Atypical Adult-Onset Still's Disease Presenting With Seizures and Myocarditis Complicated by Macrophage Activation Syndrome.

Adult-onset Still's disease (AOSD) is a rare multi-systemic inflammatory disorder characterized by high spiking fevers, nonpruritic, salmon-colored rash, and severe polyarthralgia. Laboratory features typically include elevation in white blood cells, liver enzymes, and ferritin. Central nervous system and cardiac involvements, particularly myocarditis, are rare. Macrophage activation syndrome (MAS) is a well-described complication of AOSD, leading to a high mortality rate. Herein, we describe a case of AOSD complicated by MAS in a 32-year-old male presenting with atypical clinical manifestations, including recurrent seizures, scaly, pruritic, and hyperpigmented rash, and right heart failure due to lymphocytic myocarditis. The patient exhibited a delayed onset of fever, leukocytosis, and transaminitis that initially deterred eligibility for Yamaguchi criteria for AOSD. Bone marrow and lymph node biopsies did not show malignancy, infection, or hemophagocytosis. However, soluble interleukin-2 receptor alpha or soluble CD-25 was elevated. The patient experienced significant improvement on combination therapy of anakinra, methotrexate, and stress-dose steroids. HScore was later indicative of a high probability for MAS. Outpatient management involved prednisone, cyclosporine, and canakinumab for MAS. Seizure and myocarditis are possible presenting features of atypical AOSD. Early recognition of non-criteria AOSD and MAS and prompt initiation of therapy may prevent mortality.

Metformin in Systemic Lupus Erythematosus: Investigating Cardiovascular Impact and Nephroprotective Effects in Lupus Nephritis.

OBJECTIVE: Systemic lupus erythematosus (SLE) is characterized by widespread organ inflammation. Metformin, commonly used for diabetes mellitus type 2, has been explored for its anti-inflammatory potential in SLE. This study investigates the association of metformin use on renal and cardiovascular outcomes in patients with SLE. METHODS: This is a retrospective study. We used the multicenter research network (TriNetX) database from 88 health care organizations globally. Patients with SLE aged 18 and above, admitted between January 1, 2014, and April 21, 2024, were included. Propensity score matching compared patients with SLE on metformin with those not on metformin, considering demographics, laboratory results, comorbidities, and baseline medication use. The study assessed outcomes, including lupus nephritis (LN), chronic kidney disease (CKD), and major adverse cardiovascular events (MACEs) at one and five years after SLE diagnosis. RESULTS: We identified 9,178 patients with SLE on metformin and 78,983 patients with SLE not on metformin. After propensity score matching, patients with SLE on metformin had higher levels of hemoglobin A1C, whereas patients not on metformin had higher levels of urea nitrogen. When comparing both groups, the risk of developing LN (risk ratio [RR] = 1.70 [1.17-2.41]; P = 0.004), CKD (RR = 1.27 [1.07-1.52]; P = 0.007), and MACEs (RR = 1.21 [1.00-1.46]; P = 0.04) was significantly higher among patients not on metformin at one year after SLE diagnosis. After five years, the risk of LN and CKD was also higher in patients with SLE not on metformin. MACE risk was no longer significant after five years of diagnosis between both groups. CONCLUSION: Patients with SLE not on metformin have a higher risk of developing LN, CKD, and MACEs compared with patients treated with metformin. Metformin's anti-inflammatory potential offers promise as a complementary therapy for SLE. Nonetheless, further research and clinical trials are needed to clarify its mechanisms, optimal dosage, and long-term effects.

Race and Gender on the Mortality of Giant Cell Arteritis in Hospitalized Patients: A 15-Year National Inpatient Study.

