Israel Medical Association Journal

Background: With regard to ethnic predilections for Gaucher disease, the most common storage disorder, Ashkenazi Jews are at risk for the non-neuronopathic form (type I), Norbottnian Swedes are at risk for the sub-acute neuronopathic form (type III), and perhaps Arabs are at risk for the very rare cardiac variant of the sub-acute neuronopathic form (type IIIc) for which there is a relatively tight genotype-phenotype correlation. Type II, the acute infantile form, being the rarest form, has not been associated with any ethnic predilection.

Objectives: To examine whether Arab ethnicity influences the Gaucher phenotype.

Methods: We reviewed the records of all Arab patients in a referral clinic of 586 patients in Israel.

Results: There were 46 patients (7.8%) of Arab ethnicity: 23 (50%) had type I disease, 16 (34.8%) had type IIIc disease, 4 (8.7%) had type IIIb disease, and 3 (6.5%) had type II disease. Type IIIc disease was characterized by genotype-phenotype correlation with homozygosity for the D409H (1342C) mutation. All five Bedouin patients (10.9%) had the R48W (C259T) mutation on at least one allele.

Conclusions: For all genotypes, disease severity among Arab patients was relatively similar to that reported among other Caucasian patients. Apparently Arab ethnicity does not impact phenotypic expression in Gaucher disease in a unique manner. The predilection for type IIIc may be a result of consanguinity.
 

Background: A polymeric diet rich in transforming growth factor-beta 2 used as a single nutrient has been shown to induce remission in 79% of children with Crohn's disease.

Objectives: To summarize the experience of several pediatric gastroenterology units in Israel using a TGFβ2[1]-enriched polymeric diet (Modulen IBD) supplementation in children and adolescents with Crohn's disease.

Methods: In a retrospective study we reviewed the charts of 28 children with Crohn's disease (10 girls, 18 boys) who received, in addition to conventional treatment, Modulen IBD™ as a supplement to their regular nutrition. These children were compared with 18 children supplemented with standard polymeric formula (Ensure Plus®) and 18 children without formula supplementation. We recorded clinical manifestations, growth, and the Pediatric Crohn's Disease Activity Index before and after initiation of the polymeric diet.

Results: The Modulen-treated children showed a significant decrease in PCDAI[2] from 34.3 to 15.7 (P < 0.0001). A significant decrease in PCDAI was recorded also in the Ensure Plus group, from 35 to 22 (P = 0.02) but not in the non-supplemented group. Significant improvements in body mass index (P = 0.01) and erythrocyte sedimentation rate (P = 0.03) were recorded at follow-up (median 3.4 months) only in the Modulen IBD group.

Conclusions: In this cohort of children with Crohn's disease, supplementation of the diet with Modulen IBD as well as supplementation with Ensure Plus was associated with a decrease in PCDAI. The children supplemented with Modulen IBD also showed improvement in BMI[3], suggesting an additional advantage of nutritional therapy in children with this disease.

Background: Atopic dermatitis or atopic eczema is an itchy inflammatory skin condition with a predilection of the skin flexures. Most cases start in children although some have been reported in adults. Patients with moderate to severe disease refractory to topical corticosteroid or calcineurin inhibitors may require second-line treatment such as phototherapy or systemic immunosuppressants. Methotrexate therapy has been suggested to be a useful immunosuppressant in adult atopic dermatitis.

Objectives: To further determine the efficacy of low dose methotrexate therapy in adults with new-onset atopic dermatitis or with idiopathic eczema.

Methods: All adult patients with new-onset atopic dermatitis or idiopathic eczema treated by methotrexate in our clinics from 2004 to 2006 were included in the study. All had failed prolonged therapy with oral antihistamines and local corticosteroid creams. Methotrexate, 10–20 mg, was given orally once a week along with folic acid supplements 5 days a week. Additional therapies included predominantly emollients. During the entire treatment period the investigators made global assessments of the clinical response.

Results: Nine patients diagnosed with late-onset atopic dermatitis (n=6) or idiopathic eczema (n=3) were treated with methotrexate. All patients responded to the drug. The initial response was noted after 3–7 weeks. Six patients achieved complete remission after 3 months of methotrexate therapy and three patients had significant improvement. One patient's the condition worsened after achieving a complete response while on methotrexate and it was withdrawn completely. No serious adverse events were noted during treatment.

Conclusions: Low dose methotrexate is an effective therapeutic alternative for late-onset atopic dermatitis or idiopathic eczema in patients unresponsive to local and other systemic therapies.
 

Background: Iron deficiency is the most common single cause of anemia worldwide. Treatment consists of improved nutrition along with oral, intramuscular or intravenous iron administration.

Objectives: To describe the efficacy and adverse effects of intravenous iron sucrose therapy in a group of children with iron deficiency anemia who did not respond to oral iron therapy.

Methods: We conducted a prospective investigation of 45 children, aged 11 months to 16 years, whose oral iron therapy had failed. The children attended the Pediatric Ambulatory Care Unit where they received intravenous iron sucrose infusion.

Results: Forty-four of the 45 patients were non-compliant. Nine had Helicobacter pylori gastritis and 16 patients suffered from intestinal malabsorption from different causes. Before treatment, the blood mean hemoglobin concentration was 7.43 g/dl (range 5–10.1 g/dl). Fourteen days after treatment the mean hemoglobin concentration increased to 9.27 g/dl (SD 1.23) and 6 months later to 12.40 g/dl (SD 1.28). One patient demonstrated a severe side effect with temporary and reversible reduced blood pressure during treatment.

