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Pulmonary, Critical Care, and Sleep Pearls |

A 58-Year-Old Man With Fatigue, Weight Loss, and Diffuse Miliary Pulmonary Opacities FREE TO VIEW

Udit Chaddha, MD; Rebekah English, DNP; Jessica Daniels, MD; Rajat Walia, MD, FCCP; Atul C. Mehta, MD, FCCP; Tanmay S. Panchabhai, MD, FCCP
Author and Funding Information

aDepartment of Pulmonary, Critical Care and Sleep Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA

bNorton Thoracic Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ

cDepartment of Pathology, St. Joseph’s Hospital and Medical Center, Phoenix, AZ

dDepartment of Pulmonary Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, OH

CORRESPONDENCE TO: Tanmay S. Panchabhai, MD, FCCP, Norton Thoracic Institute, St. Joseph’s Hospital and Medical Center, 500 W Thomas Rd, Ste 500, Phoenix, AZ 85013


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2017;151(6):e131-e134. doi:10.1016/j.chest.2016.11.015
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Case Presentaion  A 58-year-old man presented with a 6-month history of profound fatigue and a weight loss of 35 to 40 pounds. He reported occasional night sweats and mildly painful knees and elbows without swelling or redness. He denied respiratory symptoms, rashes, or fevers. He had no respiratory symptoms. The patient’s history was significant for rheumatoid arthritis (with arthralgias and joint involvement), paroxysmal atrial fibrillation, and hypothyroidism. His medications included digoxin and metoprolol. He had been taking methotrexate and low-dose prednisone (5 mg) for approximately 10 years but discontinued taking these medications 2 years prior to current presentation. Originally from West Virginia, the patient had relocated to Arizona during the early 1980s. There was no history of international travel or TB. He had no exposure history to birds, bird feathers, or mold; however, he did report exposure to dust at his current job as a home building superintendent. He reported a 10 pack-year history of smoking, having quit 20 years ago. His family history was significant for renal sarcoidosis in his mother.

Figures in this Article

Physical examination was normal.

A chest radiograph revealed diffuse micronodular miliary opacities with enlarged mediastinal lymph nodes (Figs 1A, 1B). His serologic tests for Coccidioides immitis (antibodies against IgM and IgG according to enzyme immunoassay), urine Histoplasma antigen, QuantiFERON-TB Gold (Quest Diagnostics), and HIV (according to enzyme-linked immunosorbent assay) were negative. The hypersensitivity pneumonitis panel was negative. Autoimmune serologic tests, including antinuclear antibodies, rheumatoid factor, anti-cyclic citrullinated peptide, and antineutrophil cytoplasmic antibodies, were also negative. Serum angiotensin-converting enzyme and calcium levels were elevated, at 151 U/L (normal, < 40 U/L) and 11.2 mg/dL, respectively.

Figure 1
Figure Jump LinkFigure 1 (A) Posteroanterior and (B) lateral chest radiographs show diffuse micronodular opacities throughout the lungs.Grahic Jump Location

CT scanning of the chest revealed diffuse, randomly distributed pulmonary nodules in a miliary pattern (Figs 2A, 2B). Also seen were enlarged bulky mediastinal lymph nodes in the subcarinal and right and left paratracheal regions (Figs 2C, 2D). His spirometry and lung volume results were normal, and diffusion capacity was mildly reduced.

Figure 2
Figure Jump LinkFigure 2 Computed tomogram of the chest in lung windows showing (A, B) diffuse miliary micronodules throughout the lungs (black arrows). C, D, Bulky paratracheal and subcarinal adenopathy (white arrows) can also be seen on the mediastinal windows.Grahic Jump Location

What is the diagnosis?

Diagnosis: Miliary sarcoidosis

Sarcoidosis is a multisystem granulomatous disease of unknown etiology, characterized by noncaseating granulomas that mainly involve the lung and the thoracic lymph nodes. Patients with pulmonary sarcoidosis often present with respiratory symptoms such as cough and dyspnea and/or systemic symptoms (eg, fever, weight loss, malaise). Typical imaging patterns suggestive of sarcoidosis include the presence of symmetrical bilateral hilar and mediastinal adenopathy, with subpleural, peribronchovascular, and perilymphatic nodules commonly involving the upper lobes. Sarcoid nodules represent aggregates of granulomas that can coalesce to form macronodules. Fibrosis with linear opacities, architectural distortion, and traction bronchiectasis becomes prominent in approximately 20% of the patients. Pleural involvement in sarcoidosis is very rare. The presence of a pleural effusion warrants evaluation for other causes. Sarcoidosis is diagnosed when histologic evidence of noncaseating granulomas supports characteristic clinicoradiologic findings, after exclusion of other known causes of granulomas. Conditions such as TB, leprosy, fungal infections, berylliosis, hypersensitivity pneumonitis, Crohn’s disease, and primary biliary cirrhosis must be ruled out, making sarcoidosis a diagnosis of exclusion. Local sarcoid-like reactions can be seen at sites of chronic inflammation or in lymph nodes draining a malignant lesion. BAL fluid analysis with a high CD4-to-CD8 ratio is a useful adjunct in making the diagnosis of sarcoidosis when interpreted in a suitable clinical scenario.

