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Manganese in the therapy of disseminated lupus erythematosus.

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Manganese in the Therapy of Disseminated
Lupus Erythematosus
Bg PAULD. REDLEAF
On the basis of a reported relationship
between manganese depletion and the
hydralazine syndrome, the possible therapeutic role of this metal in systemic
lupus erythematosus was studied. hlanganese glycerophosphate was administered to six patients with the latter disease without favorable effects, suggesting
that the hydralazine syndrome and systemic lupus erythematosus have different
pathogenic mechanisms.
Super le base del reportate relation inter
le depletion de manganese e le syndrome
de hydralazina, le possibile rolo therapeutic de iste metallo in systemic lupus
erythematose esseva studiate. Glvcerophosphato de manganese esseva administrate a sex patientes con le morbo mentionate. Le absentia de effectos favorabile suggere que le syndrome de hydralazina e systemic lupus erythematose
es governate per differente mechanismos
pathogenic.
T
HE SYNDROME which sometimes develops following the use of hydralazine resembles spontaneous lupus erythematosus in many respects.’ For
this reason recent studies implicating manganese depletion as an etiologic
factor in hydralazine disease are of considerable interest.2
Hydralazine chelates several trace metals. When given to cockerels, perosis,
a disease produced by manganese deficiency,” results. Perosis can be prevented by the simultaneous administration of manganese citrate.‘ Manganese
glycerophosphate prevents the convulsions which normally follow hydralazine
administration in rats,2 whereas several other trace metals are ineffective.
Furthermore, the glomerular “wire-loop” lesions of hydralazine disease in
dogs are prevented by the concomitant administration of manganese.‘
In human patients manganese inhibits the in vitro formation of the l u p s
erythematosus cell; in contrast, copper, cobalt, zinc and iron do not show
this effecte2 Finally, symptomatic benefit in two patients with spontaneous
lupus erythematosus given manganous ion has been reported.’ These findings prompted the following clinical evaluation of manganese therapy in
oiir patients with lupus erythematosus.
METHODSAND CASESELECTION
The author attempted to see all patients with lupus erythematosus on the adult medicine
wards and out-patient clinics of the University of Minnesota Hospitals during the period
from September, 1956 through April, 1357. All patients with the clinical diagnosis of
disseminated lupus erythematosus, substantiated by positive L.E. clot preparations, were
~
~~~
From the Department of Medicine, Uniuersity of Minnesota Hospitals, Minneapolis,
Mhn.
The uuthor wishes to express his nppreciution for the encouragement offered b y Dr.
C . J. Watson and Dr. Louis Tobian, ns well us for the cooperution of the staff of the
Department of Medicine in making the prescnt study possible.
This inves$igation was undertaken during the tenure of a post-doctoral fellowship of
the National Heurt Institute of the Nuticmul Institutes of Health, Public Health Seruice.
112
hfANGANESE I N DISSEMINATED LUPUS ERYTHEMATOSUS
113
included in this study. One patient died one week after hospitalization, and therapy in
this case could not be evaluated. Two patients considered to have rheumatoid arthritis,
despite positive clot tests,’ were not included.
The small number of patients available precluded a double-blind investigation. TO
enable us to include subjective responses in our evaluation, a placebo was administered
initially for a period of about two weeks. Thereafter manganese glycerophosphate was
given as a capsule in the suggested dose of 300 mg. three times daily after meals,’ for
a period of at least seven weeks. Ambulatory patients were examined at intervals of
two or three weeks, and appropriate laboratory studies, including hemoglobin determination, white blood counts and differentials, erythrocyte sedimentation rates, serum albumin
and globulin, and L.E. clot tests, were obtained.
Five female patients and one male patient completed the course of manganese therapy.
Their ages ranged from 26 to 55 years. The disease had been present from two to
nine years. Arthralgia, fever, asthenia, pleurisy or skin lesions were present in all when
manganese therapy was started. Four patients were receiving prednisone or hydrocortisone, which was continued at the same dosage during the administration of manganese.
RESULTS
There was no evidence of benefit, either subjectively or on physical
examination, as a result of manganese therapy. Erythrocyte sedimentation
rates remained elevated with remarkably little fluctuation. Anemia and
leukopenia, when present, persisted. Serum proteins were unchanged. L.E.
clot tests remained positive in all patients throughout therapy.
DISCUSSION
Evaluation of therapy of a disease as uncommon as lupus erythematosus
is made more difficult by the occurrence of spontaneous fluctuations or re-
missions. In six consecutive patients, none the less, evidence of benefit was
lacking with doses of manganese previously reported adequateS5While this
may not exclude possible value in some cases, analysis of the present results
reveals less than one chance in twenty that as many as 40 per cent of patients
with lupus might be expected to respond.
In a recent study6 manganese was found to be ineffective in the treatment of rheumatoid arthritis.
The disparity between our results and those of Comens raise the possibility that the pathogenesis of spontaneous lupus erythematosus and of
hydralazine disease may differ fundamentally, despite their similar clinical
manifestations.
SUMMARY
Because of its favorable effect in hydralazine disease, manganese therapy
was evaluated in six consecutive patients with disseminated lupus erythematosus. In no patient was there subjective or objective evidence of benefit.
This small series was statistically adequate to assure the likelihood that a
majority of patients with lupus erythematosus will not respond to manganese.
Our results suggest that the pathogenetic mechanism of lupus erythematosus,
which is still unknown, may differ from that of clinically similar hydralazine
disease.
114
PAUL D. REDLEAF
REFERENCES
1. Morrow, J. D., Schroeder, H. A. and
Perry, H. M., Jr.: Studies on the control of hypertension by Hyphex. 11.
Toxic reactions and side effects. Circidation 8:829, 1953.
2. Comens, P.: Manganese depletion as an
etiological factor in hydralazine disease. Am. J. Med. 20:944, 1956.
3. Wilgus, H. S., Jr., Norris, L. C. and
Heuser, G. F.: The role of certain
inorganic elements in the cause and
prevention of perosis. Science 84:252,
1936.
4. Slocumb, C. H.:
Rheumatic complaints
during chronic hypercortisonism and
syndromes during withdrawal of cortisone in rheumatic patients. Proc. Staff
Meet. Mayo Clinic 28.455, 1953.
5. Comens, P.: Personal communication.
6. Bepler, C. R. and Rogers, F. R.: A
double blind study using manganese
against placebo in rheumatoid arthritis. Am. J. Med. Sc. 234:459, 1957.
P ~ i r D.
l Redleof, M.D., Ireland Army Hospital, Fort Knox,
&j.
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disseminated, lupus, erythematosus, therapy, manganese
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