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A Rare Case of MDA-5-Positive Amyopathic Dermatomyositis with Rapidly Progressive Interstitial Lung Disease Following COVID-19 mRNA Vaccination - a Case Report [Case Report]

Wang, Shuwei; Noumi, Bassel; Malik, Fardina; Wang, Shudan
We report a rare case of new-onset MDA-5-positive amyopathic dermatomyositis with rapidly progressive interstitial lung disease (RP-ILD) following the second dose of the COVID-19 mRNA vaccine. Our patient was a previously healthy Asian female in her 60 s who presented with fatigue, dyspnea on exertion, and typical dermatomyositis (DM) rashes without muscle involvement two weeks after receiving the second dose of the COVID-19 mRNA BNT162b2 vaccine. Workup revealed high titer MDA-5 antibodies, abnormal pulmonary function tests, and ground-glass opacities on chest imaging. She had good response to early aggressive therapy with high-dose steroids, intravenous (IV) rituximab, mycophenolate mofetil, and intravenous immunoglobulin (IVIG). This case highlights the potential immunogenicity of COVID-19 mRNA vaccines and the possibility of new-onset systemic rheumatic syndromes after vaccination. More studies are needed to understand a definitive causal relationship and improve surveillance of adverse immunological events following COVID-19 vaccinations.
PMID: 36530960
ISSN: 2523-8973
CID: 5506892


Buyon, J; Deonaraine, K; Carlucci, P; Masson, M; Fraser, N; Phoon, C; Roman, A; Izmirly, P; Saxena, A; Belmont, M; Penfield, C; Mi, Lee Y; Nusbaum, J; Solitar, B; Malik, F; Rackoff, P; Haberman, R; Acherman, R; Sinkovskaya, E; Albuhamad, A; Makhoul, M; Satou, G; Pinto, N; Moon-Grady, A; Howley, L; Levasseur, S; Matta, J; Lindblade, C; Rubenstein, A; Haxel, C; Kohari, K; Copel, J; Strainic, J; Doan, T; Bermudez-Wagner, K; Sheth, S S; Killen, S; Tacy, T; Kaplinski, M; Drewes, B; Clancy, R; Cuneo, B
Introduction Fetal cardiac disease is strongly associated with maternal anti-SSA/Ro antibodies, but gaps in our knowledge include the influence of antibody specificity and titer, maternal diagnosis, overall non-cardiac adverse pregnancy outcomes (APOs), optimal surveillance protocols, and efficacy of rapid treatment. Methods The multi-center Surveillance and Treatment To Prevent Fetal AV Block Likely to Occur Quickly (STOP BLOQ) study recruited pregnant women with commercially positive anti-Ro antibodies and stratified them into high and low titers of anti-Ro60 and Ro52 based on a research ELISA, using a cutoff defined by that obtained for 50 mothers with previous AVB offspring. Mothers with anti-Ro60 and/or 52 antibodies at or above 1,000 I.U. were trained to perform FHRM. From 17-25 weeks of gestation, FHRM was completed 3x/day in addition to weekly or biweekly fetal echocardiograms (echo). Mothers texted all audio sounds to the coordinating center. Texts deemed abnormal by mothers were immediately sent to an on call pediatric cardiologist who either reassured if FHRM was normal or referred for emergency fetal echo in < 6 hours if abnormal. Results 250 anti-Ro pregnant women (22% Hispanic, 50% white, 12% Black, 12% Asian, 4% other) have been consented, including 28 whose previous child had AVB. Of mothers tested to date, 153 were provided home monitors given high titer anti-Ro60 and/or 52 antibodies (26 high titer anti-Ro60 alone, 21 high titer anti-Ro52 alone,105 high titer antibodies to both antigens). The 83 patients with low titers were surveilled with echos per local standard of care. Regarding maternal diagnosis, of 161 assessed to date, 39% were asym/UAS, 11% RA, 31% SS, 19% SLE. Antibody titers did not significantly differ by ethnicity, race or diagnosis (table 1). Non-AVB APOs occurred in 18% and were not predicted by Ro60 or 52 titers but rather SLE diagnosis (table 2). In total, 24,759 FHRM audiotexts were received from 131 patients (90 of whom have delivered) during the monitoring period. Of these, 22 were evaluated by the on-call pediatric cardiologist, who prompted an emergency echo (all completed in < 6 hrs). In 11 cases, the emergency echo was normal. In 9, there were premature atrial contractions, confirming the mother's perception. In 2 with 2degree block on urgent echo (both treated per protocol with IVIG and dexamethasone), 1 reverted to normal sinus rhythm and the other progressed to 3degree block. In 2 others, the mother did not perceive abnormal FHRM for > 24 hrs, echo identified 3degree block, and retrospective cardiology review of FHRM audio captures identified an abnormality prior to obtaining the echo. All 4 AVB developed in fetuses of mothers with high titer antibodies to both Ro60 and 52 (mean 32,451 and 34,991 respectively). Of the 18 mothers with a previous AVB child who followed the 400mg hydroxychloroquine PATCH protocol, 1 developed AVB in accord with the results of Step 1 in that study. Conclusion These data support that APOs in this clinically diverse group of mothers are not influenced by anti-Ro titer or specificity, but rather SLE diagnosis. All conduction defects were initially identified by FHRM and in mothers with high titer anti-Ro60 and 52. Hydroxychloroquine continues to show efficacy in reducing the AVB recurrence rate with rapid intervention of emergent block being promising
ISSN: 2053-8790
CID: 5513372

