Successful treatment of a patient with primary Sjögren's syndrome with Rituximab

We report the course of a 55-year-old woman, the first patient with primary Sjögren's syndrome and distal renal tubular acidosis but without lymphoma to be treated with B-cell depletion using Rituximab. Rapidly after B-cell depletion, remarkable improvement in xerostomia occurred, while serological findings and tubular acidosis have been unchanged. In labial salivary gland biopsy, lymphocyte infiltration and particularly CD20-positive cells decreased strikingly. Aquaporin 1 (AQP-1) expression in myoepithelial cells was very low before treatment and increased noticeably. Apical AQP-5 in acinus cells likewise increased following Rituximab. In contrast, basolateral NKCC1 was expressed at unchanged intensity before and following Rituximab. The improvement has been sustained and still is most gratifying 10 months after treatment. B-cell depletion may be effective treatment in Sjögren's syndrome. Likewise, it may now be possible to separate the immunologic phenomena in Sjögren's syndrome from the consequences of prolonged hyposalivation when studying the pathophysiology of xerostomia.     

Long-Term Durability of Crohn’s Disease Treatment with Infliximab

BACKGROUND: There is a paucity of data providing insight into the durability of Crohn's disease treatment with infliximab for periods longer than 12 months. Our aim was to assess the long-term durability of infliximab therapy. MATERIALS AND METHODS: A total of 198 Crohn's patients under a maintenance regimen with infliximab, with at least a 30-month follow-up, were evaluated retrospectively. Long-term response maintenance was estimated using Kaplan-Meier analysis. The effect of specific variables was calculated using logistic regression and proportional hazard regression analyses. RESULTS: Maintenance of response rates at 72 months was estimated to be 66.4% for initial responders and 58.2% for all patients treated. Concurrent immunomodulators enhanced response maintenance in all patients treated, particularly if started >3 months before the initiation of infliximab therapy. Smoking significantly decreased the maintenance of response in initial responders. CONCLUSIONS: Infliximab treatment of Crohn's disease is reasonably durable beyond 12 months. Concurrent immunosuppressive therapy may increase - and smoking may decrease - long-term response maintenance.     

Treatment of Crohn’s Disease with Leflunomide as Second-Line Immunosuppression

The aim of this study was to assess the potential of leflunomide, an immunosuppressant in rheumatoid arthritis, as a second-line immunosuppression treatment of patients with Crohn's disease refractory or intolerant to azathioprine. The study cohort consisted of 24 patients. The primary end point was steroid-free remission, and secondary end points were changes in the Crohn's disease activity index (CDAI) and steroid intake, responsiveness of arthralgias and adverse events. Results were expressed in medians (quartiles). The remission rate increased from 21 to 42% by week 16 (P < 0.05). In the intention-to-treat analysis, the CDAI decreased from 219 to 87 (P = 0.018) and the steroid intake from 25 to 3 mg/day (P = 0.033). In the per-protocol analysis, the CDAI decreased from 182 to 87 (P = 0.0183) and the steroid intake from 45 to 4 mg/day (P = 0.0778). Patients with arthralgias improved significantly. However, adverse side effects were frequent. Leflunomide may improve disease activity, especially in terms of arthralgias, and reduce steroid intake. Adverse events were more frequent in our patients than has been reported in controlled studies for rheumatoid arthritis but corresponded to those found in post-marketing studies.     

Reversible Cardiomyopathy Associated with Multicentric Castleman Disease: Successful Treatment with Tocilizumab, an Anti—Interleukin 6 Receptor Antibody

Multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder characterized by systemic lymphadenopathy and inflammatory symptoms that are associated with the overproduction of interleukin 6 (IL-6). Although several nonlymphoid organs can also be damaged in MCD, only a few cases with cardiac complications have been reported to date. We report a case of congestive heart failure in a female patient with MCD. On admission, her echocardiogram revealed a dilated and diffusely hypokinetic left ventricle. No stenosis was evident in the coronary angiogram. A histopathologic examination of a myocardial biopsy specimen showed mildly hypertrophic myocytes without infiltration of plasma cells or amyloid deposits. Repeated administration of an anti-IL-6 receptor antibody, tocilizumab (formerly known as MRA), gradually improved the ventricular wall motion over 6 months without any additional treatment for heart failure, suggesting the involvement of IL-6 in the pathogenesis of her cardiomyopathy. This report is the first of MCD complicated by heart failure treated successfully with tocilizumab. Administering tocilizumab in cases of MCD with unexplained cardiac dysfunction is worthwhile, because such a complication could be reversible.     

