Elsevier

Autoimmunity Reviews

Volume 13, Issues 4–5, April–May 2014, Pages 383-387
Autoimmunity Reviews

Review
Diagnostic criteria for sarcoidosis

https://doi.org/10.1016/j.autrev.2014.01.035Get rights and content

Abstract

Sarcoidosis is a multiorgan system disease that often presents insidiously. The diagnosis is often made fortuitously upon routine chest radiography or that done for other reasons. Blacks are more commonly affected than whites and age of onset is typically adolescents to young adults. Lung involvement is common and symptoms may include cough, dyspnea and chest pain. Extrapulmonary symptoms may include the skin, joint and eye findings. Bilateral hilar adenopathy is the classic finding on chest radiograph. Anemia or other cell line deficiencies, elevated liver enzymes, hypercalciuria, and EKG abnormalities may also be present. Angiotensin converting enzyme levels may be elevated but are not diagnostic. Histopathological confirmation of noncaseating granulomas is essential for diagnosis. It is generally performed through a biopsy of the most peripheral site possible, although transbronchial biopsy is commonly required. Finally, other possible etiologies must be evaluated and differentiated with a particular emphasis on tuberculosis due to the multiple overlapping symptoms and findings. Newer techniques such as proteomics and transcriptional gene signatures may contribute to the understanding of the pathophysiology of sarcoidosis, and may even serve as diagnostic tools in the future.

Introduction

Sarcoidosis is a multisystem disease that primarily affects adolescents and adults most commonly between the ages of 10 and 40. The overall prevalence of sarcoidosis appears to be between 10 and 20 per 100,000 people. It is characterized by the presence of noncaseating granulomas in the lymph nodes, lung, skin, joint or eyes. The onset is often insidious, and in children, it is particularly asymptomatic. In symptomatic pediatric patients, extra-pulmonary manifestations are more commonly observed, in contrast to adults [1]. There is a significant geographical and racial variation. It is 3–4 times more common in blacks compared to whites and familial clustering has been reported [2]. The lifetime risk of sarcoidosis in African Americans is 2.4%, compared to 0.8% for whites. Blacks also seem to have more acute and aggressive disease compared to whites.

Making the diagnosis under the age of 5 years is rare, as the prevalence in this age group is only about 0.06 per 100,000. By the mid-teenage years of 14–15, the prevalence has climbed to about 1 new patient per 100,000 and the clinical presentation is similar to that of adults [3]. Females have a higher incidence than males [4].

Section snippets

Diagnostic criteria

Sarcoidosis is a very heterogeneous disease, both in terms of presentation and severity. The pathophysiology of sarcoidosis is unclear, but it is likely that a heterogeneous set of triggers leads to the formation of noncaseating granulomas throughout multiple organ systems in genetically susceptible individuals. There appears to be a predilection for the lungs, but other sites can be involved. The presence of different phenotypes renders it difficult to develop clear and concise diagnostic

Clinical features consistent with sarcoidosis

The clinical history is of critical importance in establishing a diagnosis of sarcoidosis. As sarcoidosis has been reported to occur following exposure to certain “toxic” or “chemical” agents, a comprehensive occupational and environmental history may be helpful. Sarcoidosis has been associated with heavy metal exposures such as beryllium and its salts (Salem Sarcoid), although the American Thoracic Society criteria list berylliosis as a separate entity [4]. In some cases, the trigger is not

Laboratory and radiographic studies in the diagnosis of sarcoidosis

Laboratory tests to support the diagnosis include complete blood count (CBC), electrolytes, BUN/Cr, liver enzymes, alkaline phosphatase, calcium, urinalysis including urinary calcium and creatinine, immunoglobulins and angiotensin converting enzyme (ACE). The CBC may show leukopenia, anemia, thrombocytopenia or pancytopenia. Liver enzymes, alkaline phosphatase and immunoglobulins may be elevated. Hypercalciuria is defined as urinary calcium to creatinine ratio of > 0.2 for normal patients over

Histopathologic confirmation of noncaseating granulomas

Though the cumulative evidence on history and exam as outlined above may be highly suggestive of sarcoidosis, they remain nonspecific. A history and physical examination consistent with findings in sarcoidosis are of utmost importance, but still the diagnosis must be confirmed by histopathological evaluation showing noncaseating granulomas (Fig. 4). Discrete well-formed non-necrotizing granulomas are the hallmark of sarcoidosis. Lesions often consist of a cluster of epitheloid and

Masqueraders

A differential diagnosis of sarcoidosis is shown in Table 1. Adenopathy may be seen in other entities such as leukemia or infectious mononucleosis. Cough and dyspnea can be consistent with asthma or viral infections. Uveitis may also be infectious or associated with spondyloarthridities. Ocular and facial palsies may be seen in Lyme disease or herpes zoster infections. Liver enzyme elevation can be seen in many disease states, and sarcoidosis existing as an overlap syndrome with other

Biomarkers and future directions

The advent of molecular biology and computerized laboratory medicine has ushered in a period where advanced methods of diagnosing and monitoring disease have been made possible through the use of proteomics and transcription patterns. An understanding of the molecular biology of sarcoidosis may lead to the identification of particular micro-RNAs that play a regulatory role in the disease, and which may also generate new avenues of diagnosis and treatment.

Definition of biosignatures that are

Discussion

In summary, sarcoidosis is a multisystem granulomatous disease with a variety of presenting symptoms and findings. A comprehensive history and physical examination should identify any predispositions to sarcoidosis, as well as any pulmonary, skin, joint and eye findings that support the diagnosis. An environmental and occupational history is the key, as exposure to various heavy metals has been associated with sarcoidosis. Serological evaluation should look for abnormalities in the liver

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