See

discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/20861327

Myasthenia gravis presenting as isolated

respiratory failure

Article in Chest · February 1990

DOI: 10.1378/chest.97.1.232 · Source: PubMed

CITATIONS READS

33 72

3 authors, including:

Joseph D Zibrak
Harvard University
28 PUBLICATIONS 999 CITATIONS

SEE PROFILE

All content following this page was uploaded by Joseph D Zibrak on 24 April 2017.

The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the original document
and are linked to publications on ResearchGate, letting you access and read them immediately.
 Myasthenia gravis presenting as isolated
respiratory failure.
K M Dushay, J D Zibrak and W A Jensen

Chest 1990;97;232-234
DOI 10.1378/chest.97.1.232
The online version of this article, along with updated information and services
can be found online on the World Wide Web at:
http://chestjournal.chestpubs.org/content/97/1/232

Chest is the official journal of the American College of Chest Physicians. It has
been published monthly since 1935. Copyright1990by the American College of
Chest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights
reserved. No part of this article or PDF may be reproduced or distributed
without the prior written permission of the copyright holder.
(http://chestjournal.chestpubs.org/site/misc/reprints.xhtml) ISSN:0012-3692

Downloaded from chestjournal.chestpubs.org by guest on July 10, 2011

© 1990 American College of Chest Physicians
 In summary, this report provides strong evidence that W hen pulmonary physicians evaluate patients with
sulindac can produce an isolated pulmonary hypersensitivity progressive respiratory insufficiency, it is important
reaction. When pulmonary infiltrates develop in patients to consider neuromuscular disease in the differential diag-
receiving sulindac therapy a drug reaction should be consid- nosis, as emphasized by the patient who is the subject of
ered as the possible cause. this report.

REFERENCES CASE REPORT

1 ParkCD, SpectorR, HeadStreamT, GoldbergM. Serious adverse A64-year.oldwaterpipe installerwas diagnosed as having obesity-
reactions associated with sulindac. Arch Intern Med 1982; hypoventilation syndrome associated with recurrent cor pulmonale.
142:1292-94 Three months earlier, he had presented to another hospital with
2 FeIn M. Sulindac and pneumonitis. Ann Intern Med 1981; 95:245 peripheral edema and weight gain. Values of a room air blood gas
3 Smith FE, Lindberg PJ. Life-threatening hypersensitivity to analysis were as follow: Po2, 61 mm Hg; Pco,, 51 mm Hg; pH,
sulinclac. JAMA 1980; 244:269-70 7.37; (lhble 1) and the chest x-ray film showed a reduction in lung
4 Sprung DJ. Sulindac causing a hypersensitivity reaction with volumes interpreted as poor inspiratory effirt. No other abnormal-
peripheral and mediastinal lymphadenopathy. Ann Intern Med ities were noted. Spirometry showed FEy, of 2.20 (60 percent of
1982; 97:564 predicted); FVC, 2.78 (54 percent); FEV,/FVC, .78; FEF25-75,
5 Huff BB, ad. Physicians desk reference. 42nd ad. Oradell, NJ: 2.39 (68 percent) with no change after bronchodilator therapy. He
Medical Economics Co mc, 1988:1293-95 was treated with diuretics and discharged with diagnoses of hyper-
6 BuscagliaAJ, Cowden FE, Brill H. Pulmonary infiltrates associ- tension, restrictive lung disease ofunspecified efioloaji and chronic
Med with naproxen. JAMA 1984; 251:65-6 hypoxia.
7 Nader DA, Schillaci RF. Pulmonary infiltrates with eosinophilia Over the next six weeks, he noted increasing letharg#{231} weakness,
due to naproxen. Chest 1983; 83:280-82 dyspnea on exertion, pedal edema, cyanosis, and weight gain. On
examination, a right sided S3 gallop, crackles at both lung bases,
and 3+ pedal edema were
noted. An arterial blood gas analysis on
room air showed worsening CO2 retention and hyposemia spirom-
eti’ was unchanged. In spite of treatment with diuretics and
Myasthenia Gravis Presenting as intravenous aminophylline, his dyspnea worsened, and he was
Isolated Respiratory Failure* transferred to the New England Deaconess Hospital.
On admission, he reported loud snoring, five to six years of
Kevin M. Dushay, M.D.;t .k’seph D. Zibrak, M.D.. FC.C.P4 and
daytime hypersomnolence, fatigue, and nocturnal apneic spelk In
William A. Jensen, M.D., FC.C.P
addition, he complained of a lump in his throat, some difficulty
A patient with myasthenia gravis presenting as respiratory swallowing, and several episodes of diplopia over the past two
months. His medications were hydrochiorothiazide (Dyazide), dii-
failure was unusual in his lack ofperipheral neuromuscular
tiazem, captopril, coichicine, and probenecid. He denied alcohol
involvement, negative results on many commonly used
and cigarette use. On examination, he was tachypneic, and had
diagnostic tests, and lack ofresponse to firstline therapeutic diminished breath sounds at the right lung base
without cracides or
measures. Review of the pertinent literature revealed zx wheezes, an irregular rhythm without murmur or gallop, and a liver
previously described presentation of myasthenia gravis in span of 8 cm. Laboratory test results were significant fr the fol-
this manner. (Chest 1990; 97:232-34) lowing: hematocrit, serum bicarbonate,
50.6 45 mEciJL
percent;
arterial blood gas on 1.5 L/min of Poe, 91 mm Hg;
I-IF=inspiratory force; MEPP=miniature end plate potential pH, 7.32; Pco2, 56 mm Hgt7.32;
nasal cannula
and chest x-ray film showing
borderline cardiomegaly, normal pulmonary vasculature, and ate-
Fmm the Section of Pulmonary and Critical Care Medicine, New lectasis at both lung bases. Spirometry showed FEV,, 1.62 (43
England Deaconess Hospital, Boston. percent); FVC, 1.98 (42 percent); FEV,/FVC, .82; FEFmax, 3.86
tFellow. (43 percent); Dco, 17.78 (57 percent).
tlnstructor in Medicine; presently at San Jose, CA.
Rnt ?quedS: Dr. Dushay, New England Deaconess Hospital, Over the next 24 hours, the patient deteriorated, developing
Boston 02215 respiratory distress and paradoxical abdominal motion without

