Phenotypes of organ involvement in sarcoidosis

Abstract

Sarcoidosis is a highly variable, systemic granulomatous disease of hitherto unknown aetiology. The GenPhenReSa (Genotype-Phenotype Relationship in Sarcoidosis) project represents a European multicentre study to investigate the influence of genotype on disease phenotypes in sarcoidosis.The baseline phenotype module of GenPhenReSa comprised 2163 Caucasian patients with sarcoidosis who were phenotyped at 31 study centres according to a standardised protocol.From this module, we found that patients with acute onset were mainly female, young and of Scadding type I or II. Female patients showed a significantly higher frequency of eye and skin involvement, and complained more of fatigue. Based on multidimensional correspondence analysis and subsequent cluster analysis, patients could be clearly stratified into five distinct, yet undescribed, subgroups according to predominant organ involvement: 1) abdominal organ involvement, 2) ocular-cardiac-cutaneous-central nervous system disease involvement, 3) musculoskeletal-cutaneous involvement, 4) pulmonary and intrathoracic lymph node involvement, and 5) extrapulmonary involvement.These five new clinical phenotypes will be useful to recruit homogenous cohorts in future biomedical studies.

Clinical phenotyping: role in treatment decisions in sarcoidosis

“…Two recent phenotypes have been specifically described to help with genetic studies. In the study by SCHUPP et al [15], a large population of sarcoidosis patients from various clinics in Europe were evaluated. The authors grouped the clinical features of these patients and identified some associations.…”

“…Two studies by GRUNEWALD and co-workers [3,8] investigated HLA-DR markers in sarcoidosis patients with Löfgren syndrome and were able to differentiate patients with an excellent prognosis versus those with a 50% chance of having chronic disease. The study by SCHUPP et al [15] identified clustering of symptoms so that further studies of genetic markers could be done on those patients with different clusters of organ disease.…”

Screening Sarcoidosis Patients for Occult Disease

“…113 Splenomegaly is often associated with hepatomegaly in sarcoidosis. 123,127 As with hepatic sarcoidosis, splenic nodules are not specific for splenic sarcoidosis, and infections such as tuberculosis and lymphoma should be considered. Lymphoma is a particular concern, as there appears to be an association between these two diseases.…”

Nonlife-Threatening Sarcoidosis

“…Numerous knowledge gaps exist in this regard, including the independent contributions of the environmental exposure profile, host factors and socioeconomic status, and the complex and poorly understood genetic and epigenetic variables. 18,28,29 The initial presentation and outcomes of sarcoidosis may be related to gender, race, age, and genetic and geographic factors. 13,23,30 African Americans are affected more frequently than White Americans.…”

“…8 More serious complications of sarcoidosis are pulmonary fibrosis, renal failure, cardiac involvement, neurosarcoidosis, defacing lupus pernio, and vision loss due to posterior uveitis. 17,18 Patients at risk of poor outcomes include those with treatment-resistant pulmonary sarcoidosis (especially fibrotic disease and pulmonary hypertension) as well as those with cardiac, neurological, and multiorgan disease. 20,23,24 Depending on the duration of observation, the mortality risk due to sarcoidosis is approximately 5%.…”