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Cutaneous Sodium and Potassium Determined by Reverse Iontophoresis*
CUTANEOUS SODIUM AND POTASSIUM DETERMINED BY REVERSE IONTOPHORESIS* B. F. BENJAMIN, D.M.D., PH.D. AND THEODORE CORNBLEET, M.D., PsD.
For a long time now observers have been pointing out the possibffity sodium
and potassium ions in the skin may be significant in some dermatoses, but progress was hampered by the difficulty of electrolyte determinations. Investigators usually use blood analyses to gain an insight, but blood electrolytes do not necessarily parallel those in the skin. Eichelberger, Eisele, and Wetzler (1) did much work analyzing skin slices for electrolytes, but their method is obviously not suitable for routine clinical determinations. The same restriction applies to the use of radioactive isotopes. In this paper we are presenting another method of determining skin electrolytes and changes of electrolytes under various pathological conditions. Urbach (2) showed a long time ago that the skin stores electrolytes. Zheutlin (3) analyzed human skin and epidermis and found the following values expressed as meq/kg wet weight. Whole skin: Na—96.0 and K—16.O, which gives a proportion of 6:1. Epidermis: Na—46.1 and K—80.5 with a proportion of 0.57:1. Caehn (4) likewise analyzed various skin structures. He found also more K than Na in the epidermis, while the cutis showed high Ca and low K values. In the sweat glands the K was high and in the sebaceous glands he found mainly Ca. Luithien (5) studied the effect of diet on skin electrolytes in the rabbit. On a diet of oats (acidotic) all ions decreased with a relative increase of potassium over sodium, calcium, and magnesium. A low sodium chloride diet had the same effect. A green fodder diet (alkalotic) caused an increase of calcium with a decrease mainly of potassium. He also found an increased cutaneous irritability with high potassium and low calcium content of the skin and vice versa. According to Urbach (3) carnivorous animals show a low potassium and high calcium content of the skin, which is reversed in herbivorous animals. He also observed the sodium content of the human skin to increase 15—20% on a high intake of sodium chloride. Borelli (6) found an increase of cutaneous potassium in acute inflammation and a decrease in chronic inflammation. METHODS
l.
VO w
LJpP +
_.— iN T%'
RELIERSI'
The methods of determination have been described in detail in a previous paper, (1). A diagram (Fig. 1) illustrates the arrangement. An open cup is fixed to the flexor forearm by means of elastic bands and ifiled with dilute lithium nitrate solution. In the cup is a metal plate, which is the anode of an electric current. The cathode is a large metal plate covered with gauze saturated with lithium nitrate, on which the extensor surface of the forearm rests. The solution in * From the Departments of Clinical Science and Dermatology, University of Illinois College of Medicine and the Cook County Hospital, Chicago. Presented at the fifteenth annual meeting of The Society for Investigative Dermatology, Inc., San Francisco, Cali-
fornia, June 19—20, 1954. 287
288
TRE JOURNAL OF INVESTIGATIVE DERMATOLOGY
Dry cell
Switch
battery 50 v
Fia. 1. Arrangement of subject and apparatus
the cup is the contact medium between the anode and the skin. A current of 4 milliamperes is supplied for five minutes. This causes migration of the positive ions (sodium and potassium) to the negative electrode, i.e., into the lithium solution. After the application of the current the solution is syphoned out of the cup and analyzed in the flame photometer. A second cup, similar to the first one but without the electric current, serves as control. The values obtained in this cup are considered contamination and are deducted from the values obtained in the experimental solution to obtain the "true values". We include only these latter ones in our results. In addition to the concentration of the sodium and potassium ions each, the sum of the two different ions is given. This summation has to be looked at with caution, as it depends upon the time of current flow and in a small number of tests, as presented here, it is subject to experimental error. Nonetheless it is included for its possible significance. The third column shows the Na/K ratio. This factor is least subject to experimental error and may therefore be most significant (to be relied upon). In an earlier paper (6) we recorded the effects of age, sex, environmental conditions and sweating upon cutaneous electrolytes. In another study the effect of various systemic conditions known to affect blood electrolytes (congestive heart failure, low sodium diet, etc.) was
