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Effect of atropine sulfate in pulmonary hypertrophic osteoarthropathy.

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822
CASE REPORT
EFFECT OF ATROPINE SULFATE IN PULMONARY
HYPERTROPHIC OSTEOARTHROPATHY
EDRICK LOPEZ-ENRIQUEZ, A. RAPHAEL MORALES, and FRANCISCO ROBERT
A 49-year-old patient with pulmonary hypertrophic osteoarthropathy was treated with 0.4 mg of atropine sulfate every 4 hours for 14 days. A good clinical
response was obtained as measured by handgrip
strength, range of motion, and quantitative thermography. Chemical vagotomy supports the hypothesis of
the vagal reflex as the pathophysiological mechanism in
pulmonary hypertrophic osteoarthropathy.
Several pathophysiologic mechanisms have been
proposed for pulmonary hypertrophic osteoarthropathy
(1). One theory is that the syndrome results from a
neuroreflexogenic afferent stimulus conducted by the
vagus nerve (2).
This report describes the results of chemical vagotomy in a case of pulmonary hypertrophic osteoarthropathy.
CASE REPORT
A 49-year-old man enjoyed good health until
April 1976 when he noticed a “lump” in his right thigh.
In June 1976 he was admitted to the San Juan Veterans
Administration Hospital, with a large mass in the right
thigh a biopsy corroborated the diagnosis of fibrohisFrom the University of Puerto Rico School of Medicine and
the San Juan Veterans Administration Hospital, Rio Piedras, Puerto
Rim.
Edrick L6pez-Enriquez, MD: Rheumatology Section, Department of Medicine, University of Puerto Rim School of Medicine;
A. Rafael Morales, MD: Department of Medicine, San Juan Veterans
Administration Hospital; Francisco Robert, MD: Department of
Medicine, San Juan Veterans Administration Hospital.
Address reprint requests to Edrick L6pez-Enriquez, MD,
Riverside K-13, San Germln, Puerto Rim 00753.
Submitted for publication December 14, 1979; accepted in
revised form February 29, 1980.
Arthritis and Rheumatism, Vol. 23, No. 7 (July 1980)
tiocytic sarcoma grade I11 with bone and lung metastases. Treatment with Adriamycin, nitrosourea, and cyclophosphamide was given for 18 months. Local and
metastatic lesions disappeared by December 1977. In
June 1978 the patient developed dry cough and dyspnea
on exertion, and chest x-ray films showed recurrence of
the pulmonary lesions, but the patient refused further
chemotherapy. In September 1978 the patient returned
to the hospital with severe articular pains. The phalangeal, wrist, and knee joints were severely swollen. He
was unable to bend his wrists or close his hands. The
fingers were clubbed. The interphalangeal joints were
hot, red, and swollen, and films of the hands showed
evidence of periostitis (Figure 1). Periostitis was also
noted in the lower third of the tibiae and the fibulae. He
had bilateral nonpitting leg edema and tender gynecomastia. He had lost 20 pounds in the preceding 2
months. Chest films showed huge radiopaque peripheral lung masses.
He was restricted to a wheelchair. Grip strength
was 10 mm Hg in the right hand and 5 mm Hg in the
left hand (mean of three readings). The mean skin temperature by quantitative thermography was 95.2”F in
the right hand and 94.9”F in the left hand.
The patient refused further cancer chemotherapy
or surgical intervention. After the study protocol was
explained to him and his family, he received 0.4 mg of
atropine sulfate subcutaneously every 4 hours for a period of 14 days. The doses were sufficient to produce
midriasis and dry mouth and a pulse ranging from 100
to 120 beats per minute. Other vital signs and urinary
output remained normal. On the third day of receiving
atropine, the patient noticed a subjective improvement
with increase in the range of motion of the hands and
fingers. By the seventh day there was noticeable im-
ATROPINE IN PULMONARY HYPERTROPHIC OSTEOARTHROPATHY
823
Figure 1. Periostitis in all metacarpal bones and on the third, fourth, and fifth proximal phalanges of both
hands
provement in the range of motion of both hands and
fingers. The strength of the handgrip in the right hand
increased from 10 mm Hg to 80 mrn and in the left hand
from 5 mm Hg to 75 mm Hg (mean of three readings);
thermographic indices fell to a mean of 90.8"F in the
right hand and 91.9"F in the left hand. On the
fourteenth day of therapy, the patient could already use
his hands and take care of himself, and articular pain
had abated. Therapy was then changed to oral probanthine, 15 mg every 6 hours. This treatment was well
tolerated and the improvement in his hands was sustained until his death in December 1978. An autopsy
permission was not granted.
