Page 1027 - Clinical Immunology_ Principles and Practice ( PDFDrive )

990 Part seven Organ-Specific Inflammatory Disease

OPPORTUNITIES FOR PROGRESS IN SARCOIDOSIS
Pulmonary Hypertension
Small retrospective case series have suggested that pulmonary
vasodilator treatment can reduce pulmonary artery pressure On tHe HOrIZOn
and improve exercise dyspnea and 6-minute walk distance in • Diagnostic and prognostic tools based on:
49
patients with sarcoidosis who have pulmonary hypertension. • Genotyping
The benefit of vasodilator therapy on survival rates remains • Genomic/microbiome/proteomic and immunological signatures
uncertain. 50 • Improvements in imaging techniques to assist in assessment of organ
involvement
Cardiac Sarcoidosis • Multicenter clinical trials of immune-altering therapies for treatment
of sarcoidosis
Initial treatment consists of cardiac medications (antiarrhythmic
therapy, diuretics, and afterload-reducing agents) along with
corticosteroid therapy that may reverse heart block, reduce We have the necessary foundations for making rapid progress
arrhythmias, and improve cardiac function. Corticosteroids are in understanding sarcoidosis. Although there is considerable
recommended in moderate doses as some studies have found clinical heterogeneity, distinct clinical phenotypes are well
no difference in 5-year survival rates for patients treated with established, from acute sarcoidosis (Löfgren syndrome) to chronic
prednisone >30 mg/day versus <30 mg/day. Higher doses are progressive organ disease. It is known that the genetic basis of
often used initially for intractable arrhythmias or heart block. sarcoidosis predominantly resides within the MHC. Immunologi-
Cardiomyopathy may require long-term treatment, and cytotoxic cal hallmarks of the disease include noncaseating granulomas
drugs are often used for steroid sparing. Small case series have and highly polarized Th1 and Th17 immunity with proinflam-
suggested that TNF inhibitors may be useful, but caution is matory cytokines, such as TNF, at sites of disease, associated
advised with regard to their use, since these agents can worsen with reduced Treg activity. Evidence from multiple centers suggests
congestive heart failure in nonsarcoidosis cardiomyopathy. that mycobacterial and possibly propionibacterial organisms may
Automatic implantable defibrillators and/or pacemakers are trigger sarcoidosis. The recent identification of innate immune
indicated in patients at risk for sudden death from serious pathways, one of which involves SAA, suggests mechanisms that
arrhythmias or heart block, although their prophylactic use may explain the pathogenesis of chronic sarcoidosis in the absence
remains controversial. The effectiveness of radiofrequency ablation of active chronic infection. The challenge for the next 5–10 years
for prevention of arrhythmias in cardiac sarcoidosis remains is to translate these laboratory discoveries into clinical tools to
uncertain. assist the clinician in providing the diagnosis and prognosis for
individual patients. Newer therapies are sorely needed for the
Neurosarcoidosis treatment of patients with sarcoidosis, particularly those who
High doses of oral corticosteroids (60–80 mg/day) or high-dose have chronic disease and generally require long-term maintenance
pulse intravenous therapy are often used for serious CNS involve- therapy. The potential for curing this disease is suggested by a
ment. Tapering should be performed over several months after remission rate of >50%, although progress toward this goal awaits
confirming suppression of inflammation by objective criteria a better understanding of the mechanisms that allow remission
(e.g., serial MRI scans). With the exception of cranial neuropathies, to occur. Research that integrates assessment of clinical phenotype,
neurosarcoidosis tends to be chronic and requires long-term genetic background, and individual immunophenotypical and
therapy. environmental triggers in different subgroups of patients may
offer the best chance for rapid progress.
Depression/Fatigue/Pain
Small case series have highlighted the existence of small-fiber Please check your eBook at https://expertconsult.inkling.com/
neuropathy and autonomic neuropathy in sarcoidosis, particu- for self-assessment questions. See inside cover for registration
larly in patients with pain. A few case reports have suggested details.
that anti-TNF therapies may be beneficial in small-fiber
neuropathy, but their role in sarcoidosis remains undefined. REFERENCES
Intravenous immunoglobulin (IVIG) has also been effective
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