Fm. 2. Method of evaluating cadaver skin
289
SODIUM AND POTASSIUM DETERMINED BY IONTOPHORESIS
studied. All tests in this series were made on apparently normal skin, unless otherwise mentioned. RESULTS
The data to be presented are preliminary. They are given as an indication of the possible usefulness of the method. Any changes from the normal are considered purely an indication of the need and direction of future work. The data showed a marked increase of electrolytes in eczema, much more for sodium than potassium at uninvolved sites. Over lesions the ions were in even greater concentration, but again sodium was disproportionately high, higher than present in any other dermatosis we examined. In disseminated lupus erythematosus there was a decrease of both ions, but this was more pronounced for potassium and, therefore, the ratio increased. ACTH restored the levels toward the normal. The discoid form of lupus erythematosus showed a normal cutaneous ionic distribution. In pemphigus there was a decrease of potassium and an increase of sodium. This change was corrected—even overcorrected—in one patient after ACTH. One patient each with deimatitis venenata and with stasis dermatitis had an increase of sodium and a decrease of potassium, while one patient with dermatomyositis showed a change in the opposite direction. TABLE I The relative concentrations of sodium and potassium of the skin in some dermatological conditions (All values are given as microequ./l.) Number of subjects
67
3 3 4 2 2 2 1 1 1 1
8
92 Total
Diagnosis
Controls Eczema (apparently normal areas) Eczema (on lesion) Disseminated lupus erythematosus Disseminated lupus erythematosus (after ACTH) Discoid lupus erythematosus Pemphigus (normal areas) Pemphigus (after ACTH) Stasis dermatitis (ulcer) Dermatitis venenata Dermatomyositis Other skin diseases: 3 numinular eczema 1 alopecia areata 1 lichen simplex chronicus 1 xanthomatosis 1 pityriasis rosea 1 pyoderma
K
Na
Ratio Total
14.6 35.4 2.43 50.0 17.2 48.7 2.83 65.9
21.4 69.8 3.26 91.4 11.3 34.2 3.03 45.5 13.9 36.0 2.58 49.9 13.4
35.9 2.68 49.3
9.5 46.5 4.90 56.0 18.0 37.0 2.05 55.0 10.0 53.0 5.30 63.0 10.0 53.5 5.35 63.5 18.0 32.0 1.77 50.0
14.1
35.6 2.53 49.7
290
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
A number of other dermatological cases did not display any electrolyte disturbances. DISCUSSION
The relative concentrations of sodium and potassium obtained in this study indicates that they are the products of a mixture of intracellular fluid and sweat and interstitial fluid. This can be seen by considering the relative proportion of
the two ions. In reverse iontophoresis this is 2.52:1. In interstitial fluid it is about 29:1, intracellular fluid 0.032:1, in sweat about 7:1 (Berenson and Burch, 8), in whole skin 6:1, and in epidermis (Zheutlin and Fox, 9) 0.57:1. The last two values were obtained from tissue analyses and include free as well as bound ions. The aberrations we found are pronounced, so it is not likely they represent deviations of concentration in one or more of the compartments, because changes in the latter are usually comparatively small. It seems more probable the results reflect true situations in the various compartments of the skin. Thus we may expect a relative increase of sodium in edema or increased capillary permeability, and an increase of potassium in dehydration, in cellular catabolism and in increased permeability of the cellular wall. These are at present purely assumptions, but it is better to have some working theory and unify future study. In eczema, apparently normal areas of the skin show decided increases in both sodium and potassium, so that the ratio between the two is not greatly changed from the normal. The total of both present, however, is distinctly raised. When one examines the affected areas there is a still greater increase in these electrolytes, so that the total for both is almost twice that in normal controls. Sodium, however, is increased more than potassium. The increased sodium is represented, of course, in the characteristic edema found in eczema, while the elevated potassium represents, in part at least, dissolution of cells. One wonders whether these values could be a factor in the production of the accompanying pruritus. In systemic lupus erythematosus, sodium in normal areas remains unchanged, but a decrease in potassium upsets the normal ratio between the two electro-
