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Direct access to dermatologists
Volume 7 Number 6 December, 1982
Lars F6rstr6m and Richard Winkelmann while a research fellow at the Mayo Clinic. t We studied prostaglandin E concentrations in human eccrine sweat. In seven male and seven female normal volunteers, we found respective concentrations to average 0.48 - 0.28 ng/ml and 0.77 +-- 0.52 ng/ml (mean _+_standard error). One male patient with hyperhidrosis had a significant elevation in PGE2 activity (2 ng/ml (p < 0.0001)), whereas one female patient studied had a level not significantly different from controls (0.58 ng/ml). Since indomethacin can block the synthesis of prostaglandins and prostaglandins, at least in the kidney, can increase sodium and water excretion, 2 a relationship between indomethacin, eccrine gland prostaglandins, and hyperhidrosis may very well exist. More data certainly need to be acquired, but it is interesting how old drugs, such as aspirin or indomethacin, have over the past decade acquired new therapeutic significance (i.e., treatment of dysmenorrhea, :~ patent ductus in neonates, 4 urticarial vasculitis, s Bartter's syndrome), 6 possibly as a direct consequence o f their ability to block prostaglandin synthesis. Possibly, if some cases of hyperhidrosis are found to be associated with increased levels of prostaglandins in eccrine sweat, therapeutic benefit may be derived from treatment with nonsteroidal antiinflammatory drags.
Marc E. Goldyne, M.D., Ph.D. Department of Dermatology and Medicine University of California, San Francisco Rosalind Russell Arthritis Research Laboratory San Francisco General Hospital 1001 Potrero Ave., Room 3300 San Francisco, CA 94110
REFERENCES i. F~Srstr6m L, Goldyne ME, Winkelmann RK: Prostaglandin activity in human eccrine sweat. Prostaglandins 7: 459-484, 1974. 2. Johnston HH, Herzog JP, Lauler DP: Effect of prostaglandin E1 on renal hemodynamics, sodium and water excretion. Am J Physiol 213:939-946, 1967. 3. Henzl MR, et al: Primary dysmenorrhea: The therapeutic challenge. J Reprod Med 25(suppl 4):226-235, 1980. 4. Friedman WF, et al: Blockers of prostaglandin synthesis: A novel therapy in the management of the premature human infant with patent ductus arteriosus. Adv Prostaglandin Thromboxane Res 4:373-381, 1978. 5. Millns JL, et al: The therapeutic response of urticarial vasculitis to indomethacin. J AM ACAD DERMATOL 3:349-355, 1980. 6. Gill JR Jr, et al: Bartter's syndrome: A disorder characterized by high urinary prostaglandins and a dependence of hyperreninemia on prostaglandin synthesis. Am J Med 61:43-51, 1976.
Correspondence
801
Reply
To the Editor: I am grateful to Dr. Goldyne for sharing his data on prostaglandin concentrations in normal eccrine sweat and in patients with hyperhidrosis. His data suggest two types o f hyperhidrosis. One type is associated with increased PGE2. This type might respond to medicines such as indomethacin, which inhibit PGE2 synthesis. The other type is not associated with increased PGE2 and may be expected not to improve with treatment with indomethacin. Of additional interest would be learning which of these conditions is acquired and which inherited. The patient I reported had art acquired condition. I have seen several children with hyperhidrosis palmaris et plantaris who outgrew the condition about 1 to 2 years after menarche. It would be interesting to learn the PGE2 sweat concentrations in such cases.
John R. Tkach, M.S., M.D. 300 North Willson Bozeman, MT 59715
D i r e c t access to d e r m a t o l o g i s t s
To the Editor: Murrell stressed the importance o f "direct access" to the continued viability of our specialty (J AM ACAD DERMATOL 6:944, 1982). He pointed out that this free choice of physician is not present in many prepaid plans. I think all dermatologists should realize that there are at least three different types of plans, and an appropriate response to the absence o f direct access in these may vary.
