Quality of Life, Anxiety, and Depression in Patients With Early-Stage Mycosis Fungoides and the Effect of Oral Psoralen Plus UV-A (PUVA) Photochemotherapy on it
Thomas Graier, Regina Fink-Puches, Stephanie Porkert, Roland Lang, Sophie Pöchlauer, Gudrun Ratzinger, Adrian Tanew, Sylvia Selhofer, Paul-Gunther Sator, Angelika Hofer, Alexandra Gruber-Wackernagel, Franz J Legat, Pablo Augusto Vieyra-Garcia, Franz Quehenberger, Peter Wolf, Thomas Graier, Regina Fink-Puches, Stephanie Porkert, Roland Lang, Sophie Pöchlauer, Gudrun Ratzinger, Adrian Tanew, Sylvia Selhofer, Paul-Gunther Sator, Angelika Hofer, Alexandra Gruber-Wackernagel, Franz J Legat, Pablo Augusto Vieyra-Garcia, Franz Quehenberger, Peter Wolf
Abstract
Background: Little is known about psychological discomfort and quality of life (QoL) in early stage mycosis fungoides (MF) and the effect of psoralen plus UV-A (PUVA) on it. Objective: To evaluate QoL, anxiety, and depression with validated instruments in early stage MF patients and whether PUVA treatment improves it. Methods: Patients with stage IA to IIA MF were treated with PUVA twice weekly for 12-24 weeks, followed by maintenance treatment or not, in a prospective randomized clinical trial. Patients completed a questionnaire on DLQI as well as the Hospital Anxiety and Depression Scale (HADS) prior to therapy, after their last PUVA exposure, and after the PUVA maintenance or observance phase. Results: For 24 patients with early stage MF, completed questionnaires were available and analyzed. Prior to treatment, 17% reported strong (DLQI > 10) and 29% moderate impairment (DLQI 6-10) in QoL; 33% of patients reported HADS scores indicating anxiety, and 21% reported scores indicating depression. PUVA significantly improved overall QoL by reducing mean DLQI scores by 58.6% (p = 0.003), HADS-A by 30% (p = 0.045), and HADS-D by 44% (p = 0.002). Improvements in QoL and psychological well-being seemed to be sustained, irrespective of maintenance treatment or not. Limitations: Small sample size. Conclusions: PUVA sustainably improves QoL and psychological well-being in patients with early stage MF. Clinical trial registration: ClinicalTrials.gov identifier: NCT01686594.
Keywords: PUVA; anxiety; depression; mycosis fungoides; phototherapy; quality of life.
Copyright © 2020 Graier, Fink-Puches, Porkert, Lang, Pöchlauer, Ratzinger, Tanew, Selhofer, Sator, Hofer, Gruber-Wackernagel, Legat, Vieyra-Garcia, Quehenberger and Wolf.
Figures
References
- Demierre MF, Gan S, Jones J, Miller DR. Significant impact of cutaneous T-cell lymphoma on patients' quality of life: results of a 2005 National cutaneous lymphoma foundation survey. Cancer. (2006) 107:2504–11. 10.1002/cncr.22252
- Molloy K, Jonak C, Woei-A-Jin FJSH, Guenova E, Busschots AM, Bervoets A, et al. . Characteristics associated with significantly worse quality of life in mycosis fungoides/Sézary syndrome from the prospective cutaneous lymphoma International prognostic index (PROCLIPI) study. Br J Dermatol. (2019) 182–770–9. 10.1111/bjd.18089
- Hodak E, Lessin S, Friedland R, Freud T, David M, Pavlovsky L, et al. . New insights into associated co-morbidities in patients with cutaneous T-cell lymphoma (mycosis fungoides). Acta Derm Venereol. (2013) 93:451–5. 10.2340/00015555-1496
- Sampogna F, Frontani M, Baliva G, Lombardo GA, Alvetreti G, Di Pietro C, et al. . Quality of life and psychological distress in patients with cutaneous lymphoma. Br J Dermatol. (2009) 160:815–22. 10.1111/j.1365-2133.2008.08992.x
- Herbosa CM, Semenov YR, Rosenberg AR, Mehta-Shah N, Musiek AC. Clinical severity measures and quality of life burden in patients with mycosis fungoides and Sézary syndrome: comparison of generic and dermatology-specific instruments. J Eur Acad Dermatology Venereol. (2019) 34:995–1003. 10.1111/jdv.16021
