Elevated Serum Angiotensin-converting Enzyme Research Articles

Retrograde Radiographic Development in Pulmonary Sarcoidosis

A 48-year-old man with dyspnea, cough, and fever was found to have a diffuse ground-glass pulmonary lesion without lymphadenopathy on chest X-ray. The lesion shifted to the peripheral lung zones 2 months later when transbronchial biopsy demonstrated noncaseating granulomas with Langhans type giant cells. After 6 more months, prominent bilateral hilar lymphadenopathy and highly elevated serum angiotensin-converting enzyme confirmed the diagnosis of pulmonary sarcoidosis. Such a course is quite rare in that it goes the opposite way of the conventional staging system.

Association of peripheral multifocal choroiditis with sarcoidosis: A study of thirty‐seven patients

To assess the clinical spectrum of peripheral multifocal choroiditis (PMC) and its association with sarcoidosis. Thirty-seven patients examined between November 1997 and November 2001 who met all diagnostic criteria for PMC were included in this retrospective study. Patients were assessed for the following signs of sarcoidosis: typical changes on chest radiography or computed tomography; predominantly CD4 lymphocytosis in bronchoalveolar lavage fluid; elevated serum angiotensin-converting enzyme levels; elevated gallium uptake; and noncaseating granuloma on biopsy. Most of the patients were female (30 of 37; 81%) and white (30 of 37; 81%). Mean +/- SD age at onset was 57.5 +/- 18.7 years. Seven (19%) of the 37 patients had biopsy-proven sarcoidosis and 18 patients (49%) with presumed sarcoidosis met at least 2 of the above-mentioned criteria for sarcoidosis but had normal biopsy results. Twelve patients (32%) had an indeterminate diagnosis. Patients with presumed sarcoidosis did not differ from those with proven sarcoidosis as regards the above-mentioned criteria, except for noncaseating granuloma, implying that more than two-thirds of patients (predominantly whites) had underlying sarcoidosis. Most patients with positive gallium scintigraphy had increased mediastinal uptake, as described in sarcoidosis. Patients with underlying sarcoidosis had more severe visual impairment due to cystoid macular edema (CME). Weekly methotrexate (0.3 mg/kg) seemed to control CME. White patients with PMC should be considered to have sarcoidosis. The identification of sarcoidosis in patients with severe ocular disease can help with therapeutic choices.

A case of renal sarcoidosis: a special reference to calcium metabolism as a diagnostic and the therapeutic implications

Sarcoidosis is a systemic granulomatous disease of unknown etiology and is associated with a wide variety of renal disorders including nephrolithiasis, hypercalciuria, hypercalcemia, nephrocalcinosis, tubular defect, glomerulonephritis, and granulomatous interstitial nephritis. We report a case of renal sarcoidosis in which we could not detect any evidence of extrarenal involvements that was diagnosed by renal biopsy and abnormal calcium metabolism incompatible with chronic renal insufficiency. On laboratory findings, decreased creatinine clearance, proteinuria, hypercalcemia, hypercalciuria, and mildly elevated serum angiotensin-converting enzyme (ACE) were seen. Serum intact parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,alpha-25 vit D) were lower and higher than normal range, respectively, whereas the patient was already in chronic renal insufficiency. He was treated with oral corticosteroid. Serum ACE tended to fall, and 1,alpha-25 vit D level decreased with substantial fall of serum calcium and daily calcium excretion. In contrast, intact PTH increased slowly in accordance with a fall of serum calcium compatible with the level of renal impairment. Creatinine clearance and daily excretion of protein improved. The case reported here may propose that serial measurement of serum level of 1,alpha-25 vit D, calcium level, and magnitude of daily calcium excretion into urine is a simple and meaningful tool to detect the therapeutic response in sarcoidosis with abnormal calcium metabolism.