Successful Induction of Long-Term Remission Using Rituximab in a Patient with Refractory Hairy Cell Leukemia—Japanese Variant

We report the case of a 76-year-old man with hairy cell leukemia (HCL)-Japanese variant who underwent rituximab therapy. HCL proved refractory to treatment with pentostatin and cladribine, and the number of hairy cells in the peripheral blood continued to increase after splenectomy. The patient was treated with rituximab (375 mg/m2 intravenously weekly for 4 cycles), and hairy cells disappeared from the peripheral blood on the day after the first administration. Complete remission continued for 18 months after treatment. Although they produce high response rates in typical HCL, nucleoside analogs are associated with an inferior clinical response in HCL-Japanese variant, and repetitive administration of these agents increases the risk of serious infections. This encouraging result suggests that rituximab therapy should be considered as salvage therapy for refractory HCL-Japanese variant.     

Successful treatment of reactive hemophagocytic syndrome by plasmapheresis and high-dose γ-globulin in a patient with systemic lupus erythematosus

A 31-year-old woman who had been administered corticosteroid and immunosuppressive agents for systemic lupus erythematosus (SLE) without flare-up was diagnosed as having reactive hemophagocytic syndrome (HPS) with severe disseminated intravascular coagulation. The causative underlying disease was uncertain, but it was not the SLE itself. Her fulminant HPS with increased serum ferritin and inflammatory cytokines (sIL-2R, TNF-α, IL-6, and IFN-γ) was successfully treated with plasmapheresis and high-dose γ-globulin therapy. Received: December 24, 1999 / Accepted: June 28, 2000     

Treatment of enterocutaneous fistula in Crohn’s Disease with adipose-derived stem cells: a comparison of protocols with and without cell expansion

Background  Expanded adipose-derived stem cells (ASC) have been shown to be effective in treating Crohn’s patients with enterocutaneous fistulas. It is possible that unexpanded cells corresponding to the stromal vascular fraction (SVF) may also be effective. Materials and methods  A subpopulation of patients from a previous proof-of-concept phase I study with enterocutaneous fistulas received autologous expanded ASCs. The same selection criteria for inclusion were applied to patients who underwent SVF implantation to treat enterocutaneous fistulas. After tract curettage, cell suspensions (either SVF cells from lipoaspirate or expanded ASCs) were injected into the tract walls, and the fistulous tract was sealed with fibrin adhesive (with or without cells). Results  In the series that received ASCs, four fistulas could be evaluated, and cure was achieved in three out of four cases. In the series that received SVF cells, four fistulas were evaluated, with cure achieved in one out of four cases. Conclusions  Although a comparison of case series cannot be considered firm evidence, a therapeutic protocol that uses expansion prior to implantation does seem to be more effective than one that uses SVF cells directly from a lipoaspirate sample.     

Successful treatment of a patient with rheumatoid arthritis and IgA-κ multiple myeloma with tocilizumab

A 63-year-old woman receiving tumor necrosis factor (TNF) inhibitors for rheumatoid arthritis (RA) was found to have smoldering IgA-kappa type multiple myeloma (MM). Retrospective examination of stored serum samples revealed a steady increase of serum IgA levels after the start of TNF inhibitor therapy. The patient's articular symptoms showed marked exacerbation when TNF inhibitors were discontinued because of fear of worsening the MM. Tocilizumab improved RA symptoms dramatically and stabilized serum IgA levels for 13 months after a transient steep rise. This case suggests that tocilizumab can be used safely in patients with inflammatory disorders with coexisting MM.     

