Hypermobility spectrum disorders: A review.

It remains a clinical challenge identifying when joint hypermobility (JH) is responsible for pain. Previous nomenclature utilized terms such as (benign) joint hypermobility syndrome (JHS) but this was updated in 2017 as advances in genetics provide a basis for nearly all variants of Ehlers-Danlos syndrome (EDS) with the exception of hypermobile EDS (hEDS). New terminology describes hypermobility spectrum disorders (HSDs) as the updated term for JHS. Diagnosis of a subtype of HSDs should be considered in patients who have JH coupled with the presence of secondary musculo-skeletal manifestations (trauma, chronic pain, disturbed proprioception, and other manifestations) and at the exclusion of hEDS. Extra-articular manifestations are common. Treatment relies on management strategies for other chronic pain syndromes with a multidisciplinary approach likely optimal. Lifestyle modifications focus on weight loss and exercise. Physical therapy helps strengthen periarticular muscles, improving mobility. Pharmacologic therapies focus on judicious use of non-steroidal anti-inflammatory drugs and acetaminophen. Serotonin and norepinephrine reuptake inhibitor may help widespread pain. Avoidance of opioids remains prudent. The purpose of this review is to provide clinicians the rationale for the update in nomenclature, understand the musculoskeletal and extra-articular manifestations of the subtypes of HSDs, considerations when making the diagnosis, and treatment.

Recognizing Gender Parity in Military Medicine: An Analysis of Plenary Speakers and Award Recipients at Military American College of Physicians Chapter Meetings.

INTRODUCTION: Despite the advances toward gender parity in medicine, a gap exists in the recognition of women physicians at academic and subspecialty medical conferences as plenary speakers and award winners. Conferences are cornerstones in the practice of medicine because they serve as platforms to showcase physicians' successes and disseminate work. The selection of who is honored at such events can impact an individual's career by creating networks that may lead to future opportunities. Additionally, the trend of who is honored may create expectations in the minds of trainees and early career physicians about what qualities help an individual achieve success. Our group sought to determine whether there was a gender gap in award recognition and speakership opportunities at the American College of Physicians (ACP) annual military chapter meetings. METHODS: This was a cross-sectional study with data extracted from publicly available conference programs for the Army-Air Force annual ACP meetings and the Navy annual ACP meetings. Five years of data erewere reviewed for invited plenary speakers. Ten years of data were reviewed for award recipients. For an award to be included, it had to have a preset description and criteria for recipient selection. Awards not given annually or awards given for less than 3 years were excluded. Individuals' gender was determined based on the first name and confirmed through internet searches of pronoun descriptors from professional websites. Comparisons were done using Fisher's exact test and chi-square tests when appropriate, with statistical significance set at a two-tailed P-value of <.05. RESULTS: Women comprised 26-30% of the chapter membership and there was no significant difference in gender distribution between the chapters. Fourteen of the 69 plenary speakers were women (20%), with significantly fewer women presenters in the Navy as compared to men. Thirty-six of the 134 award winners were women (27%), which was not significantly different from the overall chapter gender distributions. While women recipients of lifetime, teaching, research, and medical student awards were not significantly different from chapter gender distribution, women faculty were significantly more likely to receive an award for teaching than for research, with women receiving 13 of the 28 teaching awards (41%), and none of the 10 faculty research awards. CONCLUSIONS: The military chapter ACP meetings reviewed mirrored civilian data in many ways, although military plenary speaker and award recipient distributions were more representative of the gender distribution of the branches. Review of the nomination process, planning committee selection, and opportunities for diversity training could be optimized to ensure that future conferences have a gender-balanced representation of individuals being honored. Improving upon current practices is important for the growth and retention of women military physicians.

Tocilizumab in the treatment of myocardial infarction.

Tocilizumab (TCZ) is an important biologic response modifier that rheumatologists routinely employ in the treatment of several systemic autoimmune diseases. TCZ binds to interleukin (IL)-6 receptors, inhibits cellular activation, and mitigates inflammation by IL-6. In mid-2017, TCZ was approved by the US Food and Drug Administration for its first nonrheumatologic condition, the treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome in patients 2 years of age or older. With this approval and with the increasing use of TCZ off-label for other non-rheumatologic conditions such as Castleman's Disease and its variant TAFRO syndrome, where else might TCZ be successfully utilized as treatment? Recently interesting data has been published regarding possible use of TCZ in the treatment of myocardial infarction. This review focuses on the role of IL-6 and its receptor in myocardial inflammation and association with adverse clinical outcomes. Discussed are one animal study and two human trials that have been published studying the effect of TCZ in patients with acute myocardial infarction. Finally, this review summarizes the current data and makes recommendations for future clinical trial development in what hopefully will be a promising application of TCZ for a serious nonrheumatologic condition.

