Narrowband ultraviolet B phototherapy in psoriasis reduces proinflammatory cytokine levels and improves vitiligo and neutrophilic asthma

Dear Editor, Psoriasis, neutrophilic asthma and vitiligo vulgaris are three immune‐mediated diseases in which raised serum levels of proinflammatory T helper (Th) 1/Th17 cytokines have been detected. Psoriasis is considered a systemic disease with several comorbidities, and the role of high levels of cytokines referable to Th1–Th17 patterns in the pathogenesis of these comorbidities remains to be clarified.1 2 3 Monozygotic twins, aged 69 years, affected by psoriasis and vitiligo were referred to the outpatient clinic of the internal medicine department of the University of Brescia, Brescia, Italy, because of poorly controlled asthma. Both twins had asthma, which had been treated with montelukast 10 mg daily, inhaled corticosteroid and a long‐acting β2 agonist (fluticasone 250 μg/formoterol 10 μg) twice daily in the preceding 6 months. Physical examination revealed high respiratory rates (22 and 26 breaths per min, respectively) with signs of accessory muscle use and, on auscultation, decreased breathing sounds with inspiratory and expiratory wheezing. Pulse oximetry was 94% and 92%, respectively, on room air. A chest radiograph of both twins showed bronchial thickening, hyperinflation and focal atelectasis consistent with asthma. Spirometry detected, respectively, a forced expiratory volume in the first second (FEV1) of 64% and 66% of the predicted volume, and a Tiffeneau index of 70% and 71% of the predicted value. The patients reported moderate limitations of daily activities and a mean of three asthma attacks weekly, suggesting the presence of severe uncontrolled asthma.3 In both twins a chest computer tomography scan was performed during inspiration, and demonstrated air trapping. Immunology examinations resulted in negative antinuclear antibody, extractable nuclear antigen and rheumatoid factor, no eosinophilia and normal total IgE, erythrocyte sedimentation rate, C‐reactive protein and procalcitonin levels. Serum levels of interleukin (IL)‐17, IL‐1β, IL‐6, IL‐8, IL‐12 and tumour necrosis factor (TNF)‐α were higher than normal, whereas IL‐4 was in the normal range (Table 1). Hence, sputum induction was performed to characterize asthma inflammatory phenotype showing a neutrophilic pattern. Afterwards, the twins underwent an exhaled breath condensate test, analysed with an enzyme‐linked immunosorbent assay, which showed a lymphocyte Th1/Th17 cytokine pattern (Table 1).4 After these assessments the dose of formoterol and fluticasone was doubled, and an anticholinergic (tiotropium bromide 18 μg) once daily was added. Associated with the asthma, the patients had severe psoriasis, with a Psoriasis Area Severity Index (PASI) score of 23 and 25, respectively. Body surface area score was 40 in both cases. In addition, patches of vitiligo occurred on the hands and feet in both twins. Only one twin consented to undergo a treatment cycle for psoriasis with narrowband ultraviolet B phototherapy three times a week, while the other refused all dermatological care. After 3 months, the twins were re‐examined. The twin who underwent phototherapy presented a clear improvement of psoriasis, with a PASI of 12 and a partial follicular repigmentation of the patches of vitiligo. In the same patient we observed an improvement of laboratory parameters, including a reduction in the level of cytokines in the serum (Table 1). Moreover, this twin had controlled asthma without daily symptoms and/or daily life activity limitations, with a functional respiratory improvement (FEV1 81%; Tiffeneau index 80%). The other twin, who was treated with the same asthma therapy, showed only slight improvement in the limitations of daily activities and in the laboratory parameters of airway obstruction (FEV1 72%; Tiffeneau index 76%). Values of exhaled breath condensate, induced sputum, fractional exhaled nitric oxide and spirometric data before and after psoriasis treatment in monozygotic twins IL, interleukin; TNF, tumour necrosis factor; FEV1, forced expiratory volume in the first second; FVC, forced vital capacity. Predicted values are given in parentheses. Values of exhaled breath condensate, induced sputum, fractional exhaled nitric oxide and spirometric data before and after psoriasis treatment in monozygotic twins IL, interleukin; TNF, tumour necrosis factor; FEV1, forced expiratory volume in the first second; FVC, forced vital capacity. Predicted values are given in parentheses. Only the twin treated for both asthma and psoriasis achieved good control of the asthma, psoriasis and vitiligo, while the second twin experienced less improvement in the asthma, without any change in psoriasis and vitiligo. In addition, we showed that, at baseline, the median serum levels of TNF‐α, IL‐1, IL‐6, IL‐8, IL‐17 and IL‐12 were significantly higher in both patients compared with findings in normal controls, and that they decreased only in the twin who was successfully treated with phototherapy. Psoriasis, vitiligo and neutrophilic asthma are autoimmune skin diseases.1 2 5 6 In psoriatic skin, the production of Th1 and Th17 cytokines is upregulated,7 leading to raised serum levels that correlate with disease severity and extension.7 8 Vitiligo is also frequently associated with other autoimmune conditions (up to 23% of patients), including psoriasis in 8% of cases.2 In addition, in this study, levels of IL‐17 were found to be increased both in serum and lesional skin, suggesting a pivotal pathogenetic role for this cytokine, which may favour the skewing of the immune response to Th1 and Th17 cells.5 Asthma is a well‐known chronic inflammatory airway disorder, and biological studies on the pathogenesis of asthma have shown (using bronchoalveolar lavage and induced sputum) that different cell populations are involved in different inflammatory phenotypes of asthma.3 In particular, in neutrophilic asthma, a prevalence of Th1 lymphocytes and interferon‐γ was found.6 In addition, the presence of Th17 cells and enhanced production of IL‐17 have been directly documented in lung tissue,9 and a single nucleotide polymorphism in IL17A and IL17F was found to confer susceptibility for neutrophilic asthma.10 In conclusion, we speculate that in these three different manifestations of Th1/Th17 dysregulation, phototherapy could improve the regulatory mechanisms that control both psoriasis and neutrophilic asthma, decreasing proinflammatory cytokine spillover from skin. Moreover, phototherapy can enhance the effects of asthma therapy, thus suggesting a pivotal role of Th1 and TH17 in developing neutrophilic systemic inflammation. Funding sources: none. Conflicts of interest: none declared.