Adalimumab Treatment in Children with Refractory Crohn’s Disease

Information on safety and efficacy of adalimumab in children with Crohn’s disease (CD) is limited. We present a case-series of 14 children with severe CD treated with adalimumab during a 3.5-year period. Fourteen children (nine boys, five girls), aged 13.9 years (range 1.9–19.1) were treated with adalimumab during 12.5 months (range 7–42). All had steroid or immunosuppression-drugs refractory disease. Ten patients (71%) had been previously treated with infliximab, 13/14 were treated with different immunosuppressive drugs and all were steroid-dependent or resistant. Seven children (50%) showed full clinical response and 5/14 (35%) improved partially. Two children (15%) had loss of response after a period of transient improvement. Adalimumab treatment enabled complete steroids withdrawal in 8/14 (57%) of steroid-dependent children. Currently, five children are in complete remission with adalimumab monotherapy for a median 14 months (range 9–24). Adalimumab may induce and maintain remission in children with severe, refractory CD. Prospective safety and efficacy confirmation of this data in children is necessary.     

Frequency of Multi-dimensional COPD Indices and Relation with Disease Activity Markers

Abstract

Our aim was to describe the population-based distribution of several COPD multi-dimensional indices and to evaluate their relationship with daily physical activity, co-morbidity, health status and systemic inflammatory biomarkers. From a population-based sample of 3,802 subjects aged 40–80 from the EPI-SCAN study, 382 subjects (10.2%) with a post-bronchodilator FEV₁/FVC<0.7 were identified as COPD. Smoking habits, respiratory symptoms, quality of life, co-morbidities, lung function and inflammatory biomarkers were recorded. Health status and daily physical activity were assessed using the EQ-5D and LCADL questionnaires, respectively. The new GOLD grading and the BODE, ADO, DOSE, modified DOSE, e-BODE, BODEx, CPI, SAFE and HRS indices were determined.

A notable dispersion in the total scores was observed, although 83–88% of the COPD patients were classified into the mildest level and 1–3% in the most severe. The SAFE index was the best independent determinant of daily physical activity; the SAFE and ADO indices were associated with presence of co-morbidity; and the SAFE and modified DOSE indices were independently related to health status. The systemic biomarkers showed a less consistent relation with several indices. In a population-based sample of COPD patients, the SAFE index reaches the highest relation with physical activity, co-morbidity and health status.     

Successful treatment of giant condyloma acuminatum with combination retinoid and interferon-γ therapy

Giant condyloma acuminatum, or Buschke-L?wenstein tumour, is a unique variant of anogenital warts. It is characterized by locally aggressive behaviour but rarely metastasizes. Many treatment strategies such as radical surgery, radiation and chemotherapy have been used to treat it but their efficacy is often poor and the recurrence rates are high. We report a case of 16-year-old girl who was treated with oral retinoid combined with intramuscular interferon-γ. All lesions cleared within three months. During a follow-up period of more than two years, no recurrence has developed. This relatively painless, non-scarring treatment may represent a novel therapeutic option.     

Successful Treatment of mesenteric vasculitis caused by henoch–Schönlein purpura with methylprednisolone pulse therapy

Although mesenteric vasculitis due to Henoch–Schönlein purpura (HSP) is relatively uncommon, it is the most life-threatening manifestation associated with high mortality. We describe a 15-year-old boy with HSP who had massive gastrointestinal bleeding and ileus but delayed onset of the purpuric rash. Abdominal ultrasonography revealed thickening of both small and large intestinal walls, and CT found prominent mesenteric vessels with comb sign and double wall of the bowel. These findings were consistent with mesenteric vasculitis and bowel ischaemia. The ischaemic intestine recovered after methylprednisolone pulse therapy and surgical intervention was avoided. Our report suggests that corticosteroid pulse therapy may help controlling HSP with massive gastrointestinal haemorrhage and ischaemic bowel due to widespread mesenteric vasculitis.     

