The authors conclude that although recent findings reinforce the hypothesis that transmissible agents, particularly mycobacteria, may be causative in some sarcoidosis cases, the matter remains controversial due to the inability to consistently isolate microorganisms in pathological specimens. Whatever the etiology, they suggest that future studies focus on specific disease phenotypes to identify more homogeneous populations for analysis. Unraveling how genetic risk factors and environmental triggers interact to determine the disease is challenging but will inevitably have an impact on both diagnostic and therapeutic strategies in granulomatous lung diseases.
 

Cardiac sarcoidosis (CS) is a rare but potentially fatal condition that may present with a wide range of clinical manifestations including congestive heart failure, conduction abnormalities, and most notably, sudden death. Recent advances in imaging technology allow easier detection of CS, but the diagnostic guidelines with inclusion of these techniques have yet to be written. It has become clear that minimally symptomatic or asymptomatic cardiac involvement is far more prevalent than previously thought. Because of the potential life-threatening complications and potential benefit of treatment, all patients diagnosed with sarcoidosis should be screened for cardiac involvement. Patients with CS and symptoms such as syncope need an aggressive workup for a potentially life-threatening etiology.
 

Researchers assessed antioxidant and inflammatory status in sarcoidosis and the potential of the flavenoid quercetin to mitigate the occurring inflammation.  Their results suggest sarcoidosis patients might benefit from antioxidant supplementation not only by empowering the relatively low protection against ROS but also by reducing inflammation.

Researchers in Italy collected data from 80 consecutive outpatients with sarcoidosis and found 44% endorsed at least one psychiatric DSM-IV axis I diagnosis. Specifically, 25% of subjects met the criteria for Major Depressive Disorder, 6.3% for Panic Disorder, 6.3% for Bipolar Disorder, 5% for Generalized Anxiety Disorder and 1.3% for Obsessive Compulsive Disorder. They conclude sarcoidosis is associated with a high rate of psychiatric comorbidity and may contribute to a poorer quality of life.  A referral for a psychiatric or psychological evaluation and counseling should be considered for many of the sarcoidosis patients.
 

While sarcoidosis generally inflicts a greater morbidity on African-American compared with Caucasian patients, no studies have examined whether racial differences exist in the intensity of the histologic hallmark of sarcoidosis, noncaseating granulomas. This retrospective case series included 187 patients with biopsy confirmed of sarcoidosis.  The authors found that averall, African-American patients had a twofold greater median granuloma density than Caucasians. They conclude a greater granuloma density in bronchiolar lung tissue of African-American sarcoidosis patients may explain racial differences in diagnostic yield by lung biopsy and disease severity at diagnosis.
 

Crohn's disease and sarcoidosis are chronic inflammatory diseases that share several clinical and immunological features, including the occurrence of granulomas.  A genome-wide association study of 382 CD patients, 398 SA patients and 394 control individuals found a significant association at SNP rs1398024 on chromosome 10p12.2, with an odds ratio (OR) for both diseases of 0.81.  Researchers in this German study demonstrate that the combined analysis of different, albeit clinically related, phenotypes (sarcoidosis and Chrohn's) can lead to the identification of common susceptibility loci.
 

Familial clustering of cases and ethnic variation suggest a genetic influence on the susceptibility to sarcoidosis. Monozygotic and dizygotic twins enrolled in either the Danish or the Finnish population-based, national Twin Cohorts (61,662 pairs in total) were linked to diagnostic information on sarcoidosis obtained from the Danish National Patient Registry or the Social Insurance Institution, Finland, registry of reimbursed medication using the 8th and 10th editions of the International Classification of Diseases. A total of 210 twin pairs with at least one subject with a diagnosis of sarcoidosis were identified. Compared to the general population we found an 80-fold increased risk of developing sarcoidosis in co-twins of affected monozygotic brothers or sisters. The increased risk in dizygotic twins was on the other hand only 7-fold.   This study suggests that genetic factors play an important role in the susceptibility to sarcoidosis and result should encourage the search for molecular genetic markers of susceptibility to the disease.
 

The aim of this study was to describe clinical features and long-term survival in childhood sarcoidosis. In total, 46 ethnic Caucasian Danish children (aged <16 yrs, 24 males) with sarcoidosis were identified in 1979–1994. The authors conclude that in Danish children, sarcoidosis had a favorable prognosis. The majority recovered, but some developed chronic active disease and impairment of pulmonary function, demanding continuous medical treatment. Prognosis was not related to the age at onset of disease. Erythema nodosum was associated with a good prognosis, and central nervous system involvement with a poor prognosis.
 