BACKGROUND: Critical appraisal of mortality in giant cell arteritis (GCA) through a racial lens is imperative as gender and racial disparities remain a global healthcare concern. OBJECTIVE: To analyze the impact of race and gender on the mortality of GCA in United States (US)-hospitalized patients. METHODS: In this retrospective cohort study, the National Inpatient Sample (NIS) database from January 2003 to December 2018 was searched to identify all patients aged >18 years hospitalized with giant cell arteritis. Patients' baseline characteristics were summarized using descriptive statistics. Inferential statistics were done for categorical and continuous variables. Multivariate logistic regression, adjusting for patient and hospital-level cofounders was performed to find an association between race and outcomes of interest. RESULTS: Over the 15-year study period, a total of 8,352 patients (72.7% White, 14.5% Black or African American, 7.6% Hispanic, 2.2% Asian, 0.4% Alaska Native, and 2.6% under-represented populations) were hospitalized for GCA. The mean age at diagnosis was 73.6 ± 0.12 years. Women represented 71.9% of GCA patients and had a lower risk of mortality (OR 0.463, 95% CI: 0.235 - 0.912, p <0.05). Patients with GCA were hospitalized for an average of 4.64 days ± 0.04 days and 0.55% died. The mortality rate was lowest in Black or African American (0.1%) populations and highest among Alaska Native patients (8%). Mortality was 68% lower in those who had temporal artery biopsy (OR 0.32, 95% CI: 0.16-0.64, p <0.05). CONCLUSION: GCA disproportionally affected female patients, but mortality was higher in male patients. Alaska Native patients had the least number of hospitalizations but the highest in-hospital mortality rate. Black or African Americans had the lowest mortality rate.

Focal Alveolar Hemorrhage Secondary to Hydralazine-Associated Antineutrophilic Cytoplasmic Antibody Vasculitis.

Hydralazine is rarely associated with antineutrophilic cytoplasmic antibody (ANCA) vasculitis. In the appropriate clinical scenario, such as in a patient with pulmonary, renal, or cutaneous manifestations, finding antibodies against nuclear and cytoplasmic neutrophil antigens may suggest drug-induced vasculitis after exposure to hydralazine. We present the case of an elderly man diagnosed with focal alveolar hemorrhage with elevated concentrations of anti-myeloperoxidase antibody, anti-proteinase-3 antibody, and antinuclear antibodies in the setting of prolonged hydralazine therapy. We observed a rapid clinical improvement with hydralazine discontinuation and systemic corticosteroids. We did not observe further disease activity while on mycophenolate mofetil six months later.

Secondary pigmentary glaucoma following cosmetic laser treatment to alter iris colour.

Cosmetic alteration of iris colour with implants, along with its secondary complications, is already well described in the literature. However the use of cosmetic iris laser is relatively novel. We report on a rare case of bilateral secondary pigmentary glaucoma, in a young patient who underwent such a treatment to cause a change in iris pigmentation. Data on the safety of such procedures are lacking. Ophthalmic healthcare professionals should be aware of the potentially devastating consequences and encourage caution in patients seeking this novel treatment.

Osteonecrosis of Bilateral Distal Femurs in a Pregnant Patient Following Antenatal Betamethasone.

Corticosteroid therapy is a known risk factor for osteonecrosis, more commonly with chronic use and high cumulative dose. Osteonecrosis (avascular necrosis) has been described in pregnancy involving primarily the femoral head. To our knowledge, only rare cases of femoral meta diaphysis or knee osteonecrosis in pregnancy have been documented in the literature. We report a 28-year-old woman with sickle cell trait and beta-thalassemia trait who developed severe bilateral knee pain shortly after corticosteroid therapy. She was 34-weeks pregnant when she presented with the signs of preterm labor and was found to have oligohydramnios and preeclampsia. She was given two intramuscular injections of betamethasone 12 mg one day apart to enhance the fetal lung maturity. Within hours of the second injection, she developed acute and severe bilateral knee pain affecting her mobility and ambulation. Bilateral knee x-rays were unremarkable. Given the severity and persistence of her pain, magnetic resonance imaging (MRI) of bilateral lower extremities was done few days later and showed signs of early osteonecrosis involving bilateral distal femoral meta diaphysis and right lateral femoral condyle. Other than the steroid therapy she had received, no additional extrinsic risk factors for osteonecrosis were identified. Potential intrinsic risk factors were thought to include her combined sickle-beta-thalassemia traits and pregnancy. She was diagnosed with steroid-induced osteonecrosis, given the temporal relationship. Her presentation was unique, because osteonecrosis affected unreported sites during pregnancy, and it started shortly after a brief course of antenatal steroid. She was treated conservatively with analgesics, and outpatient orthopedic follow-up was recommended. She was advised to avoid prolonged weight-bearing and strenuous activities. On a follow-up appointment two months later, she was still complaining of bilateral knee pain with ambulation though it was less severe. She did not return for follow-up thereafter. We suggest the possibility of osteonecrosis in pregnancy involving uncommon sites, such as distal femur and femoral condyle in this case, following one or two doses of systemic steroid. Obstetricians need to consider osteonecrosis when evaluating an unexplained musculoskeletal pain after betamethasone that is used for preterm labors. More studies, including reporting more cases with unusual presentation and prospective studies following pregnant patients receiving steroid therapy, are needed to better understand the causes, associations, management, and clinical course of osteonecrosis in pregnancy.