lytes. ACTH elevates the potassium and restores the normal ratio and total quantity of both ions. In discoid lupus erythematosus the individual electrolyte levels, their ratio, and total all remain unchanged. A contrast to the findings for lupus erythematosus is seen in dermatomyositis where we found potassium was increased. This may reflect, of course, dissolution of tissue. In pemphigus the serum sodium is reduced in proportion to the severity of the patient's condition. On the other hand, potassium may be increased in some
cases. In the skin we found a sizeable increase in sodium and a decrease in potassium in contrast. Here the skin represents a large reservoir for sodium paralleling the diffusely edematous character of the skin. Whether or not these electrolyte changes are factors in laying the basis for the Nikolsky phenomenon will take further work and observations to determine. After administering ACTH the alterations in the cutaneous sodium and potassium each reversed itself. The
sodium level went down to the normal and there was a material increase of
SODIUM AND POTASSIUM DETERMINED BY IONTOPHORESIS
291
potassium, the latter even overshooting the normal level. The facility of the restoration of the normal electrolyte pattern after displaying ACTH may provide some clue as to the prognosis. In stasis dermatitis of the leg with ulcer, reverse iontophoresis at the forearm showed a large increase in sodium and a moderate decrease in potassium. It is of interest that the presence of this increased sodium as an attraction for water may be a factor predisposing the skin at a distance toward the changes we call "ids" found so often to follow or in conjunction with varicose dermatitis and ulcers. We found a similar situation with dermatitis venenata where the apparently
normal skin showed a marked increase in sodium and moderate reduction in potassium. Could these changes in electrolyte content with water-holding potentialities account for the inherent tendency of contact dermatitis to spread? Several other skin disturbances such as alopecia areata, nummular eczema, pityriasis rosea, and pyoderma, even when extensive did not show derangements of the electrolytes in the uninvolved areas. Further experience may tell us why some diseases leave distant cutaneous areas unchanged while other dermatoses upset the normal order there. SUMMARY
In several dermatoses reverse iontophoresis removed concentrations of sodium
and potassium from the uiiinvolved skin indicating it is altered and only apparently normal. If further experience confirms these preliminary results some of these changes may help explain some clinical facts, such as the tendency to form "ids" in some cases of stasis eczema and ulcers, the tendency of dermatitis venenata to spread to distant sites, some characteristics of the skin in pemphigus such as acting as a reservoir for water and sodium, and the waterlogging of the skin in atopic eczema. These results are obviously preliminary and based on an insufficient number of cases. They suggest fundamental alterations, but need much more work to corroborate them. REFERENCES 1. EIcHELBEBGEE, L. C., EISELE, W. AND WETZLEE, D.: The distribution of water, nitrogen
and electrolytes in the skin. J. Biol. Chem., 151: 177—189, 1943. Proc. Soc. Exp. Biol. Med., 58: 97, 1945. Am. J. Physiol., 159: 57, 1949. Am. J. Physiol., 160: 295, 1950. Am. J. Physiol., 161: 328, 1951. J. Lab. Clin. Med., 39: 737, 1952. J. Lab. Clin. Med., 40: 284, 1952. J. Clin. Invest., 30: 1157, 1952. 2. URSACH, E.: Skin Diseases, Nutrition and Metabolism. New York 1946. 3. ZHHUTUN, H. E. C. AND Fox, C. L.: Sodium and potassium content of human epidermis. Arch. Dermat. & Syph., 61: 397-400, 1950. 4. DAHUN, W.: Uber die Potassium und Calcium Verteilung in der normalen Haut. Dermat. Wchen., 82: 425, 1926.
5. LUITHLHN, F.: Das gegenseitige Kation Verhaitnis bei verschiedener Ernahrung und bei Saurevergiftung. Arch. f. Exper. Path. u. Pharmak., 68: 209—230, 1912:69: 365—374, 1912.
6. BORNLLI, F.: Research on quantitative variations of potassium of the blood and skin in normal and pathological conditions. Derm. Sifilografo, 7: 353, 1932.
292
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
7. BENrAMIN, F. B., KEMPEN, R., MTJLDEE, A. C. AND Ivy, A. C.: The Sodium-Potassium
Ratio of the Human Skin as Obtained by Reverse lontophoresis. J. App!. Physiol. (in press)
8. BEEENSON, C. S. AND Buacii, G. E.: A study of the Na, K, Cl content of thermal sweat of man collected from small isolated areas of the skin. J. Lab. Clin. Med., 42: 58—77, 1953.
9. ZnuTu, H. E C., AND Fox, C. L.: Sodium and PotassIum Content of Human Epidermis. Arch. Dermat. & Syph., 61: 397—400, 1950.
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
94
linolenic acid extract. Arch. This pdf is a scanned copy UV of irradiated a printed document.
