2483

□ 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

2484

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

2485

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

1. Criado E, Sanchez M, Ramirez J, et al. Pulmonary sarcoidosis:typical and atypical manifestations at high-resolution CT with pa-thologic correlation. Radiographics 30: 1567-1586, 2010.

2. Hutchinson J. Cases of Mortimer’s malady. Arch Surg London 9:307-314, 1898.

3. Iwai K, Tachibana T, Takemura T, Matsui Y, Kitaichi M,Kawabata Y. Pathological studies on sarcoidosis autopsy. I. Epide-miological features of 320 cases in Japan. Acta Pathol Jpn 43:372-376, 1993.

4. Morimoto T, Azuma A, Abe S, et al. Epidemiology of sarcoidosisin Japan. Eur Respir J 31: 372-379, 2008.

5. Chugh IM, Agarwal AK, Arora VK, Shah A. Bilateral miliary pat-tern in sarcoidosis. Indian J Chest Dis Allied Sci 39: 245-249,1997.

6. Hatzakis K, Siafakas NM, Bouros D. Miliary sarcoidosis follow-ing miliary tuberculosis. Respiration 67: 219-222, 2000.

7. Hodges HK, Lee PY, Hausmann JS, Teot LA, Sanford EL, LevinKW. Hypercalcemia and miliary sarcoidosis in a 15-year-old boy.Arthritis Rheum 65: 2112, 2013.

8. Kumar P, Jaco MJ, Pandit AG, et al. Miliary sarcoidosis with sec-ondary Sjögren’s syndrome. J Assoc Physicians India 61: 505-507, 2013.

9. Bostantzoglou C, Samitas K, Gkogkou C, Zervas E, Gaga M. Me-diastinal widening and miliary chest radiograph pattern in a mid-dle aged man: could it be sarcoidosis? BMJ Case Rep 2014:204884, 2014.

10. Luetkens JA, Zoghi S, Rockstroh JK, Naehle CP. Pulmonary sar-coidosis shortly after spinal tuberculosis infection: a diagnosticchallenge. BMJ Case Rep 2014: 203333, 2014.

11. Jamilloux Y, Bonnefoy M, Valeyre D, Varron L, Broussolle C,Seve P. Elderly-onset sarcoidosis: prevalence, clinical course, andtreatment. Drugs Aging 30: 969-978, 2013.

12. Valeyre D, Prasse A, Nunes H, Uzunhan Y, Brillet PY,Muller-Quernheim J. Sarcoidosis. Lancet 383: 1155-1167, 2014.

13. Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl JMed 357: 2153-2165, 2007.

14. Bradley B, Branley HM, Egan JJ, et al. Interstitial lung diseaseguideline: the British Thoracic Society in collaboration with theThoracic Society of Australia and New Zealand and the Irish Tho-racic Society. Thorax 63: 1-58, 2008.

15. Breen RA, Leonard O, Perrin FM, et al. How good are systemicsymptoms and blood inflammatory markers at detecting individu-als with tuberculosis? Int J Tuberc Lung Dis 12: 44-49, 2008.

Ⓒ 2015 The Japanese Society of Internal Medicine

http://www.naika.or.jp/imonline/index.html