Miliary sarcoidosis has been infrequently reported in the literature. Of the nine reported cases in the English literature with this condition, most presented in their fourth to fifth decade of life; two patients were diagnosed earlier (at 15 and 24 years of age). Two of the nine were women, and three patients were asymptomatic from a respiratory standpoint. It is difficult to draw meaningful conclusions regarding miliary sarcoidosis based on the scant data available on this condition. Definite answers can only come with more published experience, but it seems that this presentation of sarcoidosis is more common in middle-aged men. Respiratory symptoms seem to be milder in the reported cases compared with other parenchymal forms of sarcoidosis. Hypercalcemia, weight loss, and fatigue may be more common due to extensive involvement of the lung parenchyma with noncaseating granulomas.

In miliary sarcoidosis, the micronodules are dispersed randomly throughout the lungs with no topographic predilection. Such random nodules are often small (and hence termed miliary, meaning “similar to millet seeds”) and, as with perilymphatic nodules, tend to exhibit high-density, sharp margins. A miliary pattern is typically seen in other diseases such as infections (TB, histoplasmosis, and coccidioidomycosis), hematogenous metastases (thyroid, renal cell, pancreas, or breast carcinoma), and pneumoconiosis (silicosis). These conditions should be ruled out in patients presenting with a miliary pattern on imaging. Rarely, miliary nodules can also be seen with hypersensitivity pneumonitis, respiratory bronchiolitis, pulmonary Langerhans cell histiocytosis, and varicella infections.

Results of transbronchial lung biopsies have a high diagnostic yield (100%) in the reported patients with miliary sarcoidosis. Glucocorticoids are the cornerstone of sarcoidosis treatment. Most evidence suggests that these medications improve both respiratory symptoms and radiographic abnormalities; however, it is debatable whether asymptomatic patients with miliary sarcoidosis with normal lung function need immunosuppression therapy with corticosteroids. All reported cases of miliary sarcoidosis have shown a good response to corticosteroid therapy. Of these, only one patient had disease recurrence but stayed in remission after his second course of glucocorticoid therapy. Although it is not apparent why sarcoidosis so infrequently presents with miliary opacities, it certainly needs to be on the differential diagnosis, even in areas endemic for TB and fungal infections.

Clinical Course

The patient in our study presented a complex clinical situation, as he lived in a coccidioidomycosis-endemic area and had a family history of sarcoidosis. Results of extensive serologic infectious evaluations were negative, and the only positive laboratory data were elevated levels of angiotensin-converting enzyme and serum calcium. The patient underwent endobronchial ultrasound-guided transbronchial needle aspiration with transbronchial biopsies and BAL. Both lymph node aspirates from the right paratracheal and subcarinal lymph nodes and transbronchial biopsy specimens (Figs 3A, 3B) revealed noncaseating granulomas. BAL fluid analysis revealed lymphocytosis (19%) with a CD4-to-CD8 ratio of 1.97. Cultures (mycobacterial, fungal, and bacterial) were negative on BAL, endobronchial ultrasound-guided transbronchial needle aspiration specimens, and transbronchial biopsies at 4 weeks.

Figure 3
Figure Jump LinkFigure 3 Histologic sections (hematoxylin and eosin stain) of transbronchial lung biopsy specimens showing noncaseating granulomas (black arrows) in (A) 200× magnification and (B) 400× magnification. Also depicted is a multinucleated giant cell (red arrow) at the center of the granuloma.Grahic Jump Location

Given the patient’s profound weight loss, fatigue, and hypercalcemia, prednisone (0.5 mg/kg) was initiated. At 6 weeks, he felt much better and was no longer experiencing fatigue and had gained about 15 pounds in weight. Serum calcium levels were back to normal (9.5 mg/dL), and chest radiography showed significant improvement in the previously noted miliary nodular pattern. The patient’s spirometry results remained stable, and diffusion capacity normalized. He will continue therapy with prednisone for another 4 weeks followed by a slow taper.

  • 1.

    Sarcoidosis rarely presents with a micronodular miliary pattern. The diagnosis is made by demonstrating noncaseating granulomas on biopsy, after conditions such as miliary TB, endemic fungal infections such as histoplasmosis and coccidioidomycosis, pneumoconiosis, and hematogenous metastases have been excluded.

  • 2.

    Based on the scant data available, miliary sarcoidosis commonly affects middle-aged men.

  • 3.

    Patients with miliary sarcoidosis present with milder respiratory symptoms but frequently develop systemic illness associated with fatigue, weight loss, or hypercalcemia.

  • 4.

    Transbronchial lung biopsy specimens have an excellent yield for detecting noncaseating granulomas, similar to other presentations of sarcoidosis.

  • 5.

    Extensive microbiologic evaluation with cultures from both BAL fluid and lung biopsy specimens to rule out fungal and mycobacterial infections should be pursued. Glucocorticoid therapy is efficacious in treating this condition.

Financial/nonfinancial disclosures: None declared.

Other contributions: CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.


Figures

Figure Jump LinkFigure 1 (A) Posteroanterior and (B) lateral chest radiographs show diffuse micronodular opacities throughout the lungs.Grahic Jump Location
Figure Jump LinkFigure 2 Computed tomogram of the chest in lung windows showing (A, B) diffuse miliary micronodules throughout the lungs (black arrows). C, D, Bulky paratracheal and subcarinal adenopathy (white arrows) can also be seen on the mediastinal windows.Grahic Jump Location
Figure Jump LinkFigure 3 Histologic sections (hematoxylin and eosin stain) of transbronchial lung biopsy specimens showing noncaseating granulomas (black arrows) in (A) 200× magnification and (B) 400× magnification. Also depicted is a multinucleated giant cell (red arrow) at the center of the granuloma.Grahic Jump Location

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