Although impaired health-related quality of life (HRQOL) has been reported in patients with sarcoidosis, there is currently no sarcoidosis-specific questionnaire in Japan. The 29-item Sarcoidosis Health Questionnaire (SHQ), originally developed in the United States, is the only sarcoidosis-specific HRQOL questionnaire currently available. The primary aim of this study was to develop and validate a Japanese version of the SHQ.
The SHQ was translated into Japanese following the forward-backward procedure. The reliability and validity of the Japanese version of the SHQ were examined. One hundred twenty-two Japanese patients with biopsy-proven sarcoidosis were evaluated by the SHQ, the Medical Outcomes Study 36-item short form (SF-36), the St. George's Respiratory Questionnaire (SGRQ), chest radiography, an electrocardiogram, laboratory blood tests, pulmonary function tests, an echocardiogram, and assessments of dyspnea and depressive symptoms. The SHQ was found to have acceptable levels of internal consistency (Cronbach's coefficient α values = 0.68 to 0.91). SHQ scores correlated significantly with scores on the SF-36 and SGRQ. The domain or total scores on the SHQ also significantly correlated with serum levels of the soluble interleukin-2 receptor, the percentage of the predicted forced vital capacity, pulmonary arterial systolic pressure, dyspnea, and depressive symptoms. Also, the SHQ scores of patients who had one or two organ systems affected by sarcoidosis were significantly different from those of patients who had three or more organ systems involvement.
The Japanese version of the SHQ can be used to assess the HRQOL of patients with sarcoidosis.
To compare the differences in vision and health-related quality of life (HRQOL) of individuals with ocular and non-ocular sarcoidosis; and to examine the impact of specific demographic and clinical factors on the noted differences.
A cross-sectional study using non-randomized prospective cohort was conducted at the National Eye Institute (protocol number: 06-EI-0239, NCT00379275) from August 31, 2006 until November 15, 2007. Each participant completed vision and HRQOL questionnaires, the Sarcoidosis Health Questionnaire (SHQ) and the National Eye Institute Visual Function Questionnaire (NEI-VFQ), along with a demographic/environmental exposure survey. Clinical data were collected through an ophthalmic exam as part of the research protocol.
The study enrolled 75 biopsy-proven and 20 clinically presumed sarcoidosis participants which were divided into two cohorts, ocular (N = 60) and non-ocular groups (N = 35). The ocular group had significantly lower (P < 0.01) total NEI-VFQ scores compared to the non-ocular group. Multiple linear regression analysis showed that participants with ocular sarcoidosis who had an annual household income of < $50,000 (P < 0.01) had significantly lower total SHQ scores while participants with ocular sarcoidosis whose visual acuity was 20/100 or worse had significantly lower total NEI-VFQ scores (P = 0.03).
Ocular involvement impacts both overall and vision-related quality of life among sarcoidosis patients. Lower economic status appears to have a significant impact on the quality of life of sarcoidosis patients. Assessment of visual function and general health status provide pertinent information for individuals with sarcoidosis and should be included in their care to assess burden of their disease on their quality of life.
Health-related quality of life; Vision-related quality of life; Ocular sarcoidosis; Pulmonary sarcoidosis; Burden of disease
The 6-min walk test (6MWT) is a useful tool to assess prognosis and functional impairment in various pulmonary diseases.
To evaluate functional capacity during various stages of pulmonary sarcoidosis and develop a scoring system clinical radiological physiological score (CRP) that can potentially be used to assess the functional status among patients with sarcoidosis.
MATERIALS AND METHODS:
We performed a retrospective study on 26 patients diagnosed with pulmonary sarcoidosis from 2001 to 2007. All patients completed the 6MWT. The parameters assessed during the test included spirometry, arterial blood gas, 6-min walk distance (6MWD), Borg dyspnea score, and initial and end oxygen saturation.
Females covered a significantly shorter distance than males (343 m (223–389) vs. 416.5 m (352–500); P < 0.0001). In addition, females had a significantly lower SpO2 at the end of the 6MWT than males (90.5 (61–99) vs. 96 (75–98); P < 0.03). The 6MWD was inversely correlated with the final Borg score (ρ = −0.603, P = 0.004) and the CRP score (ρ = −0.364, P = 0.047) and positively correlated with forced expiratory volume in 1 s (FEV1) % (ρ = 0.524, P = 0.006) and forced vital capacity (FVC) % (ρ = 0.407, P = 0.039).
