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Development of antinuclear antibodies during minoxidil therapy.

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1. Tan EM: Antinuclear antibodies and the LE cell phenomenon, Rheumatology and Immunology. Edited by AS Cohen. New York, Grune & Stratton, Inc, 1979, pp 80-85
2. Dubois EL, Editor: The clinical picture of systemic lupus
erythematosus, Lupus Erythematosus. Second edition. Los
Angeles, University of Southern California Press, 1974, p
37 1
3. Rose NR, Hjort T, Rumke P, Harper MJK, Vyazov 0:
Techniques for detection of iso- and autoantibodies to human spermatozoa. Clin Exp Immunol23:175-199, 1976
4. Gusdon J P Maternal immune responses in pregnancy, Immunology of Human Reproduction. Edited by JS Scott,
WR Jones. New York, Academic Press, 1976, p 103
Development of antinuclear antibodies during
minoxidil therapy
To the Editor:
Minoxidil is a potent vasodilator with direct action on arteriolar smooth muscle (1). Numerous studies
have documented the effectiveness of minoxidil in reducing severely elevated blood pressure, and some side
effects have been noted-hypertrichosis, sodium retention (2), pericardial effusion (3), and serosanguinous
bullae (4). The development of a positive antinuclear
antibody (ANA) within months of starting minoxidil
therapy provides the basis for this letter.
A 35-year-old woman was referred for minoxidil
therapy due to refractory hypertension. Her history was
remarkable for asthma and chronic glomerulonephritis.
In September 1977, after a brief period of maintenance
hemodialysis, she received a renal transplant from an
HLA-identical sibling. Despite good allograft function,
refractory hypertension developed (180/ 120 mmHg).
Medications employed at the time of her referral (May
1978) included furosemide, prazosin, and clonidine.
Extensive evaluation (including arteriography,
selective venous renins, and allograft rejection studies)
revealed no cause for her hypertension. Results of baseline serologic studies prior to transplantation and in
1978 were normal, including VDRL, C3, CH50, ANA,
and rheumatoid factor (RF). Four months after starting
minoxidil, at a dose of 15 mg/day, a speckled ANA pattern at a titer of 1 :320 was noted. Multiple determinations over 10 months utilizing 3 different commercial
kits demonstrated a homogeneous pattern at a titer of
1:320. Other serologic studies remained normal, including C3, C4, CH50, RF, VDRL, LE preparation, cryoglobulins, and direct and indirect Coombs tests.
Several months later, the patient was hospitalized on 4 occasions with viral respiratory infection, hy-
pokalemia and hypercalcemia, positive blood cultures
from the previous admission, fever, and a new diastolic
murmur. Significant findings at the last admission were
a temperature of 38.5"C, pulse 90, respirations 20,
blood pressure 146/70, hypertrichosis, and Cushingoid
facies. The cardiac examination revealed a laterally displaced apical impulse, S4, midsystolic murmur (old),
and III/VI early diastolic murmur (new). Results of
laboratory studies were normal except for serum K+ of
3.0 mEq/liter, LDH 483 IU/liter, and proteinuria. An
echocardiogram demonstrated normal valvular function
but large anterior and posterior pericardial effusions.
The patient died on the second hospital day of cardiac
arrest and cardiac tamponade despite vigorous resuscitative efforts following aspiration of the effusion in the
catheterization site. At autopsy, subacute bacterial
endocarditis was noted with hemopericardium and generalized atherosclerosis. There was no evidence of vasculitis in any organ.
Drug-induced antinuclear antibodies have been
reported with a variety of drugs, but with only 2 antihypertensive agents, hydralazine and methyldopa (5).
The temporal relationship of the positive ANA (September 1978) to the introduction of minoxidil (May
1978) and the previously negative results while using
other drugs suggests a role for minoxidil. This is supported by consistently normal complement values, homogeneous ANA pattern, and absence of vasculitis. The
recurrence of severe hypertension requiring intensive
care after omission of minoxidil in a previous patient
precluded a trial of withdrawal and rechallenge. Additional patients under our care have developed transiently positive tests for ANA at a titer of 1:40. This
transiently positive ANA test has been mentioned in 2
other reports (2,6), but the titers and fluorescent pattern
were not specified.
