Clinical Presentation and Treatment of High-Risk Sarcoidosis

Abstract

Sarcoidosis is a multisystem disease of unknown cause with heterogeneous clinical manifestations and variable course. Spontaneous remissions occur in some patients, whereas others have progressive disease impacting survival, organ function, and quality of life. Four high-risk sarcoidosis phenotypes associated with chronic inflammation have recently been identified as high-priority areas for research. These include treatment-refractory pulmonary disease, cardiac sarcoidosis, neurosarcoidosis, and multiorgan sarcoidosis. Significant gaps currently exist in the understanding of these high-risk manifestations of sarcoidosis, including their natural history, diagnostic criteria, biomarkers, and the treatment strategy, such as the ideal agent, optimal dose, and treatment duration. The use of registries with well-phenotyped patients is a critical first step to study high-risk sarcoidosis manifestations systematically. We review the diagnostic and treatment approach to high-risk sarcoidosis manifestations. Appropriately identifying these disease subgroups will help enroll well-phenotyped patients in sarcoidosis registries and clinical trials, a necessary step to narrow existing gaps in understanding of this enigmatic disease.

Keywords: cardiac sarcoidosis; high-risk sarcoidosis; multiorgan sarcoidosis; neurosarcoidosis; progressive pulmonary sarcoidosis.

Figure 1.

Cardiac imaging of a patient with cardiac sarcoidosis. (A) Cardiac magnetic resonance late gadolinium enhancement (LGE) image showing LGE in a pattern that is multifocal, subepicardial, and septal predominant and involves the right ventricular free wall (red arrows). (B) Corresponding fluorodeoxyglucose positron emission tomography image showing fluorodeoxyglucose uptake in a similar pattern, largely matching the LGE (white arrows).

Figure 2.

Overview of the management approach to CS in cases with known extracardiac sarcoidosis. ^aAll patients with extra-CS who do not have cardiac symptoms undergo a screening ECG. The absence of ECG abnormalities and symptoms suggests a low likelihood of CS. Conversely, patients with symptoms suggestive of cardiac disease or ECG abnormalities undergo further evaluation with CMR and/or ambulatory ECG. ^bCMR findings of myocardial involvement include ventricular dysfunction and late gadolinium enhancement (particularly in multifocal distributions involving the interventricular septum and the subepicardium). The location and burden of late gadolinium enhancement may also provide information for sudden cardiac death risk from CS (85, 90). ^cAntiinflammatory therapy is commonly with corticosteroids and antimetabolites, usually methotrexate. Corticosteroids are tapered to minimize steroid side effects and toxicity. Antimetabolites are usually maintained for a prolonged duration of at least 24 months before consideration of tapering. ^dSee Table 3. Monitoring with an implantable loop recorder is considered in patients with worrisome but infrequent symptoms. When there is an indication for internal cardiac defibrillator implantation, a dual-chamber device is considered. In those with impaired left ventricular systolic function and ventricular dyssynchrony, biventricular pacing is considered, as it could improve both short- and long-term VT-free survival. An electrophysiology study for ventricular arrhythmia induction to risk stratify is needed in some patients (137). ^eIn cases in which the CMR is suggestive of CS, cPET with perfusion imaging may further define sarcoidosis activity and establish a baseline for future comparison, particularly if AICD implantation precludes future CMR imaging. ^fThe presence and degree of myocardial inflammation on cPET, left ventricular ejection fraction, high-grade conduction system abnormality, and presence of rhythm abnormalities aid in decisions regarding antiinflammatory treatment and dose changes based on disease activity on follow-up evaluation. AICD = automatic internal cardiac defibrillator; AV = atrioventricular; CAD = coronary artery disease; CMR = cardiac magnetic resonance; cPET = cardiac positron emission tomography; CS = cardiac sarcoidosis; EF = ejection fraction; ECG = electrocardiogram; EP = electrophysiology; FDG = fluorodeoxyglucose; LVEF = left ventricular ejection fraction; TNF = tumor necrosis factor; TTE = transthoracic echocardiography; VF = ventricular fibrillation; VT = ventricular tachycardia.