Female gender, FEV1%, final Borg score, FVC%, CRP score, and SpO2 at the end of the 6MWT are associated with reduced 6MWD. It appears that Saudi patients diagnosed with sarcoidosis have a markedly reduced walking distance compared with other races. The effect of race and ethnicity and the utility of the CRP score as a potential marker to assess functional status require further exploration.
Functional status; pulmonary sarcoidosis; 6-min walk test
The authors assessed the relation of hormonal and pregnancy-related factors to the incidence of sarcoidosis in the Black Women's Health Study. On biennial questionnaires, participants (US black women aged 21–69 years at baseline) reported data on diagnoses of sarcoidosis, reproductive history, and medication use. Cox regression models, adjusted for age, education, geographic region, smoking, and body mass index, were used to estimate incidence rate ratios and 95% confidence intervals. During 694,818 person-years of follow-up from 1995 through 2009, 452 incident cases of sarcoidosis were identified. The incidence of sarcoidosis decreased as age at menopause increased (P-trend = 0.03). Both later age at first full-term birth and having a more recent birth were associated with a reduced incidence of sarcoidosis. In models that included both factors, the incidence rate ratios were 0.60 (95% confidence interval: 0.37, 0.97) for age at first birth ≥30 years versus <20 years (P-trend = 0.05) and 0.73 (95% confidence interval: 0.43, 1.24) for <5 years since last birth versus ≥15 years (P-trend = 0.15). No significant associations were observed with age at menarche, parity, lactation, oral contraceptive use, or female hormone use. These results suggest that later full-term pregnancy and longer exposure to endogenous female hormones may be related to a reduced risk of sarcoidosis.
African Americans; hormones; prospective studies; reproduction; risk factors; sarcoidosis; women; women's health
We assessed the relationship between physiologic parameters, computed tomography patterns, 6 minute walk distance (6MWD) and the distance-saturation product [DSP; defined as the product of the 6MWD and the lowest oxygen saturation during the 6 minute walk test (6MWT)]. In addition, we investigated factors affecting 6MWD in patients with pulmonary sarcoidosis.
We performed a retrospective study of patient demographics, treatment, pulmonary function, 6MWT, echocardiography and computed tomography results.
Fifty nine patients were included in this study. Their mean+standard deviation age was 47.5 years + 12.5 years, and 42 (71.2%) were female. Mean pulmonary function parameters for forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and total lung capacity (TLC) results, as percentages of predicted values, were 77.6 ± 22.2, 77.1 ± 22.8 and 78.7 ± 16.1, respectively. Comparison of the DSP with distance walked revealed a significant correlation with factors underlying reduced 6MWD, including gender, pulmonary function indices, partial pressure of oxygen (PaO2), and Borg dyspnea score. Other factors were significantly associated with DSP but not distance; these included lung fibrosis (p = 0.02), pulmonary hypertension (p = 0.01) and systemic therapy (p = 0.04). Backward elimination stepwise multiple regression analysis revealed that gender, and FEV1 were independent predictors of 6MWD, but FEV1 was more strongly related when DSP applied [DSP, R2 = 0.53, p = 0.02; distance, R2 = 0.45, p < 0.0001].
Our findings reveal that, compared to 6MWD alone, the DSP is correlated with a greater number of factors associated with reduced 6MWT performance. Therefore, the DSP may be a useful indicator of functional status in patients with sarcoidosis. Additional large-scale studies are warranted to validate our findings.
