Acute Lupus Pneumonitis With Normal

Chest Radiograph
Irawan Susanto and Jay I. Peters

Chest 1997;111;1781-1783
DOI 10.1378/chest.111.6.1781
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10 DiSalvo TG, O'Gara PT. Torsades de pointes caused by
high-dose intravenous haloperidol in cardiac patients. Clin
Cardiol 1995; 18:285-90
11 Shalev A, Hermesh H, Munitz H. Mortality7 from neuroleptic
malignant syndrome. J Clin Psychiatry 1989; 50:18-25
12 Settle EC, Ayd FJ. Haloperidol: a quarter century of experi¬
ence. J Clin Psychiatry7 1983; 44:440-48
13 Dixon L, Thaker G, Conley R, et al. Changes in psychopa-
thology and dyskinesia after neuroleptic withdrawal in a
double-blind design. Schizophrenia Res 1993; 10:267-71
14 Lieberman J. Cholinergic rebound in neuroleptic withdrawal
syndromes [letter]. J Clin Psychiatry 1981; 42:179
15 Eppel AB, Mishra R. The mechanism of neuroleptic with¬
drawal. Can J Psychiatry 1984; 29:508-09
16 Luchins DL, Freed WJ, Wyatt RJ. The role of cholinergic
supersensitivity in the medical symptoms associated with
withdrawal of antipsychotic drugs. Am J Psychiatiy 1980;
137:1395-98
17 Nelli AC, Yarden PE, Guazzelli M, et al. Parkinsonism
following neuroleptic withdrawal. Arch Gen Psychiatry 1989;
46:383-84
18 Casey DE. Neuroleptic-induced acute extrapyramidal syn¬
dromes and tardive dyskinesia. Psychiat Clin North Am 1993;
16:589-610
19 Casey DE. Tardive dyskinesia. West J Med 1990; 153:535-41
20 Adams F. Emergency intravenous sedation of the delirious,
medically ill patient. J Clin Psychiatry 1988; 49(suppl):22-6
21 Seneff MG, Mathews RA. Use of haloperidol infusions to
control delirium in critically ill adults. Ann Pharmacother
1995; 29:690-93
22 Pohlman AS, Simpson KP, Hall JB. Continuous intravenous
infusions of lorazepam versus midazolam for sedation during
mechanical ventilatory7 support: a prospective, randomized
study. Crit Care Med 1994; 22:1241-47
23 Menza MA, Murray GB, Holmes VF, et al. Decreased
extrapyramidal symptoms with intravenous haloperidol. J Clin
Psychiatiy 1987;'48:278-80
24 Tsang MW, Shader Rl, Greenblatt DJ. Metabolism of halo¬
peridol: clinical implications and unanswered questions.
J Clin Psychopharmacol 1994; 14:159-62
25 Subramanyam B, Pond SM, Eyles DE, et al. Identification of
potentially neurotoxic pyridinium metabolite in the urine of
schizophrenic patients treated with haloperidol. Biochem
Biophys Res Commun 1991; 181:573-78
26 Busto U, Sellers EM, Naranjo CA, et al. Withdrawal reaction
after long-term therapeutic use of benzodiazepines. N Engl
J Med 1986; 315:854-59
27 Rosebush PI, Mazurek MF. Catatonia after benzodiazepine
withdrawal. J Clin Psychopharmacol 1996; 16:315-19
28 Lane JC, Tennison MB, Lawless ST, et al. Movement disor¬
der after withdrawal of fentanyl infusion. J Pediatr 1991;
119:649-51
29 Tune L, Carr S, Hoag E, et al. Anticholinergic effects of drugs
commonly prescribed for the elderly: potential means for
assessing risk of delirium. Am J Psychiatiy 1992; 149:1393-94
Acute Lupus Pneumonitis With
Normal Chest Radiograph*
Irawan Susanto, MD, FCCP; and Jay I. Peters, MD, FCCP
Patients with acute lupus pneumonitis (ALP) usually
have hypoxemia, patchy infiltrates evidenced on a
