Current management of sarcoidosis I: pulmonary, cardiac, and neurologic manifestations.

PURPOSE OF REVIEW: Sarcoidosis is a systemic disease characterized by noncaseating granulomatous inflammation of multiple organ systems. Pulmonary, cardiac, and neurologic involvements have the worst prognosis. Current recommendations for the therapeutic management and follow-up of sarcoidosis involving these critical organs will be reviewed. RECENT FINDINGS: In those sarcoidosis patients requiring immunosuppressive therapy, corticosteroids are used first at varying doses depending on the presenting manifestation. Patients with symptomatic pulmonary, cardiac, or neurologic involvement will be maintained on corticosteroids for at least a year. Many require a second immunosuppressive agent with methotrexate used most commonly. Anti-tumor necrosis factor agents, especially infliximab, are effective and recommendations for their use have been proposed. SUMMARY: Evidence-based treatment guidelines do not exist for most sarcoidosis clinical manifestations. Therefore, clinical care of these patients must rely on expert opinion. Patients are best served by a multidisciplinary approach to their care. Future research to identify environmental triggers, genetic associations, biomarkers for treatment response, and where to position new steroid-sparing immunosuppressive agents is warranted.

An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features.

Many patients with an idiopathic interstitial pneumonia (IIP) have clinical features that suggest an underlying autoimmune process but do not meet established criteria for a connective tissue disease (CTD). Researchers have proposed differing criteria and terms to describe these patients, and lack of consensus over nomenclature and classification limits the ability to conduct prospective studies of a uniform cohort.The "European Respiratory Society/American Thoracic Society Task Force on Undifferentiated Forms of Connective Tissue Disease-associated Interstitial Lung Disease" was formed to create consensus regarding the nomenclature and classification criteria for patients with IIP and features of autoimmunity.The task force proposes the term "interstitial pneumonia with autoimmune features" (IPAF) and offers classification criteria organised around the presence of a combination of features from three domains: a clinical domain consisting of specific extra-thoracic features, a serologic domain consisting of specific autoantibodies, and a morphologic domain consisting of specific chest imaging, histopathologic or pulmonary physiologic features.A designation of IPAF should be used to identify individuals with IIP and features suggestive of, but not definitive for, a CTD. With IPAF, a sound platform has been provided from which to launch the requisite future research investigations of a more uniform cohort.

White matter microstructure and cognition in non-neuropsychiatric systemic lupus erythematosus.

OBJECTIVE: This study examined white matter (WM) structural and metabolic alterations in relation to cognition in patients with non-neuropsychiatric systemic lupus erythematosus (non-NPSLE). BACKGROUND: SLE can produce cognitive impairment even without overt neuropsychiatric features, but the pathogenesis of this dysfunction is not well understood. Our preliminary study of non-NPSLE found evidence correlating cognitive impairment with increased choline/creatine (Ch/Cr) in frontal lobe WM. METHODS: Subjects included 60 non-NPSLE patients and 24 controls. Magnetic resonance imaging and magnetic resonance spectroscopy were performed, and a battery of neuropsychologic tests was administered. Structural and metabolic measures were analyzed and correlated with neuropsychologic data. RESULTS: No significant differences were found in total brain, gray matter, and WM volumes, or in frontal WM N-acetylaspartate/Cr, but the non-NPSLE group had significantly increased Ch/Cr in frontal WM. A WM cognitive score (WMCS) that included the Paced Auditory Serial Addition Task, Letter Fluency, and Animal Naming was found to correlate with total WM volume, and lower WMCS correlated with higher left frontal WM Ch/Cr. CONCLUSIONS: Non-NPSLE patients had frontal WM metabolic changes that correlated with cognitive impairment, whereas no cerebral atrophy or WM axonal damage was evident. These data confirm and extend our previous observations supporting the role of microstructural WM changes in the cognitive impairment of non-NPSLE patients. The data also suggest that the WMCS may be sensitive to cognitive dysfunction from myelin damage that develops before axonal injury.

The Effect of Pre-Appointment Consultation Triage on Patient Selection and Revenue Generation in a University Rheumatology Practice.