Treatment of patients with advanced mycosis fungoides and Sézary syndrome with alemtuzumab

OBJECTIVES: Alemtuzumab (anti-CD52, Campath-1H) has recently been shown to be effective in the treatment of a range of hematological malignancies, including B-cell chronic lymphocytic leukemia and T-cell prolymphocytic leukemia. We undertook a phase II study to evaluate the safety, tolerability and efficacy of alemtuzumab in patients with relapsed or refractory advanced stage cutaneous T-cell lymphoma. PATIENTS AND METHODS: A total of eight patients were enrolled, seven with mycosis fungoides/Sézary syndrome (MF/SS) and one with large-cell transformation of MF. Seven patients had disease refractory to multiple previous therapies. Alemzumab (30 mg) was administered intravenously three times per week for 12 wk or until maximum response. RESULTS: The overall response rate was 38%, with three patients achieving partial remission, two patients with stable disease and three patients with progressive disease (PD) during treatment. The time to progression was short, with all patients developing PD within 4 months of starting alemtuzumab. Response duration in the three PR patients was also brief, with responses lasting less than 3 months in all three cases. Significant hematological and immunosuppressive toxicity was observed, with both grade 3-4 cytopenias and significant infectious complications occurring in a majority of cases. CONCLUSIONS: Our findings suggest that in heavily pretreated, refractory, advanced stage MF/SS, although alemtuzumab has biological activity, it is associated with significant toxicity and only modest clinical utility. As such, combination regimens incorporating alemtuzumab merit further investigation in this difficult to treat patient group.     

Fistulating Anal Crohn’s Disease: Results of Combined Surgical and Infliximab Treatment

Introduction Infliximab is a monoclonal antibody against tumor necrosis factor-alpha, which has been shown to be effective in fistulating Crohn’s disease. The safety of infliximab in patients with potential perianal sepsis is uncertain. This study was designed to assess the safety and outcome of infliximab therapy combined with surgery for patients with fistulating anal Crohn’s disease. Methods All patients receiving infliximab for fistulating anal Crohn’s disease between 2000 and 2004 were studied. Patients’ demographics, clinical findings, magnetic resonance imaging, and examination under anesthesia were recorded. Perianal Crohn’s disease activity index before and 8 to 12 weeks after three infusions of infliximab (5 mg/kg) were recorded. Routine policy was to insert drainage seton sutures at the time of preinfliximab examination under anesthesia and then remove it after the second infusion. Complications of treatment and outcome at the last clinic follow-up were recorded. Results Twenty-two patients underwent infliximab treatment (6 males; median age, 35 (range, 16–60) years). Twenty-one patients had preinfliximab examination under anesthesia: 12 required abscess drainage; 17 had at least one drainage seton suture inserted. Fourteen patients underwent pretreatment magnetic resonance imaging to identify clinically occult collections. All but one patient were established on immunomodulator therapy before infliximab treatment. Perianal Crohn’s disease activity index improved significantly after infliximab infusion (preinfusion: median, 11, range, 8–17; postinfusion: median, 8, range, 5–16; P< 0.001). There were no serious complications of infliximab treatment. At median follow-up of 21 (range, 4–31) months, only four patients achieved sustained fistula healing. Five patients have required defunctioning or proctectomy. Four patients have required repeated infusions of infliximab. Conclusions Infliximab therapy in combination with examination under anesthesia/seton drainage is a safe and effective short-term treatment for fistulating anal Crohn’s disease. Long-term fistula healing rates are low. Presented at the Tripartite Colorectal Meeting, Dublin, Ireland, July 5 to 7, 2005.     

Effect of Short-Term Partial Enteral Nutrition on the Treatment of Younger Patients with Severe Crohn’s Disease

Background/Aims

To analyze the effect of short-term supportive temporary partial enteral nutrition therapy for treating severe pediatric Crohn’s disease (CD).

Methods

We conducted a prospective, open-label study in pediatric patients with CD (n=78) from January 2007 to December 2011. The CD patients were divided into three groups according to disease severity (mild, moderate, and severe). Seventeen patients with severe CD received short-term partial enteral nutrition (SPEN) in addition to their general diet for 4 weeks after the induction of remission with medical treatment. This SPEN group was further divided into two groups by age (<13 years, ≥13 years). Nutritional parameters and Pediatric Crohn’s Disease Activity Index scores were analyzed at the initial enrollment and following 1 year of treatment for all groups.

