27

Cavitary Pulmonary Nodules

with Systemic Lupus
Erythematosus: Differential
Downloaded from www.ajronline.org by 114.125.76.37 on 06/23/21 from IP address 114.125.76.37. Copyright ARRS. For personal use only; all rights reserved

Diagnosis

W. Richard Webb1 Cavitary pulmonary nodules rarely occur in patients with systemic lupus erythema-
Gordon Gamsu1 tosus and the lupuslike syndrome associated with mixed connective tissue disease.
Although it has been suggested that such cavitary nodules represent areas of vasculitis
and ischemic necrosis, five of seven occurrences of cavitary nodules in a series of six
patients with systemic lupus erythematosus or mixed connective tissue disease proved
to be the result of infection or pulmonary embolism. The causes in the other two cases
are unknown, but no attempt was made to obtain a biopsy in either instance. It was
concluded that vasculitis with ischemic necrosis is not a common cause of cavitary
pulmonary nodules in patients with lupus.

The pulmonary manifestations of lupus erythematosus and the lupuslike syn-

drome associated with mixed connective tissue disease are numerous and varied;
they include pneumonias, atelectasis, pulmonary edema (‘ ‘lupus lung’ ‘), pulmo-
nary hypertension, and hemorrhage [1 , 2]. Also several cases of systemic lupus
erythematosus with cavitary pulmonary nodules have been reported, but they
have not been well documented [3, 4]. Although it has been suggested [3] that
cavitary nodules in patients with systemic lupus erythematosus represent a
primary manifestation of the disease itself (presumably areas of vasculitis with
ischemic necrosis), in our experience most such lesions are attributable to other
causes, specifically infection or pulmonary embolism producing infarction.

Materials and Methods

During a 6-year period, 798 patients were admitted to our institution for treatment of
systemic lupus erythematosus or a lupuslike syndrome associated with mixed connective
tissue disease. Five of these patients also had cavitary pulmonary nodules; these five and
a sixth patient who had systemic lupus erythematosus and a cavitary nodule constitute our
study group. The six patients were females, 1 6-42 years old.
Five were classified as having systemic lupus erythematosus on the basis of a combi-
nation of clinical, biochemical, and hematologic abnormalities [5-fl. Although only two had
extractable nuclear antigen determinations made, findings in both were characteristic of
systemic lupus erythematosus with mild elevation of antibodies to the nonribonuclear
protein component of extractable nuclear antigen. All five had the nephrotic syndrome, and
in all, antinuclear antibodies and either anti-DNA antibodies or lupus erythematosus cells
were present. In all four with measured levels of serum complement, values were decreased.
Received January 21 1980 accepted after . ‘ . ‘ ‘

revision July 1 6 1 980 ‘ The other patient was considered to have mixed connective tissue disease because of
the presence of high titers of antibody (1:102,400) to the ribonuclear protein component
fornia S:n Francco, CA 94143 Address repnnt of extractable nuclear antigen and elevated levels of serum complement. Her disease
requests to W. R. Webb. otherwise closely resembled systemic lupus erythematosus in its clinical presentation, and
AJR 136:27-31, January 1981 symptoms included facial rash, arthralgias, alopecia, and polyserositis. She also experi-
0361-803X/81/1361-0027 $00.00 enced some dysphagia resulting from esophageal dysmotility. Her renal function was
© American Roentgen Ray Society normal.
 28 WEBB AND GAMSU AJR:136, January 1981

TABLE 1 : Cavitary Pulmonary Nodules in Patients with Systemic Lupus Erythematosus and Mixed Connective Tissue Disease

Response to Treatment
case Age
Respiratory Symptoms Radiographic Findings Cultures Pathologic Findings
0.
Steroids Antibiotics

1 42 Fever, cough, 2.5 cm CN RLL - - - Autopsy: bilateral renal

chest pain vein thrombosis, pulmo-
Downloaded from www.ajronline.org by 114.125.76.37 on 06/23/21 from IP address 114.125.76.37. Copyright ARRS. For personal use only; all rights reserved

nary embolism, necrotic

pulmonary infarct RLL
2 25 Fever, cough, Diffuse consolidation + . . . - Biopsy: vasculitis, pulmo-
dyspnea nary hemorrhage
Fever, cough; 3 cm CN RUL . . . + (afebrile) Pseudomonas aerugi- ...

nosa (bronchial brush-

ing)
Fever, cough 1 .5 mm CN LLL, in- . . . . . . Aspergillus fumigatus Autopsy: multiple pulmo-
creased size RUL CN (sputum, pleural fluid) nary abscesses contain-
ing Aspergillus, asper-
gillosis bronchopneu-
monia
3 16 Fever, cough, 4 cm CN RUL . . . + (afebrile, CN No growth (on antibi- Lung aspirate: inflamma-
chest pain thin-walled) otics) tory cells, mixed Gram-
positive cocci and
Gram-negative bacilli
4 22 Fever, chest pain 2 cm CN LLL . . . + (afebrile, CN Staphylococcus (blood), ...

resolved) Serratia (sputum)

5 31 Fever 1 cm CN left apex + + . . . ...