OBJECTIVE: To evaluate the effectiveness of pre-appointment consult screening to identify patients with autoimmune and inflammatory rheumatic disease (AIRD) and to evaluate the revenue implications of routine outpatient care of patients with AIRD compared to that of non-AIRD patients. METHODS: Using data in the electronic medical records, we retrospectively analyzed all new outpatients who were referred for rheumatology consults during a 9-month period for a final diagnosis and revenue generation for routine outpatient care over 1 year following the consult review or initial evaluation. RESULTS: A total of 961 patients were referred to the outpatient rheumatology clinic and underwent pre-appointment triage. Overall, 673 patients were approved for evaluation of AIRD, and 288 patients were denied rheumatology consultation. Patients were seen an average of 13 days after the consult review. Among patients who were approved for consult, 597 came for evaluation, with 357 diagnosed as having an AIRD and 240 with a non-AIRD. Among patients who were denied a consult, 128 had 1-year follow-up data, with 6 patients eventually diagnosed as having an AIRD (consult triage sensitivity 98%, positive predictive value 60%). The consult triage system allowed more AIRD patients to be seen over a 1-year period. Revenue data for outpatient care was available for 318 of 357 patients with an AIRD and 192 of 240 non-AIRD patients and showed that care for patients with an AIRD generates 44 times more revenue compared to care for non-AIRD patients ($5,877 per AIRD patient versus $134 per non-AIRD patient; P < 0.001). CONCLUSION: Pre-appointment consult screening is an effective method to identify patients with an AIRD. This approach enables timely access to care for patients with the highest need for evaluation and results in significantly more revenue generation.

Unique characteristics of systemic sclerosis sine scleroderma-associated interstitial lung disease.

STUDY OBJECTIVES: To describe the characteristics of systemic sclerosis sine scleroderma (ssSSc)-associated interstitial lung disease (ILD) presenting as idiopathic interstitial pneumonia (IIP). DESIGN: Retrospective review of six patients with ssSSc-associated ILD diagnosed after referral for evaluation of IIP. MEASUREMENT AND RESULTS: All patients were white, their mean age was 56 years (range, 37 to 86), and gender was evenly divided. Sclerodactyly, skin thickening, and digital edema were absent in all patients. All patients had scattered telangiectasia, and four patients had Raynaud phenomenon with abnormal nailfold capillaroscopy findings. All described gastroesophageal reflux, and three patients had esophageal dysmotility by esophagography. All had restrictive pulmonary physiology and a reduced diffusion capacity. High-resolution CT revealed nonspecific interstitial pneumonia (NSIP) or usual interstitial pneumonia (UIP) radiographic patterns. Of the three patients who underwent surgical lung biopsy, two patients had NSIP and one patient had UIP pathologic patterns. Five patients had asymptomatic pericardial effusions and elevated pulmonary artery pressures by echocardiography. All patients had nucleolar-staining anti-nuclear antibodies (ANAs), and one patient was anti-Scl-70 positive. All five anti-Scl-70-negative patients were anti-Th/To positive, and the anti-Scl-70-positive patient was anti-Th/To negative. CONCLUSIONS: In the presentation of an IIP, the presence of a nucleolar-staining ANA, telangiectasia, Raynaud phenomenon with abnormal capillaroscopy findings, gastroesophageal reflux, or pericardial disease suggests underlying systemic sclerosis. These findings should aid clinicians in the evaluation and treatment of patients with otherwise undefined ILD.

Antiphospholipid antibodies as a cause of pulmonary capillaritis and diffuse alveolar hemorrhage: a case series and literature review.

OBJECTIVES: To discuss the clinical manifestations and possible pathogenic mechanisms of the unusual syndrome of diffuse alveolar hemorrhage (DAH) and pulmonary capillaritis without thrombosis in the setting of the primary antiphospholipid antibody syndrome (PAPS). METHODS: Four men with DAH and capillaritis in the setting of PAPS are identified. Their clinical presentations, laboratory, radiographic, and pathologic findings are reviewed as is their clinical course and response to therapy. In addition, the literature regarding DAH and pulmonary capillaritis in the setting of PAPS is reviewed. RESULTS: The patients presented with dyspnea, hemoptysis, fever, hypoxia, and diffuse alveolar infiltrates; none had evidence of acute thromboembolic disease. All secondary causes of DAH were ruled out. All patients had positive testing for the lupus anticoagulant and high-titer anticardiolipin antibodies, including antibodies against the beta-2-glycoprotein I antigen. Three cases had lung biopsies that revealed pulmonary capillaritis and DAH with no evidence of thrombosis. All patients improved with high-dose corticosteroids. Recurrent disease in the setting of aggressive immunosuppression responded to intravenous immunoglobulin. Antiphospholipid antibody-mediated endothelial cell activation in the absence of thrombosis may induce capillaritis as seen in these cases. CONCLUSIONS: The syndrome of DAH and pulmonary capillaritis is further defined. Evidence supports a causative relationship between PAPS, pulmonary capillaritis, and DAH in the absence of thromboembolic disease. Further elucidation of a possible nonthrombotic mechanism of antiphospholipid antibody-mediated pathology is needed to guide future therapies for this unusual manifestation of PAPS.

