I II I I Psoriasis treatment at the Dead Sea: A natural selective ultraviolet phototherapy David J. Abels, M.D., and Jonathan Kattan-Byron, M.D. Beer-Sheva, Israel A naturally filtered ultraviolet spectrum of sunlight along with other natural factors are utilized in the management of psoriasis at the Dead Sea area in Israel. In 110 patients with psoriasis, 85.5% achieved complete clearing or excellent improvement. These results compare favorably with other therapeutic regimens used today in the treatment of psoriasis. Since systemic medications are avoided, the potential risks may be considerably lessened. Therefore, this therapeutic modality may be considered in the management spectrum of psoriasis. (J AM ACAD DERMATOL12:639-643, 1985.) Since the advent of PUVA, ~ the combination of psoralen (P) and long-wave ultraviolet radiation (UVA), the management of psoriasis has taken on a new dimension. Numerous scientific articles have been written discussing this form of treatment and elucidating the principles involved that are presently being defined. Concurrent with this knowledge, much more is now understood about photobiologic mechanisms and the UV spect r a m . 2'3 Along with this basic knowledge, phototherapy has progressed today into a well-accepted treatment in most major medical centers. Selective ultraviolet phototherapy (SUP), first described in the European literature, is currently gaining popularity and many phototherapy units are now utilizing this principle# Climatotherapy, defined as a treatment combining the natural elements of a specific geographic location, has been used at the Dead Sea in Israel for over twenty years. 5'6 Because of its unique position, the treatment at the Dead Sea mainly consists of the patients being exposed to a UV spectrum of long-wave ultraviolet light found nat- From the Division of Dennatology, Soroka University Hospital and Faculty of Health Sciences, Ben Gurion University of the Negev. Accepted for publication Nov. 15, 1984. Reprint requests to: Dr. David J. Abels, 5 Nitza Blvd., Apartment 26, Netanya, Israel 42269. urally in high intensity7 only in that area of the world and, in addition, a sea rich in natural minerals and salts. This study of 110 patients with psoriasis confirms the value of this treatment with the results comparable to other established treatments used today in the management of psoriasis. METHODS During the period of time from the end of March 1983 to June 1983, we investigated 110 patients enrolled in a Dermatology Clinic at the Dead Sea in Israel sponsored by the Israeli government. Since the study was primarily designed for the treatment of psoriasis, patients with other skin diagnoses were eliminated from the study. Ten patients with psoriasis were also excluded: one because excessive alcoholic intake interfered with treatment compliance; a second patient because he remained under treatment for only 1 week, which is considered insufficient time; a third patient was not included because her primary diagnosis was in doubt; the fourth, because he failed to follow the treatment regimen; the fifth, because her primary diagnosis was psoriatic arthritis and she had no skin involvement; and the last five patients, because they left the treatment without a final examination. All the other patients were randomly included and no selective basis was utilized. As mentioned, all patients included in this study had a diagnosis of psoriasis. The main type was plaque or patchy involvement with six patients having psoriasis guttata. The psoriatic involvement was visually estimated at the start and conclusion of treatment and the 639 640 Journal of the American Academyof Dermatology Abels and Kattan-Byron Table I. Incidence and improvement with severity of involvement Percent involvement prior to treatment Number (and percentage) of patients prior to treatment 0-9 10-19 20-29 30-100 13 (11.8%) 24 (21.8%) 30 (27.3%) 43 (39.1%) patients were examined always by the same two physicians, providing relative consistency to the findings. The treatment consisted primarily of sun exposure beginning with 10 to 20 minutes, depending on the skin type, in the m6rning and the same in the afternoon, with an increase in increments of 10 minutes each day until a maximum of approximately 6 hours per day was reached. Bathing in the Dead Sea was highly variable but routinely it began with 5 minutes in the morning and the same in the afternoon, increasing every 3 days another 5 minutes until 30 minutes in the morning and 30 minutes in the afternoon was obtained. All patients were examined on a daily basis and the treatment was adjusted as required. Topical medications included petrolatum, body and bath oils, and various concentrations of sulfur-salicylic acid ointments principally used for keratolytic purposes. In selected patients, a tar ointment was added toward the end of treatment, mainly for its UV-enhancing effect. Scalp treatments were administered by a nurse on a daily basis as