(resolved slowly using

maintenance steroids
and anti-TB therapy)
6 34 Dyspnea, chest Multiple 1 -4 cm CNs - - - . . . ...

pain, hypoxemia

Note-All patients were female. Cases 1 -5 had systemic lupus erythematosus; case 6 had mixed connective tissue disease. CN = cavitary nodule, RLL = right lower lobe, RUL =

right upper lobe, LLL = left lower lobe, + = positive, - = negative, TB = tuberculosis.

Results

The six patients had seven occurrences of cavitary nod-

ules detected radiographically (table 1 ). In one patient, a
cavitary nodule (fig. 1 ) was found to be a necrotic pulmonary
infarction at autopsy. Renal vein thrombosis had resulted in
pulmonary embolism, and recurrent pulmonary embolism
was the cause of death.
In three occurrences, autopsy, bronchial brushing, or lung
aspiration proved the nodules to be abscesses. Bacteria
resulted in two occurrences and fungus resulted in one (fig.
2). One of these three patients died as a result of progressive
fungal pneumonia. One other case probably represented a
bacterial lung abscess because blood and sputum cultures
were positive and the patient responded rapidly to antibiotic
therapy with resolution of the cavity.
In the two other cases, the causes of cavitary nodules are
unknown. One was a solitary upper lobe cavity that resolved
slowly during treatment with antituberculous and mainte-
nance steroid medications. In this patient, sputum smears
and cultures were negative as were a tuberculosis skin test
and tests for serum precipitins to Aspergillus and Candida
species. In the other patient with mixed connective tissue
Fig. 1 -Case 1 . Coned-down view of right lower lobe. disease (fig. 3), gallium scan showed diffuse pulmonary
Peripheral cavitary nodule. Second, less well defined nod- uptake, compatible with pulmonary vasculitis. Multiple cay-
ule at diaphragm may contain small cavity. At autopsy,
both proved to be necrotic infarctions resulting from pul- itary nodules subsequently developed and persisted despite
monary emboli. antituberculous medication and an increase in dosages of
 AJR:136, January 1981 PULMONARY NODULES WITH SLE 29

4’
Downloaded from www.ajronline.org by 114.125.76.37 on 06/23/21 from IP address 114.125.76.37. Copyright ARRS. For personal use only; all rights reserved

#{149} #{149},#{149}j

Fig. 2.-Case 2. A, Cavity in right upper lobe yielded Pseudomonas on cavity larger and thicker walled; small cavitary nodule (arrow). Aspergillus
bronchial brushing. Diffuse consolidation from pulmonary vasculitis and hem- demonstrated at autopsy.
orrhage 3#{189}weeks before had cleared. B, 1 month later. Right upper lobe

steroids and cytotoxic drugs. Serologic and skin tests for dysmotility. However, in all other respects, her symptoms
tuberculosis and fungi were negative, and sputum and blood resembled those of systemic lupus erythematosus.
cultures revealed no pathogens. Perfusion lung scan mdi- The differential diagnosis of cavitary lung nodules in pa-
cated a low probability of pulmonary embolism. tients with systemic lupus erythematosus has rarely been
discussed, and we know of no previously reported cases of
cavitary nodules in patients with mixed connective tissue
Discussion
disease. Four of the seven occurrences of cavitary nodules
In most clinical settings, the diagnosis of systemic lupus seen in our patients were proved or suspected to be the
erythematosus is based on the presence of a characteristic result of infection. Pulmonary embolism and infarction oc-
combination of symptoms and biochemical or hematologic curred in one additional case (case 1 ). In one patient with
abnormalities such as skin rash, Raynaud phenomenon, systemic lupus erythematosus and one with mixed connec-
alopecia, arthralgias, serositis, and lupus erythematosus tive tissue disease the causes of the cavitary nodules must
cells [5-7]. Mixed connective tissue disease, a syndrome be considered unknown-possibly vasculitis. However, in
closely related to but considered distinct from systemic neither patient were attempts made to diagnose these le-
lupus erythematosus, can manifest clinical findings identical sions by bronchial brushing or biopsy.
to systemic lupus erythematosus [8]. It is usually distin- Infection is common in patients with systemic lupus ery-
guished from systemic lupus erythematosus on the basis of thematosus or mixed connective tissue disease because of
immunologic studies [8, 9]. In general, mixed connective a combination of steroid therapy and immunodeficiency
tissue disease is defined by the presence of relatively high inherent in the disease processes [1 1 ]. In fact, pneumonia
titers (usually greater than 1 : 1 00,000) of antibody to & is one of the most common pulmonary complications of
ribonuclear protein component of extractable nuclear anti- systemic lupus erythematosus [2], with a reported incidence
gen, while systemic lupus erythematosus is characterized of 31 %-76% [1 2-1 4]. Pneumonias in patients with systemic
by low titers of antibody (usually less than 1 : 1 ,000) to a lupus erythematosus are mostly due to bacteria, but tuber-
nonribonuclear protein fraction. Furthermore, unlike pa- culosis and fungal infections are also common causes.
tients with systemic lupus erythematosus, patients with Among 1 1 1 patients with systemic lupus erythematosus
mixed connective tissue disease rarely have renal disease; studied by Levin [2], pneumonia developed in 1 6, bacterial
there is a higher incidence of symptoms and signs sugges- infection in eight, tuberculosis in four, and fungal infection
tive of scleroderma or polymyositis and, in general, patients in four.
with mixed connective tissue disease respond better to Bacterial pneumonia with cavitation (lung abscess) was
treatment and have a better prognosis [8-10]. In our study, reported in nine (16%) of 54 patients with systemic lupus
one patient was classified as having mixed connective tissue erythematosus studied at autopsy [14]. In the same series,
disease on the basis of immunologic abnormalities, the one patient had active caseous tuberculosis. Fungal infec-
absence of renal disease, and the presence of esophageal tions in patients with systemic lupus erythematosus also
 30 WEBB AND GAMSU AJR:136, January 1981

