Scleroderma is a disease characterized by immune activation, vasculopathy, fibroblast stimulation, and connective tissue fibrosis. End-organ damage occurs due to progressive tissue fibrosis and vasculopathy. Markers of incipient vasculopathy have not been well studied in scleroderma. However, reduced renal functional reserve and proteinuria are common indicators of progressive vasculopathy in diabetic and hypertensive vasculopathy. Recent studies suggest a strong association between renal involvement and outcomes in scleroderma, with a threefold increased risk of mortality from pulmonary hypertension if renal insufficiency is present. We review the types of renal involvement seen in scleroderma and the data to support the use of renal parameters including proteinuria, glomerular filtration rate, and renal vascular dynamics measured with Doppler ultrasound to identify subclinical renal insufficiency. Further studies are warranted to investigate the use of renal parameters as prognostic indicators in scleroderma.
Chronic leg ulcers are a significant cause of morbidity and mortality and account for considerable healthcare and socioeconomic costs. Leg ulcers are a recognized complication of immune disease, and the purpose of this study was to establish the prevalence of immune disease in a cohort of patients with chronic wounds, and to compare wound outcomes in the subjects with and without immune disease. Retrospective chart review was completed on consecutive patients scheduled with the plastic surgeon in the Georgetown University Center for Wound Healing between January 1 and March 31, 2009. Of the 520 patients scheduled for appointments, 340 were eligible for inclusion. The prevalence of immune disease was higher than expected with 78 of 340 patients (23%) having associated immune disease. At presentation, wounds in patients with immune disease had a significantly larger mean surface area (33.4cm2 (69.05) compared to 22.5 cm2 (63.65), p=0.02). Split thickness skin graft (STSG) and bioengineered alternative tissue (BAT) graft data was available on 177 grafts from 55 subjects. There was a significantly lower response rate to STSG in subjects with immune disease (50% compared to 97%, p=0.0002), but response rates to BAT were not different. The association between immune diseases and chronic wounds may provide unique insights into pathways of wound healing, and warrants further study.
Bioengineered alternative tissue; Immune disease; Rheumatoid arthritis; Split thickness skin graft; Systemic lupus erythematosus
Aromatase inhibitors (AIs) are widely prescribed for post-menopausal hormone receptor-positive breast cancer; however, musculoskeletal symptoms limit their tolerability. The purpose of this study was to determine whether joint pain in women receiving AIs is associated with inflammatory arthritis as measured by the disease activity score-28 (DAS-28), and to evaluate association with tenosynovitis on ultrasound. A total of 48 postmenopausal women with stage I–III breast cancer and hand pain were recruited from the Lombardi Comprehensive Cancer Center. Those receiving AIs were cases (n = 25), and those not receiving AIs were controls (n = 23). During a single study visit, subjects underwent blinded rheumatologic evaluation, DAS-28, health assessment questionnaires, autoantibodies, inflammatory markers, hand X-ray, and hand Duplex ultrasound. There were no significant differences between cases and controls in DAS-28, or inflammatory markers. A positive ANA (titer > 1:160) was found in ten patients, four of whom met criteria for autoimmune disease (two with rheumatoid arthritis and two with Sjogren’s syndrome, equally distributed among cases and controls). This highlights the importance of considering underlying autoimmune disease in subjects with musculoskeletal complaints. Morning stiffness was more prolonged in women receiving AIs, but this did not reach statistical significance (P = 0.07). Ultrasound evidence of flexor tenosynovitis was common in both groups. Although tenosynovitis was not correlated with AI use (P = 0.26), there was a trend toward an association between tenosynovitis and morning stiffness (P = 0.089). While aromatase inhibitor-induced musculo-skeletal symptoms (AIMSS) were more common in subjects receiving AIs, they were not unique to AI users. There was no association between presence of AIMSS features and other chemotherapy or medication exposures. Although the majority of subjects had been using AIs for more than 6 months, this study did not find evidence for inflammatory arthritis in women with hand pain receiving AIs. Further studies are needed to develop a case definition of AIMSS, and to confirm whether these symptoms are attributable to AI use.