Comparing Corticosteroid Preparation and Dose in the Improvement of Shoulder Function and Pain: A Randomized, Single-Blind Pilot Study.

INTRODUCTION: Shoulder pain may arise from inflammation of the bursa separating the supraspinatus tendon from the coracoacromial ligament and acromion. The optimal treatment dose and preparation of intrabursal corticosteroid injection are unknown. METHODS: This single-blinded equivalence study recruited 62 subjects randomizing them to one of following four arms: methylprednisolone 20 mg, methylprednisolone 40 mg, triamcinolone acetonide 20 mg, or triamcinolone acetonide 40 mg. QuickDASH, subject-reported pain, and adverse events were recorded in time of injection, 3 days later, 3 wks later, and 6 wks later. Primary outcome was QuickDASH improvements 6 wks after injection. RESULTS: All four groups were equally matched regarding age, sex, ethnicity, and site injected. Six weeks after injection, no statistically significant changes were noted in QuickDASH improvement (as compared with time of injection) among the four arms. There were no statistically significant differences at 6 wks regarding improvement in pain. There were no statistically significant differences noted in adverse events among the four arms. CONCLUSIONS: Neither dose nor preparation of injectable corticosteroid influences magnitude of improvement in function or pain experienced. Although this study provides clinically relevant insight regarding corticosteroid dose and type when managing shoulder pain, the modest sample size may limit the conclusions that can be made about efficacy and adverse effects.

Short-term application of tocilizumab during myocardial infarction (STAT-MI).

Acute myocardial infarction (MI) occurs when blood supply falls below critical levels and normal cellular maintenance mechanisms fail. Interleukin-6 (IL-6) is a proinflammatory cytokine released in MI and associated with poor clinical outcomes. Tocilizumab (TCZ) is a humanized monoclonal antibody against the IL-6 receptor. In a randomized, double-blinded, placebo controlled trial we assigned subjects admitted with MI a single TCZ dose of 162 mg subcutaneously vs. placebo in addition to standard of care medications and interventions. Primary outcome was a change in major adverse cardiac events (MACE) 30 days after enrollment. Secondary outcomes assessed changes in CRP 30 days after enrollment, changes in QT/QTc, and monitoring for trends in adverse events. Futility analysis was performed as subject enrollment slowed and no trends were noted in either the primary or secondary outcomes. Twenty-eight subjects were enrolled; 12 to TCZ and 16 to placebo. No statistically significant differences were noted between study arms regarding demographics, comorbidities, or medical/interventional therapies received. No statistically significant differences in MACE were observed. CRP increased after administration of TCZ but this was not statistically significant. No adverse events or safety signals were observed. Though futility analysis suggested that the primary outcome was not likely achievable as our recruitment slowed, we did not observe any adverse events or safety trends. Building on this information, future studies should be conducted to assess a true benefit from TCZ as adjunct therapy for MI. The work reported herein was performed under United States Air Force Surgeon General approved Clinical Investigation FKE20140029 and has been registered at ClinicalTrials.gov under identifier NCT02419937.

Genomic sequencing of uric acid metabolizing and clearing genes in relationship to xanthine oxidase inhibitor dose.

It remains unclear why the dose of xanthine oxidase inhibitors (XOI) allopurinol or febuxostat varies among patients though they reach similar serum uric acid (SUA) goal. We pursued genomic sequencing of XOI metabolism and clearance genes to identify single-nucleotide polymorphisms (SNPs) relate to differences in XOI dose. Subjects with a diagnosis of Gout based on the 1977 American College of Rheumatology Classification Criteria for the disorder, who were on stable doses of a XOI, and who were at their goal SUA level, were enrolled. The primary outcome was relationship between SNPs in any of these genes to XOI dose. The secondary outcome was relationship between SNPs and change in pre- and post-treatment SUA. We enrolled 100 subjects. The average patient age was 68.6 ± 10.6 years old. Over 80% were men and 77% were Caucasian. One SNP was associated with a higher XOI dose: rs75995567 (p = 0.031). Two SNPs were associated with 300 mg daily of allopurinol: rs11678615 (p = 0.022) and rs3731722 on Aldehyde Oxidase (AO) (His1297Arg) (p = 0.001). Two SNPs were associated with a lower dose of allopurinol: rs1884725 (p = 0.033) and rs34650714 (p = 0.006). For the secondary outcome, rs13415401 was the only SNP related to a smaller mean SUA change. Ten SNPs were identified with a larger change in SUA. Though multiple SNPs were identified in the primary and secondary outcomes of this study, rs3731722 is known to alter catalytic function for some aldehyde oxidase substrates.