1. The closed-panel HMOs (for profit and not for profit): A person joining such a plan agrees to give up his free choice of physician. In most o f these there is no direct access to a dermatologist. As a matter of fact there may be no direct access to a physician. It is not unusual for a patient to be seen instead by a nurse practitioner or physician's assistant. The other physicians in the community can do no more than try and be sure people are aware of the importance of free choice of physician and realize that once they join "the p l a n " they will only be seen by physicians employed by the HMO. 2. Physician-sponsored IPAs: M a n y of these have suffered from adverse selection. This was due to their starting out with a defensive posture. Their purpose was to keep the patients they had when a closed-panel H M O appeared in their area. The problem with this was that it meant they had sicker subscribers, and this led to
802
Journal of the American Academy of Dermatology
Correspondence
deficits. Executive directors of such plans have had to try and reduce the "red i n k " and they have stopped direct access, when they could, even if it was allowed initially. A n y educational campaign in an area where such an I P A exists of what our specialty can provide in the way o f service is likely to be counterproductive. 3. Venture capitol IPAs (for profit)l: These plans follow the lead of the closed-panel HMOs in that they stress avoiding adverse selection by soliciting young working people. In some, primary care physicians are paid on a capitation basis, and specialists to whom subscribers are referred are paid on a fee-for-service basis. In others all physicians are paid on a capitation basis. Generally, direct access is not a feature of such plans. Promotion o f what our specialty can provide in the way o f service would probably meet a stone wall from such a plan. The possibility of a mix of these and perhaps other plans in a particular geographic area should be taken into consideration, if our specialty decides to have a public education program.
Harvey J. Cohen, M.D. /70 Maple Ave. White Plains, NY 10601
REFERENCE 1. Saward E, Sorensen A: Competition, profit and the HMO. N Engl J Med 306:929-931, 1982.
About 35% to 50% of patients experience side effects such as gastrointestinal disturbances, headaches, confusion, or anemia from indomethacin therapy, and 20% must stop its use. ~ I made a computer-assisted thorough literature review and found forty-one relevant references. There were eleven clinical trial studies, with a total of 873 patients, in which no patients were found to have elevations of blood glucose or liver enzymes, z In contrast, six studies, with a total of 442 patients, revealed that 7% of the patients had a significant increase of at least one liver enzyme. 3 In thirteen studies totaling 649 patients, no elevated blood sugar was reported during indomethacin therapy. 4 However, in three studies totaling 169 patients, 1.7% developed elevated blood sugar during indomethacin therapy? Psoriatic arthritis is not listed as an approved indication for indomethacin therapy. While these risks are l o w - - l i v e r damage, 3%-7%, and hyperglycemia, 0.3%-1.7%, they should be kept in mind when using indomethacin for psoriatic arthritis. Diabetic patients are especially prone to a rise in blood glucose from indomethacin therapy, according to this literature search. Indomethacin may unmask a genetic subpopulation of diabetics or prediabetics, a phenomenon of potential use in diabetes research. I am grateful to Sharon L. Kasdin, M,D., for helping with the literature search.
John R. Tkach, M.S., M.D. 300 North Willson Bozeman, MT 59715
I n d o m e t h a c i n . i n d u c e d hyperglycemia in psoriatic arthritis To the Editor:
REFERENCES
The following case and literature review illustrate the need for dermatologists to remember that indomethacin can induce hyperglycemia and hepatotoxicity. Case report. A 30-year-old man had an 8-year history of moderately severe psoriasis that was very hard to treat and a 1-year history of mild progressive psoriatic arthritis. His internist treated his arthritis with indomethaein, 50 mg four times daily, for 4 months with improvement. There was no past history or family history of diabetes. On dermatologic hospitalization, complete blood count, urinalysis, and biochemical survey were normal except that blood sugar was 145 mg/dl (normal, 65-114) and alkaline phosphatase, 105 IU (normal, 23-85). These values remained elevated during the first 4 days o f hospitalization. One week after stopping indomethacin, these chemistry values had returned to normal.
t. Goodman LS, Gilman A: The pharmacologic basis of therapeutics. Toronto, 1975, Macmillan Publishing Co., p. 342. 2. Rothermich NO: An extended study of indomethacin. JAMA 195:531-536, 1966. 3. Bruckner FE, Randle APH: Use of indomethacin in rheumatoid arthritis. Ann Phys Med 8: 100, 1965. 4. Herne N, et al: Results of clinical tests with indomethaein in 72 patients. Nice Med 6: 137-145, 1968. 5. Katz AM, et al: A clinical trail of indomethacin in rheumatoid arthritis. CIin Pharmacol Ther 6:25-30, 1965.
