Itch and pain share numerous mechanistic similarities. Patients with chronic itch conditions (for instance atopic dermatitis or neuropathic itch) often experience symptoms such as mechanical ...alloknesis and hyperknesis. These dysesthesias are analogous to the pain-associated phenomena allodynia and hyperalgesia, which are often observed, for example, in neuropathic pain conditions. Mechanical itch dysesthesias represent abnormal sensory states (caused by neuroplastic changes), wherein considerable itch is evoked, for instance by light cutaneous stimuli such as from clothing (alloknesis), or where increased itch is perceived in response to normally itch-evoking stimuli (hyperknesis). These itch sensitization phenomena have been explored in experimental human studies, observed in chronic itch patients, and in animal models of itch. Limited attention has been paid to these sensory phenomena in clinical studies, and it is unknown how they respond to antipruritics. Psychophysical quantitative sensory testing can quantify the presence, severity, and spatial extent of itch dysesthesias in chronic itch patients, providing a proxy measurement of itch sensitization. This review outlines current assessment techniques, knowledge on the mechanisms of mechanical alloknesis and hyperknesis, and presents the diverse results derived from clinical studies exploring the presence of itch dysesthesias in chronic itch patients. A key role of quantitative sensory testing and neuronal sensitization in patients with chronic pain is accepted and used in clinical assessments. However, the precise mechanisms and potential clinical implications of itch sensitization in chronic itch patients remain to be evaluated.
Subpopulations of primary nociceptors (C- and Aδ-fibers), express the TRPV1 receptor for heat and capsaicin. During cutaneous inflammation, these afferents may become sensitized, leading to primary ...hyperalgesia. It is known that TRPV1
+
nociceptors are involved in heat hyperalgesia; however, their involvement in mechanical hyperalgesia is unclear. This study explored the contribution of capsaicin-sensitive nociceptors in the development of mechanical and heat hyperalgesia in humans following ultraviolet-B (UVB) irradiation. Skin areas in 18 healthy volunteers were randomized to treatment with 8% capsaicin/vehicle patches for 24 h. After patches removal, one capsaicin-treated area and one vehicle area were irradiated with 2xMED (minimal erythema dose) of UVB. 1, 3 and 7 days post-UVB exposure, tests were performed to evaluate the development of UVB-induced cutaneous hyperalgesia: thermal detection and pain thresholds, pain sensitivity to supra-threshold heat stimuli, mechanical pain threshold and sensitivity, touch pleasantness, trans-epidermal water loss (TEWL), inflammatory response, pigmentation and micro-vascular reactivity. Capsaicin pre-treatment, in the UVB-irradiated area (Capsaicin + UVB area), increased heat pain thresholds (
P
< 0.05), and decreased supra-threshold heat pain sensitivity (
P
< 0.05) 1, 3 and 7 days post-UVB irradiation, while mechanical hyperalgesia resulted unchanged (
P
> 0.2). No effects of capsaicin were reported on touch pleasantness (
P
= 1), TEWL (
P
= 0.31), inflammatory response and pigmentation (
P
> 0.3) or micro-vascular reactivity (
P
> 0.8) in response to the UVB irradiation. 8% capsaicin ablation predominantly defunctionalizes TRPV1
+
-expressing cutaneous nociceptors responsible for heat pain transduction, suggesting that sensitization of these fibers is required for development of heat hyperalgesia following cutaneous UVB-induced inflammation but they are likely only partially necessary for the establishment of robust primary mechanical hyperalgesia.
The global application of the skin prick test (SPT) is attributed to the low costs, easy execution, and invivo approach. Still, the healthcare professionals’ technique and the lancet shape may ...challenge the standardization of the method. Thus, we investigated the influence of the shape of the lancet and the applied weight on the wheal size of SPT. Two allergic and one non-allergic individual were tested with allergens (Dermatophagoides pteronyssinus and Phleum pratense) and histamine solution (positive control), respectively. Horizontally (HS) and diagonally (DS) shouldered lancets with the same tip length (1 mm) were tested under two different conditions: either 60 g or 120 g weight pressure. The wheal size induced by the 4 different combinations was measured. The higher-weight device (120 g) induced a significantly larger and less variable wheal response with the tested allergens and histamine. However, the shape of the lancet affected the wheal size more than the applied weight. The least variable response was measured to histamine for the horizontal-shouldered lancet combined with the higher weight, whereas the same lancet with the lower weight resulted in a significant number of false negative results.