24. Wynn, C. H. and Iqbal, M.: Isolation of rat
skin lysosomes and a comparison with liver Path., 80: 91, 1965. and spleen lysosomes. Biochem. J., 98: lOP, 37. Nicolaides, N.: Lipids, membranes, and the 1966.
human epidermis, p. 511, The Epidermis
Eds., Montagna, W. and Lobitz, W. C. Acascopic localization of acid phosphatase in demic Press, New York. human epidermis. J. Invest. Derm., 46: 431, 38. Wills, E. D. and Wilkinson, A. E.: Release of 1966. enzymes from lysosomes by irradiation and 26. Rowden, C.: Ultrastructural studies of kerathe relation of lipid peroxide formation to tinized epithelia of the mouse. I. Combined enzyme release. Biochem. J., 99: 657, 1966. electron microscope and cytochemical study 39. Lane, N. I. and Novikoff, A. B.: Effects of of lysosomes in mouse epidermis and esoarginine deprivation, ultraviolet radiation and X-radiation on cultured KB cells. J. phageal epithelium. J. Invest. Derm., 49: 181, 25. Olson, R. L. and Nordquist, R. E.: Ultramicro-
No warranty is given about the accuracy of the copy.
Users should refer to the original published dermal cells. Nature, 216: 1031, 1967. version of1965. the material. vest. Derm., 45: 448, 28. Hall, J. H., Smith, J. G., Jr. and Burnett, S. 41. Daniels, F., Jr. and Johnson, B. E.: In prepa1967.
Cell Biol., 27: 603, 1965.
27. Prose, P. H., Sedlis, E. and Bigelow, M.: The 40. Fukuyama, K., Epstein, W. L. and Epstein, demonstration of lysosomes in the diseased J. H.: Effect of ultraviolet light on RNA skin of infants with infantile eczema. J. Inand protein synthesis in differentiated epi-
C.: The lysosome in contact dermatitis: A ration. histochemical study. J. Invest. Derm., 49: 42. Ito, M.: Histochemical investigations of Unna's oxygen and reduction areas by means of 590, 1967. 29. Pearse, A. C. E.: p. 882, Histochemistry Theoultraviolet irradiation, Studies on Melanin, retical and Applied, 2nd ed., Churchill, London, 1960.
30. Pearse, A. C. E.: p. 910, Histacheini.stry Thearetscal and Applied, 2nd ed., Churchill, London, 1960.
31. Daniels, F., Jr., Brophy, D. and Lobitz, W. C.: Histochemical responses of human skin fol-
lowing ultraviolet irradiation. J. Invest. Derm.,37: 351, 1961.
32. Bitensky, L.: The demonstration of lysosomes by the controlled temperature freezing section method. Quart. J. Micr. Sci., 103: 205, 1952.
33. Diengdoh, J. V.: The demonstration of lysosomes in mouse skin. Quart. J. Micr. Sci., 105: 73, 1964.
34. Jarret, A., Spearman, R. I. C. and Hardy, J. A.:
Tohoku, J. Exp. Med., 65: Supplement V, 10, 1957.
43. Bitcnsky, L.: Lysosomes in normal and pathological cells, pp. 362—375, Lysasames Eds., de Reuck, A. V. S. and Cameron, M. Churchill, London, 1953.
44. Janoff, A. and Zweifach, B. W.: Production of inflammatory changes in the microcirculation by cationic proteins extracted from lysosomes. J. Exp. Med., 120: 747, 1964.
45. Herion, J. C., Spitznagel, J. K., Walker, R. I. and Zeya, H. I.: Pyrogenicity of granulocyte lysosomes. Amer. J. Physiol., 211: 693, 1966.
46. Baden, H. P. and Pearlman, C.: The effect of ultraviolet light on protein and nucleic acid synthesis in the epidermis. J. Invest. Derm.,
Histochemistry of keratinization. Brit. J. 43: 71, 1964. Derm., 71: 277, 1959. 35. De Duve, C. and Wattiaux, R.: Functions of 47. Bullough, W. S. and Laurence, E. B.: Mitotic control by internal secretion: the role of lysosomes. Ann. Rev. Physiol., 28: 435, 1966. the chalone-adrenalin complex. Exp. Cell. 36. Waravdekar, V. S., Saclaw, L. D., Jones, W. A. and Kuhns, J. C.: Skin changes induced by
Res., 33: 176, 1964.
