Dimitrios K. Christodoulou

Axillary hidradenitis suppurativa successfully treated with infliximab in a Crohn’s disease patient

Accident and Emergency department after a road traffic accident. He reported that, 2 days earlier, he had started to hear male voices talking about him in a derogatory manner. He also described visual hallucinations taking the form of strangers sitting in his room conversing with him. He was unaware that these experiences could be related to his recent steroid therapy, and he refused to leave his house. On the day of the accident, he started taking alcohol to combat the hallucinations. Some time later, he reported hearing a knock at his door and described seeing a group of unknown men on his doorstep commanding him to rob a nearby petrol station. He described being distracted by seeing the intruders follow him in a car and, as a consequence, he crashed into a disused railway line. Surprisingly, he escaped with relatively minor injuries. He was admitted to the hospital and continued to experience both complex visual and auditory hallucinations, constantly needing reassurance from nursing staff. There was no evidence of any mood disturbance, disorientation or alteration of consciousness. Psychiatric assessment established a diagnosis of steroid-induced psychosis. He was commenced on haloperidol 2.5 mg t.i.d., lorazepam 2 mg as required, and his steroids were reduced. He responded rapidly and was completely free of psychotic symptoms within a week. He was discharged on prednisolone 15 mg daily and had remained well at 1-month follow-up. This case illustrates the potentially serious nature of psychiatric symptoms arising from steroid therapy. There is some evidence of a dose-related effect but little information regarding other risk factors. In one study, psychiatric symptoms were recorded in 1.3% of patients receiving more than 40 mg of steroids, 4.6% of those receiving 40 – 80 mg daily, and 18.4% in patients on doses higher than 80 mg daily (3). However, reports also exist of adverse effects after exposure to very low doses, and there does not appear to be a correlation between dose and time of onset or type of disorder (4). Moreover, there is no evidence to suggest that past psychiatric history, previous steroid induced psychiatric disorder, or specific medical disorders help to identify individuals at risk (5). Clearly, identifying risk factors and measures to prevent steroid-related psychiatric disorders require further study. However, in the absence of clear clinical predictors, physicians need to be aware of the range of psychiatric disorders arising in the context of steroid use. We would strongly recommend that all patients treated with steroids, particularly at higher doses, are educated as to possible psychiatric symptoms associated with steroid use. Ideally, assessment of mental state including cognitive assessment should be carried out at baseline and repeated once the patient commences therapy. If there is evidence of emerging psychopathology, then a psychiatric consultation may be indicated. Information facilitating informed consent in the usage of these drugs might obviate the level of distress arising for patients developing psychiatric symptoms and avoid potentially fatal outcomes.

Spectrum and frequency of ophthalmologic manifestations in patients with inflammatory bowel disease: a prospective single-center study.

Background: The frequency and spectrum of ophthalmologic manifestations in patients with inflammatory bowel disease (IBD) has been reported to vary among studies; however, rare and silent manifestations have not been extensively studied. Methods: This was a prospective study of 60 patients diagnosed with IBD who underwent full ophthalmologic examination, including visual acuity, slit lamp examination of the anterior segments, intraocular pressure, and fundus examination accompanied by color photography. Thirty‐seven (61,7%) patients were diagnosed with ulcerative colitis (UC) and 23 (38,3%) with Crohns disease (CD). Data from 276 control individuals were used for the determination of the prevalence of dry eye in our area. Results: Ophthalmologic manifestations were diagnosed in 26 (43%) patients (14 UC, 12 CD; 12 males and 14 females). Conjunctivitis was diagnosed in 1 patient (CD), episcleritis in 2 patients (UC), and iridocyclitis in 3 (CD). Fundus examination showed 1 patient (CD) with unilateral choroiditis, 1 (UC) with retinal vasculitis, and 1 (CD) with optic neuritis. Retinal pigment epithelium disturbances (RPED) were present in 3 patients (1 CD, 2 UC) and 2 had serous retinal detachment. In total, 13/60 patients (22%) had dry eye compared with the 11% prevalence in controls. Eight patients developed glucocorticosteroid‐induced cataracts, 2 of them treated surgically. Conclusions: This study demonstrated the prevalence of the spectrum of ophthalmologic manifestations in the IBD population, including some rare and silent findings that may merit consideration and early intervention.

A prospective evaluation of dermatological side-effects during alpha-interferon therapy for chronic viral hepatitis.