To the Editor Aluminium contact allergy is mainly seen in children with itching vaccination granulomas following immunization with aluminium-adsorbed vaccines, but may also occur in adults following ...allergen-specific subcutaneous immunotherapy, SCIT, as these vaccines too are aluminium-adsorbed. 1 Traditional method of determining sensitization to aluminium is patch testing, an in vivo skin test considered the gold standard for detecting contact allergy. 2 Still, it has the disadvantage of only detecting the allergic response in the skin, and not systemic reactions. Both the patch test and the LPT test may have low sensitivity for detecting aluminium contact allergy in adults. 4 Other possible explanations for the negative test results are that the T cell-dependent inflammation in the granulomas is not caused by aluminium, as granulomas have various histopathological findings, 7 or perhaps the aluminium allergy has diminished due to the time interval between induction/elicitation and testing as reported in other studies. 8 Moreover, the lack of specific proliferation in the LTT system could also be due to the formulation of aluminium or lagging formation of aluminium-protein hapten complexes in vitro. Since oral intake of aluminium may generate a systemic response with cutaneous eruptions in children with vaccination granulomas, 9 a study on the lymphocyte reactivity characterizing the possibility of systemic reactions in these children would be of great interest. CONFLICT OF INTEREST STATEMENT None.
Little is known about endogenous descending control of itch. In chronic pain, descending pain inhibition is reduced as signified by lowered conditioned pain modulation. There are indications that ...patients with chronic itch may also exhibit reduced endogenous descending inhibition of itch and pain. This study aimed to investigate whether and the extent to which itch can be modulated by conditioning itch and pain stimuli. Twenty-six healthy volunteers participated. The study consisted of 5 conditions designed to systematically assess endogenous modulation of itch or pain: 1) itch-induced modulation of contralateral itch, 2) pain-induced modulation of contralateral itch, 3) pain-induced modulation of ipsilateral itch, 4) pain-induced modulation of contralateral pain, and 5) itch-induced modulation of contralateral pain. Conditioning stimuli were cold pressor-induced pain and histamine-evoked itch, whereas the test stimuli were electrical stimulation paradigms designed to evoke itch or pain. Pain was significantly reduced (conditioned pain modulation-effect) by the conditioning pain stimulus (P < .001), but not by the conditioning itch stimulus (negative control condition). Itch was significantly reduced (conditioned itch modulation-effect) by contra- as well as ipsilateral applied conditioning pain (both P < .001), whereas conditioning itch stimulation only marginally reduced itch. Endogenous descending itch inhibition through mechanisms that are independent of segmental gating can be readily evoked by heterotopic conditioning pain stimulation. However, robust descending inhibition of itch cannot be evoked with conditioning itch stimulation.
The study showed a hierarchical prioritization favoring pain-induced central descending modulation of itch as well as pain in humans. Future studies addressing potential aberrations in pain-evoked descending modulation of itch in chronic itch patients are warranted.
Skin prick test (SPT) is a common test for diagnosing immunoglobulin E-mediated allergies. In clinical routine, technicalities, human errors or patient-related biases, occasionally results in ...suboptimal diagnosis of sensitization.
Although not previously assessed qualitatively, lancet weight is hypothesized to be important when performing SPT to minimize the frequency of false positives, false negatives, and unwanted discomfort.
Accurate weight-controlled SPT was performed on the volar forearms and backs of 20 healthy subjects. Four predetermined lancet weights were applied (25 g, 85 g, 135 g and 265 g) using two positive control histamine solutions (1 mg/mL and 10 mg/mL) and one negative control (saline). A total of 400 SPTs were conducted. The outcome parameters were: wheal size, neurogenic inflammation (measured by superficial blood perfusion), frequency of bleeding, and the lancet provoked pain response.
The mean wheal diameter increased significantly as higher weights were applied to the SPT lancet, e.g. from 3.2 ± 0.28 mm at 25 g to 5.4 ± 1.7 mm at 265 g (p<0.01). Similarly, the frequency of bleeding, the provoked pain, and the neurogenic inflammatory response increased significantly. At 265 g saline evoked two wheal responses (/160 pricks) below 3 mm.
The applied weight of the lancet during the SPT-procedure is an important factor. Higher lancet weights precipitate significantly larger wheal reactions with potential diagnostic implications. This warrants additional research of the optimal lancet weight in relation to SPT-guidelines to improve the specificity and sensitivity of the procedure.
Data from real-world use of new systemic treatments in atopic dermatitis (AD) is important for assessing safety and efficacy. The aim of this study is to describe the baseline characteristics of ...adult patients with moderate-to-severe AD enrolled in the Danish nationwide Severe and ChRonic Atopic dermatitis Treatment CoHort (SCRATCH) database, between October 2017 and August 2021. A total of 282 adult patients were included. Most (62%) were men, the median age at baseline was 43 years (interquartile range (IQR) 29–54 years), and median age at onset of AD was 1 year (IQR 0–6 years). The median Eczema Area and Severity Index at treatment initiation was 19.1 (IQR 11.9–25.7); median Patient Oriented Eczema Measure 21.0 (IQR 16.0–25.0); median Dermatology Life Quality Index 13.0 (IQR 7.0–19.0); and median itch and sleep numerical rating scale scores 8.0 (IQR 6.0–9.0) and 6.0 (IQR 4.0–8.0). Differences were found between the sexes. This registry will provide a source for future efficacy and safety studies.
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