Outcome of Sarcoidosis

doi:10.1016/j.ccm.2008.03.006

Clinics in Chest Medicine

Volume 29, Issue 3, September 2008, Pages 565-574

https://doi.org/10.1016/j.ccm.2008.03.006 Get rights and content

Sarcoidosis is a chronic granulomatous inflammatory disease of unknown etiology with heterogeneous outcome. Based on the natural history or clinical treatment course, the outcomes of cases can be divided into two wings: spontaneous regression (self-limited disease) or progression of extensive fibrotic lesions as a postgranulomatous fibrosis. In addition to examining these outcomes, this article focuses on several related concepts, including chronicity (persistence of the lesions), relapse/recurrence, deterioration, and mortality. It also reviews the outcomes from the point of view of relevant clinical phenotypes, the natural disease course, the effects of treatment, and the effects of lung transplantation. Finally, it considers the effects of pulmonary hypertension, various genetic factors on the outcomes, and the efficacy of several novel therapeutic drugs in treating sarcoidosis.

Section snippets

Spontaneous regression

The clinical expression, natural history, and prognosis of sarcoidosis are highly variable [2]. Spontaneous regression occurs in nearly two thirds of patients, but Siltzbach's scheme and the authors' experience suggest that this takes several years in most cases. Clarification of the natural history of sarcoidosis is confounded by the influence of corticosteroid therapy, which usually is offered to patients who have signs and symptoms. In the classic report from Katz [9], 60% to 80% of patients

Persistence and chronicity

In most patients, sarcoidosis evolves into chronic courses. Acute onset with good prognosis can be expected in cases with erythema nodosum (EN), anterior uveitis, and acute arthritis. There has been discussion on how long patients who have sarcoidosis should be followed to identify cases in the chronic stage.

In the authors' study, they selected a special population of patients who were asymptomatic, whose disease had been detected when they were in their 20s, and who had no extrathoracic

Relapse and recurrence

In most the large series published to date, one third to one half of patients who had sarcoidosis were treated with corticosteroids [10]. Patients stabilize or improve with treatment, but 16% to 74% of them relapse when the corticosteroids are tapered or discontinued [7], [10], [12].

In a large study from the United States, 337 patients who had sarcoidosis were divided into three groups: spontaneous remission, corticosteroid-induced remission, and recalcitrant [13]. The rate of relapse was 74%

Deterioration

Deterioration usually means a progression of pulmonary fibrosis, cardiac failure, prominent decrease in visual acuity, and impaired activity of daily living caused by neuromuscular lesions in patients who have sarcoidosis.

One study reported 17 deaths by sarcoidosis among a population of 254 patients followed for 27 years from the initial diagnosis at admission [15]. In this report, respiratory symptoms at presentation were independently related to overall mortality. A similar result has been

Mortality and morbidity

According to death certificate reports of 26,866,600 people who died from 1979 to 1991 in the United States, 5791 deaths were caused by sarcoidosis or a complication of the disease. This mortality rate seems to be low. The reported mortality caused by sarcoidosis varies by region, sex, and race. The age-adjusted mortality rates increased from 1.3 deaths per 1 million population in 1979 to 1.6 deaths per 1 million population in 1991 among men, and from 1.9% to 2.5%, respectively, among women.

Organ involvement of sarcoidosis and outcomes

A large population of sarcoidosis patients (818) was analyzed retrospectively to study the prognoses for individual manifestations of the disease [24]. EN, acute arthritis, and BHL were confirmed to have good prognoses, while cor pulmonale, nephrocalcinosis, lupus pernio, and upper respiratory mucosal involvement had unfavorable clinical courses. Hepatomegaly carried a worse prognosis than splenomegaly or pulmonary involvement without BHL. These results reflected the classical understanding

Clinical phenotypes

The WASOG (World Association of Sarcoidosis and Other Granulomatous Disorders) task group tried to define clinical phenotypes in association with clinical outcomes in sarcoidosis patients diagnosed according to the standardized diagnostic instrument proposed by the ACCESS study [25]. The clinical phenotypes were defined at least 5 years after detection or onset. Five years was identified as the start of a chronic phase, based on rates of remnant shadows on chest radiographs (see Fig. 1). At the

Genotypes, clinical phenotypes, and clinical outcomes

An interplay between genetic and environmental factors has been considered in the pathogenesis of sarcoidosis. No single causative environmental factor has been identified from the ACCESS study. Family clustering and differences in the racial incidence of sarcoidosis support an inherited susceptibility. Although several susceptibility genes have been reported, few of them are associated with clinical outcomes. As part of the ACCESS study, one group tested the hypothesis that sibling pairs who

