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Original Research: DIFFUSE LUNG DISEASE |

Characterization of Chronic Fatigue in Patients With Sarcoidosis in Clinical RemissionPostinflammatory Fatigue in Sarcoidosis FREE TO VIEW

Ingrid H. E. Korenromp, MSc; Cobi J. Heijnen, PhD; Oscar J. M. Vogels, MD, PhD; Jules M. M. van den Bosch, MD, PhD; Jan C. Grutters, MD, PhD
Author and Funding Information

From the Department of Pulmonology (Ms Korenromp and Drs van den Bosch and Grutters), and the Department of Neurology (Dr Vogels), St. Antonius Hospital Nieuwegein; the Laboratory of Neuroimmunology and Developmental Origins of Disease (Ms Korenromp and Dr Heijnen), and the Division Heart and Lungs (Drs van den Bosch and Grutters), University Medical Center Utrecht, Utrecht, The Netherlands.

Correspondence to: Cobi J. Heijnen, PhD, University Medical Center Utrecht, Utrecht, 584EA, The Netherlands; e-mail: C.Heijnen@umcutrecht.nl


Died December 1, 2010.

Funding/Support: This study was partly funded by the Dutch Sarcoidosis Society.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2011 American College of Chest Physicians


Chest. 2011;140(2):441-447. doi:10.1378/chest.10-2629
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Background:  Patients with sarcoidosis frequently complain of fatigue, even when sarcoidosis has come into clinical remission. The primary aim of this study was to assess the severity of fatigue in patients with sarcoidosis in clinical remission and to characterize it according to the international criteria for chronic fatigue syndrome (CFS). Furthermore, we evaluated whether fatigue is associated with depression and anxiety, health status, and patient-reported sleep quality, and we recorded physical activity levels and muscle strength as objective assessments of fatigue.

Methods:  Data on 75 patients with sarcoidosis in clinical remission were obtained by questionnaires (Checklist Individual Strength [CIS], Symptom Checklist-90, Beck Depression Inventory for primary care, Medical Outcomes Study 36-Item Short-Form Health Survey), standardized interview (CFS criteria), sleep diary, accelerometer, and muscle strength tests.

Results:  Fatigue severity mean score in patients with sarcoidosis in clinical remission was high (CIS fatigue severity 30.5 ± 15.5), and criteria for CFS were met in 47% of fatigued participants. Median time since diagnosis was 9 years. Fatigue was associated with depression (P = .01), anxiety (P = .013), and reduced health status (P < .001). Scores on sleep quality were normal. Physical activity levels were reduced in fatigued participants. Muscle strength, particularly handgrip (P = .006) and quadriceps strength (P < .001), was significantly associated with fatigue.

Conclusions:  Fatigue in patients with sarcoidosis in clinical remission is a frequent symptom and can be characterized as a severe and long-lasting problem, symptomatically similar to CFS. Psychologic distress and reduced health status are associated with fatigue. Interestingly, we observed significantly reduced physical activity and muscle weakness in fatigued patients.

Figures in this Article

Fatigue appears to be one of the most commonly reported complaints of patients with sarcoidosis.1-6 Fatigue may persist not only at the onset and during the active phase of this multisystemic granulomatous disorder but also when clinically no disease activity can be detected any more.

This persistent fatigue was labeled postsarcoidosis chronic fatigue syndrome (CFS), and the symptoms were described as “profound symptoms of myalgia, fatigue, sleep reversal and low-spiritedness. The symptoms are out of proportion to the lack of physical signs and the absence of objective evidence of sarcoidosis.”7 Since then, researchers have referred to the term “postsarcoidosis CFS.”8-10 However, to the best of our knowledge, no study has investigated the exact features of fatigue in cases of sarcoidosis that are clinically in remission.

Still, doctors are recurrently confronted with patients with sarcoidosis with quiescent disease who suffer from a constellation of symptoms. Persistent and disabling fatigue is their most prominent complaint, often leading to reduced quality of life and labor disputes for incapacity to work.

