HSS Rheumatology Annual Report 2017-2018

Advancing Rheumatology
Division of Rheumatology | Annual Report 2017–2018

Table of Contents
2017 –2018 Achievements and
Fast Facts
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Cutting-Edge Initiatives
Identifying high-risk pregnancies
in patients with lupus
Improving outcomes for RA patients
undergoing joint replacement
Creating a better future for
scleroderma patients
Advancing high-value care and
outcomes for patients
Targeting interferon for better
control of lupus
Defining a new form of arthritis
in cancer patients
Improving bone health in patients
with ankylosing spondylitis
New possibilities for
scleroderma treatment
Using precision medicine to refine
RA treatment
Battling bone loss with a promising
microRNA-targeting therapy
Unraveling the molecular
mysteries of lupus
A promising new target for treating
autoimmune diseases
Investigating stem cells for
repairing fibrotic skin
Optimizing postsurgical outcomes
Complex Cases
Empowering Patients Through
Support and Education Programs
Rheumatology Leaders of the Future
Notable References
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Message from the Physician-in-Chief
and Chief of the Division of
Rheumatology
HSS rheumatologists have a long history of
commitment to advancing our field through
our many leadership roles, our engagement
in the education of future physicians, and
our contributions to unraveling the complex
mechanisms responsible for autoimmune and
inflammatory rheumatic diseases.
I want to congratulate Anne R. Bass, MD,
Attending Physician, on completing her term as
Chair of the American College of Rheumatology’s
(ACR) Committee on Rheumatology Training and
Workforce Issues. In view of the acknowledged
need to grow the number of adult rheumatologists
and pediatric rheumatologists in the U.S., recruiting
and training physicians is a high priority nationally
and at HSS. Dr. Bass has done an outstanding
job in her ACR role and as Director of the HSS
Rheumatology Training Program.
HSS rheumatologists also have high visibility and
critical roles in the programs at our academic
partner institution, Weill Cornell Medicine. Jane
E. Salmon, MD, Attending Physician, serves as
Associate Dean for Faculty Affairs. Juliet B. Aizer,
MD, Assistant Attending Physician, and Edward J.
Parrish, MD, Assistant Attending Physician, have
designed significant portions of the curriculum
for first- and second-year medical students and
guide nearly all members of our faculty in teaching
activities at the medical school.
“HSS rheumatologists and scientists are revolutionizing the care of patients
with some of the most challenging, complex medical conditions through
transformative research and global professional education.”
— Louis A. Shapiro, President and Chief Executive Officer, and Todd J. Albert, MD, FACS,
Surgeon-in-Chief and Medical Director, Korein-Wilson Professor of Orthopaedic Surgery
On cover, top left: From Nathalie Burg, MD, Instructor. Lower right: From Shipman et al., “A protective Langerhans cell-keratinocyte axis that is
dysfunctional in photosensitivity.” Science Translational Medicine 15 Aug 2018: Vol. 10, Issue 454, eaap9527. Reprinted with permission from AAAS.

Perhaps only second to our focus on expert
patient care is our commitment to studying the
mechanisms of lupus, scleroderma, myositis and
other rheumatic diseases: Why do they occur? Why
do they affect some people and not others? Why
are they more common in women than in men?
HSS has a long history of supporting physicianscientists.
Over the last five years, we’ve recruited
seven junior faculty members who are pursuing
careers in clinical and translational research. We
also founded the HSS Rheumatology Council, a
committee of supporters and donors dedicated to
raising the Rheumatology Division’s visibility and
enabling research.
Working in partnership with the Development
Department, we initiated a research grant program
and were pleased to award the first Rheumatology
Council Grants to the following physicians:
• Karmela K. Chan, MD,
Assistant Attending Physician
• Jessica K. Gordon, MD,
Assistant Attending Physician
• Nathalie Burg, MD, Instructor
• David R. Fernandez, MD, PhD,
Assistant Attending Physician
Other grant recipients include Bella Mehta,
MBBS, MD, Assistant Attending Physician,
who received the C. Ronald MacKenzie Young
Scientist Endowment Award. Michela Manni, PhD,
Instructor, received the Lockshin Fellowship Award
from the Barbara Volcker Center for Women and
Rheumatic Disease.
Our five Centers of Excellence and Division of
Pediatric Rheumatology facilitate collaboration
among physicians with disease-related academic
interests. Clinical care, research and patient
support are organized through most of the
Centers. Dr. Salmon, Director of the Lupus and
Antiphospholipid Syndrome Center of Excellence,
and colleagues oversee the recruitment of
patients for translational research studies on
lupus and APS and prioritize interventional clinical
trials of candidate therapeutics. The Center also
works closely with HSS social workers to lead
support groups and educational programs for
patients. HSS has been dedicated to advancing
the understanding of the immunopathogenesis
of systemic lupus erythematosus for many years,
and we continue to identify biomarkers that
predict complications of disease and molecular
targets that hold promise of leading to new
drug therapies.
Dr. Gordon and Robert F. Spiera, MD, Director of
the Scleroderma, Vasculitis & Myositis Center of
Excellence and Attending Physician, have worked
closely with Franck Barrat, PhD, Senior Scientist
at the HSS Research Institute, to study the role of
plasmacytoid dendritic cells in systemic sclerosis.
They have identified Toll-like receptor 8 as a novel
pathway for immune system activation in patients
with the disease. Drs. Gordon and Spiera are also
designing investigator-initiated studies of novel
therapeutics and participating in multicenter
sponsored clinical trials.
HSS rheumatologists recognize the value of
close collaboration with basic scientists in the
laboratory as well as with orthopaedic surgeons.
With the rich patient resources available at
HSS, clinical data and synovial tissue samples
collected at the time of arthroplasty have been
studied to characterize the cell populations
that are associated with flares in rheumatoid
arthritis. Vivian P. Bykerk, MD, Director of the
Inflammatory Arthritis Center of Excellence
and Associate Attending Physician, and Susan
M. Goodman, MD, Director of the Integrative
Rheumatology and Orthopedic Center of
Excellence and Attending Physician, have
established protocols that provide the clinical
data necessary for productive analysis of
tissue samples. These researchers and their
collaborators are using machine learning to
analyze gene expression data from synovial
tissue cells in relation to pathologic patterns of
tissue histology in rheumatoid arthritis patients.
In our Bone Health and Osteoporosis Center
of Excellence, Emily M. Stein, MD, Associate
Attending Physician and Associate Scientist, is
working closely with the HSS Spine Service to
study bone quality.
Our commitment to young investigators and the
success of their academic careers will ensure
that we sustain our long tradition of leadership in
rheumatology and our history of advancing patient
care. Our application of current technologies
to characterize the molecular mechanisms that
underlie the diseases we treat exemplifies our
unwavering commitment to achieve better lives for
our patients.
Mary K. Crow, MD
Physician-in-Chief
Chair, Department of Medicine
Chief, Division of Rheumatology
Benjamin M. Rosen Chair in Immunology and
Inflammation Research
Joseph P. Routh Professor of Rheumatic Disease Medicine