Histoplasmosis With Tenosynovitis of the Hand and Hypercalcemia Mimicking Sarcoidosis

We report on an otherwise healthy 47-year-old male who developed subacute tenosynovitis of the hand associated with night sweats and inguinal lymphadenopathy. He had a past history of granulomatous mediastinal lymphadenitis with positive histoplasmosis serology 11 years previously. Carpal tunnel exploration with biopsy demonstrated granulomatous inflammation. Granulomatous inflammation, hypercalcemia, and an elevated serum angiotensin converting enzyme (ACE) level suggested the diagnosis of sarcoidosis, however histoplasmosis infection could eventually be diagnosed. This unusual presentation of histoplasmosis underscores the fact that the diagnosis of sarcoidosis requires careful exclusion of other causes of granulomatous inflammation, particularly infectious agents. Even in the setting of an elevated ACE level and hypercalcemia, the possibility of an infectious etiology must be considered before establishing a diagnosis of sarcoidosis.

Common variable immunodeficiency in a six-year-old boy with sarcoidosis

Introduction Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder characterized by hypogammaglobulinemia and recurrent infections. Sarcoidosis, a multi-system granulomatous disease, could co-exist with CVID as documented in adult case reports. The association is still unclear. Immunologic defect and abnormal host response are possible explanations. Patients with CVID and sarcoidosis present with hypogammaglobulinemia rather than hypergammaglobulinemia as seen in sarcoidosis alone. Review of literature showed a paucity of case reports in children. We describe a six-year-old child who had a diagnosis of sarcoidosis with eventual diagnosis of CVID. Case report A six-year-old boy presented at age five with dyspnea, fever, rash, and inguinal lymphadenopathy. He had splenomegaly, anemia and thrombocytopenia. Mediastinal lymph node biopsy demonstrating noncaseating granuloma and an elevated serum angiotensin converting enzyme level of 181U/L (normal 14-70) led to the diagnosis of sarcoidosis. He was treated with systemic corticosteroids. Since infancy, he presented with persistent cough, nasal congestion, recurrent otitis media and sinusitis. At age six, he was hospitalized for pneumonia unresponsive to multiple courses of oral antibiotics. Immune work-up revealed an IgG of 13mg/dl (normal: 504–1465), IgA of <6 (27–195), IgM of 23 (24–214), and IgE of 10 (0–59). The finding of hypogammaglobulinemia without evidence of secondary causes of immunodeficiency led to the diagnosis of CVID. His recurrent sino-pulmonary infections ceased after initiation of monthly intravenous immunoglobulin therapy. Conclusion Although CVID and sarcoidosis are rare childhood diseases, children with sarcoidosis with recurrent infections should be evaluated for CVID. Conversely, patient with CVID should be monitored for sarcoid activity.

Bilateral parotid swelling caused by sarcoidosis

Sarcoidosis is a multisystem granulomatous disease characteristically causing bilateral hilar lymphadenopathy. Salivary gland swellings also are seen, which mandate recognition by the dental profession. The authors describe a patient whose diagnosis of sarcoidosis was tenuous. Ocular involvement and an elevated serum angiotensin-converting enzyme level suggested a diagnosis of sarcoidosis. Confirmation with a tissue biopsy was achieved only when the clinicians recognized that salivary gland swelling probably represented a manifestation of the disease. Steroid therapy was instituted. It is important for the dental practitioner to be familiar with the salivary gland manifestation of sarcoidosis. Early recognition and intervention aborts or slows disease progression.

