Successive treatment with cyclosporine and infliximab in steroid-refractory ulcerative colitis.

OBJECTIVES: Rescue therapy with either cyclosporine (CYS) or infliximab (IFX) is an effective option in patients with intravenous steroid-refractory attacks of ulcerative colitis (UC). In patients who fail, colectomy is usually recommended, but a second-line rescue therapy with IFX or CYS is an alternative. The aims of this study were to investigate the efficacy and tolerance of IFX and CYS as a second-line rescue therapy in steroid-refractory UC or indeterminate colitis (IC) unsuccessfully treated with CYS or IFX. METHODS: This was a retrospective survey of patients seen during the period 2000-2008 in the GETAID centers. Inclusion criteria included a delay of <1 month between CYS withdrawal (when used first) and IFX, or a delay of <2 months between IFX (when used first) and CYS, and a follow-up of at least 3 months after inclusion. Time-to-colectomy, clinical response, and occurrence of serious adverse events were analyzed. RESULTS: A total of 86 patients (median age 34 years; 49 males; 71 UC and 15 IC) were successively treated with CYS and IFX. The median (± s.e.) follow-up time was 22.6 (7.0) months. During the study period, 49 patients failed to respond to the second-line rescue therapy and underwent a colectomy. The probability of colectomy-free survival (± s.e.) was 61.3 ± 5.3% at 3 months and 41.3 ± 5.6 % at 12 months. A case of fatal pulmonary embolism occurred at 1 day after surgery in a 45-year-old man. Also, nine infectious complications were observed during the second-line rescue therapy. CONCLUSIONS: In patients with intravenous steroid-refractory UC and who fail to respond to CYS or IFX, a second-line rescue therapy may be effective in carefully selected patients, avoiding colectomy within 2 months in two-thirds of them. The risk/benefit ratio should still be considered individually.

[Functional bowel disorders: impact and limitations of evidence-based medicine]. / Troubles fonctionnels intestinaux: apports et limites de la médecine basée sur les preuves.

Although tremendous efforts have been carried out to explore the physiopathology, classification and therapeutic modalities of functional bowels disorders, these conditions still elude the classical anatomical-clinical approach. This article summarizes recent advances in the field, discusses critically their impact on daily clinical practice and provides some practical recommendations.

[Persistent diarrhea in the returned traveler]. / Diarrhée persistante du voyageur.

Persistent diarrhea in a returned traveler is a frequent presenting complaint and may result from three etiologic groups: persistant infections, non-infectious post-gastroenteritis processes (in particular postinfectious irritable bowel syndrome) and appearance of an unrelated cause of chronic diarrhea. This article reviews the most frequent diseases involved and provides management guidelines for primary care physicians.

[Celiac disease in disguise]. / Maladie coeliaque de l'adulte: le jeu des masques.

Contrarily to a widely prevalent opinion, celiac disease frequently affects adults, and only rarely reveals itself by the classical triad of diarrhea--weight loss--nutritional deficiency. In addition to isolated deficiencies, most frequently iron and calcium-vitamin D, celiac disease is commonly associated with atypical, sometimes very commonplace manifestations, such as abdominal symptoms reminiscent of those of irritable bowel syndrome, or type I diabetes. The diagnostic process is now made easier by the availability of antitransglutaminase antibodies dosage, a simple, trustworthy, sensitive and specific test. This review article discusses the many clinical pictures which should prompt the clinician to rule out celiac disease, and provides practical guidelines as to the use and interpretation of serologic tests.

Low-dose oral microemulsion ciclosporin for severe, refractory ulcerative colitis.

BACKGROUND: The optimal modalities of treatment with oral microemulsion ciclosporin in patients with severe, steroid-refractory ulcerative colitis are uncertain. AIM: To assess the applicability, in terms of efficacy and tolerability, of a standard oral microemulsion ciclosporin treatment protocol targeting relatively low blood ciclosporin concentrations, in patients with severe, steroid-resistant ulcerative colitis. PATIENTS AND METHODS: Patients with a severe attack of ulcerative colitis and no satisfactory response to intravenous corticosteroids were started on oral microemulsion ciclosporin. Dosages were adapted according to a standard protocol, targeting a blood predose ciclosporin concentration (C0) of 100-200 ng/mL. Patients without a clinical response on day 8 were scheduled for colectomy. RESULTS: Sixteen patients were enrolled. A clinical response was observed in 14/16 (88%). The mean clinical activity index scores and concentrations of C-reactive protein on days 0, 4 and 8 were 11.8, 6.7 and 4.1, and 50.3, 19.3 and 9.7 mg/L respectively. The mean C0 (days 0-8) was 149 pg/mL. The mean creatinine clearance rates on days 0 and 8 were 88 and 96 mL/min. One patient had an acute elevation of transaminases that resulted in discontinuing ciclosporin. CONCLUSIONS: Even when dosed for a target C0 of 100-200 ng/mL, oral microemulsion ciclosporin for severe, steroid-refractory ulcerative colitis achieves an efficacy similar to that attained with higher, potentially more toxic levels. The oral route should replace intravenous treatment in this clinical setting.