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1997 by the American College of Chest Physicians
chest x-ray film, and an incomplete response to
corticosteroids with high mortality. In contrast, lu¬
pus patients with a syndrome of acute reversible
hypoxemia (SARH) have hypoxemia with normal
chest x-ray films and a rapid response to corticoste¬
roids. We present a case of biopsy-proven ALP with
normal initial chest x-ray films, and a normal CT
scan. We hypothesize that a continuum of vascular
and parenchymal abnormalities may exist in the
lungs of lupus patients. This case also illustrates the
insensitivity of routine chest radiographs in demon¬
strating mild or early pneumonitis.
(CHEST 1997; 111:1781-83)
Key words: corticosteroids; hypoxemia; lupus; pneumonitis
Abbreviations: ALP acute lupus pneumonitis; SARH syn¬
= =
drome of acute reversible hypoxemia
A cute lupus pneumonitis (ALP) traditionally has been
^*- characterized
by the presence of fever, dyspnea, tachy-
pnea, hypoxemia, and patchy infiltrates evidenced on a
chest x-ray film. This diagnosis can be made only after
excluding other causes, especially infections. Histologi¬
cally7, ALP presents as acute alveolitis, with alveolar wall
necrosis, hemorrhage, edema, hyaline membrane forma¬
tion, interstitial pneumonitis, capillaritis, or capillary
thrombi.1 In contrast, lupus patients with a syndrome of
acute reversible hypoxemia (SARH) were reported to have
acute hypoxemia without any pulmonary parenchymal
involvement.2 The hypoxemia was rapidly reversed by
corticosteroids. However, histologic specimens were not
available from any7 of these patients. We present a case of
histologically proven ALP with a normal chest x-ray film
and CT scan on presentation.
Case Report
A 56-year-old woman presented with dyspnea and bilateral
pleuritic chest pain of 2 weeks' duration. She had no orthopnea,
paroxysmal nocturnal dyspnea, leg swelling, fever, chills, cough,
or hemoptysis. Seven months earlier, she was treated for facial
cellulitis which was painful, erythematous, and swollen over the
malar areas. Her past medical histoiy was significant for uncom¬
plicated hepatitis C-related cirrhosis, chronic sinusitis, and hy¬
pertension. She had no histoiy of smoking. At the time of
admission, she was receiving nadolol, thiamine, and folate.
Physical examination revealed a well-nourished woman in no
acute distress with a BP of 140/80 mm Hg, a pulse of 60 beats per
minute, a respiratory7 rate of 20 breaths per minute, and a
temperature of 36.3°C. Physical examination revealed nontender
sinuses. Her lungs were clear, and her heart rate was regular with
*From the Department of Medicine, Division of Pulmonary
Diseases/Critical Care Medicine, the University of Texas Health
Science Center at San Antonio and, the South Texas Veterans
Health Care System, Audie L. Murphy Memorial Veterans
Hospital Division, San Antonio, Tex.
Manuscript received September 16, 1996; revision accepted
December 16.
Reprint requests: Irawan Susanto, MD, FCCP, the University of
Texas Health Science Center at San Antonio, Department of
Medicine, Div of Pulmonary Diseases/Critical Care Medicine,
7703 Floyd Curl Dr, San Antonio, TX 78284-7885
CHEST / 111 / 6 / JUNE, 1997 1781
 a* *%r *x. \% **43T.i *%**;£.1/cl^wi