Results

Nutritional status improved substantially after 1 year of treatment in the severe CD group. Nutritional status in the SPEN group improved considerably more than that in the non-SPEN group. Additionally, the <13-year-old group demonstrated better nutritional status improvement than the ≥13-year-old group.

Conclusions

SPEN may be effective in pediatric patients with severe CD for improving nutritional status and moderating disease severity.     

The Strictured Anastomosis: Successful Treatment by Corticosteroid Injections—Report of Three Cases and Review of the Literature

Abstract Clinically significant anastomotic strictures usually only occur with very low colorectal anastomoses below the level of the peritoneal reflection. The reported rate averages 8 percent and has been attributed to tissue ischemia, localized sepsis, anastomotic leak, proximal fecal diversion, radiation injury, inflammatory bowel disease, and recurrent rectal cancer. Most patients will have symptoms of obstipation, frequent small bowel movements, and bloating. Symptomatic strictures are often approached by dilation (balloon or Hegar) or less often repeat resection. Many of these patients have anastomoses that are too low to consider repeat resection. Strictureplasty with linear stapling devices, stricture resection by use of the circular stapling device, and repeat dilations have all been described. Steroid injections into the stricture have been described in strictured esophagogastric anastomoses but have not been commonly used for strictured coloproctostomies. We describe three cases of coloanal stricture following resections that were complicated by postoperative pelvic abcesses, anastomatic leaks, and pelvic fibrosis. Two cases had undergone low coloanal anastomosis that was protected by a loop ileostomy and developed as significant stricture in the early postoperative period. The third case was managed without a protective loop ileostomy. These were initially managed by repeated dilation of the anastomosis. Each episode was followed by rapid recurrence of the stricture. All patients underwent subsequent dilation with injection of 40 mg of triamcinolone acetate (divided dose in four quadrants) into the stricture and subsequent complete resolution of the stricture. Those patients with loop ileostomies had them taken down and all have been followed for up to 12 months without clinical or endoscopic evidence of recurrent stricture.The views expressed in this article are those of the author and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government.     

Racial Differences in Disease Activity and Quality of Life in Patients with Crohn’s Disease

Background

The existing literature on racial differences in Crohn’s disease (CD) activity and quality of life (QOL) is limited and extrapolated from surrogate measures.

Aim

The aim of our study was to compare objective markers of disease activity and QOL over time by race.

Study

A clinical data repository of inflammatory bowel disease (IBD) patients at University of Maryland, Baltimore IBD Program, was used. CD patients from 2004 to 2009 were included if they had greater than or equal to two clinic visits with disease activity and QOL scores during the study period. Differences in disease activity and QOL were compared by race over time.

Results

A total of 296 patients with CD met inclusion criteria; of these, 19 % (56/296) were African Americans (AA) and 81 % (240/296) were Caucasian. Baseline disease activity and QOL scores did not differ by race (p > 0.05). Caucasians had a steady decline in disease activity and increase in QOL. AA experienced a similar pattern of change in disease activity and QOL scores over time; however, the declines were not statistically significant between groups. At each time point post-baseline, disease activity and QOL scores were similar between races.

Conclusion

We found that Caucasian and AA patients with CD had similar disease activity and QOL scores at initial presentation and over time. Thus, AA do not represent a more severe subgroup of CD patients to treat. These findings have important implications for clinicians that care for patients with CD.     

Treatment of Barrett’s esophagus with high-grade dysplasia and intramucosal adenocarcinoma

High-grade dysplasia and intramucosal adenocarcinoma are premalignant and malignant lesions of the esophagus. The incidence of lymphatic or systemic metastases is low and esophagectomy is curative in most patients. Until recently, complete removal of the neoplastic tissue was reliably accomplished with only esophagectomy. New technologies have been developed that allow endoscopic mucosal resection and ablation with preservation of the esophagus for these lesions. Optimal treatment of the patient requires consideration of not only the stage of the lesion but also the pathophysiology of the esophagus and the severity of the underlying reflux disease. Only with this approach can outcomes be optimized for both the dysplasia or cancer and the patient’s reflux disease and long-term quality of life. In this article, we summarize the experience from a surgical center’s perspective.