Table 1-Arterial Blood Gas Determinations and Pbdmonary Function Tests

Pco2 Dco,
Date Po, mm Hg pH FEy,, L FVC, L Ratio FEF25-75, Us TLC, L R\ L mVmin/mm Hg

58/87 61 51 7.37
5(11/87 2.20 (.56) 2.78 (.54) 78 2.39 (.68)
&“2iB7 2.35 (NA)* 2.83 (NA) 82 2.93 (NA) 3.92 (NA) 1.78 (NA) 14.79 (NA)
7/31/87 66 46 7.36
103 82 7.30 (on 3IJmin O)
73 71 7.38 (on1.5IJminO)
2.35 (.61) NA (.57)
&6’87 91 56 7.32 (on 1.5LJmin O)
&‘7/87 1.62 (.43) 1.98 (.42) 82 17.78 (.57)
&.#B7 45 103 7.28 (on 1.OIJmin O)
51 89 7.33 (on 24% Venturi mask)
12/2/87 3.03 (.80) 3.76 (.79) 81 3.19 (.85)

VaIue not available.

232 Mhenia Gravis Presenting as Iaoated ReepWatory Failum (A,shay Zibrak, en)

Downloaded from chestjournal.chestpubs.org by guest on July 10, 2011

© 1990 American College of Chest Physicians
 Table 2-Weaning Mechanics and interventions

Date VT, L Vc, L IF, cm H20

8/7/87 .200 1.OQ .. ,... .. . . - 11 S5

8/13/87 .250 -8
.225 .600 - 11 (on 0.25mg neostigmine q4h)
8/15/87 .300 .800 - 16 (neostigmine continued)
8/17/87 .213 .550 -5 (neostigmine discontinued 8/16/87)
8/18/87 .400 .800 - 14 (neostigmine restarted at 0.5 mg q4h 8/17/87)