Prevalence, Predictors, and Disease Activity of Sacroiliitis Among Patients with Crohn's Disease

Levine, Irving; Malik, Fardina; Castillo, Gabriel; Jaros, Brian; Alaia, Erin; Ream, Justin; Scher, Jose U; Hudesman, David; Axelrad, Jordan
BACKGROUND:Sacroiliitis is an inflammatory arthritis of the sacroiliac joints and is associated with inflammatory bowel disease (IBD). Yet, sacroiliitis often goes undiagnosed in IBD, and the clinical association between IBD disease activity and sacroiliitis is not well established. Patients with Crohn's disease (CD) often receive magnetic resonance enterography (MRE) to assess disease activity, affording clinicians the opportunity to evaluate for the presence of sacroiliitis. We aimed to identify the prevalence and disease characteristics associated with sacroiliitis in CD patients undergoing MRE. METHODS:All CD patients undergoing MRE for any indication between 2014 and 2018 at an IBD referral center were identified. The MREs were reviewed for the presence of sacroiliitis based on bone marrow edema (BME) and structural lesions. We analyzed demographics, IBD characteristics, clinical and endoscopic disease activity, and management between CD patients with and without sacroiliitis. RESULTS:Two hundred fifty-eight patients with CD underwent MRE during the study period. Overall, 17% of patients had MR evidence of sacroiliitis, of whom 73% demonstrated bone marrow edema. Female gender, back pain, and later age of CD diagnosis were associated with sacroiliitis (P = 0.05, P < 0.001, P = 0.04, respectively). Disease location and CD therapy were not associated with sacroiliitis on MRE. Clinical, endoscopic, and radiographic disease activity were not associated with sacroiliitis on MRE. CONCLUSION/CONCLUSIONS:Sacroiliitis is a common comorbid condition in CD. With limited clinical clues and disease characteristics to suggest sacroiliitis, physicians may utilize MRE to identify sacroiliitis, especially in CD patients with back pain.
PMID: 32793977
ISSN: 1536-4844
CID: 4557222

Utility of magnetic resonance imaging in Crohn's associated sacroiliitis: A cross-sectional study

Malik, Fardina; Scherl, Ellen; Weber, Ulrich; Carrino, John A; Epsten, Madeline; Wichuk, Stephanie; Pedersen, Susanne J; Paschke, Joel; Schwartzman, Sergio; Kroeber, Georg; Maksymowych, Walter P; Longman, Randy; Mandl, Lisa A
OBJECTIVE:Prevalence of sacroiliitis in Crohn's disease (CD) is variable depending on defining criteria. This study utilized standardized sacroiliac joint (SIJ) magnetic resonance imaging (MRI) to identify sacroiliitis in CD patients and its association with clinical and serological markers. METHODS:Consecutive adult subjects with CD prospectively enrolled from an inflammatory bowel disease clinic underwent SIJ MRI. Data collected included CD duration, history of joint/back pain, human leukocyte antigen-B27 status, Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Disease Activity Index, Harvey Bradshaw Index (HBI) for activity of CD, Ankylosing Spondylitis Disease Activity Score, and various serologic markers of inflammation. Three blinded readers reviewed MRIs for active and structural lesions according to the Spondyloarthritis Research Consortium of Canada modules. RESULTS:Thirty-three CD patients were enrolled: 76% female, 80% White, median age 36.4 years (interquartile range 27.2-49.0), moderate CD activity (mean HBI 8.8 ± SD 4.5). Nineteen subjects (58%) reported any back pain, 13 of whom had inflammatory back pain. Four subjects (12%) showed sacroiliitis using global approach and 6 (18%) met Assessment of SpondyloArthritis international Society MRI criteria of sacroiliitis. Older age (mean 51.2 ± SD 12.5 vs. 37.2 ± 14; P = .04), history of dactylitis (50.0% vs. 3.4%, P = .03) and worse BASMI (4.1 ± 0.7 vs. 2.4 ± 0.8, P ≤ .001) were associated with MRI sacroiliitis; no serologic measure was associated. CONCLUSION/CONCLUSIONS:There were 12%-18% of CD patients who had MRI evidence of sacroiliitis, which was not associated with back pain, CD activity or serologic measures. This data suggests that MRI is a useful modality to identify subclinical sacroiliitis in CD patients.
PMID: 33528900
ISSN: 1756-185x
CID: 4788282