Figure 1. Normal admission chest x-ray film, posteroanterior

view.

the presence of an S4 gallop. Results of an examination of the

abdomen and the extremities were within normal limits. On
admission, the WBC count was 7,500/mm3, the hemoglobin level
was 13 gm/dL, the platelet count was 73,000/mm3, prothrombin
time was 14 s, partial thromboplastin time was 34 s, total bilirubin
value was 2.4 mg/dL, aspartate aminotransferase was 115 IU/L,
alanine amino transferase was 107 IU/L, alkaline phosphatase Figure 2. This transbronchial biopsy specimen shows focal
was 78 IU/L, and erythrocyte sedimentation rate w7as 111 mm/h. infiltrates of neutrophils and monocytes (double arrows). An
With the patient breathing room air, blood gas determinations alveolar wall abruptly merges into the area of capillaritis (single
were as follows: pH, 7.48; Pco2, 25 mm Hg; and Po2, 65 mm Hg. arrow) [hematoxylin-eosin, original X450]).
=

The patient's initial chest x-ray film revealed no parenchymal

infiltrates (Fig 1), which was confirmed by a CT scan of the chest
with contrast medium. She had normal spirometry7 values and
(29% predicted), and a
lung volumes, Areduced diffusion capacity7showed Discussion
14.2% shunt. pulmonary7 angiogram no abnormalities.
Her electrocardiogram showed no ischemic changes; an echocar¬
The patient fulfilled the American College of Rheumatol¬
diogram demonstrated normal left ventricular size and function. ogy criteria for the diagnosis of systemic lupus erythematosus
The antinuclear antibody titer w7as 1:2,560. Her C3 and C4 levels (rash; serositis; leukopenia, lymphopenia, and thrombocyto-
w7ere depressed. The IgG anticardiolipin antibodies were present
in moderate titer. Two days after admission, her blood cell counts
revealed leukopenia (2,700/mm3) and lymphopenia (1,026/mm3)
in addition to thrombocytopenia.
Bronchoscopy was performed less than 24 h after the chest CT
scan. Transbronchial lung biopsy revealed alveolar hemorrhage,
focal areas of pneumonitis, and capillaritis (Fig 2). The patient
developed persistent postbronchoscopy fevers without an infec¬
tious source despite extensive workup. Empiric therapy with
intravenous antibiotics was started. Her chest x-ray films still
showed no infiltrates. Another chest CT scan 5 days after
bronchoscopy showed significant changes with vascular promi¬
nence and bibasilar alveolar interstitial infiltrates in the depen¬
dent regions (Fig 3).
The patient w7as treated with prednisone, 40 mg po bid, and
intravenous administration of antibiotics was continued. She
subjectively improved and defervesced despite the persistence of
hypoxemia. Her diagnosis at discharge was ALP. On outpatient
follow-up 3 months after discharge, her diffusion capacity had
increased to 58% of predicted. Fifteen months after discharge, Figure 3. Another chest CT scan showing vascular prominence
her diffusion capacity w7as 65% of predicted, and the patient's and bibasilar alveolar interstitial infiltrates in the dependent
hypoxemia had slowly improved. regions.
1782 Selected Reports
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1997 by the American College of Chest Physicians
penia; and antinuclear antibody positivity) 3 Her lung biopsy
was consistent with ALP, although her initial chest x-ray film
and CT scan lacked parenchymal infiltrates. This case illus¬
trates the lack of correlation between pulmonary radio-
graphic and histologic findings and that absence of radio-
graphic infiltrates does not rule out histologic abnormalities.
The patient's hypoxemia may be partially explained by
the presence of cirrhosis.4 Shunt fractions up to 28% have
been reported with severe cirrhosis.5 This may explain the
residual mild hypoxemia despite significant improvement
in the diffusion capacity following steroid therapy.
Lupus patients with SARH were reported to present with
transient hypoxemia and a clear chest x-ray film or CT scan
and to respond to steroids within 72 h.2 In contrast, patients
with ALP usually present with patchy infiltrates, and the
response to steroids is slow. Many patients with ALP require
mechanical ventilatory support. In the early series described