ARA 290 (a peptide designed to activate the innate repair receptor that arrests injury and initiates cytoprotection, antiinflammation and healing) reduces allodynia in preclinical neuropathy models. We studied the safety and efficacy of ARA 290 to reduce symptoms of small fiber neuropathy (SFN) in patients with sarcoidosis. A total of 22 patients diagnosed with sarcoidosis and symptoms of SFN were enrolled in a double-blind, placebo-controlled exploratory trial consisting of three times weekly intravenous dosing of ARA 290 (2 mg; n = 12) or placebo (n = 10) for 4 wks. Inclusion criteria were a diagnosis of neuropathy and a spontaneous pain score of ≥5 (Brief Pain Inventory [BPI]). Endpoints assessed were changes in pain intensity and the small fiber neuropathy screening list (SFNSL) score, quality of life (SF-36), depressive symptoms (Inventory of Depressive Symptomatology [IDS]) and fatigue (Fatigue Assessment Scale [FAS]). No safety concerns were raised by clinical or laboratory assessments. The ARA 290 group showed significant (p < 0.05) improvement at wk 4 in SFNSL score compared with placebo (Δ −11.5 ± 3.04 versus Δ −2.9 ± 3.34 [standard error of the mean]). Additionally, the ARA 290 group showed a significant change from baseline in the pain and physical functioning dimensions of the SF-36 (Δ −23.4 ± 5.5 and Δ −14.6 ± 3.9, respectively). The mean BPI and FAS scores improved significantly but equivalently in both patient groups. No change was observed in the IDS. ARA 290 appears to be safe in patients with sarcoidosis and can reduce neuropathic symptoms.
18F-FDG PET/CT (PET) is useful in assessing inflammatory activity in sarcoidosis. However, no appropriate indications are available. The aim of this study was to develop a prediction rule that can be used to identify symptomatic sarcoidosis patients who have a high probability of PET-positivity.
We retrospectively analyzed a cohort of sarcoidosis patients with non organ specific persistent disabling symptoms (n = 95). Results of soluble interleukin-2 receptor (sIL-2R) assessment and high-resolution computed tomography (HRCT) were included in the predefined model. HRCT scans were classified using a semi-quantitative scoring system and PET findings as positive or negative, respectively. A prediction model was derived based on logistic regression analysis. We quantified the model’s performance using measures of discrimination and calibration. Finally, we constructed a prediction rule that should be easily applicable in clinical practice.
The prediction rule showed good calibration and good overall performance (goodness-of-fit test, p = 0.78, Brier score 20.1%) and discriminated between patients with positive and negative PET findings (area under the receiver-operating characteristic curve, 0.83). If a positive predictive value for the presence of inflammatory activity of ≥90% is considered acceptable for clinical decision-making without referral to PET, PET would be indicated in only 29.5% of the patients. Using a positive predictive value of 98%, about half of the patients (46.3%) would require referral to PET.
The derived and internally validated clinical prediction rule, based on sIL-2R levels and HRCT scoring results, appeared to be useful to identify sarcoidosis patients with a high probability of inflammatory activity. Using this rule may enable a more effective use of PET scan for assessment of inflammatory activity in sarcoidosis.
Clinical prediction rule; High-resolution computed tomography; Soluble interleukin-2 receptor; PET; Sarcoidosis
Fatigue has been identified in more than one-half of patients with sarcoidosis. Although fatigue is not synonymous with impaired quality of life, most studies of sarcoidosis identify fatigue as a major cause of impaired quality of life.
To test the hypothesis that stimulants may have a role in the treatment of fatigued sarcoidosis patients, even without objective evidence of daytime sleepiness.
This was a double-blind, placebo-controlled, crossover study of sarcoidosis patients followed up in one sarcoidosis clinic Sarcoidosis patients with fatigue received either armodafinil or placebo with eight weeks of therapy for each arm and a two week washout period before crossover to the other treatment. Initial armodafinil dose was 150 mg and increased to 250 mg after four weeks. Patients underwent polysomnography and multiple sleep latency testing (MSLT) the following day. Patients with an apnea/hypopnea index <6/hour received either armodafinil or placebo. Polysomnography with MSLT was repeated after each treatment arm.
Fifteen patients received the study drug. Fatigue was assessed using the Fatigue Assessment Scale (the lower the score, the less the fatigue) and the Functional Assessment of Chronic Illness Therapy—Fatigue (FACIT-F) (the higher the score, the less the fatigue). After eight weeks of therapy, there was a significant improvement in the Fatigue Assessment Scale during armodafinil treatment (median −4.5, range −20, 5) compared with placebo treatment (median 3.5, range −9, 14, P < 0.05) and for the FACIT-F (armodafinil: median 9, range −12, 26 vs. placebo: median −5, range −17, 11, P < 0.005). This improvement in fatigue was seen for both those with and without shortened sleep onset latency time during the MSLT.
