Management Challenges in Sarcoidosis
From the New Cross Hospital, Wolverhampton, UK.
Abstract
- Objective: To discuss the management of sarcoidosis.
- Methods: Review of the literature.
- Results: Sarcoidosis is a challenging multisystem disorder of uncertain etiology characterized by granulomatous inflammation in the affected organs. Treatment is dependent on the severity of disease and organ involvement at the time of diagnosis. Glucocorticoids have traditionally been considered first-line pharmacologic treatment; however, a significant proportion of patients do not require drug treatment due to the propensity toward spontaneous disease remission. Treated patients who fail to respond to corticosteroids or develop significant adverse effects can be offered a second-line agent, eg, methotrexate. Anti-TNF therapy may be considered as a treatment option in carefully selected patients with refractory disease after discussion of potential adverse effects followed by close monitoring at a specialist center.
- Conclusion: Further research into therapeutic options is likely to unveil novel agents with different mechanisms of action and better safety profiles than those seen with currently available immunosuppressive regimens.
Sarcoidosis is a multisystem disorder of uncertain etiology characterized by granulomatous inflammation in the affected organs. The diagnosis of sarcoidosis is best supported by histological evidence of noncaseating granuloma formation. It is a disease with a generally good prognosis; less than 5% patients die from the disease, with cause of death usually secondary to respiratory failure or cardiac or neurologic involvement. This review aims to discuss the management of sarcoidosis with a special emphasis on the management challenges resulting from the myriad clinical manifestations and potential complications seen in this chronic multisystem disease.
Case Study
Initial Presentation
A 40-year-old African-American man presents to his primary care physician with symptoms of fatigue, dry cough, exertional breathlessness, dry and painful eyes, generalized arthralgia, and multiple skin lesions for 3 months. He has a history of essential hypertension and is a former smoker with 10 pack-year history. He is not on any regular medications. Examination reveals bilateral cervical lymphadenopathy and multiple skin lesions on trunk. The rest of the systemic examination (including respiratory and cardiovascular system) is normal.
Workup
The patient’s initial bloodwork showed a mild degree of lymphopenia (1.1 × 109/L, normal range 1.5–4.5). Other bloodwork results, bone profile and immunology screen (including ANA, rheumatoid factor, immunoglobulins, and extractable nuclear antigen antibodies) were negative. Angiotensin-converting enzyme (ACE) was elevated at 149 U/L (normal range 5–58), while serum calcium and vitamin D levels (including vitamin D3) were normal. The findings on CT scan along with the biochemical profile suggest a plausible diagnosis of 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.