DISCUSSION
Pulmonary hypertropic osteoarthropathy, Marie
Bamberger syndrome, is characterized by the peculiar
association of intrathoracic lesions with clubbing of the
digits, swelling of the distal third of the limbs, and a
characteristic radiographic appearance of new bone formation at the distal end of long bones, which may also
be noted in the phalanges. The syndrome may include
thickening of the skin over the forehead and neck and
bilateral tender gynecomastia. All of these findings were
present in this patient. The most frequent intrathoracic
lesion associated with the syndrome is primary cancer
of the lung. Rarely, as in this case, it may be associated
with pulmonary metastasis. The syndrome also occurs
in over 50% of patients with pleural mesotheliomas (3).
Regression of osteoarthropathy usually follows
surgical removal of the primary or metastatic intrathoracic lesion, or occurs after effective chemotherapy
or radiotherapy. Some authors have claimed symptomatic relief with the use of indomethacin, others with
adrenergic blockade with propranolol plus dibenzyline
(4) with more or less good results. Since Hansen ( 5 )
proposed the vagal reflexogenic hypothesis, surgical
vagotomy has been successfully performed in several
patients with Marie Bamberger syndrome. Chemical vagotomy with atropine was performed by d'Eshougues
(6) in 2 patients with pulmonary hypertrophic osteoarthropathy .
LOPEZ-ENRIQUEZ ET AL
824
After our patient’s refusal of further surgical
treatment and chemotherapy, we performed a chemical
vagotomy with atropine sulfate. After 2 weeks of treatment the patient was using his hands with minimal discomfort, something he could not do prior to therapy
because of severe pain. The patient’s objective improvement was also demonstrated by showing an increase in
handgrip strength of 70 mm Hg in both right and left
hands and an increase in the range of motion and decrease in thermographic indices of 4.4’F in the right
hand and 4.O”F in the left hand. Clinical improvement
persisted after therapy was changed to probanthine and
continued for 4 months, until the time of his death. Our
results support the vagal reflexogenic hypothesis as a
pathophysiologic mechanism in pulmonary hypertrophic osteoarthropathy. This form of therapy should
be considered in patients who suffer this disabling disease.
REFERENCES
1. Calabro JJ: Cancer and arthritis. Arthritis Rheum 10552564, 1967
2. Flavell G: Reversal of pulmonary osteoarthropathy by vagotomy. Lancet 1:260, 1956
3. Wierman WH, Clagett OT, MacDonald JR: Articular
manifestations in pulmonary diseases: an analysis of their
occurrence in 1024 cases in which pulmonary resection was
performed. JAMA 155:1459, 1954
4. Reardon G, Collins AJ, Bacon PA: The effect of adrenergic
blockade in hypertrophic pulmonary osteoarthropathy.
Postgrad Med J 1976: 52 (605):170-73
Hansen
JL: Bronchial carcinoma presenting as arthralgia.
5.
Acta Med Scand suppl266:467, 1952
6. d’Eshougues JR, Gille C, Smadja A: Interet du sulfate
d’atropine dans les formes “rheumatoides” de la maladie
de Pierre Mane: a propos du proies-verbal. Bull SOCMed
Hosp Paris 113:343-345, 1962
Low Back Pain
The Harvard Medical School Department of Continuing Education announces a course entitled “Low Back Pain” to be held October 3-4, 1980 at the Lenox Hotel in Boston. The course will
be given by the Departments of Neurology, Orthopedics, Neurosurgery, Medicine, Anesthesia, Radiology, and Psychiatry of the Affiliated Hospitals Center, Inc. and Harvard Medical School.
For additional information, contact Harvard Medical School, Department of Continuing
Education, 25 Shattuck Street, Boston, MA 02115.
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atropine, effect, sulfate, pulmonaria, osteoarthropathy, hypertrophic
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