Armodafinil treatment led to a significant reduction in fatigue in sarcoidosis patients. This effect was seen even in patients who did not have excessive daytime somnolence.
Sarcoidosis; fatigue; sleep apnea; daytime somnolence; armodafinil
Sarcoidosis is a systemic, inflammatory disease of unknown aetiology, influenced by stressful life events and associated with a high incidence of alexithymic personality traits, and of depressive symptoms. The medical literature on sarcoidosis has called for a psychotherapeutic intervention to modify the perceived state of disease, the influence of stressful events and the depressive condition. Few studies have described cases treated with psychotherapy, and no information is available on its long-term outcome.
We present the case of a patient with chronic sarcoidosis and periodical reacutizations with constantly pathological ESR. Twenty-four years after the diagnosis, a dynamic supportive-expressive psychotherapy for psychosomatic alexithymic patients was added to the medical therapy. At the beginning and at the end of the psychotherapy, and for the long-term outcome evaluations, Kellner's symptom questionnaire (SQ) was used to investigate psychological distress. The SQ scores, initially pathological, were normal at the end of the psychotherapy and for the following three years. Psychotherapy, without antidepressive drugs, resolved the depression. The depressive symptoms disappeared, along with the normalization and stabilization of the ESR. After three years, the outcome was positive. This is the first study describing a successful psychotherapy and its long-term outcome on a patient with sarcoidosis.
We report a now 6-year-old African-American male with both Alagille syndrome and pediatric sarcoidosis. With a prior JAG1 mutation positive diagnosis of Alagille syndrome, he presented to the hospital with a subacute, predominantly respiratory febrile condition, eventually diagnosed as sarcoidosis. A liver biopsy revealed paucity of bile ducts and scattered epithelioid granulomas, while a skin biopsy showed granulomatous angiitis, a manifestation of sarcoidosis not yet reported in a pediatric patient. He has subsequently been treated with corticosteroids, mycophenolate mofetil, and infliximab with clinical response. Alagille syndrome and sarcoidosis have not yet been reported in the medical literature in the same patient to the best of our knowledge. We briefly review these two seemingly unrelated conditions and propose a possible common pathogenic mechanism.
Sarcoidosis; Alagille syndrome; Granulomatous angiitis; Granuloma; JAG1; NOTCH1; T lymphocyte
In order to provide national data on the epidemiology of sarcoidosis in the United States, data from the National Center for Health Statistics were examined for the period 1968 to 1984. Sarcoidosis appeared among the diagnoses of over 20,000 hospital discharges in recent years. It was mentioned on 605 death certificates in 1982, and as underlying cause of death on 339.
In blacks, rates of hospital discharge with the diagnosis were eight times those of whites in 1981, and death rates were 20 times those of whites at ages 15 to 44 years. Women had higher rates than men. Both hospitalization and mortality data may give distorted pictures of this frequently mild or asymptomatic condition. Furthermore, no information was available on the percentage of diagnoses confirmed by biopsy, or on severity of disease in hospitalized patients.
Race-specific hospital discharge rates must be interpreted with caution in this survey. Nevertheless, patterns were generally consistent with studies of prevalence and incidence. Further descriptive and analytic studies of the epidemiology of sarcoidosis are needed to help identify modifiable risk factors and possible causes.
Sarcoidosis is a systemic disorder of unknown aetiology characterised by its pathological hallmark of non-caseating granuloma. Definitive diagnosis requires compatible clinical and imaging features as well as pathogenic identification of non-caseating granulomas in at least one organ. The disease has a wide variety of clinical and radiological manifestations but is associated with low mortality. However, cardiac involvement which is clinically only identified in 5% significantly worsens prognosis due to complications such as congestive heart failure, ventricular tachyarrhythmia, pulmonary hypertension or conduction disturbance leading to sudden death. Cardiac involvement is implicated in 77–85% of deaths directly related to sarcoidosis. Autopsy series in sarcoidosis patients show cardiac involvement with sarcoidosis in up to 79% cases. This case details the clinical course of a 56-year-old female who had experienced refractory cardiac dysrhythmias for many years in the context of also having biopsy proven pulmonary sarcoidosis. She had failed multiple antiarrhythmics as well as pacemaker and implantable cardioverter defibrillator placement. It was not until she presented as a potentially fatal ventricular tachycardia that the possibility of cardiac involvement from her sarcoidosis was entertained as the aetiology of her cardiac problems. Confirmation of myocardial sarcoidosis with PET CT imaging and subsequent treatment with prednisone resulted in her clinical improvement.
