pulmonary sarcoidosis presenting with miliary opacities
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□ CASE REPORT □
Pulmonary Sarcoidosis Presenting with Miliary Opacities
Masato Taki, Naoya Ikegami, Chisato Konishi, Satoshi Nakao, Tomoko Funazou,
Ryo Ariyasu, Masanori Yoshida, Kazuhiko Nakagawa, Kyouhei Morita, Moon Hee Hwang,
Chie Yoshimura, Toshiaki Wakayama and Yasuo Nishizaka
Abstract
Lung lesions often appear in patients with sarcoidosis; however, miliary opacities are rare. We herein re-
port the case of a 40-year-old woman with pulmonary sarcoidosis who presented with dyspnea on exertion.
Subsequent computed tomography showed miliary opacities, and the presence of granulomas was confirmed
by a transbronchial lung biopsy. Glucocorticoid therapy was initiated and the symptoms and miliary opacities
rapidly improved. Although miliary sarcoidosis is uncommon, physicians should consider sarcoidosis in addi-
tion to tuberculosis, malignancy, and pneumoconiosis when presented with miliary opacities.
Key words: sarcoidosis, miliary, granuloma, glucocorticoid therapy
(Intern Med 54: 2483-2486, 2015)(DOI: 10.2169/internalmedicine.54.4681)
Introduction
Sarcoidosis is a disease of unknown etiology that results
in the formation of granulomas in any organ. Lung lesions
are a common feature of sarcoidosis, typically presenting as
nodules along the bronchi, vessels, and subpleural regions;
interlobular septal thickening; and bilateral perihilar opaci-
ties. However, miliary opacities are rare, and few case re-
ports currently exist in the literature (1).
On presentation with miliary opacities of the lung, the
differential diagnosis is generally of tuberculosis, metastatic
lung tumor, or pneumoconiosis. Because sarcoidosis can
present in this manner and is curable with simple glucocorti-
coid therapy, sarcoidosis must be excluded.
We herein report the case of a woman with miliary sar-
coidosis whose signs and symptoms completely resolved
following glucocorticoid therapy. Furthermore, the disease
did not recur six months after the end of therapy, despite the
extensive lung involvement at the diagnosis.
Case Report
A 40-year-old housewife with no notable previous ill-
nesses presented to our hospital with a 6-month history of
exertional dyspnea. She had quit smoking at 38 years of age
and had not consumed any medicines or supplements. She
had not changed her residential location in recent years, and
her living environment had not changed. Auscultation re-
vealed no rales in either lung field, and the patient had a
regular heart rhythm and no heart murmurs. At presentation,
the respiratory function test revealed a vital capacity (VC)
of 2.43 L, %VC of 83.6%, forced expiratory volume in one
second (FEV1) of 2.06 L, FEV1% of 88.0%, and a diffusing
capacity of the lung for carbon monoxide/predicted value of
48.8%. According to these results, a diminished diffusing
capacity was indicated, but not a restrictive or obstructive
ventilatory impairment.
Further investigation was therefore performed. The pa-
tient’s laboratory findings at presentation showed normal to-
tal white blood cell (WBC) and C-reactive protein (CRP)
levels. In addition, most of the lung cancer markers were
normal. However, the levels of both sialyl Lewisx-i antigen
and angiotensin-converting enzyme (ACE) were increased at
67 U/mL and 39.8 U/L, respectively (Table 1). Chest radi-
ography showed miliary nodules, and computed tomography
(CT) confirmed diffuse fine pulmonary nodules with bilat-
eral swelling of the hilar and mediastinal lymph nodes
(Fig. 1). These nodules were not prominent in the perilym-
phatic distribution, such as in the bronchovascular bundle
Department of Respiratory Medicine, Osaka Red Cross Hospital, Japan
Received for publication December 8, 2014; Accepted for publication February 1, 2015
Correspondence to Dr. Masato Taki, qyfjy370qyfjy370@yahoo.co.jp
Intern Med 54: 2483-2486, 2015 DOI: 10.2169/internalmedicine.54.4681
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Figure 1. A) A chest radiograph obtained at presentation showing miliary opacities. B), C) A chest computed tomography scan obtained at presentation showing miliary opacities in the upper and mid-dle lung fields.
A B C
Figure 2. Hematoxylin and Eosin staining of the lung biopsy showing a non-caseating epithelioid cell granuloma (original magnification: 100×).
Table 1. Laboratory Findings on Presentation.
