Management of resistant mucocutaneous herpes simplex infections in AIDS patients: a clinical and virological challenge.

BACKGROUND: The use of highly active antiretroviral therapy (HAART) has been associated with a marked decrease in the prevalence of opportunistic infections in HIV-infected patients. However, chronic mucocutaneous herpes simplex virus (HSV) infection remains a difficult clinical challenge. OBJECTIVE: The aim of the study was to optimize the diagnosis and follow-up of chronic HSV-2 infection in HIV-infected patients and to correlate clinical data with CD4 cell count, in vitro HSV virological resistance and histology. METHODS: A retrospective case series was collected from a specialist out-patient clinic providing consultations to patients with infectious skin diseases. Clinical, biological, virological and histological data were analysed. RESULTS: Seven HIV-infected patients with genital and perianal herpes simplex infection were followed over 10 years. Ulcerative and pseudo-tumoral forms were observed. Lesions occurred at various stages of immune suppression (CD4 counts from 1 to 449 cells/µL). Clinical resistance to conventional anti-herpetic drugs was correlated with the in vitro resistance of HSV in 70% of cases. CONCLUSIONS: Chronic mucocutaneous HSV infection in AIDS patients remains a rare but regularly observed infection in very immunosuppressed patients or those with unstable immunity during HAART. Virological results obtained from mucocutaneous samples were in most cases found to be correlated with clinical evolution and should therefore be used in making decisions on treatment. Despite efficient antiviral therapy, mucocutaneous healing is slow in the majority of cases.

Intralesional infliximab in noninfectious cutaneous granulomas: three cases of necrobiosis lipoidica.

BACKGROUND: Necrobiosis lipoidica is a rare granulomatous noninfectious skin disease. Treatment of this chronic debilitating disease is of importance because ulceration of the plaques may induce important psychological and physical morbidity. OBJECTIVE: Infliximab, an anti-TNF-α chimeric monoclonal antibody used intravenously and intralesionally for other extradermatological granulomatous diseases including Crohn's disease and sarcoidosis, was administered by intradermal injection in necrobiosis lipoidica. The aim of this study was to evaluate the efficacy and safety profile of a locally delivered drug compared to its systemic use. PATIENTS AND METHODS: Weekly injections of intralesional infliximab for 3 weeks were followed by a 1-week treatment interruption. This treatment schedule was repeated thrice. RESULTS: Two patients who benefitted from complete treatment experienced almost complete remission for up to 18 months. The third patient, who had treatment interruptions, showed partial improvement. No serious side effects were noticed, although the injections caused pain. CONCLUSIONS: This is the first report about the efficacy and safety of a therapy consisting of intralesional injections of infliximab for a granulomatous skin disease. Although this approach was clearly effective for necrobiosis lipoidica, the disease recurred several months after treatment interruption, raising the question of the need for maintenance therapy. Further controlled long-term trials are thus necessary.

Tuberculosis screening in patients with psoriasis before antitumour necrosis factor therapy: comparison of an interferon-gamma release assay vs. tuberculin skin test.

BACKGROUND: Antitumour necrosis factor (anti-TNF) treatments may reactivate latent tuberculosis infection (LTBI). For detecting LTBI, the tuberculin skin test (TST) has low sensitivity and specificity. Interferon-gamma release assays (IGRA) have been shown to be more sensitive and specific than TST. OBJECTIVE: To compare the TST and the T-SPOT.TB IGRA for identifying LTBI in patients with psoriasis before anti-TNF treatment. METHODS: A retrospective study was carried out over a 4-year period on patients with psoriasis requiring anti-TNF treatment. All were subjected to the TST, T-SPOT.TB and chest X-ray. Risk factors for LTBI and history of bacillus Calmette-Guérin (BCG) vaccination were recorded. The association of T-SPOT.TB and TST results with risk factors for LTBI was tested through univariate logistic regression models. Agreement between tests was quantified using kappa statistics. Treatment for LTBI was started 1 month before anti-TNF therapy when indicated. RESULTS: Fifty patients were included; 90% had prior BCG vaccination. A positive T-SPOT.TB was strongly associated with a presumptive diagnosis of LTBI (odds ratio 7.43; 95% confidence interval 1.38-39.9), which was not the case for the TST. Agreement between the T-SPOT.TB and TST was poor, kappa = 0.33 (SD 0.13). LTBI was detected and treated in 20% of the patients. In 20% of the cases, LTBI was not retained in spite of a positive TST but a negative T-SPOT.TB. All patients received an anti-TNF agent for a median of 56 weeks (range 20-188); among patients with a positive TST/negative T-SPOT.TB, no tuberculosis was detected with a median follow-up of 64 weeks (44-188). One case of disseminated tuberculosis occurred after 28 weeks of adalimumab treatment in a patient with LTBI in spite of treatment with rifampicin. CONCLUSION: This study is the first to underline the frequency of LTBI in patients with psoriasis (20%), and to support the use of IGRA instead of the TST for its detection. Nevertheless, there is still a risk of tuberculosis under anti-TNF therapy, even if LTBI is correctly diagnosed and treated.