Rheumatoid arthritis in patients with HIV: management challenges.

Over the past few decades, HIV has been transformed from a once-uniformly fatal disease to now a manageable but complex multisystem illness. Before highly active antiretroviral therapy (HAART), reports suggested that HIV-infected patients with rheumatoid arthritis (RA) would experience remission of their disease. It has now become clear that RA can develop in HIV-infected patients at any time, independent of HAART. Choosing the right medication to treat symptoms related to RA while avoiding excess weakening of the immune system remains a clinical challenge. Agents such as hydroxychloroquine and sulfasalazine might best balance safety with efficacy, making them reasonable first choices for therapy in HIV-infected patients with RA. More immune suppressing agents such as methotrexate may balance safety with efficacy, but data are limited. Corticosteroids such as prednisone may also be reasonable but could increase the risk of osteonecrosis. Among biologic response modifiers, tumor necrosis factor α inhibitors may balance safety with efficacy, but perhaps when HIV replication is controlled with HAART. Monitoring RA disease activity remains challenging as only one retrospective study has been published in this area. Those with HIV infection and RA can experience comorbidities such as accelerated heart disease and osteoporosis, a consequence of the chronic inflammatory state that each illness generates. Although HIV-infected patients are at risk for developing the immune reconstitution inflammatory syndrome when starting HAART, it appears that immune reconstitution inflammatory syndrome has a minimal effect on triggering the onset or the worsening of RA.

Necrotizing Autoimmune Myopathy: A Unique Subset of Idiopathic Inflammatory Myopathy.

Necrotizing autoimmune myopathy (NAM) is a recently recognized entity within the spectrum of idiopathic inflammatory myopathies. Diagnosis critically rests on histopathologic demonstration of macrophage predominant myocyte destruction, with few to no lymphocytes. We report our experience with identifying and treating this subset of inflammatory myositis, highlighting the importance of muscle biopsy in diagnosis, association with statin use and malignancy, and challenges of therapy.We present 3 cases that presented to 2 hospitals within our academic system in calendar year 2014 with acute/subacute onset of profound proximal muscle weakness and markedly elevated creatine kinase levels. All patients had been exposed to statins for varying periods. While each electromyogram (EMG) study showed changes with a diffuse inflammatory myopathy, it was not until muscle biopsy was performed when histopathologic features consistent with NAM solidified the diagnosis in all 3 cases. While high-dose glucocorticoids helped provide some degree of improvement in symptoms, none of our cases returned to their preillness baseline independent functioning. Additional immunosuppressive therapy was considered in each case but limited because of comorbidities.These cases demonstrate the importance of pursuing muscle biopsy in all patients with proximal muscle weakness and markedly elevated creatine kinase levels. While symptoms appear consistent with polymyositis, only through muscle biopsy can the diagnosis of NAM be made. Statins have been implicated in NAM, acting through an antibody-dependent mechanism. Combination immunosuppressive therapy has been advocated, but our patient's comorbidities precluded safe use of medications beyond glucocorticoids.

Hepatitis C Virus in the US Military Retiree Population: To Screen, or Not to Screen?

BACKGROUND: In 2012, the Centers for Disease Control (CDC) recommended hepatitis C virus (HCV) screening for those born between 1945 and 1965. Prior recommendations endorsed screening based on risk factors (RFs). Because United States (US) military retirees have had at least 20 years of access to free comprehensive health care, mandatory physical fitness tests, periodic health assessments and mandatory drug screening, we hypothesized that the prevalence of HCV amongst military retirees is lower than the national average. Thus the new CDC screening guidelines may not be applicable or cost effective in this particular population. METHODS: A quality improvement (QI) initiative implemented the new birth-cohort CDC screening guidelines for the internal medicine (IM) clinic of our hospital (QI group). An age-matched group from the same IM clinic, screened based on RFs for HCV infection, served as the comparator (RF group). The prevalence of the anti-HCV antibody and chronic infection was determined and compared with each other and with the national average. RESULTS: The prevalence of the HCV antibody was 2.1% and 2.3% in the QI and RF groups, respectively (odds ratio (OR): 1.08, 95% CI: 0.37 - 3.21, P = 1.000). The prevalence of chronic infection was 0.4% and 1.8% in the QI and RF groups, respectively (OR: 4.39, 95% CI: 0.80 - 24.13, P = 0.083). When our data were compared with the national average, there were no statistical differences in the prevalence of the HCV antibody; however, there was statistically more viral clearance, and subsequently less chronic infection, in the QI group versus the national average. CONCLUSIONS: The military retiree population did not have a lower prevalence of the HCV antibody than the American populace whether screened based on age or traditional RFs. Thus, the CDC guidelines are applicable in this population. One interesting finding of this study is the higher rate of viral clearance in military retirees when compared with the national average. It is therefore possible that military retirees may be more likely to have natural viral eradication than the civilian population.

