Christina Bax, MD

All Publications

• Novel therapeutic targets in dermatomyositis. The Journal of dermatology Bax, C., Aghdasi, C., Fiorentino, D. 2024

  Abstract

  Dermatomyositis (DM) is a systemic autoimmune disease with variable clinical presentations, including inflammation in the skin, muscle, lungs, and/or joints. Current therapeutic strategies in DM typically include broad immunosuppression; however, the currently used modalities are not universally effective and are associated with various side effects, including risk of infection. There is currently a highly unmet need for more effective and well-tolerated therapies. Recent years have witnessed increased interest in pharmaceutical development of new therapeutic strategies for DM. This review aims to summarize the landscape of therapies that are currently being tested or planned in patients with DM. These therapies have a wide variety of immunological targets, including T cells, B cells, inflammatory signaling pathways, type I interferons, autoantibodies, and other targets.

  View details for DOI 10.1111/1346-8138.17170

  View details for PubMedID 38433369

• Herbal supplement Spirulina stimulates inflammatory cytokine production in patients with dermatomyositis in vitro. iScience Bax, C. E., Diaz, D., Li, Y., Vazquez, T., Patel, J., Grinnell, M., Ravishankar, A., Maddukuri, S., Keyes, E., Yan, D., Bashir, M., Werth, V. P. 2023; 26 (11): 108355

  Abstract

  Spirulina, an herbal supplement and popular ingredient in health foods, is a potent stimulant of the immune system. Spirulina use is temporally associated with the onset or exacerbation of Dermatomyositis (DM), an autoimmune connective tissue disease that frequently affects the skin and muscle. In this study, we investigated the effect of Spirulina on peripheral blood mononuclear cells (PBMCs) in DM and Healthy Controls (HCs), showing that Spirulina stimulates Interferon β (IFNβ), Tumor necrosis factor α (TNFα), and Interferon γ (IFNγ) production of DM PBMCs primarily via Toll-Like Receptor 4 (TLR4) activation using ELISA (enzyme linked immunosorbent assay) and flow cytometry. We show that classical monocytes and monocyte-derived dendritic cells are stimulated by Spirulina and are activated via TLR4. Skin from patients with Spirulina-associated DM exhibits an inflammatory milieu similar to that of idiopathic DM but with a stronger correlation of TLR4 and IFNγ.

  View details for DOI 10.1016/j.isci.2023.108355

  View details for PubMedID 38026219

  View details for PubMedCentralID PMC10665953

• Frequency of immunostimulatory herbal supplement use among patients with autoimmune skin disease. Journal of the American Academy of Dermatology Ravishankar, A., Bax, C. E., Grinnell, M., Yan, D., Concha, J. S., Pappas-Taffer, L., Shields, B. E., Dany, M., Clark, A. K., Feng, R., Okawa, J., Werth, V. P. 2022; 87 (5): 1093-1095

  View details for DOI 10.1016/j.jaad.2021.12.050

  View details for PubMedID 34998955

  View details for PubMedCentralID PMC9365079

• A prospective cohort study comparing the performance of interferon gamma release assays in autoimmune skin diseases. Journal of the American Academy of Dermatology Yan, D., Gaffney, R., Krain, R., Keyes, E., Concha, J. S., Feng, R., Schulz, S., Pappas-Taffer, L., Borucki, R., Ravishankar, A., Bax, C., Okawa, J., Werth, V. P. 2022; 86 (4): 948-949

  View details for DOI 10.1016/j.jaad.2021.03.087

  View details for PubMedID 33812955

• Temporal Outcomes after Rituximab Therapy for Pemphigus Vulgaris. The Journal of investigative dermatology Tovanabutra, N., Bax, C. E., Feng, R., Kushner, C. J., Payne, A. S. 2022; 142 (4): 1058-1064.e7