Prognostic role of serum ACE activity on outcome of type 2 diabetic patients on chronic ambulatory peritoneal dialysis

Overexpression of the renin-angiotensin system is important in the pathogenesis of macroangiopathy (MA). Patients with diabetes with end-stage renal failure have elevated serum angiotensin-converting enzyme (ACE) activity compared with their nonuremic counterparts. Because their major cause of death is MA, the significance of serum ACE activity on outcome of this group of patients is studied. We performed a prospective cohort study of 49 patients with type 2 diabetes on continuous ambulatory peritoneal dialysis (CAPD) therapy. Baseline serum ACE activity was determined by a modified spectrophotometric method and followed up at a median of 34 months. The prevalence of MA (defined as ischemic heart disease, sudden cardiac arrest, stroke, or peripheral vascular disease) and all-cause mortality rates were studied. Risk for MA is associated with serum ACE activity (median with MA, 69.0 U/L [range, 46.0 to 100.1 U/L] versus without MA, 57.2 U/L [range, 36.3 to 81.0 U/L]; P = 0.02). At the end of follow-up, 48% of patients (24 of 49 patients) died, 70% of MA. The group that died had increased baseline serum ACE activity (nonsurvivors, 65.0 U/L [range, 33.5 to 100.0 U/L] versus survivors, 49.4 U/L [range, 36.4 to 86.5 U/L]; P < 0.05) and MA rates (nonsurvivors, 77% versus survivors, 36%; P < 0.01). Cox regression analysis performed with age, sex, mean blood pressure, body mass index, metabolic control, Kt/V, residual renal function, serum albumin level, and ACE activity showed that baseline serum ACE activity (P = 0.033) is an independent predictor for mortality in patients with type 2 diabetes on CAPD therapy. Among patients with type 2 diabetes on CAPD therapy, serum ACE activity is associated with risk for MA and is an independent predictor for mortality. Whether ACE inhibition will have a beneficial effect on the outcome of these patients needs further investigation. © 2002 by the National Kidney Foundation, Inc.

58-Year-Old Man With Fatigue and Flank Pain

58-Year-Old Man With Fatigue and Flank Pain

Sarcoidosis presenting with facial palsy and uveitis

A 43-year-old woman presented with peripheral facial palsy and bilateral anterior uveitis. The diagnosis of sarcoidosis was established by an elevated serum angiotensin-converting enzyme level, hilar adenopathy on chest x-ray film, restrictive ventilatory impairment on pulmonary function testing, and a transbronchial biopsy specimen showing noncaseating epithelioid granulomas with Langhans giant cells. A complete ophthalmic examination is important in patients with peripheral facial palsies to search for signs of systemic disease.

Influence of angiotensin converting enzyme (ACE) genotype on interpretation of diagnostic tests for serum ACE activity.

The discovery that an insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene influences the circulating concentration of ACE may have implications for the proper use of serum ACE activity measurements in screening for sarcoidosis. To determine whether the sensitivity of the serum ACE test improves if ACE genotype is taken into account. A retrospective determination of ACE genotype and clinical diagnosis was done in 54 patients with serum ACE activity above the upper limit of the reference range for the insertion (II) genotype. ACE was measured by radioenzymatic and spectrophotometric techniques, and genotype by PCR. When serum ACE values determined diagnostically were related to the appropriate genotype-specific reference range, sensitivity and specificity for diagnosis of sarcoidosis were 65-70% and 58% respectively, compared to 47-57% and 77% with a reference range unsegregated for genotype. ACE genotyping may be helpful in determining the diagnostic significance of mildly elevated serum ACE activity in patients with the II and ID genotypes.

Serum lysozyme levels and clinical features of sarcoidosis.

Serum lysozyme is used as a marker of sarcoidosis disease activity. In this study we examined the association between lysozyme levels and the clinical features of sarcoidosis and thus the clinical usability of this parameter in a large population. One hundred ten sarcoidosis patients from central Japan were examined for clinical features and serum lysozyme level at the first visit to our hospital and on a regular basis thereafter. The sensitivity of lysozyme for predicting sarcoidosis was 79.1%, whereas that of serum angiotensin-converting enzyme (ACE) was 59.0%. Even in the cases without an elevated serum ACE level, a value of 72.1% was obtained. The serum lysozyme level demonstrated a significant tendency to increase with the number of organs involved (p < 0.01). There were significant differences among the four radiographic stages (p < 0. 05). The maximum serum lysozyme levels of patients without a disappearance of abnormal shadows on chest radiography within 5 years were significantly greater than those of individuals with a disappearance (p < 0.05). A positive correlation between serum lysozyme and serum ACE levels was observed. Because serum lysozyme is much less specific for sarcoidosis than serum ACE, its diagnostic value may be limited. However, the sensitivity was high even when serum ACE levels were within normal limits and correlated well with clinical features in sarcoidosis. Therefore, this parameter seems suitable for disease monitoring in proven cases.

