From the Department of Dermatology, Faculty of Medicine, Tohoku University, Sendai ; Director : Prof. M. It S

Transcription

1 The Tohohu Journal of Experimental Medicine, Vol. 60, Nos. 3-4, 1954 Responsiveness of Sweat Glands to Adrenaline in Skin Diseases. I Yoshio By Saito From the Department of Dermatology, Faculty of Medicine, Tohoku University, Sendai ; Director : Prof. M. It S (Received for publication, October 15, 1953) The progress in the physiology of sweating has been remarkable in recent years, but from the dermatological point of view, there are as yet many problems awaiting solution. In 1948 Prof. Wada1)2) with his co worker of Tohoku University, devised a method for visualizing the response of human sweat glands, by which he disproved the common notion that human sweat glands are unresponsive to adrenaline. By determining the minimal effective threshold concentration of adrenaline applied intra dermally, he attempted to measure the excitability of sweat glands. In the present investigation, determination of the threshold values was per formed using his method, in 971 subjects (835 patients with skin diseases, 57 patients with urogenital diseases and 79 healthy persons). Tested subjects. Patients of our Clinic treated since the year of 1950, leprosy patients in Tohoku Shinseien Leprosorium, students and nurses. Method of experiment. The extensor side of the forearm was painted with 2.4% iodine-absolute alcohol solution and dried completely. Then 0.2 cc. of adrenaline in various concentrations (10-4, 10-5, 10-6, 10-7, 10-8, 10-9, in 0.9% saline solution) was injected intradermally into the treated skin. The part was then coated with a mixture of 100 g. of fine starch powder and 100 cc. of castor oil, so that any trace of sweating would show as black spots. The measurement was undertaken 15 minutes later, or in cases when no sweating appeared at time, 30 minutes after the in jection. The minimal effective concentration of adrenaline when the sweating began to show in spots distributed evenly on the original wheal of injection was determined and the reciprocal of the value was taken to express the threshold. For control 0.9% physiological saline was used. The tests were made with the subject seated on a chair in most cases. The room temperature stood at 8 Ž-31 Ž. As the atmospheric humidity was sure to affect the sweating, a hygrometer was used to measure and register the humidity for taking it into consideration. 237

2 238 Y. Saito Results of experiment. See Table I. TABLE I Adrenaline Sweating Threshold Values in Various Dermatoses

3 Responsiveness of Sweat Glands to Adrenaline TAB L E I-Concluded *, no response to 10-4 concentration.

4 240 Y. Saito COMMENT Wada et al.l)2) reported that the value of excitability for any individual. is constant throughout the year, standing at 10-7 for adults in normal health. and tending to show the higher threshold at younger and older ages, al though the mechanism of local sweating by adrenaline and its physiological significance are not yet clear. Sonnenschein3) also reported that local sweating may be caused by adrenaline and this sweating is different from sweating by acethylcholine in following three points, the latter i) accom panies activity of the axon reflex, úa) is inhibited by atropine úb) but not by dibenamine. Haimovici4) proposed the theory of adrenergic innerva tion of sweat glands but Sonnenschein5) and others rejected the proposition. They contended that the sweat gland cells respond directly to adrenaline and that though adrenaline and acetylcholine are chemically different, it may be that the same gland cells respond to both synergistically, rather than that different cells show respective sensitivity to the two agents. There have been found few compelling reasons to support the theory of adrenergic innervation although the theory of sympathetic innervation is prevalent at present. For the mechanism of sweating caused by intradermal injection of adrenaline, I would prefer the supposition that the gland cells respond directly to adrenaline, without the interference of the sudorific nerves, as Wada et al. have maintained. The healthy control subjects in my experiment showed the threshold value of 10-7in most cases, in agreement with the results by Wada2), Ki mura6), etc. In various skin diseases, including every age classes from 8 to 70 years and considering the difference in humidity at the time of tests, the values of 10-7 and 10-1 were considered as normal, the values of 10-8, 10-9, and as hyperexcitable, the values of 10-5 and 10-4 as hypoexcitable and non-response to the concentration of 10-4 as negative. The total outcome of the test for the adrenaline sweating threshold (hereinafter designated as A. S. T.) of all the 835 subjects with skin diseases is shown in Table I. The majority had the A. S. T. value of 10-7, but the skin disease patients tend to show the higher value in comparison with the healthy controls. The same tendency was also observable in the patients with urogenital diseases. Details in various diseases are as follows: 1) Allergic diseases. In contact dermatitis patients who showed conspicuous redness and swelling as well as edema in many cases, their A. S. T. generally measured 10-1, with more hypoexcitable but less hyper excitable cases, while among the patients of eczema acutum with sporadic papules, hyperexcitable cases were somewhat more common than in the above. Hypoexcitation was remarkable among lichenous patients such as with eczema chronicum, lichen Vidal, neurodermitis disseminata and