  Abstract

  Pemphigus vulgaris is an autoimmune blistering disease characterized by autoantibodies that target desmoglein adhesion proteins. Rituximab and corticosteroids are Food and Drug Administration‒approved therapies for pemphigus vulgaris. As newer treatments for pemphigus enter clinical trials, analysis of clinical and serologic outcomes after rituximab therapy as a function of time is essential to guide clinical trial design. In this study, we report detailed temporal and serologic outcomes of rituximab treatment of pemphigus vulgaris. The maximal prevalence of complete remission off oral systemic therapy after a single cycle of rituximab was 32.4% at 12 months or 43.1% by 36 months, including additional rituximab cycles. Using receiver operating characteristic curves to develop prediction models for complete remission after a single cycle of rituximab, >90.7% reduction in average desmoglein 3 ELISA titers from baseline to months 3‒9 was 94% sensitive, and an average absolute titer ≤130 RU/ml between months 3 and 9 was 96% specific, for achievement of complete remission off oral systemic therapy. All patients with negative titers at 6‒9 months ultimately achieved complete remission off oral systemic therapy. This dataset of clinical and serologic outcomes for patients with pemphigus vulgaris after rituximab therapy will facilitate clinical trial planning and also guide clinician and patient expectations after rituximab therapy.

  View details for DOI 10.1016/j.jid.2021.09.013

  View details for PubMedID 34710389

  View details for PubMedCentralID PMC8957519

• Cannabinoid type 2 receptor (CB2R) distribution in dermatomyositis skin and peripheral blood mononuclear cells (PBMCs) and in vivo effects of LenabasumTM. Arthritis research & therapy Maddukuri, S., Patel, J., Diaz, D. A., Chen, K. L., Wysocka, M., Bax, C., Li, Y., Ravishankar, A., Grinnell, M., Zeidi, M., Reddy, N., Concha, J. S., Bashir, M. M., Okawa, J., White, B., Werth, V. P. 2022; 24 (1): 12

  Abstract

  Lenabasum is a cannabinoid type 2 receptor (CB2R) reverse agonist that demonstrates anti-inflammatory effects in vivo and in vitro in dermatomyositis (DM) and is currently being investigated for therapeutic potential. The purpose of our study is to investigate CB2R distribution as well as the effects of lenabasum in DM.Immunohistochemistry staining (IHC) was utilized to examine immune cell and cytokine production changes in lesional DM skin biopsies from lenabasum and placebo-treated patients. CB2R expression in various immune cell populations within DM skin was investigated with image mass cytometry (IMC), whereas flow cytometry elucidated CB2R expression in DM peripheral blood mononuclear cells (PBMCs) as well as cytokine production by CB2R-expressing cell populations.After 12 weeks of lenabasum treatment, IHC staining showed that CD4+ T cells, CB2R, IL-31, IFN-γ, and IFN-β cytokines were downregulated. IFN-γ and IFN-β mRNA decreased in lesional DM skin but not in PBMCs. IMC findings revealed that CB2R was upregulated in DM lesional skin compared to HC skin and DM PBMCs (p<0.05). In DM skin, CB2R was upregulated on dendritic cells, B cells, T cells, and macrophages while dendritic cells had the greatest expression in both DM skin and PBMCs (p<0.05). These CB2R+ cells in the skin produce IL-31, IL-4, IFN-γ, and IFN-β.Our findings of differential CB2R expression based on location and cell type suggest modes by which lenabasum may exert anti-inflammatory effects in DM and highlights dendritic cells as potential therapeutic targets.

  View details for DOI 10.1186/s13075-021-02665-x

  View details for PubMedID 34983619

  View details for PubMedCentralID PMC8725283

• A case of disseminated Lyme disease in a child with skin of color. Pediatric dermatology Bax, C. E., Clark, A. K., Oboite, M., Treat, J. R. 2021; 38 Suppl 2: 140-141

  Abstract

  Disseminated Lyme disease requires treatment to prevent severe sequelae, particularly neurologic. We report here a case of disseminated Lyme disease in a patient with skin of color. Pediatric dermatologists must maintain a high clinical suspicion for Lyme disease and be aware of how typical cutaneous findings may appear differently in skin of color.