2
Division of Rheumatology
2017–2018 Achievements
#3 in the nation
for Rheumatology by U.S. News & World Report “Best Hospitals”
(2018–2019 rankings)
The Division of Rheumatology, the Department of Social
Work Programs and the Digital Communications team created
LupusMinder, a smartphone app that helps lupus patients manage
their condition. In 2018, the app received a Platinum award in
the category of Best Native Mobile App from the eHealthcare
Leadership Awards.
Mary K. Crow, MD, Physician-in-Chief and Chief, Division
of Rheumatology, received the Presidential Gold Medal
from the American College of Rheumatology (ACR)
in 2018. It is awarded in recognition of outstanding
achievements in rheumatology over the course of a career.
Dr. Crow is Co-Chair of the Scientific Advisory Board
of the Lupus Research Alliance and a member of the
Executive Committee of the Lupus Clinical Investigators
Network (LuCIN).
Franck Barrat, PhD, Senior Scientist; Robert F. Spiera,
MD, Director of the Scleroderma, Vasculitis & Myositis
Center of Excellence and Attending Physician; Jessica
K. Gordon, MD, Assistant Attending Physician; David
R. Fernandez, MD, Assistant Attending Physician; and
other HSS investigators published a significant study
in Science Translational Medicine in 2018 identifying
the plasmacytoid dendritic cell and Toll-like receptor
8 as important contributors to the pathogenesis of
systemic sclerosis.
Anne R. Bass, MD, Attending Physician, served as Chair
of the ACR Committee on Rheumatology Training and
Workforce Issues.
Vivian P. Bykerk, MD, Director of the Inflammatory
Arthritis Center of Excellence and Associate Attending
Physician, is the lead investigator of a rheumatoid arthritis
(RA) study funded by the National Institutes of Health
(NIH) and partnering pharmaceutical companies as part
of the Accelerating Medicines Partnership (AMP). The
study is focused on identifying molecular processes in
synovial tissue that reflect disease flare.
Doruk Erkan, MD, MPH, Associate Attending Physician and
Clinical Co-Director of the Mary Kirkland Center for Lupus
Care, is Executive Committee Chair of the international APS
research network APS ACTION (Antiphospholipid Syndrome
Alliance for Clinical Trials and International Networking).
Susan M. Goodman, MD, Director of the Integrative
Rheumatology and Orthopedic Center of Excellence and
Attending Physician, led the expert panel that created the
first-ever Guideline for the Perioperative Management
of Antirheumatic Medication in Patients With Rheumatic
Diseases Undergoing Elective Total Hip or Total Knee
Arthroplasty. The Guideline is sponsored by the American
College of Rheumatology and the American Association of
Hip and Knee Surgeons.
Kyriakos A. Kirou, MD, DSc, Assistant Attending
Physician, is the HSS Site Director of LuCIN.
Michael D. Lockshin, MD, Director of the Barbara
Volcker Center for Women and Rheumatic Disease and
Attending Physician, is author of The Prince at the Ruined
Tower: Time, Uncertainty & Chronic Illness, which was
published in 2017.
Dr. Lockshin and Dr. Erkan are editors of
Antiphospholipid Syndrome: Current Research Highlights
and Clinical Insights, which was published in 2017.
Theresa T. Lu, MD, PhD, Associate Scientist, was
awarded a research grant from the Lupus Research
Alliance to study the involvement of the lymphatic
system in ultraviolet light-induced cutaneous lupus.
Catherine H. MacLean, MD, PhD, Chief Value
Medical Officer and Director of the HSS Center for the
Advancement of Value in Musculoskeletal Care, was
named in the inaugural “Notable Women in Health Care
in NYC” list in Crain’s New York Business. In addition,
she serves on and is the immediate past chair of the
performance measures committee for the American
College of Physicians.
Bella Mehta, MBBS, MD, Assistant Attending Physician,
received the ACR Distinguished Fellow Award in 2018.

Hospital for Special Surgery 3
Karen B. Onel, MD, Chief of the Division of Pediatric
Rheumatology and Attending Physician, is Chair of the
Childhood Arthritis and Rheumatology Research Alliance
(CARRA) Ethics Committee. She is Co-Chair of the CARRA
Systemic Juvenile Idiopathic Arthritis working group.
Jillian Rose, LCSW, MPH, Director of Community
Engagement, Diversity and Research, received the
Distinguished Educator Award from the Association of
Rheumatology Health Professionals in 2018.
Linda A. Russell, MD, Director of the Bone Health
and Osteoporosis Center of Excellence and Associate
Attending Physician, was appointed by the American
College of Rheumatology as a member of its Committee
on Rheumatologic Care.
Jane E. Salmon, MD, Director of the Lupus and
Antiphospholipid Syndrome Center of Excellence and
Attending Physician, and Dr. Crow were named Honorary
Members of the European League Against Rheumatism
(EULAR) in 2018 and 2017, respectively. They are among
the first four Americans to achieve this honor, which
recognizes their contributions to research, education and
service to EULAR.
Dr. Salmon is a member of the Steering Committee of
LuCIN and the Scientific Advisory Board of the Lupus
Research Alliance. She was named a Master of the
American College of Rheumatology in 2017.
Lisa R. Sammaritano, MD, Associate Attending
Physician, was Principal Investigator of the American
College of Rheumatology Reproductive Health in
Rheumatic Diseases Guideline.
Robert F. Spiera, MD, Director of the Scleroderma,
Vasculitis & Myositis Center of Excellence and Attending
Physician, was a member of a group of investigators that
designed and executed a clinical trial for a new therapy
for giant-cell arteritis. Tocilizumab, an interleukin (IL)-6
blocking agent, was the first therapy approved by the
U.S. Food & Drug Administration and European Medicines
Agency for this indication.
Dr. Spiera is Chair of the Medical and Scientific Advisory
Board of the Scleroderma Foundation, Tri-State Chapter.
He and Jessica K. Gordon, MD, Assistant Attending
Physician, are members of this Board.
Dr. Spiera and Dr. Gordon are members of the National
Medical and Scientific Advisory Board of the Scleroderma
Foundation.
Sarah F. Taber, MD, Assistant Attending Physician,
is a co-author of the chapter on Systemic Lupus
Erythematosus in Childhood and Adolescence in the
2018 edition of Dubois’ Lupus Erythematosus and
Related Syndromes.
Fast Facts
Division of Rheumatology
The Division of Rheumatology comprises five Centers of Excellence and the Division of Pediatric Rheumatology.
The Centers bring together HSS faculty and staff members with an interest in a particular disease area to
develop projects and new research initiatives. They include physicians and healthcare professionals from other
departments, such as Orthopaedics, Social Work, Nursing and Research.
• Bone Health and Osteoporosis Center of Excellence
• Inflammatory Arthritis Center of Excellence
• Integrative Rheumatology and Orthopedic Center of Excellence
• Lupus and Antiphospholipid Syndrome Center of Excellence
• Scleroderma, Vasculitis & Myositis Center of Excellence
• Division of Pediatric Rheumatology
Adult rheumatologists
36 36,027
Pediatric rheumatologists
5 2,969
Scientists
9 2,728
Perioperative
17 medicine physicians 15,665
9
Rheumatology
support and
education programs for patients
Adult rheumatology
patient visits
Pediatric rheumatology
patient visits
Endocrinology
patient visits
Perioperative
patient visits
All figures pertain to the 2017–2018 academic year.

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Division of Rheumatology
Identifying high-risk pregnancies
in patients with lupus
Most women with lupus can
have successful pregnancies,
but some develop complications,
such as preeclampsia, fetal
and neonatal death, and
fetal growth restriction. We
cannot predict in whom these
adverse outcomes will occur.
In experimental laboratory
models, complement activation
causes adverse pregnancy
outcomes. To investigate the
role of complement in patients,
Jane E. Salmon, MD, Collette
Kean Research Chair, Attending
Physician and Director of the
Lupus and Antiphospholipid
Syndrome Center of Excellence;
Michael D. Lockshin, MD, Director
of the Barbara Volcker Center
for Women and Rheumatic
Disease and Attending Physician;
and Lisa R. Sammaritano, MD,
Associate Attending Physician,
and colleagues mined the data
and samples from PROMISSE
(Predictors of Pregnancy
Outcome: Biomarkers in
Antiphospholipid Antibody
Syndrome and Systemic Lupus
Erythematosus). The results of
their study, which was published
in the Annals of the Rheumatic
Diseases in April 2018, included
the evaluation of 487 pregnant
women with SLE and/or aPL
antibodies and 204 pregnant
healthy controls. At each
month of pregnancy, samples
were obtained to measure
complement activation products
in patients’ blood. Adverse
pregnancy outcomes occurred
in approximately 20 percent of
SLE and/or aPL pregnancies
and were associated with
lupus anticoagulant, history of
hypertension, and non-white
race. Levels of complement
products early in pregnancy
were significantly higher in
A recent finding by Jane E. Salmon, MD, Director of the Lupus and
Antiphospholipid Syndrome Center of Excellence and Attending Physician
(left), may help pregnant women with lupus have healthy babies, such as
the patient shown at right. Marta M. Guerra, MS, Project Coordinator for
Dr. Salmon’s study (center), admires the baby.
patients who experienced
pregnancy complications.
These findings suggest that,
as in the experimental models,
complement activation
contributes to abnormal placental
development, which leads to
pregnancy complications.
TNF-α is released by
inflammatory cells as a
consequence of complement
activation, and it too contributes
to placental dysfunction,
preeclampsia and fetal growth
restriction in experimental
models. To translate these
findings to patients, Dr. Salmon
and her team are conducting
a trial in which they will treat
pregnant women with APS and
SLE at high risk for serious
pregnancy complications with
certolizumab, a TNF inhibitor used
Dr. Salmon’s
research suggests
that complement
activation contributes
to abnormal placental
development, which
leads to pregnancy
complications.
to treat rheumatoid arthritis and
psoriatic arthritis that does not
cross the placenta. “If the trial
prevents pregnancy complications
in patients with SLE and APS, it
may also prevent preeclampsia
in women without autoimmune
disease who are at risk for
placental insufficiency,” says
Dr. Salmon. “We hope our studies
of SLE and APS have implications
for the general population.”

