Drug-induced pseudo-Sezary syndrome: a case report and literature review.

Pseudo-Sezary syndrome is a benign lymphoproliferative disorder, which clinically and pathologically mimics true Sezary syndrome. In this article, a case of pseudo-Sezary syndrome and review the literature has been reported. The patient was a 51-year-old man who developed erythroderma and palmoplantar keratoderma. The patient's medication history included fosinopril and combination metoprolol/hydrochlorothiazide. Flow cytometry showed a population of 2500 "Sezary-like" CD4726 T cells per microliter in the peripheral blood. Skin biopsy showed numerous atypical lymphocytes with epidermotropism, and there was matching dominant T-cell clonality in the skin and peripheral blood. After stopping all antihypertensive medications, the eruption resolved in its entirety.

Meta-analysis of randomized controlled trials on effect of angiotensin-converting enzyme inhibitors on cancer risk.

The renin-angiotensin system is an important mediator of tumor progression and metastasis. A recent meta-analysis of randomized controlled trials reported an increased risk of cancer with angiotensin receptor blockers. It is unknown whether angiotensin-converting enzyme (ACE) inhibitors may have a similar effect. Our primary objective was to determine the effect of ACE inhibitors on cancer occurrence and cancer death. Our secondary objective was to determine the effect of ACE inhibitors on occurrence of gastrointestinal (GI) cancers given previous concerns of increased risk. Systematic searches of SCOPUS (covering MEDLINE, EMBASE, and other databases) and the Food and Drug Administration official web site were conducted for all randomized controlled trials of ACE inhibitors. Trials with ≥1 year of follow-up and enrolling a minimum of 100 patients were included. Fourteen trials reported cancer data in 61,774 patients. This included 10 trials of 59,004 patients providing information on cancer occurrence, 7 trials of 37,515 patients for cancer death, and 5 trials including 23,291 patients for GI cancer. ACE inhibitor therapy did not have an effect on occurrence of cancer (I(2) 0%, risk ratio [RR] 1.01, 95% confidence interval [CI] 0.95 to 1.07, p = 0.78), cancer death (I(2) 0%, RR 1.00, 95% CI 0.88 to 1.13, p = 0.95), or GI cancer (RR 1.09, 95% CI 0.88 to 1.35, p = 0.43). In conclusion, ACE inhibitors did not significantly increase or decrease occurrence of cancer or cancer death. There was also no significant difference in risk of GI cancer.

Successful treatment of fosinopril-induced severe cholestatic jaundice with plasma exchange.

OBJECTIVE: To describe a case of fosinopril-induced severe cholestatic jaundice successfully treated with plasma exchange. CASE SUMMARY: A 78-year-old Taiwanese male presented with yellowish skin and generalized itching one month after starting fosinopril 10 mg once a day. Other drugs taken by the patient were excluded as the probable cause of jaundice. Diagnostic modalities, including abdominal ultrasound, computed tomography, and endoscopic retrograde cholangiopancreatography, revealed no evidence of biliary tract obstruction or intraabdominal tumor. According to the Council for International Organizations of Medical Science (CIOMS) scale, fosinopril was a highly probable cause of the patient's jaundice. Liver biopsy showed cholestasis without bile duct damage. Based on results of the CIOMS scale assessment and pathological characteristics of the liver, the diagnosis was highly probable that fosinopril had induced cholestatic jaundice in our patient. During hospitalization, the patient developed severe jaundice and liver failure, despite conservative treatment and withdrawal of fosinopril. He underwent a 5-day course of plasma exchange therapy, and the serum bilirubin level declined rapidly after treatment. His liver function returned to normal 2 months after treatment. DISCUSSION: Angiotensin-converting enzyme (ACE) inhibitor-induced hepatotoxicity is rare and only a few cases, with most involving captopril, have been reported in the English-language literature. Hepatotoxicity caused by fosinopril is extremely rare. Most ACE inhibitor-induced hepatotoxicity is mild and transient, but it can be fatal. Although orthotopic liver transplantation (OLT) is the standard method for treating drug-induced liver failure, plasma exchange therapy is an alternative therapeutic method or a bridge to OLT for treating liver failure. CONCLUSIONS: Plasma exchange therapy may play a valuable role in the treatment of fosinopril-induced cholestatic jaundice and liver failure. This intervention can be considered for temporary liver support until recovery or OLT.

Simultaneous posterior ischemic optic neuropathy, cerebral border zone infarction, and spinal cord infarction after correction of malignant hypertension.

A 31-year-old woman developed bilateral posterior ischemic optic neuropathy and infarctions of the cerebral arterial border zones and spinal cord after correction of malignant hypertension. Although a few reports have described patients with neurologic abnormalities after treatment of malignant hypertension, full clinical and neuroimaging documentation of this combination of findings has not occurred. This case report suggests that the relative hypotension of autoregulatory failure induced by treatment of malignant hypertension may give rise to these neurologic complications.

Transient recurrent ascites.