A prospective assessment of cytomegalovirus infection in active inflammatory bowel disease.

BACKGROUND: The prevalence and clinical significance of cytomegalovirus infection is reportedly high in patients with refractory inflammatory bowel disease but is unknown in unselected patients with active disease. METHODS: In patients admitted for active inflammatory bowel disease, we prospectively studied the presence and significance of cytomegalovirus infection using anti-cytomegalovirus antibodies, cytomegalovirus viraemia and antigenaemia and cytomegalovirus inclusions and cytomegalovirus immunochemistry staining in ileocolonic biopsies. RESULTS: A total of 64 patients were included (ulcerative colitis, n = 23; Crohn's disease, n = 41), 18 of whom had been on high-dose oral steroids and 11 on immunosuppressants. Anti-cytomegalovirus IgG and IgM were positive in 42 (66%) and 3 (5%) patients respectively. Blood or urine cytomegalovirus replication markers were found in 4 (6%) patients, all of whom had ulcerative colitis. Three patients had cytomegalovirus viraemia and received anti-viral treatment with ganciclovir. Only one of these patients had cytomegalovirus antigenaemia and also associated biopsy-proven cytomegalovirus colitis, probably as a primary cytomegalovirus infection. This patient is the only one who benefitted from anti-viral therapy. CONCLUSIONS: Cytomegalovirus infection is infrequent in in-patients with active inflammatory bowel disease. Systematic search of cytomegalovirus replication markers should not be performed. Isolated viraemia without associated antigenaemia or direct demonstration of cytomegalovirus in ileocolonic biopsies does not warrant anti-viral therapy.

Pseudomembranous colitis: an unusual cause of neutrocytic ascites.

Severe cases of pseudomembranous colitis (PMC) may be associated with intraperitoneal fluid accumulation. However, the characteristics of the liquid are seldom described. Specifically, neutrocytic ascites has only been reported once. We report a case of a severe PMC complicated by a highly neutrocytic ascites which remained culture-negative. We discuss the possible mechanisms leading to ascites formation in this condition and review ascitic fluid characteristics in patients with PMC.

[Clinical presentation of primary cytomegalovirus infection in a non-immunodepressed adult]. / Présentation clinique de l'infection primaire a cytomégalovirus chez l'adulte non immunodéprimé.

In the immunocompromised patients and during foetal life an acute infection due to the cytomegalovirus (CMV) causes great morbidity. In adults without predisposing factors the acute infection with CMV is rarely symptomatic, but can also provoke fever, fatigue, headache and anorexia for weeks. The peripheral blood smear shows big atypical lymphocytes within a relative lymphocytosis. The suspicion of the CMV infection is confirmed by the serological evidence of IgM anti-CMV antibodies. There is no etiological treatment, the evolution is spontaneously favorable most of the time. Establishing the diagnosis is reassuring for the patient and for the physician and avoids unnecessary analyses and treatments. We describe a series of 11 adults without predisposing factors who contracted an acute cytomegalovirus infection.

Symptomatic primary infection due to human immunodeficiency virus type 1: review of 31 cases.

In this series of 31 patients with acute infection due to human immunodeficiency virus (HIV) type 1, the male-to-female ratio was 3.4:1 and the mean age was 31.3 years. Sexual transmission accounted for 83.9% of cases; 45.2% of the patients were homosexual and 38.7% were heterosexual. The mean duration of symptoms and signs was 21 days (range, 5-60 days). Fever (87.1%) and skin rash (67.7%) were most commonly reported. Physical examination findings were abnormal for 96% of the patients; the oral cavity (76.7%) and the skin (73.3%) were the most frequently involved sites. Thirteen of 25 patients with sexually acquired infection had genital or oral ulcers, whereas five intravenous drug users had none (P = .052). Thrombocytopenia was the most common hematologic abnormality and was detected in 17 of 23 patients tested. P24 antigenemia, an initially negative screening test for HIV antibody, and a low CD4+ lymphocyte count were noted in 23 of 29, 23 of 30, and 14 of 21 tested patients, respectively.

Human immunodeficiency virus type 1 nucleic acids detected before p24 antigenemia in a blood donor.