OBJECTIVE Alpha-interferon therapy may occasionally account for immune-mediated phenomena. This study was conducted in an attempt to investigate the incidence of the development of immune-mediated dermatological diseases during alpha-interferon therapy in patients with chronic viral hepatitis. The latter has not been evaluated prospectively, whereas most of the previous studies examined small numbers of interferon treated patients or consisted of case reports. DESIGN A prospective case-control study. SETTING A tertiary referral centre. PARTICIPANTS One hundred and twenty consecutive patients with chronic viral hepatitis (67 with hepatitis B, 45 with hepatitis C, six with both hepatitis viruses, and two with delta hepatitis) were evaluated during a course of alpha-interferon therapy. In addition, 120 consecutive patients with chronic liver diseases (disease control group), who had never received alpha-interferon therapy, were evaluated during the period of the study (at least for 12 months). INTERVENTIONS Recombinant alpha-interferon at a dose of 4.5 or 5 million units subcutaneously (s.c.) three times per week for 6 to 12 months was administered to patients with hepatitis B. The patients with chronic hepatitis C were treated with 3 million units s.c. three times per week for 12 to 18 months. The patients with chronic hepatitis B and C infections received 4.5 million units for 6 months, and then 3 million units for an additional 6 to 12 months. Finally, the patients with chronic delta hepatitis received 5 million units for 1 year or more. MAIN OUTCOME MEASURES To assess prospectively the incidence of these dermatological disorders during alpha-interferon therapy and to estimate if there is any relationship between their development and the clinical, laboratory or other characteristics of the patients with chronic hepatitis. RESULTS Three to 6 months after the initiation of alpha-interferon three patients with chronic viral hepatitis (two with hepatitis C and one with hepatitis B) developed lichen planus, whereas one patient with hepatitis C developed relapsing aphthous stomatitis. The development of these disorders was significantly associated only with the presence of antinuclear antibodies before the initiation of alpha-interferon (P=0.000000). None of the patients from the disease control group had such a manifestation during the follow-up. Lichen planus resolved after the end of therapy in all of them. In contrast, therapy was discontinued in the patient who developed aphthous stomatitis, owing to the painful lesions. CONCLUSIONS This study demonstrated that alpha-interferon may rarely (3.3%) induce immune-mediated dermatological disorders, especially lichen planus. The development of these disorders may reflect a subclinical or covert autoimmune background of patients, as suggested by the presence, although in low titres, of antinuclear antibodies. However, when lichen planus developed, it was mild, did not require the discontinuation of therapy and resolved after alpha-interferon administration had ceased.

Frequency of extraintestinal manifestations in patients with inflammatory bowel disease in Northwest Greece and review of the literature.

BACKGROUND Inflammatory bowel disease mainly affects the bowel but also has extraintestinal manifestations. AIMS To report the frequency of extraintestinal manifestations in patients with inflammatory bowel disease in Northwest Greece. PATIENTS; The data files of 256 inflammatory bowel disease patients (diagnosis between 1983-19971 were analysed. METHODS Retrospective investigation of patient files. RESULTS In patients with ulcerative colitis: 13.9% (30/215) had developed skin manifestations, 6% (13/215) had kidney stones, 1.39% (3/215) had iridocyclitis, 1.86% (4/215) had primary sclerosing cholangitis, 4.18% (9/215) had sacroiliitis, 8.31% (18/215) had peripheral arthalgias, 2.3% (5/215) had colitic arthritis and finally 1.39% (3/215) had deep vein thrombosis). In patients with Crohns disease: 24.3% (9/37) had developed skin manifestations, 5.4% (2/37) had kidney stones, 2.7% (1/37) had iridocyclitis, 16.2% (6/37) had sacroiliitis, 8.1% (3/37) had peripheral arthralgias, 5.4% (2/37) had colitic arthritis and, finally, 8.1% (3/37) had deep vein thrombosis. Sacroiliitis (p = 0.01), deep vein thrombosis (p = 0.04) and erythmema nodosum (p = 0.01) were more common in patients with Crohns disease. CONCLUSIONS Extraintestinal manifestations are not rare in patients with inflammatory bowel disease, especially in Crohns disease patients, in our area, but have, generally, a mild profile.

High prevalence of elevated liver enzymes in blood donors : associations with male gender and central adiposity