From the literature we know that postinfectious or postinflammatory fatigue is a common feature. For example, > 40% of patients with inflammatory bowel disease in remission suffer from fatigue.11 Similar reports are found in patients with rheumatoid arthritis,12 infectious mononucleosis,13 cancer survivors,14,15 and Q fever.16 The pattern of symptoms found in all these conditions matches surprisingly well and seems to be similar to that seen in CFS,17 although in these cases a known precipitating disease process is present.

The aim of this study was to determine the severity of fatigue after sarcoidosis and to characterize it according to the international criteria for CFS.17 Moreover, we determined whether fatigue is associated with depression and anxiety symptoms, patient-reported sleep quality, and health status. Finally, this study recorded physical activity levels and muscle strength as objective assessments.

Study Population

One hundred ninety-three patients with sarcoidosis were invited to participate in the study either during their consult at the outpatient clinic of the St. Antonius Hospital Nieuwegein or by letter from their former treating pulmonary physician. They were selected from a database of 800 patients with sarcoidosis, irrespective of the presence of complaints of fatigue. Selection criteria included: (1) sarcoidosis diagnosed according to the latest American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and Other Granulomatous Disorders statement on sarcoidosis,18 and (2) the probability to meet the inclusion and exclusion criteria (Table 1)19 on the basis of available medical records. Out of 193 patients, 115 responded to the invitation, and 88 of them were eligible for screening. After signing the informed consent, they were tested for inclusion and exclusion criteria. The inclusion criteria focus on the clinical remission of sarcoidosis, whereas the exclusion criteria rule out other causes and disabilities that might also explain the presence of fatigue. All criteria are listed in Table 1.

Table Graphic Jump Location
Table 1 —Inclusion and Exclusion Criteria

CRP = C-reactive protein; Dlco = diffusing capacity of lung for carbon monoxide; sACE = serum angiotensin-converting enzyme; sIL-2R = soluble IL-2 receptor; VC = vital capacity.

After screening, 75 (out of 88) participants were included. Thirteen participants were excluded because of signs of active disease (increased serum soluble IL-2 receptor [sIL-2R], serum angiotensin-converting enzyme [sACE], calcium, or C-reactive protein [CRP] values) (eight); Löfgren syndrome as disease onset (two); thyroid disorder (one); diabetes (one), and participation was judged as too demanding (one). Medical Research Ethics Committee of the St. Antonius Hospital Nieuwegein, The Netherlands approved the study protocol (MEC ID: R-06.38A, GOV ID: NL14786.100.06).

Measurements

Fatigue, health status, depression, and anxiety were measured with questionnaires (Checklist Individual Strength [CIS] 20r,20 Medical Outcomes Study 36-Item Short-Form Health Survey [SF-36],21,22 Beck Depression Inventory for primary care [BDI-pc],23 and Symptom Checklist-90 [SCL-90],24,25 respectively). The CIS questionnaire completely focuses on fatigue and has excellent psychometric properties. The CIS is widely used to assess fatigue in other diseases as well;20 therefore, the use of this questionnaire enables the comparison of fatigue scores associated with different conditions.

Criteria for CFS were evaluated according to the international guidelines stated by the Centers for Disease Control and Prevention (CDC)17 by means of a standardized interview. Criteria are summarized in Table 2. Data on sleep quality were obtained by sleep diary (7 days).

Table Graphic Jump Location
Table 2 —Criteria for CFS According to the International Guidelines Stated by the CDC17

CDC = Centers for Disease Control and Prevention; CFS = chronic fatigue syndrome.

a 

In this study, sarcoidosis was acknowledged as a precipitating trigger, even though disease activity at the time of study was clinically absent.

Levels of physical activity were registered by an accelerometer (Actilog V3.0; Nijmegen, The Netherlands).26 Participants were instructed to wear this motion device on the ankle during 14 consecutive days and nights, except while bathing, swimming, and during activities in rainy weather conditions. Registrations < 7 days were omitted from further analysis. A cutoff of 91 accelerations per day was considered as average general physical activity level.26 Values for activity levels on weekdays and levels during the weekend were analyzed separately. Respiratory muscles strength tests were tested by maximal inspiratory pressure (Pimax) and maximal expiratory pressure (Pemax) performed with a Master Screen Body (Jaeger; Würtzburg, Germany), handgrip strength (dominant side) with Jamar (Sammons Preston; Bolingbrook, Illinois), and quadriceps peak torque (dominant side) with Cybex (Cybex International, Inc; Medway, Massachusetts). All measurements on muscle strength were expressed as percentages of predicted values, normalized for age, sex, height, and body weight.

