Definition of the Clinical Characteristics of Patients with Moderate and Severe Atopic Dermatitis for Whom Narrow-Band UVB (NB-UVB) and Medium-Dose UVA1 Phototherapies Are Still Valuable Treatment Options at the Age of Biologics.

Narrow-band (NB) UVB and UVA1 have been successfully used for the treatment of atopic dermatitis (AD) since the 1980s, but the clinical indications for their use "at the age of biologics" remain to be assessed. From 2013 to 2017, 145 patients underwent a first treatment cycle with phototherapy. They achieved a median final EASI score of 9.90 with UVA1 and 13.70 with NB-UVB. The rates of patients achieving an IGA score of 0/1 persistent for at least 6 months were 33% with UVA1 and 28% with NB-UVB, and the rates with an EASI90 improvement were 10.9% with UVA1 and 11.0% with NB-UVB. The cut-off baseline EASI values for a good probability to achieve a 0/1 IGA were 24.4 with UVA1 and 24.7 with NB-UVB. A 0/1 IGA persistent for at least 6 months was more likely to be achieved by patients with a history of flares interspersed with periods of mild or no disease. From 2018, we only enrolled patients with the above-mentioned characteristics. The number of treated patients was lower, but the final EASI score, the rate of patients achieving IGA 0/1 persistent for at least 6 months, and EASI90 were significantly higher. Medium-dose UVA1 and NB-UVB phototherapies remain useful for the treatment of AD patients with a baseline EASI score lower than 24.4 and 24.7, respectively, and a medical history of flares followed by prolonged periods of complete or near-complete remission.

Bath-PUVA still represents a valuable treatment option for the subsets of psoriatic patients who are not eligible to or rejecting systemic treatments and are not responsive to NB-UVB phototherapy.

BACKGROUND: Photochemotherapy with bathwater delivery of psoralens plus UVA exposures (bath-PUVA) is mainly used for those psoriatic patients who are not responsive to narrowband (NB)-UVB phototherapy and oral-PUVA therapy and belong to two categories (1) patients with psoriasis without systemic comorbidities who do not need long-term continuous treatment and (2) patients who have contraindications to immunosuppressive drugs and oral-PUVA or refuse systemic drugs, including oral ingestion of psoralens, for personal reasons. However, it is not known how many patients belong to the second group and how much bath-PUVA is effective and safe for them. METHODS: We have reviewed the treatment results of a cohort of 120 patients with clinical indication to bath-PUVA for the above-mentioned reasons between 2010 and 2019. These patients were selected among 2640 patients with moderate and severe psoriasis who were treated in our department in the same time interval. RESULTS: Ninety-six patients completed at least one treatment cycle with bath-PUVA. A per-protocol analysis showed that average number of treatment sessions was 21.3 ± 9.0 and the cumulative UVA dose was 80.4 ± 60.0 J/cm2 . The average PASI scores decreased from 20.8 ± 7.9 to 5.1 ± 5.4 (p < .01). Sixty-seven (69.7%) patients achieved at least a 75% improvement (PASI75 ) and, of them, 38 (39.6%) had an improvement greater than 90% (PASI90 ). Adverse effects were mild and transitory. CONCLUSION: These findings demonstrate that bath-PUVA is still a valuable treatment option for a high number of patients who reject systemic treatments or have contraindications to systemic immune-modifying drugs and have had a limited or no improvement with NB-UVB phototherapy.

Pretreatment with an Aerosol Foam Containing Calcipotriene and Betamethasone Strongly Improves the Efficacy of Narrow-Band UVB Phototherapy.

BACKGROUND: Narrow-band (NB) UVB has been combined with a number of topical treatments. However, there have been no specific data regarding treatment results of a fixed combination of calcipotriene 50 µg/g plus betamethasone 0.5 mg/g aerosol foam (Cal/BD) combined with NB-UVB phototherapy so far. OBJECTIVES: To assess the efficacy of Cal/BD foam coupled to twice-weekly NB-UVB and whether this combined regimen requires fewer UVB treatments and a lower cumulative UVB dose compared to phototherapy alone. METHODS: This cross-sectional, prospective, parallel-group study enrolled 187 consecutive moderate-to-severe psoriatic patients who were allocated to two groups in a 1:2 ratio. The overall duration of the treatment cycle was 12 weeks. At baseline and after 2, 4, 8 and 12 weeks, we registered the modified (not considering head lesions) PASI, the number of Cal/BD applications, the NRS score for itching and the adverse effects. RESULTS: The combined regimen was more effective in clearing psoriasis [final mPASI: 2.1 (0; 8.2) versus 4.4 (0; 19.6); p < 0.01] and reducing itching [(final NRS score for itching: 0 (0; 3) versus 1 (0; 4); p < 0.01]. Fewer exposures [12 (4; 20) versus 24 (8; 24); p < 0.01] and a lower cumulative UVB dose [6.1 (5.4; 9.3) J cm-2 versus 13.1 (9.8; 19.7) J cm-2; p < 0.01] were required. A higher number of patients achieved complete clearance [47 (74.6%) versus 58 (46.8%) patients (p < 0.001)]. Both treatments were well tolerated without acute adverse effects. CONCLUSION: Cal/BD + NB-UVB is a very effective treatment that produces a rapid improvement in clinical lesions and itching and can be considered a valuable alternative to systemic treatments for psoriasis.