Research increasingly suggests that sarcoidosis results from an interplay of environmental and genetic factors.  Although the recently completed ACCESS (A Case-Control Etiologic Study of Sarcoidosis) study was not able to definitively identify a single cause for sarcoidosis, it did yield important findings regarding familial and environmental risks that have advanced our understanding of this disease.  Family clustering and differences in racial incidence of sarcoidosis support an inherited susceptibility to sarcoidosis. Siblings of patients with sarcoidosis have about a fivefold increased risk of developing sarcoidosis.  In addition, two recent genome scans have been reported in sarcoidosis. One in African Americans reporting linkage to chromosome 5 and the other in German families reporting linkage to chromosome 6. The author concludes that advances in genotyping and statistical analysis are helping to clarify the genetics of sarcoidosis.
 

The lungs are the most commonly affected organ in sarcoidosis.  Ninety percent or more of people with sarcoidosis have lung involvement, whether they have symptoms or not.  This Japanese study investigated early pulmonary involvement of 24 sarcoidosis patients using an imaging method called scintigraphy.  Comparing results from chest computed radiography (CR), high resolution computed tomography (HRCT) and scintigraphy with (99m)Tc-DTPA aerosol against confirmed biopsies, they conclude that pulmonary clearance scintigraphy with (99m)Tc-DTPA aerosol may be useful for assessing pulmonary involvement before radiological changes are evident.
 

Fibered confocal fluorescence microscopy (FCFM) is a new technique that produces microscopic imaging of a living tissue through a 1-mm fiberoptic probe that can be introduced into the working channel of the bronchoscope.   Researchers in France analyzed the microscopic structure of normal and diseased bronchial lining using FCFM during bronchoscopy and found that this procedure represents a minimally invasive method to study specific alterations associated with premalignant bronchial lesions within the body. They conclude the technique may also be useful to study the bronchial wall in nonmalignant chronic bronchial diseases, like sarcoidosis.
 

Using 33 non-smoking sarcoidosis patients, researchers in Spain evaluated the bronchoalveolar lavage fluid to determine whether quantities of white blood cells would provide predictive information as to the future course of their disease.  They found that increased percentages of specific white blood cells in the bronchoalveolar lavage fluid from patients with sarcoidosis were associated with a poor outcome and a higher probability to need treatment.
 

In this retrospective study, researchers in Turkey evaluated 492 consecutive patients with sarcoidosis to evaluate the seasonal pattern of symptoms by age and by both genders.  According to chest X-ray examinations, 185 patients had stage 1, while 307 patients in control group had stages 0, 2, 3 and 4.  Demographic features, presenting clinical features, course of the disease, initial diagnostic methods and both the month and the age at the initial diagnosis for each patient were analyzed.  The distribution of cumulative monthly presentations for patients with stage 1 peaked in April (108% above the average) and was lowest in October, November and December (48% below the average).  Their findings additionally suggest seasonal patterns were influenced by age and by gender.  They recommend further prospective studies to better understand disease development and possible  interactions among age, gender and the disease.
 

Lofgren's syndrome is a form of acute sarcoidosis that occurs for a short period with specific symptoms and which affects specific areas of the body.  Inflammation usually includes the skin of the legs (erythema nodosum), the joints and the lymph glands in the chest and occurs along with a fever.  In evaluating 150 patients, researchers in Sweden conclude that manifestations of Lofgren's syndrome differ between men and women, with skin inflammation found predominantly in women while a inflammation around the ankle joints or ankle arthritis without EN is seen preferentially in men.
 

1 Sept 2006

Genetic characterization and fine mapping of susceptibility loci for sarcoidosis in African Americans on chromosome 5. Hum Genet. 2006 Aug 4; Epub ahead of print.

Sarcoidosis, a systemic granulomatous disease, likely results from both environmental agents and genetic susceptibility. In the United States, African Americans are both more commonly and more severely affected than Caucasians. Previously, a sarcoidosis genetic linkage study consortium was established to recruit African-American affected sibling pair families to identify chromosomal regions that may harbor sarcoidosis susceptibility genes and to determine if environmental factors modify any genetic effects (SAGA Study - SArcoid Genetic Analysis).  Researchers report a follow up to the first genome scan for sarcoidosis susceptibility genes in African Americans.  Like the original, the present study included 229 African American nuclear families ascertained through two or more siblings with sarcoidosis and found the strongest signal was at marker D5S407 (P=0.005) on 5q11.2, using both full and half sibling pairs.  The results support, in an African American population, a sarcoidosis susceptibility gene on chromosome 5q11.2, and a gene protective for sarcoidosis on 5p15.2.  In addition, researchers conclude that multiple susceptibility loci for sarcoidosis exist in African Americans and that some may have interdependent effects on disease development.
 

