Endocrine and dermatological concomitants of mental stress.

The role of psychosocial stress in the etiology and clinical course of psoriasis and atopic dermatitis still remains to be elucidated. In this study, we assessed neuroendocrine, dermatological, and cognitive responses in healthy subjects and in subjects suffering from psoriasis and atopic dermatitis, respectively. Perceived stress increased the most in psoriatics during the stressor exposure but tended to return faster to baseline in this group than was found for atopics and healthy controls. Growth hormone secretion was attenuated during stress in patients with skin disorders. Overall, neuroendocrine reactivity was similar in the three groups. Dermal flare reactivity was enhanced in healthy controls but perceived itch enhanced in atopics in response to stress. Stress per se was not an important discriminator between groups. Coping style and other cognitive factors turned out to be of significant importance to predict skin reactivity rather than a specific skin disease. The study suggests that psychosocial stress affects the skin reactivity and that cognitive factors modulate such effects. However, a specific skin condition explains only a fraction of the overall variance in skin reactivity to specific stressors.

Pain development and consumption of analgesics after oral surgery in relation to personality characteristics.

In the present study a survey has been performed of the pain development and analgesic intake in 100 patients following elective oral surgery of impacted third molars in relation to preoperative assessment of personality characteristics. Our results show that no sex differences existed preoperatively concerning personality characteristics, concerning postoperative pain development or analgesic consumption. Fourteen patients reported no pain at all and 40 patients did not use any analgesics in the postoperative period. We also found a good correlation between total sum of pain scores and analgesic intake. Patients undergoing surgery in the morning reported a lower total sum of pain scores, reported pain at fewer occasions and tended to require less analgesics than patients being subjected to surgery in the afternoon. The patients who reported a total sum of pain scores in the upper percentile during the postoperative period rated their general health worse, as rated on the General Health (GH) questionnaire, and used more analgesics than did patients in the lower percentile. Also, patients not using any analgesics reported less symptoms of distress according to the GH scale as compared to patients using analgesics. In general, however, less than 10% of the variance in postoperative pain and consumption of analgesics could be explained by the preoperative factors studied.

Influence of grenz rays and psychological factors on experimental pruritus induced by histamine and compound 48/80.

The interaction between grenz rays and experimentally induced pruritus was evaluated in 14 healthy subjects. Grenz rays were administered once weekly for 4 weeks on restricted areas of the upper arms. Pruritus was evoked by intradermal injection of histamine and the histamine liberator compound 48/80. The results were compared with unconditioned values and with those obtained following a placebo treatment procedure. The influence of psychosocial and psychosomatic factors was also evaluated. Grenz-ray therapy reduced itch but not flare responses. The influence of grenz rays was, however, not statistically different from that observed after placebo treatment. Psychosocial and psychosomatic factors were good predictors of individual skin responsiveness. The results indicate that grenz rays do not interfere with experimental histamine-induced pruritus more than placebo and emphasize the importance of knowing individual characteristics and coping strategies.

Psoriatic arthritis treated with oral colchicine.

We investigated the use of colchicine in psoriatic arthritis to determine if we could confirm the good results obtained in an earlier, uncontrolled study. Twelve of 15 patients with psoriatic skin lesions and arthritis completed a 16-week placebo controlled double blind crossover study. A significant improvement was noted in grip strength, Ritchie's index, joint size, joint pain and overall therapeutic assessment. Psoriatic skin lesions were not improved by colchicine. The few side effects observed were related to gastrointestinal intolerance, which were usually controlled by temporarily reducing the dose of the drug. Our results indicate that 1.5 mg colchicine daily is an effective treatment for psoriatic arthritis.

Influence of naloxone on relief of acute oro-facial pain by transcutaneous electrical nerve stimulation (TENS) or vibration.