A blood donation from a 46-year-old homosexual man was discarded because of elevated alanine aminotransferase levels. Thirteen days later, the patient presented with symptomatic primary human immunodeficiency virus type 1 (HIV-1) infection. Virologic investigations were performed retrospectively on blood samples (including the donated blood) obtained before the symptoms. The HIV-1 genome was present, either integrated in mononuclear cell DNA or circulating in plasma, 39 days before the appearance of p24 antigen and 65 days before the appearance of HIV-1 or HIV type 2 antibody. It is concluded that p24 antigenemia is present during only a fraction of the seronegative "window" period. This case illustrates the risk of infection associated with blood transfusion in spite of HIV-1 antibody testing and stresses the need to improve nontechnical exclusion procedures as well as non-antibody-based diagnostic tests.

[ALAT and viral RNA as risk factors in 68 blood donors with anti-hepatitis C antibodies]. / Facteurs de risque, ALAT et RNA viral chez 68 donneurs de sang avec anticorps anti-hépatite C.

AIM: Determine the risk factors in blood donors with anti hepatitis C antibodies (anti-HCV ab) possible liver involvement and evaluation of their infectious potential by a search for viral RNA in blood. METHODS: Between July 1990 and October 1991, 19,632 blood donors were screened for hepatitis C. Antibodies to HCV were detected in 74 donors (2nd generation ELISA, Abbott). We evaluated the risk factors, determined ALAT levels and looked for circulating RNA virus by amplification of the non-coding region of the viral genome (RTPCR) in 68 of these 74 donors screened. A control was chosen arbitrarily from 103 donors with high ALAT levels, but with no antibodies to HCV nor detectable circulating viral DNA. RESULTS: The prevalence of anti-HCV ab in blood donors in 0.37%. No risk factor was found in 29 donors (43%). Parenteral exposure (former i.v. drug addiction and history of transfusions) was found to be the mode of transmission of hepatitis C in 23 donors (34%). History of NANB jaundice (non-post transfusion) was reported in 1 donor (1%). The remaining 15 donors (22%) were found to have minor risk factors - either isolated or in combination (exposure, tatoos, multiple sexual partners). Former i.v. drug addiction (p = 0.0000006) as well as a history of transfusions (p = 0.0071) are significantly more frequent in the group of donors with antibodies to HCV. None of the 35 sexual partners of the tested donors proved to be positive. 21 donors (30%) had high ALAT (+2 SD). Viral RNA was detected in blood of 26 donors (38%). The proportion of cases with positive viral RNA was 61% if only those donors with high ALAT levels were taken into consideration (13 positive of 21). CONCLUSIONS: Risk factors were found in 39 donors (57%) with antibodies to HCV. History of parenteral exposure was found to be significantly more frequent than in the control group (p = 0.0000054). Sexual transmission within couples was not demonstrated in the population tested. A positive PCR test is a probable indicator of a continuous viral replication and reflects a possible chronic hepatic involvement as well as a potential infectivity. This test is positive in at least 38% of donors with antibodies to HCV and in more than 60% of those who, in addition, have high ALAT levels.

Hepatitis C: a possible etiology for cryoglobulinaemia type II.

Out of 15 successive patients with mixed essential cryoglobulinaemia type II (monoclonal IgM kappa/IgG), 13 had serological evidence for hepatitis C infection as shown by specific enzyme immunoassays and immunoblot. RNA was purified from the serum of seven patients and hepatitis C sequences were identified in five following reverse transcription and DNA amplification. The liver histology showed chronic active hepatitis with or without cirrhosis in the 12 patients with hepatitis C who had a liver biopsy. The two patients without serological evidence of hepatitis C suffered from haematological malignancies. Hepatitis C may be a major etiological agent of cryoglobulinaemia type II.

[HTLV-I/II in Switzerland: apropos of 4 case reports]. / HTLV-I/II en Suisse: à propos de quatre observations.

HTLV-I/II (human T-cell lymphotropic virus type I and II) infection is endemic in South Japan, Subsaharan Africa, the Caribbean and in regions of South America and of the United States. The infection almost always remains asymptomatic but is also associated with two distinct diseases: tropical spastic paraparesis (TSP), and adult T-cell leukemia (ATL). Although very rare in Europe, HTLV-I/II infection may occur in patients originating from endemic areas. We report the cases of four patients seropositive for HTLV-I/II, all of them living in Switzerland. Three of them originate from Zaire; the fourth is a Swiss female married to a Taiwanese. One patient has TSP; one has pyramidal signs along with systemic vasculitis-associated neuropathy; the third is HIV-position with stage III B infection, without symptoms of TSP or ATL; the last is entirely asymptomatic.