Treatment of atopic dermatitis with dupilumab: experience from a tertiary referral centre.

BACKGROUND: Management of moderate-to-severe atopic dermatitis (AD) frequently requires treatment with systemic therapies. Dupilumab is the first biological agent approved for treatment of moderate-to-severe AD. Although promising results have appeared in clinical trials, real-life data on efficacy and safety are lacking. OBJECTIVES: To assess effectiveness and safety of treatment with dupilumab in the real-life clinical setting at a Danish tertiary referral centre. METHODS: All patients with AD treated with dupilumab from October 2017 to October 2018 at Bispebjerg Hospital, Denmark, were included in the study. Patients were evaluated three times: at treatment initiation and at 1 and 3 months after first dupilumab injection. At each visit, disease activity was assessed by severity score (Eczema Area and Severity Index, EASI), patient-reported outcomes (Dermatology Life Quality Index, DLQI, pruritus and sleep score) and serological markers [immunoglobulin (Ig)E, eosinophil count and lactate dehydrogenase (LDH)]. RESULTS: A total of 43 patients were included in the study. The mean reduction in EASI score from baseline was 19.6 points (72.4%) at 1-month and 22.6 points (76.7%) at 3-month follow-up. EASI, DLQI, pruritus score, sleep score, IgE and LDH were all statistically significantly reduced between baseline and 1- and 3-month follow-up. Mean reductions in EASI score and LDH at 3-month follow-up were significantly correlated (P = 0.003). One patient (2.3%) discontinued treatment due to side-effects, and seven patients (18.4%) developed conjunctivitis during the study period. CONCLUSION: The effectiveness and safety of dupilumab treatment in a real-life clinical setting are comparable to that of phase 3 clinical trials. LDH is suggested as a potential serological marker predictive of treatment response.

Sequels to tattoo removal by caustic products.

BACKGROUND: Caustic products are used as affordable alternatives to laser removal of tattoos. OBJECTIVE: Describe a series of patients with sequels after tattoo removal by caustic products. METHODS: 11 patients with complications referred from 2013 to 2017 were studied. Objective findings, sequels, corrective treatments, cost and psychological aspects were obtained. Numeric Rating Scale (NRS, score 10 extremely dissatisfied) was used to describe patient satisfaction with tattoos before and after removal. RESULTS: Scarring and residual tattoo pigments were detected in all patients. Chronic itching (73%), redness (73%) and swelling (64%) were frequent. Patients were less satisfied with their tattoo after removal attempts; Average NRS prior to removal was 7.5 (range 5-10), and afterwards 8.9 (range 4.5-10), t test non-significant. Removal was performed by medical professionals (82%) and cosmetologists (18%), involving the marketed injection brands Tatt2Away and Rejuvi. Ten patients had corrections eg. laser, plastic surgery or cover-up tattoos. Private expense for corrections was mean 1.953 EUR, not including consultations provided by the Hospital. CONCLUSION: Tattoo removal by caustic products can cause severe and chronic sequels with dissatisfaction despite therapeutic interventions to correct disfiguring changes. Removal by caustic products is freely permitted. Products are obscured and liability and consumer protection is unacceptable; limitation is needed.

MR scanning, tattoo inks, and risk of thermal burn: An experimental study of iron oxide and organic pigments: Effect on temperature and magnetic behavior referenced to chemical analysis.

BACKGROUND: Tattooed persons examined with magnetic resonance imaging (MRI) can develop burning sensation suggested in the literature to be thermal burn from the procedure. MRI-induced thermal effect and magnetic behavior of known tattoo pigments were examined ex vivo. MATERIALS AND METHODS: Magnetic resonance imaging effects on 3 commonly used commercial ink stock products marketed for cosmetic tattooing was studied. A main study tested 22 formulations based on 11 pigment raw materials, for example, one line of 11 called pastes and another called dispersions. Samples were spread in petri dishes and tested with a 0.97 T neodymium solid magnet to observe visual magnetic behavior. Before MRI, the surface temperature of the ink was measured using an infrared probe. Samples were placed in a clinical 3T scanner. Two scans were performed, that is, one in the isocenter and one 30 cm away from the center. After scanning, the surface temperature was measured again. Chemical analysis of samples was performed by mass spectroscopy. RESULTS: Mean temperature increase measured in the isocenter ranged between 0.14 and 0.26°C (P < .01) and in the off-center position from -0.16 to 0.21°C (P < .01). Such low increase of temperature is clinically irrelevant. Chemical analysis showed high concentrations of iron, but also nickel and chrome were found as contaminants. High concentration of iron was not associated with any increase of temperature or any physical draw or move of ink. CONCLUSION: The study could not confirm any clinically relevant temperature increase of tattoo pigments after MRI.