Depending on the location, dermatoses can produce blemishes that severely impair quality of life and require highly effective treatment that is otherwise used for extensive skin involvement. We report the case of a 39-year-old, otherwise healthy male disfigured by an 8 × 7-cm hypopigmented and centrally atrophic annular plaque with erythematous indurated borders in an area of scar tissue on his forehead. Skin biopsies revealed non-caseating granulomas, and hilar involvement was identified, leading to the diagnosis of systemic sarcoidosis stage II with cutaneous involvement. The lesions proved resistant to multiple therapies, but responded within 4 months to adalimumab with regression of the lesion and inflammatory infiltrate. The visual analogue scale of disease activity decreased from 7/10 to 3.5/10, and the Dermatology Life Quality Index from 16/30 to 3/30 points. In conclusion, TNF-α inhibition can control inflammation and disfigurement by cutaneous sarcoidosis and restore quality of life.
Cutaneous sarcoidosis; Systemic sarcoidosis; Sarcoidosis treatment; Adalimumab; TNF-α antagonist
Background: Skeletal muscle weakness is assumed to be present in patients with sarcoidosis but has never been reported in a consecutive group of patients. Moreover, its relationship with previously observed exercise intolerance and reduced health status has never been studied in these patients.
Methods: Pulmonary function, skeletal and respiratory muscle forces, peak and functional exercise capacity, health status, and the circulating levels of inflammatory and anabolic markers were determined in 25 patients with sarcoidosis who complained of fatigue (15 men) and in 21 healthy subjects (13 men).
Results: Patients with sarcoidosis had lower respiratory and skeletal muscle forces, reduced exercise capacity and health status, higher anxiety and depression scores, and higher circulating levels of tumour necrosis factor-α than healthy subjects (all p⩽0.01). Its soluble receptor p75 tended to be higher (p = 0.04). Circulating levels of interleukin (IL)-6, IL-8, insulin-like growth factor I and its binding protein 3 were not significantly different between the two groups. Skeletal muscle weakness was related to exercise intolerance, depression, and reduced health status in patients with sarcoidosis, irrespective of age, sex, body weight and height (p⩽0.05). Quadriceps peak torque was inversely related to fatigue but not to the circulating levels of inflammatory or anabolic markers. The mean daily dose of corticosteroids received in the 6 month period before testing was related to quadriceps peak torque only in patients who received oral corticosteroids.
Conclusion: Skeletal muscle weakness occurs in patients with sarcoidosis who complain of fatigue and is associated with reduced health status and exercise intolerance.
Agents that target pro-inflammatory cytokines may be useful in pulmonary sarcoidosis.
To determine effectiveness of a non-selective cyclic nucleotide phosphodiesterase (PDE) inhibitor, pentoxifylline (POF).
Randomized, double-blind, placebo-controlled trial
Clinical Research Center, National Institutes of Health.
27 patients with biopsy-confirmed pulmonary sarcoidosis receiving prednisone.
Placebo or POF (1200-2000 mg/day) for 10 months, as prednisone was tapered.
Primary endpoints: sustained improvement in two or more pulmonary function parameters, or a combination of one pulmonary function parameter and dyspnea.
Except for one patient, primary endpoints were not reached in POF-treated patients. Therefore, a post hoc analysis was performed. The observed relative risk reduction for flares associated with POF treatment was 54.9% (95% CI 0.21, 0.89) and the absolute risk reduction was 50.6% (95% CI 0.22, 0.80). Compared to placebo treatment, in the POF group, the mean prednisone dose was lower at 8 and 10 months (p = 0.007 and 0.01 respectively), and there was a trend towards less prednisone usage over the entire study period (p = 0.053), as determined by cumulative change analysis.