Indocyanine green angiographic features in ocular sarcoidosis

Objective To determine indocyanine green (ICG) angiographic features and evaluate the extent of choroidal involvement in proven cases of posterior ocular sarcoidosis. Design Nonrandomized controlled trial. Participants Nineteen patients (14 females, 5 males; average age, 56 ± 4 years) with clinically typical posterior sarcoidosis (biopsy-proven in 6 cases and fulfilling the other diagnostic criteria in 13 cases) participated, with 10 control subjects (average age, 48 ± 7 years). Criteria for the diagnosis of sarcoidosis were a positive biopsy result or the presence of at least three of the following four criteria: elevated serum angiotensin-converting enzyme, elevated lysozyme, cutaneous anergy, and hilar lymph node enlargement. Intervention Indocyanine green angiography was performed according to a standard angiographic protocol used in inflammatory disorders. Main outcome measures Indocyanine green angiographic features and proportion of choroidal inflammatory involvement were measured. Results Indocyanine green angiographic features could be classified into four main patterns. The first pattern is hypofluorescent choroidal lesions in the early and intermediate phases, irregularly distributed, invisible on funduscopy or fluorescein angiography, and localized in the midperiphery (63% of patients), in the macula (11%) or in both regions (26%) with an average dot diameter of 0.31 ± 0.03 disc diameters. These lesions either became isofluorescent in the late phase of the angiogram (Type 1, present in all patients) or remained hypofluorescent (Type 2, present in 84% of patients). The second pattern is focal hyperfluorescent pinpoints visible in the intermediate and late phases (in 89% of patients). The third pattern is fuzzy choroidal vessels with leakage in the intermediate phase of the angiogram, and the fourth pattern is diffuse late zonal choroidal hyperfluorescence with staining in the late phase of the angiogram, both features being present in all patients. Conclusions Indocyanine green angiography allowed the authors to assess and quantify the hitherto unknown extent of choroidal involvement in ocular sarcoidosis. Furthermore, characteristic ICG findings might represent an additional valuable tool for diagnosing and monitoring this disease.

Peripheral Multifocal Chorioretinitis: A Distinct Clinical Entity?

Objective: The purpose of the study is to delineate the clinical features, complications, visual prognosis, and associated systemic diseases of peripheral multifocal chorioretinitis.Design: The study design was a retrospective study.Participants: Of 828 patients with uveitis, 53 patients (6.4%) fulfilled all 3 of the following criteria: (1) the presence of multiple (>10), small, round, punched-out lesions in the peripheral retina; (2) the absence of central chorioretinal lesions; and (3) an associated intraocular inflammatory reaction.Results: The majority of patients were elderly white females with bilateral ocular involvement. The presenting symptoms consisted of vitreitis and/or iritis, papillitis, and numerous retinal punched-out lesions in the periphery. On initial examination, the complications included cystoid macular edema (CME) (48%), glaucoma (25%), and cataracts (19%), resulting in a mean visual acuity of 20/80. After more than 2 years of followup, CME was found in 72% and cataract in 62% of the affected eyes. Submacular neovascularization never developed. The final mean visual acuity was 20/60; this was mainly dependent on the presence of CME (eyes with CME visual acuity was 20/80, eyes without CME; visual acuity was 20/50). In 25% of patients, an association with sarcoidosis was observed (histologic and radiologic diagnoses), and an additional 29% of patients had elevated serum angiotensin-converting enzyme levels.Conclusions: Within the spectrum of multifocal chorioretinitis, the authors have defined a distinct clinical entity of peripheral multifocal chorioretinitis. The recognition of this clinical entity may be valuable because of its specific symptoms, prognosis, and association with sarcoidosis.