For a long time now observers have been pointing out the possibffity sodium
and potassium ions in the skin may be significant in some dermatoses, but progress was hampered by the difficulty of electrolyte determinations. Investigators usually use blood analyses to gain an insight, but blood electrolytes do not necessarily parallel those in the skin. Eichelberger, Eisele, and Wetzler (1) did much work analyzing skin slices for electrolytes, but their method is obviously not suitable for routine clinical determinations. The same restriction applies to the use of radioactive isotopes. In this paper we are presenting another method of determining skin electrolytes and changes of electrolytes under various pathological conditions. Urbach (2) showed a long time ago that the skin stores electrolytes. Zheutlin (3) analyzed human skin and epidermis and found the following values expressed as meq/kg wet weight. Whole skin: Na—96.0 and K—16.O, which gives a proportion of 6:1. Epidermis: Na—46.1 and K—80.5 with a proportion of 0.57:1. Caehn (4) likewise analyzed various skin structures. He found also more K than Na in the epidermis, while the cutis showed high Ca and low K values. In the sweat glands the K was high and in the sebaceous glands he found mainly Ca. Luithien (5) studied the effect of diet on skin electrolytes in the rabbit. On a diet of oats (acidotic) all ions decreased with a relative increase of potassium over sodium, calcium, and magnesium. A low sodium chloride diet had the same effect. A green fodder diet (alkalotic) caused an increase of calcium with a decrease mainly of potassium. He also found an increased cutaneous irritability with high potassium and low calcium content of the skin and vice versa. According to Urbach (3) carnivorous animals show a low potassium and high calcium content of the skin, which is reversed in herbivorous animals. He also observed the sodium content of the human skin to increase 15—20% on a high intake of sodium chloride. Borelli (6) found an increase of cutaneous potassium in acute inflammation and a decrease in chronic inflammation. METHODS
l.
VO w
LJpP +
_.— iN T%'
RELIERSI'
The methods of determination have been described in detail in a previous paper, (1). A diagram (Fig. 1) illustrates the arrangement. An open cup is fixed to the flexor forearm by means of elastic bands and ifiled with dilute lithium nitrate solution. In the cup is a metal plate, which is the anode of an electric current. The cathode is a large metal plate covered with gauze saturated with lithium nitrate, on which the extensor surface of the forearm rests. The solution in * From the Departments of Clinical Science and Dermatology, University of Illinois College of Medicine and the Cook County Hospital, Chicago. Presented at the fifteenth annual meeting of The Society for Investigative Dermatology, Inc., San Francisco, Cali-
fornia, June 19—20, 1954. 287
288
TRE JOURNAL OF INVESTIGATIVE DERMATOLOGY
Dry cell
Switch
battery 50 v
Fia. 1. Arrangement of subject and apparatus
the cup is the contact medium between the anode and the skin. A current of 4 milliamperes is supplied for five minutes. This causes migration of the positive ions (sodium and potassium) to the negative electrode, i.e., into the lithium solution. After the application of the current the solution is syphoned out of the cup and analyzed in the flame photometer. A second cup, similar to the first one but without the electric current, serves as control. The values obtained in this cup are considered contamination and are deducted from the values obtained in the experimental solution to obtain the "true values". We include only these latter ones in our results. In addition to the concentration of the sodium and potassium ions each, the sum of the two different ions is given. This summation has to be looked at with caution, as it depends upon the time of current flow and in a small number of tests, as presented here, it is subject to experimental error. Nonetheless it is included for its possible significance. The third column shows the Na/K ratio. This factor is least subject to experimental error and may therefore be most significant (to be relied upon). In an earlier paper (6) we recorded the effects of age, sex, environmental conditions and sweating upon cutaneous electrolytes. In another study the effect of various systemic conditions known to affect blood electrolytes (congestive heart failure, low sodium diet, etc.) was
Fm. 2. Method of evaluating cadaver skin
289
SODIUM AND POTASSIUM DETERMINED BY IONTOPHORESIS
studied. All tests in this series were made on apparently normal skin, unless otherwise mentioned. RESULTS
