Menachem Itzchaki

11 Skeletal involvement in Gaucher's disease

Perhaps the most variable of all the symptoms attributed to Gauchers disease is that of bone involvement, both in the Type 1 and Type 3 forms of the disease. Expression of skeletal involvement in Gaucher patients ranges from asymptomatic disease, with or without radiological signs, to symptomatic disease, which can be severe and engender considerable pain and disability. Herein we discuss the imaging techniques currently available to document the presence and progression of bone involvement as well as the various forms of medical and surgical management that are employed to help the Gaucher patient cope with skeletal disease.

Bone density changes with enzyme therapy for Gaucher disease

Gaucher disease is the most common lysosomal storage disease. Enzyme replacement therapy engenders improvement in hematological and visceral parameters; however, improvement in bone density (BMD) with treatment has not been confirmed. This study presents follow-up of BMD in the first ten patients in Israel treated with low-dose recombinant enzyme for up to 108 months. BMD at femoral neck and lumbar spine was determined by dual-energy X-ray absorptiometry (DEXA) at the start of the trial, after 3–6 months, after 18–24 months, and at the most recent follow-up. BMD in all patients was very low at onset and never normalized. There was a decrease in BMD in all patients at 3–6 months. Older patients (four women, two men; >30 years of age) showed some improvement in BMD during treatment. Younger patients (four females; 18–23 years of age) did not show a statistically significant improvement. These findings might reflect the failure of patients with Gaucher disease to achieve expected peak bone density at appropriate chronological milestones despite treatment. Nonetheless, the z-scores of the older patients were better than those of the younger patients, implying some catch-up period. Yet, some patients with Gaucher disease evince rapid onset of osteoporosis in early adulthood. Enzyme treatment per se, as well as attendant improved well-being and increased physical activity, may induce amelioration in BMD at this later stage. One may consider adding anti-osteoporosis therapy in young adults to induce earlier “catch up” to peak bone mass, and then enzyme replacement in later adulthood to prevent decrements in bone mass related to Gaucher cell infiltration.

Kingella kingae infections in children.

Kingella kingae is a beta-hemolytic gram-negative bacillus. It was first described in the 1960s by EO King and has been reported as a cause of osteo-articular pediatric infections since the early 1980s. We performed a retrospective review of all pediatric cases of invasive K. kingae infection between 1997 and 2002, in order to define the incidence, clinical presentation and outcome of invasive K. kingae infections in a pediatric population. During the study period, a total of 24 pediatric patients with K. kingae infection were identified. There were 15 blood culture isolates of K. kingae, out of a total of 1151 (1.3%) positive blood cultures, and 9 synovial fluid culture isolates out of a total of 76 (11.8%) positive synovial fluids. Fifteen patients had osteo-articular infections and 9 had primary bacteremia without osteo-articular infection. Outcome was favorable in all cases and only in 2 patients with knee joint infection was surgical intervention performed, by means of formal knee arthrotomy. All patients recovered uneventfully, in 7 cases without any intervention and in the others with intravenous or oral antibiotic. In conclusion, invasive K. kingae infection is not uncommon in Israel. It usually has a mild course and thus is not always detected and treated. As K. kingae grows best in blood culture broth, blood and joint fluid should always be inoculated into blood culture bottles in suspected cases. This bacterium is highly sensitive to betalactame antibiotics and infection resolves quickly with antibiotic treatment. Surgical intervention for osteo-articular infection is seldom indicated.

Serum levels of osteoprotegerin and osteoprotegerin polymorphisms in Gaucher disease