needed and consisted mainly of localized applications of sulfur-salicylic acid ointments. Shampooing of the scalp was with a 5% cetrimide shampoo with or without tar added. At no time was any other topical or systemic medication used in the treatment. No topical or systemic corticosteroids were utilized. The patients underwent treatment from a minimum of 14 days to a maximum of 42 days, with the average patient stay at the Dead Sea being 26 days. RESULTS Of the 110 patients included in this study, 56 were male and fifty-four, female. The youngest was 10 and the oldest, 76, with the average 43 years of age. The range of psoriatic involvement at the beginning of treatment was from 1% t o 9 0 % (Table I) with the average involvement at the start of 29%. The percentage improvement was classified into groups (Table II) and defined as minimal improve- Number (and percentage) of patients with complete clearing or excellent improvement 13 18 28 35 (100%) (75%) (93.3%) (81.4%) ment, 5% to 20%, no patients; definite improvement, 20% to 50%, one patient; considerable im-~ provement, 50% to 80%, fifteen patients; excellent improvement, 80% to 95%, 32 patients; complete clearing, 95% to 100%, sixty-two patients. The percentage improvement was estimated relative to the original extent of disease. Forty-three patients had 30% or greater coverage with psoriasis (Table I). In analyzing the patients in this group, 81.4% showed complete clearing or excellent improvement. In the group with 20% to 29% involvement, 93.3% had complete clearing or excellent improvement. Those with 10% to 19% involvement had 75% complete clearing or excellent improvement, and all thirteen patients with 0% to 9% involvement showed complete clearing or excellent improvement. Included in other findings, thirty-one patients (28%) gave a history or had evidence of psoriatic arthropathy. Virtually all patients expressed some degree of improvement in their arthritic symptoms at the time of discharge. Fifty-two patients (47%) revealed nail changes characteristic of psoriasis. No significant complications were encountered. Occasionally a patient experienced transient pustules primarily on the legs that cleared with topical antibiotics. Unrelated ear or skin infections occurred infrequently and responded to appropriate therapy. In a few patients, a pruritic sunburn-like erythema or a sun sensitivity appeared early in treatment but always resolved after several days' avoidance of sun exposure to the affected areas. Only very rarely did blistering accompany the sunburn-like erythema, and it responded to local treatment. DISCUSSION The Dead Sea area, situated 390 meters below sea level, is the lowest place on earth and conse- Volume 12 Number 4 April, 1985 Psoriasis treatment at Dead Sea 641 Table II. Treatment response Definition Psoriasis worse No change Minimal improvement (less scaling and/or erythema) Definite improvement (moderate flattening of plaques; less scaling and erythema) Considerable improvement (considerable flattening of all plaques; minimal erythema and scaling) Excellent improvement (almost complete flattening of all plaques; minimal erythenaa or scaling) Complete clearing (complete flattening of all plaques; no erythema or scaling but variable pigmentation may remain) Percent involvement improved* Number of patients 0 0 5-20 0 0 0 0 0 0 20-50 1 0.9 50-80 15 13.6 80-95 32 29.1 95-100 62 56.4 Percent of patients *Compared to original involvement of psoriasis. quently has certain characteristic atmospheric and climatic features present at no other location in the world. First, the Dead Sea itself has the highest concentration of salts found in any natural body of water. These salts are present in a total concentration of 33% as compared, for example, to the Great Salt Lake in Utah at 20% to 27% or the ocean, at 3%. Magnesium chloride is the salt with the highest concentration at 50%, with sodium chloride, 25%, calcium chloride, 12%, and potassium chloride, 4%. 8 In the sea, bromides are also found in significant concentration. These elemental properties of the sea are combined with unique photobiologic characteristics that are also present only in this area. The sunburn spectrum of ultraviolet light is very weak at the D e a d S e a 9 because of a continuous haze that develops over the water. This haze or mist occurs from an extraordinarily high water evaporation estimated at two billion cubic meters per year. Subsequently, the majority of UVB sunburning rays are filtered out, thus allowing a greater exposure to the longer wavelength UVB and penetrating natural UVA rays. 7 These two major factors, the sea and the sun, have served as a basis for the management of many different medical illnesses at the Dead Sea, par- ticularly dermatologic disorders. Psoriasis has been the main skin disease treated, although atopic dermatitis, neurodermatitis, vitiligo, acne, and ichthyosis have responded to this treatment. From our experience and also that of others, t° the