Hospital for Special Surgery 5
Improving outcomes for
RA patients undergoing
joint replacement
Although rheumatoid arthritis
(RA) patients have experienced
improvements in healthrelated
quality of life and
functional status, rates of total
hip replacement and total
knee replacement procedures
have remained stable. Most
RA patients who undergo
arthroplasty are taking diseasemodifying
antirheumatic drugs
and biologic therapies, which
are known to increase their risk
of developing a prosthetic joint
infection. As a result, patients
are typically instructed to stop
taking their medications prior
to surgery. This may increase
their risk of having a flare
perioperatively, which may have
a negative effect on rehabilitation
efforts and outcomes.
To investigate patient-reported
RA flares, HSS researchers
launched the RA Perioperative
Flare Study. This is likely the
first study to prospectively
assess postoperative, patientreported
flares of RA in patients
undergoing THA and TKA using
the RA-FQ, a validated, patientreported
outcome instrument for
identifying RA flares.
In the study, which was published
in The Journal of Rheumatology
in May 2018, 120 HSS patients
answered a questionnaire each
week for six consecutive weeks
after surgery. Patients who
reported flares after surgery were
compared to those who did not
experience them. Lead author
Susan M. Goodman, MD, Director
of the Integrative Rheumatology
and Orthopedic Center of
Excellence and Attending
From left to right: Mark P. Figgie, MD, Chief of the Surgical Arthritis Service,
Allan E. Inglis MD Chair in Surgical Arthritis, and Attending Orthopaedic
Surgeon, and Susan M. Goodman, MD, Director of the Integrative
Rheumatology and Orthopedic Center of Excellence and Attending
Physician, are investigating flares in RA patients after arthroplasty.
Physician, and colleagues found
that 63 percent of the patients
experienced a flare by six weeks
after surgery. The patients who
flared had significantly higher
disease activity at baseline, but
preoperative antirheumatic
medication withdrawal was not an
independent risk factor for flares.
To improve outcomes and
reduce the risk of infection in
RA patients, HSS researchers
are investigating the effects
of changing the perioperative
medication protocol. “We can
withhold biologic medications
for one-dose intervals around
the time of surgery,” says
Dr. Goodman. “Now we’re looking
at pain and functionality in these
patients after a year.”
Rheumatoid arthritis
patients who
experienced flares
after arthroplasty
had significantly
higher disease
activity at baseline.

6
Division of Rheumatology
Creating a better future for
scleroderma patients
Scleroderma is one of the
most debilitating rheumatic
diseases. It is associated with
significant morbidity and
disability and has the highest
rate of all-cause mortality
among the rheumatic diseases.
To date, no medication has
been specifically approved for
this condition. Fortunately,
HSS physicians and scientists
have made significant progress
in investigating promising
new treatment options. One
area of focus is lenabasum,
a cannabinoid receptor
type 2 (CB2) agonist. In
2017, Robert F. Spiera, MD,
Director of the Scleroderma,
Vasculitis & Myositis Center
of Excellence and Attending
Physician, led a Phase II
study of the drug sponsored
by Corbus Pharmaceuticals.
It demonstrated acceptable
safety and tolerability and
suggested a possible benefit
in scleroderma patients. He
presented the results at the
2017 American College of
Rheumatology Annual Meeting.
CB2 receptors are expressed on
immune system cells, including
T cells, macrophages and B
cells. They appear to modulate
immune function. “Triggering
these cells turns off the
propagation of the inflammation
phase of the innate immune
response and promotes
expression of resolvins, which
contribute to resolving the
inflammatory response, thereby
ultimately diminishing tissue
fibrosis,” says Dr. Spiera.
In a one-year, open label
extension study that followed
the Phase II trial, patients
taking lenabasum continued to
see significant improvements
in inflammation and fibrosis.
From left to right: Jessica K. Gordon, MD, Assistant Attending Physician,
and Robert F. Spiera, MD, Director of the Scleroderma, Vasculitis & Myositis
Center of Excellence and Attending Physician, are studying two drugs that
may be effective in scleroderma patients.
Dr. Spiera presented these
results at the European League
Against Rheumatism Congress
in Amsterdam in June 2018. Now
HSS is the lead site for a yearlong
Phase III trial of lenabasum,
which is currently enrolling
patients around the world.
Positive results could help to
advance the drug on the path to
FDA approval. “What’s appealing
about this drug is it appears to
be very safe,” says Dr. Spiera.
Unlike medications that
suppress the immune system,
lenabasum doesn’t appear to
increase the risk of infection.
Dr. Spiera is also optimistic
about belimumab. In an HSSsponsored,
investigator-initiated
trial of the drug, patients with
early diffuse scleroderma who
received the medication saw
significant improvements in skin
thickness scores. The findings
were published in Arthritis and
Rheumatology in January 2018.
The researchers also
determined that the drug
affects patients’ gene
expression in skin biopsies.
“Significant decreases in the
expression of B-cell signaling
and pro-fibrotic gene pathways
were observed in patients who
improved on the drug and not
in those who didn’t improve,”
says Dr. Spiera. This supports
the idea that the drug was
having an effect on the relevant
cellular mechanisms. Dr. Spiera
and his colleague, Jessica
K. Gordon, MD, Assistant
Attending Physician, plan to
initiate a larger study of this
strategy, which will begin in
early 2019.
Although there’s a long road
ahead for getting a new drug
to market, the prospects are
promising. “It will be very
exciting if either drug pans
out,” says Dr. Spiera. “This is a
totally unmet need.”

Hospital for Special Surgery 7
Advancing high-value care
and outcomes for patients
Catherine H. MacLean, MD, PhD, Chief Value Medical Officer, is studying
patient-reported outcome measures, or PROMs.
Our commitment to providing
value-based care is reflected in
our high-quality services and
low complication rates. “HSS
leads the country in performance
on a number of different safety
measures,” says Catherine H.
MacLean, MD, PhD, Chief Value
Medical Officer. “As a result,
our total cost for an episode of
care is lower than that of other
hospitals.” While safety is of
paramount importance, patients
come to HSS to get better. So we
are focused on studying patientreported
outcome measures,
or PROMs. “We’re measuring
PROMs as a standard of care
because we want to understand
how our patients are doing in
terms of improving their pain
and functional status,” says
Dr. MacLean.
HSS physicians also aim to be
responsible when prescribing
medications. “Rheumatologists
are the stewards of a number of
very expensive drugs, including
adalimumab, infliximab,
etanercept and rituximab—four
of the five drugs with the highest
dollar sales worldwide,” says
Dr. MacLean. “These medications
are often effective for rheumatoid
arthritis (RA) patients, but there
are less expensive alternatives
that may be appropriate for
certain patients. By routinely
assessing disease activity and
patient outcomes, we can be
more thoughtful about the drugs
we prescribe.” At the same time,
physicians need to have open,
honest conversations with their
patients about the costs of
medical care—in particular, these
very expensive medications,
which cost thousands of dollars
per month. Given the choice
between two similarly effective
drugs, patients might prefer the
less expensive option, especially
if they have a high co-pay or
no insurance.
The highest value care for
rheumatoid arthritis is that which
prevents long-term disease or
joint damage. Hence, our first
objective is to treat early and
aggressively with the best drug
for the individual patient, be that
a conventional drug or a more
expensive biologic one. This has
resulted in a marked reduction in
the development of joint damage,
deformity and disability. “When
I was a fellow, there were always
wheelchairs in the rheumatology
waiting room,” says Dr. MacLean.
“They are a pretty rare sight
these days.”
How a rheumatologist became Chief Value Medical Officer
Catherine H. MacLean, MD, PhD, is a
rheumatologist as well as Chief Value
Medical Officer. She currently directs the
HSS Center for the Advancement of Value
in Musculoskeletal Care. In this role, Dr.
MacLean develops programs, systems
and tools to deliver high-value care at
HSS and beyond. She has had a full and
varied career, with stints in academic
medicine, research and the insurance
industry. After attending Washington
University School of Medicine in St.
Louis, Dr. MacLean completed training
in internal medicine at Harbor-UCLA
Medical Center and rheumatology at
UCLA Center for the Health Sciences. As
part of UCLA’s first Scientific Training and
Advanced Research fellowship class, she
also earned a PhD in health services from
UCLA’s School of Public Health. Upon
completing her training, she joined the
faculty at UCLA with joint appointments
at the RAND Corporation and the West
Los Angeles VAMC, where her research
focused on defining, measuring and
improving healthcare quality. She was
recruited by Anthem/WellPoint to help
drive quality improvement and eventually
led quality and care management
programs there. In 2015, she joined HSS.
Dr. MacLean was the principal
investigator on many academic research
projects at UCLA and RAND, and has
been a director, chair or participant on
numerous national committees and
panels related to healthcare quality and
value. She is the immediate past chair of
the performance measures committee at
the American College of Physicians (ACP)
and currently serves on the ACP’s Quality
Improvement Learning Collaborative
Task Force and the National Committee
for Quality Assurance’s Bone and Joint
Measurement Advisory Panel.