Refractory chronic cutaneous sarcoidosis responsive to dose escalation of TNF-alpha antagonists.

Cutaneous sarcoidosis may be a chronic disease with important morbidity requiring aggressive therapy. The efficacy of different anti-tumor necrosis factor alpha(anti-TNF-alpha) treatments in refractory cutaneous and systemic sarcoidosis has been reported previously. We report the first patient with chronic cutaneous sarcoidosis who responded to dose escalation of anti-TNF-alpha agents that have been ineffective at the standard dosage, illustrating that the optimal dosing regimen has still to be defined for this indication before considering difficult-to-treat patients as nonresponders. Our case report also illustrates that the fusion protein etanercept, even used at a high dosage, may be less effective for the treatment of cutaneous sarcoidosis than the monoclonal antibodies infliximab and adalimumab.

[Scleroedema adultorum Buschke in a diabetic subject: intravenous immunoglobulin therapy]. / Scléroedème de Buschke chez un diabétique: traitement par immunoglobulines intraveineuses.

BACKGROUND: Scleroedema adultorum Buschke (SB) is a rare disease involving scleroedema of the neck and shoulders. It can extend to the rest of the trunk and the limbs but characteristically spares the extremities. Three types of SB are distinguished: the first is acute and develops after an infectious disease, the second is of insidious evolution and is associated with monoclonal gammopathy, and the third is associated with type 2 diabetes. PATIENTS AND METHODS: We report the case of a type 2 diabetic patient presenting with progressive, oedematous timbering of the trunk associated with impaired mobility, dysphagia and restrictive respiratory syndrome. SB was diagnosed on the basis of clinical presentation and histology. Treatment was mandatory because of the adverse impact of the disease. A therapy that would not worsen the patient's comorbidities had to be chosen. Intravenous immunoglobulins were thus initiated with excellent response as of the first cycle regarding trunk mobility and dysphagia. Cutaneous rigidity improved steadily until the end of treatment (eight cycles). CONCLUSION: Therapeutic abstention is the rule in SB if it has no severe functional repercussions. Nevertheless, there is no clearly indicated treatment once therapy becomes necessary. Control of underlying diabetes usually does not improve the scleroedema and the metabolic syndrome contraindicates most of the treatments reported in the literature. In this article, we suggest a new treatment of SB in the diabetic patient.

Infliximab then efalizumab, the 'hit and run' approach does not work.

BACKGROUND: In a previous paper we described 2 patients treated with a sequential biologic therapy for chronic plaque psoriasis. We used infliximab as an induction treatment followed by efalizumab. We extended this approach to 3 other patients. OBJECTIVE: The purpose was to show the feasibility of a sequential approach with biologicals. METHODS: Five patients received three infusions of infliximab followed by weekly injections of efalizumab from week 10 on. RESULTS: The most important findings, summarized in a table, show that none of the patients continued the treatment for more than a year either because of non-responsiveness or because of spontaneous stopping. Moreover, 4 out of 5 patients did not respond or had serious adverse events on reintroduction of infliximab. CONCLUSION: Overall, we cannot recommend sequential therapy using infliximab and efalizumab.

Long-term control with etanercept (Enbrel) of a severe acrodermatitis continua of Hallopeau refractory to infliximab (Remicade).

Hallopeau's acrodermatitis is characterized by the presence of aseptic pustules on an inflammatory basis of the periungual or subungual region. The cyclic recurrences induce important physical and psychological morbidity. By analogy to the efficacy of TNF-alpha antagonists in the treatment of generalized pustular psoriasis, our patient illustrates the long-term efficacy and safety of etanercept (Enbrel) in the treatment of Hallopeau's acrodermatitis refractory to infliximab (Remicade). This treatment alternative should in consequence be considered in patients with a recalcitrant form of a potentially debilitating disease.

Transient bacteremia following endoscopic injection sclerotherapy of esophageal varices.

The incidence of transient bacteremia following endoscopic injection sclerotherapy of esophageal varices was evaluated in 18 patients subjected to 40 sessions of injection sclerotherapy. Blood cultures were obtained before sclerotherapy and at five minutes, 30 minutes, and 24 hours after sclerotherapy. The injectors as well as the endoscope were cultured before and after the procedure. Blood cultures were positive in two patients after injection sclerotherapy (Enterobacter cloacae and Staphylococcus species, coagulase-negative, respectively) for an incidence of 5% of transient bacteremia. Pseudomonas aeruginosa was the most frequent bacteria isolated from the injector after sclerotherapy. We conclude that the incidence of transient bacteremia after sclerotherapy is no higher than routine upper-intestinal endoscopy.