principal climatic factor at the Dead Sea accounting for the benefit seen, particularly in psoriasis, most likely is the naturally filtered spectrum of UVA and the longer wavelength UVB. Because of this, we are most probably dealing with a form of natural selective ultraviolet phototherapy (NSUP). PUVA, the combination of psoralen and longwave ultraviolet radiation (UVA), is considered today as one of the major therapeutic modalities in the management of psoriasis. Since it demonstrates a high clearance rate, nearly 90%, 11 it has to be considered as a treatment to which other therapeutic regimens are compared, z2,~3The results in our study of 110 patients with psoriasis treated with NSUP showed that by classifying the patients according to their percentage improvement (Table II), 56.4% had complete clearing and 29.1%, excellent improvement. Grouped together, 85.5% had complete clearing or excellent improvement of their psoriasis. This overall figure combining complete clearing and excellent improvement together would support the treatment value with 642 Journal of the American Academy of Dermatology Abels and Kattan.Byron NSUP and its overall efficacy would compare favorably with PUVA. AI! our patients responded to treatment with just one obtaining less than considerable improvement (Table II). In another study done at the Dead Sea, 1° 77% had complete clearing or marked improvement, which is near our finding of 85.5% complete clearing or excellent improvement, To draw any further comparisons with this study is difficult because of the lack of quantification of their groups, but their findings generally correlate with our results. It should be noted that in addition to NSUP, the treatment schedule in this study included topical medications mainly used for lubrication and keratolytic purposes. A tar ointment was added in selected patients toward the termination of treatment primarily for its UV-potentiating effect. Future data may show that a combination therapy of NSUP with an active antipsoriatic medication may significantly enhance the treatment results. The average stay at the Dead Sea for our patients was 26 days. Even though the minimum stay was only 14 days, the eleven patients who stayed for this period of time had an average clearing of 87.5%. Many patients did not show significant improvement until the third or fourth week; therefore, we usually suggest that patients undergo treatment for a minimum of 3 weeks and preferably for a period of 4 weeks. Since some patients did experience substantial improvement after 14 days, it is likely that future work will demonstrate that on an individual basis, the period of time to achieve maximum benefit will vary between 14 and 28 days. Psychotherapeutic influences certainly play a role in the patients' overall improvement at the Dead Sea. Grouped together for several weeks in a relaxed, pleasant atmosphere allows those affected with this chronic skin disorder to share and discuss similar frustrations and apprehensions. Many realize for the first time that they are not alone in their suffering, and visualizing their own improvement along with that of others serves as an important psychologic stimulus to their general progress. Three additional areas requiring objective confirrnation and further study are the response seen in psoriatic arthritis, possible adverse side effects, and the recurrence or relapse rate. An added ad- vantage of NSUP was its benefit with psoriatic arthropathy. Twenty-eight percent of our patients had arthritic symptoms and all benefited from the treatment. Detailed investigation should now be undertaken to demonstrate conclusively the benefits of this treatment in psoriatic arthritis and precisely what part the sea and its minerals may also play in the therapeutic result. Other important factors needing evaluation are particularly the long-term side effects. .4 Since NSUP eliminates entirely the taking of systemic medications, such as psoralens, we are not as concerned, for instance, about the potential ophthalmologic hazards 15 and the patients do not have to wear protective glasses during or after therapy. The carcinogenic, j6,1v mutagenic, ts and immunologic t9 complications of the other treatments for psoriasis are now just beginning to be recognized. No investigations of these parameters have as yet been carried out at the Dead Sea, but currently we are unaware of any skin cancer appearing in any of our patients who were treated at the Dead Sea prior to this study. This certainly requires further confirmation with large numbers of patients. In the future, we also hope to study the problem of premature aging of the skin, which may possibly be a potential complication. 