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The Pre-treatment Gut Microbiome is Associated with Lack of Response to Methotrexate in New Onset Rheumatoid Arthritis

Artacho, Alejandro; Isaac, Sandrine; Nayak, Renuka; Flor-Duro, Alejandra; Alexander, Margaret; Koo, Imhoi; Manasson, Julia; Smith, Philip B; Rosenthal, Pamela; Homsi, Yamen; Gulko, Percio; Pons, Javier; Puchades-Carrasco, Leonor; Izmirly, Peter; Patterson, Andrew; Abramson, Steven B; Pineda-Lucena, Antonio; Turnbaugh, Peter J; Ubeda, Carles; Scher, Jose U
OBJECTIVES/OBJECTIVE:Although oral methotrexate (MTX) remains the anchor drug for RA, up to 50% of patients do not achieve a clinically adequate outcome. Concomitantly, there is a lack of prognostic tools for treatment response prior to drug initiation. Here we study whether inter-individual differences in the human gut microbiome can aid in the prediction of MTX efficacy in new-onset RA (NORA). METHODS:16S rRNA gene and shotgun metagenomic sequencing were performed on the baseline gut microbiomes of drug-naïve, NORA patients (n=26). Results were validated in an additional independent cohort (n=21). To gain insight into potential microbial mechanisms, ex vivo experiments coupled with metabolomics analysis evaluated the association between microbiome-driven MTX depletion and clinical response. RESULTS:Our analysis revealed significant associations between the abundance of gut bacterial taxa and their genes with future clinical response, including orthologs related to purine and methotrexate metabolism. Machine learning techniques were applied to the metagenomic data, resulting in a microbiome-based model that predicts lack of response to MTX in an independent group of patients. Finally, MTX levels remaining after ex vivo incubation with distal gut samples from pre-treatment RA patients significantly correlated with the magnitude of future clinical response, suggesting a possible direct effect of the gut microbiome on MTX metabolism and treatment outcomes. CONCLUSIONS:Together, these results provide the first step towards predicting lack of response to oral MTX in NORA patients and support the value of the gut microbiome as a possible prognostic tool and as a potential target in RA therapeutics.
PMID: 33314800
ISSN: 2326-5205
CID: 4717542

Cryoglobulinemic Vasculitis in a Rheumatoid Arthritis Patient [Letter]

Thomas, Dominik; Homsi, Yamen; Stokar, Evan
PMID: 33190855
ISSN: 1538-2990
CID: 4716272

SARS-CoV-2 provoked scleroderma renal crisis in a patient with a recent elective medical abortion [Meeting Abstract]

Guan, M L; Hossain, M; Homsi, Y
LEARNING OBJECTIVE #1: Recognize the presentation of autoimmune disease following recent viral illness, particularly SARS-CoV-2. LEARNING OBJECTIVE #2: Diagnose and manage scleroderma renal crisis. CASE: A 35-year-old G3P1 woman with hypertension and iron deficiency anemia presented with one week of headache, dyspnea and vaginal bleeding after elective first trimester abortion. Physical exam notable for blood pressure of 266/144 mmHg. Creatinine was 5.16 mg/dL, elevated from 0.9 mg/dL one year prior. Hemoglobin was 9.4 g/dL, platelet count 49,000/uL and peripheral blood smear showed moderate schistocytes. Lactate dehydrogenase (LDH) was 1,829 IU/L and haptoglobin was undetectable. Direct antiglobulin test was negative. Patient was positive for SARS-CoV-2 by nasopharyngeal swab. She was started on nicardipine drip for hypertensive emergency. Plasmapheresis exchange therapy was initiated for empiric treatment of thrombotic thrombocytopenic purpura (TTP). Platelet count and LDH improved, although haptoglobin remained low. On hospital day three, ADAMTS13 activity returned as 72 percent, excluding TTP. She developed diffuse facial and anterior chest telangiectasias (Figure 1). Given refractory hypertension, elevated creatinine, and diffuse telangiectasias, scleroderma renal crisis was suspected (1, 2, 3). Notably, patient had no autoimmune disease history. Captopril was initiated and plasmapheresis exchange therapy continued for five days, after which platelet count recovered. Autoimmune work-up demonstrated positive ANA with titer of 1:640, nucleolar pattern on immunofluorescence and positive Sjogren's antibody Anti-SS-A greater than 8 AI. Anti-double-strand DNA antibody and anti-Smith antibody were negative. Repeat creatinine two months after admission was 1.8 mg/dL. IMPACT/DISCUSSION: The temporal nature of hypertensive emergency following SARS-CoV-2 infection implicates SARS-CoV-2 as a causal factor in triggering scleroderma renal crisis. Despite testing positive for SARS-CoV-2 infection during admission, the patient remained asymptomatic throughout her hospital course, without respiratory complaints, fever or anosmia. Infectious diseases have been hypothesized in the pathogenesis of autoimmune conditions. Parvovirus B19 and CMV serve as potential triggers for scleroderma by causing defects in vasculogenesis and bone marrow suppression (4). SARS-CoV-2 disrupts the endothelium, leading to both a pro- coagulative state and increased inflammation (5). It may drive autoimmune syndromes in genetically susceptible individuals, correlating with reports of atypical Kawasaki disease in children with concomitant SARS-CoV-2 infection (6, 7, 8). Perhaps an underlying autoimmune condition such as scleroderma was unmasked in the pro-inflammatory state instigated by our patient's SARSCoV-2 infection.
CONCLUSION(S): It is critical to recognize initial manifestations of autoimmune conditions following acute SARS-CoV-2 infection. Our case emphasizes the need for further research into a link between SARS-CoV-2 infection and autoimmune disease
ISSN: 1525-1497
CID: 4986712

