Recent Publications by CFE Educators

BACKGROUND

Ankylosing spondylitis (AS), an inflammatory arthritis that affects the axial skeleton, predisposes patients with severe disease to falls and spinal fractures. Advanced imaging has improved the process of fracture detection. In spite of increased knowledge about early diagnosis and management of AS, little attention is being paid to the environmental hazards that pose a risk for patient outcome.

OBJECTIVES

To identify risk factors for falls and fractures and evaluate imaging modalities in the detection of fractures in AS patients.

METHODS

A case report and review of the literature using PubMed for English articles from 2000 to 2013 regarding AS patients׳ risk factors for falls and fractures and imaging modalities used to diagnose fracture in this population.

RESULTS

Potential impairments in balance and coordination in the AS population include vestibular dysfunction, thoracolumbar kyphosis, and deficits in proprioception. A common and significant environmental risk factor for falls includes the use of a tub-shower arrangement. Furthermore, osteoporosis is a well-known complication of AS, which can predispose to a fracture. Lastly, there are no comprehensive studies that have evaluated the ability of advanced imaging modalities to identify an acute spine fracture in this patient population.

CONCLUSIONS

AS patients with advanced disease are at an increased risk of falls and fractures due to many factors including but not limited to a rigid spine and difficulty with peripheral vision. A tub-shower arrangement commonly found in homes and hotel rooms is a major hazard. A consistent approach to diagnosis of fractures involving advanced imaging recommendations should be considered.

Costello syndrome (CS) is a RASopathy characterized by a wide range of cardiac, musculoskeletal, dermatological, and developmental abnormalities. The RASopathies are defined as a group of syndromes caused by activated Ras/mitogen-activated protein kinase (MAPK) signaling. Specifically, CS is caused by activating mutations in HRAS. Although receptor tyrosine kinase (RTK) signaling, which is upstream of Ras/MAPK, is known to play a critical role in craniofacial and dental development, the craniofacial and dental features of CS have not been systematically defined in a large group of individuals. In order to address this gap in our understanding and fully characterize the CS phenotype, we evaluated the craniofacial and dental phenotype in a large cohort (n = 41) of CS individuals. We confirmed that the craniofacial features common in CS include macrocephaly, bitemporal narrowing, convex facial profile, full cheeks, and large mouth. Additionally, CS patients have a characteristic dental phenotype that includes malocclusion with anterior open bite and posterior crossbite, enamel hypo-mineralization, delayed tooth development and eruption, gingival hyperplasia, thickening of the alveolar ridge, and high palate. Comparison of the craniofacial and dental phenotype in CS with other RASopathies, such as cardio-facio-cutaneous syndrome (CFC), provides insight into the complexities of Ras/MAPK signaling in human craniofacial and dental development.

Cannabis is the most widely used illicit drug in the United States, with lifetime prevalence of use estimated at 42% to 46%. The antiemetic properties of cannabis are well-known by the medical community and the general public; however, less well-recognized is the paradoxical potential for certain chronic users to develop hyperemesis. We describe in this case a patient with prior extensive work-up for nausea and vomiting and previous diagnosis of cyclic vomiting syndrome who presented with characteristic features of cannabinoid hyperemesis syndrome. We review the current literature for this condition and highlight potential mechanisms for its pathogenesis.

BACKGROUND

Information regarding dosing of low-molecular-weight heparins (LMWH) for therapeutic anticoagulation in hemodialysis (HD) patients is limited. The aim of this study was to retrospectively compare the safety and efficacy of enoxaparin versus unfractionated heparin (UFH) for therapeutic anticoagulation in HD patients.

MATERIALS AND METHODS

This retrospective chart review evaluated HD patients treated with subcutaneous enoxaparin that were matched based on the indication for anticoagulation with patients treated with intravenous UFH to achieve therapeutic anticoagulation. Primary outcome measures included 30-day incidence of thromboembolic events and major bleeding. Secondary outcomes included rehospitalization within 30days, length of stay, and mortality.

RESULTS

One hundred sixty-four patients were evaluated, 82 in each group. The average daily dose of enoxaparin used to target therapeutic levels was 0.7±0.2mg/kg/day (range=0.4-1). Comparing enoxaparin to UFH, there was no significant difference in major bleeding (6.1% vs 11%, p=0.4) or thromboembolism (0% vs 2.4%, p=0.5). Hospital length of stay was shorter in the enoxaparin group (20±53.8 vs 28.9±44.5days, p=0.02); there was no significant difference between groups in mortality or readmission. Adjusting for risk factors for bleeding there was a slight but statistically non-significant difference between enoxaparin versus UFH (OR=0.77, 95%CI: 0.2-3.5, p=0.73).

CONCLUSIONS

These findings suggest that therapeutic dosing of enoxaparin, in doses that ranged from 0.4-1mg/kg/day, was as safe as intravenous UFH in providing therapeutic anticoagulation in stable patients requiring chronic hemodialysis.

Scleroderma en coup de sabre typically presents with a cutaneous induration, but involvement of the underlying bone, eye, and brain is common. We report on 4 pediatric cases with atypical initial clinical presentations. All cases were seen at the University of California San Francisco. Patients 1 and 2 presented to the Pediatric Rheumatology Clinic with uveitis and orbital pseudotumor in December 2009 and March 2010, respectively. Patients 3 and 4 were mimicking acquired demyelinating disorders of the brain, acute demyelinating encephalomyelitis and multiple sclerosis, and were referred to the Pediatric Multiple Sclerosis center in 2008.

OBJECTIVE

To identify genetic associations with severity of radiographic damage in ankylosing spondylitis (AS).

METHOD

We studied 1537 AS cases of European descent; all fulfilled the modified New York Criteria. Radiographic severity was assessed from digitised lateral radiographs of the cervical and lumbar spine using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). A two-phase genotyping design was used. In phase 1, 498 single nucleotide polymorphisms (SNPs) were genotyped in 688 cases; these were selected to capture >90% of the common haplotypic variation in the exons, exon-intron boundaries, and 5 kb flanking DNA in the 5' and 3' UTR of 74 genes involved in anabolic or catabolic bone pathways. In phase 2, 15 SNPs exhibiting p0.05 were genotyped in a further cohort of 830 AS cases; results were analysed both separately and in combination with the discovery phase data. Association was tested by contingency tables after separating the samples into 'mild' and 'severe' groups, defined as the bottom and top 40% by mSASSS, adjusted for gender and disease duration.

RESULTS

Experiment-wise association was observed with the SNP rs8092336 (combined OR 0.32, p=1.2×10(-5)), which lies within RANK (receptor activator of NFκB), a gene involved in osteoclastogenesis, and in the interaction between T cells and dendritic cells. Association was also found with the SNP rs1236913 in PTGS1 (prostaglandin-endoperoxide synthase 1, cyclooxygenase 1), giving an OR of 0.53 (p=2.6×10(-3)). There was no observed association between radiographic severity and HLA-B*27.

CONCLUSIONS

These findings support roles for bone resorption and prostaglandins pathways in the osteoproliferative changes in AS.