Statistical Analyses

After determining fatigue severity for the total study group, participants were split into a fatigued and a nonfatigued group according to the standard cutoff for severe fatigue on the CIS subscale fatigue severity (≥ 35).20 Prior to analysis, all variables were tested for normality. Results are given in percentages, means ± SD, and medians and interquartile ranges (IQRs). Student t tests, Mann Whitney U tests, and binomial tests were performed to analyze differences between the two groups. The significance level for all analyses was set at P < .05. Data analysis was performed using Statistical Package for the Social Sciences, version 16.0 (SPSS, Inc; Chicago, Illinois).

Study Population

Seventy-five patients with histopathologically proven sarcoidosis were included. In all patients no disease activity could be detected: Serum parameters (sACE, serum sIL2-R, CRP, calcium) were normal; lung function was within normal range. At the time of diagnosis, 12 patients had extrapulmonary localization of sarcoidosis, but physical examination at the time of study revealed no clinical signs of disease activity in any organs. Two patients presented with slight bihilar lymphadenopathy (one fatigued, one nonfatigued); roentgenogram revealed no abnormalities in all other patients. Median time since diagnosis was 9 years (IQR, 5-17 years).

According to the cutoff score on the CIS subscale fatigue severity, the total study group was divided in two groups. Thirty-eight participants (21 men, 17 women) were classified as nonfatigued; 37 as fatigued (12 men, 25 women). Characteristics of both groups are summarized in Table 3. No differences were found between both groups with respect to age, BMI, demographics, time since diagnosis, and history of corticosteroid use, except for gender: The fatigued group represented more women (25 of 37 vs 17 of 38 in the nonfatigued group). Therefore, all analyses were controlled for gender differences. In addition, we found a significant difference for one of the inflammation markers at disease onset: The nonfatigued group had significantly higher sACE levels than the fatigued group (P = .006) (Table 3).

Table Graphic Jump Location
Table 3 —Characteristics of Nonfatigued and Fatigued Groups

Data are presented as mean ± SD, No. (%), or median (IQR) unless otherwise stated. The standard cutoff score of ≥ 35 for severe fatigue on the CIS subscale fatigue severity was used to split the study population. CIS = Checklist Individual Strength; ESR = erythrocyte sedimentation rate; IQR = interquartile range. See Table 1 legend for expansion of other abbreviations.

a 

Because a number of patients were diagnosed with sarcoidosis in other hospitals, some data were missing. Number of patients in which data were available: fever, 33 nonfatigued and 29 fatigued; ESR, 31 nonfatigued and 30 fatigued; CRP, 23 nonfatigued and 20 fatigued; sACE, 29 nonfatigued and 24 fatigued.

Severity of Fatigue

Overall, 76% of the total study population perceived severe complaints of fatigue during the onset and active phase of the sarcoidosis, and in 56% of these patients this fatigue persisted until current evaluation. Evaluation of present feelings of fatigue in the total study group revealed a mean score of 30.5 ± 15.5 on the subscale fatigue severity of the CIS. Performing a split based on the cutoff on this subscale showed a mean of 17.16 ± 7.02 for the nonfatigued group and a mean of 44.69 ± 7.08 for the fatigued group. No significant differences between mean scores of fatigued men and fatigued women were found (fatigued women: 45.76 ± 6.6 vs fatigued men: 43.08 ± 5.88, P = .20).

CDC Criteria for CFS

Seventeen out of 37 fatigued participants (47%) met the CDC criteria completely. The presence of fatigue-related symptoms in nonfatigued and fatigued participants is shown in Table 4. All fatigue-related symptoms were significantly more frequent in the fatigued group. Interestingly, no significant differences were found between men and women, except for multijoint pain, which was significantly more often reported by fatigued women (76% fatigued women vs 25% fatigued men, P = .02).