Bone involvement in Gaucher disease causes disability and reduced quality of life; loss of function and pain are important indications for enzyme replacement therapy. The purpose of this study was to ascertain whether osteoprotegerin (OPG), which decreases osteoclast activity, is indicative of incipient bone involvement by comparing OPG serum levels to Gaucher disease severity (SSI) and bone mineral density (BMD), and to correlate bone and disease markers to OPG polymorphisms: OPG1‐2(A163G), OPG3‐4(T129C) and OPG5‐6(C1217T). Of 554 patients, 173 Ashkenazi Jewish patients with non‐neuronopathic Gaucher disease were enrolled and 32 healthy Ashkenazi Jews served as controls. Serum OPG levels were detected by enzyme‐linked immunosorbent assay and BMD was obtained by dual X‐ray absorptiometry. OPG polymorphisms were determined in 63 randomly chosen patients. Serum OPG values for patients were not greater than in controls, but showed a statistically significant trend to increase with age (P = 0·057). No correlation existed between OPG levels and BMD or with genotype or other disease markers. A significant correlation was noted between OPG5‐6 genotype and SSI. A significant difference was found between the allele distributions of each OPG polymorphism when compared with Caucasians and Ashkenazi Jews. OPG levels probably do not predict BMD in Gaucher disease and hence are not indicative of osteoporosis in Gaucher disease.

The 1226G (N370S) Gaucher mutation among patients with Legg-Calve-Perthes disease.

Legg-Calve-Perthes disease (LCPD) is an avascular necrosis of the femoral head with an annual incidence of 5-15/100,000. The estimated incidence of Gaucher disease, a lysosomal recessive storage disease, is 1:850, with a carrier rate of 1:17.5 for the 1226G (N370S) mutation among Ashkenazi Jews in whom there is a predilection. Since clinical and radiological findings of avascular hip necrosis due to either Gaucher disease or LCPD may be indistinguishable, misdiagnosis may occur. The purpose of this study was to evaluate the incidence of 1226G Gaucher mutation in a cohort of radiologically confirmed LCPD patients (diagnosed 1986-2000) in Israel. Enzyme assay was performed for confirmation of affected versus carrier status in patients with the 1226G mutation. In all, 78 LCPD patients, 86% males, 51% with severe bone disease, were studied. Family history was negative for Gaucher disease. Ethnic origin was 39% Ashkenazi Jewish, 6% Arab, and 55% other ethnicities. One Ashkenazi Jewish LCPD patient was homozygous for the 1226G mutation, and 4 LCPD patients were carriers: 3 Ashkenazi Jewish and 1 Arab patient. The frequency of the 1226G mutation among the LCPD patients was increased relative to historical Ashkenazi Jewish Israeli controls (P = 0.01). Since Gaucher disease may be misdiagnosed as LCPD, glucocerebrosidase enzyme testing is recommended among Ashkenazi Jewish children diagnosed with LCPD.

Traumeel S® for pain relief following hallux valgus surgery: a randomized controlled trial

BackgroundIn spite of recent advances in post-operative pain relief, pain following orthopedic surgery remains an ongoing challenge for clinicians. We examined whether a well known and frequently prescribed homeopathic preparation could mitigate post-operative pain.MethodWe performed a randomized, double blind, placebo-controlled trial to evaluate the efficacy of the homeopathic preparation Traumeel S® in minimizing post-operative pain and analgesic consumption following surgical correction of hallux valgus. Eighty consecutive patients were randomized to receive either Traumeel tablets or an indistinguishable placebo, and took primary and rescue oral analgesics as needed. Maximum numerical pain scores at rest and consumption of oral analgesics were recorded on day of surgery and for 13 days following surgery.ResultsTraumeel was not found superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial, however a transient reduction in the daily maximum post-operative pain score favoring the Traumeel arm was observed on the day of surgery, a finding supported by a treatment-time interaction test (p = 0.04).ConclusionsTraumeel was not superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial. A transient reduction in the daily maximum post-operative pain score on the day of surgery is of questionable clinical importance.Trial RegistrationThis study was registered at ClinicalTrials.gov. # NCT00279513

Poor results of drilling in early stages of juxta-articular osteonecrosis in 12 joints affected by Gaucher disease