Radiation exposure in rheumatology practice.

BACKGROUND: Patients encountered in rheumatology practice often have concerns about radiation exposure from the imaging procedures used to diagnose and monitor their diseases. However, such imaging procedures normally deliver radiation doses that are associated with only a low level of risk. OBJECTIVES: To review and quantify the radiation doses delivered by the various imaging procedures commonly ordered in a rheumatology practice and to compare those doses with background radiation exposure in the United States. METHODS: The authors reviewed and compiled literature on radiation exposure from background radiation and diagnostic imaging procedures. The review included a Medline search through December 2003. RESULTS: Radiation doses from medical imaging procedures are so low that they do not have a clinically significant effect on mortality rates. In comparison to our normal daily exposures from naturally occurring background radiation and daily activities, the exposures from medical procedures are quite small. Moreover, the International Commission for Radiological Protection (ICRP) recommends that dose limits should not be applied to medical exposures in nonpregnant patients. Rather, the ICRP recommends that the medical exposure be justified and the protection be optimized so that the dose to the patient is as low as is compatible with the medical purpose. CONCLUSIONS AND RELEVANCE: Appropriate care of patients within the rheumatology practice frequently necessitates the use of imaging procedures that utilize ionizing radiation, such as radiographs, computed tomography scans, and bone densitometry. If ordered prudently, the benefits of these imaging procedures supersede the risks imposed by their radiation exposures.

Sleep apnea in male patients with the fibromyalgia syndrome.

PURPOSE: Fibromyalgia is a common pain syndrome that is often associated with sleep disturbances. The most characteristic pattern noted on formal sleep study is alpha-wave intrusion on delta-wave sleep. This nonrestorative sleep pattern may be endogenous, or caused by any of a number of sleep disturbances. Our goal was to determine the frequency of sleep apnea and its relationship to a nonrestorative sleep pattern in our patients with fibromyalgia syndrome. PATIENTS AND METHODS: All new fibromyalgia patients seen in the Rheumatology Clinic at Fitzsimons Army Medical Center were screened using history and physical examination for suspicion of sleep apnea. When this condition was suspected, the patients underwent formal polysomnography to delineate any sleep disturbance. RESULTS: Four of 92 women, and 13 of 25 men with the new diagnosis of fibromyalgia syndrome underwent polysomnography. Of the women, 2.2% (2 of 92) had significant sleep apnea at formal evaluation; both were obese and had obstructive findings. In contrast, 44% (11 of 25) of the men had significant sleep apnea. CONCLUSIONS: Sleep apnea is not a significant cause of fibromyalgia symptoms in females. In male patients with fibromyalgia, sleep apnea was observed in a large percentage. Fibromyalgia may be a marker for occult sleep apnea in males.

Osteoporosis for the practicing neurologist.

Osteoporosis is a common condition of impaired bone strength leading to fractures. A targeted history, physical exam, and blood work can help elucidate potentially reversible causes of low bone mass. In the neurology office, particular attention should be paid to the patient on glucocorticoids or antiepileptic medications, as these have distinct detrimental effects on bone. Patients can be risk-stratified by using the FRAX calculator, a tool that can help determine whether the patient is at sufficient risk of fracture to warrant pharmacologic therapy. Nonpharmacologic treatments such as calcium, vitamin D, and exercise should be discussed with the patient. The cornerstone of pharmacologic therapy has been treatment with bisphosphonates, but newer medications are available as well for the high-risk patient.

Connective tissue disease-associated interstitial lung disease: a call for clarification.