Aromatase inhibitor; Arthralgia; Breast cancer; Ultrasound; Tenosynovitis
Indirect immunofluorescence antinuclear antibodies (IIF-ANA) are detected in approximately 90% of scleroderma patients, and the staining pattern correlates with scleroderma-specific antibody subsets. Solid-phase ANA assays that are dependent on multiplex bead technology (MULTIPLEX-ANA) are replacing immunofluorescence in many commercial labs; however, performance of these assays has not been compared to IIF-ANA in scleroderma. The purpose of this study was to evaluate whether a proportion of scleroderma patients have negative testing on MULTIPLEX-ANA assays and demonstrate whether negative MULTIPLEX-ANA is associated with particular scleroderma-specific autoantibodies. A retrospective chart review was completed on all 238 scleroderma patients evaluated in the Georgetown scleroderma clinic between June 1, 2008 and May 31, 2009. Autoantibody results, demographics, and scleroderma features were collected. Data were analyzed using unpaired t test and Mann–Whitney U test for continuous variables, and Fisher’s exact test for dichotomous variables. Simple kappa coefficient was used to measure the level of agreement between MULTIPLEX-ANA and IIF-ANA results. Two-tailed p values <0.05 were considered significant. MULTIPLEX-ANA testing was available in 57 patients and only 29 (51%) tested positive. In contrast, IIF-ANA was positive in 91% of these patients. Using simple kappa coefficient, there was a good agreement between the MULTIPLEX-ANA, and presence of Scl70, RNP, and centromere antibodies (0.76; 95% CI 0.59, 0.92), but there was no agreement between MULTIPLEX-ANA and presence of other IIF-ANA patterns including nucleolar ANA (−0.40; 95% CI −0.64, −0.16). Because RNA polymerase III and nucleolar antibodies are seen in 43% of the entire scleroderma population, we are concerned that these false-negative tests could result in delays in referral and diagnosis. Until the MULTIPLEX-ANA assays can be modified to include the antigens for RNA polymerase III and the nucleolar ANA subsets, IIF-ANA remains the recommended screening test for ANA in suspected scleroderma.
Antinuclear antibody; Autoantibody; IF-ANA; Immunofluorescence; Multiplex; Scleroderma
We present the case of a young man with type II diabetes, stage III chronic kidney disease, hypertension, obstructive sleep apnea and diabetes who presented to the Georgetown University Hospital Center for Wound Healing with refractory lower extremity ulcers. Autoimmune work-up was negative. However, chromosome analysis showed a genetic variant of Klinefelter’s syndrome (48 XXYY). Lower extremity ulceration is a recognised complication of Klinefelter’s syndrome. The pathogenesis of ulcers in this endocrinopathy is unclear, but associations with abnormalities of fibrinolysis and prothrombotic states are reported. This case emphasises the importance of considering Klinefelter’s syndrome in the differential diagnosis of a sterile male patient with non healing lower extremity ulcers.
Fibrinolysis; Klinefelter’s syndrome; Leg ulcer; Prothrombotic
Muslin wrapping is a commonly utilized alternative technique in the treatment of aneurysms that are not amenable to direct clipping. In this case report, we describe two patients from different institutions who both required aneurysm wrapping with gauze/muslin for aneurysm reinforcement. Both patients developed an inflammatory foreign body response to muslin visible on MRI that resulted in a vasculitic stenosis. The onset of TIAs was at 6 months and 1 month postoperatively, respectively. The stenoses rapidly progressed to near occlusion despite antiplatelet therapy, and in one case, an aggressive corticosteroid regimen. One patient eventually developed leptomeningeal collateral flow that allowed tolerance of the stenosis, while the other patient required microsurgical bypass. These cases reports are the first to our knowledge that describe the adverse effects of muslin wrapping without adhesive reinforcement, as well as one of few reports to include follow-up angiographic imaging.
Muslin; Gauzoma; Intracranial stenosis; Vasculitis; MRI; Aneurysm
Nondigital lower extremity ulcers are a difficult to treat
complication of scleroderma, and a significant cause of morbidity.
The purpose of this study was to evaluate the prevalence of
nondigital lower extremity ulcers in scleroderma and describe the
associations with autoantibodies and genetic prothrombotic states.
A cohort of 249 consecutive scleroderma patients seen in the
Georgetown University Hosptial Division of Rheumatology was
evaluated, 10 of whom had active ulcers, giving a prevalence of
4.0%. Patients with diffuse scleroderma had shorter disease
duration at the time of ulcer development (mean 4.05 years ± 0.05)
compared to those with limited disease (mean 22.83 years ± 5.612, P value .0078).