- Semenov YR, Rosenberg AR, Herbosa C, Mehta-Shah N, Musiek AC. Health-related quality of life and economic implications of cutaneous T-cell lymphoma. Br J Dermatol. (2019) 182:190–6. 10.1111/bjd.17941
- Jonak C, Porkert S, Oerlemans S, Papadavid E, Molloy K, Lehner-Baumgartner E, et al. . Health-related quality of life in cutaneous lymphomas: past, present and future. Acta Derm Venereol. (2019) 99:640–6. 10.2340/00015555-3171
- Mourad A, Gniadecki R. Overall survival in mycosis fungoides: a systematic review and meta-analysis. J Invest Dermatol. (2020) 140:495–7.e5. 10.1016/j.jid.2019.07.712
- Jawed SI, Myskowski PL, Horwitz S, Moskowitz A, Querfeld C. Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): part II prognosis, management, and future directions. J Am Acad Dermatol. (2014) 70:223.e1–17. 10.1016/j.jaad.2013.08.033
- Trautinger F, Eder J, Assaf C, Bagot M, Cozzio A, Dummer R, et al. . European organisation for research and treatment of cancer consensus recommendations for the treatment of mycosis fungoides/Sezary syndrome - update 2017. Eur J Cancer. (2017) 77:57–74. 10.1016/j.ejca.2017.02.027
- Prince HM, Kim YH, Horwitz S, Dummer R, Scarisbrick J, Quaglino P, et al. . Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial. Lancet. (2017) 390:555–66. 10.1016/S0140-6736(17)31266-7
- Duvic M, Kuzel TM, Olsen EA, Martin AG, Foss FM, Kim YH, et al. . Quality-of-life improvements in cutaneous T-cell lymphoma patients treated with denileukin diftitox (ONTAK). Clin Lymphoma. (2002) 2:222–8. 10.3816/CLM.2002.n.003
- Illidge T, Chan C, Counsell N, Morris S, Scarisbrick J, Gilson D, et al. . Phase II study of gemcitabine and bexarotene (GEMBEX) in the treatment of cutaneous T-cell lymphoma. Br J Cancer. (2013) 109:2566–73. 10.1038/bjc.2013.616
- Talpur R, Demierre MF, Geskin L, Baron E, Pugliese S, Eubank K, et al. . Multicenter photopheresis intervention trial in early-stage mycosis fungoides. Clin Lymphoma Myeloma Leuk. (2011) 11:219–27. 10.1016/j.clml.2011.03.003
- Quaglino P, Pimpinelli N, Berti E, Calzavara-Pinton P, Alfonso Lombardo G, Rupoli S, et al. . Time course, clinical pathways, and long-term hazards risk trends of disease progression in patients with classic mycosis fungoides: a multicenter, retrospective follow-up study from the Italian group of cutaneous lymphomas. Cancer. (2012) 118:5830–9. 10.1002/cncr.27627
- Ling TC, Clayton TH, Crawley J, Exton LS, Goulden V, Ibbotson S, et al. . British association of Dermatologists and British photodermatology group guidelines for the safe and effective use of psoralen-ultraviolet A therapy 2015. Br J Dermatol. (2016) 174:24–55. 10.1111/bjd.14317
- Gallini A, Misery L, Paul C, Le Maître M, Aractingi S, Joly P, et al. Carcinogenic risks of Psoralen UV-A therapy and Narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review. J Eur Acad Dermatology Venereol. (2012) 26:22–31. 10.1111/j.1468-3083.2012.04520.x
- Stern RS. The risk of melanoma in association with long-term exposure to PUVA. J Am Acad Dermatol. (2001) 44:755–61. 10.1067/mjd.2001.114576
- Stern RS, Nichols KT, Väkevä LH. Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet a radiation (PUVA). N Engl J Med. (1997) 336:1041–5. 10.1056/NEJM199704103361501
- Vieyra-Garcia P, Fink-Puches R, Porkert S, Lang R, Pöchlauer S, Ratzinger G, et al. Evaluation of low-dose, low-frequency oral Psoralen-UV-A treatment with or without maintenance on early-stage mycosis fungoides: a randomized clinical trial. JAMA Dermatol. (2019) 155:538–47. 10.1001/jamadermatol.2018.5905
- Duvic M, Hymes K, Heald P, Breneman D, Martin AG, Myskowski P, et al. . Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results. J Clin Oncol. (2001) 19:2456–71. 10.1200/JCO.2001.19.9.2456
- Duvic M, Martin AG, Kim Y, Olsen E, Wood GS, Crowley CA, et al. Phase 2 and 3 clinical trial of oral bexarotene (Targretin capsules) for the treatment of refractory or persistent early-stage cutaneous T-cell lymphoma. Arch Dermatol. (2001) 137:581–93.