8
Division of Rheumatology
Targeting interferon for
better control of lupus
HSS has been a leader in the
quest to better understand
systemic lupus erythematosus
(SLE), thanks in large part to
research directed by Mary K.
Crow, MD, Physician-in-Chief
and Chief of the Division of
Rheumatology. About 17 years
ago, she and two other groups
observed that type I interferon
was responsible for the genes
expressed in blood from lupus
patients. This suggested that
a virus or virus-like stimulus
might play a role in the wide
range of immune alterations and
autoimmunity associated with
SLE. This finding became known
as the “interferon signature” and
continues to be an important
way of characterizing lupus
patients for research.
Over the last decade, Dr. Crow
and her team identified an
association between a positive
interferon signature and
active and severe disease.
They also found that the
interferon signature was
associated with the presence
of autoantibodies that target
RNA or RNA-binding proteins.
That observation indicated that
immune complexes containing
RNA, as well as RNA within
cells, might be triggers for the
production of type I interferon.
This was confirmed in other
studies. “Our lab has been
particularly interested in the
potential role of RNA encoded by
endogenous virus-like elements
in our own genomes—LINE-1
retrotransposons—as drivers
of type I interferon in SLE,”
says Dr. Crow. “We showed
that cells from patients with
SLE or Sjogren’s syndrome
express elevated RNAs encoding
LINE‐1 and that LINE-1 RNA can
induce the production of type I
interferon. Overall, we think that
type I interferon is responsible
for many of the immune system
alterations in SLE patients.”
Currently, Dr. Crow is studying
agents aimed at reducing the
interferon signature—and the
production or action of type I
interferon. “We are continuing
to investigate the role of
endogenous retroelements
as drivers of type I interferon
production, but we have
Left: SLE is characterized by
sustained activation of the type I
interferon pathway, in contrast to
the brief expression of interferon
after a viral infection.
Above, top: Mary K. Crow, MD, Physician-in-Chief and Chief of the Division
of Rheumatology (center), and her research team discuss their findings on
the role of type I interferon in systemic lupus erythematosus.
expanded the scope of our
research to include additional
molecular pathways involved
in SLE,” says Dr. Crow. “We
are currently analyzing gene
expression data that we think
will provide new insights into
mechanisms responsible for
lupus nephritis, an important
organ system manifestation
of SLE and a reason for poor
patient outcomes.”

Hospital for Special Surgery 9
Defining a new form of
arthritis in cancer patients
“Studying a new form
of arthritis linked to
immunotherapy drugs
may help us to figure
out the immunologic
pathways that lead
to arthritis. That may
allow us to target those
pathways early on and
potentially prevent RA in
the general population.”
Anne R. Bass, MD,
Attending Physician
Anne R. Bass, MD, Attending Physician, examines a patient who is taking
immunotherapy medications.
Immunotherapy drugs known
as “checkpoint inhibitors” can
have dramatic, often lifesaving
benefits for cancer patients.
But they are also known to
have problematic side effects.
“Patients are staying on these
drugs for longer periods of
time, and we’re starting to see
arthritis as a side effect more
commonly,” says Anne R. Bass,
MD, Attending Physician. “My
theory is that some patients
are genetically predisposed to
arthritis and develop it when
they take these immunestimulating
therapies.”
Collaborating with oncologists
at a major New York City
cancer center, Dr. Bass has
been working to clinically
define this new form of
inflammatory arthritis,
which causes joint swelling
and pain and occasionally is
associated with rheumatoid
arthritis (RA) markers in
the blood. In some patients,
symptoms resemble RA, and
in others, they are similar
to polymyalgia rheumatica.
Dr. Bass is investigating
why and how the condition
develops on an immunological
level and is establishing
treatment protocols. One key
question: Is the “RA-like” form
of inflammatory arthritis the
same as the RA that develops
in people who haven’t taken
immunotherapy drugs? “If it
is, then these patients offer
an opportunity to study RA
developing over a compressed
period of time,” says Dr. Bass.
This shortened timeline “may
enable us to identify predictors
for RA and figure out the
immunologic pathways that
lead to arthritis. That may allow
us to target those pathways
early on and potentially prevent
RA in the general population.”
While we aim to treat the
arthritis that develops in
cancer patients who are taking
immunotherapy medications, we
don’t want to interfere with the
curative effects of the drugs by
suppressing the immune system
too much. Says Dr. Bass: “This
is an important opportunity
for clinical and research
collaboration with our oncology
colleagues, especially now that
immunotherapy is being used
for an ever-expanding array
of cancers.”

10
Division of Rheumatology
Susan M. Goodman, MD, Director of the Integrative Rheumatology and Orthopedic Center of Excellence and
Attending Physician, and HSS colleagues are studying the effects of the drug secukinumab on the skeleton.
Improving bone health in patients
with ankylosing spondylitis
While people with ankylosing
spondylitis (AS) tend to
experience overactive bone
growth and develop abnormal
bone spurs, they are also prone
to osteoporosis. Studies have
estimated that the prevalence
of osteoporosis is as high as
25 percent for these patients—
more than double the 10 percent
prevalence in the general
population. Although these
patients produce more cortical
bone, the trabecular bone is
abnormally weak. As a result,
they are at risk of spinal fractures,
which can lead to changes in
posture and pain.
Bisphosphonates, calcium and
vitamin D can be prescribed
to prevent fractures, but AS
patients don’t respond well
to these therapies. In 2018,
HSS physicians launched a
pilot study to investigate the
effects of secukinumab—a
monoclonal antibody used to
treat autoimmune diseases—
on the skeleton. The drug is
currently approved for treatment
of AS, moderate to severe plaque
psoriasis and psoriatic arthritis.
It targets interleukin-17A and
may protect against bone loss
by suppressing the function of
osteoclasts and promoting the
activity of osteoblasts.
In the study, which will last two
years, patients with the condition
will undergo assessments, such
as X-ray imaging of the skeleton to
measure bone density and scoring
of the spine for the presence
of spurs or erosions. “What
makes the disease so disabling
is new bone formation that fuses
the vertebrae,” says Susan M.
Goodman, MD, Director of the
Integrative Rheumatology and
Orthopedic Center of Excellence
and Attending Physician, who is
leading the study. “Preliminary
data supporting the use of the
drug suggest that you don’t get
“Preliminary data
supporting the use
of secukinumab, a
monoclonal antibody
used to treat
autoimmune diseases,
suggest that AS
patients don’t get
the bony proliferation
as rapidly.”
Susan M. Goodman, MD, Director
of the Integrative Rheumatology
and Orthopedic Center of
Excellence and Attending Physician
the bony proliferation as rapidly.”
Study participants will also
be tested for markers of bone
growth and resorption, as well as
inflammation levels. If the results
are positive, Dr. Goodman’s team
will study the drug’s effects in a
larger patient population.