Angiotensin-converting enzyme (ACE) inhibitors are widely used in heart diseases. We describe a case of a young woman treated with fosinopril. She started experiencing abdominal pain, vomiting and diarrhoea with peritoneal signs on physical examination three years after her treatment has been initiated. She presented ascites and signs of ileitis on imaging studies. She even underwent surgery. The diagnosis of ACE inhibitor-induced angiooedema of the small bowel was made after the fourth episode. Fosinopril was stopped and the symptoms never recurred. The case we describe illustrates clinical presentation, radiological findings and difficulty of making an accurate diagnosis in such a patient.

Cardiorenal protective effects of vasopeptidase inhibition with omapatrilat in hypertensive transgenic (mREN-2)27 rats.

Vasopeptidase inhibitors simultaneously inhibit both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). The aim of this study was to determine the cardiorenal effects of the vasopeptidase inhibitor omapatrilat in the transgenic m(Ren-2)27 rat which exhibits fulminant hypertension and severe organ pathology. At 6 weeks of age, male Ren-2 rats were randomized to receive no treatment (N = 10), the ACE inhibitor fosinopril 10 mg/kg/day (N = 10), or omapatrilat 10 mg/kg/day (N = 10) or 40 mg/kg/day (N = 10) by daily gavage for 24 weeks. Various cardiorenal functional and structural parameters were assessed. Compared to controls, all treatment groups reduced hypertension in control Ren-2 rats, with both doses of omapatrilat reducing systolic blood pressure significantly more than fosinopril (control, 178 +/- 3 mmHg; fosinopril 10 mg/kg/day, 130 +/- 4 mmHg; omapatrilat 10 mg/kg/day, 110 +/- 3 mmHg; omapatrilat 40 mg/kg/day, 91 +/- 3 mmHg). Omapatrilat dose-dependently reduced cardiac hypertrophy, caused a greater inhibition of renal ACE than fosinopril, and was the only treatment to inhibit renal NEP. Attenuation of albuminuria, glomerulosclerosis and cardiorenal fibrosis occurred to a similar degree with omapatrilat and fosinopril. Omapatrilat confers cardiorenal protection in the hypertensive Ren-2 rat. Although inhibition of tissue NEP may contribute to the superior blood pressure reduction by omapatrilat, overall, the results are consistent with the central role that angiotensin II plays in renal and cardiac fibrosis in this model of hypertension.

Ramipril-associated hepatotoxicity.

CONTEXT: Angiotensin-converting enzyme inhibitors are prescribed for many cardiovascular and renal diseases. Adverse hepatic events, especially cholestasis, have rarely been reported with captopril, enalapril, lisinopril, and fosinopril. To date, hepatic injury associated with ramipril has not been reported. OBJECTIVE: To describe 3 patients who developed hepatitis, with or without jaundice, after receiving ramipril. DESIGN: Medical records and liver biopsies of the 3 patients were reviewed. Clinical, laboratory, and histologic findings were compared with findings in other cases of angiotensin-converting enzyme inhibitor-induced liver injury reported in the literature. RESULTS: The 3 patients were middle-aged men. In 2 patients, jaundice appeared 4 and 8 weeks after starting ramipril. Bilirubin levels peaked at 15.5 and 5 mg/dL, and alkaline phosphatase values peaked at 957 and 507 U/L. Aminotransferase levels were mildly elevated. Endoscopic retrograde cholangiopancreatography and ultrasonography showed no bile duct obstruction. Liver biopsies from the jaundiced patients were similar, with cholestasis, duct necrosis, and extravasation of bile, ductular proliferation, and portal inflammation. Cholestasis improved in 1 patient 6 weeks after stopping ramipril and was prolonged for 14 months in the other, in whom biliary cirrhosis was present on biopsy. The third patient developed hepatitis without jaundice 3 weeks after starting ramipril; symptoms resolved after stopping the drug. Ramipril-associated liver injury is similar to that seen with other angiotensin-converting enzyme inhibitors, but liver biopsy findings of duct necrosis and extravasation of bile have not been reported previously. CONCLUSION: Prolonged cholestatic hepatitis and biliary cirrhosis may result from the use of ramipril. Monitoring of liver enzymes is advisable for patients starting on ramipril.

Fosinopril-induced prolonged cholestatic jaundice and pruritus: first case report.

We report a case of fosinopril-induced prolonged cholestatic jaundice and pruritus in a 61-year-old man, with no previous hepatobiliary disease, who presented with asthenia, jaundice and itching 3 weeks after starting fosinopril therapy. Other drugs taken by the patient were not considered probable causes. The diagnostic evaluation showed no biliary obstruction and other possible causes of intra-hepatic cholestasis were excluded. Liver biopsy showed cholestasis without bile duct damage. The disease ran a severe course during the 2 months of hospitalization, with prolonged itching for 6 months, eventually controlled with oral naltrexone. Jaundice subsided after 4 months, with anicteric cholestasis persisting for more than 18 months. Similar occurrences have been reported with other inhibitors of angiotensin-converting enzyme (mostly captopril), but this is the first case of an important adverse reaction to fosinopril.

ACE inhibitor-induced angioedema of the intestine: Case report, incidence, pathophysiology, diagnosis and management.

