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CLIMATOTHERAPY OF PSORIASIS AND HYPERTENSION IN ELDERLY PATIENTS AT THE DEAD-SEA
Pharmacological Research, Vol. 34, No. 1/2, 1996
CLIMATOTHERAPY OF PSORIASIS AND HYPERTENSION IN ELDERLY PATIENTS AT THE DEAD-SEA AVRAHAM P. KUSHELEVSKY*, MARCO HARARI†, EUGENIA HRISTAKIEVA†¶ and JASHOVAM SHANI‡§ Department of Nuclear Engineering, Ben-Gurion University, Beer-Sheva, †Deutsches Medizinisches Zentrum (DMZ), Ein-Bokek, The Dea-Sea and ‡Department of Pharmacology, The Hebrew University School of Pharmacy, Jerusalem, Israel Accepted 23 July 1996 The responses of various age-groups of psoriatic patients to a four-week period of climatotherapy at the Dead-Sea was compared in three separate studies. In the first study, plaque clearance following climatotherapy was evaluated in a group of 688 psoriatics, as a function of age, sex and duration of the disease. Neither the age of the patient when treated, nor the duration of the disease, appeared to influence the degree of plaque clearance. However, when the age at onset of the disease was evaluated as the comparative parameter - a decrease in the rate of response with increasing patients’ age was recorded. In the second study, the type and incidence of side effects after climatotherapy was studied in 502 patients aged over 65, and in more than 4,500 younger psoriatics. There was no difference in the type and frequency of side effects between the two age-groups. The most frequent side effects were: slight sun burn (8.2%), sun allergy (5.0%), common cold (3.4%), leg oedema (2.0%), diarrhea (1.4%) and herpes simplex (0.8%). In all cases the side-effects disappeared within a few days. In the third study, the reduction in the diastolic and systolic blood pressures in a group of 1,142 hypertensive psoriatics was evaluated as a function of time. It was demonstrated that while there was no significant age-dependent difference in lowering their diastolic blood pressure throughout the study, differences in lowering systolic measurements between the younger (<40 y) and older (>65 y) hypertensive patients were highly significant. On the basis of these studies we conclude that psoriatics aged 65 and over benefit from climatotherapy at the Dead-Sea no less than younger patients, and that, irrespective of age, high blood pressure is not a contraindication for this treatment in psoriatic patients at the Dead-Sea. 1996 The Italian Pharmacological Society KEY WORDS: psoriasis, climatotherapy, blood pressure, side effects, hypertension, Dead-Sea.
INTRODUCTION The Dead-Sea in Israel is well known in the medical community, as a climatotherapy center, for the treatment of some dermatological and rheumatic conditions [1]. In the case of psoriasis, 85% of the patients treated at the Dead-Sea show a marked improvement in the psoriatic condition, following a four-week stay in the area. This remarkable rate of success has been attributed to a number of factors that include: high mineral content of the sea [2], a unique solar UV spectrum (feeble UVB radiation) that enhances solar phototherapy [3], high air bromine concentration and increased oxygen partial pressures
*Author to whom correspondence should be addressed. §Affiliated with the David R. Bloom Center for Pharmacy. ¶Permanent address: Faculty of Medicine, Trakia University, State Zogura, Bulgaria. 1043–6618/96/070087–05/$25.00/0
in the Dead-Sea basin, situated 400 m below sea level [4]. Many studies on the improvement of psoriasis after a treatment schedule of four weeks at the Dead-Sea have demonstrated improvement in up to 85% of the patients staying at the area under strict medical supervision, but none of these studies clearly correlated the age and sex of the patients with their response to balneotherapy [5, 6]. Moreover, fears have been raised that elderly patients, and in particular elderly patients suffering from hypertension, may not respond well to treatment at the Dead-Sea [7]. Only one report rebutting this notion was published in the medial literature, based on measurements of a small group of 19 healthy male hotel workers, who commuted daily between Arad and the Dead-Sea (a drop in altitude of 1,035 m), revealing a significant drop in their systolic and diastolic blood pressures at the Dead-Sea as compared to those measured earlier on the same days at Arad [7]. 1996 The Italian Pharmacological Society
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In that study, the age-range of all participants was too narrow for population-wide statistics. In order to clarify this issue, three retrospective surveys of three separate large and uniform groups of psoriatic patients treated in the area were carried out, sub-grouped in each survey according to age, and the following questions were considered: (a) Is the rate of success of the climatotherapy of psoriasis at the Dead-Sea age-dependent? (b) Do elderly patients suffer a higher incidence of side effects following the treatment at the Dead-Sea? and, (c) are there age-dependent differences in the reduction in blood pressure that occurs during the period of treatment? Answers to these questions will allow physicians to decide whether psoriatics of specific age and sex are likely to benefit more than others from climatotherapy at the Dead-Sea.