Rilonacept in the treatment of subacromial bursitis: A randomized, non-inferiority, unblinded study versus triamcinolone acetonide.

INTRODUCTION: Subacromial bursitis is caused by inflammation of the bursa that separates the superior surface of the supraspinatus tendon from the overlying coraco-acromial ligament and acromion. While multiple cytokines are implicated, interleukin-1 beta appears to play a prominent role. Rilonacept, an interleukin-1 trap, may be an alternative to corticosteroid injection for the management of this condition. METHODS: This single center, randomized, non-inferiority, unblinded study recruited 33 subjects over 9 months. Twenty subjects received 160mg intrabursal injection of rilonacept and 13 received a 6mL mixture of lidocaine, bupivacaine, and 80mg triamcinolone acetonide. QuickDASH, subject reported pain, and adverse events were recorded at time of injection, 2 days later, 2 weeks later, and 4 weeks later. Primary outcome was improvement in QuickDASH 4 weeks post-injection. Secondary outcomes were improvement in subject reported pain and occurrence of adverse events at 4 weeks. RESULTS: Both study groups were equally matched for age, gender, ethnicity, and site of bursa injection. Both medications demonstrated a statistically significant improvement in QuickDASH 4 weeks post-injection, but triamcinolone acetonide injection offered greater improvement (P=0.004). Both medications demonstrated improvement in subject reported pain but between group comparison at 4 weeks showed that triamcinolone was superior (P=0.044). No statistically significant differences in adverse events were noted between groups, but subjects who received rilonacept experienced more episodes of diarrhea and headache. CONCLUSIONS: While improvement in QuickDASH and pain was noted with a single intrabursal injection of rilonacept at 4 weeks, injection with triamcinolone acetonide was more efficacious. This trial was registered with www.clinicaltrials.gov (NCT01830699).

A case of relapsing kikuchi-fujimoto disease.

Kikuchi-Fujimoto disease (KFD) or histiocytic necrotizing lymphadenitis was first described in Japan in 1972. It is described as a benign syndrome most commonly involving cervical lymphadenopathy, fever, and night sweats. The etiology of KFD is unknown but it is thought to be triggered by an autoimmune or viral process with an exaggerated T-cell-mediated immune response. KFD can mimic other serious conditions such as lymphoma, systemic lupus erythematosus (SLE), herpes simplex, and Epstein Barr virus. Diagnosis is confirmed histopathologically. Kikuchi's disease is typically reported to have a self-limiting course, resolving within several months and with a low recurrence rate between 3% and 4%. There is no specific treatment for KFD but any treatment is generally directed towards symptomatic relief with antipyretics and anti-inflammatory medications. In severe cases corticosteroids have been used. Here we describe a case of a previously healthy 26-year-old female that presented with fever and cervical lymphadenopathy. Malignancy and infections were ruled, and she was diagnosed with KFD histopathologically by lymph node biopsy. Her case is a severe case of KFD that despite treatment with multiple courses of corticosteroids and an immune modulating agent, relapsed.

Persistent Lymphadenopathy due to IgG4-Related Disease.

A 28-year-old healthy female presented to her primary care physician with lymphadenopathy, fatigue, malaise, and night sweats. Symptoms persisted despite conservative treatment and eventually the patient underwent multiple lymph node resections and a bone marrow biopsy before a diagnosis of IgG4-related disease (IgG4-RD) was made. IgG4-RD is a relatively new disorder first histopathologically recognized within the last decade. As the disease can affect a single organ or multiple organs, symptoms can vary greatly among patients. With symptoms ranging from mild, such as lower extremity edema, to severe, such as spinal cord compression, IgG4-RD must be considered in appropriate patients. Diagnostic criteria have been proposed based on organ involvement, serum IgG4 levels, and histopathological criteria. Diagnosis can be difficult to make with many studies suggesting different values for diagnostic criteria, such as the level of tissue IgG4+/IgG+ cell ratio to delineate IgG4-RD. Treatment consists of high dose glucocorticoids as a first line therapy with some patients choosing instead to simply undergo observation. This case illustrates the difficulty in diagnosis and the need for increased awareness among medical professionals.