5 Responsiveness of Sweat Glands to Adrenaline. I 241 atopic dermatitis, especially in the second and the third of the above. This fact may be accepted as natural when we remember that Kochs7) has pointed out the disturbance of sweating secretion influenced by the vegetative nervous disharmony among atopic dermatitis patients. In pruritus cutaneus, on the other hand, the A. S. T. showed results not much different from those obtained with the healthy controls, and it may be noted that this disease with strong itching, but no eruption, showed dif ferent A. S. T. from the eruptive diseases. While among urticaria patients rather many hypoexcitable cases were found, there were few of them among patients of erythema exsudativum multiforme and erythematodes, only one case of negative response being observed in erythematodes acutus. But among erythema annulare and erythema nodosum more hypoexcitable cases were noted, while one out of two erythema annulare centrifugum Darier showed 10-8 and the other Thus in the patients with various exsudative erythemas a difference in excitability was observed in accordance with the difference in the type of the clinical manifestations. While in the purpura there are found equal cases of high and low A. S. T., the one case of erythema annularis teleangiectodes Majocchi had the A. S. T. of and that of Schamberg's disease By toxicodermia, there were many high A. S. T. cases, but many causative factors make it difficult to discuss these results in same category. There was not a case of A. S. T. above 10-5 among the keratodermia tylodes palmaris progressive patients, all being in the hyperexcitable category, and it may be recalled with interest from the view point of pathogenetic mechanism that this disease is localized on the palms where sweating is most pronounced and that Kitamura8) has reported on the disturbance of sweating prevalent among the patients of the disease. In summary, it may be noted that the A. S. T. value in allergic patients show different tendencies according to the type of clinical manifestation of the disease. 2) Seborrheic Diseases. Eczema seborrhoicum in adult and acne rosacea patients showed hyperexcitability in most cases. These results coincide with the prevalence of primary sympatheticotony of type S. by Abe9) of our Clinic by means of adrenaline test with blood pressure as index. By acne vulgaris, however, little difference from normal health could be found. 3) Hyperidrosic Diseases. Among the osmidrosis axillae and hyper idrosis localis patients hypoexcitable cases prevailed, giving suggestion on the pathogeny of such hyperidrosic diseases. 4) Keratotic diseases. In ichthyosis vulgaris, no difinite tendency of deviation was observable, but in keratosis palmoplantaris hereditaria no case had higher A. S. T. than This fact does not surprise us when we recall that Prof. Ito10) of our Clinic has pointed out the clearly observa-

6 242 Y. Saito ble physiogenetic difference between the two diseases. Two cases of pityriasis rubra pilaris showed a conspicuous rise of A. S. T. Therefore, it is interesting that good results were obtained by Katabira11) et al. of our Clinic in treating it with benzylimidazolin. Psoriasis showed both hyper and hypoexcitability. In erythrodermia were many cases of high A. S. T. observed. 5) Bullous diseases. The epidermolysis bullosa hereditaria and dermatitis herpetiformis Duhring that are associated with disorder in pituitary adrenal system, and herpes zoster cases showed no hyperexcita bility, all showing conspicuous tendency of hypoexcitability. 6) Pigmentary diseases. Most of vitiligo and leucodermie post lesionnelle showed no hyperexcitability and all cases of nevus systematicus depigmentosus showed normal value. In nevus pigmentosus and nevus fuscocaeruleus ophthalmomaxillaris Ota, the prevailing tendency was for hypoexcitability. No case in the chloasma showed normal A. S. T. 7) Depilated diseases. Most of the alopecia areata cases had A. S. T. of 10-7, mingled with a comparatively large number of low A. S. T. cases. In other cases of alopecia the situation was similar, in parallel with the results of adrenaline test with blood pressure index by Abe9) of our Clinic and with Tsukada's12) observation of a tendency to vegetative nervous dysharmony in alopecia areata. 8) Perniosis. Upon classifying the cases into those of the type of erythema exsudativum multiforme and those of the type of cyanosis-swell ing, the former included more numerous cases of hyperexcitability than the latter. It may be recalled that Fujisawa14) of our Clinic reported that the former showed nearly normal capillary resistence values and the latter high values. The three cases of acrocyanosis showed hypoexcitability without exception, showing a difference existing between this disease and common perniosis. 9) Congenital diseases. The great majority of the cases had the A. S. T. of 10-5, and little difference in the sweating excitability was ob served by the patients from that of the normal. 10) Leprosy. As most of the cases complained of sensory anesthesia, I had to select non-anesthetic spots in many cases outside the extensor side of the forearm for the test. Many of the cases failed to respond at the dilution of 10-4, showing an extreme degree of hypoexcitability. The more advanced the clinical manifestation in leprosy, the more numerous became the cases of negative response. Thus it was easy to understand that in not only the anesthetic areas but also.in the non-anesthetic areas of the skin there can be found degenerated sweating function. 11) Tuberculous diseases. Kimura and. Otsuji15) reported that.tuberculosis pulmonalis cases showed a tendency to higher A. S. T. in