  View details for DOI 10.1111/pde.14770

  View details for PubMedID 34515362

• Highly Multiplexed Mass Cytometry Identifies the Immunophenotype in the Skin of Dermatomyositis. The Journal of investigative dermatology Patel, J., Maddukuri, S., Li, Y., Bax, C., Werth, V. P. 2021; 141 (9): 2151-2160

  Abstract

  Dermatomyositis (DM) is a rare, systemic autoimmune disease that most frequently affects the skin, muscles, and lungs. The inflammatory infiltrate in the skin has not been fully characterized, and, in this study, we took a single-cell, unbiased approach using imaging mass cytometry. Substantial monocyte‒macrophage diversity was observed, with the CD14+ population correlating positively with Cutaneous Dermatomyositis Disease Area and Severity Index scores (P = 0.031). The T-cell compartment revealed CD4+ T, CD8+ T, and FOXP3+ T cells. Activated (CD69+) circulating memory T cells correlated positively with Cutaneous Dermatomyositis Disease Area and Severity Index scores (P = 0.0268). IFN-β protein was highly upregulated in the T-cell, macrophage, dendritic cell, and endothelial cell populations of DM skin. Myeloid dendritic cells expressed phosphorylated peroxisome proliferator‒activated receptor γ, phosphorylated IRF3, IL-4, and IL-31, and their quantity correlated with itch as measured in Skindex-29. Plasmacytoid dendritic cells colocalized with IFN-γ in addition to the known colocalization with IFN-β. Nuclear phosphorylated peroxisome proliferator‒activated receptor γ expression was found in the DM endothelium. Imaging mass cytometry allows us to characterize single cells in the immune cell population and identify upregulated cytokines and inflammatory pathways in DM. These findings have important implications for the development of future targeted therapies for DM.

  View details for DOI 10.1016/j.jid.2021.02.748

  View details for PubMedID 33766508

  View details for PubMedCentralID PMC8384654

• Plasma-derived DNA containing-extracellular vesicles induce STING-mediated proinflammatory responses in dermatomyositis. Theranostics Li, Y., Bax, C., Patel, J., Vazquez, T., Ravishankar, A., Bashir, M. M., Grinnell, M., Diaz, D., Werth, V. P. 2021; 11 (15): 7144-7158

  Abstract

  Objectives: Extracellular vesicles (EVs) are lipid bilayer membrane vesicles that are present in various bodily fluids and have been implicated in autoimmune disease pathogenesis. Type I interferons (IFN), specifically IFN-β, are uniquely elevated in dermatomyositis (DM). The stimulator of interferon genes (STING) works as a critical nucleic acid sensor and adaptor in type I IFN signaling with possible implications in autoimmune diseases such as DM. In the current study, we investigated whether circulating EVs contribute to proinflammatory effects in DM, whether these proinflammatory responses are mediated by the STING signaling pathway, and if so, by what mechanism STING is activated. Methods: We collected and characterized EVs from plasma of healthy controls (HC) and DM patients; analyzed their abilities to trigger proinflammatory cytokines release by ELISA, and explored STING signaling pathway activation using immunoblot and immunofluorescent staining. STING signaling pathway inhibitors and RNAi were used to further investigate whether STING was involved in EVs-triggered proinflammatory response. DNase/lipid destabilizing agent was utilized to digest EVs and their captured DNA contents to evaluate how EVs triggered STING-mediated proinflammatory response in DM. Results: EVs isolated from DM plasma triggered proinflammatory cytokines including type I IFN release with STING signaling pathway activation. The activated STING pathway was preferentially mediated by dsDNA captured by EVs. Suppression of STING or its downstream signaling proteins attenuated the EVs-mediated proinflammatory response. Conclusions: Plasma-derived, DNA containing-EVs induced STING-mediated proinflammatory effects in DM. Targeting the STING pathway may be a potential therapeutic approach for DM.