- Stadler R, Otte HG, Luger T, Henz BM, Kühl P, Zwingers T, et al. . Prospective randomized multicenter clinical trial on the use of interferon α-2a plus acitretin versus interferon α-2a plus PUVA in patients with cutaneous T-cell lymphoma stages I and II. Blood. (1998) 92:3578–81. 10.1182/blood.V92.10.3578
- Phan K, Ramachandran V, Fassihi H, Sebaratnam DF. Comparison of narrowband UV-B with Psoralen-UV-A phototherapy for patients with early-stage mycosis fungoides: a systematic review and meta-analysis. JAMA Dermatol. (2019) 155:335–41. 10.1001/jamadermatol.2018.5204
- Holahan HM, Farah RS, Fitz S, Mott SL, Ferguson NN, Mckillip J, et al. . Health-related quality of life in patients with cutaneous T-cell lymphoma? Int J Dermatol. (2018) 57:1314–9. 10.1111/ijd.14132
- Guitart J. Psoralen plus UV-A therapy in the 21st century. JAMA Dermatol. (2019) 155:529–31. 10.1001/jamadermatol.2018.5844
- Dixon JR. The International conference on harmonization good clinical practice guideline. Qual Assur. (1999) 6:65–74. 10.1080/105294199277860
- Williams JR. Public health classics. Bulletin of the World Health Oranization. (2008) 86:650–2. 10.2471/BLT.08.050955
- Mart E, Arias-santiago S, Valenzuela-salas I, Garrido-colmenero C, Dermatology F, Quality L. Quality of life in persons living with psoriasis patients. J Am Acad Dermatol. (2014) 302–7. 10.1016/j.jaad.2014.03.039
- Patel KR, Singam V, Vakharia PP, Chopra R, Sacotte R, Patel N, et al. . Measurement properties of three assessments of burden used in atopic dermatitis in adults. Br J Dermatol. (2019) 180:1083–9. 10.1111/bjd.17243
- Heald P, Mehlmauer M, Martin AG, Crowley CA, Yocum RC, Reich SD. Topical bexarotene therapy for patients with refractory or persistent early-stage cutaneous T-cell lymphoma: results of the phase III clinical trial. J Am Acad Dermatol. (2003) 49:801–15. 10.1016/S0190-9622(03)01475-0
- Rencz F, Gulácsi L, Péntek M, Szegedi A, Remenyik É, Bata-Csörgo Z, et al. . DLQI-R scoring improves the discriminatory power of Dermatology life quality index in psoriasis, pemphigus and morphea patients. Br J Dermatol. (2019) 182:1167–75. 10.1111/bjd.18435
- Gahalaut P, Mishra N, Soodan PS, Rastogi MK. Effect of oral puvasol on the quality of life in indian patients having chronic plaque psoriasis. Dermatol Res Pract. (2014) 2014:291586. 10.1155/2014/291586
- Strober B, Papp KA, Lebwohl M, Reich K, Paul C, Blauvelt A, et al. . Clinical meaningfulness of complete skin clearance in psoriasis. J Am Acad Dermatol. (2016) 75:77–82.e7. 10.1016/j.jaad.2016.03.026
- Norlin JM, Nilsson K, Persson U, Schmitt-Egenolf M. Complete skin clearance and Psoriasis area and severity index response rates in clinical practice: predictors, health-related quality of life improvements and implications for treatment goals. Br J Dermatol. (2020) 182:965–73. 10.1111/bjd.18361
- Väkevä L, Niemelä S, Lauha M, Pasternack R, Hannuksela-Svahn A, Hjerppe A, et al. . Narrowband ultraviolet B phototherapy improves quality of life of psoriasis and atopic dermatitis patients up to 3 months: results from an observational multicenter study. Photodermatol Photoimmunol Photomed. (2019) 35:332–8. 10.1111/phpp.12479
- Simpson EL, Gadkari A, Worm M, Soong W, Blauvelt A, Eckert L, et al. . Dupilumab therapy provides clinically meaningful improvement in patient-reported outcomes (PROs): a phase IIb, randomized, placebo-controlled, clinical trial in adult patients with moderate to severe atopic dermatitis (AD). J Am Acad Dermatol. (2016) 75:506–15. 10.1016/j.jaad.2016.04.054
- Simpson EL, Bieber T, Eckert L, Wu R, Ardeleanu M, Graham NMH, et al. . Patient burden of moderate to severe atopic dermatitis (AD): insights from a phase 2b clinical trial of dupilumab in adults. J Am Acad Dermatol. (2016) 74:491–8. 10.1016/j.jaad.2015.10.043
- Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. (1983) 67:361–70. 10.1111/j.1600-0447.1983.tb09716.x
- Marron SE, Tomas-aragones L, Boira S. Anxiety, depression, quality of life and patient satisfaction in Acne patients treated with oral Isotretinoin. Acta Derm Venereol. (2013) 93:701–6. 10.2340/00015555-1638