Twenty-eight patients suffering acute pain following operative removal of impacted third molars took part in the present study. In 20 patients who reported pain reduction exceeding 25% of the initial pain intensity during vibratory stimulation (100 Hz) or TENS (2 or 100 Hz), only 1 patient (given 2 Hz TENS) reported pain increase after injection of 0.8 mg naloxone (i.v.). In 8 patients, not treated with afferent stimulation, 2 experienced increase in pain intensity after naloxone injection. The results show that pain relief using TENS or vibration is not influenced by naloxone.

Psychological predictors of neuroendocrine responses to mental stress.

Neuroendocrine reactions to a number of stressors have been subject to numerous studies. The sympathetic adreno-medullary system's sensitivity to mental as well as physical stressors is well documented, and increased attention has recently been focused on neuropeptides and steroid hormones in relationship to stress. There is, however, a scarcity of studies examining the relationship between psychosocial and neuroendocrine factors during stress and assessing possible interactions by means of multivariate models. The present study confirms that the sympathetic adreno-medullary system is sensitive to mental stressors. The study also shows that neuroendocrine and physiological stressor reactions vary greatly from one individual to another. Thus, certain psychosocial and personality factors appear to have strong predictive values with regard to stressor-induced neurophysiological reactions. Further studies are certainly needed to enhance our understanding of individual differences in neurophysiological reactions to apparently identical stressors. Such investigations may increase our understanding of why certain people develop illnesses during prolonged strain while others do not.

Inhibition of complement dependent experimental inflammation in human skin by different heparin fractions.

The anticoagulant activity of heparin is dependent on its affinity for antithrombin III (AT III) and on its molecular weight. In contrast, heparin fractions differing in these respects are equally effective inhibitors of the human complement system in vitro. In this study we designed and evaluated a model to investigate the effects of different heparin fractions on a complement dependent inflammation. Locally administered heparin, in a dose-dependent manner, inhibited the flare, itch and wheal responses induced by intradermal injection of heat-aggregated human IgG (HAGG). These reactions were also inhibited by the antihistamine mepyramine, favouring the view that HAGG activates complement and that the observed inflammatory response is mediated by anaphylatoxin liberation of histamine. Similar cutaneous reactions induced by trypsin, which can generate C3a and C5a by proteolysis of C3 and C5, the histamine liberator compound 48/80 or histamine were inhibited by mepyramine but not by heparin. Thus it is strongly suggested that heparin inhibits the HAGG induced reactions by modulating the early pre-C3 steps of complement activation. On a weight basis heparin fractions differing in AT III-affinity or in average molecular weight (5,000 and 16,000 D) were equally potent modulators of the HAGG-induced inflammation. We conclude that heparin can inhibit an apparently complement-dependent inflammation irrespective of its AT III-affinity or of its size, and suggest that a heparin with low anticoagulant activity could be of value as a modulator of inflammation and should be useful in investigating the consequences of complement inhibition in inflammation.

The influence of extrasegmental mechanical vibratory stimulation and transcutaneous electrical nerve stimulation on histamine-induced itch.

The effect of peripheral conditioning stimulation on experimentally induced pruritus was studied in 12 healthy volunteers. Itch was induced by intradermal injections of histamine on the upper arms. Vibration at 100 Hz and transcutaneous electrical nerve stimulation (TENS) at 2 and 100 Hz were applied extrasegmentally (dorsal aspect of the lower part of the leg, ipsilateral to the injected arm) for a period of 5 min following induction of itch. The effect of a 5 and 30 min stimulation period before itch elicitation was also studied as well as the influence of placebo stimulation. No significant effects were obtained with 100 Hz vibration and 100 Hz TENS, and none with placebo stimulation, whereas significant itch reduction was seen using 2 Hz TENS. The local skin flare response following histamine injections was not altered following conditioning stimulation of any type.

Stress and psoriasis: psychoendocrine and metabolic reactions in psoriatic patients during standardized stressor exposure.