Objective Nonalcoholic fatty liver disease is an increasingly recognized condition, but its exact prevalence is unknown. In this prospective, multicenter study, we evaluated the prevalence of elevated alanine aminotransferase, aspartate aminotransferase, and &ggr;-glutamyl-transpeptidase levels as indirect markers of nonalcoholic fatty liver disease in volunteer blood donors as well as their associations with epidemiological and anthropometrical characteristics. Methods Alanine aminotransferase, aspartate aminotransferase and &ggr;-glutamyl-transpeptidase levels were determined in blood donors from four transfusion centers during the morning sessions of a 3-month period. Cases with positive hepatitis B surface antigen, anti-hepatitis C virus, anti-HIV or elevated liver enzymes and alcohol abuse were excluded. Results Abnormal liver enzymes were found in 17.6% of 3063 participants (alanine aminotransferase: 14.5%, aspartate aminotransferase: 4.6%, &ggr;-glutamyl-transpeptidase: 4.7%). Individuals with abnormal compared with those with normal liver enzymes or alanine aminotransferase values were more frequently men and had higher weight, body mass index, waist, hip and neck circumference (P<0.001 for all comparisons). The prevalence of abnormal liver enzymes was also associated with the transfusion center ranging between 8.8 and 22.1% (P<0.001) and alcohol consumption (P=0.001). In multivariate analysis, presence of elevated enzymes was independently associated with male sex, higher weight or body mass index, higher waist circumference and transfusion center. Conclusions More than 15% of Greek blood donors exhibit elevated liver enzymes, most likely as a result of unrecognized nonalcoholic fatty liver disease. The prevalence of nonalcoholic fatty liver disease is mainly associated with male sex, obesity and waist circumference, but it may range significantly among different population groups.

Cutaneous nevi pigmentosus during infliximab therapy in a patient with Crohn's disease: Fallacy or coincidence?

To the Editor: The probable association of anti–tumor necrosis factor (TNF) monoclonal antibody therapy with malignant conditions has been recently reported in two patients with inflammatory bowel disease (IBD) (1). This report implied the questionable role of anti–TNFtherapy in inducing lymphomas in two patients with Crohn’s disease. However, in a later study (2), it was suggested that the preclinical data and the early clinical experience presented for anti–TNF(infliximab) do not provide evidence for a causal relationship between TNFantagonism and the development of lymphoid or nonlymphoid cancers. Moreover, no evidence exists about the impact of infliximab on benign or hyperplastic conditions. We reported a 30-year-old man with Crohn’s disease who developed cutaneous nevi pigmentosus (Fig. 1) during infliximab infusions. The patient has been treated for the past 8 years with azathioprine (150 mg/d), methylprednisolone (8 mg/d), and mesalazine (3 g/d). Half a year ago, because of severe disease exacerbations, the patient began infliximab therapy (infusions every 8 weeks), which resulted in a very good clinical response. In the eighth month of infliximab therapy, the patient noticed colored nevi on the top of his left shoulder, one of which was continuously growing upward. After a dermatologic consultation, this nevus was surgically removed. Histology of the nevus was compatible with benign nevus pigmentosus, and the patient is now carefully being followed up, with no other lesions appearing. The questionable role of anti–TNFtherapy in inducing malignancy or hyperplastic conditions is yet to be clarified; premalignant conditions should also be included in this panel of discussion. Definitively answering this question is difficult because individuals with IBD have been reported to have an increased risk of malignancies, including increased risk of malignant melanoma in patients with Crohn’s disease (3). Moreover, patients with IBD who receive azathioprine, especially those with fair complexion, should be informed about the potential hazards of sunbathing. According to one case report, a woman with IBD who had frequently sunbathed developed intraepidermal carcinoma of the skin after 8 years of azathioprine treatment (4). Although there is an increased risk of nonmelanoma skin cancer in immunosuppressed transplant recipients, a similar danger has never been reported in patients with IBD. Unless the absolute risk of the development of malignancies (colonic and extracolonic) in patients with IBD is assessed extensively, no statements about the hyperplastic or carcinogenesis effects of any kind of therapy, especially the new biologic agents, should currently be generalized or adopted as guidelines.

High CA 19-9 levels in benign biliary tract diseases: Report of four cases and review of the literature

For years, CA 19-9 has been proposed as a marker for epithelial-type gastrointestinal cancers, even though it is well known that its diagnostic specificity is low. Here we describe cases of extremely high CA 19-9 levels in benign biliary tract diseases. The first case involved a 77-year-old male patient with choledocholithiasis and jaundice who was found to have CA 19-9 levels of 98,628 UI/ml. The second case was a 63-year-old male patient with autoimmune cholangitis and a CA 19-9 level of 250 IU/ml. The third case was a 74-year-old male patient with cholelithiasis and choledocholithiasis who developed acute cholangitis. CA 19-9 levels were elevated to 14,950 UI/ml during the episode. The fourth case involved a 73-year-old man with biliary colic and jaundice following an acute open cholecystectomy procedure who had a transient 100-fold increase in CA 19-9 (2230 IU/ml).

Association of Helicobacter pylori infection with cardiovascular disease—Is it just a myth?