Hospital for Special Surgery 11
New possibilities for
scleroderma treatment
Scleroderma, one of the most
life-threatening rheumatic
diseases, is among the most
challenging to understand and
treat. But breakthrough research
from the lab of Franck Barrat,
PhD, Michael R. Bloomberg Chair
and Senior Scientist, could lead
to new therapeutic possibilities.
Dr. Barrat’s research focuses
on plasmacytoid dendritic
cells (pDCs), which normally
produce interferon to combat
infection. In a study published in
Science Translational Medicine
in January 2018, Dr. Barrat
and HSS and international
colleagues revealed that pDCs
are chronically activated in
scleroderma patients. They
infiltrate the skin, where
they trigger fibrosis and
inflammation. “In the field
of scleroderma, people have
focused on how to stop
fibrosis,” says Dr. Barrat.
“But the correlation between
inflammation and the main
players that drive inflammation
in fibrosis hasn’t been explored
as much. This is pointing us in a
direction that people had not
looked at before.” As a result,
the finding has generated
considerable excitement from
scientists and industry. “Some
companies are looking really
hard at this now,” says Dr. Barrat.
Top: In our model, the secretion of CXCL4, a marker of systemic sclerosis
(SSc), by patients’ plasmacytoid dendritic cells (pDCs) is due to the
aberrant presence of TLR8 on these cells. CXCL4 potentiates the IFN
production by pDCs, which promotes the autoimmune response and
potentially fibrosis in patients. Depleting pDCs prevented disease in a
preclinical model of scleroderma, suggesting that pDC is an essential
cell type involved in the pathogenesis of SSc.
Bottom, from left to right: Jessica K. Gordon, MD, Assistant Attending
Physician, and Franck Barrat, PhD, Senior Scientist, as well as other
HSS researchers, discovered that plasmacytoid dendritic cells (pDCs)
are chronically activated in scleroderma patients, opening the door to
investigations of new treatments.
In a disease model, Dr. Barrat and
colleagues showed that depleting
pDCs prevented fibrosis. The
research has helped to delineate
important mechanisms of the
aberrant cell activity. It has
implicated a receptor on the
surface of pDCs, called TLR8,
as a culprit behind the cell
activity. As a result, there may
be several potential therapeutic
targets and some existing drugs
as possible candidates for
study in scleroderma patients.
“We have identified pDCs as
potentially very important in the
establishment and development
of fibrosis,” says Dr. Barrat.
“Now we can investigate new
therapeutic options for targeting
the cells, the ways they become
activated, and some of the
product they make.”
These findings have led to new
research funding, including
nearly $1.8 million in grants from
the National Institutes of Health
and the Scleroderma Research
Foundation. “What excites me
is all of the possibilities that
this research has opened up,”
says Dr. Barrat. “We’ve put
scleroderma on the map.”

12
Division of Rheumatology
Using precision medicine
to refine RA treatment
The promise of precision
medicine is to personalize
therapy for patients with
notoriously difficult-to-treat
diseases such as rheumatoid
arthritis (RA). To that end, HSS
scientists and physicians are
investigating differences in RA
patients’ responses to drugs as
part of the five-year Accelerating
Medicines Partnership (AMP)
study, funded by the National
Institutes of Health and
partnering pharmaceutical
companies. Our researchers
are also investigating molecular
pathways involved in flares.
“We’re trying to discover new
pathways, which could lead
to new therapeutic targets,”
says Lionel B. Ivashkiv, MD,
Richard L. Menschel Chair and
Chief Scientific Officer, David
H. Koch Chair for Arthritis and
Tissue Degeneration Research,
and Director of the David Z.
Rosensweig Genomics Research
Center. “The ultimate goal is
to use this information to help
us choose the best drug for
each patient at the beginning
of treatment.”
“Using advanced genomic
technologies involving single
cells, we are studying synovial
tissue samples to find out how
they relate to disease activity
in the patient,” says Vivian P.
Bykerk, MD, lead investigator
of the RA study, Director of the
Inflammatory Arthritis Center
of Excellence and Associate
Attending Physician. In the first
phase of the study, which is
now complete, our researchers
were able to identify eight new
cell types in RA joints using
next-generation sequencing
techniques. “These are
subsets we’d want to target
with new drugs,” says Laura
Donlin, PhD, Co-Director of the
Derfner Foundation Precision
Medicine Laboratory and
Assistant Scientist.
In the second phase of the
study, which is currently
underway, our researchers are
following a large cohort of RA
patients who will have tissue
samples taken before and after
a new treatment is provided.
Researchers will monitor them
and look for commonalities
that could serve as biomarkers
for treatment response. “HSS
is a critical player in the AMP
consortium because we provide
unique scientific expertise
and patient resources,” says
Dr. Ivashkiv. “This study has
changed the way we perform
translational research, have
scientific collaborations,
and link clinical data with
scientific data.”
From left to right: Laura Donlin, PhD, Co-Director of the Derfner Foundation Precision Medicine Laboratory and
Assistant Scientist, and Vivian P. Bykerk, MD, Director of the Inflammatory Arthritis Center of Excellence and
Associate Attending Physician, review data for the AMP study.

Hospital for Special Surgery 13
Baohong Zhao, PhD, Assistant Scientist, has identified two different methods for protecting against excessive
osteoclast formation and bone destruction in disease models of osteoporosis and rheumatoid arthritis.
Battling bone loss with
a promising microRNAtargeting
therapy
Small non-coding RNA molecules
that are approximately 21 to
25 nucleotides in length, or
microRNAs (miRNAs), regulate
gene expression and functions
in a variety of biological and
pathological settings. While
miRNA-based therapies have
recently shown significant
promise in the treatment of
diseases like cancer, diabetes
and hepatitis C, their use
has been underexplored in
osteoporosis and rheumatoid
arthritis—until now. Baohong
Zhao, PhD, Assistant Scientist
in the Arthritis and Tissue
Degeneration Program and The
David Z. Rosensweig Genomics
Research Center, has been using
miRNA-sequencing techniques
to profile genome-wide changes
in miRNAs that are involved in
the differentiation of osteoclasts.
She has identified two different
methods for protecting against
excessive osteoclast formation
and bone destruction in disease
models of ovariectomy-induced
osteoporosis and rheumatoid
arthritis. One approach involves
using a genetic knockout of
miR-182 and the other involves
a specific inhibitor targeting
miR-182. “Our exciting genetic
evidence and outstanding
pharmacological results
obtained from disease models
provide a proof of concept for
the efficacy of therapeutic
targeting of miR-182 to prevent
bone loss and highlight the
translational implications
of targeting miR-182 in
treating osteolytic diseases,”
says Dr. Zhao. “Now we are
collaborating with translational
researchers to see if we can
develop more appropriate
approaches to deliver a miR-
182 inhibitor to patients with
osteoporosis and arthritis to
suppress bone loss.”
While developing a safe and
effective delivery system
for this therapy is a priority,
Dr. Zhao hopes that this
miRNA will eventually be used
as a biomarker to predict the
progression of these diseases to
prevent bone loss early on.

14
Division of Rheumatology
Unraveling the molecular
mysteries of lupus
HSS Research Institute scientists
are conducting studies at the
molecular level to uncover new
targets for lupus treatment.
Alessandra Pernis, MD, The
Peter Jay Sharp Chair in Lupus
Research and Senior Scientist, is
identifying molecular pathways
of autoimmunity in the disease.
Her work focuses on B cells,
important players in autoimmune
disease, including a subset called
age-associated B cells, also
known as ABCs. Dr. Pernis has
discovered that ABC cells play two
key roles in autoimmunity. “They
can behave like B cells by making
autoantibodies, and they can
behave like inflammatory cells by
making inflammatory cytokines,”
she says. “Understanding the
pathways that regulate these cells
could represent a major advance
in lupus as well as autoimmunity
in general.”
Using genome-wide transcriptional
and epigenetic analysis of ABCs,
Dr. Pernis and her team have
uncovered the mechanism
by which ABCs are regulated.
“The majority of patients with
autoimmunity are women, but
until now we have not been able
to find a molecular link,” says
Dr. Pernis. “This is the first time
we can see clear differences in
males and females and how they
behave at the transcriptional
as well as the epigenetic level.”
This research will enable us to
uncover new treatment targets.
Separately, Theresa T. Lu,
MD, PhD, Associate Scientist,
whose research is supported
by the St. Giles Research Chair,
is making headway toward
understanding photosensitivity,
whereby the sun’s ultraviolet
(UV) light can trigger skin rashes
as well as flares in patients.
Photosensitivity affects 30 to
60 percent of lupus patients.
Dr. Lu’s research centers on
Langerhans cells, immune
cells in the top layer of skin. In
a study published in Science
Translational Medicine in 2018,
Dr. Lu, HSS colleagues and
scientists at other institutions
found that in healthy people,
these cells protect the skin from
UV damage. “With UV exposure,
Langerhans cells normally
activate ADAM17, a molecule
that activates epidermal growth
factor receptor (EGFR) ligands,
helping skin cells to survive,”
says Dr. Lu. In lupus models,
Langerhans cells expressed less
of the ADAM17 molecule, so
they were less able to protect
the skin. However, when EGFR
ligand was added to the skin
in lupus models, fewer lesions
developed. More research is
needed, but “stimulating EGFR
in the skin may be an approach
to ameliorating photosensitivity
and systemic disease in lupus
patients,” says Dr. Lu.
Above: Langerhans cells (in red) sit
among and protect the keratinocytes
(in blue) in the skin epidermis.
Photo Credit: William D. Shipman,
PhD, Lu Lab, Autoimmunity and
Inflammation Program
Left, from left to right:
Alessandra Pernis, MD, Senior
Scientist, is identifying molecular
pathways that play key roles in
lupus, and Theresa T. Lu, MD,
PhD, Associate Scientist, is
gaining a better understanding of
photosensitivity in lupus patients.