The data to be presented are preliminary. They are given as an indication of the possible usefulness of the method. Any changes from the normal are considered purely an indication of the need and direction of future work. The data showed a marked increase of electrolytes in eczema, much more for sodium than potassium at uninvolved sites. Over lesions the ions were in even greater concentration, but again sodium was disproportionately high, higher than present in any other dermatosis we examined. In disseminated lupus erythematosus there was a decrease of both ions, but this was more pronounced for potassium and, therefore, the ratio increased. ACTH restored the levels toward the normal. The discoid form of lupus erythematosus showed a normal cutaneous ionic distribution. In pemphigus there was a decrease of potassium and an increase of sodium. This change was corrected—even overcorrected—in one patient after ACTH. One patient each with deimatitis venenata and with stasis dermatitis had an increase of sodium and a decrease of potassium, while one patient with dermatomyositis showed a change in the opposite direction. TABLE I The relative concentrations of sodium and potassium of the skin in some dermatological conditions (All values are given as microequ./l.) Number of subjects
67
3 3 4 2 2 2 1 1 1 1
8
92 Total
Diagnosis
Controls Eczema (apparently normal areas) Eczema (on lesion) Disseminated lupus erythematosus Disseminated lupus erythematosus (after ACTH) Discoid lupus erythematosus Pemphigus (normal areas) Pemphigus (after ACTH) Stasis dermatitis (ulcer) Dermatitis venenata Dermatomyositis Other skin diseases: 3 numinular eczema 1 alopecia areata 1 lichen simplex chronicus 1 xanthomatosis 1 pityriasis rosea 1 pyoderma
K
Na
Ratio Total
14.6 35.4 2.43 50.0 17.2 48.7 2.83 65.9
21.4 69.8 3.26 91.4 11.3 34.2 3.03 45.5 13.9 36.0 2.58 49.9 13.4
35.9 2.68 49.3
9.5 46.5 4.90 56.0 18.0 37.0 2.05 55.0 10.0 53.0 5.30 63.0 10.0 53.5 5.35 63.5 18.0 32.0 1.77 50.0
14.1
35.6 2.53 49.7
290
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
A number of other dermatological cases did not display any electrolyte disturbances. DISCUSSION
The relative concentrations of sodium and potassium obtained in this study indicates that they are the products of a mixture of intracellular fluid and sweat and interstitial fluid. This can be seen by considering the relative proportion of
the two ions. In reverse iontophoresis this is 2.52:1. In interstitial fluid it is about 29:1, intracellular fluid 0.032:1, in sweat about 7:1 (Berenson and Burch, 8), in whole skin 6:1, and in epidermis (Zheutlin and Fox, 9) 0.57:1. The last two values were obtained from tissue analyses and include free as well as bound ions. The aberrations we found are pronounced, so it is not likely they represent deviations of concentration in one or more of the compartments, because changes in the latter are usually comparatively small. It seems more probable the results reflect true situations in the various compartments of the skin. Thus we may expect a relative increase of sodium in edema or increased capillary permeability, and an increase of potassium in dehydration, in cellular catabolism and in increased permeability of the cellular wall. These are at present purely assumptions, but it is better to have some working theory and unify future study. In eczema, apparently normal areas of the skin show decided increases in both sodium and potassium, so that the ratio between the two is not greatly changed from the normal. The total of both present, however, is distinctly raised. When one examines the affected areas there is a still greater increase in these electrolytes, so that the total for both is almost twice that in normal controls. Sodium, however, is increased more than potassium. The increased sodium is represented, of course, in the characteristic edema found in eczema, while the elevated potassium represents, in part at least, dissolution of cells. One wonders whether these values could be a factor in the production of the accompanying pruritus. In systemic lupus erythematosus, sodium in normal areas remains unchanged, but a decrease in potassium upsets the normal ratio between the two electro-
lytes. ACTH elevates the potassium and restores the normal ratio and total quantity of both ions. In discoid lupus erythematosus the individual electrolyte levels, their ratio, and total all remain unchanged. A contrast to the findings for lupus erythematosus is seen in dermatomyositis where we found potassium was increased. This may reflect, of course, dissolution of tissue. In pemphigus the serum sodium is reduced in proportion to the severity of the patient's condition. On the other hand, potassium may be increased in some