  View details for DOI 10.7150/thno.59152

  View details for PubMedID 34158841

  View details for PubMedCentralID PMC8210592

• Establishing cut-off values for mild, moderate and severe disease in patients with pemphigus using the Pemphigus Disease Area Index. The British journal of dermatology Krain, R. L., Bax, C. E., Chakka, S., Ahmed, S., Feng, R., Payne, A. S., Werth, V. P. 2021; 184 (5): 975-977

  View details for DOI 10.1111/bjd.19718

  View details for PubMedID 33314027

  View details for PubMedCentralID PMC8102311

• Response of dermatomyositis to the antimalarial quinacrine: A retrospective cohort study. Journal of the American Academy of Dermatology Ravishankar, A., Yan, D., Bax, C. E., Concha, J. S., Feng, R., Werth, V. P. 2021; 84 (4): 1157-1160

  View details for DOI 10.1016/j.jaad.2020.07.081

  View details for PubMedID 32712056

  View details for PubMedCentralID PMC7854791

• Wong-Type Dermatomyositis in an African American Patient. Arthritis & rheumatology (Hoboken, N.J.) Bax, C. E., Grinnell, M., Concha, J. S., Werth, V. P. 2021; 73 (4): 630

  View details for DOI 10.1002/art.41629

  View details for PubMedID 33345443

  View details for PubMedCentralID PMC8005440

• The effects of immunostimulatory herbal supplements on autoimmune skin diseases. Journal of the American Academy of Dermatology Bax, C. E., Chakka, S., Concha, J. S., Zeidi, M., Werth, V. P. 2021; 84 (4): 1051-1058

  Abstract

  The use of herbal supplements that promise to improve immune health has gained popularity among dermatology patients. However, there is little to no evidence that herbal supplements improve dermatologic conditions. Several in vitro and in vivo studies have shown that Spirulina platensis, Aphanizomenon flos-aqua, Chlorella, Echinacea, and alfalfa activate immune cells via certain cytokines and chemokines. Case reports suggest the association of ingesting immunostimulatory herbs and the clinical onset or flares of diseases characterized by an exaggerated immune response such as lupus erythematosus, dermatomyositis, and autoimmune blistering disorders. Therefore, it is imperative to investigate the prevalence of herbal supplement use in this patient population. In addition, in vitro studies should examine the underlying mechanisms by which herbs stimulate immune pathways that are already overactive in autoimmune patients.

  View details for DOI 10.1016/j.jaad.2020.06.037

  View details for PubMedID 32553683

  View details for PubMedCentralID PMC7736300

• Identifying the required degree of disease clearance to improve quality of life in pemphigus vulgaris. The British journal of dermatology Bax, C. E., Ravishankar, A., Yan, D., Concha, J., Kushner, C. J., Zamalin, D., Feng, R., Payne, A. S., Werth, V. P. 2021; 184 (3): 573-575

  View details for DOI 10.1111/bjd.19625

  View details for PubMedID 33090460

• New-onset head and neck dermatitis in adolescent patients after dupilumab therapy for atopic dermatitis. Pediatric dermatology Bax, C. E., Khurana, M. C., Treat, J. R., Castelo-Soccio, L., Rubin, A. I., McMahon, P. J. 2021; 38 (2): 390-394

  Abstract

  Head and neck dermatitis after dupilumab therapy for atopic dermatitis has been frequently reported in adults and only rarely in adolescents. No cases detailing disease course and treatment response have previously been described in adolescents.This case series presents five adolescent patients who developed new-onset or worsening head and neck dermatitis after dupilumab therapy for atopic dermatitis. All five patients improved after oral antifungal therapy.The clinical features, treatment response, and potential disease pathogenesis in pediatric patients are described. Adolescents with new-onset head and neck dermatitis after dupilumab therapy may clinically improve with antifungal therapy, suggesting that Malassezia species may be a contributing factor or antifungal therapy may be an effective antiinflammatory agent.