MATERIALS AND METHODS
Clinical improvement in psoriatic patients Improvement in the psoriatic condition was surveyed in 688 European psoriatics, mostly German (320 males and 368 females), who stayed during 1995 for at least 28 days in the Carlton Hotel on the DeadSea shore, and were under medical supervision in the Deutsches Medizinisches Zentrum (DMZ) clinic, located on the grounds of that hotel. For assessing the improvement in their psoriatic condition, the percentages of patients in whom complete plaque clearance or marked reduction in skin area covered by plaques occurred, were recorded. The first check-up was performed within 24 h of their arrival in Israel, and then they were inspected on a weekly basis, for four consecutive weeks. For comparative purposes the patients were grouped either by age, by the duration of their disease in years or by their age at onset of the disease. In all three divisions the age-groups were: <10 y, 10–20 y, 30–40 y, 40–50 y, 50–60 y and >60 y.
Side effects of Climatotherapy In a separate study, 502 psoriatic patients (238 males and 264 females), age 65 and older, were evaluated for improvement in their psoriatic condition and for monitoring their side effects from climatotherapy. These side effects were recorded and compared with the incidence and frequency of side-effects recorded in over 4,500 younger patients (<65 y of age), that were supervised in the DMZ clinic for the past five years.
Pharmacological Research, Vol. 34, No. 1/2, 1996
Deutsches Medizinisches Zentrum (DMZ) clinic. Their files were selected from files of over 11,400 patients, based on the fact that their blood pressure was measured at least three times during their stay, the first time within 24 h of their arrival by air in Israel. The patients in this retrospective study were divided into two groups: (a) 437 hypertensive psoriatics, some of them on anti-hypertensive medication, and some that were never before treated for their (mostly mild) hypertension. The diastolic blood pressure of these patients, upon arrival at the Dead-Sea, was 90 mm Hg or higher. Their anti-hypertensive medication (or lack of mediation) was not significantly changed during their 28-day stay at the DeadSea; (b) 705 psoriatics who had never been diagnosed as ‘hypertensives’, and whose diastolic measurement upon arrival was lower than 90 mm Hg. The age and sex of all patients were recorded. The first measurements were taken in all patients on the morning following their arrival at the Dead-Sea, thereafter defined as day ‘1’. The cut-off point of the diastolic pressure of 90 mm Hg was based on the American Heart Association definition of elevated arterial blood pressure, as being higher or equal than 140/90, with emphasis on the diastolic level [8]. Each of the two groups (a and b) were sub-divided into three age groups: >45, 45–65 and >65 years, and each age-group was sub-divided into the two sexes, producing a total of six groups of patients. Diastolic and systolic blood pressure were recorded for each of them once weekly during their stay. Blood pressure measurements were performed by the same physician and nurse in the mornings, before commencing outdoor treatment. A standard cuff manometer was used, with the patients in a sitting position. The fourth Korotkoff sound was taken as the index for diastolic pressure. The blood pressure values were fed into a computer, and the paired t-test was calculated for each patient, comparing the systolic and diastolic values found on day ‘1’ with those registered on subsequent days. Differences between groups were calculated by Analysis of Variance (ANOVA) and the Student’s paired t-test, wherever applicable. For the graphic representation - all hypertensive diastolic curves were adjusted to 100 mm Hg and all hypertensive systolic curves - to 155 mm Hg.
RESULTS
Plaque clearance Retrieving blood-pressure data The blood-pressure data analysed in the present study was taken retrospectively from files of 1,142 European psoriatics, mostly German (583 male and 559 females), who stayed for 28 days on the Dead-Sea shore, and were under medical supervision in the
The distribution of the psoriatic plaque clearance, within the patient population studied (n=688), by the patient age, at the time of treatment, is shown in Fig. 1. This figure clearly demonstrates that except for the very young age-group (<10 y; n=4), there was no significant difference between any of the age-groups in
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Fig. 2. Percentage of psoriatics totally cleared of their psoriatic plaques after a four-week climatotherapy at the Dead-Sea, correlated with duration of the disease.
the percentage of patients totally cleared of their plaques during their stay at the Dead-Sea. In general, between 65.4% and 71.4% of the patients achieved total clearance, and up to 85% achieved partial clearance at the end of the treatment. Similarly, no differences were found between patients grouped according to the duration of their disease (from its onset until the 1995 treatment). In general, between 60.0% and 71.4% of the patients achieved full clearance, irrespective of the length of time that elapsed from the first appearance of the disease. One exception were patients suffering from psoriasis for a period of 40–49 years. These patients achieved a higher rate of clearance of 78.6% (Fig. 2). A significant difference was also found in the clearance rate between patients whose disease first appeared between the ages of 10–19 years (77.8%) and patients in which the disease appeared for the first time after the age of 60 (56.2% clearance). A less significant age-dependence in the relation between full plaque clearance and the age the patients first began to suffer from psoriasis. Our data suggest that the rate of full clearance is somewhat lower when the disease first appears late in life (Fig. 3).