Tattoo removal by Q-switched yttrium aluminium garnet laser: client satisfaction.

BACKGROUND: Tattoo removal by Q-switched yttrium aluminium garnet (YAG) lasers is golden standard; however, clients' satisfaction with treatment is little known. OBJECTIVE: To determine clients' satisfaction with tattoo removal. METHODS: One hundred and fifty-four tattoo removal clients who had attended the private clinic 'Centre for Laser Surgery', Hellerup, Denmark, from 2001 to 2013 completed a questionnaire concerning outcome expectations, level of pain experiences and satisfaction with tattoo removal. The laser surgeon and his team were blinded from data handling. The study design included a minimum 2-year postlaser treatment observation period from 2013 to 2015. RESULTS: Overall, clients were satisfied with their laser treatment; 85% assessed their treatment and results to be acceptable to superb, while 15% assessed their treatment and results to be inferior to unacceptable. Effectiveness relative to colour of tattoo on a scale from 0 (no effect) to 10 (complete removal) scored a mean of blue 9.5, black 9.4, yellow 8.9, red 8.8 and green 6.5. Clients were dissatisfied with green pigment remnants, which could mimic bruising. One hundred and twenty-nine clients (84%) experienced moderate to extreme pain during treatment. Twenty-eight (20%) developed minor scarring. There were many reasons for tattoo removal; e.g. stigmatisation (33%), conspicuousness (29%) and poor artistic quality (22%). One hundred and two clients had expected complete removal of tattoos without a blemish, expectations that were only partly fulfilled. During the treatment period, clients adjusted expectations and adapted more realistic views of outcomes. CONCLUSION: The majority of clients were satisfied with Q-switched YAG laser removal of tattoos despite high pretreatment expectations which were only partly met. The study supports YAG lasers for tattoo removal as acceptable therapy of today, with room for new approaches.

Allergic reactions in red tattoos: Raman spectroscopy for 'fingerprint' detection of chemical risk spectra in tattooed skin and culprit tattoo inks.

AIM: The aim of this study was to assess the feasibility of Raman spectroscopy as a screening technique for chemical characterisation of tattoo pigments in pathologic reacting tattoos and tattoo ink stock products to depict unsafe pigments and metabolites of pigments. MATERIALS/METHODS: Twelve dermatome shave biopsies from allergic reactions in red tattoos were analysed with Raman spectroscopy (A 785-nm 300 mW diode laser). These were referenced to samples of 10 different standard tattoo ink stock products, three of these identified as the culprit inks used by the tattooist and thus by history the source of the allergy. Three primary aromatic amine (PAA) laboratory standards (aniline, o-anisidine and 3,3'-dichlorobenzidine) were also studied. RESULTS: Application of Raman spectroscopy to the shave biopsies was technically feasible. In addition, all ten inks and the three PAA standards could be discriminated. 10/12 shave biopsies provided clear fingerprint Raman signals which differed significantly from background skin, and Raman spectra from 8/12 biopsies perfectly matched spectra from the three culprit ink products. The spectrum of one red ink (a low cost product named 'Tattoo', claimed to originate from Taiwan, no other info on label) was identified in 5/12 biopsies. Strong indications of the inks 'Bright Red' and 'Crimson Red' were seen in three biopsies. The three PAA's could not be unambiguously identified. CONCLUSION: This study, although on a small-scale, demonstrated Raman spectroscopy to be feasible for chemical analysis of red pigments in allergic reactions. Raman spectroscopy has a major potential for fingerprint screening of problematic tattoo pigments in situ in skin, ex vivo in skin biopsies and in tattoo ink stock products, thus, to eliminate unsafe ink products from markets.

Histopathology and immune histochemistry of red tattoo reactions. Interface dermatitis is the lead pathology, with increase in T-lymphocytes and Langerhans cells suggesting an allergic pathomechanism.