Table Graphic Jump Location
Table 4 —Presence of Fatigue-Related Symptoms of CFS in Nonfatigued and Fatigued Groups

Data are presented as percentages. See Table 2 legend for expansion of other abbreviation.

Depression and Anxiety Symptoms

Mean score on the BDI-pc and on the SCL-90 subscale depression were significantly higher in the fatigued group (P < .01, P = .004). Three participants (all fatigued) showed scores above the BDI-pc cutoff of 4, indicating that they could be considered as having clinical depression. However, supplementary analysis revealed that the high scores of these individual participants did not explain differences between both groups.

Mean scores on the SCL-90-subscale anxiety showed significantly higher scores in fatigued participants in comparison with nonfatigued participants (nonfatigued, 11.89 ± 2.84; fatigued, 14.31 ± 4.81; P = .013). The differences between groups observed with BDI-pc and SCL-90 could not be explained by gender.

Health Status

In all nine dimensions of the generic health questionnaire SF-36, fatigued participants scored significantly lower (all P < .001) (Fig 1). No differences between fatigued men and fatigued women were found, except for health status; the fatigued men in particular described their health as decreased compared with a year ago. In addition, the dimension vitality of the SF-36 (generally accepted as an accurate measurement of fatigue) correlated strongly with the CIS subscale fatigue severity (as used to identify the fatigued group in this study) (r = −0.684, P < .001).

Figure Jump LinkFigure 1. Mean scores on SF-36 in nonfatigued and fatigued groups. All P < .001. SF-36 = Medical Outcomes Study 36-Item Short-Form Health Survey.Grahic Jump Location
Patient-Reported Sleep Quality

Means of total self-reported night sleep time did not differ significantly between both groups (nonfatigued, 6:46 h ± 90 min; fatigued, 7:18 h ± 51 min; P = .057). Although there was a trend toward napping more minutes during daytime in fatigued participants (nonfatigued, 10 ± 20.49 min; fatigued, 22 ± 31.71 min), this difference did not reach statistical significance (P = .052). Moreover, the percentage of days that the fatigued group reported to awake unrefreshed was significantly higher (nonfatigued, 14.51% ± 17.66%; fatigued, 46.16% ± 28.74%; P < .001). In all analyses, gender did not explain the differences between groups.

Physical Activity

Analysis included data of 32 nonfatigued and 29 fatigued participants. Fourteen registrations were omitted (seven shorter than 7 full days and nights and seven due to technical problems). On weekdays the fatigued group achieved a mean value of 75.14 ± 24.09 accelerations per day vs 82.06 ± 27.69 in the nonfatigued group (P = .30), whereas on days during the weekend the mean values were, respectively, 66.93 ± 29.43 (fatigued) and 79.81 ± 31.99 (nonfatigued) (P = .10).

Compared with the norm score (91 accelerations per day), we found activity levels in both groups below general norm score on weekdays and during the weekend. Mean values of the fatigued group, however, were significantly reduced compared with the norm score (weekdays, P = .001; weekend days, P < .001).

Muscle Strength

Three participants could not complete the quadriceps muscle strength test (all nonfatigued) because of technical problems. Figure 2 shows the results of the four muscle strength tests: Pimax, Pemax, handgrip, and quadriceps. On all tests, the mean score of the fatigued group was significantly lower than the mean of the nonfatigued group.

Figure Jump LinkFigure 2. A, Scores on Pimax. B, Scores on Pemax. C, Scores on handgrip strength. D, Scores on quadriceps strength. Scores are expressed as a percentage of predicted values in nonfatigued and fatigued participants, presented in box plots with medians. Differences between both groups were significant in all tests (P < .006). Pimax = maximal inspiratory pressure; Pemax = maximal expiratory pressure.Grahic Jump Location