Osseous Sarcoid Mimicking Metastatic Cancer [Letter]

Sidhu, Gurinder; Homsi, Yamen
PMID: 32171468
ISSN: 1538-2990
CID: 4353382

Fatal Disseminated Aspergillosis in a Patient with Systemic Lupus Erythematosus [Case Report]

Hardie, Rochelle; James-Goulbourne, Tracian; Rashid, Monsoon; Sullivan, Jeremy; Homsi, Yamen
Patients with systemic lupus erythematosus (SLE) are at increased risk for infection including opportunistic infections. Fungal infection in particular can be difficult to diagnose and treat and often can be life-threatening in the immunocompromised patient. We present a case in which a patient with SLE presented to the hospital with shortness of breath and cough. Throughout the hospital course, the patient's condition continued to decline leading to acute respiratory failure, and eventually, the patient expired. Postmortem autopsy revealed invasive fungal aspergillosis infection involving the heart, lungs, and brain. Earlier diagnosis and treatment with empiric antifungals may improve survival in these patients.
PMID: 32181030
ISSN: 2090-6625
CID: 4353522

Comparative analysis of clinical, laboratory and therapeutic strategies among blacks with rhupus, SLE and RA [Meeting Abstract]

Kabani, N; Pathiparampil, J; Abduraimova, M; Freeman-Beman, L; Terebelo, S; Hasan, A; Grant, C; Salgado, J; Bhamra, M; James-Goulbourne, T; Amin, K; Homsi, Y; McFarlane, I
Background/Purpose : Rhupus is the overlap of SLE and RA. While a few studies have been conducted among Rhupus patients, no studies have focused on Black population with Rhupus. Our aim was to describe the clinical, laboratory, radiographic and therapeutic profiles of predominantly Black patients with Rhupus and to compare this group with age and sex-matched patients with SLE and with RA. Methods : Retrospective chart review of SLE and RA overlap patients followed at 2 large urban hospitals. Rhupus patients were identified by ICD codes and compared to age and sex matched cohort of SLE only and RA only groups. Descriptive statistics using SPSS version 24 were applied to analyze the differences between the three cohorts. Results : 38 patients met the ACR criteria for both RA and SLE (Rhupus) with 94.7% being women, mean age of 50.9+/-14.4 (SEM). Blacks represented 81.6% with a BMI of 28.6+/-7.3Kg/m 2 . 50% had hypertension, 71.1% had at least one cardiovascular (CV) risk factor and 26.3% had 3 or more CV risk factors. Mean ESR = 58.28 +/- 5.45 and CRP = 28.94 +/- 8.8. There were no significant differences in CV risk factors, CV outcomes and inflammatory markers between the three cohorts. The rate of leukopenia and CRP levels were significantly higher in the Rhupus compared to the SLE and RA groups. Compared to RA only group there were higher rates of smoking and ANA positivity among Rhupus populations. Leukopenia and positive RF and ACPA rates were frequent among Rhupus patients compared to RA only cohort. Corticosteroids, MTX, and biologic DMARDs use did not differ between Rhupus and RA cohorts. Rate of utilization of other-than-MTX DMARDs and the combination of steroid with DMARDs was higher among the Rhupus compared to the RA only cohort. When comparing Rhupus and SLE patients, the rates of mucocutaneous lesions, serositis, neurologic manifestations, and laboratory values including autoantibodies were no different between the groups. Smoking, arthritis, hand XR abnormalities, erosions, seropositive RA were more frequent among