Fig. 3.-Case 6. A, Gallium scan. Diffuse

pulmonary uptake of isotope suggestive of vas-
culitis. B, Several poorly defined nodules in right
upper lobe, largest of which is cavitary. C, 1
month after B. Right upper lobe nodules have
cleared but new nodules now visible in both
midlung zones. Cavitary right lung nodule. D, 2
months after C. Right lung nodule resolved, but
Downloaded from www.ajronline.org by 114.125.76.37 on 06/23/21 from IP address 114.125.76.37. Copyright ARRS. For personal use only; all rights reserved

left lung nodule now has central cavity.

cause cavitary nodules, and common organisms responsible lesions due to vasculitis and those due to infection is impor-
are Aspergillus, Nocardia, Cryptococcus, and Candida [2, tant. The treatment of patients with pulmonary vasculitis
1 5]. In our study, three of the seven occurrences of cavitary requires increasing the dosage of immunosuppressive drugs
nodules were proved or suspected to be bacterial ab- [3].
scesses; in a fourth, it was secondary to aspergillosis (table In one of our patients, the cavitary nodule represented
1). In three of these four cases, the nodules were single, necrosis within an area of pulmonary infarction. This infarc-
although occasionally bacterial infections, Nocardia, and tion, in turn, was the result of renal vein thrombosis and
fungal diseases such as aspergillosis demonstrate multiple pulmonary embolism. Renal vein thrombosis can occur as
lesions. It must be emphasized that without needle aspira- a result of any chronic renal disease. Because patients with
tion, bronchoscopy, bronchial brushing, or open biopsy, an lupus nephritis often have nephrotic syndrome, the symp-
infection can be difficult to diagnose in patients with sys- toms of renal vein thrombosis may be masked. Necropsy of
temic lupus erythematosus. Because the treatment of op- 54 patients with systemic lupus erythematosus disclosed
portunistic infection in such patients often requires a de- that three (5.5%) had pulmonary infarction and two of these
crease in steroid dosage, the distinction between cavitary three had cavitation [14].
 AJR:136, January 1981 PULMONARY NODULES WITH SLE 31

Systemic lupus erythematosus and mixed connective tis- 4. Gould DM, Daves ML. Roentgenologic findings in systemic
sue disease can demonstrate similar pathologic findings in lupus erythematosus: an analysis of 1 00 cases. J Chronic Dis
the lung, specifically a necrotizing vasculitis [1 6-1 8]. In 1955;2: 136-1 45
patients with systemic lupus erythematosus, histologic find- 5. Cohen AS, Reynolds WE, Franklin EC, et al. Preliminary criteria
ings in the lungs include fibrinoid necrosis and hyaline for the classification of systemic lupus erythematosus. Bull
Rheum Dis 1971;21 :643-648
degeneration of interstitial tissues, alveolar walls, and the
Downloaded from www.ajronline.org by 114.125.76.37 on 06/23/21 from IP address 114.125.76.37. Copyright ARRS. For personal use only; all rights reserved