8 Aug 2006

ACE I/D-corrected Z-scores to identify normal and elevated ACE activity in sarcoidosis. Respir Med. 2006 Aug 8; Epub ahead of print.

The value of elevated serum angiotensin-converting enzyme (ACE) activity in the diagnosis and follow-up in sarcoidosis is a matter of ongoing debate.  ACE activity is influenced by polymorphisms, or genetic variants, in the ACE gene. Tests that do not use genotype-specific reference intervals for ACE activity may lead to a less precise interpretation of ACE activity.  In order to assess whether determination of ACE activity requires the ACE I/D genotype to be taken into account, researchers in the Netherlands established ACE I/D-corrected reference intervals in 200 healthy volunteers.  ACE activities in sarcoidosis patients were then expressed as a Z-score (standard score) related to these reference intervals.  This data demonstrates a convenient and accurate way to circumvent the use of different intervals by introducing a Z-score for ACE activity and suggests the need to re-investigate the possible clinical value of serum ACE activity in sarcoidosis.
 

1 July 2006

Transforming growth factor-beta gene polymorphisms in sarcoidosis patients with and without fibrosis. Chest. 2006 Jun;129(6):1584-91.

Pulmonary fibrosis, or scarring of the lungs, develops in approximately 25% of patients with chronic sarcoidosis. Transforming growth factor-beta (TGF–β) is a chemical messenger protein identified as having a central role in fibrosis. Researchers in the Netherlands assessed patients and control subjects over a four-year follow up period to determine whether genetic variations in the three isoforms, or versions, of this protein might contribute to pulmonary fibrosis in sarcoidosis patients. This study is the first to suggest the implication of genetic variation of TGF–β3 in the development of pulmonary fibrosis in sarcoidosis patients.
 

1 June 2006

A new tool to assess sarcoidosis severity. Chest. 2006 May;129(5):1234-45.

Sarcoidosis is a granulomatous disorder that primarily affects the lung, however, other organs are frequently involved. There are no comprehensive scoring systems for sarcoidosis disease severity. Researchers reviewed clinical data on 104 patients with biopsy-confirmed sarcoidosis and independently scored disease severity using a visual analog scale.  From their analysis, they derived an objective disease severity scoring system that incorporates data on demographics, pulmonary function and organ involvement to produce a whole-body sarcoidosis assessment. They suggest this preliminary tool has potential applicability in the assessment of disease severity in sarcoidosis research.
 

1 May 2006

Relationship between Symptoms and Quality of Life in a Sarcoidosis Population. Respiration. 2006 Apr 7; Epub ahead of print.

Sarcoidosis is a multi-system disease and patients may suffer from various symptoms. However, the relationship between frequently reported symptoms and quality of life (QOL) has not yet been studied.  Researchers conducted a cross-sectional observational study on 150 sarcoidosis patients in Croatia to assess symptoms and QOL using the World Health Organization Quality of Life Assessment Instrument.  The four most frequently mentioned symptoms were fatigue, breathlessness, reduced exercise capacity and arthralgia, or joint pain.  Being female, using corticosteroids and fatigue were sited as factors which impacted physical and psychological health as well as level of independence, with fatigue the most important symptom in predicting QOL.  Researchers recommend to focus not only on objective health parameters, but also on fatigue in the management of sarcoidosis.
 

1 Apr 2006

Bayesian logistic regression using a perfect phylogeny. Biostatistics. 2006 Mar 23; Epub ahead of print.

Haplotypes are sets of genes on a single chromosome. Haplotype data capture genetic variation among individuals in a population and among populations. An understanding of this variation and the ancestry of haplotypes is important in genetic association studies of complex diseases like sarcoidosis. Using a candidate gene study of sarcoidosis, researchers introduce a new method for detecting associations between disease and haplotypes which uses a statistical approach based on probability to incorporates new information and even prior knowledge (Bayes’ theorem) and logistic regression to create an evolutionary history (phylogeny). Environmental factors, as well as their interactions with variations in the genetic code (SNPs) can be incorporated into the regression framework.
 

1 Mar 2006

The effect of genetic diversity on angiogenesis. Exp Cell Res. 2006 Mar 10;312(5):561-74.