Psychoendocrine and metabolic reactions during standardized stressor exposure (color-word conflict test and forced mental arithmetics) were studied in ten psoriatic and ten matched healthy subjects. During resting conditions, the groups were similar with regard to psychologic and biochemical variables, except for plasma glucose, which was slightly elevated in the psoriatic group. During stressor exposure, the psoriatic group reported significantly higher strain levels. Blood pressure, pulse rate, plasma glucose, and urinary adrenaline excretion increased in both groups during exposure, with more pronounced increases of the latter two in the psoriatic group. Serum cortisol, prolactin, progesterone and urinary cortisol decreased in both groups during stressor exposure. The decrease in serum cortisol was more pronounced in the psoriatic group. Thus, no psychoendocrine differences were found between the healthy and psoriatic subjects during resting conditions. In contrast, during a standardized stressor exposure, psoriatic subjects reported higher levels of strain, which was accompanied by higher levels of urinary adrenaline and lower levels of plasma cortisol. These results fit the hypothesis that psoriatic patients perceive certain challenging situations as more stressful than do nonpsoriatic controls, and react accordingly in their differential psychoendocrine reaction pattern. Possible pathophysiologic implications of the different pituitary-adrenocortical and sympatho-adrenomedullary reactions in psoriatics submitted to stressor exposure are discussed.

Psychological predictors of pruritus during mental stress.

Experimentally-induced mental stress activates the psychoneuroendocrine systems. The cutaneous (itch and flare) responses of human skin to intradermal injection of histamine remain despite this unaltered. Major interindividual differences, however, exist in both neurophysiological reactions and cutaneous reactivity. The individual skin responses are interrelated to the urinary adrenaline response pattern. Psychosomatic status and psychosocial factors were in this study observed to be good predictors of skin responsiveness assessed by a multivariate model. We suggest that future studies on stress and pruritus should take these aspects into consideration. Knowledge of individual characteristics and coping strategies might help us understand why some patients suffer form itching in response to stress while others do not.

Experimental pruritus evoked by platelet activating factor (PAF-acether) in human skin.

Cutaneous pruritic effects of synthetic platelet activating factor (PAF-acether) and, in particular, its interference with dermal mast cells, were studied in human volunteers. Intradermal injections of 10-100 ng produced dose-dependent flare and itching responses. The cutaneous reactions were inhibited by local administration of the H1 antihistamine mepyramin. The cutaneous responses were also markedly reduced in histamine-depleted skin. These findings indicate that the cutaneous responses produced by PAF-acether were mediated via an indirect and mainly histamine-dependent mechanism.

Pruritus during standardized mental stress. Relationship to psychoneuroendocrine and metabolic parameters.

The influence of experimentally-induced emotional stress on pruritic response of human skin was studied in healthy subjects. Experimental activation of the psychoneuroendocrine system was produced by standardized stressors, i.e. a colour-word-conflict test (Stroop-test) and a subsequent mental arithmetic problem. Pruritus was elicited by intradermal injection of histamine. Results obtained were compared with reported feelings of stress, and stress-induced physiological and biochemical changes. Reported stress levels were evaluated by a visual analogue scale. The physiological and biochemical observations included pulse rate, blood pressure, endocrine and metabolic parameters. The experimental model produced adequate psychoneuroendocrine stress reactions. Cutaneous responses to histamine remained despite this unaltered. The cutaneous responses were unrelated to reported stress levels as well as to physiological and biochemical variables prior to stressor exposure. The individual cutaneous reactions to stressor exposure were related to the adrenaline response pattern. Degree of control, ability to predict, and time limitation of the experimental situation may be important factors influencing the experimental outcome.

The influence of mechanical vibratory stimulation and transcutaneous electrical nerve stimulation on experimental pruritus induced by histamine.