Background and purpose Gaucher disease is heterogeneous. One of the most devastating complications is bone involvement, ranging from mild osteopenia to osteonecrosis, but no markers have been discovered to predict onset and/or progression. We describe our experience in a large referral center using drilling for juxta-articular osteonecrosis in young patients with Gaucher disease. Patients and methods We retrospectively reviewed medical data from all patients who were recommended to undergo drilling for osteonecrosis of juxta-articular bone of the femoral head, the humeral head, or upper tibia for acute osteonecrosis at a pre-collapse stage. Results 11 patients (mean age 34 years) underwent drilling of 12 joints with juxta-articular osteonecrosis; 3 (mean age 51 years) refused intervention. 9 joints that were drilled showed advancing joint degeneration within 0.5 to 4 years. 3 joints have undergone replacement. Of the 3 joints that did not undergo drilling, 2 have undergone replacement and 1 has collapsed with osteoarthritis. Interpretation We found equally poor outcome with and without drilling. Effective intervention can only be achieved by improving our understanding of bone physiology and pathophysiology in Gaucher disease.

Hip arthroplasty in patients with Gaucher disease.

Patients with Gaucher disease suffering from the consequences of femoral head osteonecrosis deserve a treatment modality that will eliminate pain, preserve ambulation and hopefully will endure long enough to allow satisfactory daily life. Total hip arthroplasty fulfills these 3 objectives. The rate of complications during anesthesia and during surgical procedure is comparable to otherwise healthy population if the Gaucher patients are carefully evaluated pre-surgery and prepared by a medical team familiar with all aspects of the disease. With prompt preparation, meticulous procedure, and careful post-operative care, patients with Gaucher disease may benefit from long-lasting hip prostheses. It is to be hoped that newer types of implants would allow longer revision-free periods even in this young patient population who have developed avascular necrosis, and a greater hope for patients with Gaucher disease would be that early administration of bone-specific therapies may prevent osteonecrosis.

anaesthesia for total hip replacement in Gaucher's disease

EDITOR: Gaucher’s disease, the most common lysosomal storage disorder, is an enzymatic defect with consequent accumulation of undegraded glucocerebroside in cells of the monocyte–macrophage system [1]. Most patients present with enlargement of the spleen and liver resulting in hypersplenism, with thrombocytopaenia generally more significant than anaemia. Skeletal involvement, particularly osteonecrosis of large joints and pathological fractures, invariably is the most significant cause of morbidity and decreased quality of life. In spite of enzyme replacement therapy, osteopaenia and osteonecrosis continue to be clinically important. The need for total hip replacement (THR), and subsequent revision, is relatively common in these patients at a relatively young age. With regard to the anaesthetic management for orthopaedic surgery in patients with Gaucher’s disease, only one case report appears in the literature of an adult with a sub-capital hip fracture who underwent subarachnoid anaesthesia [2]. We wish to report the anaesthetic management of all cases seen in our institution for THR or revision from 1990 to 2005. Patient characteristics and perioperative data are summarized from the clinical records and presented in Table 1. There were 14 patients, 10 males and 4 females, who underwent THR. Five of these underwent a revision. Six patients (43%) were homozygous for the mild N370S (1226) mutation; eight patients (57%) had been splenectomized; and six patients (43%) had pulmonary hypertension at the time of surgery. Fiftythree percentage of patients underwent general anaesthesia. Five of the operations (21%) were performed with preoperative platelet counts 80 103mm 3. Perioperative blood product transfusion was required in 68% of the operations. All patients with general anaesthesia were orally intubated utilizing direct laryngoscopy and ventilated with tidal volume 6–8 mL kg 1 and respiratory rate of 10–16 min 1. There were no difficulties in airway management. All patients were given preoperative antibiotic prophylaxis mainly with cefamezine; nonetheless, 37% experienced postoperative wound infections presenting significantly higher rates compared to similar patients in our institution (2%) and the rate reported in medical literature (0.3–2%) [3]. A wound infection was defined as one of the following: wound redness, excessive pain, tissue necrosis, local oedema, purulent discharge from the operation wound and maximal temperature 38.5 and/or white cell count 10000. Other complications included one inadvertent spinal, one failed spinal and one patient with severe postoperative thrombocytopaenia (21 103mm 3). Joint replacement for patients with Gaucher’s disease is an important therapeutic intervention that dramatically reduces pain, improves functionality and increases quality of life. For patients with Gaucher’s disease, the preoperative evaluation of haematological Correspondence 265