Angiogenesis is the process by which new blood vessels are formed from existing vessels.  In mammals, variations in different genes are thought to alter this process.  Genetic diversity in angiogenesis-regulating genes has been linked to increased susceptibility to multiple angiogenesis-dependent diseases in humans including cancer, arthritis, atherosclerosis, cardiovascular disease, endometriosis, diabetic retinopathy, psoriasis and sarcoidosis.  Recent studies have used genome sequences from other species to dissect the complexity of the genetic diversity that regulates angiogenesis.  Gene mapping in mouse models has identified the position of several genes involved in the process.   Comparing the human genome sequence with those of other organisms helps identify regions of similarity and difference, providing critical clues about the structure and function of human genes.
 

1 Feb 2006

Autoimmune and chronic inflammatory disorders and risk of non-Hodgkin lymphoma by subtype. J Natl Cancer Inst 2006 Jan 4;98(1):51-60.

Some autoimmune and chronic inflammatory disorders are associated with increased risks of non-Hodgkin lymphoma (NHL).  Researchers in Denmark and Sweden conducted a population-based case-control study of 3055 NHL patients and 3187 matched control subjects.  Patients were asked about their history of autoimmune and chronic inflammatory disorders, markers of severity and treatment. Risks of NHL were increased in association with certain diseases including rheumatoid arthritis, primary Sjogren syndrome, systemic lupus erythematosus, and celiac disease.  However, sarcoidosis, psoriasis, and inflammatory bowel disorders were not associated with increased risk of NHL overall or of any NHL subtype.
 

1 Dec 2005

Involvement of discoidin domain receptor 1 in the deterioration of pulmonary sarcoidosis. Am J Respir Crit Care Med. 2005 Dec;33(6):565-73.

Although the lungs are affected in more than 90% of patients with sarcoidosis, the symptoms and severity of disease can vary greatly. Researchers in Japan sought to identify the mechanism which led to worse outcomes, or deterioration, in lung disease. In looking at 33 patients with sarcoidosis with pulmonary infiltrates, they found increased levels of DDR1, an enzyme involved in cell communication, and conclude that it is associated with the deterioration of lung disease.
 

1 Oct 2005

Difficulties in the differentiation of chronic inflammatory diseases of the central nervous system--value of cerebrospinal fluid analysis and immunological abnormalities in the diagnosis.  Acta Neurol Scand. 2005 Oct;112(4):207-13.

A number of systemic diseases can affect the nervous system including lupus erythematodes, Behcet's disease, Sjogren's syndrome (SS) and sarcoidosis.  These diseases can be difficult to diagnose because neurologic symptoms can be confused with those of another chronic inflammatory disease, multiple sclerosis (MS).  Because these diseases are treated differently, it is important to distinguish between them.  When reviewed individually, neither clinical signs nor specific tests such as blood tests or cerebrospinal fluid (CSF) analysis are able to differentiate between the diseases with certainty.  However when researchers compared all typical clinical and CSF findings together, differentiation of the respective diseases, and diagnosis was possible.
 

1 Sept 2005

Usefulness of quantifying serum KL-6 levels in the follow-up of uveitic patients with sarcoidosis.  Graefes Arch Clin Exp Ophthalmol. 2005 Aug 23;:1-5 [Epub ahead of print]

The appearance of sarcoidosis outside of the lung is common in certain populations, for example more patients in Japan have heart and eye complications from the disease. Comparing 36 patients with uveitis to the same number of healthy controls, researchers in Japan found that measuring blood levels of KL-6, a molecule that consists of protein and carbohydrates, was useful to diagnose sarcoidosis as well as to follow-up diagnosed cases because levels were less affected by systemic medication than other blood tests.
 

1 Aug 2005

Relationship of environmental exposures to the clinical phenotype of sarcoidosis. Chest. 2005 Jul;128(1):207-15.

Sarcoidosis is a multi-system disease that causes inflammation of the body’s tissues. Symptoms typically depend on which organ the disease affects. Using 718 patients at 10 A Case Control Etiologic Study of Sarcoidosis (ACCESS) centers, researchers reviewed the duration and intensity of patient exposures to different environmental elements and found that systemic and pulmonary-only sarcoidosis may be caused by different environmental exposures. Findings that include African-Americans' exposure to wood burning and Caucasians' exposure to agricultural organic dust are associated with different phenotypes of sarcoidosis also suggests that African-Americans and Caucasians are either affected differently by the same exposures or that they come into contact with different exposures.
 

1 July 2005

Genome-wide search for sarcoidosis susceptibility genes in African Americans.  Genes Immun. 2005 Jun 9; [Epub ahead of print].