muscle weakness elsewhere, An arterial blood gas analysis on 1.0 assessing improvement in respiratory mechanics-though
11mm was Po2, 45 mm Hg; Pco2, 103 mm Hg; pH, 7.28. Pulmonary Osserman and Genkins’ 1966 reviews of the edrophonium
mechanics results disclosed: tidal volume of 200 ml, vital capacity test stated less than 0.5 percent of cases require more than
of 1.0 L, and inspiratory force of - 11 cm H20, A standard
10 mg to produce a response. Standard repetitive nerve
edrophonium (Tensilon) test was performed with no change in IF
stimulation and electromyography’ also were not helpful.
or VC. The patient was mtubated and mechanical ventilation begun
Ultimately, serologic studies confirmed the diagnosis.
(Table 2).
Despite conventional treatment with acetylcholinesterase
Electrolytes, ESR, CT scan of the head, noninvasive venous
studies of the lower extremities, repeat edrophonium test, electro- inhibitors and steroids, respiratory insufficiency persisted

myogram including cranial nerves, and repetitive nerve stimulation and extubation was not possible. Plasmapheresis, as reported
of brachial plexus, median, ulnar, and spinal accessory nerves all by Pinching and Peters, and others,7b0 was then employed
were subsequently normal. Studies for heavy metal exposure were with success.
negative. During this period, the patient complained of intermittent
vertical diplopia, but dysconjugate gaze was not observed. CONCLUSIONS
Because of persistent clinical suspicion of myasthenia gravis, an
This case of myasthenia gravis was unusual in three
empiric trial of neostigmine, 0.25 mg every four hours, was begun.
respects: the patient presented with what appeared to be
While the patient’s baseline pulmonary mechanics (TV, 250 ml; VC,
800 ml; IF, - 8 cm H20) were unchanged after four hours, his primary respiratory failure of unknown etiology; associated

diplopia had resolved. Neostigmine was therefore continued and symptoms of myasthenia were suggested by history but
after 48 hours, respiratory mechanics had improved. When neostig- could not be verified by objective means. Diagnosis was
mine was discontinued, mechanics deteriorated significantly. Neo- difficult despite a correct clinical impression in that several
stigmine was therefore reinstituted at an increased dose (0.5 mg edrophonium trials as well as other standard tests for
q4h) with definite improvement in respiratory mechanics. myasthenia gravis were negative. Treatment following diag-
Myasthenia gravis was confirmed when an antistriated muscle
nosis with accepted firstline agents, acetylcholinesterase
antibody titer was reported at 1:80 and an acetylcholine receptor
inhibitors and corticosteroids, failed to produce an adqe-
antibody titer was reported at greater than 1:30 (normal <1:0.8).
quate response such that plasmapheresis was required
Neostigmine was increased to 1.0 mg q4h and prednisone 60 mg
before the patient could be weaned from ventilatory support.
0 qd was added. However, only with the institution of plasma-
pheresis was he successfully extubated. This case illustrates the need to consider myasthenia
gravis, as well as other motor neuron disorders, in evaluating
DISCUSSION individuals presenting with acute respiratory failure. The

Myasthenia gravis can frequently be complicated by

former should be aggressively pursued beyond conventional
firstline tests, since diagnosis can be difficult and effective
respiratory failure . ‘ However, myasthenic involvement lim-
treatment is available.
ited solely to the muscles ofventilation has not been reported
in well-characterized patients. In retrospective series of 22
REFERENCES
myasthenics requiring mechanical ventilation reported by
Gracey et 2, only four presented in this manner. None was 1 Lisak RP, Barchi RI. Myasthenia gravis. Philadelphia: WB
Saunders Co, 1982
described as having isolated respiratory failure. The conclu-
2 Gracey DR, Divertie MB, Howard FM. Mechanical ventilation
sions of two earlier series by Ferguson et a? (31 patients)
for respiratory failure in myasthenia gravis: two-year experience
and Ashworth and Hunt& (13 patients) were similar. The
with 22 patients. Mayo Clin Proc 1983; 58:597-602
latter speeffically stated that, “respiratory failure was never 3 Ferguson IT, Murphy RP, Lascelles RG. Ventilatory failure in
the first symptom of the disease.” Factors leading to respi- myasthenia gravis. J Neurol Neurosurg Psychiatry 1982; 45:217-
ratory failure in these reports included myasthenic crisis, 22
cholinergic crisis, brittle crisis, steroid induced crisis, post- 4 Ashworth B, Hunter AR. Respiratory failure in myasthenia
operative state, and other medical conditions typically gravis. Proc Roy Soc Med 1971; 64:489-90
requiring mechanical ventilation not unique to myasthenia 5 Mier AK, Havard CWH. Diaphragmatic myasthenia in mother

