European Guideline on Chronic Pruritus In cooperation with the European Dermatology Forum (EDF) and the European Academy of Dermatology and Venereology (EADV) Elke Weisshaar1, Jacek C Szepietowski2, Florence Dalgard3, Simone Garcovitch4, Uwe Gieler5, Ana Gimenez-Arnau6, Julien Lambert7, Tabi Leslie8, Thomas Mettang9, Laurent Misery10, Ekin Savk11, Markus Streit12, Erwin Tschachler13, Joanna Wallengren14, Sonja Ständer15 1 Department of Clinical Social Medicine, Environmental and Occupational Dermatology, Ruprecht-Karls-University Heidelberg, Germany 2 Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Poland 3 Department of Dermatology and Venerology, Skane University Hospital, Lund University, Malmö, Sweden and National Centre for Dual Diagnosis, Innlandet Hospital Trust, Brummundal, Norway 4 Institute of Dermatology, F. Policlinico Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy 5 Department of Psychosomatic Dermatology, Clinic for Psychosomatic Medicine, University of Giessen, Germany 6 Department of Dermatology, Hospital del Mar- Institut Mar d’Investigacions Mèdiques (IMIM), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain 7 Department of Dermatology, University Hospital of Antwerp, University of Antwerp, Belgium 8 Department of Dermatology, Royal Free Hospital, London, UK 9 Department of Nephrology, DKD Helios Wiesbaden, Germany 10 Department of Dermatology, University Hospital Brest, France 11 Department of Dermatology, Adnan Menderes University, Aydin, Turkey 12 Department of Dermatology, Kantonsspital Aarau, Switzerland 13 Department of Dermatology, Medical University Vienna, Austria 14 Lund University, Skane University Hospital, Department of Clinical Sciences Lund, Dermatology and Venereology, Lund, Sweden 15 Department of Dermatology, Center for Chronic Pruritus, University Hospital Muenster, Germany Corresponding authors: Sonja Ständer M.D. Center for Chronic Pruritus, Department of Dermatology University Hospital Münster Von-Esmarch-Str. 58 D-48149 Münster, Germany Tel: 0049-251-8356510 Fax: 0049-251-8352559 Email: [email protected] Elke Weisshaar M.D. Dept. Clinical Social Medicine, Occupational and Environmental Dermatology Ruprecht-Karls University Heidelberg Voßstr. 2 D-69115 Heidelberg, Germany Tel: 0049-6221-568752 Fax: 0049-6221-565584 Email: [email protected] 1 Abstract Pruritus is a frequent symptom in medicine. Population-based studies show that every 5th person in the general population has suffered from chronic pruritus (CP) at least once in the lifetime with a 12-month incidence of 7%. In patient populations its frequency is much higher depending on the underlying cause, ranging from around 25% in haemodialysis patients to 100% in skin diseases such as urticaria and atopic dermatitis (AD). Pruritus may be the result of a dermatological or non-dermatological disease. Especially in non-diseased skin it may be caused by systemic, neurological or psychiatric diseases, as well as being a side effect of medications. In a number of cases CP may be of multifactorial origin. Pruritus needs a precise diagnostic work-up. Management of CP comprises treatment of the underlying disease and topical treatment modalities, including symptomatic antipruritic treatment, ultraviolet phototherapy and systemic treatment. Treating CP needs to be targeted, multimodal and performed in a step- wise procedure requiring an interdisciplinary approach. We present the updated European guideline on chronic pruritus by a team of European pruritus experts from different disciplines. This version is an updated version of the guideline that was published in 2012 and updated in 2014 (www.euroderm.org). Conflict of Interest: see table enclosed Financial support: none Composition of the guideline group: experts in the field from Europe. More than 30% are European Academy of Dermatology and Venereology (EADV) members 2 Abbreviations and explanations AD Atopic dermatitis AEP Atopic eruption of pregnancy CGRP Calcitonin gene-related peptide CKD Chronic kidney disease CNS Central nervous system CNPG Chronic nodular prurigo CP Chronic pruritus (longer than 6 weeks) CPG Chronic prurigo CSU Chronic spontaneous urticaria DIF Direct immunofluorescence ICP Intrahepatic cholestasis of pregnancy IFSI International Forum on the Study of Itch IIF Indirect immunofluorescence IL Interleukin Itch Synonym of pruritus NRS Numerical rating scale NSAID Non-steroidal anti-inflammatory drugs PAR Proteinase-activated receptor PBC Primary biliary cirrhosis PEP Polymorphic eruption of pregnancy PG Pemphigoid gestationis Pruritus A skin sensation that elicits the urge to scratch PUO Pruritus of undetermined origin PTH Parathyroid hormone PV Polycythaemia vera RCT Randomised controlled trials SSRI Selective serotonin re-uptake inhibitors TRP Transient receptor potential UP Uremic pruritus UV Ultraviolet VAS Visual analogue scale VIP Vasoactive intestinal peptide VRS Visual rating scale 3 1 The challenge of writing this guideline ......................................................................... 5 2 Definitions and clinical classification............................................................................ 6 3 Epidemiology of chronic pruritus ................................................................................. 7 4 The clinical picture of chronic pruritus ......................................................................... 9 4.1 4.1.1 Chronic Pruritus in lesional and non-lesional skin ......................................................... 9 4.1.2 Pruritus in kidney disease .............................................................................................. 9 4.1.3 Pruritus in hepatobiliary diseases (cholestatic pruritus) .............................................. 10 4.1.4 Pruritus in metabolic and endocrine diseases ............................................................. 11 4.1.5 Pruritus in malignancy .................................................................................................. 11 4.1.6 Pruritus in infectious diseases ..................................................................................... 12 4.1.7 Pruritus in neurological diseases ................................................................................. 13 4.1.8 Pruritus in psychiatric diseases .................................................................................... 14 4.1.9 Drug-induced chronic pruritus ...................................................................................... 14 4.2 Specific patient populations ................................................................................................. 15 4.2.1 Chronic pruritus in the elderly ...................................................................................... 15 4.2.2 Chronic pruritus in pregnancy ...................................................................................... 15 4.2.3 Chronic pruritus in children .......................................................................................... 16 5 Diagnostic management ......................................................................................... 178 5.1 Patient history and clinical examination ............................................................................. 178 5.2 Diagnostic algorithm and diagnostics .................................................................................. 21 6 Therapy .................................................................................................................. 212 6.1 Therapy: general principles including emollients ............................................................... 212 6.2 Causative therapy and aetiology-specific treatment ............................................................ 23 6.3 Topical therapy .................................................................................................................... 24 6.3.1 Local anaesthetics ....................................................................................................... 24 6.3.2 Zinc, menthol and camphor ......................................................................................... 25 6.3.3 Capsaicin ..................................................................................................................... 26 6.3.4 Topical glucocorticosteroids ......................................................................................... 27 6.3.5 Tacrolimus and pimecrolimus ...................................................................................... 28 6.3.6 Acetylsalicylic acid ....................................................................................................... 29 6.3.7 Doxepin ........................................................................................................................ 30 6.3.8 Topical mast cell inhibitors ........................................................................................... 30 6.4 Systemic therapy ................................................................................................................. 30 6.4.1 Antihistamines .............................................................................................................. 30 6.4.2 Mast cell inhibitors........................................................................................................ 33 6.4.3 Glucocorticosteroids ...................................................................................................