BACKGROUND: The majority of tattoo reactions are affiliated to red pigmented areas and often suspected to be allergic in nature. A sizeable series of biopsies of such reactions has not previously been performed. The aim of this study was to type and grade epidermal and dermal changes in tattoo reactions to red/red nuances by microscopy and immunochemistry relevant for the assessment of a possible allergic pathomechanism. METHODS: Skin biopsies were taken from red tattoo reactions, graded by conventional microscopy and stained for T and B-lymphocytes, Langerhans cells, macrophages and tumour necrosis factor (TNF)-α. RESULTS: The study included 19 biopsies from 19 patients. The culprit colours were red/pink (n = 15) and purple/bordeaux (n = 4). Interface dermatitis was clearly the lead pathology found in 78% of samples, overlapped with granulomatous (in 32%) and pseudolymphomatous reaction patterns (in 32%). Epidermal hyperkeratosis (in 89%) was common as was leakage of red pigment across the dermo-epidermal junction, with transepidermal elimination (in 28%). The dermal cellular infiltration was dominated by T-lymphocytes (in 100%), Langerhans cells (in 95%) and macrophages (in 100%). TNF-α was common. CONCLUSION: The predominant histological pattern of chronic tattoo reactions in red/red nuances is interface dermatitis. T-lymphocytes and Langerhans cells are increased suggesting an allergic pathomechanism. TNF-α may contribute to reactions. In many cases, overlapping reactive patterns were identified.

Patients with tattoo reactions have reduced quality of life and suffer from itch: Dermatology Life Quality Index and Itch Severity Score measurements.

BACKGROUND: Tattoos are a trend with increasing side-effects. The burden of local reaction with swelling, itching and discomfort may impel sufferers to consult medical assistance. OBJECTIVES: To assess tattoo reactions and their influence on quality of life and itching by utilizing the Dermatology Life Quality Index (DLQI) scoring system and Itch Severity Scale (ISS). METHODS: Patients attending the 'Tattoo Clinic' at Bispebjerg University Hospital, Denmark with tattoo problems spanning more than 3 months were invited. Forty patients participated during September-November 2012. Patients attending their routine consultations completed the ISS and DLQI questionnaires. RESULTS: Patients with tattoo reactions experienced reduced quality of life, DLQI score 7.4 and were burdened by itch, ISS score 7.2. Both DLQI and ISS results attained the level of discomfort of known skin diseases such as psoriasis, pruritus and eczema albeit the typical tattooed affected areas are smaller. CONCLUSION/DISCUSSION: Sufferers of tattoo reactions have reduced quality of life and are often burdened by itching attaining the level of other cumbersome afflictions recognized as dermatological diseases associated with itch. Tattoo reactions warrant diagnosis and treatment with same professional intent shared with other skin diseases.

Photosensitivity and photodynamic events in black, red and blue tattoos are common: A 'Beach Study'.

OBJECTIVES: To find the prevalence of complaints in people having tattoos, with emphasis on chronic complaints, photosensitivity and photodynamic events. METHODS: Individuals sunbathing from June to September 2011 at the beaches of Denmark were invited to participate as they are prone to report tattoos and sun habits reliably. Sun-related and non-sun-related problems in tattoos were determined along with participants' use of sunscreen. Skin type was categorized, as were motifs and colours associated with problems. RESULTS: Of 467 sunbathers, 146 (31.3%) had tattoos. A total of 144 sunbathers with 301 tattoos accepted inclusion. Complaints were experienced in 60/144 (42%), of which 31/60 (52%) were sun related, such as swelling (58%), itching/stinging/pain (52%) and redness (26%). Reactions independent of sun were 29/60 (48%), such as reactions to heat 12/29 (41%) and cold 1/29 (4%). Red, blue and black tattoos predominantly caused sun-related complaints followed by the remaining colours. By number, problems in black tattoos dominated as black was far more frequent. DISCUSSION/CONCLUSION: Complaints such as swelling, itching, stinging, pain and redness are common, predominantly in black and red tattoos, but also frequent in blue tattoos, thus, not confined to one specific colour or chemical entity or class of pigment. Symptoms may switch on and off in seconds, typically not of the weal-and-flare type. Photochemical reactions to pigment or pigment-breakdown products in situ in the skin with induction of reactive oxygen species (ROS) is presumed to be one causative mechanism. Another possible mechanism especially relevant in black may be induction of ROS due to effects of aggregation of carbon black nanoparticles.

High-frequency ultrasound imaging of tattoo reactions with histopathology as a comparative method. Introduction of preoperative ultrasound diagnostics as a guide to therapeutic intervention.