The cause of sarcoidosis is not yet known, however, genetic predisposition does appear to be important.  In the US, sarcoidosis frequently occurs more often and more severely among African Americans than among Caucasians.  This study looked at 229 African-American families where two or more siblings had a history of sarcoidosis, to try to determine the specific physical location of a susceptibility gene on a chromosome.  Based on their findings, the researchers conclude that it is likely that more than one gene influences sarcoidosis susceptibility in African Americans.
 

6 June 2005

Fungal infections as a complication of therapy for sarcoidosis. QJM. 2005 Jun;98(6):451-6.

Sarcoidosis granulomas (masses of inflamed tissue, or lumps) result from a response of the immune system. Most medications used to treat sarcoidosis suppress the immune system. This can leave a person more likely to get sick from an infection.  In addition, fungal infections may be difficult to distinguish from sarcoidosis.   In this retrospective study, researchers in Ohio looked at the notes from 753 patients seen over an 18 month period and found that only seven patients (0.9%) developed fungal infections - suggesting that fungal infections occur rarely in treated patients with sarcoidosis.  However, deterioration of chest X-ray, especially a localized infiltrate (collection of of inflammatory cells), warrants investigation.
 

1 May 2005

Pulmonary hypertension in advanced sarcoidosis: epidemiology and clinical characteristics.  (Eur Respir J. 2005 May;25(5):783-8.)

Pulmonary hypertension is a condition in which the pressure of the blood vessels in the lungs is elevated. This causes the heart and lungs to strain to provide enough oxygen to the body. Pulmonary hypertension is common in advanced sarcoidosis and associated with poor outcomes, but little is known about which sarcoidosis patients are likely to develop it. Researchers reviewed the records of 363 patients in the United States and found that patients who needed higher levels of supplemental oxygen often had pulmonary hypertension. They suggest more aggressive screening for pulmonary hypertension be considered in patients with sarcoidosis.
 

1 Apr 2005

Deficiency of a subset of T-cells with immunoregulatory properties in sarcoidosis. (Lancet. 2005 Mar 16;365(9464):1062-72.)

Sarcoidosis is a multisystem disorder that predominantly involves the lungs and is characterized by T-cell response and granuloma formation, for which the explanation is unknown. A newly identified subset of T-cells with immunoregulatory functions has been shown in animal studies to protect against disorders with increased T-cell responses similar to sarcoidosis. Researchers took blood samples from 60 patients with sarcoidosis and found that these cells were absent or greatly reduced in all patients.  The deficiency was found in both acute and resolved disease and was unrelated to systemic corticosteroid therapy.  The authors conclude that the loss of immunoregulation by these cells could explain the amplified and persistent T-cell activity in sarcoidosis and may provide new insight into the development of sarcoidosis and draw attention to a potential target for new treatments.
 

1 Mar 2005

Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of sarcoidosis. (Eur Respir J. 2005 Mar;25(3):405-9.)

Bronchoscopy is a test in which a flexible tube is inserted through the mouth to examine the airways of the lungs. In 30% of patients with suspected sarcoidosis, bronchoscopy with biopsy, or removal of tissue, is unsuccessful as a diagnostic tool and a more invasive mediastinoscopy is done to surgically remove tissue from the lymph nodes. In this study of 51 patients, researchers used a technique called “endoscopic ultrasound-guided fine-needle aspiration” (EUS-FNA) as a nonsurgical alternative to diagnose sarcoidosis by aspirating lymph nodes in the chest from the esophagus. Thirty-six patients (71%) had previously undergone a nondiagnostic bronchoscopy. EUS-FNA demonstrated a high yield in diagnosing sarcoidosis in 41 of 50 patients (82%) without complications.
 

1 Feb 2005

Histopathological Features of Conjunctival Sarcoid Nodules Using Noninvasive In Vivo Confocal Microscopy. (Arch Ophthalmol. 2005 Feb;123(2):274-6.)

In patients with inflammatory diseases of the eyes, biopsy of lesions may be helpful in confirming the diagnosis of sarcoidosis. A technique called "in vivo confocal microscopy" (IVCM) allows for noninvasive examination of the eye at the cellular level and has been used to describe diseases of the cornea. Researchers performed noninvasive IVCM on sarcoid granulomas in the eyes of a patient with skin, biopsy-proven sarcoidosis and uveitis. Results were compared with a conjunctival biopsy specimen to detail the typical microscopic features seen in sarcoidosis.
 

1 Jan 2005

Long-term follow-up CT scan evaluation in patients with pulmonary sarcoidosis. (Chest. 2005 Jan;127(1):185-91.)