This commentary highlights the present dilemmas surrounding the classification of a patient with interstitial pneumonia who has clinical features suggesting an associated connective tissue disease but the features fall short of a clear diagnosis of connective tissue disease-associated interstitial lung disease under the current rheumatologic classification systems. This commentary illustrates what we perceive to be the limitations in the present approach to the classification of this group of patients and discusses problems with redefining the diagnosis of undifferentiated connective tissue disease to encompass patients with interstitial pneumonia. Finally, we advocate not only for a multidisciplinary approach to evaluation, but also disease classification and offer a proposal to define them as a distinct phenotype--lung-dominant CTD--for which prognostic, therapeutic, and pathobiologic implications can be tested in future, hopefully multiinstitutional, studies.

Antibodies against N-methyl-D-aspartate receptors in patients with systemic lupus erythematosus without major neuropsychiatric syndromes.

PURPOSE: Approximately 14-54% of patients with systemic lupus erythematosus without a history of major neuropsychiatric syndromes (nonNPSLE) have cognitive deficits. Elevated N-methyl-D-aspartate (NMDA) receptor antibodies (anti-NR2) have been reported in 35% of patients with SLE, but few studies have utilized controls or a composite memory index. We hypothesized that serum anti-NR2 would be elevated in nonNPSLE compared to healthy controls, and that elevated anti-NR2 would be associated with memory dysfunction and depression. METHODS: Subjects included 43 nonNPSLE patients with a mean age of 36.5 (SD=9.0) and mean education level of 14.7 years (SD=2.5). Twenty-seven healthy control subjects with similar demographic characteristics were also enrolled in this study. A global Cognitive Impairment Index (CII) and a Memory Impairment Index (MII) were calculated using impaired test scores from the ACR-SLE neuropsychological battery. Serum samples were analyzed using a standard ELISA for anti-NR2. RESULTS: Elevations of serum anti-NR2 were found in 14.0% of the nonNPSLE and 7.4% of the controls (p=0.47). There was no relationship between elevated anti-NR2 status and higher CII or performance on the MII. No relationship between levels of depressive symptoms and anti-NR2 was found. CONCLUSIONS: The frequency of elevated anti-NR2 was low (14.0%) in this sample of SLE patients and not significantly different from controls. A relationship was not found between the presence of anti-NR2 in serum and global cognitive or memory indices, or with depression. Results suggest that serum anti-NR2 is not likely related to mild cognitive dysfunction in SLE patients without a prior history of NPSLE.

Cognitive and neurologic status in patients with systemic lupus erythematosus without major neuropsychiatric syndromes.

OBJECTIVE: To examine neuropsychological and neurologic functioning in systemic lupus erythematosus (SLE) patients without histories of overt neuropsychiatric disorders (non-NPSLE patients). METHODS: Sixty-seven non-NPSLE patients and 29 healthy controls were administered a standardized neurologic examination and measures of cognition, depression, and self-reported cognitive functioning. RESULTS: Non-NPSLE patients scored lower than controls on the total score of the neurologic examination (P < 0.0001). Item analysis indicated that the physician's description of mentation and mood was the only item that differed significantly between patients with SLE and controls (P = 0.004). Compared with controls, non-NPSLE patients had significantly higher rates of impairment on logical reasoning (P = 0.012) and verbal memory (P = 0.03), and trends toward greater impairment on visual attention (P = 0.06) and working memory (P = 0.098). There were no significant differences between non-NPSLE patients and controls on a cognitive impairment index (CII): 20.9% of non-NPSLE patients and 13.8% of controls were impaired. Patients with SLE scored higher on depressive symptoms (P < 0.0001) and perceived cognitive difficulties (P = 0.001) compared with controls. CONCLUSION: The utility of a standardized neurologic examination in SLE for excluding overt neurologic dysfunction and assuring a non-NPSLE group selection was demonstrated. In contrast to our earlier study, we did not find differences between non-NPSLE patients and controls on the CII. Slightly lower CII scores in non-NPSLE patients and higher CII scores in controls may have reduced cognitive differences between these groups. Non-NPSLE patients demonstrate specific decline in the areas of attention, memory, and reasoning; continued studies of associated brain regions are warranted.

Anti-th/to-positivity in a cohort of patients with idiopathic pulmonary fibrosis.