by Matthay et al,6 7 out of the 12 patients with ALP receiving
high-dose steroids required salvage dierapy with azathio¬
prine, and mortality remained at 50%. Aldiough the patient
described here had histologic findings consistent with ALP,
her clinical course was less severe than that of the patients in
die series by Matthay et al.6
Central to the pathophysiology of SARH and ALP is
pulmonary vascular involvement. Acute injury to the alveolar
capillary unit forms the basis for ALP.1 In SARH, transient
leukocyte sequestration with complement activation is
thought to occur in die pulmonary microvasculature.2
Recently, endothelial cells from the skin biopsy of lupus
patients were found to demonstrate increased expressions
of adhesion molecules.7 These molecules are involved in
local leukocyte trafficking across the endothelium and may
participate in the pathogenesis of vascular inflammation.
Treatment with corticosteroids early may significantly
attenuate vascular injury, partly due to its ability to
downregulate the expression of endothelial adhesion mol¬
ecules.8 However, the vascular inflammatory cascade may
progress to frank microangiitis and hemorrhage, leading to
serious tissue damage and less steroid responsiveness, the
way ALP has traditionally been described. We hypothesize
that ALP may represent an extension of SARH in the
continuum of pulmonary microvascular inflammation.
We conclude diat routine chest radiographs may be
insensitive to the presence of ALP. Since a high-resolution
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1997 by the American College of Chest Physicians
chest CT scan is superior to routine chest radiographs and
conventional CT scans in demonstrating pulmonary intersti¬
tial opacities, it also may aid in the evaluation of lupus
patients who present with hypoxemia and a normal chest
x-ray film.9 Finally, it is possible that SARH and ALP may not
represent distinct clinicopadiologic entities but rather differ¬
ent levels of severity within the spectrum of the pulmonary
vascular inflammatory process associated with lupus.
ACKNOWLEDGMENT: The authors wish to thank Dr. Jacque¬
line J. Coalson, Professor and Interim Chair of Pathology at the
University of Texas Health Science Center at San Antonio, for
her assistance in the evaluation of transbronchial biopsy speci¬
mens and the preparation of the photomicrographs.
REFERENCES
1 Wiedemann
HP, Matthay RA. Pulmonary7 manifestations of
the collagen vascular diseases. Clin Chest Med 1989; 10:677-
722
2 Abramson SB, Dobro J, Eberle MA, et al. Acute reversible
hypoxemia in systemic lupus erythematosus. Ann Intern Med
1991; 114:941-47
3 Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria
for the classification of systemic lupus erythematosus. Arthri¬
tis Rheum 1982; 25:1271-77
4 Bates DV. Miscellaneous conditions. In: Bates DV, Macklem
PT, Christie RV, eds. Respiratoiy function in disease. 3rd ed.
London: WB Saunders, 1989; 350-62
5 Edell ES, Cortese DA, Krowka MJ, et al. Severe hypoxemia
and liver disease. Am Rev Respir Dis 1989; 140:1631-35
6 Matthay RA, Schwarz MI, Petty TL, et al. Pulmonary
manifestations of systemic lupus erythematosus: review of
twelve cases of acute lupus pneumonitis. Medicine 1974;
54:397-409
7 Belmont HM, Buyon J, Giorno R, et al. Up-regulation of
endothelial cell adhesion molecules characterizes disease
activity in systemic lupus erythematosus. Arthritis Rheum
8
1994; 37:376-83
Cronstein BN, Kimmel SC, Levin Rl, et al. A mechanism for
the antiinflammatoiy effects of corticosteroids: the glucocor¬
ticoid receptor regulates leukocyte adhesion to endothelial
cells and expression of endothelial-leukocyte adhesion mole¬
cule 1 and intercellular adhesion molecule 1. Proc Natl Acad
Sci USA 1992; 89:9991-95
9 Mathieson JR, Mayo JR, Staples CA, et al. Chronic diffuse
infiltrative lung disease: comparison of diagnostic accuracy of
CT and chest radiography. Radiology 1989; 171:111-16
CHEST/111 /6/JUNE, 1997 1783
 Acute Lupus Pneumonitis With Normal Chest Radiograph
Irawan Susanto and Jay I. Peters
Chest 1997;111; 1781-1783
DOI 10.1378/chest.111.6.1781
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