A computed tomographic (CT) scan is a complicated kind of x-ray that gives a better picture of the lungs than an ordinary chest x-ray.  In this retrospective study, researchers looked at the first and last high-resolution CT (HRCT) scans of 40 patients with pulmonary sarcoidosis with an average period of 7.4 years between the two scans.  HRCT scan findings were them compared to pulmonary function tests.  Researchers identified specific patterns on the initial HRCT scans that were helpful in predicting the outcomes of patients with sarcoidosis, specifically those patients likely to develop severe respiratory problems.
 

1 Nov 2004

Early detection of cardiac involvement in patients with sarcoidosis by a non-invasive method with ultrasonic tissue characterization. (Heart. 2004 Nov;90(11):1275-80.)

This Japanese study sought to identify a non-invasive test for the early detection of heart involvement in patients with sarcoidosis. Twenty-two consecutive patients with biopsy proven sarcoidosis were selected and divided into two groups: 8 patients with cardiac involvement (diagnosed by tests including thallium, gallium and PET scans) and 14 patients without cardiac involvement. All of these patients had normal findings on conventional two dimensional echocardiograms. Researchers used a test “cyclic variation of myocardial integrated backscatter” (CV-IB) which uses ultrasound to measure a specific area of muscle in the heart. This test discriminated 75% of patients with cardiac sarcoidosis from those with non-cardiac sarcoidosis, whereas two dimensional echocardiographic did not discriminate between these two groups.
 

1 Oct 2004

Prevalence of coeliac disease in patients with sarcoidosis. Eur J Gastroenterol Hepatol. 2004 Sep;16(9):911-5.

Genetic research has suggested an association between sarcoidosis and celiac disease.  Celiac disease is an inherited, autoimmune disease in which the lining of the small intestine is damaged in response to ingestion of gluten and other proteins found in wheat, barley, rye, possibly oats and their derivatives.  Blood tests and biopsy in this pilot study of 102 sarcoidosis patients (47 males, 55 females) and 105 (52 males, 53 females) healthy, ethnically matched, controls demonstrated a moderately increased prevalence of celiac disease in Irish patients with sarcoidosis.
 

3 Sept 2004

A Case Control Etiologic Study of Sarcoidosis: Environmental and Occupational Risk Factors. Am J Respir Crit Care Med. 2004 Dec 15;170(12):1324-30. Epub 2004 Sep 3.

Past research suggests that environmental factors may be associated with sarcoidosis risk.  This case control study tested the theory that environmental and occupational exposures are associated with sarcoidosis. Ten centers recruited 706 newly diagnosed patients with sarcoidosis and an equal number of control subjects of matching age, race and sex. Test subjects answered questions regarding occupational (or job-related) and nonoccupational exposures. The study did not identify a single, predominant cause of sarcoidosis but did identify several exposures associated with sarcoidosis risk, including insecticides, agricultural employment and microbial bioaerosols.
 

1 August 2004

Sarcoidosis and granuloma genes: a family-based study in African-Americans. (Eur Respir J. 2004 Aug;24(2):251-7.)

The evidence for a genetic component in the cause of sarcoidosis includes familial grouping, associations with genetic variants and tissue similarity. Unfortunately, the majority of genetic associations with sarcoidosis have not been consistently replicated.  This study at the Henry Ford Health System in Detroit, Michigan used a family-based study design and attempted to replicate previously reported associations between sarcoidosis and three attractive candidate genes studied primarily in case-control samples. From looking at 225 nuclear families, the authors conclude that in African-Americans, the angiotensin converting enzyme, vitamin D receptor and tumour necrosis factor-alpha genes are not significant risk factors for sarcoidosis susceptibility.
 

1 July 2004

Epidemiology of sarcoidosis and its genetic and environmental risk factors. Rev Med Interne. 2004 Jul;25(7):494-500. In French.

Studies of incidence and distribution show that sarcoidosis is a world-wide disease. This review of the scientific literature indicates that disease frequency is influenced by multiple predisposition factors. The most important factors identified by the author are racial, sex, age, familial grouping, genetic and/or an infective agent. The authors conclude that sarcoidosis occurs in patients when environmental factors (infective agent, climate, country) and predisposition ones (race, sex, familial grouping) happen in connection with one another.
 

1 June 2004

NHLBI Working Group: Future Directions in Sarcoidosis Research. Am J Respir Crit Care Med. 2004 Sep 1;170(5):567-71. Epub 2004 May 13.