Although our exploratory post hoc analysis suggested that POF reduced flares and had steroid-sparing effects, given the study limitations, definitive conclusions cannot be drawn regarding the efficacy of POF in pulmonary sarcoidosis. In addition, gastrointestinal side-effects, at the doses used, would seem to limit the use of POF in treating pulmonary sarcoidosis. Overall, however, this trial may provide a basis for using more specific, better-tolerated, PDE inhibitors in future clinical trials.
pentoxifylline; phosphodiesterase; sarcoidosis; steroid-sparing; pulmonary function
Charts and radiographs of sarcoidosis patients seen at a private university hospital and at a municipal hospital were reviewed to determine whether there was a difference in the severity of disease retrospectively. A standardized abstract form was used to identify and abstract information on new and continuing sarcoidosis patients seen at either Georgetown University Medical Center (GUMC) or District of Columbia General Hospital (DCGH) during a 2-year period. Because there were too few white sarcoidosis patients for comparison, analysis was done for African-American patients only. African-American patients at GUMC were slightly older, with a higher percentage of women. For GUMC patients, 76% had private insurance and 21% had public insurance, and for DCGH patients, one-half had public insurance and 29% had no insurance. Significantly fewer GUMC patients (7% versus 36%) reported moderate to severe dyspnea. Chest radiographs showed a larger percentage of patients with stage 1 disease at GUMC and more patients with stage 4 disease at DCGH. Spirometry showed more impairment of forced expired volume in one second (FEV1) in GUMC patients, but diffusing capacity of the lung for carbon monoxide (DLCO) values were significantly lower among DCGH patients. Less than 8% of GUMC patients showed disease progression compared with almost one-third of DCGH patients. These results demonstrate that substantially less severe pulmonary sarcoidosis was seen in African-American patients treated at a private, nonprofit university hospital compared with a municipal hospital. Factors that determine the use of municipal hospitals, such as limited financial access to care and sources of patients, may have played a major role in the differences seen.
To report an undiagnosed case of systemic sarcoidosis manifesting with bilateral acute posterior multifocal placoid pigment epitheliopathy (APMPPE).
A 26-year-old Caucasian man was referred for management of unilateral visual loss together with a paracentral scotoma developing 2 weeks after a flu-like syndrome. Clinical signs and ancillary diagnostic investigations suggested APMPPE. Laboratory tests demonstrated elevated serum angiotensin converting enzyme and lysozyme levels. Chest CT-scan disclosed moderate hilar lymph node calcifications but QuantiFERON-TB gold test was negative and bronchoalveolar lavage and biopsies were unremarkable. Accessory salivary gland biopsy disclosed epithelioid and gigantocellular granuloma formation without caseum, confirming a diagnosis of sarcoidosis. The fellow eye was involved a few days later and the patient complained of dyspnea. Echocardiography disclosed severe granulomatous myocardial infiltration and high dose corticosteroids and intravenous cyclophosphamide were initiated. Systemic treatment controlled both cardiac and ocular lesions, and was tapered accordingly.
The constellation of “white dot syndromes” and systemic symptoms necessitates a general work-up to exclude granulomatous disorders such as sarcoidosis or tuberculosis. Delayed diagnosis of cardiac sarcoidosis may have life-threatening consequences and the ophthalmologist may be the first physician to diagnose the condition.
APMPPE; Sarcoidosis; Dyspnea; Indocyanine Green Angiography; OCT
The use of anti-tumor necrosis factor (TNF) agents to treat joint manifestations of sarcoidosis has not been described. We evaluated the efficacy and safety of three such biologics in patients with these symptoms refractory to conventional therapy (nonsteroidal anti-inflammatory drugs, corticosteroids, and/or disease-modifying antirheumatic drugs).
This retrospective study, covering January 2001 to September 2011, examined clinical–biological parameters collected before anti-TNF treatment (age, sex, duration of disease evolution, drugs taken), and at introduction and under anti-TNF therapy (number of painful and swollen joints, visual analog scale score of global disease activity, disease-activity score of 28 joints with erythrocyte sedimentation rate or C-reactive protein, TNF-antagonist duration). At 3, 6, and 12 months, anti-TNF impact on joints and the therapeutic response according to European League Against Rheumatism criteria used for rheumatoid arthritis were assessed.
