Seminars in respiratory and critical care medicine
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Semin Respir Crit Care Med · Jun 2014
ReviewSarcoidosis-associated pulmonary hypertension and lung transplantation for sarcoidosis.
Pulmonary hypertension (PH) is a significant complication of sarcoidosis, occurring in approximately 6 to > 20% of cases, and markedly increases mortality among these patients. The clinician should exercise a high index of suspicion for sarcoidosis-associated PH (SAPH) given the nonspecific symptomatology and the limitations of echocardiography in this patient population. The pathophysiology of PH in sarcoidosis is complex and multifactorial. ⋯ In this article, we review the epidemiology, diagnosis, prognosis, and treatment considerations for SAPH. Lung transplantation (LT) is a viable therapeutic option for sarcoid patients with severe pulmonary fibrocystic sarcoidosis or SAPH refractory to medical therapy. We discuss the role for LT in patients with sarcoidosis, review the global experience with LT in this population, and discuss indications and contraindications to LT.
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For treatment of sarcoidosis, one should develop a long-term management plan. Factors to be considered include the organ involvement and severity of symptoms. Different organ manifestations may require different treatments. ⋯ These include cytotoxic agents such as methotrexate, biologic agents such as the antitumor necrosis factor antibody infliximab, and other anti-inflammatory drugs such as hydroxychloroquine. In some cases, anti-inflammatory drugs may not help. Examples include pulmonary hypertension and fibrosis.
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Semin Respir Crit Care Med · Jun 2014
ReviewSarcoidosis and common variable immunodeficiency: similarities and differences.
Common variable immunodeficiency (CVID) is a primary immunodeficiency that is characterized by hypogammaglobulinemia and poor/absent specific antibody production. Granulomatous and lymphocytic interstitial lung disease (GLILD) is an increasingly recognized complication of CVID, occurring in 10 to 20% of patients. GLILD is characterized by non-necrotizing granuloma, lymphocytic interstitial pneumonitis and follicular bronchiolitis-histological patterns that are typically present in the same biopsy. ⋯ The presence of noncaseating granuloma in the lung along with some of the extrapulmonary features of GLILD may lead to an incorrect diagnosis of sarcoidosis. However, GLILD differs from sarcoidosis in several important ways including mode of presentation, extrapulmonary manifestations, radiographic abnormalities on high-resolution computed tomography scan of the chest, and laboratory features (serum immunoglobulins, bronchoalveolar lavage, and histopathology). The misdiagnosis of sarcoidosis in a patient with CVID and GLILD can lead to inappropriate treatment and increase the morbidity and mortality of the disorder.
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A consensus statement found in most peer-reviewed literature on sarcoidosis is that the etiology of sarcoidosis is unknown. It is timely to review whether this statement should be revised. Many infectious agents meet the basic requirements of inducing granulomatous inflammation and immunologic responses consistent with sarcoidosis including oligoclonal expansion of CD4+ T cells, polarized Th1 and possibly Th17 responses, and dysregulated regulatory T-cell function. ⋯ The hypothesis that chronic sarcoidosis is caused by a viable, replicating mycobacterial or other infection has no direct pathologic, microbiologic, or clinical evidence. A novel hypothesis links microbial triggers to a sarcoidosis outcome from the accumulation of aggregated proinflammatory serum amyloid A within granulomas, providing a mechanism for chronic disease in the absence of any viable tissue infection. Further studies are needed to provide more definitive evidence for these competing hypotheses before the statement that the etiology of sarcoidosis is unknown becomes obsolete.
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Semin Respir Crit Care Med · Jun 2014
ReviewCellular activation in the immune response of sarcoidosis.
Sarcoidosis is a chronic granulomatous disorder characterized by an accumulation of lymphocytes and macrophages in the alveoli. Ultimately, long-lasting, nontreated disease results in a distortion of the microarchitecture of the lower respiratory tract. Our current understanding of its pathogenesis is that several sequential immunological events finally resulting in granuloma formation are involved: (1) dependent on a susceptible genetic background described by a variety of functional polymorphisms (2) the exposure to one or several still elusive antigen(s), leads to (3) an activation of macrophages, (4) an attainment of T cell immunity against the antigen(s) mediated by antigen processing and presentation by macrophages, and finally to (5) induction of granuloma formation. ⋯ The important role of alveolar macrophages, T lymphocytes, regulatory T cells, and various cytokines/chemokines in orchestrating the induction, evolution, and immunoregulation of the sarcoid granulomatous/fibrotic lesions will be underscored. Although an etiological agent for sarcoidosis has not been identified, plausible "sarcoid antigens" including mycobacterial antigens such as mKatG or ESAT-6, antigens from Propionibacterium acnes, or even self-antigens will be discussed. It is possible that not one single causative agent exists but several germs, microbial products, or inorganic substances might induce pathogenetic mechanisms leading to a disease called sarcoidosis.