gravis. Only a single case report was found describing a and child. Postgrad Med J 1985; 61:725-27
6 Osserman KE , Genkins C . Critical reappraisal of the use of
patient who initially presented with ocular myasthenia and
edrophonium (Tensilon) chloride tests in myasthenia gravis and
later returned with isolated respiratory failure.
significance of clinical classification. Ann NY Acad Sci 1966;
Unlike previously described cases, our patient’s myas-
135:312-34
thenic involvement was limited to the ventilatory muscula-
7 Pinching AJ, Peters DK. Remission of myasthenia gravis follow-
ture, and multiple tests commonly used to confirm clinical ing plasma-exchange. Lancet 1976; 2:1373-76
suspicion of myasthenia gravis were negative. It is possible 8 Dau PC. Plasmapheresis therapy in myasthenia gravis. Muscle
that 10 mg of edrophonium was an inadequate test dose for Nerve 1986; 9:519-22

CHEST I 97 I 1 I JANUARY, 1990 233

Downloaded from chestjournal.chestpubs.org by guest on July 10, 2011

© 1990 American College of Chest Physicians
 9 Pollard JD, Basten A, Hassall JE, Kronenberg H, Dawkins R. any ventilation and led to massive inhalation. He never used a mask
Current trends in the managenient of mvasthenia gravis: plas- to reduce inhalation, whereas the French legislation requires the
mapheresis and imthunosuppressive therapy. Aust NZ J Med use of such protective devices.
1980; 10:212-17 The findings from physical examination, cardiac function, routine
10 Gracey DR. Howard FM, Divertie MB. Plasmapheresis in the biologic analyses, and chest x-ray films were normal. A CT scan
treatment of ventilator-dependent niyasthenia gravis patients: showed (1) a diffuse interstitial process more pronounced in the
report of four cases. Chest 1984; 85:739-43 periphery of the lower lobes and (2) right paratracheal hypodense
(- 40 UH) lymph node enlargement (Fig 1).
Hypoxemia and a slight decrease in the DSS were found. In
contrast, other pulmonary function tests, including plethysmo-
graphic evaluation of compliances, were normal (Table 1).
A BAL was performed and showed an increase in total cell
Interstitial Pulmonary Disease numbers and lymphocyte percentage. Light microscopy of a trans-

Induced by Occupational Exposure bronchial

lymphocytes
biopsy
and
showed
AMs, some
mixed
of them
alveolitis
presenting
involving
unusual
both normal
cytoplas-
to Paraffin* mic vacuoles. Diagnostic investigations failed to demonstrate any
evidence of systemic disease, of infectious or hypersensitivity
Jean-Louis Pujol, MI).; (;ilbe-t Barn#{233}on, MI).;
pneumonitis, and the patient did not present any evidence of
Jean Bousquet, MI).; Fran#{231}ois-Bernard Miclici, AID., FCC.?;
endogenous dislipidosis or gastroesophagal reflux.
and Philippe Godard, M.D.
In March 1985, a surgical open l)iopsy of the right middle lobe
was performed. Light microscopy following hematoxylin-eosin, PAS,
An occupational interstitial pulmonary disease was oh-
and tnchrome stainings disclosed a uniform interstitial pneumonitis
served in a 59-year-old workman after five years of massive with fibrosis. The alveoli were filled with extracellular lipoid droplets
exposure to aerosolized paraffin. Histologic studies of open- and large AMs containing lipid vacuoles. Some of them were
lung biopsy showed a lipoid pneumonia characterized by multinucleated foam histiocytes (Touton giant cells). Lymphocytes
(1) alveolitis involving large lipid-laden macrophages and were also involved in the alveolitis without granuloma organization.
(2) interstitial fibrosis. Electron microscopy ofAMs disclosed Some histiocytes were present in thickened interalveolar septum
features of paraffin-laden cytoplasmic vacuoles. Successive in which numerous collagen fibers were seen (Fig 2). Lipoid
treatments included prednisolone and cyclophosphamide. pneumonia was diagnosed.
A new BAL was performed after the open-lung biopsy. Electron
Despite these treatments and withdrawal from exposure,
microscopy of the AMs disclosed an aspect of foam cells with
the pulmonary function became impaired progressively,
cvtoplasmic vacuoles of various sizes unstained by osmic acid, a
resulting in restrictive syndrome and severe exertional
specific feature of mineral oil (Fig 3).
dyspnea. Concomitantly, PMNs harvested by BAL in- A daily dose of prednisolone (1.5 mg/kg) was begun in March
creased, whereas initial lymphocytosis decreased. This is 1985. Then dosage was slowly decreased until a daily maintenance
the first case observed of occupational interstitial fibrosis dosage ofO.5 mg/kg was reached. In November 1985, corticosteroids
in which electron-microscopic findings clearly established were discontinued because ofclinical impairment. An immunosup-
a relationship with an exposure to paraffin. This observation pressive treatment by cyclophosphamide (2 mg/kg daily per os) was
also emphasizes the switch from alveolitis to fibrosis in the begun and maintained for four months. Cyclophosphamide induced