Endoscopy water source: tap or sterile water?

The purpose of this study was to determine whether the endoscopic water source holds potential for transmission of pathogens. Phase I of the study used tap water and clean water bottles; Phase II used sterile water and steam-sterilized water bottles. In both phases, a control bottle filled with water from the appropriate source was set up. Cultures were taken from both the controls and endoscopy water sources before the day's procedures were started and at the end of the day. Each phase contained 100 to 106 sets of samples. Many of the tap water samples were positive for normal flora found in city water sources. No clinically significant complications were identified during either phase of the study. The use of tap water and clean water bottles was found to carry no greater risk than using sterile water and sterile bottles. The practice of using tap water will result in significant cost savings. Further study will be needed to look at the integrity of the endoscope and water bottle design in preventing transmission of pathogens.

Percutaneous endoscopic gastrostomy: a randomized prospective comparison of early and delayed feeding.

BACKGROUND: It has been customary to initiate feeding through percutaneous endoscopic gastrostomy (PEG) tubes 24 hours or more after placement of these tubes. Recent changes in practice environment and emphasis on early discharge of hospitalized patients prompted us to evaluate early PEG feeding in a randomized prospective manner. METHODS: Forty-one patients were included in the study. After an informed consent, the patients were randomly assigned to two groups. Groups I (21 patients) received tube feedings 3 hours and Group II (20 patients) received feedings 24 hours after PEG placement. All patients received an Iso-osmolar formula by continuous infusion at 30 ml/hour for the first 24 hours of feeding. The rates were then increased to 70 ml/hour. Residual volumes, tube length, peristomal leakage, and vital signs were checked, and a global assessment was done every 4 hours. Evaluation by a physician was done every 24 hours for 72 hours. If the residual volume was more than 60 ml (significant residual volume), the tube feedings were held for 2 hours. Patients exited the study at 72 hours from the time of procedure. All deaths were recorded to calculate 30-day mortality. RESULTS: One patient (Group 2) died during the study period. Three patients (two in Group 1 and one in Group 2) had a significant residual volume. One patient (Group 1) had local skin infection requiring treatment. None of the patients had any signs of peritonitis or systemic infection. CONCLUSION: Early PEG tube feeding (3 hours after tube placement) is as safe as next day feeding in elderly patients.

Risks of intra-abdominal nonshunt surgery in cirrhotics.

We have reviewed the risks of various nonshunt intra-abdominal operations in cirrhotic patients. Most of these studies are retrospective reviews with limitations. Among various risk stratifications in cirrhosis, Child-Pugh classification is sufficiently informative. Elective surgery can be done safely in patients with Child's A or B class. Operations in Child's C patients and emergent surgery carry formidably high mortality. Limiting the extent of surgery, controlling ascites, correcting coagulation abnormality and malnutrition and aggressively treating infection, might reduce mortality. Laparoscopic cholecystectomy and endoscopic sphincterotomy in cirrhotics seem to be promising in reducing mortality and morbidity.

Length of esophageal cancer and degree of luminal stenosis during upper endoscopy predict T stage by endoscopic ultrasound.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasonography (EUS) is considered to be the most accurate modality for T staging of esophageal cancer. This study attempted to determine whether endoscopic features such as the length and degree of luminal stenosis in esophageal cancer can predict the T stage on EUS. PATIENTS AND METHODS: Thirty-five patients with newly diagnosed esophageal adenocarcinoma or squamous-cell carcinoma undergoing EUS prior to initiation of any treatment were included in the study. The length of the tumor was assessed prospectively during esophagogastroduodenoscopy (EGD) before EUS in 22 patients. Radial EUS was then performed in these patients. The other 13 patients had sufficient luminal stenosis to prevent complete advancement of the echo endoscope through the tumor. In these 13 patients, the length of the esophageal cancer was not examined, but the T and N stage up to the level of maximum advancement of the echo endoscope through the tumor were noted. RESULTS: All 13 patients with luminal stenosis had at least a T3 (n = 12) or T4 (n = 1) lesion up to the level of maximum advancement of the echo endoscope. Among the 22 patients in whom the length of the esophageal cancer was measured, the mean length in the 13 patients with a T1 or T2 lesion on EUS was 2.6 cm. The mean length in the nine patients with T3 esophageal cancer was 7.1 cm. The difference in the mean length of T1 or T2 lesions (2.6 cm) was significantly different ( P < 0.001) from the mean length of T3 lesions (7.1 cm). Using a clinical diagnostic testing approach, when > or = 5 cm length was used as a criteria for diagnosing T3 lesions, the sensitivity was 89 %, specificity 92 %, positive predictive value 89 %, and negative predictive value 92 %. There was also a suggestion of increased chances of lymph-node metastases with increasing length of esophageal cancer. CONCLUSIONS: In esophageal carcinoma, endoscopic features such as the length of the cancer and the degree of luminal stenosis correlate with T staging on EUS. Esophageal cancers that are > or = 5 cm in length, or are sufficiently stenotic to prevent passage of an endoscope, are much more likely to be T3 or higher-stage lesions, while those that are < 5 cm in length have a greater chance (92 %) of being T1 or T2.