Comparison between radiography and magnetic resonance imaging for the detection of sacroiliitis in the initial diagnosis of axial spondyloarthritis: a cost-effectiveness study

Gorelik, Natalia; Tamizuddin, Farah; Rodrigues, Tatiane Cantarelli; Beltran, Luis; Malik, Fardina; Reddy, Soumya; Koo, James; Subhas, Naveen; Gyftopoulos, Soterios
OBJECTIVE:The purpose of our study was to determine the cost-effectiveness of radiography and MRI-based imaging strategies for the initial diagnosis of sacroiliitis in a hypothetical population with suspected axial spondyloarthritis. MATERIALS AND METHODS/METHODS:A decision analytic model from the health care system perspective for patients with inflammatory back pain suggestive of axial spondyloarthritis was used to evaluate the incremental cost-effectiveness of 3 imaging strategies for the sacroiliac joints over a 3-year horizon: radiography, MRI, and radiography followed by MRI. Comprehensive literature search and expert opinion provided input data on cost, probability, and utility estimates. The primary effectiveness outcome was quality-adjusted life-years (QALYs), with a willingness-to-pay threshold set to $100,000/QALY gained (2018 American dollars). RESULTS:Radiography was the least costly strategy ($46,220). Radiography followed by MRI was the most effective strategy over a 3-year course (2.64 QALYs). Radiography was the most cost-effective strategy. MRI-based and radiography followed by MRI-based strategies were not found to be cost-effective imaging options for this patient population. Radiography remained the most cost-effective strategy over all willingness-to-pay thresholds up to $100,000. CONCLUSION/CONCLUSIONS:Radiography is the most cost-effective imaging strategy for the initial diagnosis of sacroiliitis in patients with inflammatory back pain suspicious for axial spondyloarthritis.
PMID: 32382977
ISSN: 1432-2161
CID: 4430602


Levine, Irving; Malik, Fardina; Castillo, Gabriel; Jaros, Brian; Alaia, Erin; Ream, Justin; Scher, Jose; Hudesman, David; Axelrad, Jordan E.
ISSN: 0016-5085
CID: 5524192

Magnetic resonance enterography as a screening tool to detect sacroiliitis in crohn's disease: Association with clinical and endoscopic Markers of Crohn's Disease Activity [Meeting Abstract]

Malik, F; Levine, I; Castillo, G; Jaros, B; Alaia, E; Ream, J; Axelrad, J E; Hudesman, D P; Scher, J
Background/Purpose : Prevalence of sacroiliitis (SI) in Crohn's disease (CD) varies widely (range 4% -39%), depending on criteria utilized to define the disease (e.g. inflammatory back pain, plain radiographs or MRI). Sacroiliitis may remain underdiagnosed in CD patients given lack of association with clinical symptoms of back pain and CD activity. However, patients with CD often undergo magnetic resonance enterography (MRE) to assess extent, severity of small bowel CD and radiographic healing, affording clinicians the opportunity to evaluate for the presence of active and/or chronic SI. We sought to identify the prevalence of sacroiliitis in CD patients utilizing MRE and determine its relationship with CD activity, especially with concurrent biologic therapy. Methods : All CD subjects undergoing MRE between years 2014-2018 at a large IBD referral center were identified. A musculoskeletal radiologist, blinded to clinical data, reviewed all MRE exams for the presence of acute bone marrow edema (BME) lesions and chronic lesions suggestive of acute and chronic SI, respectively. A second radiologist, also blinded, assessed MRE for mucosal CD activity using validated measures. Charts were reviewed for demographics, IBD characteristics, presence of back pain, clinical and endoscopic activity of CD, and Crohn's therapies within 3 months of MRE. Comparisons were made between CD subjects with and without SI using chi-square test. Univariate and multivariate logistic regression were used to determine risk factors of SI. Results : 258 subjects with CD underwent MRE during the study period with a mean age of 35 years old, 53% (n=138) were male, and mean duration of CD at the time of MRE was 9 years. Few reported back pain (8%) and 14% had previously seen a rheumatologist. Overall, 17% (n=45) of patients had MR evidence of sacroiliitis (Table 1). Female gender, presence of back pain, and later age of CD diagnosis were associated with signs of sacroiliitis (p=0.05, p< 0.001, p=0.04 respectively; Table 2). Stricturing phenotype was associated with a lower rate of SI (7% vs. 24%; p=0.018), but inflammatory or penetrating phenotypes were not. CD location, activity as noted by clinical scores, endoscopic disease activity, or radiographic disease activity on MRE, were not associated with sacroiliitis (Table 2). On multivariable analysis, back pain was associated with the presence of sacroiliitis on MRE (OR 3.0, 95% CI 1.1-5.6; p=0.04). Concurrent CD therapy with biologics did not lower the risk of sacroiliitis. Conclusion : Although often underdiagnosed, SI is a common comorbid condition in CD. While recent history of back pain was associated with the presence of sacroiliitis visualized on MRE, no correlations were found with other clinical and endoscopic markers of CD activity. Moreover, concurrent CD therapy, especially biologics, was not associated with a lower risk of sacroiliitis on MRE. With limited clinical clues and CD characteristics to suggest sacroiliitis, gastroenterologists can utilize MRE as a screening tool to detect SI and refer CD patients to rheumatologists. Presence of SI on MRE in CD patients with back pain may help identify a subset of individuals likely to benefit from switching to therapies with proven efficacy in axial SpA
ISSN: 2326-5205
CID: 4633642

