterations clinically evident but also those in the surrounding skin field cancerization, that most likely hosts genetic alterations and is the site of initial gradual replacement of normal cells with tumoral cells. This paper reports the most recent evidences from a careful review of the literature's key articles of the treatment of AKs and suggests guidelines for the clinicians. The guidelines indicated by the authors have also been based on practical evaluations and their own clinical experience. The present conclusions may be modified by new findings in the field of oncologic research.

Blisters on psoriatic lesions treated with TL-01 lamps.

BACKGROUND: Asymptomatic blisters on psoriatic plaques are an uncommon adverse effect of TL-01 (UVB narrow-band 312 nm) phototherapy. OBJECTIVE: We report 7 new cases aiming to clarify the pathogenesis. METHODS: Blisters were biopsied at different times after onset. Blood porphyrins and antibodies to nuclear antigens and the cell surface of keratinocytes were investigated. RESULTS: We observed 7 asymptomatic blistering eruptions strictly limited to recovering psoriatic plaques. Biopsies taken within 24 h showed junctional detachment and apoptotic necrosis of basal keratinocytes. After 48 and 72 h, the blisters were intraepithelial, due to basal cell regeneration, and were no longer evident at 96 and 120 h. Dermal inflammation was always mild. Direct immunofluorescence tests as well as stainings for p53 protein did not show substantial changes. Blood investigations were negative. CONCLUSIONS: TL-01 blisters are caused by the quick reduction of acanthosis and desquamation before defensive mechanisms, i.e. the increase in the thickness of the stratum corneum and pigmentation, develop. However, the pathogenetic mechanisms of apoptosis of keratinocytes remain unknown.

Narrow band UVB (311 nm) phototherapy and PUVA photochemotherapy: a combination.

BACKGROUND: Psoralen-UVA (PUVA) photochemotherapy is widely used for the treatment of psoriasis despite concerns of skin carcinogenesis from high cumulative UVA doses and number of treatments. OBJECTIVE: We attempted to determine whether combined bath-PUVA with narrow-band (311 nm) phototherapy improves efficacy and reduces long-term toxicity. METHODS: Twelve psoriatic patients underwent phototesting with 311 nm lamps and, after topical bath-water psoralen sensitization, with 311 nm, UVA, or both radiations. Patients were treated with bath-PUVA on one side of the body and with bath-PUVA plus 311 nm exposures (bath-PUVA-311 nm) on the other side. On both sides, four weekly treatments were delivered and UVA doses were increased once weekly whereas 311 nm doses were adjusted at each exposure. RESULTS: Psoralen sensitization did not modify the erythematous threshold to 311 nm radiation. However, 311 nm exposures enhanced the phototoxic activity of bath-PUVA. Bath-PUVA-311 nm cleared psoriasis with fewer exposures and lower cumulative UVA doses under the same minimally erythemogenic conditions. CONCLUSION: Combination with 311 nm exposures enhanced the phototoxic and therapeutic activities of bath-PUVA.

Bath-5-methoxypsoralen-UVA therapy for psoriasis.

BACKGROUND: After oral intake, 5-methoxypsoralen (5-MOP) is as effective as 8-MOP for PUVA therapy for psoriasis, with a lower incidence of acute cutaneous side effects. OBJECTIVE: We compared bath-water delivery of 5-MOP and 8-MOP for photochemotherapy of psoriasis. METHODS: Twenty-two patients underwent phototesting with 0.0003% 5-MOP or 8-MOP aqueous solutions. Twelve patients with palmar psoriasis were studied with a side-to-side comparison, and 10 patients with recurrent plaque-type psoriasis were treated with one therapy or the other. RESULTS: Minimal phototoxic dose (MPD) values were 2.8 +/- 1.2 J/cm2 with 8-MOP and 2.0 +/- 1.2 J/cm2 with 5-MOP (p < 0.01). Both therapies cleared palmar lesions but 8-MOP required more UVA irradiation (46.3 +/- 21.0 J/cm2 vs 30.2 +/- 21.5 J/cm2; p < 0.01) and more exposures (21.0 +/- 6.0 vs 17.0 +/- 5.0; p = 0.02). Bath-5-MOP-UVA was also more effective in the treatment of plaque-type psoriasis (cumulative UVA doses, 56.8 +/- 39.2 vs 59.1 +/- 27.9 J/cm2; number of exposures, 20.0 +/- 5.7 vs 21.6 +/- 4.7), but these differences were not significant (p = NS). Patients developed an intense tan significantly earlier with 5-MOP than with 8-MOP (3.5 +/- 0.5 weeks vs 4.4 +/- 0.5 weeks; p < 0.01). CONCLUSION: Bath-5-MOP-UVA was more phototoxic than bath-8-MOP-UVA. It was more effective in the treatment of palmar psoriasis, whereas its greater pigmentogenic activity appeared to have an adverse effect on therapeutic effectiveness in the treatment of plaque-type psoriasis.