Ten patients’ data were evaluated; some of them had received several anti-TNF agents (median [range] duration on each biotherapy was 10 [4–30] months), which enabled analysis of 19 prescriptions. The total duration of anti-TNF exposure was 17.6 patient-years, which was started a median of 3 (0.33–17) years after sarcoidosis diagnosis. The median numbers of painful and swollen joints were 1 (0–28) and 0 (0–9), respectively. Despite rapid efficacy, after 1 year of treatment, clinical (especially joint) and biological parameters were comparable to pretreatment, and only the corticosteroid dose was significantly lower (P=0.03). One case of mild skin toxicity was noted.
TNF antagonists allowed significant steroid sparing and were well tolerated, but do not seem to be effective against sarcoidosis joint involvement.
sarcoidosis; anti-TNF; arthritis; adalimumab; etanercept; infliximab
Most patients referred for lung biopsy have a focal lesion that is likely to be a carcinoma and fine needle aspiration (FNA) is usually sufficient to confirm diagnosis. Percutaneous cutting needle biopsy (CNB) is an important and potential diagnostic technique when non carcinomatous disease is suspected or when the pulmonary disease is unclear, so tissue architecture is very important.
We present a case of a 24 year old male arrived at our hospital with dyspnea and unusual computed tomography (CT) findings of sarcoidosis. Chest X-ray and CT scan revealed multiple masses in both lungs suggesting lung metastasis. Bronchoscopy and bronchoalveolar lavage did not reveal any malignant cells. None of the laboratory examinations revealed any primary extrapulmonary tumor. The patient underwent CT-guided core needle biopsy. Histopathological examination confirmed the diagnosis of sarcoidosis.
CT-guided core needle biopsy is a very helpful diagnostic tool in order to determine the benign or malignant nature of a thoracic lesion.
Patients with significant cardiac sarcoidosis are at increased risk of sudden death from ventricular dysrhythmias or conduction disturbances. We report two patients whose initial manifestation of cardiac sarcoidosis was nonsustained ventricular tachycardia unresponsive to standard antiarrhythmic measures. Endomyocardial biopsy aided the diagnosis in each patient. This technique is helpful in establishing the diagnosis of cardiac sarcoidosis, which causes life-threatening ventricular dysrhythmias.
Sarcoidosis is a multisystem disease of unknown cause. Life-threatening complications or sudden death can occur when the disease involves the heart. Because cardiac sarcoidosis has diverse clinical presentations, its diagnosis can be a major challenge for clinicians. It is very rare for the initial manifestation of cardiac sarcoidosis to be sustained ventricular tachycardia, especially in a patient with no prior symptoms or history of the disease.
Herein, we discuss the case of a 41-year-old black man who presented with nausea, vomiting, and palpitations on the day after he had consumed alcoholic beverages heavily. Electrocardiographic examination revealed sustained monomorphic ventricular tachycardia. An automatic implantable cardioverter-defibrillator corrected the patient's abnormal heart rhythm, and therapy with steroids and β-blockers resolved his symptoms. We describe the process that led to the diagnosis of cardiac sarcoidosis in this patient.
Cardiomyopathies/diagnosis/physiopathology; defibrillators, implantable; diagnosis, differential; echocardiography; magnetic resonance imaging/methods; sarcoidosis/diagnosis/drug therapy/physiopathology/radiography; tachycardia, ventricular/etiology/physiopathology/therapy; treatment outcome
Sarcoidosis is a polygenic disease with diverse phenotypic presentations characterized by an abnormal antigen-mediated Th1 type immune response. At present, progress towards understanding sarcoidosis disease mechanisms and the development of novel treatments is limited by constraints attendant to conducting human research in a rare disease in the absence of relevant animal models. We sought to develop a computational model to enhance our understanding of the pathological mechanisms of and predict potential treatments of sarcoidosis.
Based upon the literature, we developed a computational model of known interactions between essential immune cells (antigen-presenting macrophages, effector and regulatory T cells) and cytokine mediators (IL-2, TNFα, IFNγ) of granulomatous inflammation during sarcoidosis. The dynamics of these interactions are described by a set of ordinary differential equations. The model predicts bistable switching behavior which is consistent with normal (self-limited) and “sarcoidosis-like” (sustained) activation of the inflammatory components of the system following a single antigen challenge. By perturbing the influence of model components using inhibitors of the cytokine mediators, distinct clinically relevant disease phenotypes were represented. Finally, the model was shown to be useful for pre-clinical testing of therapies based upon molecular targets and dose-effect relationships.