Pulmonary Aspergillosis Complicated by Hemophagocytic Lymphohistiocytosis: A Case Report and Literature Review.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome involving excessive immune activation. It can be primary (familial) or secondary (triggered by infection, malignancy, or rheumatological disease). This is a case of a previously healthy 43-year-old African American woman who presented with fever and confusion. The patient was eventually diagnosed with pulmonary aspergillosis and responded well to antifungal therapy. She met the diagnostic criteria of HLH-2004 trial for hemophagocytic lymphohistiocytosis. She also fulfilled the 2019 classification criteria for systemic lupus erythematosus (SLE) without the classical signs and symptoms of SLE. HLH management includes supportive management, treatment of underlying condition, and immunosuppressive treatment. Etoposide and dexamethasone are commonly used treatments for HLH; however, underlying active infection can limit the treatment options. In our case, the patient was treated with steroids and hydroxychloroquine. Her condition gradually improved and she recovered without complications. Based on our literature review, we encountered six cases of HLH secondary to Aspergillosis with a mean age of approximately 47 years. The diagnosis of HLH is often delayed because of nonspecific presentation. Early identification and treatment are crucial to improve the survival rate.

Has the Sun Protection Campaign in Australia Reduced the Need for Pterygium Surgery Nationally?

BACKGROUND: The Slip! Slop! Slap! Sunsmart safety campaign was an Australian initiative implemented in the 1980s. To assess this campaign's effect on pterygium, we examined the rate of pterygium surgery across Australia and described the prevalence and associations of pterygium in Perth, Australia's sunniest capital city. METHODS: The rate of pterygium surgery was examined using Australian Medicare data. A cross-sectional analysis of the Generation 1 (Gen1) cohort of the Raine Study was performed to investigate the prevalence of pterygium in Perth. We investigated the association between pterygium and conjunctival ultraviolet autofluorescence (CUVAF) area, an objective biomarker of sun exposure, and demographics and health variables derived from a detailed questionnaire. RESULTS: Between 1994 and 2017, the rate of Medicare funded pterygium surgery in Western Australia fell 11%, well below the national average decline of 47%. Of the 1049 Gen1 Raine Study participants, 994 (571 females; mean age 56.7 years, range = 40.9-81.7) were included in the analysis. The lifetime prevalence of pterygium was 8.4% (n = 83). A higher prevalence of pterygium was associated with outdoor occupation (p-trend = 0.007), male sex (p-trend 0.01) and increasing CUVAF area (p-value <0.001). CONCLUSIONS: The effect of Australia's Slip! Slop! Slap! Sunsmart safety campaign on pterygium been mixed. Since 1994, the rate of private pterygium surgery has declined significantly in all Australian states except Western Australia. Perth, Western Australia, has the highest pterygium prevalence of any mainland-Australian cohort. Higher CUVAF area, male sex, and outdoor occupation were associated with an increased risk of pterygium.

Characteristics of Acute Gout Flare in Patients Initiated on Intravenous Bumetanide for Acute Heart Failure Exacerbation.