cases. In the skin we found a sizeable increase in sodium and a decrease in potassium in contrast. Here the skin represents a large reservoir for sodium paralleling the diffusely edematous character of the skin. Whether or not these electrolyte changes are factors in laying the basis for the Nikolsky phenomenon will take further work and observations to determine. After administering ACTH the alterations in the cutaneous sodium and potassium each reversed itself. The
sodium level went down to the normal and there was a material increase of
SODIUM AND POTASSIUM DETERMINED BY IONTOPHORESIS
291
potassium, the latter even overshooting the normal level. The facility of the restoration of the normal electrolyte pattern after displaying ACTH may provide some clue as to the prognosis. In stasis dermatitis of the leg with ulcer, reverse iontophoresis at the forearm showed a large increase in sodium and a moderate decrease in potassium. It is of interest that the presence of this increased sodium as an attraction for water may be a factor predisposing the skin at a distance toward the changes we call "ids" found so often to follow or in conjunction with varicose dermatitis and ulcers. We found a similar situation with dermatitis venenata where the apparently
normal skin showed a marked increase in sodium and moderate reduction in potassium. Could these changes in electrolyte content with water-holding potentialities account for the inherent tendency of contact dermatitis to spread? Several other skin disturbances such as alopecia areata, nummular eczema, pityriasis rosea, and pyoderma, even when extensive did not show derangements of the electrolytes in the uninvolved areas. Further experience may tell us why some diseases leave distant cutaneous areas unchanged while other dermatoses upset the normal order there. SUMMARY
In several dermatoses reverse iontophoresis removed concentrations of sodium
and potassium from the uiiinvolved skin indicating it is altered and only apparently normal. If further experience confirms these preliminary results some of these changes may help explain some clinical facts, such as the tendency to form "ids" in some cases of stasis eczema and ulcers, the tendency of dermatitis venenata to spread to distant sites, some characteristics of the skin in pemphigus such as acting as a reservoir for water and sodium, and the waterlogging of the skin in atopic eczema. These results are obviously preliminary and based on an insufficient number of cases. They suggest fundamental alterations, but need much more work to corroborate them. REFERENCES 1. EIcHELBEBGEE, L. C., EISELE, W. AND WETZLEE, D.: The distribution of water, nitrogen
and electrolytes in the skin. J. Biol. Chem., 151: 177—189, 1943. Proc. Soc. Exp. Biol. Med., 58: 97, 1945. Am. J. Physiol., 159: 57, 1949. Am. J. Physiol., 160: 295, 1950. Am. J. Physiol., 161: 328, 1951. J. Lab. Clin. Med., 39: 737, 1952. J. Lab. Clin. Med., 40: 284, 1952. J. Clin. Invest., 30: 1157, 1952. 2. URSACH, E.: Skin Diseases, Nutrition and Metabolism. New York 1946. 3. ZHHUTUN, H. E. C. AND Fox, C. L.: Sodium and potassium content of human epidermis. Arch. Dermat. & Syph., 61: 397-400, 1950. 4. DAHUN, W.: Uber die Potassium und Calcium Verteilung in der normalen Haut. Dermat. Wchen., 82: 425, 1926.
5. LUITHLHN, F.: Das gegenseitige Kation Verhaitnis bei verschiedener Ernahrung und bei Saurevergiftung. Arch. f. Exper. Path. u. Pharmak., 68: 209—230, 1912:69: 365—374, 1912.
6. BORNLLI, F.: Research on quantitative variations of potassium of the blood and skin in normal and pathological conditions. Derm. Sifilografo, 7: 353, 1932.
292
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
7. BENrAMIN, F. B., KEMPEN, R., MTJLDEE, A. C. AND Ivy, A. C.: The Sodium-Potassium
Ratio of the Human Skin as Obtained by Reverse lontophoresis. J. App!. Physiol. (in press)
8. BEEENSON, C. S. AND Buacii, G. E.: A study of the Na, K, Cl content of thermal sweat of man collected from small isolated areas of the skin. J. Lab. Clin. Med., 42: 58—77, 1953.
9. ZnuTu, H. E C., AND Fox, C. L.: Sodium and PotassIum Content of Human Epidermis. Arch. Dermat. & Syph., 61: 397—400, 1950.
THE JOURNAL OF INVESTIGATIVE DERMATOLOGY
94
linolenic acid extract. Arch. This pdf is a scanned copy UV of irradiated a printed document.
24. Wynn, C. H. and Iqbal, M.: Isolation of rat
skin lysosomes and a comparison with liver Path., 80: 91, 1965. and spleen lysosomes. Biochem. J., 98: lOP, 37. Nicolaides, N.: Lipids, membranes, and the 1966.
human epidermis, p. 511, The Epidermis
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