Reply To the Editor: Certain medications, such as lithium, may cause exacerbations of psoriasis. On the other hand, some of the therapies for psoriasis may have serious side effects, e.g., the known potential for methotrexate to
Lars F6rstr6m and Richard Winkelmann while a research fellow at the Mayo Clinic. t We studied prostaglandin E concentrations in human eccrine sweat. In seven male and seven female normal volunteers, we found respective concentrations to average 0.48 - 0.28 ng/ml and 0.77 +-- 0.52 ng/ml (mean _+_standard error). One male patient with hyperhidrosis had a significant elevation in PGE2 activity (2 ng/ml (p < 0.0001)), whereas one female patient studied had a level not significantly different from controls (0.58 ng/ml). Since indomethacin can block the synthesis of prostaglandins and prostaglandins, at least in the kidney, can increase sodium and water excretion, 2 a relationship between indomethacin, eccrine gland prostaglandins, and hyperhidrosis may very well exist. More data certainly need to be acquired, but it is interesting how old drugs, such as aspirin or indomethacin, have over the past decade acquired new therapeutic significance (i.e., treatment of dysmenorrhea, :~ patent ductus in neonates, 4 urticarial vasculitis, s Bartter's syndrome), 6 possibly as a direct consequence o f their ability to block prostaglandin synthesis. Possibly, if some cases of hyperhidrosis are found to be associated with increased levels of prostaglandins in eccrine sweat, therapeutic benefit may be derived from treatment with nonsteroidal antiinflammatory drags.
Marc E. Goldyne, M.D., Ph.D. Department of Dermatology and Medicine University of California, San Francisco Rosalind Russell Arthritis Research Laboratory San Francisco General Hospital 1001 Potrero Ave., Room 3300 San Francisco, CA 94110
REFERENCES i. F~Srstr6m L, Goldyne ME, Winkelmann RK: Prostaglandin activity in human eccrine sweat. Prostaglandins 7: 459-484, 1974. 2. Johnston HH, Herzog JP, Lauler DP: Effect of prostaglandin E1 on renal hemodynamics, sodium and water excretion. Am J Physiol 213:939-946, 1967. 3. Henzl MR, et al: Primary dysmenorrhea: The therapeutic challenge. J Reprod Med 25(suppl 4):226-235, 1980. 4. Friedman WF, et al: Blockers of prostaglandin synthesis: A novel therapy in the management of the premature human infant with patent ductus arteriosus. Adv Prostaglandin Thromboxane Res 4:373-381, 1978. 5. Millns JL, et al: The therapeutic response of urticarial vasculitis to indomethacin. J AM ACAD DERMATOL 3:349-355, 1980. 6. Gill JR Jr, et al: Bartter's syndrome: A disorder characterized by high urinary prostaglandins and a dependence of hyperreninemia on prostaglandin synthesis. Am J Med 61:43-51, 1976.
Correspondence
801
Reply
To the Editor: I am grateful to Dr. Goldyne for sharing his data on prostaglandin concentrations in normal eccrine sweat and in patients with hyperhidrosis. His data suggest two types o f hyperhidrosis. One type is associated with increased PGE2. This type might respond to medicines such as indomethacin, which inhibit PGE2 synthesis. The other type is not associated with increased PGE2 and may be expected not to improve with treatment with indomethacin. Of additional interest would be learning which of these conditions is acquired and which inherited. The patient I reported had art acquired condition. I have seen several children with hyperhidrosis palmaris et plantaris who outgrew the condition about 1 to 2 years after menarche. It would be interesting to learn the PGE2 sweat concentrations in such cases.
John R. Tkach, M.S., M.D. 300 North Willson Bozeman, MT 59715
D i r e c t access to d e r m a t o l o g i s t s
To the Editor: Murrell stressed the importance o f "direct access" to the continued viability of our specialty (J AM ACAD DERMATOL 6:944, 1982). He pointed out that this free choice of physician is not present in many prepaid plans. I think all dermatologists should realize that there are at least three different types of plans, and an appropriate response to the absence o f direct access in these may vary.
