Normal Serum Angiotensin-converting Enzyme Research Articles

Correlation of Mantoux Test and Serum Angiotensin-Converting Enzyme (ACE) Levels with Clinically and Radiologically Diagnosed Ocular Tuberculosis and Ocular Sarcoidosis

Abstract Aim: To evaluate the role of combined Mantoux test and serum angiotensin-converting enzyme (ACE) levels in the diagnosis of ocular tuberculosis (TB) and ocular sarcoidosis. Materials and Methods: A prospective and observational study including patients with bilateral granulomatous uveitis diagnosed both radiologically and clinically as ocular TB or ocular sarcoidosis within a six-month period. CT Thorax/CT abdomen was done, and findings were noted. Mantoux test and serum ACE levels were recorded, and findings were correlated. Results: The study included a total of 60 patients: 32 patients with ocular TB and 28 patients with ocular sarcoidosis. Using Mantoux test, 84.4% in the TB group tested positive and were correctly identified (sensitivity), and 96.4% in the sarcoid group tested negative and were correctly identified as sarcoidosis. Hence, the association between Mantoux test and diagnoses was statistically significant (P < 0.001). In the TB group, 25 subjects had normal and seven had elevated serum ACE levels. In the sarcoidosis group, 22 subjects had elevated and six had normal serum ACE levels. Hence, 78.1% were correctly identified with normal serum ACE levels (sensitivity) in the TB group and 78.6% were identified with elevated serum ACE levels in the sarcoidosis group, and the proportion difference was statistically significant (P < 0.001). Conclusion: Mantoux test and serum ACE levels are cost-effective investigations and can be used for the diagnosis of ocular TB and sarcoidosis when combined with clinical and radiological evidence. The combined use of serum ACE and Mantoux test is useful in differentiating between sarcoidosis and TB.

Immune-Related Erythema Nodosum Mimicking in Transit Melanoma Metastasis on [18F]-FDG PET/CT.

Early detection of immune-related adverse events (irAEs) with immune checkpoint inhibitors (ICIs) is crucial, particularly when these are likely to mimic tumor progression, as well as sarcoid-like reactions. Here, we report the case of a 68-year woman, with a history of four primary cutaneous melanomas (thickest lesion with BRAF mutation removed from the left axilla 2 years before), who was diagnosed with BRAF V600E-mutant metastatic melanoma and treated by ICI targeting the PD-1 receptor. Follow-up whole-body positron emission tomography/computed tomography (PET/CT) using 18F-fluorodeoxyglucose ([18F]-FDG) was performed at 15 months, and FDG-avid subcutaneous nodules on her legs were detected. A biopsy from a lesion on her right leg was obtained, and histology strongly suggested erythema nodosum. Given the isolated nature of these lesions, the normal serum Angiotensin-Converting Enzyme and the context of ICI, an immune-related sarcoid-like reaction was retained as the most likely diagnosis. Recent literature in immune-oncology suggests that erythema nodosum could be directly related to ICI(s). Although erythema nodosum is a rare occurrence with imaging features overlapping with malignancy, it should be considered in the differential diagnosis of suspicious in-transit metastasis, especially when the patient is treated with ICIs and when lesions follow a bilateral distribution. In conclusion, nuclear medicine physicians should keep in mind this irAE when interpreting PET/CT scans in clinical practice in order to avoid false-positive findings.

Serum Angiotensin-Converting Enzyme Has a High Negative Predictive Value in the Investigation for Systemic Sarcoidosis