BACKGROUND AND AIM: Tattoo adverse reactions requiring diagnostic evaluation and treatment are becoming more common. The aim of this study was to assess tattoo reactions by 20-MHz ultrasonography referenced to histopathology as a comparative method. MATERIALS AND METHODS: A total of 73 individuals with clinical adverse reactions in their tattoos were studied. Punch biopsies for reference histology were available from 58 patients. The Dermascan C(®) of Cortex Technology, Denmark, was employed. Total skin thickness and echo density of the echolucent band in the outer dermis were measured. Biopsy served for diagnosis and for determination of the level of cellular infiltration in the dermis. RESULTS: In every tattoo reaction studied, the skin affected was found thicker compared with regional control of the same individual (mean difference 0.73 mm). A prominent echolucent band of mean thickness 0.89 mm was demonstrated, primarily located in the very outer dermis but propagating to deeper dermal layers parallel to increasing severity of reactions. The thickness of the echolucent band correlated with the thickness of cellular infiltration determined by microscopic examination, R = 0.6412 (P < 0.001). Special diagnoses such as granulomatous and pseudolymphomatous tattoo reactions showed no distinct characteristics by ultrasound, but mainly displayed themselves by their advanced inflammatory component. DISCUSSION AND CONCLUSION: It is demonstrated for the first time that ultrasound, with histopathology as the comparative method, can quantify the severity of tattoo reactions and non-invasively diagnose the depth of the inflammatory process in the dermis elicited by the microparticulate tattoo pigment, which itself is too minute to be imaged by ultrasound. Preoperative 20-MHz ultrasound scanning is introduced as a potentially useful method to guide therapeutic interventions by surgery and lasers.

High prevalence of minor symptoms in tattoos among a young population tattooed with carbon black and organic pigments.

BACKGROUND: The prevalence of mild adverse reactions, i.e. complaints, in tattoos is sparsely described. OBJECTIVE: The demography of tattoos in a young population representing an index population of the recent trend was studied. The prevalence of complaints related to tattoos, and tattoos by number, size, localization and colour were registered. METHODS: The data were collected through personal interviews and examinations of consecutive individuals who spontaneously attended a clinic of venereology. RESULTS: Of 154 participants with 342 tattoos, 27% reported complaints in a tattoo beyond 3 months after tattooing. The complaints were predominantly related to black and red pigments. The participants reported complaints in 16% of their tattoos. Fifty-eight per cent of those complaints were sun induced. The complaints varied in intensity but were mainly minor. Skin elevation and itching were most frequent. The responders stated overall satisfaction with 80% of all tattoos. Eight per cent of tattoos were situated on anatomical sites prohibited by Danish law. CONCLUSION: We found a remarkably high prevalence of tattoo complaints, including photosensitivity, among young individuals tattooed with carbon black and organic pigments especially red.

Microbial status and product labelling of 58 original tattoo inks.

BACKGROUND: European Council resolutions on tattoo ink introduce sterility and preservation of inks to protect customers. Inks used in Denmark are typically purchased over the internet from international suppliers and manufacturers from the US and the UK. In Denmark tattoo inks are regulated and labelled according to REACH as if they were plain chemicals. OBJECTIVE: The objective of this study was to check the microbial product safety of unopened and opened tattoo ink stock bottles. Packaging, labelling, preservation, sterility and contamination with micro-organisms were studied. METHODS: Physical inspection and culture of bacteria and fungi. RESULTS: Six of 58 unopened stock bottles (10%) were contaminated with bacteria and one of six samples (17%) of previously used stock bottles was contaminated. The bacterial species represented bacteria considered pathogenic in humans as well as non-pathogenic environmental bacteria. Yeast or moulds were detected in none of the samples. A total of 31% of the manufacturers informed only about the brand name. No information about content, sterility, risks or expiry date was indicated on the label. A total of 42% claimed sterility of their inks. A total of 54% labelled a maximum period of durability of typically 2-3 years. The physical sealing was leaking in 28% of the products. CONCLUSIONS: The European Council resolutions regarding safety of tattoo inks are not effective. Stock bottles of tattoo ink may contain bacteria pathogenic to humans and environmental bacteria, and packaging, labelling and preservation of inks are of inadequate quality. Claim of sterility can be erroneous.

Tattoo inks in general usage contain nanoparticles.