Efficacy and safety of stand-up irradiation cubicles with UVA metal-halide lamps (and a new filter) or UVA fluorescent lamps for photochemotherapy of psoriasis.

BACKGROUND: Metal-halide lamps (MHLs) and fluorescent lamps (FLs) are widely employed for PUVA therapy of psoriasis, but they have never been compared in a clinical trial. OBJECTIVE: We studied the irradiance, spectral power distribution, irradiation field and efficacy of two cabinets with standard FLs or MHLs with a new UVA filter. METHODS: The photophysical properties of the lamps were studied with a spectroradiometer. After phototesting, 22 patients with recurrent plaque type psoriasis were treated in a stand-up irradiation cubicle housing 27 standard FLs, and, at recurrence, in a cubicle with 15 MHLs. When indicated, lesions of the legs underwent supplementary exposures with small FL or MHL devices. RESULTS: MHLs had a greater emission in the longer UVA wavelengths than FIs. The MHL cubicle had a greater irradiance and a more uniform output along the vertical axis. Both cubicles were effective in a similar number of exposures. However, FLs were more phototoxic and lower cumulative UVA doses were administered although the total duration of exposures was longer. Eleven patients treated with FLs and 7 patients with MHLs required supplementary treatments of the legs. The number, cumulative UVA dose and total duration of these exposures were significantly greater with FLs. CONCLUSION: Cabinets with MHLs increase the number of patients treated in the same time period and reduce the number of patients needing supplementary treatments of the legs. Cumulative UVA doses are greater with MHLs, but their emission is prevalent in the less erythematogenic and carcinogenic longer UVA wavelengths.

Antinuclear antibodies are not induced by PUVA treatment in patients with uncomplicated psoriasis.

BACKGROUND: Previous investigations of antinuclear antibody (ANA) prevalence in patients undergoing PUVA therapy reported contrasting results. However, ANA tests were performed on low-sensitivity substrates that do not allow investigation of anti-Ro (SS-A) antibodies. OBJECTIVE: We assessed ANAs on a highly sensitive substrate. METHODS: ANAs were assayed on HEp-2 cells at regular intervals in 238 patients with psoriasis who were treated with PUVA therapy for 1 to 5 years and in 118 untreated control subjects with psoriasis. In addition, radioimmunoassay and counterimmunoelectrophoresis studies of anti-DNA and anti-extractable nuclear antigen antibodies were performed. RESULTS: Low titers of ANA developed in three patients in at least two consecutive determinations and in 10 patients in a single determination despite continuing treatments. The positive conversion rate was not statistically significant. Radioimmunoassay counterimmunoelectrophoresis studies of anti-DNA and anti-extractable nuclear antigen antibodies were never positive. CONCLUSION: In our experience PUVA therapy does not represent a risk factor for the induction of anti-Ro antibodies and other ANAs.

Ocular side effects of PUVA-treated patients refusing eye sun protection.

We have investigated short- and long-term ocular side effects of psoralen plus UVA (PUVA) therapy in 82 patients who refused to wear UVA blocking sunglasses after the treatments. They had received 321.7 +/- 328.8 J/cm2 of UVA in 148.8 +/- 113.9 exposures over 2-4 years. Results were compared with findings obtained in 749 patients who shielded their eyes. They received 402.6 +/- 302.2. J/cm2 of UVA in 167.8 +/- 136.9 treatments over 2-6 years. 20 patients refusing eye sun protection developed conjunctival hyperemia and 21 patients decreased lacrimation. Among patients who adequately protected the eyes, we observed 5 cases of conjunctival hyperemia and 1 case of decreased lacrimation. Lens opacities did not develop in any patient. Adequate eye sun-protection is thus needed to avoid acute toxicity of cornea and conjunctiva but lens opacities do not appear to be a side effect of long-term PUVA-therapy.