To examine whether measurement of serum angiotensin-converting enzyme (ACE) is useful in diagnosing sarcoidosis in undifferentiated uveitis. Evaluation of a diagnostic test. Data collection was performed from 1035 consecutive subjects presenting with uveitis to Moorfields Eye Hospital undergoing measurement of serum ACE as part of baseline investigations for underlying systemic disease. The main outcome measures were sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of elevated serum ACE. Mean age of the sample was 41.7 years and 56.1% of subjects were female. Sarcoidosis was the underlying cause for the uveitis in 110 subjects (10.6%) and was more common in adults, female subjects, black subjects, and subjects with intermediate uveitis or panuveitis. ACE was elevated in 196 subjects (18.9%) and elevated levels were observed in 85 subjects eventually diagnosed with underlying sarcoidosis (true positive 77.3%) and in 111 subjects with an alternate diagnosis (false positive 12.0%). In adult subjects, sensitivity of serum ACE was 78.1%, specificity 90.0%, and PPV 43.6%, but the NPV was 97.0%. The test performed well, with area under curve (AUC) 0.897 (95% confidence interval [CI] 0.854-0.941). Serum ACE performed less well in distinguishing sarcoid uveitis in pediatric subjects, with sensitivity 60.0%, specificity 78.5%, and PPV 10.0%, but again NPV was high at 96.9% and AUC was 0.828 (95% CI 0.571-1.000). Serum ACE had a very high negative predictive value for sarcoid uveitis, eliminating the need for further screening tests in subjects with normal serum ACE, unless clinical suspicion was high.

Clinical and biochemical presentation of sarcoidosis with high and normal serum angiotensin-converting enzyme

Objectives: The presentation of sarcoidosis can involve symptoms from all organs and the diagnosis is therefore often difficult. A raised serum level of serum angiotensin-converting enzyme (sACE) can be detected in 41–58% of patients. However, whether the sACE level per se reflects the severity of the sarcoid inflammation at the onset of the disease is not well described. The purpose of this study was to investigate the clinical and laboratory significance of high versus normal sACE levels in sarcoidosis.Method: Journal data were retrospectively extracted from 101 patients from our clinic. Clinical and biochemical data were compared between patients with high sACE levels (> 115 U/L) on at least one occasion and normal sACE levels (< 115 U/L).Results: In total, 48% (n = 48) of the patients had high ACE and 52% (n = 53) had normal ACE. The most common extrapulmonary manifestation for both groups was arthritis, followed by skin and eye involvement, but none of these differed between the two groups. Serum ionized calcium was significantly higher in the high sACE group, with a correlation coefficient of 0.112 (p = 0.460).Conclusion: Our study demonstrates that serum ionized calcium is significantly higher in the high sACE group but there was no statistical correlation to sACE. No other clinical or biochemical differences were observed.

Serum angiotensin-converting enzyme for diagnosis and therapeutic evaluation of sarcoidosis.

We have expanded our studies evaluating the usefulness of serum angiotensin-converting enzyme assays for supporting a diagnosis of active sarcoidosis. Increased concentrations (>35 units/ml, >2 SD above the mean for normal control subjects) were found in 57.8 per cent of 391 patients with sarcoidosis; 23.3 per cent of these patients were either receiving corticosteroid medication or had a diagnosis of inactive or resolved disease and had normal serum angiotensin-converting enzyme activity. Thus, 75.3 per cent of the patients with active, untreated disease had increased serum concentrations of angiotensin-converting enzyme. Serum concentrations of angiotensin-converting enzyme tended to be higher in blacks with sarcoidosis than in whites with sarcoidosis. Pediatric control subjects had higher concentrations of angiotensin-converting enzyme than adults; values greater than 50 units/ml were required for the concentration to be considered to be significantly increased. Patients placed on steroid therapy had s...

Prognostic value of serum angiotensin-converting enzyme activity for outcome of community-acquired pneumonia

In a previous study, a relation between decreased serum angiotensin-converting enzyme (ACE) activity and physiological parameters was observed in patients with community-acquired pneumonia. The present study aims to further assess the prognostic value of serum ACE activity for outcome of community-acquired pneumonia. This was a prospective observational study including two cohorts of patients with community-acquired pneumonia (2004-2006; n=157 and 2007-2010; n=138). Serum ACE activity was measured at time of hospital admission. Based on reference values in healthy persons, patients were divided into subgroups of serum ACE activity: normal, low and extremely low. Physiological parameters, clinical outcomes and etiology were compared between the subgroups. A total of 265 patients were enrolled in this study. Mean age was 60±19 years. In patients with low serum ACE activity (<20 U/L, n=53), compared to patients with normal serum ACE activity (≥20 U/L, n=212), C-reactive protein (CRP) was significantly increased, systolic blood pressure was significantly lower and there was a trend for higher heart rate and leukocyte counts. Furthermore, Streptococcus pneumoniae was significantly more identified in patients with low serum ACE activity. Serum ACE activity <24 U/L was independently associated with bacteremia (adjusted OR 3.93 [95% CI 1.57-9.87]). Low serum ACE activity was not prognostic for length of hospital stay nor mortality. This study did not show prognostic value for serum ACE activity regarding clinical outcome in patients with community-acquired pneumonia. Serum ACE activity <24 U/L at time of hospitalization appeared an independent indicator for the presence of bacteremia. Further research should elucidate the role of ACE in systemic infection and sepsis during pneumonia.