Background Heart failure is a clinical syndrome with significant morbidity, mortality, and financial burden. These factors are magnified in patients with associated comorbidities. Therefore, addressing such conditions is critical in decreasing healthcare costs and improving patient outcomes. Gout is a major comorbidity in patients with heart failure. Acute gout flares that occur in the context of acute heart failure exacerbations (AHFE) form an independent risk factor for increased readmissions or death. In this study, we characterized the frequency and outcomes of acute gout flares in patients treated with intravenous (IV) bumetanide for AHFE. Methods This single-center retrospective cohort study included 130 adult patients admitted in a tertiary-care hospital between August 2016 and June 2018. Chart review identified patients who were hospitalized for AHFE with International Classification of Diseases, Tenth Revision (ICD-10) diagnosis code I50, received IV bumetanide, and developed an acute gout flare. Data were analyzed using the chi-square test for categorical variables and the two-sample t-test for continuous variables. Results The annualized frequency of acute gout while receiving IV bumetanide for AHFE was 7.17%. Chronic gout patients who were on colchicine and/or allopurinol while hospitalized were less likely to develop acute gout while receiving IV bumetanide for AHFE compared with those taking neither medication (p-value =0.002). There was no significant difference in length of stay or 30-day readmissions between those who developed acute gout and those who did not. Conclusions Acute gout flares occur with a notable frequency in patients hospitalized for AHFE who are administered IV bumetanide. It is important to continue patients' outpatient gout regimens in an effort to mitigate acute gout flares during this time.

Zoster Sine Herpete Masquerading as Central Nervous System Vasculitis.

Central nervous system (CNS) vasculopathy caused by varicella zoster virus (VZV) is a rare condition. Rarer still is the development of CNS vasculopathy in the absence of a typical zoster rash, a phenomenon known as zoster sine herpete. We report a case of a 34-year-old male with HIV, non-compliant with highly active antiretroviral therapy (HAART), who presented with left-sided temporal headaches and numbness without rash. The patient had a complicated one-month hospital stay when he was initially diagnosed with mycobacterium avium complex (MAC) tuberculosis infection and treated with isoniazid, rifabutin, ethambutol, and azithromycin. Additionally, he was thought to have immune reconstitution inflammatory syndrome (IRIS) and was given steroids. Unfortunately, he presented one day post-discharge with lethargy, aphasia, and dysphagia and was found to have acute/subacute infarcts affecting multiple areas of the brain. CT angiogram (CTA) of the brain showed evidence of multifocal areas of mild to moderate stenosis throughout the intracranial arterial circulation. The patient underwent conventional angiography, which showed segmental arterial constrictions with post-stenotic dilatation consistent with vasculitis. Cerebrospinal fluid (CSF) studies eventually returned positive for VZV by polymerase chain reaction (PCR), confirming a diagnosis of VZV-induced CNS vasculopathy, or more specifically, CNS vasculopathy due to zoster sine herpete. The patient was treated with high-dose steroids as well as IV acyclovir with improvement in his symptoms. He was discharged with advice for a close follow-up with the infectious disease (ID) department. Our case highlights the importance of maintaining a high index of suspicion for varicella infection masquerading as CNS vasculitis, particularly in the absence of classic blistering shingles rash. Early detection may prevent neurological sequelae of the infection, including stroke, dissection, or neuropathy.

Sympathetic Joint Effusion in an Urban Hospital.

OBJECTIVE: Sympathetic joint effusion (SJE) and sympathetic synovial effusion (SSE) are recognized as causes of noninflammatory effusion with <2000 white blood cell (WBC) WBC/mm3 in the joint and bursa, respectively. Data on normal range SJE/SSE with <200 WBC/mm3 are unknown. We aimed to investigate the incidence, disease characteristics, and associated triggers of normal range SJE/SSE and to propose diagnostic criteria. METHODS: This retrospective study included patients hospitalized at Temple University Hospital who underwent a diagnostic arthrocentesis for joint or bursal effusion of unclear etiology from 31 January 2010 to 10 December 2016. A cohort of 72 patients with normal range synovial fluid (<200 WBC/mm3) fulfilled all inclusion criteria for detailed chart review. RESULTS: Annualized incidence of SJE/SSE was 1.2%. All 72 patients presented with joint pain and swelling. Twenty-three (32%) also had warmth and 12 (17%) had erythema. Symptom onset was hours to within 6 days in 45 (63%) patients. The most commonly affected joint was the knee (61, 85%). Concurrent pathology in close anatomical proximity to SJE/SSE in the same limb was documented in 29 (40%) patients, most of which (26 of 29, 89%) were infection, deep venous thrombosis, intramuscular fluid collection, and trauma. Less common pathology included adjacent recent hip surgery, loosening of hip prosthesis, and extracorporeal membrane oxygenation catheters. CONCLUSION: SJE/SSE is not uncommon in hospitalized patients and mimics both inflammatory and septic arthritis. It is seen with normal and noninflammatory synovial fluid. A search for a root cause in the same limb is warranted when evaluating acute or subacute painful joint effusions with normal range synovial fluid WBC count.