The impact of biologic response modifiers on hepatitis B virus infection.

INTRODUCTION: The biologic response modifiers are a diverse group of medications that have emerged over the last decade. They target pro-inflammatory cytokines or cell surface molecules that drive illnesses such as rheumatoid arthritis. Despite the greater control afforded they have also ushered in a new spectrum of side effects. As the same immunologic machinery that helps control infections such as HBV contributes to the pathogenesis of rheumatologic diseases, persistence or reactivation of the virus remains an evolving concern. AREAS COVERED: A systemic literature review was performed using the PubMed and Medline databases (1996 to January 2010) searching for the index term 'Hepatitis B' combined with the terms 'tumor necrosis factor', 'B cell', 'rituximab', 'IL-1', 'anakinra', 'IL-6', 'tocilizumab', 'CTLA-4', and 'abatacept'. All relevant articles in English were reviewed and secondary references of interest were also retrieved. This paper addresses the role of the various cytokines and cluster of differentiation molecules in controlling HBVinfection and the currently known effect that the biologic response modifiers have on viral control by the host immune response. EXPERT OPINION: The risk of HBV reactivation is greatest in HBsAg positive patients. These patients should start antiviral therapy one week before receiving a biologic response modifier. The risk of HBV reactivation in HBsAg negative patients appears very low but when HBsAb titers are low use of rituximab or TNF-α antagonists may increase the risk of reactivation.

Sternocostoclavicular hyperostosis: a review.

Sternocostoclavicular hyperostosis (SCCH) is a chronic inflammatory disorder which presents with erythema, swelling, and pain of the sternoclavicular joint. Approximately one half of patients have acne or pustular lesions with the best described association being with palmoplantar pustulosis (PPP). Extrasternal articular disease occurs in about a quarter of patients. The inflammatory process spans several years and has periods of exacerbation followed by remission. The histologic picture demonstrates a sterile osteomyelitis of the sternum and medial end of the clavicle. The diagnosis of SCCH is confirmed radiographically by hyperostosis and sclerosis of the sternum with involvement of the first rib on computed tomography (CT). The focal uptake of radiopharmaceutical on bone scintigraphy called the 'bullhead' sign is highly sensitive of SCCH. Treatment is aimed at easing pain and modifying the inflammatory process. Evidence over the last two decades suggests a role for intravenous bisphosphonates and tumor necrosis factor alpha inhibitors. A low level of awareness of SCCH often leads to a delay in diagnosis. This translates into significant morbidity and brings a psychological burden. Untreated chronic inflammation of the sternoclavicular joint leads to restricted mobility and secondary degenerative joint changes. In the search for a diagnosis, patients often undergo multiple serologic and imaging studies and in the experience of the author are referred to multiple specialists before a correct diagnosis is made. Greater awareness of SCCH is needed to prevent the irreversible physical and psychological impairments associated with the disease.

Dermatomyositis and HIV infection: case report and review of the literature.

Since the 1980s, a host of autoimmune phenomena and rheumatologic illnesses have been linked to infection with the human immunodeficiency virus (HIV). Given the broad effects of this virus on both the humoral and cell-mediated arms of the immune system, illnesses such as polymyositis and Reiter's syndrome appear to be more prevalent in HIV-infected individuals and occur in the absence of well-described predispositions. The activities of some rheumatologic illnesses exhibit an inverse relationship with the course of HIV infection, such as rheumatoid arthritis, which becomes more quiescent with advancing disease. Dermatomyositis is a rheumatologic illness that very infrequently occurs and during our review of literature only three other cases were reported. We present the case of a Caucasian male in his mid-20s who presented with acquired immunodeficiency syndrome and subsequently developed dermatomyositis. In this review, we highlight the current relationship between HIV infection and autoimmunity, the possible ways HIV infection may foster an environment favorable for the development of dermatomyositis, and review the previously reported cases of individuals with HIV infection who developed dermatomyositis. The complex issues of how to treat individuals with HIV and dermatomyositis is also discussed.

Use of tumor necrosis factor alpha inhibitors in hepatitis B surface antigen-positive patients: a literature review and potential mechanisms of action.