Psoriatic arthritis

Chapter by: Malik, Fardina; Haberman, Rebecca; Scher, Jose U.
in: Absolute Rheumatology Review by
[S.l.] : Springer International Publishing, 2019
pp. 153-173
ISBN: 9783030230210
CID: 4462612

The Prevalence and Clinical Associations of Sacroiliitis in Crohn's Disease Using a Standardized Magnetic Resonance Scoring System [Meeting Abstract]

Levine, Irving; Malik, Fardina; Castillo, Gabriel; Jaros, Brian D.; Alaia, Erin; Ream, Justin; Scher, Jose U.; Hudesman, David P.; Axelrad, Jordan E.
ISSN: 0002-9270
CID: 5524172

Effects of fatty acid supplementation in modulation of gut microbiome and T-regulatory cells in health and psoriatic disease [Meeting Abstract]

Malik, F; Manasson, J; Herrera, A; Attur, M; Reddy, S M; Yang, L; Koralov, S; Scher, J U
Background/Purpose: Psoriatic Arthritis (PsA) affects up to 30% patients with psoriasis and is characterized by wide spread synovio-entheseal inflammation. Physiologically, the human gut microbiota metabolizes dietary fiber into shortchain fatty acids (FA)- which exert anti-inflammatory effects by increasing activity of regulatory T cells (Tregs).Moreover, we have previously shown decreased abundance of Akkermansia and Ruminococcus and concomitant decrease in mediumchain FA (MCFA) levels in stool of PsA patients. We therefore hypothesized that FA supplementation may have favorable effects on gut microbiome and lead to increase in tolerance, potentially serving as therapeutic target in psoriatic disease.
Method(s): Wild type (WT)animals were fed SCFA-rich diet for 14 days followed by 16S rRNA sequencing and microbiota analysis of pellet specimens.We then evaluated effects ofMCFA-rich diet in healthy subjects. Peripheral blood and stool samples were collected at days 0, 7 and 14 for 16s rRNA sequencing and FACS. Finally, we conducted a small, prospective, proof-ofprinciple study in new-onset, drug-naive psoriatic disease patients (with or without PsA). Each participant received MCFA (1 gm 4 times a day for 6 weeks). Clinical history was obtained at baseline. Skin and joint exam were performed at baseline and follow up. Serum and stool samples were collected at baseline, weeks 3, and 6 for 16S rRNA sequencing and FACS, respectively. Wilcoxon signed-rank test was used to compare differences in Tregs before and after MCFA-rich administration.
Result(s): SCFA rich diet in WT mice led to statistically significant perturbations in gut bacterial composition 14 days into intervention, with a dramatic increase in commensals (Fig 1A; p<0.001), most notably in Akkermansia(Fig 1B). MCFA administration to healthy subjects (n=7) also led to significant changes in community structure (Fig 2A; p=0.03) and associated increases in circulating Treg cells (Fig 2B; p<0.001). These findings were also observed in psoriatic disease patients (n=4) showing a significant alteration in specific taxa, including Actinobacteria (Fig 2 C; p<0.05) and Mollicutes (p=0.09) and concomitant increase in circulatory Treg cells (Fig 2D)
Conclusion(s): In both health and psoriatic disease, MCFA supplementation is associated with distinct changes in human gut microbiota composition and peripheral Treg cells. These findings rationalize the need for a larger placebo controlled, prospective trial to study the effects of MCFA in patients with psoriasis and PsA as a potential therapy alone or in combination with DMARDs. (Figure Presented)
ISSN: 2326-5205
CID: 3704992