A Case of IgG4-related Sclerosing Mesenteritis.

A 60-year-old African-American male presented to the emergency department with abdominal pain and distention associated with decreased appetite and weight loss for several weeks. A computed tomography (CT) scan of the abdomen and pelvis showed an 8 cm mesenteric mass with surrounding stranding and poorly defined borders. The patient underwent exploratory laparotomy and complete resection of the mass since the frozen section could not give a definite diagnosis. Histopathology showed fibro-adipose tissue with lymphoid hyperplasia, vague nodular collections of foamy histiocytes with giant cell reaction, marked chronic inflammation, fat necrosis, and prominent sclerosis/fibrosis. Methenamine silver and acid-fast stains were negative for fungal and mycobacterial organisms respectively. Examination of tissue with immunohistostains showed increased immunoglobulin G4 (IgG4)-positive plasma cells. Other features observed were scattered areas of phlebitis, pockets of tissue eosinophilia, and focal storiform fibrosis leading to the diagnosis of IgG4-related sclerosing mesenteritis. The patient did not require steroids after the surgical resection and was disease free at six-month follow up.

Real-time teleophthalmology versus face-to-face consultation: A systematic review.

Introduction Advances in imaging capabilities and the evolution of real-time teleophthalmology have the potential to provide increased coverage to areas with limited ophthalmology services. However, there is limited research assessing the diagnostic accuracy of face-to-face teleophthalmology consultation. This systematic review aims to determine if real-time teleophthalmology provides comparable accuracy to face-to-face consultation for the diagnosis of common eye health conditions. Methods A search of PubMed, Embase, Medline and Cochrane databases and manual citation review was conducted on 6 February and 7 April 2016. Included studies involved real-time telemedicine in the field of ophthalmology or optometry, and assessed diagnostic accuracy against gold-standard face-to-face consultation. The revised quality assessment of diagnostic accuracy studies (QUADAS-2) tool assessed risk of bias. Results Twelve studies were included, with participants ranging from four to 89 years old. A broad number of conditions were assessed and include corneal and retinal pathologies, strabismus, oculoplastics and post-operative review. Quality assessment identified a high or unclear risk of bias in patient selection (75%) due to an undisclosed recruitment processes. The index test showed high risk of bias in the included studies, due to the varied interpretation and conduct of real-time teleophthalmology methods. Reference standard risk was overall low (75%), as was the risk due to flow and timing (75%). Conclusion In terms of diagnostic accuracy, real-time teleophthalmology was considered superior to face-to-face consultation in one study and comparable in six studies. Store-and-forward image transmission coupled with real-time videoconferencing is a suitable alternative to overcome poor internet transmission speeds.

New Roadmap for the Journey From Internist to Rheumatologist.

OBJECTIVE: Measurement is necessary to gauge improvement. US training programs have not previously used shared standards to assess trainees' mastery of the knowledge, skills, and attitudes necessary to practice rheumatology competently. In 2014, the Accreditation Council for Graduate Medical Education (ACGME) Next Accreditation System began requiring semiannual evaluation of all medicine subspecialty fellows on 23 internal medicine subspecialty reporting milestones. Since these reporting milestones are not subspecialty specific, rheumatology curricular milestones were needed to guide rheumatology fellowship training programs and fellows on the training journey from internist to rheumatologist. METHODS: Rheumatology curricular milestones were collaboratively composed by expanding the internal medicine reporting milestones to delineate the specific targets of rheumatology fellowship training within 6 ACGME core competencies. The 2006 American College of Rheumatology core curriculum for rheumatology training programs was updated. RESULTS: A total of 80 rheumatology curricular milestones were created, defining progressive learning through training; most focus on patient care and medical knowledge. The core curriculum update incorporates the new curricular milestones and rheumatology entrustable professional activities. CONCLUSION: Rheumatology curricular milestones are now available for implementation by rheumatology fellowship training programs, providing a clear roadmap for specific training goals and a guide to track each fellow's achievement over a 2-year training period. The comprehensive core curriculum delineates the essential breadth of knowledge, skills, and attitudes that define rheumatology, and provides a guide for educational activities during fellowship training. These guiding documents are now used to train and assess fellows as they prepare for independent rheumatology practice as the next generation of rheumatologists.