1. The closed-panel HMOs (for profit and not for profit): A person joining such a plan agrees to give up his free choice of physician. In most o f these there is no direct access to a dermatologist. As a matter of fact there may be no direct access to a physician. It is not unusual for a patient to be seen instead by a nurse practitioner or physician's assistant. The other physicians in the community can do no more than try and be sure people are aware of the importance of free choice of physician and realize that once they join "the p l a n " they will only be seen by physicians employed by the HMO. 2. Physician-sponsored IPAs: M a n y of these have suffered from adverse selection. This was due to their starting out with a defensive posture. Their purpose was to keep the patients they had when a closed-panel H M O appeared in their area. The problem with this was that it meant they had sicker subscribers, and this led to
802
Journal of the American Academy of Dermatology
Correspondence
deficits. Executive directors of such plans have had to try and reduce the "red i n k " and they have stopped direct access, when they could, even if it was allowed initially. A n y educational campaign in an area where such an I P A exists of what our specialty can provide in the way o f service is likely to be counterproductive. 3. Venture capitol IPAs (for profit)l: These plans follow the lead of the closed-panel HMOs in that they stress avoiding adverse selection by soliciting young working people. In some, primary care physicians are paid on a capitation basis, and specialists to whom subscribers are referred are paid on a fee-for-service basis. In others all physicians are paid on a capitation basis. Generally, direct access is not a feature of such plans. Promotion o f what our specialty can provide in the way o f service would probably meet a stone wall from such a plan. The possibility of a mix of these and perhaps other plans in a particular geographic area should be taken into consideration, if our specialty decides to have a public education program.
Harvey J. Cohen, M.D. /70 Maple Ave. White Plains, NY 10601
REFERENCE 1. Saward E, Sorensen A: Competition, profit and the HMO. N Engl J Med 306:929-931, 1982.
About 35% to 50% of patients experience side effects such as gastrointestinal disturbances, headaches, confusion, or anemia from indomethacin therapy, and 20% must stop its use. ~ I made a computer-assisted thorough literature review and found forty-one relevant references. There were eleven clinical trial studies, with a total of 873 patients, in which no patients were found to have elevations of blood glucose or liver enzymes, z In contrast, six studies, with a total of 442 patients, revealed that 7% of the patients had a significant increase of at least one liver enzyme. 3 In thirteen studies totaling 649 patients, no elevated blood sugar was reported during indomethacin therapy. 4 However, in three studies totaling 169 patients, 1.7% developed elevated blood sugar during indomethacin therapy? Psoriatic arthritis is not listed as an approved indication for indomethacin therapy. While these risks are l o w - - l i v e r damage, 3%-7%, and hyperglycemia, 0.3%-1.7%, they should be kept in mind when using indomethacin for psoriatic arthritis. Diabetic patients are especially prone to a rise in blood glucose from indomethacin therapy, according to this literature search. Indomethacin may unmask a genetic subpopulation of diabetics or prediabetics, a phenomenon of potential use in diabetes research. I am grateful to Sharon L. Kasdin, M,D., for helping with the literature search.
John R. Tkach, M.S., M.D. 300 North Willson Bozeman, MT 59715
I n d o m e t h a c i n . i n d u c e d hyperglycemia in psoriatic arthritis To the Editor:
REFERENCES
The following case and literature review illustrate the need for dermatologists to remember that indomethacin can induce hyperglycemia and hepatotoxicity. Case report. A 30-year-old man had an 8-year history of moderately severe psoriasis that was very hard to treat and a 1-year history of mild progressive psoriatic arthritis. His internist treated his arthritis with indomethaein, 50 mg four times daily, for 4 months with improvement. There was no past history or family history of diabetes. On dermatologic hospitalization, complete blood count, urinalysis, and biochemical survey were normal except that blood sugar was 145 mg/dl (normal, 65-114) and alkaline phosphatase, 105 IU (normal, 23-85). These values remained elevated during the first 4 days o f hospitalization. One week after stopping indomethacin, these chemistry values had returned to normal.
t. Goodman LS, Gilman A: The pharmacologic basis of therapeutics. Toronto, 1975, Macmillan Publishing Co., p. 342. 2. Rothermich NO: An extended study of indomethacin. JAMA 195:531-536, 1966. 3. Bruckner FE, Randle APH: Use of indomethacin in rheumatoid arthritis. Ann Phys Med 8: 100, 1965. 4. Herne N, et al: Results of clinical tests with indomethaein in 72 patients. Nice Med 6: 137-145, 1968. 5. Katz AM, et al: A clinical trail of indomethacin in rheumatoid arthritis. CIin Pharmacol Ther 6:25-30, 1965.
Reply To the Editor: Certain medications, such as lithium, may cause exacerbations of psoriasis. On the other hand, some of the therapies for psoriasis may have serious side effects, e.g., the known potential for methotrexate to