Seminars in respiratory and critical care medicine
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Semin Respir Crit Care Med · Jun 2014
ReviewClinical presentation of sarcoidosis and diagnostic work-up.
Sarcoidosis is a systemic disease of unknown cause characterized by the formation of immune granulomas which most often involve the lung and the lymphatic system. Sarcoidosis may encompass numerous different clinical presentations. Typical presentations often prompt a rapid diagnosis while in 25 to 50% of cases, diverse and less typical presentations may lead to delayed diagnosis. ⋯ The probability of diagnosis at presentation is variable from case to case and may often be reinforced with time. Some investigations are mandatory at diagnosis to assess organ involvement and disease activity. However, there are important variations in diagnostic work-up due to diverse expressions of sarcoidosis and differences in clinical practices among physicians.
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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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Semin Respir Crit Care Med · Jun 2014
ReviewSarcoidosis and chronic beryllium disease: similarities and differences.
Chronic beryllium disease (CBD) is a granulomatous lung disease that may be pathologically and clinically indistinguishable from pulmonary sarcoidosis, except through use of immunologic testing, such as the beryllium lymphocyte proliferation test (BeLPT). Similar to sarcoidosis, the pulmonary manifestations of CBD are variable and overlap with other respiratory diseases. Definitive diagnosis of CBD is established by evidence of immune sensitization to beryllium and diagnostic bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. ⋯ Extrapulmonary manifestations of CBD are rare today. Since lung-predominant sarcoidosis can very closely resemble CBD, CBD is still misdiagnosed as sarcoidosis when current or past exposure to beryllium is not recognized and no BeLPT is obtained. This article describes the similarities and differences between CBD and sarcoidosis, including clinical and diagnostic features that can help physicians consider CBD in patients with apparent lung-predominant sarcoidosis.
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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.