Fig. 3. Percentage of psoriatics totally cleared of their psoriatic plaques after a four-week climatotherapy at the Dead-Sea, correlated with the patients’ age at the onset of the disease.
Number of patients
Cleared patients after 4 weeks (%)
Fig. 1. Percentage of psoriatics totally cleared of their psoriatic plaques after a four-week climatotherapy at the Dead-Sea, of various age groups.
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2 4 6 8 10 Incidence in about 5,000 psoriatics (%)
Fig. 4. The most common side effects during a four-week climatotherapy at the Dead-Sea.
Side effects of climatotherapy Data on the type and frequency of the side effects in 502 psoriatic patients aged 65 y and over, and in 4,500 younger patients, were compared. All of the patients were treated for four weeks during 1988–1994, at the DMZ clinic. The most frequent side effects were as follows: sun burns (8.2%), sun allergy (5.0%), common cold (3.4%), oedema (2.0%), gastroenteritis (1.4%), herpes labialis (0.8%), other infections (0.8%), circulatory problems, eye infections and ear infections (<0.8% each). Altogether, 24% of the patients experienced at least one side effect, and 17% of them experienced more than one. No differences in the type and frequency of the side effects was detected between the two groups. All side effects disappeared within a few days, after an ambulatory treatment. A diagram illustrating the more frequent side effects is presented in Fig. 4.
Changes in blood-pressure An average decrease in systolic and diastolic blood pressures during the treatment period at the Dead-Sea was observed, irrespective of sex and age, in all of the groups, as shown in Fig. 5. This figure clearly demon-
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Fig. 5. Changes in diastolic and systolic blood pressure in various age-groups of hypertensive males (left) and hypertensive females (right) during a 4-week stay at the Dead-Sea. *P<0.05; d–d, >65 y; d- -d, 40–65 y; d · · · d, <40 y.
strates that while there is no significant difference between the various age groups in lowering their diastolic blood pressure throughout the study - differences in lowering the systolic measurements between the younger (<40 y) and older (>65 y) hypertensive patients, are remarkable, and highly significant. Similarly, no significant differences were noted between males and females, with the exception in the length of time the reduction in systolic blood pressure was sustained. In males it lasted about two weeks from the beginning of the treatment, in contrast to females in whom the reduction lasted over the whole four-week treatment period.
DISCUSSION The statistical success (plaque clearance) after a fourweek stay at the Dead-Sea has not changed much since Avrach et al. reported [5, 13] a 94.9% of improvement with this treatment schedule. Out of the 1,631 psoriatics followed-up carefully in this study, 34.5% were completely cleared, 43.3% showed marked improvement and 17.1% improved partially. The impressive part in Avrach’s papers was a comparison of the percentage of patients with recurrences within four weeks after cessation of the treatment, showing the Dead-Sea climatotherapy with the lowest recurrence (44%), followed by Goeckerman (45%), Dithranol (53%) and topical corticoids (95%). In another paper, Avrach (who spent many years at the International Psoriasis Treatment Center in EinBokek), reported that ‘96% were either cleared or improved during the four-week treatment period. Deterioration was found in patients with hypersensitivity to sunlight . . .’. The author elaborated by stating that ‘the acute guttate type improved quickly, the nummular and the plaque types more slowly, but still with excellent final results. The erythrodermic and generalized (more than 60% of the body surface)
types were also treated with success’ [14]. No subdivision to ages and sexes were performed in any of these studies. Very few comments have been published on sideeffects of climatotherapy at the Dead-Sea. Avrach’s report that erythrodermic and generalized (>60% of body surface) types were treated with particular precaution, e.g. they were exposed to less light, their topical applications were performed with caution and the time for their bathing in the hypertonic sea was restricted [14]. Azizi et al. [15] reported a severe sunburn reaction in a psoriatic patient following overexposure to a UV radiation source [15] and one patient developed an exfoliative dermatitis and had to be treated with systemic corticosteroids [14]. No detailed reports’ on side effects of this balneotherapy, neither sub-division of the erythrodermic and generalized psoriatic patients were given in this or in another paper in this medical field. The major finding of the present study is that the drop in blood pressure is more profound in the female psoriatics, where their initial blood pressure is lowered and remains low during all four weeks, while the drop in blood pressure of the hypertensive males is somewhat moderate, and is significant only during the first two weeks of the study. This is not surprising, as it has been suggested already before, that more women than men eventually develop hypertension, and as a consequence suffer less cardiovascular