Conclusions: These preliminary data suggest that administration of intravenous iron in pediatric patients is well tolerated and has a good clinical result, with minimal adverse reactions.

Background: Balneotherapy is an established treatment modality for musculoskeletal disease. However, few studies have examined the efficacy of spa therapy in elderly patients with degenerative spine and joint diseases.

Objectives: To assess the effects of balneotherapy on chronic musculoskeletal pain, functional capacity, and quality of life in elderly patients with osteoarthritis of the knee or chronic low back pain.

Methods: A total of 81 patients enrolled and the results of 76 were analyzed. Subjects underwent a 1 day course of 30 minute daily baths in mineral water. Changes were evaluated in the following parameters:  pain intensity, functional capacity, quality of life, use of non-steroidal anti-inflammatory or analgesic drugs, subjective disease severity perceived by the patients, investigator-rated disease severity, and severity of pain perceived by the patients.

Results: Compared to baseline, all monitored parameters were significantly improved by balneotherapy in both investigated groups. Moreover, the favorable effect was prolonged for 3 months after treatment.

Conclusions: This study showed that balneotherapy is an effective treatment modality for elderly patients with osteoarthritis of the knee or with chronic low back pain, and its benefits last for at least 3 months after treatment.
 

Background: Infliximab and etanercept have been included in the Israeli national list of health services since 2002 for rheumatoid arthritis and juvenile idiopathic arthritis, and since 2005 for psoriatic arthritis and ankylosing spondylitis. The regulator (Ministry of Health and health funds) mandates using fixed doses of infliximab as the first drug of choice and increased dosage is not allowed. For other indications (e.g., vasculitis), anti-tumor necrosis factor therapy is given on a "compassionate" basis in severe refractory disease.

Objectives: To describe our experience with anti-TNF[1] therapy in a single tertiary referral center in northern Israel and to analyze the impact of the national health policy on the results.

Methods: We reviewed the medical records of patients who received anti-TNF therapy in our institution, and analyzed demographic data, diagnosis, clinical and laboratory features, previous and current therapies, and anti-TNF treatment duration and side effects.

Results: Between 2001 and 2006, 200 patients received anti-TNF therapy for rheumatoid arthritis (n=108), juvenile idiopathic arthritis (n=11), psoriatic arthritis (n=37), ankylosing spondylitis (n=29), adult Still's disease (n=4), overlap disease (RA[2] and scleroderma or polymyositis, n=6), temporal arteritis (n=1), polyarteritis nodosa (n=1), dermatomyositis (n=1), amyloidosis secondary to RA (n=1) and Wegener's granulomatosis (n=1). Forty percent of RA patients discontinued the first anti-TNF agent due to side effects or insufficient response. Higher sedimentation rate and lower or negative rheumatoid factor predicted better response to therapy among RA patients. AS[3] and PS[4] patients had a better safety and efficacy profile. Severe infections occurred in 2% of patients. All eight patients who presented lung involvement as part of their primary rheumatic disease remained stable or improved. A significant improvement was achieved in all six patients with overlap disease.

Conclusion: Our daily practice data are generally in agreement with worldwide experience. The ‘deviations’ might be explained by the local health policy at that time. The impact of health policy and economic and administrative constraints should be taken into account when analyzing cohort daily practice data.

There has been a paradigm shift in the treatment of rheumatoid arthritis in recent years. Early and aggressive treatment with good control of disease activity has improved the prognosis of the disease, however, there is significant variability in the response of patients to different therapeutic agents. Hence it is essential to find the predictors of response to a drug at baseline so that we can avoid the delay in achieving remission and improve the outcome. Here we review the literature on available predictors for treatment response in general and specifically for methotrexate and biological agents. We also look at specific scores or indices that can help predict the response in individual patients.

Background: Peritoneal carcinomatosis is an advanced form of cancer with poor prognosis that in the past was treated mainly palliatively. Today, the definitive approach to peritoneal surface malignancy involves peritonectomy, visceral resection and perioperative intra-abdominal hyperthermic chemotherapy. The anticipated results range from at least palliative to as far as intent to cure. Proper patient selection is mandatory.

Objectives: To determine whether cytoreductive surgery and intraperitoneal hyperthermic chemotherapy can extend survival, and with minor complications only, in patients with peritoneal carcinomatosis.

Methods: Twenty-two IPHP[1] procedures were performed in 17 patients with peritoneal carcinomatosis in our institution between 1998 and 2007: 6 had pseudomyxoma peritonei, 5 had colorectal carcinoma, 3 had ovarian cancer and 3 had mesotheliomas. All patients underwent cytoreductive surgery, leaving only residual metastasis < 1 cm in size. Intraperitoneal chemotherapy was administered through four large catheters (2F) using a closed system of two pumps, a heat exchanger and two filters. After the patient’s abdominal temperature reached 41°C, 30–60 mg mitomycin C was circulated intraperitoneally for 1 hour.

Results: The patients had a variety of anastomoses. None demonstrated anastomotic leak and none experienced major complications. Six patients had minor complications (pleural effusion, leukopenia, fever, prolonged paralytic ileus, sepsis), two of which may be attributed to chemotherapy toxicity (leukopenia). There was no perioperative mortality. Some patients have survived more than 5 years.

Conclusions: IPHP is a safe treatment modality for patients with peritoneal carcinomatosis. It has an acceptable complications rate and ensures a marked improvement in survival and in the quality of life in selected patients.