6. Lie TH, Rothfield NF. An evaluation of the preliminary criteria

endothelial lining cells of pulmonary capillaries [1 7-19].
for the diagnosis of systemic lupus erythematosus. Arthritis
Arteritis can also occur with thickening of the intima and Rheum 1972;1 5:532-534
media; hyaline or fibrin thrombi within small pulmonary 7. Rabhan NB, Minkin W. Criteria for classification of systemic
vessels are found in 20%-34% of patients studied at au- lupus erythematosus. JAMA 1975;231 :846
topsy [1 7, 1 9]. Presumably these vascular abnormalities 8. Sharp GC, Irvin WS, Tan EM, Gould RG, Holman HR. Mixed
produce ischemic necrosis and are responsible for areas of connective tissue disease-an apparently distinct rheumatic
pulmonary cavitation considered to occur as a result of disease syndrome associated with a specific antibody to an
active systemic lupus erythematosus. However, documen- extractable nuclear antigen (ENA). Am J Med 1 972;52 :148-
159
tation of cavitary vasculitis in systemic lupus erythematosus
9. Sharp GC, Irvin WS, May CM, et al. Association of antibodies
has been inadequate. Wagenvoort and associates [20] re-
to ribonucleoprotein and Sm antigens with mixed connective-
ported the pathologic findings of one case of pulmonary
tissue disease, systemic lupus erythematosus and other rheu-
arteritis in a young woman with systemic lupus erythema- matic diseases. N Engl J Med 1 976;295 : 1 149-1 154
tosus resulting in ischemic necrosis of large areas of lung, 1 0. Silver TM, Farber SJ, Bole GG, Martel W. Radiological features
but no radiographs were presented and we know of no of mixed connective tissue disease and scleroderma-sys-
other cases with pathologic proof. Although multiple cavitary temic lupus erythematosus overlap. Radiology I 976;1 20:
nodules reported in two patients with systemic lupus erythe- 269-275
matosus were presumed to be due to cavitary vasculitis 11. Staples PJ, Gerding DN, Decker JL, Gordon RS Jr. Incidence
[3], the evidence that these nodules did not result from of infection in systemic lupus erythematosus. Arthritis Rheum
1974;17:1-1O
superimposed infection has been questioned [21].
In our two patients with cavitary nodules of unknown 1 2. Dubois EL, Tuftanelli DL. Clinical manifestations of systemic
lupus erythematosus: computer analysis of 520 cases. JAMA
cause, the patient with mixed connective tissue disease
1964;190:104-11 1
(case 6) seems most likely to have had pulmonary necrosis 1 3. Gross M, Esterly JR, Earle RH. Pulmonary alterations in sys-
because of vasculitis; her persistently abnormal gallium temic lupus erythematosus. Am Rev Respir Dis 1972;105:
scan findings and progressively worsening respiratory func- 572-577
tion strongly suggested diffuse pulmonary vasculitis. How- 14. Purnell DC, Baggenstoss AH, Olsen AM. Pulmonary lesions in
ever, in another of our patients (case 2), who had biopsy- disseminated lupus erythematosus. Ann Intern Med 1 955;42:
proved pulmonary vasculitis, subsequent cavitary nodules 619-628
were found to be bacterial and fungal abscesses rather than 1 5. Pillay VKG, Wilson DM, Ing TS, Kark RM. Fungus infection in
ischemic necrosis. Because infection is common, cavitary steroid-treated systemic lupus erythematosus. JAMA
1968;205:261 -265
pulmonary vasculitis must remain a diagnosis of exclusion
1 6. Alarc#{243}n-Segovia D. The necrotizing vasculitides: a new path-
and further investigation, including biopsy, should be at-
ogenic classification. Med Clin North Am 1977;61 :241-260
tempted before a final diagnosis is made.
1 7. Chin-Tang H, Hennigar GR, Lyons HA. Pulmonary dysfunction
in systemic lupus erythematosus. N Engl J Med 1965;272:
288-293
1 8. Matthay RA, Schwarz MI, Petty TL, et al. Pulmonary manifes-
REFERENCES
tations of systemic lupus erythematosus: review of twelve
1. Alarc#{243}n-Segovia D, Alarc#{243}n DG. Pleuro-pulmonary manifesta- cases of acute lupus pneumonitis. Medicine (Baltimore)
tions of systemic lupus erythematosus. Chest 1961 ;39:7-1 7 I 975;54 :397-409
2. Levin DC. Proper interpretation of pulmonary roentgen 19. Fayemi AO. Pulmonary vascular disease in systemic lupus
changes in systemic lupus erythematosus. AJR 1971;1 11: erythematosus. Am J Clin Pathol I 976;65:284-290
51 0-517 20. Wagenvoort CA, Heath D, Edwards JE. The pathology of the
3. Castaneda-Zuniga WR, Hogan MT. Cavitary pulmonary nod- pulmonary vasculature. Springfield, IL: Thomas, 1964:101
ules in systemic lupus erythematosus. Radiology 1 976;1 18: 21. Fraser RG, Pare JAP. Diagnosis of diseases of the chest, vol
45-48 2, 2d ed. Philadelphia: Saunders, 1978:897