Pulmonary hypertension as a prognostic factor

Pulmonary hypertension can be associated with sarcoidosis, although this is generally uncommon. Most cases are detected in patients who have advanced pulmonary fibrotic lesions or prominent hilar lymphadenopathy, and very few are found in association with veno-occlusive disease [35], [36], [37], [38]. This clinical manifestation is not constellated adequately in the current clinical phenotypes or in the organ involvement standardized by ACCESS. When pulmonary hypertension is diagnosed in a

Novel drug therapy and the outcome of sarcoidosis

Corticosteroid is a standard therapeutic drug for sarcoidosis patients whose clinical phenotype requires treatment. Some reports demonstrate favorable responses, although there has been debate as to whether corticosteroids should be introduced earlier or later in the clinical course [11], [45], [46], [47]. The wide distribution of the organ involvement, the presence of extrathoracic lesions, and several other prognostic factors suggest that a portion of patients in the subgroup requiring

Summary

Clinical outcomes of sarcoidosis include spontaneous regression, improvement with treatment, persistence of lesions (chronicity), relapse/recurrence, and deterioration. Based on the proposed clinical phenotypes, most patients are in the chronic stage, and more than 40% of patients are under treatment. Spontaneous regression and deterioration have similar frequencies. Several factors can be detected as prognostic factors associated with chronicity or deterioration. No definite relation can be

Acknowledgments

The article was approved by the ethical committee in Central Clinic/Research Center. The authors thank Mr. Simon Johnson for his linguistic review.

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To evaluate the epidemiology and clinical relevance of 1-year lung function decline in sarcoidosis.
A retrospective observational study at a general sarcoidosis clinic.
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Compared with a 24-month decline, a 12-month decline in lung function did not predict worse survival in sarcoidosis.
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Citation Excerpt :
Pulmonary involvement is seen in approximately 90% of affected patients [1,3,4], and respiratory failure is the most common cause of sarcoidosis-associated death [5,6]. While the long-term outcomes of sarcoidosis are highly variable [7–9], patients with extensive pulmonary fibrosis and pulmonary hypertension (PH) are reportedly at an elevated risk of mortality [10,11]. Progressive fibrosing interstitial lung disease (PF-ILD), also known as the progressive fibrosing phenotype, was recently characterized as an entity across several ILD types, such as non-specific interstitial pneumonia (NSIP), connective tissue disease-associated ILD, pneumoconiosis, and chronic hypersensitivity pneumonia (CHP) [12].
A decline in lung function is the basis of the definition of progressive fibrosing interstitial lung disease. This study aimed to evaluate the epidemiology and clinical relevance of lung function decline in sarcoidosis.
This retrospective observational study was conducted at a general sarcoidosis clinic. Lung function decline was defined as a relative 24-month decline in the percentage of predicted forced vital capacity (%FVC) of ≥10% or the percentage of predicted diffusion capacity for carbon monoxide (%DLco) of ≥15%. The frequency of lung function decline and its associations with the subsequent 24-month change in lung function and survival time were analyzed.
Of the 201 patients, 14 (7.0%) exhibited a 24-month decline in %FVC of ≥10% and 28 (16.6%) exhibited a 24-month decline in %DLco of ≥15%. A 24-month decline in lung function was not associated with a subsequent 24-month lung function decline. Eleven patients died during the median observational time of 148.3 months; 4 of the 11 deaths were associated with sarcoidosis. A 24-month decline in lung function was associated with worse survival even after the adjustment for composite physiological index (CPI) and pulmonary hypertension (PH): 24-month decline in %FVC ≥10%, hazard ratio (HR) adjusted for CPI = 21.8, HR adjusted for PH = 19.3 and 24-month decline in %DLco ≥15%, HR adjusted for PH = 6.74.
A 24-month decline in lung function can be a risk factor for mortality in sarcoidosis irrespective of CPI and PH.
Patterns of medication use and imaging following initial diagnosis of sarcoidosis
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Sarcoidosis is a rare inflammatory disease with unclear natural history. Using a large, retrospective, longitudinal, population-based cohort, we sought to define its natural history in order to guide future clinical studies.
We identified 722 newly diagnosed cases of sarcoidosis within Kaiser Permanente Northwest health care records between 1995 and 2015. We investigated immunosuppressive medication use in the two years following diagnosis, analyzed demographic and clinical characteristics, and quantified chest imaging and pulmonary function testing (PFTs) across the clinical course.
Over two years of follow-up, 41% of patients were treated with prednisone. Of those, 75% tapered off their first course within 100 days, although half of those patients required recurrent therapy. Five percent of the entire cohort remained on prednisone for longer than one year, with an average daily dose of 10–20 mg. Chest imaging was associated with early prednisone use, and chest CT was associated with changes in prednisone dose. PFTs or demographics were not associated with prednisone use. Cumulative prednisone doses were significantly higher in African Americans (1,845 mg additional) and those who had a chest CT (2,015 mg additional). Overall, PFTs were less frequently obtained than chest imaging and had no significant change over disease course.
The natural history of sarcoidosis varies greatly. For those requiring therapy, corticosteroid burden is high. Chest imaging drives medication dose changes as compared to PFTs, but neither outcome fully captures the entire history of disease. Prospective cohorts are needed with purposefully collected, repeated measures that include objective clinical assessments and symptoms.
Pulmonary Sarcoidosis: Prognostic Factors at Diagnosis in Patients from North of Portugal
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Sarcoidosis is a multisystemic granulomatous disease that affects the lungs in more than 90% of the patients. It is associated with a variable clinical course and considering all the different forms of disease presentation, there are an absence of reliable clinical prognostic markers that can predict the outcome at diagnosis.
The aim of our study was to investigate prognostic factors at diagnosis in a population of sarcoidosis patients from Northern Portugal.
A group of 110 patients with chronic evolution was compared with 129 patients with disease resolution regarding their clinical, radiologic and laboratorial features.
We found a positive association between the chronic forms and lung function impairment, radiologic stage II, lower lymphocyte CD4/CD8 and extrapulmonary disease. Löfgren syndrome and asthenia instead had a protective significant association to chronicity. Our final logistic regression model found a significant independent association between age (adjusted OR = 1.06), extrapulmonary involvement (adjusted OR = 2.68), Löfgren's syndrome (adjusted OR = 0.15) with outcome toward chronicity.
In this first study searching for prognostic factors at diagnosis in a Northern Portuguese population, we found clinical prognosis factors that have been described in other populations that should be considered whenever sarcoidosis is identified.
La sarcoidosis es una enfermedad granulomatosa multisistémica que afecta a los pulmones en más del 90% de los enfermos. Está asociada a un curso clínico variable y, considerando todas las formas diferentes de presentación de la enfermedad, hay una ausencia de marcadores de pronóstico clínico confiables que puedan predecir el resultado en el momento del diagnóstico.
El objetivo de nuestro estudio fue investigar los factores pronósticos en el momento del diagnóstico en una población de enfermos con sarcoidosis del norte de Portugal.
Se comparó un grupo de 110 enfermos con evolución crónica con 129 enfermos con resolución de la enfermedad teniendo en cuenta sus características clínicas, radiológicas y de laboratorio.
Se encontró una asociación positiva entre las formas crónicas y el deterioro de la función pulmonar, el estadio radiológico II, la relación CD4/CD8 más baja y la enfermedad extrapulmonar. Ya el síndrome de Löfgren y la astenia tuvieron una asociación protectora significativa con la cronicidad. Nuestro modelo de regresión logística final encontró una asociación independiente significativa entre la edad (OR ajustada = 1,06), la afectación extrapulmonar (OR ajustada = 2,68), el síndrome de Löfgren (OR ajustada = 0,15) y el resultado hacia la cronicidad.
En este primer estudio de búsqueda de factores pronósticos en el momento del diagnóstico en una población del norte de Portugal, fueron encontrados predictores clínicos, que se han descrito en otras poblaciones que se deben considerar cada vez que se hace el diagnóstico de una sarcoidosis.
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: This work was supported by a Grant from the Central Clinic/Research Center Foundation.