the Rhupus vs. SLE patients. However, lupus nephritis and RNP antibodies were less frequent in Rhupus compared to SLE only group. Corticosteroids, MTX, conventional and biologic DMARDs and combination therapy were more frequently used in Rhupus compared to SLE population. Conclusion : In our predominantly Black population, Rhupus patients had higher rates of smoking and ANA positivity compared to RA patients. It also had lower rate of positivity for RF or ACPA. Rates of smoking, arthritis, erosions, positivity for RF, ACPA and aCL antibodies were higher among Rhupus compared to SLE patients. These results suggest smoking to be a potential risk factor for Rhupus and might play a role in the underlying pathophysiology of this overlap syndrome. Further studies are needed to confirm our findings and elucidate risk factors and predictors of Rhupus to help develop preventive and therapeutic strategies for this important disease entity
ISSN: 2326-5205
CID: 4635512

Severe Lytic Bone Lesions in Multiple Myeloma [Letter]

Sidhu, Gurinder; Homsi, Yamen
PMID: 30711187
ISSN: 1538-2990
CID: 3683842

Extensive Calcinosis Cutis inOverlap Syndrome [Letter]

Homsi, Yamen
PMID: 30360808
ISSN: 1538-2990
CID: 3385252

A Case of Multiple Myeloma Misdiagnosed as Seronegative Rheumatoid Arthritis and Review of Relevant Literature

Schoninger, Scott; Homsi, Yamen; Kreps, Alexandra; Milojkvovic, Natasa
Multiple myeloma (MM) is a malignant plasma cell proliferation producing large numbers of monoclonal immunoglobulins. Typical MM symptoms include anemia, renal failure, hypercalcemia, and bone pain. Atypical symptoms have rarely been reported in the literature. We report a case of a 58-year-old male who presented with symmetrical inflammatory polyarthritis and was misdiagnosed with seronegative rheumatoid arthritis (RA). After failing many RA treatments and with further workup, the diagnosis of MM was made. This rare manifestation of MM carries a diagnostic challenge and causes a significant delay in treating such patients. Here, we report this unusual initial presentation with review of several cases in the English literature describing similar presentations.
PMID: 30405932
ISSN: 2090-6889
CID: 3456092

Therapeutic effect of anti-IL-5 on eosinophilic myocarditis with large pericardial effusion [Case Report]

Song, Tengyao; Jones, David Micheal; Homsi, Yamen
Eosinophilic myocarditis (EM) is a rare myocardial disease that results from various eosinophilic diseases, such as idiopathic hypereosinophilic syndrome, helminth infection, medications and vasculitis. Patients with EM may present with different severities, ranging from mild symptoms to a life-threatening condition. Diagnosis of EM is a challenge and requires an extensive workup, including endomyocardial biopsy. Treatment options are limited because EM is rare and there is a lack of randomised controlled trials. We report a case of EM that presented as cardiac tamponade, which was initially treated with high-dose prednisone and immunosuppressant medications without significant improvement. Mepolizumab (anti-interleukin (IL)-5 antibody) was then applied, leading to an increased ejection fraction and stabilised cardiac function. This case report shows, for the first time, that mepolizumab has novel effects in treating EM. Our findings suggest that mepolizumab can be used as a steroid-sparing agent for treating EM.
PMID: 28546236
ISSN: 1757-790x
CID: 3290572