Although the cause of sarcoidosis remains unclear, certain environmental, genetic, ethnic and familial factors probably modify expression of the disease. For example, African-Americans are more often and more severely affected than Caucasians, and more often have a family history of the disease. Because of the many uncertainties, the National Heart, Lung, and Blood Institute convened a working group to identify future research directions and opportunities for sarcoidosis. Recommendations include developing a tissue bank, using new methods to identify genetic factors, studying the development of the disease using human and animal models, exploring new approaches to diagnose and manage the disease and conducting randomized controlled trials to assess new therapies.
 

1 May 2004

Involvement of dendritic cells in sarcoidosis. Thorax. 2004 May;59(5):408-413.

Dendritic cells are immune cells with threadlike tentacles called dendrites used to catch antigens, which they present to T cells.  In sarcoidosis, overactive T-cell cause granulomas. This Japanese study  analyzed dendritic cells in 24 patients with sarcoidosis to determine whether dendritic cells regulate the T cell response in sarcoidosis.   Their findings suggest that dendritic cells may migrate into the affected tissues, contributing to the formation of the granulomas.
 

14 Mar 2004

Health-related quality of life (HRQL) measurement may provide unique insight into the impact that sarcoidosis has on a patient’s life.  A study at three university medical center outpatient pulmonary clinics evaluated the HRQL and mental health of 111 outpatients with sarcoidosis seen between March and July 2002.  The HRQL of sarcoidosis patients was measured using surveys and questionnaires.  Outpatients with sarcoidosis had moderate to severely low HRQL and patients receiving therapy with oral corticosteroids had significantly worse HRQL than patients who were not taking steroids.  Depression and stress levels were also assessed.  The prevalence of depression was 66% and significant stress was 55% among sarcoidosis patients.
 

1 Feb 2004

While the cause or causes of sarcoidosis are unknown, there have been significant recent advances in the understanding of genetic and immunologic features.  Genetic predisposition appears to be important in the development, presentation and course of sarcoidosis. However, to date, no gene or set of genes has been identified that sufficiently explains the development of sarcoidosis.  Studies to identify specific genes determining risk for sarcoidosis have concentrated on human leukocyte antigen (HLA) genes, which are important determinants of immune response.  Studies worldwide have implicated a multitude of HLA genes.  Most likely, the tendency to develop the disease is a product of multiple genetic factors including polymorphisms governing immune regulation, T-cell function or antigen processing and presentation.
 

1 Jan 2004

Although pulmonary disease is the most frequent manifestation of sarcoidosis, musculoskeletal symptoms are not only common, but may be the initial presentation of this systemic inflammatory process and could mimic other arthritic and autoimmune disorders. This article focuses on the rheumatological aspects of sarcoidosis and includes a review of the most recent literature, which shows new data on the diagnosis, pathogenesis, and treatment of this condition.
 

1 Dec 2003

A substantial number of sarcoidosis patients report non-specific symptoms such as pain.  This study attempted to verify small-fibre neuropathy in a group of sarcoidosis patients using various electrophysiological tests. In 74 sarcoidosis patients complaining of symptoms suggestive of small-fibre neuropathy thresholds for warm (WS) and cold sensation (CS) were determined.  Testing revealed abnormalities in 51 of the 74 patients. WS was affected more often than CS and feet were affected more often than hands.  CONCLUSIONS: Small-fibre neuropathy may be the cause of a number of unexplained symptoms in sarcoidosis.
 

1 Oct 2003

215 sarcoidosis patients from the ACCESS study underwent evaluation at study enrollment and two years later.  Data indicate that sarcoidosis tends to improve or remain stable over two years in the majority of patients. Several factors associated with improved or worse outcome over two years were identified.  Patients with erythema nodosum (red bumps on the skin) at presentation were more likely to have improvement in the chest x-ray at two-year follow-up. Patients with a lower annual family income were more likely to worsen with respect to dyspnea (shortness of breath) and more likely to have new organ involvement at two-year follow-up. The development of new organ involvement over the two year follow-up period was more common in African-Americans compared to Caucasians and more likely in those with involvement outside the lungs at study entry.
 

1 Sept 2003

1 Aug 2003

This study retrospectively evaluated the clinical symptoms of patients diagnosed with sarcoidosis at one center in Turkey over the last 36 years.  Skin involvement was diagnosed in approximately one-third of all sarcoidosis patients with a generally female majority (of 170 patients with skin involvement, 136 were female and 34 were male). When patients with skin involvement were compared to other sarcoidosis patients, it was seen that the frequency of females among those with skin involvement was significantly higher than the frequency among other sarcoidosis patients. Erythema nodosum (red bumps on the skin) was the most frequent skin lesion encountered.
 