damage [17]. The first study on the effect of a four-week bathing at the Dead-Sea on blood pressure was published in 1984 by Bernheim et al., reporting that ‘a general decrease in blood pressure was found in all male subjects (n=19) at the Dead-Sea shore’. The authors concluded that, ‘The decrease in blood pressure at the Dead-Sea shore, is undoubtedly significant in healthy subjects’, and suggested ‘further investigation in order to determine the specific factors at the Dead-Sea that may play a role in blood pressure changes’ [7]. One of our colleagues from the Hadassah Hospital in Jerusalem recalled that during reconnaissance, trips from Jerusalem to the Dead-Sea over 35 years ago, ‘a significant drop in blood pressure was recorded in all members of the medical team who made the trip’ (Z. Even-Paz, unpublished) [9]. Bernheim et al., in their report suggested that the reduction in blood pressure at the Dead-Sea level (as compared to the Arad level, over 1,000 meters higher), might be caused by high temperatures prevailing in the area, by increased atmospheric pressure (about 800 mm Hg) or by increased oxygen concentration (+10%) in the area. It is believed that the latter effect is only marginal, as the blood is normally saturated with oxygen, and we promote two other explanations. The first one has to do with the hazy atmosphere overhanging the Dead-Sea which is rich in bromides, and has been known for over a century for its sedative and mild hypnotic effect [8]. It has been
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well documented that psychological methods (i.e. relaxation, biofeedback and meditation) have established non-pharmacological therapies for hypertension [10], and that on the average a reduction of 10 mm Hg in blood pressure may be achieved with such modalities. The second explanation has to do with the high content of magnesium in the Dead-Sea brine and haze. Magnesium has been established as playing an important role in the etiology of cardiovascular pathologies and causing vascular dilatation. The vasodilator effect of magnesium has been attributed to its Ca-channel blocking property, and to modulation of intracellular free Ca2+ in vascular smooth-muscle cells [11]. We have shown previously that both Br- and Mg2+ penetrate into the circulation during the patients’ period of balneotherapy, and suggested that both elements reach the circulatory system mainly via breathing rather than by bathing in the Sea. This is our explanation to the fact that no reduction in blood pressure was noticed when patients bathed in reconstituted Dead-Sea bath salts at home [12], and no drop in blood pressure occurs when patients sit in warm-water bath for thermal vasodilatation [16]. In summary, climatotherapy at the Dead-Sea is improving remarkably the psoriatic condition of over 85% of the patients, provided they spend four consecutive weeks under medical treatment at the DeadSea. The side effects involved in such a treatment are scarce and mild, and usually disappear upon diminishing the number of hours spent outdoors and/or by ambulatory treatment. An issue of great emphasis is that high blood pressure is not a contraindication to balneotherapy at the Dead-Sea. Moreover, elderly patients benefit from this treatment at least as well as younger patients. There are indications that the rate of full clearance is somewhat lower when the disease appears in elderly people, and that the clearance is
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slower when the duration of the disease is prolonged, but these findings warrant further observations. Our results also indicate that elderly patients are not at higher risk than younger psoriatics in developing sideeffects to balneotherapy, and that the drop in blood pressure, not so abrupt in the elderly, is well tolerated by them. The mechanism of this effect is now being studied in our Department.
REFERENCES 1. Even-Paz Z, Shani J. Int J Dermatol 1989; 18: 1–9. 2. Shani J, Barak S, Levi D, Ram M, Schachner ER, Schlesinger T, Robberecht H, Van Grieken R, Avrach WW. Pharm Res Commun 1985; 17: 501–2. 3. Kushelevsky AP, Slifkin MA. Israel J Med Sci 1975; 5: 588–90. 4. Shani J, Barak S, Ram M, Levi D, Schlesinger T, Avrach WW, Roberecht H, Van Grieken R. Pharmacology 1982; 25: 297–307. 5. Avrach WW, Niorddsen AM. Ugeskr Laeg 1974; 136: 2687–90. 6. Montgomery BJ. J Am Med Assoc 1979; 241: 227–31. 7. Bernheim J, Saidi J, Kovatz S, Solan H. Israel J Med Sci 1984; 20: 1193–4. 8. Gerber JG, Nies AS. In: Gilman AG, Rall TW, Nies AS, Taylor P, eds. The pharmacological basis of therapeutics. Pergamon Press Inc., 1990; Pp. 784–813. 9. Shani J, Kushelevsky AP, Harari M, Even-Paz Z. Pharmacol Res 1995; 31: 355–9. 10. Addison WLT. Can Med Assn J 1928; 18: 281–5. 11. Altura BM, Altura BT. Magnesium 1985; 2: 226–44. 12. Engel P. Acta Medica Empirica. 1982; 31: 374–8. 13. Avrach WW. XV Intern Cong Dermatol, Mexico City, 1977. 14. Avrach WW. Proc. 2nd Intern Symp. Psoriasis. Stanford Univ. 1976; 258–61. 15. Azizi E, Kushelevsky AP, Avrach WW, SchewachMillet M. Israel J Med Sci 1982; 18: 267–70. 16. Tei C, Horikiri Y, Park JC, Jeong JW, Chang KS, Toyama Y, Tanaka N. Circulation 1995; 91: 2582–90. 17. Kaplan NM. Arch Intern Med 1995; 155: 563–7.