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Outcome of Sarcoidosis

Section snippets

Spontaneous regression

Persistence and chronicity

Relapse and recurrence

Deterioration

Mortality and morbidity

Organ involvement of sarcoidosis and outcomes

Clinical phenotypes

Genotypes, clinical phenotypes, and clinical outcomes

Pulmonary hypertension as a prognostic factor

Novel drug therapy and the outcome of sarcoidosis

Summary

Acknowledgments

Med Clin North Am

Am J Med

Clin Chest Med

J Clin Epidemiol

Chest

J Heart Lung Transplant

Chest

Am J Med

Chest

Chest

Chest

Chest

Chest

Chest

American Thoracic Society (ATS), The European Respiratory Society (ERS), and the World Association of sarcoidosis and other granulomatous disorders (WASOG). Statement of sarcoidosis

Am J Respir Crit Care Med

Clinical courses and prognoses of pulmonary sarcoidosis

Curr Opin Pulm Med

Presenting characteristics as predictors of duration of treatment in sarcoidosis

Q J Med

Treatment of pulmonary sarcoidosis. State of the art

Lung transplantation in sarcoidosis

Semin Respir Crit Care Med

Clinical presentation and natural history of sarcoidosis

Outcome of the treatment for sarcoidosis

Am J Respir Crit Care Med

British Thoracic Society Sarcoidosis Study; effects of long- term corticosteroid treatment

Thorax

Recurrent sarcoidosis: a study of 17 patients with 24 episodes of recurrence

Sarcoidosis Vasc Diffuse Lung Dis

Respiratory symptoms at presentation and long-term vital prognosis in patients with pulmonary sarcoidosis

Sarcoidosis

Predicting respiratory failure in sarcoidosis patients

Sarcoidosis Vasc Diffuse Lung Dis