Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 71-year-old woman receiving both angiotensin II receptor antagonist and calcium antagonist suffered severe systemic edema. She had been treated for essential hypertension with amlodipine for 2 years and candesartan for 3 months, and systemic lupus erythematodes (SLE) with steroids. During treatment, severe systemic edema appeared, mainly on her face, arms, and legs. At first, we suspected drug-induced edema by candesartan, so it was halted, but the edema still continued. We then considered amlodipine to be the culprit, and finally, the severe systemic edema disappeared after cessation of amlodipine. To control her blood pressure, we recommended candesartan, but 3 months late she suffered severe systemic edema again, thus the causative we drugs of her edema were thought to be both amlodipine and candesartan. Edema is a common symptom in elderly patients and we frequently observe drug-induced edema. In this case, there was underlying acceleration of blood vessel permeability induced by SLE and steroids and moreover, vasodilatation by candesartan and/or amlodipine further accelerated blood vessel permeability, and thus might have caused severe edema. It is very difficult to determine the cause of edema, especially in elderly patients, but we should consider not only one but also two or more drugs as being involved in drug-induced edema.
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PMID:[A case of severe systemic edema in an elderly hypertensive patient with systemic lupus erythematodes during long-term treatment with anti-hypertensive drugs]. 1160 22

Systemic lupus erythematosus (SLE) is an inflammatory multisystem disease of unknown etiology with immunologic aberrations. Many studies have shown that genetic and environmental factors are implicated in the development of SLE. Angiotensin-converting enzyme (ACE) affects various immune phenomena through the renin-angiotensin and kallikrein-kininogen systems by creating angiotensin II and inactivating bradykinin. We investigated the correlation between insertion/ deletion polymorphism of the ACE gene and the clinical manifestations of SLE, especially vascular involvement and lupus nephritis. Two-hundred and eleven Korean patients fulfilling the ACR criteria and 114 healthy subjects were enrolled. The ACE genotype was determined by polymerase chain reaction using genomic DNA from peripheral blood. The nephritis patients were classified by the WHO classification. In addition, the activity and chronicity index were used to assess the severity of renal involvement. We evaluated vascular involvement by the presence or absence of hypertension, Raynaud's phenomenon, livedo reticularis, antineutrophil cytoplasmic antibody and the SLICC/ACR Damage Index. The gene frequency of ACE gene polymorphism was as follows: II 39 vs 34%, ID 41 vs 50%, DD 20 vs 16% in SLE patients and controls, respectively. There was no difference in genotype frequency between both groups. There were no significant differences between the distribution of ACE gene genotypes and lupus nephritis and its related parameters, including WHO classification, activity index, chronicity index, renal dysfunction and amount of 24 h urinary protein. The ACE genotypes and alleles did not affect the presence of vascular manifestations evaluated, but the frequency of DD genotype was significantly low in SLE patients with Raynaud's phenomenon compared to those without Raynaud's phenomenon (P = 0.002 for ACE ID vs DD and II, OR 2.7, 95% CI 1.43-5.09; P=0.023 for ACE DD vs ID and II, OR 0.33, 95% CI 0.12-0.89). Also skewing from DD to II genotype was noted in patients with anti-Sm antibody compared to those without anti-Sm antibody (P = 0.025 for ACE DD vs ID and II, OR 0.21, 95% CI 0.05-0.93). The onset age of serositis was older in patients with the ID genotype than the others (ID= 34.5+/-10.8, II + DD = 25.6+/-10.2, P= 0.002). Also the onset age of malar rash was older in patients with II genotype than the others (II=26.7+/-8.4, ID+DD=21.3+/-9.0; P=0.021). The patients with I allele showed a significantly higher frequency of serositis (P = 0.022). Taken together, the I/D polymorphisms of ACE gene did not affect susceptibility of SLE, lupus nephritis and the vascular manifestations, including Raynaud's phenomenon, in Korean SLE patients, although the DD genotype was negatively associated with Raynaud's phenomenon among SLE patients. However, it would be valuable to evaluate the role of other genes potentially related to vascular events, such as endothelin, nitric oxide or angiotensin II receptor as well as ACE gene.
Lupus 2002
PMID:Angiotensin-converting enzyme gene polymorphism and vascular manifestations in Korean patients with SLE. 1263 Jul 62

Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), an inhibitor of inosine-5'-monophosphate dehydrogenase, has several immunosuppressant actions. MPA depletes guanosine and deoxyguanosine nucleotides preferentially in T and B lymphocytes, inhibiting proliferation and suppressing cell-mediated immune responses and antibody formation, major factors in acute and chronic rejection. MPA also can induce T-lymphocyte apoptosis. MPA suppresses dendritic cell maturation and can induce human monocyte-macrophage cell line differentiation, decreasing the expression of interleukin (IL)-1 and enhancing expression of the IL-1 receptor antagonist. In addition, MPA inhibits adhesion molecule glycosylation and expression and lymphocyte and monocyte recruitment. Activated macrophages produce nitric oxide (NO) and superoxide, which combine to generate tissue-damaging peroxynitrite. MPA depletes tetrahydrobiopterin and decreases NO production by inducible NO synthase without affecting constitutive NO synthase activity. By these mechanisms, MMF exerts anti-inflammatory activity, which could attenuate both acute and chronic rejection. Unlike calcineurin inhibitors, MMF is nonnephrotoxic and does not induce transforming growth factor-beta production, which is fibrogenic. MMF inhibits arterial smooth muscle cell proliferation, a contributor to graft proliferative arteriopathy, and does not increase blood pressure, cholesterol, or triglyceride levels. By decreasing high-density lipoprotein oxidation and macrophage recruitment, MMF also may delay onset/progression of graft atherosclerosis. Thus, MMF may prevent chronic rejection by several mechanisms. MMF activity is synergistic with that of other agents such as valganciclovir for treating cytomegalovirus infection. MMF also has synergistic activity with angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists in the treatment of some nephropathies in experimental animals. This combination may prevent progression toward end-stage renal disease in humans with chronic allograft, lupus, and diabetic nephropathies.
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PMID:Mechanisms of action of mycophenolate mofetil in preventing acute and chronic allograft rejection. 1625 60

Angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) reduces proteinuria and the rate of renal function deterioration in diabetic nephropathy and other glomerular diseases, but its role in quiescent lupus nephritis has not been established. We conducted a retrospective study to investigate the effects of ACEI/ARB on proteinuria and renal function in patients with persistent proteinuria (>1 g/day) despite resolution of acute lupus nephritis following immunosuppressive treatment. Fourteen out of 92 patients were included. The duration of treatment with ACEI/ARB was 52.1 +/- 35.7 months. The levels of proteinuria, serum albumin, serum creatinine, systolic and diastolic blood pressure were 1.10 to 6.90 g/day, 35.8 +/- 3.6 g/L, 102.54 +/- 34.48 micromol/L, 137.6 +/- 10.9 and 81.9 +/- 9.2 mmHg at baseline. Proteinuria and serum albumin showed significant sustained improvements after 6 and 24 months of treatment. Comparison of slopes for serial proteinuria, albumin and reciprocal of serum creatinine before and after treatment showed significant improvements in six (43%), eight (57%) and two patients, respectively. At last follow-up proteinuria remained significantly lower (0.36 g/day, P = 0.043) and albumin higher (41.3 +/- 2.2 g/L, P = 0.023). Eleven (78.6%) patients had proteinuria improved by >50%, and five had insignificant proteinuria at last follow-up. Systolic blood pressure was significantly reduced from 6 months onwards, but this did not correlate with proteinuria reduction. Diastolic blood pressure, serum creatinine, creatinine clearance, anti-dsDNA, C3 and haemoglobin were not altered. We conclude that ACEI/ARB effectively reduces proteinuria and improves serum albumin in patients with persistent proteinuria despite quiescent lupus nephritis.
Lupus 2005
PMID:Angiotensin inhibition or blockade for the treatment of patients with quiescent lupus nephritis and persistent proteinuria. 1642 74

To investigate whether the ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (E') (E/E' ratio) can detect left ventricular diastolic dysfunction more sensitively than the ratio of E to mitral peak velocity of late filling (A) (E/A ratio) in systemic lupus erythematosus (SLE). A total of 137 patients with SLE were investigated and compared with 110 age-matched and sex-matched controls retrospectively. Two-dimensional echocardiography and M-mode echocardiography including conventional and tissue Doppler imaging were performed. There were no differences in the left ventricle ejection fractions and the mean E/A ratio between the two groups. However, the mean E/E' ratio of patients was higher than that of the controls (10.4 +/- 4.0 vs 7.7 +/- 2.1, P < 0.01). Significantly higher left ventricle ejection fractions and lower E/E' ratio were found in patients with systemic lupus erythematosus receiving angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker than those not receiving (P < 0.05). Our study showed that the E/E' ratio is more sensitive than the E/A ratio for detection of the left ventricle diastolic dysfunction. Furthermore, patients who had received angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker treatment showed significantly better preservation of both systolic and diastolic function of left ventricle in comparison with those who had not received.
Lupus 2008 Mar
PMID:E/E' ratio is more sensitive than E/A ratio for detection of left ventricular diastolic dysfunction in systemic lupus erythematosus. 1837 59

Systemic lupus erythematosus is generally recognized to be a multisystem autoimmune disease with kidney involvement. However, the occurrence of other non-lupus glomerulopathies has been rarely reported in patients with systemic lupus erythematosus. It is well known that lupus nephritis may switch over time to another class according to the World Health Organization classification. It seems likely that IgA nephropathy is a clinical characteristic of a particular subset of patients with systemic lupus erythematosus. We report a 22-year-old Japanese man with recurrence of proteinuria. The renal flare occurred when he was without lupus clinical and serological activity, and renal remission was only obtained with angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker therapy. Although the incidence of IgA nephropathy is high in Japan, we believe that this is the first report of a Japanese patient in which lupus nephritis switched over time to IgA nephropathy.
Lupus 2010 Apr
PMID:IgA nephropathy in a patient with systemic lupus erythematosus. 2013 45

A 66-year-old man presented to the outpatient dermatology clinic with a chief complaint of a pruritic rash on his upper trunk and proximal upper extremities, which had been present for three weeks. Upon examination, he was found to have an erythematous, annular, and polycyclic eruption on the chest, upper back, and proximal extremities. A clinical diagnosis of subacute cutaneous lupus erythematosus (SCLE) was made. The patient was found to have a positive anti-nuclear antibody (ANA) in a speckled pattern and a positive anti-Ro antibody. A biopsy revealed an interface and lichenoid dermatitis with dermal mucin deposition, consistent with subacute cutaneous lupus erythematosus. The patient reported that he had recently been diagnosed with hypertension and began treatment with olmesartan, a potassium-sparing diuretic that blocks the angiotensin II receptor, commonly used as an antihypertensive or in patients with heart failure. Cutaneous reactions to olmesartan are rare and reported in &lt;1% of patients in post-marketing surveillance. The patient discontinued use of olmesartan and the rash completely resolved within three weeks. To date, there are no other reported cases of drug induced SCLE in patients taking olmesartan to our knowledge.
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PMID:Drug-induced anti-Ro positive subacute cutaneous lupus in a man treated with olmesartan. 3204 61