A case report of fosinopril-induced angioedema of the intestine with a chronic course accompanied by multiple acute exacerbations is described. Angiotensin-converting enzyme (ACE) inhibitor-induced angioedema of the intestine (AIAI) occurs in a minority of patients taking an ACE inhibitor. The clinical presentation encompasses acute abdominal symptoms, pronounced bowel edema and ascites with occasional facial and/or oropharyngeal swelling. AIAI is diagnosed based on the temporal relationship between the symptomatic presentation and drug use, absence of alternative diagnoses including other causes of angioedema, and the prompt resolution of symptoms upon discontinuation of the ACE inhibitor. Prompt radiological investigation (abdominal computerized tomography and/or ultrasound) is critical in making an early diagnosis and in preventing unnecessary surgical intervention. There is a female predominance of AIAI, which may reflect the interaction of estradiol with the various pathways involved in the pathophysiology of AIAI. Management of AIAI consists mainly of conservative measures and discontinuation of the ACE inhibitor. Angiotensin II receptor antagonists should not be considered as appropriate alternatives. Awareness and knowledge of AIAI are important because of the increasing use of ACE inhibitors, current delays in making the diagnosis, obvious management strategies once the diagnosis is made and the dysutility of alternative diagnoses, which may lead to considerable morbidity. AIAI must be considered in patients taking ACE inhibitors who develop gastrointestinal complaints irrespective of the duration of the therapy.

Drug-related pemphigus and angiotensin converting enzyme inhibitors.

A 105-year-old woman developed pemphigus foliaceus. She had been on fosinopril, an angiotensin-converting enzyme inhibitor (ACE inhibitor) for 4 years. Anti-intercellular cement substance antibodies were positive with titre > 160. She died during admission of an unrelated illness. A 57-year-old man developed pemphigus vulgaris after 11 months treatment with quinapril. At 14 months after developing pemphigus, this man continues on prednisone and azathioprine. We speculate that these are cases of ACE-inhibitor-related pemphigus and we review ACE-inhibitor-related pemphigus.

Isolated visceral angioedema: an underdiagnosed complication of ACE inhibitors?

Angiotensin-converting enzyme (ACE) inhibitors are known to cause potentially fatal peripheral angioedema in some patients. ACE inhibitors may also cause isolated visceral angioedema, a rarely reported complication. This article describes 2 patients who experienced this complication. Both patients came to medical attention with episodes of recurrent abdominal symptoms that had occurred while taking ACE inhibitors for hypertension. Each patient had undergone surgical procedures for symptoms that persisted after surgery and were ultimately relieved with cessation of their ACE inhibitors. These cases call attention to what may be an underappreciated cause of abdominal pain in patients presenting to emergency departments.

Transient myocardial dysfunction associated with angiotensin-converting enzyme inhibitor-induced angioedema: recognition by serial echocardiographic studies.

We report a case of a 58-year-old woman who had angiotensin converting enzyme inhibitor-induced angioedema after she underwent a biopsy of a hypopharyngeal mass. The angioedema was associated with severe transient myocardial dysfunction documented on echocardiography. She did not have anaphylaxis or coronary artery disease. To our knowledge this is the first reported case of transient myocardial dysfunction in the setting of angiotensin converting enzyme inhibitor-induced angioedema without anaphylaxis.

Tratamento da hipertensão arterial leve e moderada com fosinopril: comparaçäo de efeitos adversos com outros anti-hipertensivos / Treatment of Mild-to-Moderate Hypertension with Fosinopril. Adverse Reactions Compared with other Antihypertensives

PURPOSE--To evaluate the adverse reactions of fosinopril with other antihypertensives used as monotherapy. METHODS--Out-patients (n = 2,568) with diagnostic of mild to moderate hypertension, diastolic blood pressure (DBP) 95-115mmHg, with no antihypertensive treatment for 15 days, were included to treatment initially with fosinopril (F) 10mg, once daily, for six weeks. After this period, patients with DBP > 95mmHg had the dosage, once daily, increased to 20mg, while the others were maintained with the same dosage for six more weeks. Adverse reactions of 822 patients treated as monotherapy were grouped as absent, musculoskeletal, cardiovascular, cough, gastrointestinal, neurological, genital-urinary dysfunctions and dermatological and compared with 1,568 with F. Monotherapy consist in alpha-methyldopa (100 patients); beta-blocker (129); calcium blocker (106); diuretic (394); and another ACE inhibitors (93). RESULTS--At the end of the period without treatment, the blood pressure (BP), 165 +/- 16/105 +/- 7mmHg decreased significantly at 6th week to 144 +/- 15/91 +/- 9mmHg (p < 0.05 vs week 0) with further lowering to 139 +/- 13/86 +/- 7mmHg till the end of 12th week. BP response (DBP < or = 90mmHg) was obtained in 89per cent of the patients with F. Absence of adverse reactions were > or = 70 per cent in patients with F compared to other drugs. CONCLUSION--Fosinopril has demonstrated therapeutic efficacy and less adverse reactions compared to antihypertensives used previously as monotherapy