OBJECTIVE To test the hypothesis that Helicobacter pylori infection is associated with a higher rate of documented cardiovascular disease (CVD) in subjects undergoing elective upper gastrointestinal endoscopy. METHODS 202 consecutive patients (median age 60 years, 101 men) were studied. H. pylori infection was established by a rapid urease test in a gastric tissue sample (CLO test) and by histological examination of gastric mucosa from the stomach antrum and body. CVD was documented by completion of the Rose questionnaire. The association of H. pylori infection with CVD was determined by multivariate logistic regression modelling after adjusting for potential confounding factors. RESULTS A total of 104 (51.5%) subjects were found H. pylori positive. Forty patients had a confirmed history of CVD. Multiple logistic regression analysis verified the strong associations of CVD with established risk factors of atherosclerotic disease but not with H. pylori infection. CONCLUSION Our findings suggest that there is no association of H. pylori infection with CVD. Eradication of H. pylori to prevent CVD is not warranted.

Anemia in inflammatory bowel disease – the role of recombinant human erythropoietin

Anemia is a common problem in inflammatory bowel disease (IBD). It is related to low Karnofsky scores, loss of weight, impaired physical activity, low tolerance to the underlying disease, and a poor growth rate in children. Multiple factors can contribute to the anemia in IBD, such as iron, folic acid or B(12) deficiency, treatment with immunosuppressive drugs or sulfasalazine, hemolysis, and anemia of chronic disease. Anemia of chronic disease is characterized by impaired iron utilization, lower erythropoietin (EPO) production than needed, and a low response of bone marrow erythroid progenitor cells to EPO. In recent years, recombinant human erythropoietin (rhEPO) has been used in combination with iron for the correction of refractory anemia in IBD patients (adults or children) with good results. There is increasing evidence that rhEPO may correct refractory anemia in IBD (both ulcerative colitis (UC) and Crohns disease (CD)). In addition, such therapy may give IBD patients the opportunity to predonate blood before surgery and to avoid blood transfusions. One must not forget to exclude or correct other causes of anemia in IBD patients before administering rhEPO. Furthermore, the enhancement of erythropoiesis by EPO makes it mandatory to administer oral or intravenous iron supplementation during therapy to meet the increased demand. rhEPO is safe in IBD patients. Further studies with larger numbers of patients are needed to optimize the therapy with rhEPO in the refractory anemia of IBD.

von Willebrand factor and procoagulant imbalance predict outcome in patients with cirrhosis and thrombocytopenia

BACKGROUND & AIMS Several lines of evidence suggest that the hemostatic disorders of cirrhosis may have a significant clinical impact. We investigated the independent predictive value of components of the hemostatic system on the occurrence of ascites, variceal bleeding (VB), and survival. METHODS One hundred and two patients with thrombocytopenia (Child-Pugh class A/B/C: 34/34/34) were enrolled. Platelet counts, factors (F) II, V, VII, and VIII, antithrombin, protein C (PC), FVIII-to-PC ratio as an index of procoagulant imbalance, von Willebrand factor antigen (vWF-Ag), and model for end-stage liver disease (MELD) were evaluated. Two multivariate analyses were performed: one excluding (model 1) and one including MELD (model 2). RESULTS Higher vWF-Ag levels and FVIII-to-PC ratios were the most prominent hemostatic disorders in patients with cirrhosis. Increased levels of vWF-Ag and FVIII, and higher FVIII-to-PC ratios independently predicted the presence of ascites and varices at baseline. Independent predictors of ascites and VB during follow-up were vWF-Ag (model 1/2: p=0.001/p=0.009 and p=0.008/p=0.01, respectively) and FVIII-to-PC ratio (model 1/2: p=0.003/p=0.02 and p=0.01/p=0.03, respectively). vWF-Ag (model 1/2: p=0.007/p=0.002), FVIII-to-PC ratio (model 1/2: p=0.001/p=0.01), and MELD (p=0.02) independently predicted mortality. Patient groups with significantly higher probability of new-onset ascites, VB, and mortality were identified by certain cut-offs of vWF-Ag (213%, 466%, and 321%, respectively) and FVIII-to-PC ratio (1.99, 3.29, and 2.36, respectively). vWF-Ag and FVIII-to-PC ratio equaled MELD in mortality prediction. CONCLUSIONS Advanced cirrhosis is characterized by increased thrombotic potential. vWF-Ag and FVIII-to-PC ratio independently predict new-onset ascites, VB, and mortality. Targeting hypercoagulability could improve the outcome of patients with cirrhosis. LAY SUMMARY Higher von Willebrand factor antigen (vWF-Ag) levels and factor VIII-to-protein C (FVIII-to-PC) ratio are the prominent hemostatic disorders in patients with cirrhosis. vWF-Ag and FVIII-to-PC ratio independently predict new-onset ascites, variceal bleeding, and mortality in these patients.