7 Responsiveness of Sweat Glands to Adrenaline. I 243 comparison with healthy persons, a tendency especially remarkable in exudative type cases, while the cases with productive symptoms showed rather a contrary tendency to hyperexcitability. By the tuberculosis cutis patients, there was no such tendency as in tuberculosis pulmonalis cases, and little difference was found among the various disease types. However, the control patients of tuberculosis renalis showed A. S. T. of 10-6 in the majority of the cases, not one showing hyperexcitability, while many of the epididymitis tuberculosa patients were found to be hyperexcitable. 12) Infectious diseases. Among the folliculitis superficialis, tri chophytiae, verrucae and syphilis U latens patients the A. S. T. of 10-7 was prevalent, and the situation was little different from that among the healthy. However, among furuncle, erysipelas and pyodermia vegetans, pyaemid cases, the more advanced the clinical manifestations, the more numerous hypoexcitable cases were found. 13) In malignant skin tumor patients comparatively more cases of hypoexcitability were observed than in benign tumors. 14) No hyperexcitable case was found among sclerodermia, myxoe dema circumscripta tuberosa and pellagra patients. Not one case of hypoexcitability among pityriasis rosea Gibert cases was found. CONCLUSION In 835 cases of dermatoses, the examinations of excitability of sweat glands were performed by means of adrenaline injection and following results were obtained. 1. In allergic diseases, the excitability showed different tendencies according to the skin manifestations. 2. In seborrheic diseases and depilated diseases the excitability tends to rise in coincidence with adrenaline test with blood pressure as index. 3. In bullous diseases it falls on the contrary. 4. The leprous patients showed an extreme decrease in the excitabil ity especially in severe cases. 5. In infectious diseases the more advanced the clinical manifestation the more numerous hypoexcitable cases were found. References 1) Wada & Takagaki, Tohoku J. Exp. Med., 1948, 49, ) Wada, Science, 1950, 111, 376 ; Internat. J. Leprosy, 1951, 18, 334.3) Sonnenschein, Proc. Soc. Exp. Biol. & Med., 1949, 71, ) Haimovici, Proc. Soc. Exp. Biol., 1948, 68, 40. 5) Sonnenschein, & Kobrin, J. Appl. Physiol., 1950, 3, ) Kimura, Tohoku Igaku Zassi (Jap.), 1949, 40, 33. 7) Kochs, Archiv fur Dermat. u. Syph., 1951, 193, 365.

8 244 Y. Saito 8) Kitamura, Hifuka Seibyoka Zasshi (Jap. J. Dermat. & Vener.), 1929, 29, ) Abe, Read before the 118th Meeting of the Tohoku Dermatological Society, ) Ito, Tohoku J. Exp. Med., 1950, 53, ) Katabira et al, Hifu to Hitsunyo (Dermat. & Urol.), 1953, 15, ) Tsukada, Hifuka Seibyoka Sasshi (Jap. J. Dermat. & Vener.), 1937, 41, ) Kimura, Kekkaku (Tuberculosis), 1951, 26, ) Fujisawa, Hifuka Seibyoka Zasshi (Jap. J. Dermat. & Vener.), 1953, 63, ) Otsuji, Kosankinbyo Kenkyu-Zasshi (Jap.), 1950, 6, 176.