CLIMATOTHERAPY OF PSORIASIS AND HYPERTENSION IN ELDERLY PATIENTS AT THE DEAD-SEA AVRAHAM P. KUSHELEVSKY*, MARCO HARARI†, EUGENIA HRISTAKIEVA†¶ and JASHOVAM SHANI‡§ Department of Nuclear Engineering, Ben-Gurion University, Beer-Sheva, †Deutsches Medizinisches Zentrum (DMZ), Ein-Bokek, The Dea-Sea and ‡Department of Pharmacology, The Hebrew University School of Pharmacy, Jerusalem, Israel Accepted 23 July 1996 The responses of various age-groups of psoriatic patients to a four-week period of climatotherapy at the Dead-Sea was compared in three separate studies. In the first study, plaque clearance following climatotherapy was evaluated in a group of 688 psoriatics, as a function of age, sex and duration of the disease. Neither the age of the patient when treated, nor the duration of the disease, appeared to influence the degree of plaque clearance. However, when the age at onset of the disease was evaluated as the comparative parameter - a decrease in the rate of response with increasing patients’ age was recorded. In the second study, the type and incidence of side effects after climatotherapy was studied in 502 patients aged over 65, and in more than 4,500 younger psoriatics. There was no difference in the type and frequency of side effects between the two age-groups. The most frequent side effects were: slight sun burn (8.2%), sun allergy (5.0%), common cold (3.4%), leg oedema (2.0%), diarrhea (1.4%) and herpes simplex (0.8%). In all cases the side-effects disappeared within a few days. In the third study, the reduction in the diastolic and systolic blood pressures in a group of 1,142 hypertensive psoriatics was evaluated as a function of time. It was demonstrated that while there was no significant age-dependent difference in lowering their diastolic blood pressure throughout the study, differences in lowering systolic measurements between the younger (<40 y) and older (>65 y) hypertensive patients were highly significant. On the basis of these studies we conclude that psoriatics aged 65 and over benefit from climatotherapy at the Dead-Sea no less than younger patients, and that, irrespective of age, high blood pressure is not a contraindication for this treatment in psoriatic patients at the Dead-Sea. 1996 The Italian Pharmacological Society KEY WORDS: psoriasis, climatotherapy, blood pressure, side effects, hypertension, Dead-Sea.
INTRODUCTION The Dead-Sea in Israel is well known in the medical community, as a climatotherapy center, for the treatment of some dermatological and rheumatic conditions [1]. In the case of psoriasis, 85% of the patients treated at the Dead-Sea show a marked improvement in the psoriatic condition, following a four-week stay in the area. This remarkable rate of success has been attributed to a number of factors that include: high mineral content of the sea [2], a unique solar UV spectrum (feeble UVB radiation) that enhances solar phototherapy [3], high air bromine concentration and increased oxygen partial pressures
*Author to whom correspondence should be addressed. §Affiliated with the David R. Bloom Center for Pharmacy. ¶Permanent address: Faculty of Medicine, Trakia University, State Zogura, Bulgaria. 1043–6618/96/070087–05/$25.00/0
in the Dead-Sea basin, situated 400 m below sea level [4]. Many studies on the improvement of psoriasis after a treatment schedule of four weeks at the Dead-Sea have demonstrated improvement in up to 85% of the patients staying at the area under strict medical supervision, but none of these studies clearly correlated the age and sex of the patients with their response to balneotherapy [5, 6]. Moreover, fears have been raised that elderly patients, and in particular elderly patients suffering from hypertension, may not respond well to treatment at the Dead-Sea [7]. Only one report rebutting this notion was published in the medial literature, based on measurements of a small group of 19 healthy male hotel workers, who commuted daily between Arad and the Dead-Sea (a drop in altitude of 1,035 m), revealing a significant drop in their systolic and diastolic blood pressures at the Dead-Sea as compared to those measured earlier on the same days at Arad [7]. 1996 The Italian Pharmacological Society
88
In that study, the age-range of all participants was too narrow for population-wide statistics. In order to clarify this issue, three retrospective surveys of three separate large and uniform groups of psoriatic patients treated in the area were carried out, sub-grouped in each survey according to age, and the following questions were considered: (a) Is the rate of success of the climatotherapy of psoriasis at the Dead-Sea age-dependent? (b) Do elderly patients suffer a higher incidence of side effects following the treatment at the Dead-Sea? and, (c) are there age-dependent differences in the reduction in blood pressure that occurs during the period of treatment? Answers to these questions will allow physicians to decide whether psoriatics of specific age and sex are likely to benefit more than others from climatotherapy at the Dead-Sea.