Ulcers were bilateral in 70%. In the 10 patients
with ulcers, antiphospholipid antibodies were positive in 50%,
and genetic prothrombotic screen was positive in 70% which is
higher than expected based on prevalence reports from the general
scleroderma population. Of patients with biopsy specimens
available (n = 5), fibrin occlusive vasculopathy was seen in 100%,
and all of these patients had either positive antiphospholipid
antibody screen, or positive genetic prothrombotic profile. We
recommend screening scleroderma patients with lower extremity
ulcers for the presence of anti-phospholipid antibodies and
genetic prothrombotic states.
The American Board of Internal Medicine Certification Examination (ABIM-CE) is one of several methods used to assess medical knowledge, an Accreditation Council for Graduate Medical Education (ACGME) core competency for graduating internal medicine residents. With recent changes in graduate medical education program directors and internal medicine residents are seeking evidence to guide decisions regarding residency elective choices. Prior studies have shown that formalized elective curricula improve subspecialty ABIM-CE scores. The primary aim of this study was to evaluate whether the number of subspecialty elective exposures or the specific subspecialties which residents complete electives in impact ABIM-CE scores.
ABIM-CE scores, elective exposures and demographic characteristics were collected for MedStar Georgetown University Hospital internal medicine residents who were first-time takers of the ABIM-CE in 2006–2010 (n=152). Elective exposures were defined as a two-week period assigned to the respective subspecialty. ABIM-CE score was analyzed using the difference between the ABIM-CE score and the standardized passing score (delta-SPS). Subspecialty scores were analyzed using percentage of correct responses. Data was analyzed using GraphPad Prism version 5.00 for Windows.
Paired elective exposure and ABIM-CE scores were available in 131 residents. There was no linear correlation between ABIM-CE mean delta-SPS and the total number of electives or the number of unique elective exposures. Residents with ≤14 elective exposures had higher ABIM-CE mean delta-SPS than those with ≥15 elective exposures (143.4 compared to 129.7, p=0.051). Repeated electives in individual subspecialties were not associated with significant difference in mean ABIM-CE delta-SPS.
This study did not demonstrate significant positive associations between individual subspecialty elective exposures and ABIM-CE mean delta-SPS score. Residents with ≤14 elective exposures had higher ABIM-CE mean delta-SPS than those with ≥15 elective exposures suggesting there may be an “ideal” number of elective exposures that supports improved ABIM-CE performance. Repeated elective exposures in an individual specialty did not correlate with overall or subspecialty ABIM-CE performance.
Resident education; Gender; Elective; Subspecialty; Graduate medical education
Lower extremity ulcers are a recognized complication of rheumatoid arthritis (RA). Their prevalence has not been assessed since the advent of more aggressive disease modifying antirheumatic therapies. The purpose of this study was to establish the period prevalence of lower extremity ulcers in a modern-day unselected cohort of patients with RA, and to report the features associated with ulcer development and response to therapy. Between June 2007 and June 2010, 366 RA patients were evaluated at the Georgetown Division of Rheumatology. Data were collected and analyzed retrospectively on demographics, antibody and prothrombotic profile, comorbidities, disease activity, and outcomes. The period prevalence of ulcers in this cohort of 366 patients with RA followed over 3 years was 4.37%. Patients with ulcers were predominantly female (81.25%) and more commonly African American (56.2%). The mean disease duration at ulcer development was 25.9 years. All patients with ulcers had erosive disease and 63% were seropositive. Only five patients (31.25%) healed over a mean follow-up of 22.8 months. However, in this small sample, treatment with anti-tumor necrosis factor-α (anti-TNFα) therapy was associated with significantly higher likelihood of healing (p=0.039). In this modern-day cohort of patients with RA, we found a prevalence of lower extremity ulcers of 4.37% over 3 years. Only 31.25% of patients healed after a mean 22.8 months of follow-up. However, treatment with a biologic agent was associated with a significant increased likelihood of healing (RR 3.27, 95% CI 0.59–18.29, p=0.039).
Anti-tumor necrosis factor-α; Disease modifying antirheumatic drug (DMARD); Leg ulcer; Rheumatoid arthritis; Vasculitis; Wound healing
Primary lymphoma of the bone (PLB) accounts for 2% of all non-Hodgkin's lymphomas, and until recently it had not been well characterized in literature. Most cases present in adulthood (average age 50), with localized painful lesions in the long bones, cranium, or axial skeleton.
We describe a case of multifocal PLB in an adolescent female. In this case, the initial presentation, with migratory large joint polyarthralgias and bone pain, mimicked chronic recurrent multifocal osteomyelitis (CRMO). Had a biopsy not been performed the diagnosis would have been missed.
chronic recurrent multifocal osteomyelitis; primary lymphoma of bone; bone pain; adolescent.