This study showed that fatigue in patients with sarcoidosis in clinical remission is severe. The CIS fatigue severity scale revealed a mean score of 30.5 ± 15.5 for the total study population. According to the cutoff score of ≥ 35, 37 out of 75 patients could be classified as severely fatigued: Their mean fatigue severity score was 44.69 ± 7.08. The CIS has also been used to measure fatigue in other (auto-) immune-mediated diseases. Therefore, the use of this questionnaire enabled us to compare fatigue severity and symptoms with other diseases. Comparison of mean scores shows that fatigue severity in our study group is relatively high (multiple sclerosis: 40.2 ± 11.827; functional bowel disorders: 34.1 ± 8.520; cancer survivors: 21.1 ± 13.728). Only in CFS do patients show a higher CIS fatigue severity mean score (51.7 ± 4.6).20,27

So far, available studies on fatigue in sarcoidosis involve patients with clinically active disease. In a review by De Kleijn et al,6 the median incidence of fatigue in active sarcoidosis appeared to be 73% (IQR, 63%-78%). Because of the diversity of questionnaires used to assess fatigue, no clear picture of fatigue severity is available. Although the interpretation and quantification of fatigue severity remains a subjective parameter, which might even be disease and situation specific, we would like to propose that fatigue after sarcoidosis can be interpreted as a severe problem.

Also, evaluation of fatigue in sarcoidosis in clinical remission by applying the international CFS criteria showed profound presence of fatigue-related symptoms, such as concentration problems, pain, postexertional malaise, and unrefreshing sleep. The relevance of this last symptom was confirmed by data obtained by sleep diary. This pattern of symptoms matches remarkably well with those found in other postinflammatory fatigue reports.29

In addition, we found 47% of our fatigued study group to fully meet the CFS criteria, taking into account that in our study sarcoidosis was known as a precipitating trigger. Therefore, we propose that chronic fatigue is a long-term effect of sarcoidosis.

In this study we demonstrated that fatigue in patients with sarcoidosis in clinical remission co-occurs with depressive and anxiety symptoms. Fatigued participants scored significantly higher than nonfatigued participants on all depression and anxiety scales. Neither gender differences nor BMI and physical activity explained the enhanced levels of psychologic distress.

Although depression and anxiety often accompany symptoms of prolonged fatigue,30-32 we do not know whether these symptoms found in our study are precipitating factors, since we have no information on psychologic distress before or during the disease. Even so, it is difficult to judge whether the psychologic factors are part of the symptom constellation of fatigue or whether they reflect residual disease (inflammatory activity).

Moreover, the observed reduction in health status is significantly associated with severe fatigue: The fatigued group experienced significant reduction in physical and social functioning and indicated experiencing more problems with respect to mental health, vitality, and pain due to their health. Even though we are unable to address this observation in terms of causes and consequences, we propose that psychologic interventions in fatigued patients may profoundly improve their psychologic and health status.

Objective measurements of fatigue comparison revealed reduced activity levels and muscle weakness in the fatigued group. The latter result is in contrast with findings in patients with CFS who retain their capacity for short-duration isometric tasks33 but is in line with reports on muscle weakness in active sarcoidosis.34 However, previous corticosteroid treatment (probably the cause in active disease) was not associated with muscle weakness in our study population. Taking these data together, we hypothesize that sarcoidosis may induce muscle damage during the active phase of the disease and that this myopathy will remain unrecovered, even though clinical signs of disease activity are absent.

Some limitations of the study should be acknowledged. First, as there is no internationally accepted gold standard, the criteria for clinical remission of sarcoidosis were based on clinical experience (J. M. M. v. d. B. and J. C. G.) and literature.35,36 Therefore, we might unintentionally have included some participants with sarcoidosis at a subclinical level. 18Fluorine fluorodeoxyglucose (18F-FDG) PET scan, which is a very sensitive technique to assess active sarcoidosis,37 may detect this low-grade disease activity. In our study, eight patients had been subjected to an 18F-FDG PET scan at the time of the study. Although none of these patients showed any sign of disease activity, it would be interesting to test all fatigued participants in order to investigate if residual 18F-FDG uptake can be demonstrated in these patients.