An unusual case of acute leg weakness

A 41-year-old male presented with progressive leg weakness and difficulty with micturition. He had otherwise been well. Clinical examination was normal apart from reduced power (3–4/5) in his lower limbs and a palpable bladder. The patient was catheterized and had a 1000 ml residual volume. Initial blood tests and magnetic resonance imaging of his brain were normal, but magnetic resonance imaging of the spinal cord revealed extensive abnormality. Figures 1–3 are selected magnetic resonance images of the cervical and upper thoracic cord. Figure 1 shows extensive high signal within the cord on T2 weighting, extending from C3 to the upper thoracic region. The cord itself is expanded and the altered signal extended to the T10 level on further imaging. Figure 3 shows meningeal enhancement (arrows) and this was evident along the whole cord to the conus. There was no compressive lesion. These appearances are consistent with a transverse myelitis. Lumbar puncture showed an increased CSF white cell count, reduced glucose and increased protein levels. The patient was commenced on intravenous methylprednisolone and cefotaxime. His leg weakness progressed with power falling to 0/5. A sensory level was established at T2. Further blood tests showed a normal serum angiotensin-converting enzyme level, no evidence of tuberculosis, normal autoantibodies and negative viral screen including HIV. Syphilis serology (i.e. venereal disease research laboratory (VDRL), Treponema pallidum haemagglutination assay (TPHA) and serum enzyme-linked immunosorbent assay (ELISA)), however, was strongly positive. Further lumbar puncture showed positive CSF antibodies to Treponema pallidum. The diagnosis of syphilitic transverse myelitis was made and his antibiotics were changed to intravenous benzylpenicillin. The patient made a full neurological recovery.

Löfgren’s syndrome revisited: a study of 186 patients

PURPOSE: To evaluate the clinical features, the results of noninvasive tests and biopsies, and the outcome of patients with Löfgren’s syndrome. SUBJECTS AND METHODS: Patients diagnosed as having Löfgren’s syndrome at a university hospital in Barcelona, Spain, from 1974 to 1996, were prospectively followed. Löfgren’s syndrome was defined as the association of erythema nodosum or periarticular ankle inflammation with unilateral or bilateral hilar or right paratracheal lymphadenopathy. RESULTS: Löfgren’s syndrome was diagnosed in 186 patients. The mean age was 37 ± 11 years, and 157 (85%) were women. In 91 patients (49%), symptoms started during the spring ( P <0.0001). Erythema nodosum, periarticular ankle inflammation, or both were present at onset in 173 patients (93%). At the time of diagnosis, 161 patients (87%) had no respiratory symptoms; 151 (81%) had stage I abnormalities on chest radiograph, 29 (16%) stage II, and 6 (3%) stage 0. Five percent of patients had decreased forced vital capacity, and 15% had decreased carbon monoxide diffusing capacity. Extrathoracic involvement was infrequent. Serum angiotensin-converting enzyme levels were increased in 50% of patients. Gallium-67 scans showed hilar uptake in all the studied patients, but it yielded useful additional diagnostic information only in those with normal chest radiographs or with unilateral hilar lymphadenopathy. The diagnosis was proven with biopsy results in 63% of patients. None of the patients without histologic confirmation were subsequently found to have a diagnosis other than sarcoidosis. In the 133 patients who were followed for a mean of almost 5 years, 11 (8%) continued to have active disease, and 8 (6%) had several recurrences between 18 months and 20 years after a complete resolution. A normal serum angiotensin-converting enzyme level at diagnosis was associated with disease resolution without recurrence. CONCLUSION: Löfgren’s syndrome is usually a self-limiting form of sarcoidosis. Histologic confirmation is not necessary in typical cases. In a small number of patients, the disease may remain active or recur long after its onset, although usually with mild organ dysfunction.