BACKGROUND: To our knowledge tattooing has never been thought of as a method of introducing nanoparticles (NPs) into the human body by the intradermal route, and as such it has never been a topic of research in nanotoxicology. The content of NPs in tattoo inks is unknown. OBJECTIVES: To classify the particle sizes in tattoo inks in general usage. METHODS: The particle size was measured by laser diffraction, electron microscopy and X-ray diffraction. RESULTS: The size of the pigments could be divided into three main classes. The black pigments were the smallest, the white pigments the largest and the coloured pigments had a size in between the two. The vast majority of the tested tattoo inks contained significant amounts of NPs except for the white pigments. The black pigments were almost pure NPs, i.e. particles with at least one dimension <100 nm. CONCLUSIONS: The finding of NPs in tattoo inks in general usage is new and may contribute to the understanding of tattoo ink kinetics. How the body responds to NP tattoo pigments should be examined further.

Non-attendance rate in a Danish University Clinic of Dermatology.

AIM: To clarify the rate of non-attendance (NA) in an out-patient clinic. METHODS: Attendance lists of 3592 patients were collected daily from 21 July-21 August and 21 October-21 November, 2009. NA patients were contacted to determine extenuations. To study NA in relation to diagnosis and age, a control group of patients who attended before or after a NA was established. Furthermore, two time periods from 8:00-11:30 AM and 11:30 AM-3:00 pm were compared. RESULTS: In total, 13% NA gave no cancellation (54.2% females and 45.8% males). Divided into age groups, 496 patients 0-25 years old had appointments, but 87 (18.6%) showed NA. In the 26-65 years old, 2188 patients were planned, but 313 (14.1%) showed NA. Over 65 years old, 878 patients were planned, but 69 patients (7.9%) showed NA. NA was higher (P < 0.05) in patients 0-25 years old in comparison with the other age groups. Diagnoses had no influence on the rate of NA (P > 0.05), neither had seasons nor time of the day. The main explanations reported by the NA were: forgetfulness (34.3%), erroneous scheduling (27.7%) and various reasons (38.0%). However, 18.5% had shown NA before while 17.1% were NA first timers. CONCLUSION: The NA rate 13% of 3592 patients was mostly patient-related. Erroneous scheduling was estimated to be 3.6%. NA was more frequent among young patients. NA rate is small in comparison with non-adherence to medicines, however, of major practical and economic consequence for the health system. SMS or e-mail notification and improved scheduling are potential actions to improve NA in the routine.

Single application of a fluorescent test cream by healthy volunteers: assessment of treated and neglected body sites.

BACKGROUND: Management of dermatological self-treatment is demanding. Imperfect application of creams and ointments and poor adherence to topical treatment are common, resulting in unsatisfactory treatment outcome. OBJECTIVES: To assess the technique and precision of test subjects' self-application of a test cream. Treated and neglected skin sites were measured after intended widespread single application of a fluorescent test cream. METHODS: Twenty healthy volunteers (10 women, 10 men) were included. They were asked to treat their whole skin surface with the fluorescent test cream, except the head and neck and skin covered by underwear. Treated and untreated sites were subsequently measured under Wood's ultraviolet radiation. RESULTS: Thirty-one per cent of the skin surface that was a target for application did not show any fluorescence and thus was assumed to have been untreated. Typical neglected sites included the central back, the upper breast, the axilla with surrounding skin, the legs and the feet, particularly the sole. The posterior aspect of both trunk and extremities, not easily inspected, was more often neglected. In the treated sites the fluorescence was typically uneven. CONCLUSIONS: Qualified and motivated persons with no obvious physical limitations practised imperfect self-application of a test cream mimicking a therapeutic cream product. As much as 31% of the skin surface was neglected. Sites especially prone to nonapplication were identified. This might imply that dermatological patients on long-term self-treatment may practise local application very poorly, a problem of major therapeutic and economic importance. A fluorescent test cream can be used for research, and as an educational tool in the training of dermatological patients on how to apply local treatment.

Allergy patch test reading from photographic images: disagreement on ICDRG grading but agreement on simplified tripartite reading.