In addition, one may speculate about the linkage with persistent fatigue and disease severity at onset. Although no differences were found in total number of affected organs, presence of fever, erythrocyte sedimentation rate, and CRP between both groups at onset, the sACE concentrations at that time point were significantly higher in the nonfatigued group. This remarkable finding might suggest that a severe inflammation process at the start of the disease might contribute to recovery from fatigue. On the other hand, all other inflammation markers did not show significant differences, the median time since diagnosis had already been 9 years, and sACE concentrations at the time of the study did not differ. However, the question remains open whether severe fatigue is, in fact, the most sensitive sign of a low-grade inflammation (that has until now been undetectable by current routine investigations), which remains present many years after clinical remission of the disease. This theory would fit well with the hypothesis that sickness behavior, including fatigue and malaise, could well be induced by low-grade inflammation.32

Alternatively, we might speculate that the brain of the fatigued patient might have been sensitized by cytokines during the active phase of the disease process, leading to an alteration in the set point of regulatory systems involved in fatigue and depression.38 The latter would imply that although the production of inflammatory mediators is the same as in healthy individuals, the sensitivity of receptors for immune mediators may be increased, leading to the observed phenomenon of fatigue.

In summary, fatigue in patients with sarcoidosis in clinical remission is a severe and long-lasting problem, which is accompanied by psychologic distress and reduced health status. It co-occurs with concentration problems, pain, unrefreshing sleep, and postexertional malaise—a pattern similar to CFS. Interestingly, reduced physical activity and muscle weakness are observed in fatigued patients. Although the mechanism of this postinflammatory fatigue remains to be elucidated, the characteristics derived from this study will enable physicians to address fatigue and fatigue-related complaints in patients with sarcoidosis in clinical remission more thoroughly, and to be more aware of the severity of the problem in individual cases.

Author contributions: Ms Korenromp had full access to all the data in the study, takes responsibility for the integrity of the data, confirms an understanding of the statistical analysis methods, and states that the methods are clearly described and that they are a fair way to report the results.

Ms Korenromp: contributed to the study design, data collection, analysis and interpretation of data, and writing the manuscript, and has seen and approved the final version.

Dr Heijnen: contributed to the study design, interpretation of data, drafting and critical review of the manuscript, and has seen and approved the final version.

Dr Vogels: contributed to the study design, data collection, analysis and interpretation of data, and drafting and critical review of the manuscript, and has seen and approved the final version.

Dr van den Bosch: contributed to the study design, data collection, analysis and interpretation of data, and drafting and critical review of the manuscript, and had seen and approved the final version.

Dr Grutters: contributed to the study design, data collection, analysis and interpretation of data, and drafting and critical review of the manuscript, and has seen and approved the final version.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The sponsor approved the study protocol at the start of the investigation.

Other contributions: We thank Pieter Zanen, MD, PhD, for his statistical advice.

18F-FDG

fluorine-18 fluorodeoxyglucose

BDI-pc

Beck Depression Inventory for primary care

CDC

Centers for Disease Control and Prevention

CFS

chronic fatigue syndrome

CIS

Checklist Individual Strength

CRP

C-reactive protein

IQR

interquartile range

Pemax

maximal expiratory pressure

Pimax 5

maximal inspiratory pressure

sACE

serum angiotensin-converting enzyme

SCL-90

Symptom Checklist-90

SF-36

Medical Outcomes Study 36-Item Short-Form Health Survey

sIL-2R

soluble IL-2 receptor

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Blackwood SK, MacHale SM, Power MJ, Goodwin GM, Lawrie SM. Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression. J Neurol Neurosurg Psychiatry. 1998;654:541-546. [CrossRef] [PubMed]
 
Spruit MA, Thomeer MJ, Gosselink R, et al. Skeletal muscle weakness in patients with sarcoidosis and its relationship with exercise intolerance and reduced health status. Thorax. 2005;601:32-38. [CrossRef] [PubMed]
 
Consensus conferenceConsensus conference Consensus conference: activity of sarcoidosis. Third WASOG meeting, Los Angeles, USA, September 8-11, 1993. Eur Respir J. 1994;73:624-627. [CrossRef] [PubMed]
 
Costabel U, Ohshimo S, Guzman J. Diagnosis of sarcoidosis. Curr Opin Pulm Med. 2008;145:455-461. [CrossRef] [PubMed]
 
