Management Challenges in Sarcoidosis

• What is the next step in the workup to establish the suspected diagnosis?

The radiological findings of hilar lymphadenopathy are not confirmatory. There are a number of entities in the differential diagnoses, including tuberculosis, malignancy, lymphoma, and other granulomatous disorders such as histoplasmosis, schistosomiasis, and blastomycosis. It is important to obtain histological evidence before a definitive diagnosis of sarcoidosis can be made. This is necessary as management differs for each of the diagnostic categories mentioned above. Furthermore, diagnostic confirmation would be helpful later in the disease course if the patient develops any associated complications such as pulmonary hypertension or respiratory failure and/or need for lung transplant assessment.

As this patient had palpable cervical lymphadenopathy, an ultrasound guided biopsy of the lymph node was obtained. The histological examination demonstrated evidence of noncaseating granulomas that were well formed and highly consistent with the suspected clinical and radiological diagnosis of sarcoidosis. In addition, the special stains for acid-fast bacilli and other infections including fungi were negative.

Our practice is to evaluate patients with suspected sarcoidosis with neck ultrasound and tru-cut biopsy of cervical lymph nodes (if appropriate) as a first-line investigation, as it is less invasive than bronchoscopy/endoscopic ultrasound–guided transbronchial needle aspiration (EBUS-TBNA) or thoracoscopic lung biopsy. The diagnostic yield of EBUS-TBNA has been evaluated in a number of studies with variable results [1–5]. A large multicenter randomized clinical trial [5] of 304 patients investigated the diagnostic yield of endosonography (endobronchial and esophageal ultrasound) in comparison with bronchoscopy with transbronchial biopsy (TBB) and endobronchial biopsy. The study cohort was made up of patients with stage I/II sarcoidosis. The results showed that endosonography had a higher diagnostic yield to detect granulomas (80% vs 53%; P < 0.001) and there were no serious adverse events related to endoscopy. Hence, ultrasound-guided endoscopic procedures are becoming common first-line investigations for sarcoidosis in the absence of other readily identifiable biopsy sites such as peripheral lymph nodes in the cervical area.

• What should be done about the cutaneous and ophthalmologic symptoms in this patient?

As sarcoidosis commonly involves eyes and skin (after pulmonary involvement, which is seen in 90% of cases), the patient was referred to ophthalmology and dermatology departments for further evaluation. These assessments confirmed him to have bilateral uveitis and skin involvement with granulomatous inflammation consistent with ocular and cutaneous sarcoidosis respectively. Hence, the diagnosis of multisystem sarcoidosis was made. At this stage, the patient also mentioned symptoms of intermittent palpitations for 3 months’ duration and feeling of missing a beat, so an urgent cardiological evaluation was undertaken that showed him to have ectopic beats on Holter monitoring. However, his trans-thoracic echocardiogram and a cardiac MRI scan were normal with good biventricular function, excluding cardiac sarcoidosis as a cause of his palpitations. Cardiac involvement with sarcoidosis is clinically apparent in only 5% of cases and presents as cardiomyopathy and or cardiac arrhythmias (both tachy and bradyarrythmias). As cardiac involvement with sarcoid granulomas is usually patchy, endomyocardial biopsy has a limited diagnostic yield of < 20% [6]. In this particular case, endomyocardial biopsy was not attempted in view of normal cardiac MR and echocardiography as well as no significant cardiac dysrythmia on holter monitoring.