BACKGROUND/AIMS: The International Contact Dermatitis Research Group (ICDRG) system for clinical scoring of allergic patch test reactions is well established in clinical dermatology for detailed scoring of allergic reactions. The degree of redness and the presence of swelling, papules, vesicles and bullae are assessed based on visual examination and palpation of reactions. In photographic assessment used in research and tele-dermatology, the scoring is solely based on visual examination of photos. The aim of the study was to evaluate inter-expert variation in patch test reading using photographic images, with ICDRG reading as a reference. MATERIAL AND METHODS: Five experienced senior dermatologists each scored 55 positive patch test reactions from 16 slides in an office environment. The slides showed pictures of patch tests with different allergens. The scoring system by ICDRG with six categories for scoring was used. RESULTS: The five dermatologists performed the scoring very differently. When the scoring system was simplified to a tripartite scoring system, the scoring was performed almost similarly by the five clinicians. CONCLUSION: Based on the present results, it is proposed that the number of scoring categories should be minimized and simplified into negative (including doubtful) reactions, positive reactions and irritant reactions. Such simplified tripartite reading is proposed for research purposes and for tele-dermatology, when scoring is based on photographic images.

The hypomagnesic rat model: dermatitis-prone hairless rats with mild magnesium depletion fed a diet low in lipids did not develop pruritic dermatitis.

BACKGROUND/PURPOSE: In the hypomagnesic dermatosis of rats, low-dietary magnesium leads to lowered serum Mg2+, universal dermatitis and scratching. The model is postulated to work better if the diet also has a low content of lipids. Pruritus is seen in patients suffering from anorexia nervosa and resolves on weight restoration. Lipid depletion of the diet and/or lowered body weight may therefore be important in developing pruritus. The purpose of the present study was to investigate whether a diet low in lipids can induce pruritus in dermatitis prone rats because of mild magnesium depletion thereby focusing on the role of lipids in the hypomagnesic dermatosis rat model. METHODS: Fourteen male hairless rats, 3 weeks of age, were fed a diet deficient in lipids and with a lower content of magnesium for a 4-week period and compared with 11 controls fed a normal diet. The skin was inspected daily and transepidermal water loss (TEWL), serum Mg2+ and scratching activity were measured. At the end, skin biopsies were taken from the flank and ears. RESULTS: Serum Mg2+ was significantly lowered in the diet group (P<0.001) but the rats developed no dermatitis or increased TEWL compared with 11 rats in a control group. Biopsies were normal with no sign of inflammation. Rats in the diet group had inferior weight gain, were less active and spent more time asleep than control rats (P<0.01). Furthermore, scratching activity monitored in the last week of the study as the number of scratch-sequences per awake minute was reduced in the diet group (P<0.001). CONCLUSION: The lipid-deficient diet was not able to induce pruritic dermatitis despite the fact that the rats were dermatitis prone because of mild magnesium depletion. It is not confirmed that dietary lipid depletion plays any significant role in the hypomagnesic dermatitis rat model. The dermatitis and the model appear to be strictly dependent on efficient magnesium depletion manufactured with very low magnesium levels.

Suppression of spontaneous scratching in hairless rats by sedatives but not by antipruritics.

Experimental scratching in animals has hitherto been provoked by substances injected into the skin or central nervous system. We aimed to investigate if spontaneous scratching in the rat can be reduced by sedatives and antipruritics, and to assess if spontaneous scratching is elicited from the skin or the central nervous system. It may also be a complex behaviour related to the rat species, different from clinical itch. Eight male hairless rats were studied for 6 weeks. The animals were recorded on videotape in the middle of the day and at night, and the scratching activity was counted. The following substances were tested sequentially: midazolam, mepyramine, a eutectic mixture of lignocaine and prilocaine (EMLA, betamethasone dipropionate and a vehicle. On days 1-3 of each sequence, the test material was applied to a 42-cm(2) area on the rostral part of the back. Subsequent treatment of the whole body was made on day 4. Midazolam was injected intraperitoneally from day 1 to day 4. After 4 days of treatment, there was a wash-out phase of 3 days until the next sequence. We found a positive correlation between minutes awake and number of scratch episodes. Spontaneous scratching was lower after mepyramine on day 4 (p = 0.046) and after midazolam injections on days 1-3 (p = 0.009) and day 4 (p = 0.003). The local anaesthetic, EMLA, did not significantly influence spontaneous scratching. In conclusion, only the drugs with sedative properties suppressed spontaneous scratching, which is probably a cerebral phenomenon or otherwise explained general behaviour, rather than a reaction to skin stimuli. Thus, for testing of topically applied antipruritics, spontaneous scratching cannot be used as an animal model. Furthermore, evaluation of provocative scratching should eliminate/exclude spontaneous scratching.