Keijsers RG, Verzijlbergen FJ, Oyen WJ, et al. 18F-FDG PET, genotype-corrected ACE and sIL-2R in newly diagnosed sarcoidosis. Eur J Nucl Med Mol Imaging. 2009;367:1131-1137. [CrossRef] [PubMed]
 
Dantzer R. Cytokine, sickness behavior, and depression. Immunol Allergy Clin North Am. 2009;292:247-264. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. Mean scores on SF-36 in nonfatigued and fatigued groups. All P < .001. SF-36 = Medical Outcomes Study 36-Item Short-Form Health Survey.Grahic Jump Location
Figure Jump LinkFigure 2. A, Scores on Pimax. B, Scores on Pemax. C, Scores on handgrip strength. D, Scores on quadriceps strength. Scores are expressed as a percentage of predicted values in nonfatigued and fatigued participants, presented in box plots with medians. Differences between both groups were significant in all tests (P < .006). Pimax = maximal inspiratory pressure; Pemax = maximal expiratory pressure.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Inclusion and Exclusion Criteria

CRP = C-reactive protein; Dlco = diffusing capacity of lung for carbon monoxide; sACE = serum angiotensin-converting enzyme; sIL-2R = soluble IL-2 receptor; VC = vital capacity.

Table Graphic Jump Location
Table 2 —Criteria for CFS According to the International Guidelines Stated by the CDC17

CDC = Centers for Disease Control and Prevention; CFS = chronic fatigue syndrome.

a 

In this study, sarcoidosis was acknowledged as a precipitating trigger, even though disease activity at the time of study was clinically absent.

Table Graphic Jump Location
Table 3 —Characteristics of Nonfatigued and Fatigued Groups

Data are presented as mean ± SD, No. (%), or median (IQR) unless otherwise stated. The standard cutoff score of ≥ 35 for severe fatigue on the CIS subscale fatigue severity was used to split the study population. CIS = Checklist Individual Strength; ESR = erythrocyte sedimentation rate; IQR = interquartile range. See Table 1 legend for expansion of other abbreviations.

a 

Because a number of patients were diagnosed with sarcoidosis in other hospitals, some data were missing. Number of patients in which data were available: fever, 33 nonfatigued and 29 fatigued; ESR, 31 nonfatigued and 30 fatigued; CRP, 23 nonfatigued and 20 fatigued; sACE, 29 nonfatigued and 24 fatigued.

Table Graphic Jump Location
Table 4 —Presence of Fatigue-Related Symptoms of CFS in Nonfatigued and Fatigued Groups

Data are presented as percentages. See Table 2 legend for expansion of other abbreviation.

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White PD, Thomas JM, Kangro HO, et al. Predictions and associations of fatigue syndromes and mood disorders that occur after infectious mononucleosis. Lancet. 2001;3589297:1946-1954. [CrossRef] [PubMed]
 
Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008;91:46-56. [CrossRef] [PubMed]
 
Blackwood SK, MacHale SM, Power MJ, Goodwin GM, Lawrie SM. Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression. J Neurol Neurosurg Psychiatry. 1998;654:541-546. [CrossRef] [PubMed]
 
Spruit MA, Thomeer MJ, Gosselink R, et al. Skeletal muscle weakness in patients with sarcoidosis and its relationship with exercise intolerance and reduced health status. Thorax. 2005;601:32-38. [CrossRef] [PubMed]
 
Consensus conferenceConsensus conference Consensus conference: activity of sarcoidosis. Third WASOG meeting, Los Angeles, USA, September 8-11, 1993. Eur Respir J. 1994;73:624-627. [CrossRef] [PubMed]
 
Costabel U, Ohshimo S, Guzman J. Diagnosis of sarcoidosis. Curr Opin Pulm Med. 2008;145:455-461. [CrossRef] [PubMed]
 
Keijsers RG, Verzijlbergen FJ, Oyen WJ, et al. 18F-FDG PET, genotype-corrected ACE and sIL-2R in newly diagnosed sarcoidosis. Eur J Nucl Med Mol Imaging. 2009;367:1131-1137. [CrossRef] [PubMed]
 
Dantzer R. Cytokine, sickness behavior, and depression. Immunol Allergy Clin North Am. 2009;292:247-264. [CrossRef] [PubMed]
 
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