As a class, tumor necrosis factor (TNF)-alpha inhibitors have provided clinicians significant control over chronic inflammatory diseases. With their widespread use has come the emergence of new side effects such as the reactivation of latent infections. One such infection that may reactivate is the hepatitis B virus (HBV). It is currently unknown if HBV reactivation is a class effect or attributable to a particular TNF-alpha inhibitor. To answer this question, a comprehensive literature review to identify trends in related cases was performed. A systemic literature review was performed using the PubMed and Medline databases (1996 to January 2010) searching for the index term "Hepatitis B" combined with the terms "tumor necrosis factor," "TNF-alpha inhibitors," "etanercept," "adalimumab," "certolizumab," and "golimumab." All relevant articles in English were reviewed, and secondary references of interest were also retrieved. Thirty-five cases with hepatitis B surface antigen (HBsAg) positivity known prior to initiation of TNF-alpha inhibitors were identified. Infliximab was used in 17 cases, etanercept in 12 cases, and adalimumab in 6 cases. All six cases of clinically symptomatic hepatitis were associated with infliximab therapy. Infliximab was associated with the most cases of greater than 2-fold increase in alanine aminotransferase (six of nine cases) and greater than 1,000-fold increase in HBV DNA load (three of four). The two deaths reported occurred with infliximab therapy. Potential mechanisms of action for the reported observations include differences in molecular design, route of administration, and potency in clearing TNF-alpha. In patients with a positive HBsAg prior to starting a TNF-alpha inhibitor, infliximab has the most reported cases associated with HBV reactivation. While such reactivation may be due to a variety of reasons, clinicians prescribing TNF-alpha inhibitors to HBsAg-positive patients should consider prophylactic antiviral therapy and close monitoring for any clinical or serological evidence of hepatitis.

Use of tumor necrosis factor-alpha inhibitors in patients with chronic hepatitis B infection.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) inhibitors have emerged as a potent treatment for rheumatoid arthritis (RA), but not without significant risks. In chronic hepatitis B viral infection TNF-alpha is readily produced, and viral clearance is dependent on the amount bioavailable. Limited data suggest that TNF-alpha inhibitors may facilitate uncontrolled hepatitis B viral replication. The purpose of this article was to provide a detailed review of the role of TNF-alpha in controlling hepatitis B viral infection and the clinical impact blockade might have on viral control. METHODS: We describe a patient with chronic hepatitis B viral infection and RA treated with etanercept. We then review case reports, expert opinion, and manufacturer recommendations regarding hepatitis B viral infection, TNF-alpha, and TNF-alpha inhibitors. RESULTS: To date, 13 patients with chronic hepatitis B infection treated with TNF-alpha inhibitors have been reported: 11 with infliximab and 2 with etanercept. Some patients received antiviral therapy for hepatitis B (specifically lamivudine) before, during, or after TNF-alpha inhibitors were started. Clinically apparent reactivation of hepatitis B virus typically occurred 1 month after the 3rd dose of infliximab. Etanercept was not associated with a similar reactivation. The difference between infliximab and etanercept in viral reactivation may be linked to the pharmacologic difference of each medication. CONCLUSIONS: TNF-alpha inhibitors in general should be used cautiously in chronic hepatitis B viral infection. But if necessary, when deciding which agent to use, the clinician should consider the mechanism by which the body clears TNF-alpha.

MELAS masquerading as a systemic vasculitis.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke (MELAS) is a mitochondrial genetic disorder caused by a point mutation, resulting in the substitution of guanine for adenine at nucleotide 3243 (A3243G). It is a multisystem disorder with variable manifestations and typically presents between the first and third decades of life. It should be suspected if a patient exhibits stroke-like episodes before age 40, encephalopathy characterized by seizures, dementia, or both, and lactic acidosis, ragged-red fibers in muscle, or both. We present the case of a 26-year-old white man suspected with primary central nervous system vasculitis admitted to our facility with profound constipation from severe intestinal dysmotility. Although his gastrointestinal and neurologic symptoms did not meet criteria for a specific vasculitic syndrome, his symptoms and blood test abnormalities were concerning for such a process. MELAS was included in our differential diagnosis because his symptoms failed to fit a defined vasculitic process. When genetic testing documented the presence of the point mutation A3243G, his diagnosis was changed. This case illustrates the importance of considering a mitochondrial genetic disorder in the differential diagnosis of patients who present to Rheumatologists with suspected unusual or atypical vasculitic symptoms.