Hospital for Special Surgery 15
From left to right: Jane E. Salmon, MD, Director of the Lupus and Antiphospholipid Syndrome Center of
Excellence and Attending Physician, and Carl P. Blobel, MD, PhD, Director of the Arthritis and Tissue
Degeneration Program and Senior Scientist, have discovered that iRhom2 may be an attractive new target for
treating patients with lupus and hemophilic arthropathy.
A promising new target for
treating autoimmune diseases
HSS scientists have identified a
key protein that helps to regulate
inflammation and could become
a target for treating autoimmune
diseases. The protein iRhom2
appears to play a critical role
in causing kidney damage in
patients with lupus and seems to
contribute to osteoporosis and
joint damage in patients with
hemophilic arthropathy.
In a study published in the
April 2018 issue of The Journal
of Clinical Investigation, HSS
researchers and international
colleagues found that
inactivating iRhom2—which
regulates ADAM17, whose
substrates, such as TNF-α
and heparin-binding EGF (HB-
EGF), have been implicated in
the pathogenesis of chronic
kidney disease—prevented
inflammation and irreversible
scarring in lupus nephritis
models. These same pathways
were found to be upregulated
in kidney biopsies from lupus
patients. “The benefit of this
approach is selective and
simultaneous inhibition of two
major pathological mediators
of tissue damage in lupus,” says
Jane E. Salmon, MD, Director of
the Lupus and Antiphospholipid
Syndrome Center of Excellence,
Collette Kean Research Chair,
and Attending Physician.
In another study, published
in Blood in September 2018,
HSS researchers found that
inactivating iRhom2/TNF-α
prevented the bone erosion and
joint inflammation often seen in
hemophilic arthropathy. “This is
a major breakthrough because
it points toward exciting new
approaches for treatment of
“The benefit of
inactivating iRhom2
is selective and
simultaneous
inhibition of two major
pathological mediators
of tissue damage in
lupus.”
Jane E. Salmon, MD, Director of
the Lupus and Antiphospholipid
Syndrome Center of Excellence
and Attending Physician
these two major manifestations
of hemophilic arthropathy,” says
Carl P. Blobel, MD, PhD, Director
of the Arthritis and Tissue
Degeneration Program, Virginia F.
and William R. Salomon Chair
in Musculoskeletal Research,
and Senior Scientist.

16
Division of Rheumatology
Investigating stem cells for
repairing fibrotic skin
“We think there
are particular
subpopulations of
ADSCs that help to
repair fibrotic skin, and
we think there is a role
for immune cells.”
Theresa T. Lu, MD, PhD,
Associate Scientist
lymphotoxin to injected ADSCs
would improve ADSC survival
and effectiveness. They found
that this combined regimen was
able to partially reverse fibrosis.
The question now is how exactly
the ADSCs are working to repair
fibrotic skin. “We think there
are particular subpopulations
of ADSCs that help to repair
fibrotic skin, and we think there
is a role for immune cells,”
says Dr. Lu.
Theresa T. Lu, MD, PhD, Associate Scientist, is studying adiposederived
stromal cells (ADSCs) as a potential therapy for patients with
scleroderma and other diseases.
One of the major challenges
in managing scleroderma
patients is the lack of effective
treatments for skin fibrosis.
This condition is not only
painful and can lead to severe
joint contractures and loss
of hand function, but it can
also cause asymmetric limb
or facial growth in children.
In addition, wound healing is
compromised. Theresa T. Lu,
MD, PhD, Associate Scientist
and a member of the Division
of Pediatric Rheumatology,
and members of her lab
have been studying adiposederived
stromal cells (ADSCs),
which contribute to the repair
and regeneration of tissues,
including skin. Her lab has found
that ADSC numbers are reduced
in skin fibrosis—most likely
due to cell death—suggesting
that effective replenishment of
these cells could repair fibrotic
skin and be a possible therapy
in a multipronged approach for
scleroderma patients. In a study
published in The Journal
of Clinical Investigation,
Dr. Lu and colleagues found that
certain immune cells known
as dendritic cells help ADSCs
survive in fibrotic skin. There is
an interest in the scleroderma
field in injecting ADSCs to
repair the skin, but one of the
limitations is that ADSCs do
not survive a long time. Dr. Lu’s
group reasoned that adding
the dendritic cell-derived signal
In 2017, Dr. Lu received a
grant from the Scleroderma
Foundation to determine which
ADSC subpopulations are
reparative and which ones may
be harmful. Dr. Lu also recently
received funding from the nonprofit
organization A Lasting
Mark to begin to examine the
role of immune cells in mediating
ADSC effects. One future goal
is to find out whether ADSC
populations in children’s skin
are more or less susceptible to
damage by fibrosis compared
to adults’ skin. “We know that
children’s skin heals better
than adults’ skin,” says Dr. Lu.
“Determining whether there
are ADSC subpopulations that
are more protective in children
will help us gain a better
understanding of scleroderma—
and potentially improve therapies
for patients.”

Hospital for Special Surgery 17
Optimizing postsurgical outcomes
Ensuring that patients are
medically ready for surgery can
help improve outcomes—and
their overall experience at HSS.
“Our orthopaedic surgeons were
one of the first groups in the
nation to embrace the concept
of co-management of the
patient,” says Linda A. Russell,
MD, Director of the Division of
Perioperative Medicine, Anne
and Joel Ehrenkranz Chair in
Perioperative Medicine, and
Associate Attending Physician.
“Every single patient who’s
admitted to HSS has a surgeon
and a medical physician familiar
with the perioperative care of the
orthopaedic patient.”
Physicians in perioperative
medicine, a field that has
emerged over the last 15 years,
are assigned to follow specific
patients to help ensure continuity
of care. “Perioperative medicine
physicians see patients before
surgery and try to get them in
as good a shape as they can,”
says Dr. Russell. “They also see
patients when they’re in the
hospital. Then they’re available to
patients for up to 90 days or so
after the surgery for any related
medical conditions.”
Prior to surgery, HSS patients
are carefully assessed to identify
and address any medical
problems that could impact
surgical outcomes, including
uncontrolled diabetes, cardiac
issues, skin infections and, most
recently, obesity. “There’s a lot
of research that says if your
BMI is 40 or higher, your risk of
postoperative complications is
much higher,” says Dr. Russell.
In July 2018, the Division of
Perioperative Medicine added
a weight-loss program to help
obese patients lose at least
5 percent of their total body
weight before surgery. “We are
probably the first hospital in the
country that’s really focused on
perioperative weight loss,” says
Dr. Russell. Obese patients see a
weight-management physician
and nutritionist at HSS at least
two to three months before
surgery to jump-start healthy
eating habits and weight loss.
“We continue to follow up with
these patients after surgery
as well for long-term weight
management,” says Caroline A.
Andrew, MD, Assistant Attending
Physician, who directs the
weight management program
at HSS. “Losing weight after
surgery helps with recovery
and can reduce postsurgical
osteoarthritis, in addition to
improving other comorbidities
of obesity.”
Many obese patients have
diabetes, so perioperative
medicine practitioners help them
get the condition under control.
These patients may work with
an endocrinologist to achieve
the healthiest A1C levels prior
to surgery.
Dr. Russell’s team of physicians,
physician assistants and nurse
practitioners also work to
optimize the use of opioids and
other pain medications before
and after surgery. “A chronic
pain physician sees patients who
take opioids daily to taper pain
medications preoperatively and
design the postoperative pain
program,” she says.
After surgery, wound issues,
leg swelling and other
complications can be treated
by the perioperative medicine
staff, saving the patient a trip
to an urgent care facility or the
emergency room.
From left to right: Caroline A. Andrew, MD, Assistant Attending Physician,
and Linda A. Russell, MD, Director of the Division of Perioperative
Medicine and Associate Attending Physician, collaborate to ensure
patients are medically ready for surgery.
Over the last decade, the
Division of Perioperative
Medicine has developed
numerous surgical guidelines,
including rules about when
medications should be stopped
preoperatively and started
postoperatively; which patients
with diabetes can be cleared for
the OR; and which patients are
candidates for bilateral knee
replacements. “The goal is to
help decrease postoperative
complications and readmission
rates,” says Dr. Russell. “We also
hope the guidelines can provide
a better patient experience.”