OBJECTIVE: To evaluate the presence and clinical relevance of anti-Th/To-positivity in patients with idiopathic pulmonary fibrosis (IPF). METHODS: Antinuclear antibody (ANA) testing was performed in 285 patients with a clinical diagnosis of IPF and surgical lung biopsy-proven usual interstitial pneumonia. Twenty-five subjects (8.8%) were found to have a positive ANA with a nucleolar-staining pattern and were followed for 10 years. Immunoprecipitation analysis indicated that 13 of the 25 subjects had autoantibodies against Th/To antigen. RESULTS: All subjects presented with worsening dyspnea. Pulmonary physiology and gas exchange did not differ between those with and those without a positive ANA, those with and without a nucleolar-staining ANA, and those with and without anti-Th/To antibody positivity. Retrospective review of the clinical record revealed that none of the 25 subjects with a nucleolar-staining ANA had the characteristic cutaneous features of systemic sclerosis (SSc). Four of the 13 Th/To-positive subjects had 3 of 5 criteria of limited cutaneous SSc (CREST variant), and 9 met proposed criteria for SSc sine scleroderma. None of the 12 Th/To-negative subjects had 3 or more criteria of limited cutaneous SSc (CREST variant), and only one met proposed criteria for SSc sine scleroderma. Of the 25 subjects with nucleolar-staining ANA, cumulative survival was similar between those who were Th/To-positive and those who were Th/To-negative (log-rank test, p = 0.73). Cumulative survival was similar between the 13 Th/To-positive subjects and all other 272 IPF subjects (log-rank test, p = 0.34). CONCLUSION: Our findings indicate that a nucleolar-staining ANA is a common finding in patients with IPF, and that antibodies against Th/To are responsible for the majority of these. Given the high specificity of Th/To-positivity for SSc, our data suggest that these subjects may have SSc sine scleroderma, and that their prognosis is no different from those with IPF.

Clinical academic rheumatology: getting more than you pay for.

OBJECTIVE: Rheumatology is among the least compensated specialties in medicine today. This is a significant problem for clinical rheumatologists in academic medicine who are often expected to earn their salaries through clinical practice alone. Additionally, academic rheumatologists usually cannot generate revenue through office laboratory monitoring, radiographs, or bone densitometry to supplement their income (i.e., downstream income). The purpose of our study was to examine revenue generated from downstream income to a university by a clinical-academic rheumatologist. METHODS: Consecutive outpatients (n = 127) seen predominantly by one academic rheumatologist over one month of clinic were followed for 18 months. The total physician compensation for patient visits was calculated and compared with the revenue generated from laboratory tests, radiologic studies, consultations, and specific rheumatologic treatments and procedures performed or ordered. Medicare reimbursement rates for 2003 were used as compensation standards for all charges. RESULTS: Physician office visit billing generated 36,297 US dollars from 730 office visits. The total amount of downstream income from these office visits was 363,813 US dollars (47,386 US dollars from laboratory tests, 35,582 US dollars from radiologic studies, 8,159 US dollars from rheumatologic procedures, 261,584 from rheumatologic infusions, and 11,101 US dollars from initial consultations). Therefore, 10.02 US dollars of downstream revenue was generated for every 1.00 of office visit compensation applied to the academic rheumatologist's salary. CONCLUSION: Although academic rheumatologists struggle to bill their salaries through seeing more patients, they are clearly a bargain for a university hospital because they generate >10.00 US dollars for every 1.00 US dollars they receive for an office visit.

Cognition, MRS neurometabolites, and MRI volumetrics in non-neuropsychiatric systemic lupus erythematosus: preliminary data.

OBJECTIVE: To correlate cognitive dysfunction with structural and neurometabolic brain findings in patients with non-neuropsychiatric systemic lupus erythematosus (non-NPSLE). BACKGROUND: Over 25% of non-NPSLE patients have cognitive dysfunction, but the cerebral basis of this observation is not well understood. METHOD: Seven patients with non-NPSLE and seven control subjects were given a series of neuropsychological tests and neuroimaging with magnetic resonance imaging and magnetic resonance spectroscopy. Analyses of cognitive function and structural and neurometabolic measures of the brain were performed. RESULTS: Compared with controls, the non-NPSLE patients were significantly impaired on a global cognitive impairment index (CII). No significant differences between the groups were found in choline/creatine (Ch/Cr), N-acetylaspartic acid/Cr, or hippocampal volumes. Ch/Cr was highly associated with CII across the sample. CONCLUSIONS: This is the first study to correlate cognitive impairment with an increase in Ch/Cr ratio among patients with SLE. These results, although preliminary, suggest that changes in cerebral white matter may be important in determining the subtle cognitive impairment that may occur in patients with SLE, even in the absence of neuropsychiatric symptoms.