Activation of alveolar macrophages in pulmonary sarcoidosis: lack of correlation with serum angiotensin-converting enzyme activity.

To identify the activation of alveolar macrophages as a direct measure of disease activity in pulmonary sarcoidosis and to evaluate the possible relationship with serum angiotensin-converting enzyme (ACE) levels, we studied the morphology and function of alveolar macrophages obtained by bronchoalveolar lavage from patients with active disease (n = 12) and inactive disease (n = 5), and from normal controls (n = 11). At the time of lavage, 6 of 12 patients with active disease showed an elevation of serum ACE levels. When alveolar macrophages were cultured, more cells from active disease adhered to glass, spread out, and were positive for NBT reduction (p less than 0.001). Lysosomal enzyme (beta-galactosidase) activity was higher only in patients with active disease (p less than 0.001). In active disease, there were no significant differences in morphology or function of alveolar macrophages between higher and normal serum ACE levels. Thus, alveolar macrophages were activated in active pulmonary sarcoidosis and no correlation was found with serum ACE levels. These results suggest that serum ACE levels do not accurately reflect the activity of disease in the lung.

Normal Serum Angiotensin Converting Enzyme Activity in Patients with Newly Diagnosed Sarcoidosis

Twenty-four patients with sarcoidosis had normal serum angiotensin converting enzyme (SACE) values at time of diagnosis. Sixteen patients were in stage I and eight of these underwent complete remission and four followed a stable course. Seven of eight patients in stages II and III experienced improvement while receiving glucocorticoid treatment. In six, serial SACE measurements fell significantly, paralleling the clinical improvement. The data suggest that a normal SACE in stage I indicates a good prognosis. Patients in stages II and III with normal SACE levels may still have active disease potentially responsive to glucocorticoid treatment. The reduction of SACE while receiving treatment may be viewed as the "suppressible" SACE compartment, representing that portion of the enzyme elaborated by the granuloma or its cellular precursors. The level remaining after suppression by glucocorticoids may be considered "basal" SACE, probably related to normal turnover of SACE producing cells in vascular endothelium.

Elevation of Serum Angiotensin-Converting Enzyme Level

Serum angiotensin-converting enzyme (ACE) levels were measured in 151 patients with chronic alcoholism and alcoholic liver disease. The mean serum ACE level was elevated to 30.8 +/- 13 units/mL compared with 22.8 +/- 6 units/mL in control subjects. Approximately 30.0% of the patients had elevated ACE levels. Abstinence from alcohol for six to 27 months by 11 patients was associated with persistently normal serum ACE levels. Angiotensin-converting enzyme level elevations did not correlate with abnormalities of other liver function test results or with any acute clinical condition associated with alcoholic cirrhosis. Hypoxemia was not present in the patients with elevated serum ACE levels. Elevations of serum ACE levels in patients with alcoholic liver disease may relate to an effect of alcohol on the hepatic-sinusoidal lining cells. This elevation could interfere with the use of this test for supporting the diagnosis of sarcoidosis.

The level of angiotensin-converting enzyme as indicator of 2-year prognosis in untreated pulmonary sarcoidosis without erythema nodosum.

In order to evaluate the prognostic significance of elevated serum angiotensin-converting enzyme (SACE) in pulmonary sarcoidosis, the 2-year prognosis was studied in 33 untreated patients without erythema nodosum. Elevated SACE was found in 19 patients among whom total regression or improvement was noted in 42%, against 86% in 14 patients with normal SACE in serial measurements. The groups with and without elevated enzyme levels were not different with respect to sex, age, pulmonary changes, or extrathoracic manifestations. Thus, the findings of elevated SACE in this category of sarcoidosis patients may have some prognostic significance, pointing toward a greater risk of a chronic course.