Acta Dermato-Venereologica 99-3CompleteContent | Page 12

INVESTIGATIVE REPORT 291 Exploratory Study of Intracutaneous Histamine Stimulation in Patient Populations with Chronic Pruritus Athanasios TSIANAKAS 1,2# , Nadine NIPPE 1# , Christina Maria HAMPER 1 , Anna Friederike CORDES 3 , Claudia ZEIDLER 1 , Martin SCHMELZ 4 and Sonja STÄNDER 1 1 Center for Chronic Pruritus, Department of Dermatology and 3 Department of Pediatric Rheumatology and Immunology, University Hospital Muenster, Muenster, 2 Department of Dermatology, Fachklinik Bad Bentheim, Bad Bentheim, and 4 Department of Anesthesiology, University of Heidelberg, Mannheim, Germany # These authors shared first authorship. Chronic pruritus can be a diagnostic sign of an under- lying disease. In the intracutaneous histamine test, histamine (one of the best-known inducers of pruri- tus) may cause different reaction patterns depending on the underlying disease. The aim of this study was to determine if an intracutaneous injection of hista- mine can differentiate between the causes of chro- nic pruritus and thus be used as a diagnostic test in chronic pruritus of unknown aetiology. A total of 140 subjects with chronic pruritus with various dermato- logical, systemic or neurological diseases were inclu- ded. The intracutaneous histamine test was performed once on each subject. Erythema, wheal and pruritus intensity were measured and analysed. Significantly greater wheal size was observed in patients with sys- temic or multifactorial causes. In general, there was a significant correlation between age and wheal size. Also, noticeable differences were found between ma- les and females regarding pruritus and wheal size. In summary, the exact type of chronic pruritus could not be clearly determined based on the results of the in- tracutaneous histamine test. However, the results pro- vide valuable insights into specific reaction patterns to experimental histamine-induced itch, e.g. sex-specific differences in the neurophysiology of pruritus, which should be considered in future studies. Key words: chronic pruritus; itch; diagnostics; C-fibres; atopic dermatitis; neurophysiology. Accepted Nov 1, 2018; E-published Nov 5, 2018 Acta Derm Venereol 2019; 99: 291–297. Corr: Athanasios Tsianakas, Department of Dermatology, University Hos- pital Muenster, Von-Esmarch-Str. 58, DE-48149 Muenster, Germany. E- mail: [email protected] C hronic pruritus is defined as itch that lasts for at least 6 weeks (1). There is a wide range of potential underlying diseases (German Guideline Chronic pruri- tus) (2). These diseases can be of systemic origin (e.g. chronic renal failure, hepatic failure, chronic hepatitis C, and cholestatic pruritus) or of dermatological origin (e.g. atopic dermatitis (AD) and cutaneous autoimmune diseases, such as bullous pemphigoid or dermatitis her- petiformis). Other causes can be neurological diseases, such as brachioradial pruritus, notalgia paraesthetica, post-herpetic neuralgia or multiple sclerosis. In addition, SIGNIFICANCE Chronic itch (or pruritus) is a symptom of many underlying diseases, but clinically it is often not easy to determine the exact cause. The aim of this study was to determine whether a specific skin test, the intracutaneous histamine test, can differentiate between various potential causes of chronic itch. The results showed that the histamine test might indicate when there is a cause of chronic itch in the field of systemic, internal diseases. In addition, there were differences between male and female patients regarding the test reaction pattern. psychiatric diseases, such as depression or schizophrenia, can also cause chronic pruritus. Epidemiological studies have revealed that chronic pruritus has a point preva- lence of 13.5% in the general population (3), among the working population point prevalence shows even higher values of up to 16.8% (4). Among elderly patients the values increase to 20.3%. Determining factors are female sex, low social economic status, mental distress and atopic background (5). The most commonly known and studied mediator of pruritus is histamine (6–8). It is released by mast cells and causes pruritus by binding to the histamine 1-receptor on mechano-insensitive sensory afferents (mechano- insensitive-C-nociceptors) (9, 10). Abundant histamine release results in the clinical sign of a local wheal (ur- ticaria) with a surrounding erythema in addition to the symptom of pruritus. The erythema is of neurogenic origin and reflects the peripheral release of neuropeptides from pruriceptors following their activation by histamine, and indicates the bidirectional interaction between neur­ ones and innervated tissue. Accordingly, this reaction pattern is used as a positive control in allergological diagnostics where histamine is applied intracutaneously (11). During recent years many details of the underlying pathomechanism have been elucidated. Interestingly, histamine and the histamine 1 receptor expressed on mechano-insensitive-C-nociceptors were demonstrated to require the neuronal function of both PLCbeta3 and the TRPV1 channel to induce itch (12). Moreover, upon activation of the Toll-like receptor 4 (TLR4), expressed on sensory neurones, histamine-induced itch signal trans- duction is enhanced by potentiating TRPV1 activity (13, This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica. doi: 10.2340/00015555-3078 Acta Derm Venereol 2019; 99: 291–297