  View details for DOI 10.1111/pde.14499

  View details for PubMedID 33426747

• Environmental triggers of dermatomyositis: a narrative review. Annals of translational medicine Bax, C. E., Maddukuri, S., Ravishankar, A., Pappas-Taffer, L., Werth, V. P. 2021; 9 (5): 434

  Abstract

  Dermatomyositis (DM) is an autoimmune disease that affects the skin, lungs, and muscle. Although the pathogenesis of DM is not completely understood, several environmental triggers have been linked to DM onset or flare. This article specifically examines the effects of herbal supplements, drugs, infections, ultraviolet (UV) radiation, and environmental pollutants on the onset or exacerbation of DM. Herbal supplements such as Spirulina platensis, Aphanizomenon flos-aquae, Chlorella, Echinacea, and Alfalfa have been implicated and are frequently used in health foods. Medications such as hydroxyurea, TNF-α inhibitors, immune checkpoint inhibitors (ICI), and penicillamine, as well as certain viral infections, such as parvovirus B19, coxsackie virus, polyomavirus, Epstein-Barr virus (EBV), hepatitis, influenza, and human immunodeficiency viruses (HIV) have been associated with DM onset. Bacterial infections and vaccinations have also been linked to the development of DM. Additional environmental factors, including UV radiation and air pollutants, such as silica, biological/mineral dust, and particulate air matter from vehicle and industrial emissions, may also play a role in DM pathogenesis. Overall, there is general agreement that an autoimmune attack of the skin, muscle, and lungs in DM can be triggered by various environmental factors and warrants further investigation.

  View details for DOI 10.21037/atm-20-3719

  View details for PubMedID 33842655

  View details for PubMedCentralID PMC8033368

• Accuracy of commercial panels to evaluate myositis autoantibodies: A single-institution perspective. Journal of the American Academy of Dermatology Ravishankar, A., Concha, J. S., Yan, D., Bax, C. E., Yeguez, A. C., Casciola-Rosen, L., Werth, V. P. 2021; 84 (2): 572-574

  View details for DOI 10.1016/j.jaad.2020.08.111

  View details for PubMedID 32896596

  View details for PubMedCentralID PMC7841648

• An evidence review of face masks against COVID-19. Proceedings of the National Academy of Sciences of the United States of America Howard, J., Huang, A., Li, Z., Tufekci, Z., Zdimal, V., van der Westhuizen, H., von Delft, A., Price, A., Fridman, L., Tang, L., Tang, V., Watson, G. L., Bax, C. E., Shaikh, R., Questier, F., Hernandez, D., Chu, L. F., Ramirez, C. M., Rimoin, A. W. 2021; 118 (4)

  Abstract

  The science around the use of masks by the public to impede COVID-19 transmission is advancing rapidly. In this narrative review, we develop an analytical framework to examine mask usage, synthesizing the relevant literature to inform multiple areas: population impact, transmission characteristics, source control, wearer protection, sociological considerations, and implementation considerations. A primary route of transmission of COVID-19 is via respiratory particles, and it is known to be transmissible from presymptomatic, paucisymptomatic, and asymptomatic individuals. Reducing disease spread requires two things: limiting contacts of infected individuals via physical distancing and other measures and reducing the transmission probability per contact. The preponderance of evidence indicates that mask wearing reduces transmissibility per contact by reducing transmission of infected respiratory particles in both laboratory and clinical contexts. Public mask wearing is most effective at reducing spread of the virus when compliance is high. Given the current shortages of medical masks, we recommend the adoption of public cloth mask wearing, as an effective form of source control, in conjunction with existing hygiene, distancing, and contact tracing strategies. Because many respiratory particles become smaller due to evaporation, we recommend increasing focus on a previously overlooked aspect of mask usage: mask wearing by infectious people ("source control") with benefits at the population level, rather than only mask wearing by susceptible people, such as health care workers, with focus on individual outcomes. We recommend that public officials and governments strongly encourage the use of widespread face masks in public, including the use of appropriate regulation.