MATERIALS AND METHODS
Clinical improvement in psoriatic patients Improvement in the psoriatic condition was surveyed in 688 European psoriatics, mostly German (320 males and 368 females), who stayed during 1995 for at least 28 days in the Carlton Hotel on the DeadSea shore, and were under medical supervision in the Deutsches Medizinisches Zentrum (DMZ) clinic, located on the grounds of that hotel. For assessing the improvement in their psoriatic condition, the percentages of patients in whom complete plaque clearance or marked reduction in skin area covered by plaques occurred, were recorded. The first check-up was performed within 24 h of their arrival in Israel, and then they were inspected on a weekly basis, for four consecutive weeks. For comparative purposes the patients were grouped either by age, by the duration of their disease in years or by their age at onset of the disease. In all three divisions the age-groups were: <10 y, 10–20 y, 30–40 y, 40–50 y, 50–60 y and >60 y.
Side effects of Climatotherapy In a separate study, 502 psoriatic patients (238 males and 264 females), age 65 and older, were evaluated for improvement in their psoriatic condition and for monitoring their side effects from climatotherapy. These side effects were recorded and compared with the incidence and frequency of side-effects recorded in over 4,500 younger patients (<65 y of age), that were supervised in the DMZ clinic for the past five years.
Pharmacological Research, Vol. 34, No. 1/2, 1996
Deutsches Medizinisches Zentrum (DMZ) clinic. Their files were selected from files of over 11,400 patients, based on the fact that their blood pressure was measured at least three times during their stay, the first time within 24 h of their arrival by air in Israel. The patients in this retrospective study were divided into two groups: (a) 437 hypertensive psoriatics, some of them on anti-hypertensive medication, and some that were never before treated for their (mostly mild) hypertension. The diastolic blood pressure of these patients, upon arrival at the Dead-Sea, was 90 mm Hg or higher. Their anti-hypertensive medication (or lack of mediation) was not significantly changed during their 28-day stay at the DeadSea; (b) 705 psoriatics who had never been diagnosed as ‘hypertensives’, and whose diastolic measurement upon arrival was lower than 90 mm Hg. The age and sex of all patients were recorded. The first measurements were taken in all patients on the morning following their arrival at the Dead-Sea, thereafter defined as day ‘1’. The cut-off point of the diastolic pressure of 90 mm Hg was based on the American Heart Association definition of elevated arterial blood pressure, as being higher or equal than 140/90, with emphasis on the diastolic level [8]. Each of the two groups (a and b) were sub-divided into three age groups: >45, 45–65 and >65 years, and each age-group was sub-divided into the two sexes, producing a total of six groups of patients. Diastolic and systolic blood pressure were recorded for each of them once weekly during their stay. Blood pressure measurements were performed by the same physician and nurse in the mornings, before commencing outdoor treatment. A standard cuff manometer was used, with the patients in a sitting position. The fourth Korotkoff sound was taken as the index for diastolic pressure. The blood pressure values were fed into a computer, and the paired t-test was calculated for each patient, comparing the systolic and diastolic values found on day ‘1’ with those registered on subsequent days. Differences between groups were calculated by Analysis of Variance (ANOVA) and the Student’s paired t-test, wherever applicable. For the graphic representation - all hypertensive diastolic curves were adjusted to 100 mm Hg and all hypertensive systolic curves - to 155 mm Hg.