Sunlight-induced Painful Skin (Sun Pain): A New Differential Diagnosis in Photodermatology.

Photodermatoses are characterized by the development of skin eruptions following exposure to ultraviolet radiation or visible light. We report here the clinical findings and results of laboratory investigations and phototesting of 6 patients who experience debilitating and excruciating pain after sun exposure ("sun pain") in the absence of any skin eruption. Phototesting with sub-erythemal doses of ultraviolet A radiation triggered localized pain in 4 patients. At follow-up, 3 female patients were found to have developed fibromyalgia, 2 male patients experienced a major depressive disorder, and another male patient had a conversion disorder. One patient also developed allodynia to tactile stimuli and one developed allodynia to thermal and tactile stimuli. Psychiatric conditions should be taken into consideration in patients presenting with excruciating and debilitating pain on exposure to ultraviolet radiation, but with absence of skin eruption. Further research is needed to evaluate whether it represents a type of allodynia triggered by exposure to ultraviolet radiation.

A Short Cycle of Narrow-Band UVB Phototherapy in the Early Phase of Dupilumab Therapy Can Provide a Quicker Improvement of Severe Atopic Dermatitis.

BACKGROUND: Since the best clinical response to dupilumab is achieved after 12-16 weeks, a combination therapy at the beginning of the treatment could be a helpful strategy to reach a faster response in patients with severe atopic dermatitis (AD). OBJECTIVES: To quantify the benefit of a combination of dupilumab treatment with a short course of narrow-band ultraviolet B (NB-UVB) phototherapy. METHODS: In the present pilot study adult patients suffering from severe AD were enrolled with a 2:1 ratio to receive treatment with dupilumab alone or dupilumab plus NB-UVB phototherapy, for 12 weeks. After the twelfth week, all patients received dupilumab only. A follow-up visit took place after 16 weeks. Both clinician-oriented and patient-oriented scores were assessed at baseline (T0) and after 4 (T1), 12 (T2) and 16 (T3) weeks. RESULTS: Forty-five adult patients were enrolled in the study. Both treatment regimens were well tolerated and very effective on all measured scores (EASI, SCORAD, BSA, NRS of itching, NRS of sleep loss, DLQI, POEM and HADS), but the combined regimen led to a more robust clinical improvement of lesions and relief of symptoms after 4 weeks. However, after 12 and 16 weeks, the additional therapeutic effect of phototherapy weakened. CONCLUSION: NB-UVB phototherapy can provide a faster remission of severe AD in the first few weeks of dupilumab therapy.

Clinical, Dermoscopic and In-Vivo Reflectance Confocal Microscopy Evaluation of a Case of Graham Little-Piccardi-Lassueur Syndrome Successfully Treated with Narrowband-UVB Phototherapy.

Graham Little-Piccardi-Lassueur syndrome (GLPLS) is a rare variant of lichen planopilaris, characterized by a triad of clinical signs including follicular spinous papules on the body area, scarring alopecia of the scalp and non-scarring alopecia of the groin and/or axilla. To date, fewer than 50 cases have been described in the literature. We first report a case of GLPLS investigated with non-invasive techniques such as dermoscopy and in vivo reflectance confocal microscopy (RCM) and successfully treated with narrowband-UVB (NB-UVB) phototherapy.

Clinical and Spectrophotometric Evaluation of Skin Photoadaptation in Vitiligo Patients after a Short Cycle of NB-UVB Phototherapy.

BACKGROUND: The phenomenon of photoadaptation to narrow-band ultraviolet B (NB-UVB) radiation has been previously described in vitiligo and has usually been clinically measured by the assessment of the minimal erythema dose (MED) after phototesting. OBJECTIVES: To assess the photoadaptive response in vitiligo and healthy skin after NB-UVB phototherapy not only clinically, but also by spectrophotometry. MATERIALS AND METHODS: Fourteen patients affected by generalized vitiligo underwent NB-UVB phototherapy twice weekly for 12 weeks. Before and after phototherapy, a phototesting procedure was administered on vitiligo patches and adjacent healthy skin with a solar simulated radiation (SSR). Visual assessment of the MED took place after 24 h. A spectrophotometer was used to assess the a* value and the melanin index (MI*), as signs of skin erythema and pigmentation. The photoadaptation factor (MED-PF) and the a* photoadaptation factor (a*-PF) were calculated. RESULTS: After NB-UVB phototherapy, both vitiligo and healthy skin showed an increase in MED and MI* values and a reduction of skin erythema compared to baseline (p < 0.05). MED-PF data showed a photoadaptation in 10 (71.4%) vitiligo lesions and in 12 (85.7%) healthy skin areas. The assessment of the a*-PF showed a negative mean percentage value in all affected and unaffected skin areas. CONCLUSIONS: A short cycle of NB-UVB phototherapy can induce photoadaptation in vitiligo by increasing the MED and reducing skin erythema after stimulation with SSR. This is most likely due to the physical filter function induced by ultraviolet radiation.