- Shyu Y, Firth J, Koyanagi A, Solmi M, Alavi A, Piguet V, et al. . Depression and anxiety in adults with Hidradenitis suppurativa a systematic review and meta-analysis. JAMA Dermatol. (2019) 155:939–45. 10.1001/jamadermatol.2019.0759
- Ring J, Zink A, Arents BWM, Seitz IA, Mensing U, Schielein MC, et al. . Atopic eczema: burden of disease and individual suffering – results from a large EU study in adults. J Eur Acad Dermatol Venereol. (2019) 33:1331–40. 10.1111/jdv.15634
- Silverberg JID, Gelfand JM, Margolis DJ, Boguniewicz M, Fonacier L, Grayson MH, et al. . Symptoms and diagnosis of anxiety and depression in atopic dermatitis in U. S. adults. Br J Dermatol. (2019) 181:554-6. 10.1111/bjd.17683
- Modalsli EH, Åsvold BO, Snekvik I, Romundstad PR, Naldi L, Saunes M. The association between the clinical diversity of psoriasis and depressive symptoms: the HUNT study, Norway. J Eur Acad Dermatology Venereol. (2017) 31:2062–8. 10.1111/jdv.14449
- Yuan J, Ding R, Wang L, Sheng L, Li J, Hu D. Screening for depression in acute coronary syndrome patients: a comparison of patient health questionnaire-9 versus hospital anxiety and depression scale-depression. J Psychosom Res. (2019) 121:24–8. 10.1016/j.jpsychores.2019.03.018
- Łabuz-Roszak B, Niewiadomska E, Kubicka-Baczyk K, Skrzypek M, Dobrakowski P, Tyrpien-Golder K, et al. . Prevalence of pain in patients with multiple sclerosis and its association with anxiety, depressive symptoms and quality of life. Psychiatr Pol. (2019) 53:475–86. 10.12740/PP/94469
- Ivziku D, Clari M, Piredda M, De Marinis MG, Matarese M. Anxiety, depression and quality of life in chronic obstructive pulmonary disease patients and caregivers: an actor–partner interdependence model analysis. Qual Life Res. (2019) 28:461–72. 10.1007/s11136-018-2024-z
- Almeida E De, Simone M. Assessment of the Hospital Anxiety and Depression Scale (HADS) performance for the diagnosis of anxiety in patients with systemic lupus erythematosus. Rheumatol Int. (2017) 37:1999–2004. 10.1007/s00296-017-3819-x
- Chan CYY, Tsang HHL, Lau CS, Chung HY. Prevalence of depressive and anxiety disorders and validation of the Hospital anxiety and depression scale as a screening tool in axial spondyloarthritis patients. Int J Rheum Dis. (2017) 20:317–25. 10.1111/1756-185X.12456
- Wagner T, Augustin M, Blome C, Forschner A, Garbe C, Gutzmer R, et al. . Fear of cancer progression in patients with stage IA malignant melanoma. Eur J Cancer Care. (2018) 27:e12901. 10.1111/ecc.12901
- Licari A, Ciprandi R, Marseglia G, Ciprandi G. Behavioral sciences Anxiety and depression in Adolescents with severe asthma and in their parents : preliminary results after 1 year of treatment. Behav Sci. (2019) 9:78 10.3390/bs9070078
- Tesio V, Marra S, Molinaro S, Torta R, Gaita F, Castelli L. Screening of depression in cardiology: a study on 617 cardiovascular patients. Int J Cardiol. (2017) 245:49–51. 10.1016/j.ijcard.2017.07.065
- Preljevic VT, Østhus TBH, Sandvik L, Opjordsmoen S, Nordhus IH, Os I, et al. . Screening for anxiety and depression in dialysis patients: comparison of the hospital anxiety and depression scale and the beck depression inventory. J Psychosom Res. (2012) 73:139–44. 10.1016/j.jpsychores.2012.04.015
- Jozic I, Stojadinovic O, Kirsner RSF, Tomic-Canic M. Skin under the (Spot)-light: Cross-talk with the central hypothalamic-pituitary-adrenal (HPA) axis. J Invest Dermatol. (2015) 135:1469–71. 10.1038/jid.2015.56
- Fell GL, Robinson KC, Mao J, Woolf CJ, Fisher DE. Skin β-endorphin mediates addiction to UV light. Cell. (2014) 157:1527–34. 10.1016/j.cell.2014.04.032
- Tejeda HA, Bonci A. Shedding “uV” light on endogenous opioid dependence. Cell. (2014) 157:1500–1. 10.1016/j.cell.2014.06.009
- Bigliardi PL, Dancik Y, Neumann C, Bigliardi-Qi M. Opioids and skin homeostasis, regeneration and ageing – what's the evidence? Exp Dermatol. (2016) 25:586–91. 10.1111/exd.13021
- Felton SJ, Kendall AC, Almaedani AFM, Urquhart P, Webb AR, Kift R, et al. . Serum endocannabinoids and N-acyl ethanolamines and the influence of simulated solar UVR exposure in humans in vivo. Photochem Photobiol Sci. (2017) 16:564–74. 10.1039/C6PP00337K
Source: PubMed