RESULTS
Plaque clearance Retrieving blood-pressure data The blood-pressure data analysed in the present study was taken retrospectively from files of 1,142 European psoriatics, mostly German (583 male and 559 females), who stayed for 28 days on the Dead-Sea shore, and were under medical supervision in the
The distribution of the psoriatic plaque clearance, within the patient population studied (n=688), by the patient age, at the time of treatment, is shown in Fig. 1. This figure clearly demonstrates that except for the very young age-group (<10 y; n=4), there was no significant difference between any of the age-groups in
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Distribution by duration of disease
Fig. 2. Percentage of psoriatics totally cleared of their psoriatic plaques after a four-week climatotherapy at the Dead-Sea, correlated with duration of the disease.
the percentage of patients totally cleared of their plaques during their stay at the Dead-Sea. In general, between 65.4% and 71.4% of the patients achieved total clearance, and up to 85% achieved partial clearance at the end of the treatment. Similarly, no differences were found between patients grouped according to the duration of their disease (from its onset until the 1995 treatment). In general, between 60.0% and 71.4% of the patients achieved full clearance, irrespective of the length of time that elapsed from the first appearance of the disease. One exception were patients suffering from psoriasis for a period of 40–49 years. These patients achieved a higher rate of clearance of 78.6% (Fig. 2). A significant difference was also found in the clearance rate between patients whose disease first appeared between the ages of 10–19 years (77.8%) and patients in which the disease appeared for the first time after the age of 60 (56.2% clearance). A less significant age-dependence in the relation between full plaque clearance and the age the patients first began to suffer from psoriasis. Our data suggest that the rate of full clearance is somewhat lower when the disease first appears late in life (Fig. 3).
Fig. 3. Percentage of psoriatics totally cleared of their psoriatic plaques after a four-week climatotherapy at the Dead-Sea, correlated with the patients’ age at the onset of the disease.
Number of patients
Cleared patients after 4 weeks (%)
Fig. 1. Percentage of psoriatics totally cleared of their psoriatic plaques after a four-week climatotherapy at the Dead-Sea, of various age groups.
Sun burns
8.2% 5%
Sun allergy Common cold
3.4% 2%
Oedema
1.4%
Gastroenteritis Herpes labialis
0.8%
Other infections
0.8% 0
2 4 6 8 10 Incidence in about 5,000 psoriatics (%)
Fig. 4. The most common side effects during a four-week climatotherapy at the Dead-Sea.
Side effects of climatotherapy Data on the type and frequency of the side effects in 502 psoriatic patients aged 65 y and over, and in 4,500 younger patients, were compared. All of the patients were treated for four weeks during 1988–1994, at the DMZ clinic. The most frequent side effects were as follows: sun burns (8.2%), sun allergy (5.0%), common cold (3.4%), oedema (2.0%), gastroenteritis (1.4%), herpes labialis (0.8%), other infections (0.8%), circulatory problems, eye infections and ear infections (<0.8% each). Altogether, 24% of the patients experienced at least one side effect, and 17% of them experienced more than one. No differences in the type and frequency of the side effects was detected between the two groups. All side effects disappeared within a few days, after an ambulatory treatment. A diagram illustrating the more frequent side effects is presented in Fig. 4.
Changes in blood-pressure An average decrease in systolic and diastolic blood pressures during the treatment period at the Dead-Sea was observed, irrespective of sex and age, in all of the groups, as shown in Fig. 5. This figure clearly demon-
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Hypertensive males
Hypertensive females
150 Systolic
140
*
100
*
//
//
Blood pressure (mm Hg)
160
*
* *
Diastolic
90 80
*
0
1
4 0 1 2 2 3 Duration of balneotherapy (weeks)
3
4
Fig. 5. Changes in diastolic and systolic blood pressure in various age-groups of hypertensive males (left) and hypertensive females (right) during a 4-week stay at the Dead-Sea. *P<0.05; d–d, >65 y; d- -d, 40–65 y; d · · · d, <40 y.
strates that while there is no significant difference between the various age groups in lowering their diastolic blood pressure throughout the study - differences in lowering the systolic measurements between the younger (<40 y) and older (>65 y) hypertensive patients, are remarkable, and highly significant. Similarly, no significant differences were noted between males and females, with the exception in the length of time the reduction in systolic blood pressure was sustained. In males it lasted about two weeks from the beginning of the treatment, in contrast to females in whom the reduction lasted over the whole four-week treatment period.