A prospective controlled evaluation of endoscopic detection of angiodysplasia and its association with aortic valve disease.

BACKGROUND: In view of controversy about the association of aortic stenosis and angiodysplasia of the gut, we performed a prospective, controlled study to evaluate the relationship between aortic valve disease and gastrointestinal angiodysplasia. METHODS: Forty patients who had endoscopy for clinical indications such as gastrointestinal bleeding, anemia, polyps, colon cancer, and dyspepsia, and who were found to have angiodysplasia of the gastrointestinal tract, underwent two-dimensional and Doppler echocardiography. Thirty-seven controls matched for age, sex, indication, and nature of endoscopic examination, but without angiodysplasia, underwent similar echocardiographic examination. RESULTS: None of the patients in either group had aortic stenosis. The prevalence of aortic sclerosis, aortic insufficiency, and low left ventricular ejection fraction was similar in patients with and without angiodysplasia. CONCLUSIONS: This study does not support the role of aortic valve disease as the cause of angiodysplasia of the gastrointestinal tract. A subgroup of patients with angiodysplasia with aortic sclerosis, with or without other valvular disease (but none with aortic stenosis), had increased prevalence of gastrointestinal bleeding when compared with controls. When aortic valve disease or decreased left ventricular ejection fraction were analyzed as independent predictors, none of them in and of itself appeared to be a factor in bleeding from these gastrointestinal lesions.

Intraoperative endoscopic ultrasonography in Zollinger-Ellison syndrome.

In a 46-year-old man with Zollinger-Ellison syndrome, multiple imaging studies were negative for a primary gastrinoma. Preoperative endoscopic ultrasonography (EUS) revealed a 3.3-cm mass which appeared to be in the pancreatic head. During surgery, a celiac lymph node of the size of the mass seen by EUS was found, but the pancreatic head also felt firm and was suspicious for a mass. After resection of the celiac node, intraoperative EUS revealed no mass in the pancreatic head. Based upon intraoperative EUS findings, the pancreatic head was not resected. Histologic evidence of gastrinoma was found in the celiac lymph node and a 4 to 5 mm nodule in the duodenal wall. Postoperatively serum gastrin levels returned to normal.

Endoscopic ultrasound miniprobe-guided steroid injection for treatment of refractory esophageal strictures.

Local injection of corticosteroids into refractory esophageal strictures to decrease the restenosis rate has been reported. Here we report our efforts in three patients to render the delivery of steroids more precise, by injecting them in the thickest segment of the stricture with the guidance of a high frequency ultrasound miniprobe passed through a regular upper endoscope. Steroid injection under ultrasound miniprobe guidance may be indicated for patients who do not respond to a "blind" steroid injection without miniprobe guidance.

Is in vivo measurement of size of polyps during colonoscopy accurate?

BACKGROUND: Accurate measurement of polyp size during colonoscopy is important because of the direct correlation of size with colon cancer. Major studies of colorectal neoplasms have measured polyp size differently. It is also well documented that endoscopists underestimate polyp size frequently. The goal of this prospective study was to determine which one of the five methods of estimating polyp size during colonoscopy is most accurate. METHODS: One hundred colon polyps were measured by means of visual estimation, open biopsy forceps methods, linear probe, a ruler immediately after excision, and after fixation in formalin. The size of the polyps measured outside the body immediately after excision was considered the "gold standard" against which all measurements were compared. RESULTS: Forty-seven polyps were 5 mm or less in diameter, 33 polyps were 5.01 mm to 10 mm, and 20 polyps were more than 10 mm in size. For all polyps the mean difference versus the actual size of the polyps was 3.4% for linear probe, 6.4% for visual estimation, and 12.3% for the forceps. CONCLUSION: Measurement of polyp size by linear probe agreed best with the actual polyp size, followed closely by visual estimation. The open biopsy forceps method was the least accurate.