<Complete Blood Cell Counts> <Blood Chemistry> WBC 4,160 / L TP 7.6 g/dL
Neut 67.7 % Alb 4.4 g/dLEosino 5.3 % AST 23 IU/LBaso 1.0 % ALT 24 IU/LLymph 17.3 % T-Bil 0.5 mg/dLMono 8.7 % BUN 8.7 mg/dL
RBC 518×104 / L Cre 0.62 mg/dLHb 15.1 g/dL Na 137 mEq/LHct 43.9 % K 4.3 mEq/LPLT 28.1×104 / L Ca 9.2 mg/dL
CRP <0.2 mg/dL
<Serological Studies> normal range CEA 4.4 ng/mL 0 - 5SLX 67 U/mL 0 - 38CYFRA <1.0 ng/mL 0 - 3.5NSE 12.4 ng/mL 0 - 16.3ProGRP 41.0 pg/mL 0 - 80.9
ACE 39.8 U/L 8.3 - 21.4
and interlobular septa. Although these nodules were diffuse,
they demonstrated an upper and middle lung zone predomi-
nance. Subsequent 18F-fluorodeoxyglucose-positron emission
tomography showed strong hypermetabolism in the pulmo-
nary involvement.
We then performed diagnostic bronchoscopy. The bron-
choalveolar lavage (BAL) fluid of the right middle lobe
showed lymphocytosis (90.5%) and an elevated CD4/8 ratio
of 7.3. A transbronchial lung biopsy at the right S8 revealed
non-caseating epithelioid cell granulomas (Fig. 2), and nei-
ther tuberculosis nor malignancy was identified. Thus, we
diagnosed the patient with sarcoidosis.
During the diagnostic process, the patient developed
blurred vision due to ocular sarcoidosis. According to her
body weight of 61 kg, we initiated glucocorticoid therapy
with prednisolone at 30 mg/day, which was approximately
equal to 0.5 mg/kg. The blurred vision began to improve 1
week later. After 1 month of treatment, both the exertional
dyspnea and blurred vision had resolved and the miliary
nodules on chest radiography had disappeared. The miliary
opacities had disappeared completely on a repeat CT at 4
months following treatment (Fig. 3). We gradually tapered
the glucocorticoid dose and her treatment was discontinued
Intern Med 54: 2483-2486, 2015 DOI: 10.2169/internalmedicine.54.4681
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Figure 3. The miliary opacities disappeared on a repeat chest computed tomography scan four months after the initiation of glucocorticoid therapy.
after 1 year. The miliary sarcoidosis has not recurred for 6
months since completing the treatment.
Discussion
Sarcoidosis is a disease of unknown etiology character-
ized by non-caseating granulomas. The first case report of
sarcoidosis was by the English physician Jonathon Hutchin-
son in 1877 (2). Sarcoidosis occurs worldwide and can in-
volve any organ. Although bilateral hilar lymphadenopathy
and lung field abnormalities are common, sarcoidosis in the
Japanese population tends to present with higher rates of
ocular and cardiac involvement than in the Western popula-
tion. These features are also reflected in the difference in the
mortality rates, with pulmonary sarcoidosis the leading
cause of death in Western countries and cardiac lesions in
Japan (3). The incidence of sarcoidosis among Asians, in-
cluding the Japanese population, is lower than that in Cau-
casian and Black populations (4).
In pulmonary sarcoidosis, the typical findings include per-
ilymphatic nodules, interlobular septal thickening, and bilat-
eral perihilar opacities. These parenchymal abnormalities are
predominant in the upper and middle lung fields. In con-
trast, miliary opacities are rare and atypical (1). To the best
of our knowledge, only six cases of miliary pulmonary sar-
coidosis have been published in the English literature (5-10).
Although the peak incidence of sarcoidosis tends to be in
the third and fourth decades of life (4, 11, 12), four of the
previous reports of miliary disease were in patients in their
fifth decade. Nevertheless, a single case of a 15-year-old
with hypercalcemia and miliary sarcoidosis did not show
any anomalous clinical features other than age. Because the
present patient was also 40 years of age, it may be that the
peak incidence of miliary sarcoidosis is higher than that for
typical sarcoidosis. Five of the six previously reported cases
were men. Furthermore, despite the evidence of miliary
opacities and the confirmation of granuloma formation, three
of the cases were respiratory asymptomatic. Moreover, glu-
cocorticoid therapy was used in all cases, and only one case
had any recurrence. In the case that had recurrent disease,
sustained remission was obtained after a second course of
glucocorticoid therapy (Table 2). Thus, according to the data
from the previous case reports, miliary sarcoidosis may tend
to present in middle-aged patients, have a male preponder-
ance, and have a milder disease course. Further case reports
are necessary to confirm these findings.