Elevation of serum angiotensin converting enzyme (ACE) during treatment

It has been observed that lung tuberculosis shows a similar pathological feature with that of sarcoidosis. Serum angiotensin converting enzyme (ACE) was elevated in sarcoidosis. In the present study, serum ACE was measured in pulmonary tuberculosis patients. 1. ACE showed lower level in active tuberculosis. Elevation of serum ACE, however, was observed during the treatment. 2. Serum ACE was low in cases with chronic fibrotic pulmonary tuberculosis with extensive shadows on chest X-P. 3. Improvement of infiltrative shadows on chest X-P paralleled with the elevation of serum ACE. It was suggested that the new development of lung capillary endothelium might cause the elevation of ACE during the improving process of active pulmonary tuberculosis.

Serum Neopterin and Angiotensin-converting Enzyme In Cancer Patients

Summary An elevation of serum angiotensin-converting enzyme (ACE) has been reported in some disorders associated with immune activation, e.g. sarcoidosis, HIV infection or ulcerative colitis. Both endothelial cells and macrophages are thought to be the possible source of increased ACE levels. We have investigated serum ACE and neopterin, an indicator of macrophage activation, in 23 patients with solid tumors as well as in 8 controls. Similar ACE levels have been observed in the cancer patients and the controls (2.6 ± 2.1 vs 3.4 ± 1.1 μkat/1, while neopterin has been significantly higher in the cancer patients (15.4 ± 12.6 vs 7.2 ± 2.2 nmol/I, P&lt;O.02). No correlation has been observed between serum ACE and neopterin. We conclude that an elevation of ACE is not present in cancer patients. Macrophage activation in cancer is not accompanied by increased ACE release.

Fluorine-18 deoxyglucose uptake in sarcoidosis measured with positron emission tomography.

Regional pulmonary glucose metabolism (MRglu; mumol h-1 g-1), extravascular lung density (D(EV); g cm-3) and vascular volume (VB; ml cm-3) were measured in a single midthoracic transaxial slice (approximately 2 cm thick) using position emission tomography (PET) in seven patients with histologically proven sarcoidosis. The measurements were repeated 1-7 months later after steroid therapy (in two cases, no treatment) in order to assess MRglu as an index of inflammation and relate it to routine pulmonary function tests, chest radiography and serum angiotensin converting enzyme (SACE) levels. MRglu was computed from serial lung scans and peripheral venous blood samples for 60 min following an i.v. injection of 18F-2-fluoro-2-deoxy-D-glucose (18FDG). Both MRglu (which was increased in six of seven patients) and elevated SACE levels returned to normal in those patients treated with high-dose steroids. Regional vascular volume was normal in six of seven cases and did not change significantly with therapy. The high tissue density measured in all patients decreased significantly in two of three patients treated with 40 mg prednisolone daily. The abnormal MRglu observed in active sarcoidosis becomes normal pari passu with SACE levels during high-dose steroid therapy. We conclude that MRglu measured with 18FDG and PET may reflect "disease activity" in sarcoidosis in quantitative terms (per gram lung tissue) and in respect of disease distribution.

Non-caseating Conjunctival Granulomas in Patients with Multifocal Choroiditis and Panuveitis

This study describes a group of patients with clinical findings of peripheral punched-out lesions and panuveitis who had non-caseating granulomas found by non-directed conjunctival biopsy. A series of 10 patients seen at The University of Iowa Hospitals and Clinics between August 1989 and August 1990 with ocular findings similar to those of multifocal choroiditis with panuveitis, including peripheral punched-out chorioretinal lesions, vitritis, and frequently, cystoid macular edema, was examined. All patients underwent ophthalmic examination, ancillary testing, and non-directed conjunctival biopsy. Of the ten patients, nine were women. Results of FTA-ABS were negative for all patients. A non-directed conjunctival biopsy disclosed non-caseating granulomata in seven of the patients. Acid-fast bacilli were not detected in any specimens. Four of the seven patients with positive biopsy results had either elevated serum angiotensin-converting enzyme levels or chest x-rays consistent with sarcoid. Six of these seven patients were 58 years of age or older. It is recommended that non-directed conjunctival biopsy specimens be examined to exclude the presence of non-caseating granulomata in uveitis patients with small, inferior, peripheral, punched-out chorioretinal scars, especially in women older than 55 years of age.