  View details for DOI 10.1073/pnas.2014564118

  View details for PubMedID 33431650

• Children of the Sun: a historical look at how pediatric light therapy shaped attitudes and behaviors toward sunbathing. International journal of dermatology Bax, C. E., James, W. D. 2020; 59 (11): 1401-1408

  Abstract

  Today, parents are warned to protect their children from the sun's ultraviolet (UV) rays, the most preventable and leading cause of skin cancer. Yet, during the first half of the 20th century, the medical community widely extolled the health benefits of daily sunbaths for babies and children. What initially had begun as evidence-based medical therapies to prevent pediatric diseases, specifically tuberculosis and rickets, soon took on a life of its own as physicians, public health experts, and the general public embraced sunbathing and tanning as a means to ensure health and wellbeing for children and families. Here, we trace how specific medical therapies entered mainstream pediatric medicine and, converging with societal and cultural forces, shaped attitudes and behaviors towards sunbathing that still exist today. Understanding our complex history with the sun may shed light on the current peak of skin cancer incidence and future disease development. Moreover, it may help improve how we educate parents and children about sun safety by taking into account the current social and cultural context of medical practice and health communication.

  View details for DOI 10.1111/ijd.15185

  View details for PubMedID 32966597

• The airborne lifetime of small speech droplets and their potential importance in SARS-CoV-2 transmission. Proceedings of the National Academy of Sciences of the United States of America Stadnytskyi, V., Bax, C. E., Bax, A., Anfinrud, P. 2020; 117 (22): 11875-11877

  Abstract

  Speech droplets generated by asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are increasingly considered to be a likely mode of disease transmission. Highly sensitive laser light scattering observations have revealed that loud speech can emit thousands of oral fluid droplets per second. In a closed, stagnant air environment, they disappear from the window of view with time constants in the range of 8 to 14 min, which corresponds to droplet nuclei of ca. 4 μm diameter, or 12- to 21-μm droplets prior to dehydration. These observations confirm that there is a substantial probability that normal speaking causes airborne virus transmission in confined environments.

  View details for DOI 10.1073/pnas.2006874117

  View details for PubMedID 32404416

  View details for PubMedCentralID PMC7275719

• Visualizing Speech-Generated Oral Fluid Droplets with Laser Light Scattering. The New England journal of medicine Anfinrud, P., Stadnytskyi, V., Bax, C. E., Bax, A. 2020; 382 (21): 2061-2063

  View details for DOI 10.1056/NEJMc2007800

  View details for PubMedID 32294341

  View details for PubMedCentralID PMC7179962

• Prenatally diagnosed omphalocele: characteristics associated with adverse neonatal outcomes. Journal of perinatology : official journal of the California Perinatal Association Chock, V. Y., Davis, A. S., Cho, S., Bax, C., Fluharty, E., Weigel, N., Homeyer, M., Hudgins, L., Jones, R., Rubesova, E., Sylvester, K. G., Blumenfeld, Y. J., Hintz, S. R. 2019

  Abstract

  OBJECTIVE: To characterize factors associated with adverse neonatal outcomes in prenatally diagnosed omphalocele cases.STUDY DESIGN: Prenatally diagnosed omphalocele cases at a single referral center from 1 January 2009 to 31 December 2017 were retrospectively reviewed. Clinical variables and antenatal imaging measurements were collected. Associations between prenatal and neonatal characteristics and the adverse outcome of death or prolonged length of stay (LOS) were analyzed.RESULTS: Out of 63 fetal cases, 33 were live-born, >50% had other anomalies, and neonatal mortality was 12%. Adverse outcomes were associated with neonatal variables, including lower median 1-min Apgar score, initial mechanical ventilation, and late-onset sepsis, but not approach toomphalocele closure. With multivariate analysis, death or prolonged LOS was associated only with low lung volumes by fetal MRI (OR 34 (3-422), p=0.006).CONCLUSION: Low lung volumes by fetal MRI were associated with death or prolonged LOS in neonates with prenatally diagnosed omphalocele and may guide clinicians with counseling families.

  View details for DOI 10.1038/s41372-019-0410-1

  View details for PubMedID 31227786

• ENTREPRENEUR BROWNIE WISE <i>Selling Tupperware to America</i>'<i>s</i> <i>Women in the 1950s</i> JOURNAL OF WOMENS HISTORY Bax, C. E. 2010; 22 (2): 171-180

  View details for DOI 10.1353/jowh.0.0159

  View details for Web of Science ID 000278523800016