A Young Woman with an Abnormal Chest X-Ray
A 32-year-old woman presents for evaluation of an incidentally found abnormal CXR. She has been accepted for employment as an elementary school teacher and had a CXR performed as part of a pre-employment physical.
History
She has no symptoms to report, specifically no shortness of breath, wheezing, cough, or hemoptysis. She is quite active in her life and is able to perform all needs and activities—including athletics—without symptoms. Her overall health is excellent, without major diagnoses, and her only medication is oral contraceptives. She has never smoked.
Physical Examination
Physical exam is totally within normal limits, including a chest exam without rales, wheezing, or consolidation. There is no adenopathy in the neck, supraclavicular, or axillary regions. The breasts are normal without masses.
Laboratory Results
CBC and metabolic panels were normal. CXR shows bilateral hilar adenopathy without other masses or infiltrates. EKG is entirely normal.
(Answer and discussion on next page)
Correct Answer: C
The patient’s presentation is classic for sarcoidosis. Her demographics are typical and include female predominance, presentation prior to age 50 (even younger in women), and pulmonary involvement. The etiology of sarcoidosis remains unknown.
Due to the focus on lungs, skin and eyes, environmental causes are often considered.1 Associations are numerous and although an immune response to various common environmental triggers remains a core postulate, no specific pathophysiology has been elucidated.1 A variety of genetic associations have also been explored.
Diagnosis of Sarcoidosis
Our patient’s clinical findings are quite typical—an asymptomatic situation encountered by abnormal screening or incidental CXR. To confirm the diagnosis, in addition to the typical findings encountered here clinically and radiologically, a supporting tissue biopsy showing non-caseating epithelioid cell granulomas in the absence of organisms or particles is required.1,2 Thus Answer C is correct. Choosing where to biopsy will depend on organ involvement and the ease or accessibility of the biopsy.
In our case, the hilar adenopathy would almost surely have yielded granuloma on mediastinoscopy with node sampling, but transbronchial endoscopic biopsy is easier and safer and therefore should be performed first. Reserve mediastinoscopy for a secondary study if initial transbronchial is non-revealing. If there is obvious clinical involvement of skin, lacrimal glands, or eyes, biopsy of those tissues would be appropriate.
Answers A and D refer to ancillary tests used in a sarcoidosis evaluation. Kveim testing (choice D) seems to have a true positive rate of 50% and essentially no false positives. However, preparation of Kvein reagent involves the use of human tissue, which is not validated across sites and has no commercially prepared reagent. It is thus a very local, proprietary situation and is used less and less as time goes on.1,3
Angiotensin-converting enzyme (choice A) uses the physiology that sarcoid granuloma produce the compound and ACE levels are elevated in 60% of cases.1 However, trials have demonstrated that ACE levels are neither sensitive nor specific enough for either diagnosis or therapeutic guidance purposes.
Finally, endomyocardial biopsy (choice B) can reveal the presence of sarcoid granulomata in the 5% of cases if sarcoidosis has cardiac involvement. However, our patient has no clinical (eg, CHF, unexplained syncope) or EKG (eg, heart block or other arrhythmias) findings. This suggests cardiac involvement and endomyocardial biopsy is far more invasive than transbronchial to demonstrate granuloma and, in fact, is likely not even the optimal testing for cardiac involvement; cardiac MRI or PET scanning is recommended.1,4
Outcome of This Case
A decision was made to do a transbronchial biopsy since it was the least invasive process when the presumed organ involvement was considered. Non-caseating granulomata were seen. All special stains and cultures for AFB and other infectious organisms were negative. An EKG, as well as a complete ophthalmologic review, and an MRI of CNS were all negative. A decision to monitor the patient closely using clinical and PFT findings was made. She continues to be asymptomatic and PFT was stable at 2 years. ■
References:
1.Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Eng J Med. 2007;357(21):2153-2165.
2.Iannuzzi MC, Rybicki BA. Genetics of sarcoidosis: candidate genes and genome scans. Proc Am Thorac Soc. 2007;4(1):108-116.
3.Statement on sarcoidosis. Joint statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Associate of Sarcoidosis and Other Granulomatous Disorders adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med. 1999;160(2):736-755.
4.Nunes H, Brillet PY, Valeyre D, et al. Imaging in sarcoidosis. Semin Respir Crit Care Med. 2007;28(1):102-120.
5.Scott TF, Yandora K, Valeri A, et al. Aggressive therapy for neurosarcoidosis: long-term follow-up of 48 treated patients. Arch Neurol. 2007;64(5):691-696.
Ronald Rubin, MD is professor of medicine at Temple University School of Medicine and chief of clinical hematology in the department of medicine at Temple University Hospital, both in Philadelphia.