What Is a Rheumatologist and How Do We Make One?

OBJECTIVE: Graduate medical education is a critical time in the training of a rheumatologist, and purposeful evaluation of abilities during this time is essential for long-term success as an independent practitioner. The internal medicine subspecialties collectively developed a uniform set of reporting milestones by which trainees can be assessed and receive formative feedback, providing clarity of accomplishment as well as areas for improvement in training. Furthermore, the reporting milestones provide a schema for assessment and evaluation of fellows by supervisors. The internal medicine subspecialties were also tasked with considering entrustable professional activities (EPAs), which define the abilities of a subspecialty physician who has attained sufficient mastery of the field to be accountable to stakeholders and participate in independent practice. Although EPAs have been established for a few specialties, they had not yet been described for rheumatology. EPAs have value as descriptors of the comprehensive abilities, knowledge, and skills of a practicing rheumatologist. The rheumatology EPAs have a role in defining a specialist in rheumatology upon completion of training, and also represent the ways our specialty defines our abilities that are enduring throughout practice. METHODS: We describe the collaborative process of the development of both the subspecialty reporting milestones and the rheumatology EPAs. The reporting milestones evolved through discussions and collaborations among representatives from the Association of Specialty Professors, the Alliance for Academic Internal Medicine, the American Board of Internal Medicine, and the Accreditation Council for Graduate Medical Education. The EPAs were a product of deliberations by the Next Accreditation System (NAS) working group of the American College of Rheumatology (ACR) Committee on Rheumatology Training and Workforce Issues. RESULTS: Twenty-three subspecialty reporting milestones and 14 rheumatology EPAs were advanced and refined over the course of 3 subspecialty reporting milestone development summits and 3 ACR NAS working group meetings, respectively. CONCLUSION: The subspecialty reporting milestones and rheumatology EPAs presented here stipulate reasonable and measurable expectations for rheumatologists-in-training. Together, these tools aim to promote enrichment and greater accountability in the training of fellows. Additionally, the EPAs define, for all stakeholders, the expertise of a rheumatologist in practice.

Variable atrioventricular block in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE), a connective tissue disease characterized by the production of auto-antibodies and immune complexes, can affect all organs including the heart. The involvement of the conduction system in SLE has been less commonly described. We report a case of an asymptomatic 45-year-old woman with SLE referred to the emergency department (ED) for thrombocytopenia, and was found to have alternating first- and second-degree atrioventricular block (AVB) during routine electrocardiographic screening for hospital admission. Serial electrocardiograms (ECG) done in the ED when compared to those recorded 24 h prior revealed progression from mild first-degree AVB (PR interval = 216 ms) to significant first-degree AVB (PR interval = 510 ms), followed by second-degree AVB (Mobitz type I-Wenckebach phenomenon). The conduction abnormalities recorded over a 28-h period resolved with corticosteroid treatment. Review of the literature on the disruption of the cardiac conduction system in SLE is discussed.

Hormonal modulation of the immune system - A spotlight on the role of progestogens.

This article reviews the effects of progestogens on the innate and adaptive immunity and its role in the pathogenesis of autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. The interplay between the sex hormones such as progestogens and the immune system is very complex. Multiple factors affect immunomodulatory effects of the progestogens including fluctuations in the endogenous sex hormone levels, stress, use of exogenous hormones (dose, route and the timing of administration), and alterations in the hormonal metabolism. Although immunomodulatory effects of progesterone, especially progesterone's effect on T cells, T cell subsets and their ratios, dose effects, and the use of synthetic progestins have been studied, there are still wide open areas for further explorations of the progestogens' multifaceted impact on the immune system. Better understanding of the intricate immunomodulatory effects of the progestins may pave the path to developing clinically meaningful therapeutic interventions in certain autoimmune diseases.