Serum angiotensin converting enzyme activity in chronic beryllium disease.

Serum angiotensin converting enzyme (SACE) activity is used as a marker of sarcoidosis activity and severity, but in chronic beryllium disease (CBD) the studies of SACE give conflicting results. We examined SACE activity in 23 CBD patients, five patients with beryllium sensitization, and 25 beryllium-exposed control subjects. CBD patients underwent complete clinical evaluation, including physical examination, pulmonary function testing, exercise physiology testing, chest radiography, and bronchoscopy with bronchoalveolar lavage and biopsy. CBD SACE activity was systematically compared with these clinical markers of disease severity. Of CBD patients, 22% had elevated SACE activity. The test did not discriminate CBD patients from those in the beryllium-sensitized or beryllium-exposed groups. However, SACE activity in CBD correlated with the extent of pulmonary granulomatous inflammation as reflected by the symptom of breathlessness, the number of white cells in bronchoalveolar lavage (r = 0.44), the number of lavage lymphocytes (r = 0.58), the lavage lymphocyte percentage (r = 0.55), and the profusion of small opacities on chest radiograph (r = 0.41). The test-retest reliability of the assay was high (r = 0.84), as was the agreement between fresh and -70 degrees C frozen sera (r = 0.93). We conclude that SACE activity levels may reflect the extent of pulmonary granulomatous inflammation in CBD but that the test does not help discriminate disease from nondisease.

Serum Angiotensin-Converting Enzyme Level Is Elevated in Patients With Human Immunodeficiency Virus Infection

Serum angiotensin-converting enzyme (ACE) level is elevated in a number of disease states and medical conditions. Based on review of the medical literature, we postulated that serum ACE level elevation may occur during infection with the human immunodeficiency virus (HIV). In a prospective, controlled study, serum ACE levels of HIV-positive patients were compared with those of an HIV-negative control population. Serum ACE levels were significantly elevated in patients with the acquired immunodeficiency syndrome (55.4 +/- 11.4 U/L) and in patients with an intermediate stage of HIV infection (57.2 +/- 25.3 U/L) when compared with levels in controls (31.9 +/- 14.0 U/L). Elevated serum ACE levels occur in HIV infection and may be an important marker for this disease.

Pulmonary vascular involvement in sarcoidosis: granulomatous angiitis and microangiopathy in transbronchial lung biopsies

To evaluate the occurrence of granulomatous angiitis and microangiopathy in the lung with sarcoidosis, transbronchial lung biopsy specimens were examined from 174 cases with sarcoidosis. Granulomatous angiitis was seen in 72 cases, which corresponded to 53% of the cases with granulomata. Granulomatous angiitis showed venous involvement (65%), both venous and arterial involvement (24%) or arterial involvement only (11%). There was no significant difference in occurrence of granulomatous angiitis between upper and lower lobes. The cases with granulomatous angiitis in the lung had a higher frequency of ophthalmic symptoms and elevated serum angiotensin converting enzyme level. Basal lamina layering in the microvasculature was more often observed in the bronchial mucosa than in the alveolar walls and is not exclusively related to granulomata. Endothelial proliferation and basal lamina alterations in granulomatous angiitis may be closely associated with granulomas. The present study revealed coexistence of granulomatous angiitis and microangiopathy in the lung with sarcoidosis and suggests that both may participate in the development of pulmonary sarcoidosis.