2° The recurrence or relapse rate of the psoriasis is another important issue that also must be considered. Once more, we have no conclusive data at this time, but after interviewing several hundreds of patients who have been at the Dead Sea before, NSUP will frequently give a longer remission than other modalities without specific maintenance therapy being administered between clearance courses, t0 Patients commonly mention a 3- to 6-month period of time before noticing the beginning of a relapse and state that the psoriasis frequently does not reappear as severely. Further study and documentation should be forthcoming. REFERENCES 1, Parrish JA, Fitzpatrick TB, Tanenbaum L, et al: Photochemotherapy of psoriasis with oral methoxsalen and long-wave ultraviolet light. N Engl J Med 291:12071211, 1974. 2. Farber EM, Abel EA, Charuworn A: Recent advances in the treatment of psoriasis. J AM ACADDERMATOL8:311321, 1983. 3. Parrish JA: Phototherapy and photochemotherapy of skin diseases. J Invest Dermatol 77:167-171, 1981. Volume 12 Number 4 April, 1985 Psoriasis treatment at D e a d Sea 4. Tronnier H, Heidbuchel H: Zur therapie der psoriasis vulgaris mit ultravioletten Strahlen. Z Hautkr 51:405424, 1976. 5. Dostrovsky A, Sagher F: The therapeutic effects of the Dead Sea on some skin diseases. Harefuah 57:143-145, 1959. 6. Dostrovsky A, Shanon J: Influence of helio-balneotherapy at the Hot Spring of Zohar (Ein Bokek) on psoriasis. Harefuah 64:127-129, 1963. 7. Goldberg LH, Kushelevsky AP: Ultraviolet light measurements at the Dead Sea, in Farber EM, et al, editors: Psoriasis. Proceedings of the Second International Symposium, 1976. New York, 1977, Yorke Medical Books, pp. 461-463. 8. Sehamberg IL: Treatment of psoriasis at the Dead Sea. Int J Dermatol 17:524-525, 1978. 9. Kushelevsky AP, Slit'kin MA: Ultraviolet light measurements at the Dead Sea and at Beer-Sheba. Isr I Med Sci 11:488-490, 1975. 10. Avrach WW: Climatotherapy at the Dead Sea, in Farber EM, et al, editors: Psoriasis, Proceedings of the Second International Symposium, 1976. New York, 1977, Yorke Medical Books, pp. 258-261. 11. Bickers DR: Position papermPUVA therapy. J AM ACAD DERMATOL8:265-270, 1983. 12. Parrish JA: Treatment of psoriasis with long-wave ultraviolet light. Arch Dermatol 113:1525-1528, 1977. 643 13. Van Weelden H, Young E, Van Der Leun JC: Therapy of psoriasis: Comparison of photoehemotherapy and several variants of phototherapy. Br J Dermatol 103:1-9, 1980. 14. Current status of oral PUVA therapy for psoriasis. J AM ACAD DERMATOL1:106-117, 1979. 15. Lerman S, Megaw J, Willis I: Potential ocular complications from PUVA therapy and their prevention. J Invest Dermatol 74:197-199, 1980. 16. Hofman C, Pelwig G, Braun-Falco O: Bowenoid lesions, Bowens disease and keratoacanthoma in long-term PUVA-treated patients. Br J Dermatol 101:685-692, 1979. 17. Stem RS, Thibodeau LA, Kleinermann RA, et al: Risk of cutaneous carcinoma in patients treated with oral methoxsalen photochemotherapy for psoriasis. N Engl J Med 300:809-813, 1979. 18. Bridges B, Strauss G: Possible hazards of photochemotherapy for psoriasis. Nature 28:523-524, 1980. 19. Morison WL: Photoimmunology. J Invest Dermatol 77:71-76, 1981. 20. Abel EA, Cox AJ, Farber EM: Epidermal dystrophy and actinic keratoses in psoriasis patients following oral psoralen photochemotherapy (PUVA). J AM ACAD DERMATOL7:333-340, 1982. ABSTRACTS Clonidine treatment in paroxysmal localized hyperhidrosis Kuritzky A, Hering R, Goldhammer G, et al: Arch Neuroi 41:1210-1211, 1984 These neurologists in Israel say that for some types of localized paroxysmal hyperhidrosis, clonidine may be useful. Other antianxiety medicines sometimes help too. P.C.A. Merkel cell carcinoma (endocrine carcinoma of the skin) of the head and neck Goepfert H, Remmler D, Silva E, et al: Arch Otolaryngol 110:707-712, 1984 Merkel cell carcinomas of the skin metastasize early and often, as shown in this study of forty-one patients. Special awareness and therapy are needed. P.C.A. Filaggrin distribution in keratoacanthomas and squamous cell carcinoma Klein-Szanto AJ, Barr RJ, Reiners JJ Jr, et al: Arch Pathol Lab Med 108:888-890, 1984 Filaggrin appears to be absent from squamous cell carcinomas but plentiful in keratoacanthomas. If sustained by others, this fact may be useful in diagnosis, Filaggrin is a histidine-rich protein in the normal granular layer of skin. P.C.A. Cyclic nucleotides and calcium transport in cultured dermal fibroblasts from progressive systemic sclerosis and rheumatoid arthritis patients Grozdova MD, Khokhlova JV, Panasyuk AF, et al: Arthritis Rheum 27:1144-1149, 1984 From the USSR comes this report of abnormalities in fibroblasts in scleroderma. Epinephrine-stimulated changes in calcium-ion uptake were notable. Their choice of controls may be unsuitable. P.C.A. Extrapulmonary oat cell carcinoma Ibrahim NB, Briggs JC, Corbishley CM: Cancer 54:1645-1661, 1984 Extrapulmonary oat cell carcinomas are of interest now due similarly to endocrine cell tumors and to the view that these may be poorly formed carcinoid tumors. Some occur in skin as noted in this review, and the relation to the Merkel cell tumors is considered. Many questions remain Unanswered concerning these special neoplasms. P.C.A.