DISCUSSION The statistical success (plaque clearance) after a fourweek stay at the Dead-Sea has not changed much since Avrach et al. reported [5, 13] a 94.9% of improvement with this treatment schedule. Out of the 1,631 psoriatics followed-up carefully in this study, 34.5% were completely cleared, 43.3% showed marked improvement and 17.1% improved partially. The impressive part in Avrach’s papers was a comparison of the percentage of patients with recurrences within four weeks after cessation of the treatment, showing the Dead-Sea climatotherapy with the lowest recurrence (44%), followed by Goeckerman (45%), Dithranol (53%) and topical corticoids (95%). In another paper, Avrach (who spent many years at the International Psoriasis Treatment Center in EinBokek), reported that ‘96% were either cleared or improved during the four-week treatment period. Deterioration was found in patients with hypersensitivity to sunlight . . .’. The author elaborated by stating that ‘the acute guttate type improved quickly, the nummular and the plaque types more slowly, but still with excellent final results. The erythrodermic and generalized (more than 60% of the body surface)
types were also treated with success’ [14]. No subdivision to ages and sexes were performed in any of these studies. Very few comments have been published on sideeffects of climatotherapy at the Dead-Sea. Avrach’s report that erythrodermic and generalized (>60% of body surface) types were treated with particular precaution, e.g. they were exposed to less light, their topical applications were performed with caution and the time for their bathing in the hypertonic sea was restricted [14]. Azizi et al. [15] reported a severe sunburn reaction in a psoriatic patient following overexposure to a UV radiation source [15] and one patient developed an exfoliative dermatitis and had to be treated with systemic corticosteroids [14]. No detailed reports’ on side effects of this balneotherapy, neither sub-division of the erythrodermic and generalized psoriatic patients were given in this or in another paper in this medical field. The major finding of the present study is that the drop in blood pressure is more profound in the female psoriatics, where their initial blood pressure is lowered and remains low during all four weeks, while the drop in blood pressure of the hypertensive males is somewhat moderate, and is significant only during the first two weeks of the study. This is not surprising, as it has been suggested already before, that more women than men eventually develop hypertension, and as a consequence suffer less cardiovascular damage [17]. The first study on the effect of a four-week bathing at the Dead-Sea on blood pressure was published in 1984 by Bernheim et al., reporting that ‘a general decrease in blood pressure was found in all male subjects (n=19) at the Dead-Sea shore’. The authors concluded that, ‘The decrease in blood pressure at the Dead-Sea shore, is undoubtedly significant in healthy subjects’, and suggested ‘further investigation in order to determine the specific factors at the Dead-Sea that may play a role in blood pressure changes’ [7]. One of our colleagues from the Hadassah Hospital in Jerusalem recalled that during reconnaissance, trips from Jerusalem to the Dead-Sea over 35 years ago, ‘a significant drop in blood pressure was recorded in all members of the medical team who made the trip’ (Z. Even-Paz, unpublished) [9]. Bernheim et al., in their report suggested that the reduction in blood pressure at the Dead-Sea level (as compared to the Arad level, over 1,000 meters higher), might be caused by high temperatures prevailing in the area, by increased atmospheric pressure (about 800 mm Hg) or by increased oxygen concentration (+10%) in the area. It is believed that the latter effect is only marginal, as the blood is normally saturated with oxygen, and we promote two other explanations. The first one has to do with the hazy atmosphere overhanging the Dead-Sea which is rich in bromides, and has been known for over a century for its sedative and mild hypnotic effect [8]. It has been
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well documented that psychological methods (i.e. relaxation, biofeedback and meditation) have established non-pharmacological therapies for hypertension [10], and that on the average a reduction of 10 mm Hg in blood pressure may be achieved with such modalities. The second explanation has to do with the high content of magnesium in the Dead-Sea brine and haze. Magnesium has been established as playing an important role in the etiology of cardiovascular pathologies and causing vascular dilatation. The vasodilator effect of magnesium has been attributed to its Ca-channel blocking property, and to modulation of intracellular free Ca2+ in vascular smooth-muscle cells [11]. We have shown previously that both Br- and Mg2+ penetrate into the circulation during the patients’ period of balneotherapy, and suggested that both elements reach the circulatory system mainly via breathing rather than by bathing in the Sea. This is our explanation to the fact that no reduction in blood pressure was noticed when patients bathed in reconstituted Dead-Sea bath salts at home [12], and no drop in blood pressure occurs when patients sit in warm-water bath for thermal vasodilatation [16]. In summary, climatotherapy at the Dead-Sea is improving remarkably the psoriatic condition of over 85% of the patients, provided they spend four consecutive weeks under medical treatment at the DeadSea. The side effects involved in such a treatment are scarce and mild, and usually disappear upon diminishing the number of hours spent outdoors and/or by ambulatory treatment. An issue of great emphasis is that high blood pressure is not a contraindication to balneotherapy at the Dead-Sea. Moreover, elderly patients benefit from this treatment at least as well as younger patients. There are indications that the rate of full clearance is somewhat lower when the disease appears in elderly people, and that the clearance is
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slower when the duration of the disease is prolonged, but these findings warrant further observations. Our results also indicate that elderly patients are not at higher risk than younger psoriatics in developing sideeffects to balneotherapy, and that the drop in blood pressure, not so abrupt in the elderly, is well tolerated by them. The mechanism of this effect is now being studied in our Department.
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