Safety and effectiveness of an aggressive and individualized bath-PUVA regimen in the treatment of psoriasis.

BACKGROUND: The optimal therapeutic regimen of bath-PUVA therapy of psoriasis is still under debate. OBJECTIVE: We investigated the safety and efficacy of an aggressive and individualized bath-PUVA regimen. METHODS: Two closely matched groups of 22 psoriatic patients were treated either with 30-min baths in 0.0003% 8-methoxypsoralen (8-MOP) aqueous solution or oral administration of the drug. According to the standard European regimen, treatments were delivered 4 times a week starting with the minimal phototoxic dose. RESULTS: Complete clearing or marked improvement was observed in all the patients. However, with bath-PUVA, the same therapeutic effect required smaller cumulative UVA doses (39.3 +/- 15.8 vs. 123.8 +/- 39.9 J/cm2) and lower numbers of exposures (15.2 +/- 4.4 vs. 20.6 +/- 4.2). Both differences were significant at the 0.01 level (Student's t test). Gastro-intestinal side-effects were of course restricted to oral 8-MOP. The incidences of burns and pruritus were similar. CONCLUSION: Using an aggressive and individualized schedule, bath-PUVA therapy showed a greater efficacy than oral PUVA therapy while being just as safe.

Comparison of narrow-band (311 nm) UVB and broad-band UVA after oral or bath-water 8-methoxypsoralen in the treatment of psoriasis.

BACKGROUND: There is a disparity between the absorption spectrum of 8-methoxypsoralen and the action spectrum for psoralen-sensitized erythema. In an action spectrum corrected for unsensitized reaction 313 and 365 nm have similar efficacies. OBJECTIVE: We evaluated the relative erythemogenic and antipsoriatic efficacy of narrow-band (311 nm) UVB with and without prior psoralen exposure. We also compared the effects of narrow-band UVB and broad-band UVA after oral and bath-water psoralen exposure. METHODS: Patients with psoriasis underwent half-side comparison studies. In one group the therapeutic efficacy of 311 nm UVB with and without oral psoralen was assessed. The second group received UVA and 311 nm UVB after oral psoralen. The third group was exposed to both radiation sources after bath-water exposure. RESULTS: The erythemogenic, pigmentogenic, and therapeutic efficacy of 311 nm was increased by oral psoralen. With systemic 8-methoxypsoralen, UVA was comparable to 311 nm UVB. After bath-water exposure, 311 nm was clearly superior to broad-band UVA. CONCLUSION: The efficacy of narrow-band 311 nm UVB can be enhanced by psoralen. Narrow-band 311 nm UVB is also effective after psoralen bath-water delivery.

A reappraisal of the use of 5-methoxypsoralen in the therapy of psoriasis.

5-methoxypsoralen (5-MOP) is considered an alternative to 8-methoxypsoralen (8-MOP) for photochemotherapy of psoriasis. We have compared the clinical efficacy and tolerability of 5-MOP (1.2 mg/kg)-UVA versus 8-MOP (0.6 mg/kg)-UVA therapy in 25 patients of skin type III and IV, affected by relapsing plaque-type psoriasis of similar body involvement; indeed, the same patients were given 8-MOP during 1 year and 5-MOP during the subsequent year after relapsing. Both treatments cleared psoriatic lesions with a comparable number of exposures, but 5-MOP required significantly higher cumulative UVA doses. The difference was due to the lower phototoxicity of 5-MOP, as assessed by the determination of the minimal phototoxic dose, and to its higher tanning activity, as assessed by the weekly grading of pigmentation. Nevertheless, therapy by 5-MOP-UVA seemed particularly interesting in that it showed a higher tolerability since only 1 patient experienced nausea, whereas during therapy with 8-MOP-UVA nausea and/or vomiting occurred in 7 patients, sunburn in 6 and itching in 3. Since we have treated the same patients with the two drugs, our results were not influenced by interindividual variations of phototoxic responses, tanning ability and susceptibility to develop psoralen-induced short-term side-effects. It was concluded that, although long-term side-effects of the 5-MOP-UVA treatment have still to be determined, such treatment of psoriasis should be reappraised due to its higher tolerability in comparison to 8-MOP-UVA treatment.