1 Jul 2003

It is well established that sarcoidosis is a multisystem disorder of unknown cause and almost no organ is immune to the disease. Pulmonary (lung) and extrapulmonary (other organ) complications may occur. This requires the attention of pulmonologists as well as specialists from other medical disciplines.  An approach that coordinates the efforts of specialists with different areas of training and that focuses attention on physical as well as psychological and social aspects of this erratic disorder is recommended when treating sarcoidosis patients.
 

1 Jun 2003

Doctors at the Prince Charles Hospital in Australia prospectively studied 123 sarcoidosis patients from 1991 to 1994 to establish the incidence of neurological (brain, nervous system) involvement.  CONCLUSIONS:  Neurological involvement was found more commonly than previously reported (26%, 32/123 patients).  A formal neurological examination was recommended in all patients with sarcoidosis as neurological involvement may be overlooked.
 

29 Mar 2003

Corticosteroids remain the standard of care for treatment of sarcoidosis, but immunosuppressive drugs have proved steroid-sparing for many patients. New agents, including pentoxifylline, thalidomide, and infliximab have proved useful in selected cases. The effectiveness of these agents seems to lie in their ability to block tumor necrosis factor (TNF), especially in the treatment of chronic disease.
 

1 Jan 2003

1 Oct 2002

1 Sept 2002

15 June 2002

Some patients with sarcoidosis have unexplained pain and impairment of the sense of touch. Testing was done 31 sarcoidosis patients with pain or autonomic dysfunction, 25 had reduced warmth sensitivity, cold sensitivity, or both. Skin biopsy samples in seven consecutive patients confirmed the presence of small fiber neuropathy. Conclusion:  Some patients with sarcoidosis may have small fiber neuropathy with autonomic involvement.
 

13 Mar 2002

Corticosteroids are used in pulmonary sarcoidosis to reduce symptoms and minimize long-term damage. A systematic review of randomized trials was done to assess the effect of oral and inhaled corticosteroids on chest radiograph results, symptoms, pulmonary function and long-term outcome in pulmonary sarcoidosis.  The search identified 150 studies; 9 met the inclusion criteria, but only 8 provided usable data. CONCLUSIONS: Oral corticosteroids improved results on the chest radiograph following 6 to 24 months of treatment and produced a small improvement in vital capacity and diffusing capacity. Trials of inhaled corticosteroids were small and results too inconsistent to make firm conclusions concerning their efficacy. There are no data to suggest that corticosteroid therapy alters long-term disease progression.
 

1 Dec 2001

Despite individual reports, little evidence exists that risk of sarcoidosis is greater among family members than in the general population. Using patients enrolled in ACCESS, researchers estimated sarcoidosis familial relative risk by collecting data on disease rates in 10,862 first and 17,047 second-degree relatives. A significant elevated risk of sarcoidosis was observed among first and second-degree relatives of sarcoidosis cases compared with relatives of control subjects.  Siblings had the highest relative risk, followed by aunts and uncles, grandparents and then parents. White cases had a markedly higher familial relative risk compared with African-American cases.
 

1 Nov 2001

A Case Control Etiologic Study of Sarcoidosis (ACCESS) enrolled 736 patients with sarcoidosis from 10 clinical centers in the United States. The study population was 53% white and 44% black, with 64% female participants. Initial results indicated that in the United States organ involvement differed according to race, sex and age.  Women were more likely to have eye and neurologic involvement, have erythema nodosum, and to be age 40 yr or over  whereas men were more likely to be hypercalcemic. Black subjects were more likely to have skin involvement other than erythema nodosum, and eye, liver, bone marrow, and extrathoracic lymph node involvement.
 

1 Mar 2000

Researchers aimed to determine whether methotrexate could be steroid sparing in the first year of corticosteroid therapy in sarcoidosis. Patients with new onset sarcoidosis within four weeks of starting on prednisone were randomized to receive either methotrexate or placebo for the next year. They were seen monthly and prednisone dosage was tapered following a pre-determined schedule. Less prednisone used for the methotrexate patients versus placebo. There was also less weight gain for those patients receiving methotrexate. CONCLUSIONS: Methotrexate can be a steroid sparing agent in acute sarcoidosis.
 

1 Aug 1999

The American Thoracic Society (ATS), in collaboration with the European Respiratory Society and the World Association of Sarcoidosis and Other Granulomatous Disorders, issued a consensus statement on sarcoidosis which provides information on the epidemiology, pathogenesis, diagnosis and treatment of sarcoidosis. It was written by a 14-member panel of authorities on sarcoidosis who primarily developed the recommendations on the basis of expert opinion and consensus.

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