18
Division of Rheumatology
Complex Cases
Case 1
Eosinophilic Fasciitis
Associated with Cancer
Immunotherapy
19
Case 2
Inflammatory Erosive
Arthritis and Tendon
Rupture in Sarcoidosis
20
Case 3
Severe Lupus with
Nephritis and Catatonia;
Excellent Response to
Aggressive Treatment
21
Case 4
Subacute Bacterial
Endocarditis Masquerading
as Polymyalgia Rheumatica
22
Case 5
Retiform Purpura
Initially Concerning for
Granulomatosis with
Polyangiitis
23
HSS rheumatologists frequently receive calls from physicians around the world
asking for advice in treating complex cases. Recent calls have come from Sri Lanka,
France, Kuwait and Puerto Rico. The following five cases are excerpted from Grand
Rounds from HSS: Management of Complex Cases, which includes follow-up data
and a clinical treatment discussion.
Visit the entire list of Case references online at hss.edu/complexcases

Hospital for Special Surgery 19
Case 1 presented by David R. Fernandez, MD, PhD, and Anne R. Bass, MD
Eosinophilic Fasciitis Associated
with Cancer Immunotherapy
Case Report
A 48-year-old man was referred for
complaints of “stiffness” in his legs. One
year prior to presentation he was diagnosed
with stage IV lung adenocarcinoma (EGFR
exon 19 deletion) with lung metastases. He
was treated with nivolumab and erlotinib and
experienced 50 percent tumor regression.
Six months into treatment, he began to
note tightness and pain in his thigh and calf
muscles, shoulders, ankles and wrists. He
had trouble walking and rising from a chair.
He also noted calf cramps and leg swelling.
He denied Raynaud’s phenomenon.
Laboratory testing revealed CPK 933
and an absolute eosinophil count of 700.
CPK normalized without intervention,
but total eosinophils climbed to 3,500
over the next three months. Nivolumab
was discontinued and the patient was
referred to rheumatology. Examination
revealed thickening of the fascia of the
forearms and of the legs below the knees,
which limited mobility at the elbows,
wrists, knees and ankles. The patient
could barely pronate or supinate the
right elbow. Extension of the right wrist
was limited to 20° due to tightening
of the fascia, and there were flexion
contractures of both knees. A “groove
sign” was noted over the left leg and right
forearm (Figure 1). The superficial skin,
nailfold capillaries and joints themselves
were normal. The patient was treated
with high-dose oral corticosteroids with
moderate improvement. Deep skin biopsy
was consistent with eosinophilic fasciitis
(Figure 2). The patient continued treatment
with high-dose corticosteroids and
experienced gradual softening of the fascia
and increased mobility of the arms and,
to a lesser degree, the legs. Methotrexate
was added to his regimen to enable a rapid
steroid taper prior to lobectomy for residual
disease. The patient continued to require
low doses of prednisone 10 months after the
onset of his disease.
Discussion
Eosinophilic fasciitis is a rare disease of
unknown etiology. It is characterized by
peripheral eosinophilia and induration of
the deep fascia underlying the skin. [1] It is
generally steroid-responsive, but it often
requires prolonged therapy and not all
changes may be reversible. Eosinophilic
fasciitis can be associated with trauma,
drugs, infections, autoimmune conditions
and cancer, but to our knowledge, this
is the first case associated with cancer
immunotherapy. [2] The timing of this
patient’s presentation suggests that the
Figure 1: Photograph of the left leg demonstrating a “groove sign” along the path of a superficial vein.
nivolumab and not the cancer itself
was responsible.
Nivolumab is one of a new class of
medications directed at enhancing
antitumor immunity by inhibiting normal
checkpoints on immune cell function.
Immune checkpoint blockade has
revolutionized the treatment of many
cancers but at the expense of frequent
immune-mediated side effects. [3] The
programmed cell death-1 (PD-1) receptor
is an immune checkpoint molecule
expressed on activated T cells, which
transmits inhibitory signals to T cells and
enhances the generation of regulatory
T cells. High expression of PD-1 on T
cells can be seen in the setting of chronic
infections and is associated with a
phenomenon called “exhaustion,” which
is associated with poor T cell function and
high expression of inhibitory molecules
on T cells. [4]
Normally, cells in the peripheral organs can
increase expression of programmed cell
death ligand 1 (PD-L1) in certain settings.
However, cancer cells also frequently
express PD-L1, leading to diminished
T cell-directed immune responses
against tumors. Nivolumab blocks PD-1
signaling, leading to enhanced antitumor
immunity, but has important side effects
related to induction of autoimmunity,
such as rash, hepatitis, pneumonitis and
thyroiditis. Interestingly, the autoimmune
manifestations associated with
immunotherapy can be short-lived when
treated with steroids or tumor necrosis
factor inhibitors. They generally lack
the characteristic autoantibodies
associated with spontaneous-onset
rheumatologic diseases. [5]
This case implies a potential role for PD-1
signaling as a key tolerance mechanism,
Figure 2: Deep skin biopsy demonstrating
broad, hyalinized collagen bundles within the
fascia with deposition of mucin and a
lymphocytic and plasma cell infiltrate.
preventing the development of eosinophilic
fasciitis in susceptible individuals.
References
1. Lebeaux D, Frances C, Barete S, et al.
Eosinophilic fasciitis (Shulman disease): new
insights into the therapeutic management
from a series of 34 patients. Rheumatology
2012;51(3):557–61.
2. Pinal-Fernandez I, Selva-O’Callaghan A., Grau
JM. Diagnosis and classification of eosinophilic
fasciitis. Autoimmun Rev 2014;13(4–5):379–82.
3. Haanen JB a. G, Thienen H Van, Blank CU.
Toxicity Patterns With Immunomodulating
Antibodies and Their Combinations. Semin
Oncol 2015;42(3):423–8.
4. Wherry EJ, Kurachi M. Molecular and cellular
insights into T cell exhaustion. Nat Rev
Immunol 2015;15(8):486–99.
5. Villadolid J, Amin A. Immune checkpoint
inhibitors in clinical practice: update on
management of immune-related toxicities.
Transl lung cancer Res 2015;4(5):560–75.
Author Disclosures
Dr. David R. Fernandez does not have a financial
interest or relationship with the manufacturers
of products or services.
Dr. Anne R. Bass does not have a financial
interest or relationship with the manufacturers
of products or services.