pathogenesis of interstitial pulmonary disease. neutropenia with digestive candidiasis. Despite therapy, dyspnea
and pulmonary function became worse, and a restrictive syndrome
(Chest 1990; 97:324-36)
occurred (Table 1). Diffusing capacity (49 percent) and static

P araflin, a mineral oil, can induce alveolitis and interstitial

compliance
logic studies
(0.25
of BAL
11cm 1190)
fluid
decreased
demonstrated
concomitantly.
the progressive
Serial cyto-
decrease
fibrosis, possibly related to the activation of oil-laden of total cells and lymphocyte counts, which returned to subnormal
AMs.’2 This lipoid pneumonia is usually related to repeated values, whereas PMNs increased (Table 1). As rio clinical benefit
aspiration of paraffin-containing laxative or nasal drops.5 justified further active therapy, cyclophosphamide was discontin-
We report the first case of a workman suffering from an tied, and only long-term oxygen therapy was maintained.
interstitial pulmonary disease related to occupational par-
affin exposure.

CASE REPORT

A 59-year-old workman, a mild smoker, was admitted to the

hospital in July 1984 for exertional dyspnea. lie had been well until
May 1984. lIe had no previous medical or surgical history and had
never received long-term treatment. He had flO history of asbestos
exposure. Five years ago, he started to work for an automobile
dealer. From 1979 to May 1984, the patient was chronically expsed
to paraffin in cleaning new cars protected by paraffin, using hot
water generated l)%’ compressed air jets. This technique aerosolized
hot paraffin from car surfaces in a closed workshop (80 m) without

*Frn the Service des Maladies Respiratoires, H#{244}pital I’Aigue-

longue, Univerit#{233} de Montpellier(Drs. Pujol; Michel; and Godard),
and the Lah()ratoire d’Anatomie Pathologique, H#{244}pital Gui de
Chauliac, Universit#{233} de Monpellier, Montpellier, France.
Reprint requests: Dr Pujol, H#{244}pital Aiguelotgue, Rue P4. Flandre, FIGURE 1 . Computed tomographic scan shows diffuse interstitial
Montpellier, France 340.59 process more pronounced in periphery of lower lobes.

234 Interstitial Pulmonary Disease Induced by Occupational Exposure (PujoI et a!)

Downloaded from chestjournal.chestpubs.org by guest on July 10, 2011

© 1990 American College of Chest Physicians
 Myasthenia gravis presenting as isolated respiratory failure.
K M Dushay, J D Zibrak and W A Jensen
Chest 1990;97; 232-234
DOI 10.1378/chest.97.1.232
This information is current as of July 10, 2011
Updated Information & Services
Updated Information and services can be found at:
http://chestjournal.chestpubs.org/content/97/1/232
Cited Bys
This article has been cited by 2 HighWire-hosted articles:
http://chestjournal.chestpubs.org/content/97/1/232#related-urls
Permissions & Licensing
Information about reproducing this article in parts (figures, tables) or in its entirety can be found
online at:
http://www.chestpubs.org/site/misc/reprints.xhtml
Reprints
Information about ordering reprints can be found online:
http://www.chestpubs.org/site/misc/reprints.xhtml
Citation Alerts
Receive free e-mail alerts when new articles cite this article. To sign up, select the "Services" link to
the right of the online article.
Images in PowerPoint format
Figures that appear in CHEST articles can be downloaded for teaching purposes in PowerPoint
slide format. See any online figure for directions.

Downloaded from chestjournal.chestpubs.org by guest on July 10, 2011

© 1990 American College of Chest Physicians
View publication stats