Short-term supplementation with flavanol-rich cocoa improves lipid profile, antioxidant status and positively influences the AA/EPA ratio in healthy subjects.

We evaluated the short-term effects of a flavanol-rich cocoa (FRC) on lipid profile and selected oxidative stress biomarkers such as oxidized low-density lipoprotein (oxLDL), glutathione (GSH), and F2-isoprostane. We also assessed whether FRC modulates plasma levels of polyunsaturated fatty acids (PUFA) in healthy individuals. The subjects (n=48) were randomly assigned to a low-cocoa group (1 g/d; ~55 mg flavanols) (n=16), middle-cocoa group (2 g/d; ~110 mg flavanols) (n=16), or a high-cocoa group (4 g/d; ~220 mg flavanols) (n=16). The samples were collected at baseline, at 1, 2, and 4 h post initial consumption of FRC, and after 4 weeks of FRC supplementation. The peak plasma concentration of (-)-epicatechin metabolites reached a maximum level (578±61 nM; P<.05) at 2 h after ingestion of FRC. After 4 weeks, total cholesterol (-12.37±6.63; P<.0001), triglycerides (-3.81±2.45; P<.0001), plasma LDL (-14.98±6.77; P<.0001), and oxLDL (-95.61±41.69; P<.0001) decreased in the high-cocoa group, compared with baseline. We also found that plasma high-density lipoprotein (HDL) (+3.37±2.06; P<.0001) concentrations increased significantly in the same group. Total GSH significantly increased in all FRC-treated groups (+209.73±146.8; P<.0001), while urinary F2-isoprostane levels decreased in the middle- (-0.73±0.16; P<.0001) and high-cocoa (-1.62±0.61; P<.0001) groups. At the end of the four-week study, a significant reduction of arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio was observed in the low-(-2.62±2.93; P=.003), middle- (-5.24±2.75; P<.0001) and high-cocoa (-7.76±4.96; P<.0001) groups, compared with baseline. Despite the small sample size used in this study, these data extend previous clinical and experimental studies, providing new insights into the health benefits of cocoa flavanols.

Prevalence of Phototherapy in the Age of Biologics.

BACKGROUND: The prevalence of narrow-band ultraviolet B (NB-UVB) use in Europe for moderate and severe psoriasis is unknown, because national registries for psoriasis do not monitor this treatment. OBJECTIVES: To quantify the use of phototherapy, biologics or conventional treatments in psoriasis, in a setting where European Medicines Agency (EMA) eligibility criteria for biologics were strictly applied, and phototherapy was included among first-line treatments. METHODS: We followed a cohort of 1,090 patients who were referred to the only centre entitled to prescribe biologics and phototherapy during a 5-year period. RESULTS: The cumulative number of treatment cycles was: 1,047 with NB-UVB phototherapy, 650 with systemic treatments and 239 with biologics; 754 patients received at least 1 course of NB-UVB phototherapy, 422 at least 1 course with a systemic treatment and 137 with a biologic; 595 patients were treated only with phototherapy. CONCLUSIONS: Regular use of NB-UVB as first-line treatment for moderate and severe psoriasis and adherence to the EMA eligibility criteria for biologics led to a relatively restricted use of biologics.

Serum levels of tumor necrosis factor-alpha in patients with psoriasis before, during and after narrow-band UVB phototherapy.

BACKGROUND: Narrow-band UVB (NB-UVB) phototherapy is widely used worldwide for moderate and severe psoriasis, which is a chronic autoimmune inflammatory disease characterized by skin infiltrates of Th1-, Th17- and Th22-cells releasing locally pro-inflammatory cytokines. We investigate serum levels of tumor necrosis factor-α (TNF-α) in psoriatic patients before and after NB-UVB phototherapy. METHODS: Twenty-eight subjects with moderate/severe plaque type psoriasis were enrolled. The severity of skin involvement was rated according to the Psoriasis Area and Severity Index (PASI) score at baseline (T0) and after 4 (T1) and 12 (T2) weeks of NB-UVB treatment. At the same time points, blood samples were taken for evaluation of TNF-α levels. NB-UVB phototherapy was administered twice weekly on non-consecutive days until 12 weeks. RESULTS: The median PASI score significantly decreased from 12.0 at baseline (T0), to 6.9 after 4 weeks (T1, P<0.001) and to 0 after 12 weeks (T2, P<0.001). TNF-a serum levels significantly increased in respect to the baseline after 12 weeks of therapy. CONCLUSIONS: NB-UVB phototherapy is highly effective against psoriasis but, as it increases the TNF-α serum level, it seems unlikely that it can decrease the chronic inflammatory state that is thought to be responsible of the systemic co-morbidities of psoriasis.