Our work illustrates a dynamic computer simulation of granulomatous inflammation scenarios that is useful for the investigation of disease mechanisms and for pre-clinical therapeutic testing. In lieu of relevant in vitro or animal surrogates, our model may provide for the screening of potential therapies for specific sarcoidosis disease phenotypes in advance of expensive clinical trials.
Sarcoidosis affects the bone directly in only a minority of patients. Nonetheless, bone health should be considered in the management of all patients with sarcoidosis. Deficiency in vitamin D, an important contributor to bone health, has been linked to autoimmune disease incidence. Studies have shown that patients with sarcoidosis frequently have low levels of vitamin D-25 but may have normal or increased levels of vitamin D-1,25. In addition, granuloma formation has been linked to a failure of the innate immune system, which could be related to a deficiency in vitamin D, although this relationship has not been fully characterized. Furthermore, many patients with sarcoidosis are treated with corticosteroids, which are known to induce osteoporosis. Therefore, bone health may be impacted in several ways in sarcoidosis—by direct involvement with granulomas, vitamin D deficiency, or corticosteroid therapy.
Sarcoidosis; Bone health; Vitamin D; Calcium; Hypercalcemia; Bisphosphonates; Corticosteroids; Osteoporosis
In a series of 34 patients with sarcoidosis affecting the upper respiratory tract and nose, 26 had lupus pernio (LP) and 17 had sarcoidosis of the upper respiratory tract (SURT). In nine patients these features coexisted. A patient presenting with SURT carried a 50% risk of developing LP although one feature could be present without the other. Both were disorders of women of the child-bearing years of life. SURT, like LP, was an indicator of chronic fibrotic sarcoidosis, developing insidiously and progressing indolently over the years. It was complicated by ulceration, septal perforation, and LP. Three patients had nasal septal perforations, in two instances following submucous resection. This operation is contraindicated in patients with active sarcoidosis, particularly when granulomas are found on nasal biopsy. The Kveim-Siltzbach skin test was positive in all patients with SURT, making it invaluable in the differential diagnosis of granuloma of the nasal cavity.
In patients with sarcoidosis, sudden death is a leading cause of mortality, which may represent unrecognized cardiac involvement. Delayed-enhancement cardiovascular magnetic resonance (DE-CMR) can detect minute amounts of myocardial damage. We sought to compare DE-CMR with standard clinical evaluation for the identification of cardiac involvement.
Methods and Results
Eighty-one consecutive patients with biopsy proven extra-cardiac sarcoidosis were prospectively recruited for a parallel and masked comparison of cardiac involvement between: (1) DE-CMR, and (2) standard clinical evaluation using consensus criteria (modified Japanese Ministry of Health [JMH] guidelines). Standard evaluation included 12-lead electrocardiography and at least one dedicated non-CMR cardiac study (echocardiography, radionuclide scintigraphy, or cardiac catheterization). Patients were followed 21±8 months for major adverse events (death, defibrillator shock, or pacemaker requirement).
Patients were predominantly middle-aged (46±11 years), female (62%), African-American (73%), had chronic sarcoidosis (median, 7 years), and preserved LVEF (median, 56%). DE-CMR identified cardiac involvement in 21 patients (26%) and JMH criteria in 10 (12%, 8 overlapping), a more than two-fold higher rate for DE-CMR (p=0.005). All patients with myocardial damage on DE-CMR had coronary disease excluded by x-ray angiography. Pathology evaluation in 15 patients (19%) identified 4 with cardiac sarcoidosis; all 4 were positive by DE-CMR whereas 2 were JMH positive. On follow-up, 8 had adverse events including 5 cardiac deaths. Patients with myocardial damage on DE-CMR had a 9-fold higher rate of adverse events and a 11.5-fold higher rate of cardiac death than patients without damage.
In patients with sarcoidosis, DE-CMR is more than twice as sensitive for cardiac involvement than current consensus criteria. Myocardial damage detected by DE-CMR appears to be associated with future adverse events including cardiac death, but events were few and this needs confirmation in a larger cohort.
cardiovascular magnetic resonance; delayed-enhancement imaging; cardiac sarcoidosis