The question of endocarditis in this patient must
be addressed. Although circulating immune complexes
were not sought, no other immunologic abnormalities
associated with infective endocarditis were present-hypergammaglobulinemia, reduced complement, RF, and
cryoglobulins (7). A positive fluorescence test for ANA
has not been a recognized feature of endocarditis. Pericardial effusion and occasional tamponade have been
observed in 3% of nondialysis patients treated with minoxidil (3). Serologic studies on the pericardial fluid in
this patient were unremarkable, suggesting that the effusion and tamponade were not due to an immunologic
disorder. Therefore, the effusion and endocarditis appear to be unrelated to the serologic abnormality.
Although the development of a positive ANA
may have been a fortuitous finding in this patient, the
57 1
setting, time course, absence of vasculitis, and previous
reports suggest that this agent should be considered as
an addition to the number of drugs causing immunologic abnormalities.
The opinions and assertions contained in this paper are the author’s and not to be construed as those of
the Navy Department or the naval service at large.
Chief of Nephrology
Naval Regional Medical Center
San Diego, CA 92134
1. DuCharme DW, Freyburger WA, Graham BE, Carlson
RG: Pharmacologic properties of minoxidil: a new hypotensive agent. J Pharmacol Exp Ther 184:662-670, 1973
2. Mitchell AC, Pettinger WA: Long-term treatment of refractory hypertensive patients with minoxidil. JAMA
239:2131-2138, 1978
3. Product manograph LONITEN. Kalamazoo, MI, The Upjohn Co., November 1979, pp 1-20
4. Rosenthal T, Teicher A, Swartz J, Boichis H Minoxidil-induced bullous eruption. Arch Intern Med 138:1856-1857,
5 . Fernandez-Madrid F, Mattioli M: Antinuclear antibodies
(ANA): immunologic and clinical significance. Semin Arthritis Rheum 633-124, 1976
6. Bryan RK, Hoobler SW, Rosenzweig J, Welher JM, Purdy
JM: Effect of minoxidil on blood pressure and hemodynamics in severe hypertension. Am J Cardiol 39:796801, 1977
7. Cabane J, Godeau P, Herreman G, Acar J, Digeon M,
Bach J-F: Fate of circulating immune complexes in infective endocarditis. Am J Med 66:277-282, 1979
Clinical photography
To the Editor:
The useful, practical article “Clinical Photography in the Rheumatic Diseases’’ by Weisman and
Turner (Arthritis Rheum 23:863, 1980) prompts me to
offer the following observations, based on about 10
years’ experience with this kind of photography. The
equipment I use is similar to that employed by the
writers of the article: Nikon camera body, “Micro-Nikkor-P-C” 55 mm lens, and an inexpensive electronic
flash apparatus.
As Weisman and Turner point out, it is important to be able to make photographs when and where
the opportunity arises. Portable flash units often are
convenient to provide light for close-up photographs,
but may be inadequate if pictures of an entire limb
or torso are wanted. If high-speed film (such as Ektachrome 200) is used, it often is possible to take close-up
or more distant photographs with available light and
avoid use of the flash unit. Filters are available to correct the color imbalance otherwise introduced when fluorescent light provides the illumination. When the flash
is not used, it usually is necessary to make a series of
test exposures in the places where photographs will be
made to determine the correct exposure times for various camera-to-subject distances.
To display contours, as when it is desired to
show swelling, oblique illumination often is preferable
to frontal lighting. In this situation, a source of light
which can be separated from the camera is better than a
flash apparatus fixed to the camera.
The black velvet background recommended by
the authors may give excessive contrast for lightskinned subjects and insufficient contrast for those with
dark skin. A good background is provided by the sheets
of absorbent blue paper with plastic backing which are
used in hospitals. These contrast satisfactorily with all
skm tones and are pleasant to the eye, non-distracting,
readily available, and disposable.
Department of Medicine
Howard University
Washington, DC
To the Editor:
Dr. Reynolds makes some very practical recommendations for clinical photography, especially concerning the use of available light. It must be remembered, however, that the high efficiency of electronic
flash units allows the use of a small lens aperture, giving
a greater depth of field, an important requirement for
patient photography. Dr. Reynolds also points quite appropriately to the use of oblique lighting for contours.
With portable equipment this is not often possible but is
certainly desirable.
His final comments on background illumination
are pertinent. Neutral mid-gray or mid-blue is best
suited to skin tones and would soften the contrast that
occurs with a black background. However, when using
background materials that are found in the hospital setting, one must be careful to find objects that are
unobtrusive and neutral in texture and color. The objects that Dr. Reynolds suggests often have a texture
that is discernible and displays bright contrasty color.
These materials should be avoided. The best back-
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development, antibodies, minoxidil, antinuclear, therapy
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