The effect of conditioning mechanical vibratory stimulation and transcutaneous electrical nerve stimulation (TENS) on experimentally induced pruritus was studied on 12 healthy subjects. Pruritus was provoked by intradermal injection of histamine on the upper arm. Vibration at 10, 100 and 200 Hz and TENS at 2 and 100 Hz were applied (i) over or (ii) proximal (in the same dermatome) to the pruritic area for a period of 5 min following itch elicitation. In addition the influence of a 5 min pre-stimulatory regimen of the injection area was investigated (iii). The results obtained were compared with unconditioned values and with those obtained following a placebo conditioning procedure (i, ii). It was found that vibratory as well as electrical stimulation, for all frequencies used, reduced subjective itch intensity. Vibration at 100 Hz was the most effective mode of stimulation especially when applied directly to the pruritic area. Conditioning with 100 Hz vibration was also the most effective mode for reducing the duration of the itch response as well as the total experience of pruritus (estimated as a total itch index). Induction time to partial and maximal itch alleviation was shortest for 100 Hz vibration. The results indicate that treatment of pruritic conditions with conditioning stimulation, especially vibration, may be of therapeutic interest.

The influence of the opiate antagonist naloxone on experimental pruritus.

The antipruritic effect of naloxone hydrochloride was evaluated in a double-blind, cross-over design. Systemic pretreatment with the opiate antagonist did not interfere with the cutaneous itch and flare responses evoked by morphine or histamine, nor did it inhibit the morphine-produced potentiation of the histamine-elicited skin reactions.

Complications in the intralesional injection of triamcinolone acetonide by jet injector (Dermojet).

Two patients with lichenified eczematous lesions on the dorsal aspect of the hands were treated intralesionally with triamcinolone acetonide injected with an air-powered high-pressure device, Dermojet. The therapy was complicated by tendon rupture in one patient and by the development of a subcutaneous nodule, which was suspected to be a foreign body granulomatous reaction, in the other patient.

Photosensitivity induced by piroxicam.

A woman with rheumatoid arthritis developed an erythematous-bullous eruption on light-irradiated areas following sun exposure. Treatment with piroxicam, had been initiated 14 days earlier. The clinical picture, the relationship in time to the drug administration and a positive photopatch test gave reason to suspect piroxicam-induced photosensibility. Piroxicam (Felden) is a new non-steroid anti-inflammatory agent which was registered in Sweden in 1981. Various adverse skin reactions have been described. Thus, there has been one case of Lyell's syndrome with a fatal outcome (7), two case reports of erythema multiforme-like reactions (1, 3) and two reports of patients with erythemato-papulous and also bullous eruptions restricted to light-exposed skin areas (3).

Influence of ultraviolet light on itch and flare reactions in human skin induced by histamine and the histamine liberator compound 48/80.

The itch and flare responses induced by intradermal injection of histamine and the histamine liberator compound 48/80 were studied in healthy volunteers before and after exposure to UVB, UVA or PUVA administered 2-3 times weekly for 4 weeks. All three modalities were found to inhibit the responses induced by compound 48/80. The degree of tanning was most pronounced after PUVA and weakest after UVB, without any correlation between tanning and inhibition of itch. In contrast, when induced by histamine, the responses were not inhibited to the same extent, pronounced and significant inhibition being observed only for itching in subjects exposed to UVB. It is concluded that UVB, UVA and PUVA all might be of benefit in treating pruritic states if histamine release is involved and that UVB might have an additional effect by inducing hyposensitivity to itching stimuli.

Histamine release from rat peritoneal mast cells exposed to ultraviolet light.

After irradiation with ultraviolet light, rat peritoneal mast cells incubated with the histamine liberator compound 48/80 were found to have reduced capacity to release histamine. The action spectrum for histamine release inhibition seemed to be in the wavelength region of UVB. UV-light per se did not induce histamine liberation other than for dosages greater than or equal to 1.45 J/cm2. No such release was observed with the doses of UVA studied (3.4-20.5 J/cm2). The metabolic inhibitor 2.4-dinitrophenol (DNP), which almost completely inhibited compound 48/80-elicited histamine release, did not influence the UV-induced histamine release, indicating that the latter was not a secretory process but due to cytotoxic leakage of histamine from the cells. These results suggest that inhibition of histamine-releasing capacity or reduction of skin histamine due to photolysis of mast cells may explain the beneficial effect of UV in pruritic disorders where histamine release from mast cells is involved.