The typical differential diagnosis for miliary opacities of
the lung includes tuberculosis, metastatic lesions, and pneu-
moconiosis. Of these, tuberculosis and metastatic lesions are
hematogenous and tend to be randomly distributed, whereas
pneumoconiosis tends to present in the centrolobular and
bronchovascular bundles as in sarcoidosis. Therefore, impor-
tant diagnostic considerations include the following: any his-
tory of fever or sputum production, the duration and pro-
gression of the symptoms, a past history of malignancy,
smoking status, occupational history, the physical examina-
tion and laboratory findings (including blood tests and a
bacteriological examination), and pathological examinations.
Careful attention is therefore essential to avoid making a
misdiagnosis.
Sarcoidosis is often detected on a chest radiograph during
the routine screening in an asymptomatic patient (13) and
has a high rate of spontaneous remission (14). Therefore, in
an asymptomatic patient, it may be unnecessary to treat the
lung lesions. In the present patient, we administered gluco-
corticoid therapy because she had dyspnea on exertion; the
decision to treat was vindicated by the prompt resolution of
the symptoms and miliary opacities shortly after the treat-
ment was initiated.
We are confident that sarcoidosis was correctly diagnosed
in the present case. This is supported by the elevated serum
ACE level, the high CD4/CD8 ratio in the BAL fluid, the
presence of non-caseating epithelioid cell granulomas in the
lung tissue, and the response to glucocorticoid therapy. Fur-
thermore, the CRP level is generally elevated in up to 85%
patients with tuberculosis (15), but it was normal in the pre-
Intern Med 54: 2483-2486, 2015 DOI: 10.2169/internalmedicine.54.4681
2486
Table 2. Summary of the Five Cases of Miliary Sarcoidosis.
Reference Age/Gender Country Respiratory symptoms
Sampling method of lung tissues
Treatment
(5) 46 F India Shortness of breath
TBLB Steroid
(6) 47 M Greece Cough VATS Steroid
(7) 15 M America Nothing TBLB Steroid
(8) 45 M India Cough TBLB Steroid
(9) 48 M Greece Nothing TBLB Steroid(recurrence
once)(10) 37 M Germany Nothing TBLB Steroid
Present case
40 F Japan Dyspnea on exertion
TBLB Steroid
F: Female, M: Male, TBLB: transbronchial lung biopsy, VATS: viedo-assisted thoracic surgery
sent patient. Moreover, neither tuberculosis nor malignancy
was detected in the BAL fluid or lung tissue, no malignant
tumors appeared during the follow-up, and the patient de-
nied any occupational exposure suggestive of pneumoconio-
sis, including silicosis, asbestosis, aluminum lung, and
welder’s lung. Taken together, these findings suggested that
the patient’s disease was highly likely to be miliary sarcoi-
dosis.
The reason that sarcoidosis rarely exhibits miliary opaci-
ties is not clear. For instance, miliary opacities may occur
when granulomas uniformly appear around the peripheral
bronchus. The miliary opacities in the present case demon-
strated upper and middle lung zone predominance, which is
typical in sarcoidosis. In miliary sarcoidosis, a perilymphatic
distribution and upper and middle lung zone predominance,
demonstrating relatively mild lung involvements, are typi-
cally observed. The interstitial pulmonary tissue in the pre-
sent case was estimated to have been widely damaged in a
typical sarcoidosis-like manner according to the presence of
extensive opacities. Therefore, the diminished diffusing ca-
pacity in the present case was accountable.
Although miliary sarcoidosis is rare, unlike other diseases
presenting with miliary opacities, it is easily curable with
simple glucocorticoid therapy. Sarcoidosis should be in-
cluded in the differential diagnosis when miliary opacities
are observed in the lung. Although the clinical features of
miliary sarcoidosis (such as age, sex, race, and symptoms)
are yet to be established due to the limited number of case
reports, it is possible that there is a middle-age and male
preponderance along with a relatively mild disease course.
However, it is necessary to accumulate more case reports of
miliary sarcoidosis to clarify our understanding of this inter-
esting presentation.
The authors state that they have no Conflict of Interest (COI).
References
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4. Morimoto T, Azuma A, Abe S, et al. Epidemiology of sarcoidosisin Japan. Eur Respir J 31: 372-379, 2008.
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