20
Division of Rheumatology
Case 2 presented by Arthur M. F. Yee, MD, PhD
Inflammatory Erosive Arthritis
and Tendon Rupture in Sarcoidosis
Case Report
A 64-year-old woman was referred to
the HSS Division of Rheumatology for a
second opinion regarding chronic pain
and swelling of the right wrist and acute
loss of extension of the right small finger.
The patient had a 20-year history of
sarcoidosis, initially presenting as right
eye uveitis, retinal vasculitis and acute
polyarthritis. Evaluation at the time revealed
mediastinal lymphadenopathy, the biopsy
of which led to the diagnosis of sarcoidosis.
The patient was treated chronically for
many years with varying dosages of
prednisone before the eventual addition of
weekly methotrexate enabled subsequent
withdrawal of all corticosteroid therapies.
After several months of clinical remission,
methotrexate was also discontinued. She
remained symptom-free for several months
before developing insidiously progressive
chronic right wrist pain and swelling. MRI
demonstrated extensive inflammatory
arthritis and tenosynovitis with marked
erosions in the distal radius and ulna and
encroachment upon the extensor tendons
(Figure 1). She was treated with nonsteroidal
anti-inflammatory drugs and periodic
short courses of systemic corticosteroids
with marginal responses. After two years
of waxing and waning inflammatory right
wrist arthritis, she developed an acutely
dropped right small finger, prompting
referral to HSS.
Physical examination was notable for
moderate swelling, tenderness and
warmth of the right wrist; loss of extension
of the right small finger; and baseline loss
of visual acuity of the right eye without
active inflammation. There was no
evidence of active synovitis elsewhere.
Complete blood count, metabolic panel,
erythrocyte sedimentation rate, C-reactive
protein, angiotensin-converting enzyme,
rheumatoid factor, and anti-cyclic
citrullinated protein antibodies were normal
or negative. Large erosions of the distal
right ulna and radius were evident on plain
radiography (Figure 2).
An immediate consultation to the Hand
and Upper Extremity Service was made,
and the patient underwent prompt
synovectomy and repair of the ruptured
extensor tendons. Histopathology
showed inflammatory synovitis and
excluded infectious etiologies. After
a brief, uncomplicated postoperative
period, oral methotrexate was initiated
and was expeditiously titrated to 15 mg
weekly. The patient has done well for five
years without recurrence of inflammatory
arthritis or uveitis.
Discussion
Sarcoidosis is an enigmatic systemic
inflammatory disorder characterized
by non-caseating granulomatous
inflammation of potentially any tissue.
While nonspecific arthralgias are
common, frank inflammatory arthritis
is infrequent and can be categorized
as acute or chronic. In one recent
long-term North American series,
one‐tenth of all patients developed acute
inflammatory arthritis/periarthritis, [1]
typically oligoarticular or polyarticular,
although prevalence may range widely
depending on the population examined.
The most stereotypical presentation
is Lofgren’s syndrome (acute bilateral
ankle periarthritis, erythema nodosum,
and uveitis), which can be quite painful
but is fortunately self-limited and
nondestructive. [2] In most cases, acute
sarcoid arthritis is reminiscent of
exacerbations of inflammatory arthritis
seen in other systemic conditions,
likely reflecting nonspecific systemic
inflammatory processes rather than
direct granulomatous infiltration in the
joint. In contrast, infiltrative chronic
granulomatous synovitis, as seen
in the presented case, is much less
common, is sometimes quite resistant
to medical therapy, and occasionally
leads to local tissue injury. [3] A diverse
array of clinical scenarios, such as
bursitis, enthesopathies, sacroiliitis, and
carpal tunnel syndrome, resulting from
granulomatous inflammation have
been reported. [4]
The challenges facing HSS physicians in
this case were to first repair the ruptured
fifth extensor mechanism and then to
implement a medical regimen to prevent
recurrence. After adequate postoperative
healing and rehabilitation, medical
management was initiated.
Steroid-sparing agents are increasingly
being used for the treatment of sarcoidosis,
but none are formally approved. Nonetheless,
methotrexate has emerged as the preferred
steroid-sparing agent. [5] Controlled clinical
studies of methotrexate in the treatment
of sarcoidosis have demonstrated efficacy
in specific common phenotypes, such as
pulmonary disease, cardiomyopathy and
panuveitis. There are ample case reports
and series of use in other manifestations,
such as involvement of the skin, bone,
neuraxis, muscle, etc. [4]
The acknowledged efficacy of methotrexate
has led to the development of proposed
guidelines for its use in sarcoidosis. [5] Many
recommendations echo those for the use
of methotrexate in rheumatoid arthritis, but
some reflect the personal practice and expert
opinion of “sarcoidologists.” It is very notable
that the majority of experts recommended
weekly methotrexate maintenance dosages
of no more than 15 mg. Therefore, it is
possible that methotrexate is underutilized
in sarcoidosis.
References
1. Ungprasert P, Crowson C S, et al. Clinical
characteristics of sarcoid arthropathy: a
population-based study. Arthritis Care Res
2016; 68: 695–9.
2. Mana J, Gomez-Vaquero C, et al. Lofgren’s
syndrome revisited: a study of 186 patients.
Am J Med 1999; 107: 240–5.
3. Chu A, Ginat D, et al. Chronic sarcoid arthritis
presenting as an intra-articular knee mass.
J Clin Rheumatol 2009; 15: 190–2.
4. Yee AMF. Sarcoidosis: rheumatology
perspective. Best Pract Res Clin Rheumatol.
5. Cremers JP, Drent M, et al. Multinational
evidence-based World Association of
Sarcoidosis and Other Granulomatous
Disorders recommendations for the use
of methotrexate in sarcoidosis: integrating
systematic literature research and expert
opinion of sarcoidologists worldwide. Current
Opin Pulm Med 2013; 19: 545–61.
Author Disclosures
Dr. Yee is on a Speaker’s Bureau and has
participated on Advisory Boards for Bristol-
Myers Squibb and has stock shares in Abbvie
and Pfizer.
Figure 1: Fat-suppressed MRI (coronal view) of
the dorsum of the right wrist/hand. Bulky
inflammatory synovitis (enclosed in red oval)
impinges on the extensor digitorum longus
tendon (arrows) to the small finger.
Figure 2: Frontal view of the right wrist/hand.
Large erosions (encircled) are evident in the distal
radius and ulna.

Hospital for Special Surgery 21
Case 3 presented by Naveed Chaudhry, MD, Steven P. Salvatore, MD,
and Kyriakos A. Kirou, MD
Severe Lupus with Nephritis and
Catatonia; Excellent Response to
Aggressive Treatment
Case Report
A 34-year-old woman was diagnosed with
systemic lupus erythematosus (SLE) in
2011 after she presented with arthritis,
photosensitivity, alopecia and oral ulcers.
She was treated with short courses of
prednisone. Her serologic profile was
positive for ANA, anti-dsDNA, anti-Sm
and anti-RNP antibodies. In January 2013,
she was admitted to another hospital for
left popliteal vein deep vein thrombosis
(DVT) and pulmonary embolism (PE). She
was also noted to have nephrotic range
proteinuria and pleuropericarditis. She was
treated with anticoagulation (enoxaparin to
warfarin) and prednisone 60 mg/day with
improved symptoms.
She first presented to us in February 2013
with marked leg edema and dyspnea on
exertion. Past medical and family histories
were unremarkable. Her blood pressure
was 112/82, pulse 85, and she had 2+ leg
edema. Her Hgb was 13.9 gm/dl, serum
creatinine (Cr) 0.64 mg/dL, albumin
1.7 gm/dl, cholesterol 366 mg/dl, ESR 72
mm/hr, C3 167 mg/dL, C4 64 mg/dL, and
anti-DNA 2+.
Her urine sediment was bland, but her urine
protein-creatinine ratio (UPCR) was 5.2.
She was on prednisone 50 mg/day, and
mycophenolate mofetil (MMF) was added to
her regimen.
Her edema got much worse, however,
and she was readmitted three weeks later
(March 2013) with severe anasarca. She
received IV methylprednisolone 500 mg
daily for three days and, after switching
from warfarin to heparin, a renal biopsy
was performed. This revealed ISN/RPS
Class V membranous lupus nephritis
(Figures 1–2). MMF was discontinued
because of diarrhea, and she was treated
with IV cyclophosphamide (IVCY). The
patient was discharged on dexamethasone
9 mg, losartan 25 mg, bumetanide 1 mg,
warfarin, atorvastatin 40 mg, calcium,
vitamin D3, and alendronate 70 mg weekly.
She was readmitted to the hospital in early
April 2013 after she developed symptoms
of mania, depression and psychosis with
paranoia. She was also noted to have
severe edema and pneumonia.
The patient was treated with IV antibiotics
and diuretics, and glucocorticoids
were continued. After treatment with
haloperidol, she developed catatonia
with motor rigidity, immobility, staring,
mutism and negativism. She was not
hyperthermic, and creatine kinase and
electroencephalogram were normal.
She was treated with IV lorazepam 2 mg,
and high-dose glucocorticoids were
continued. Her mental status normalized
after a few days. Pulmonary infiltrates
cleared 11 days later and she was given
her second IVCY dose as well as IV
rituximab 1,000 mg. She was discharged
on prednisone 40 mg daily with a slow
taper. She continued with monthly IVCY
for a total of five cycles (the last one
was in August 2013) and had gradual
improvement of proteinuria and edema.
By September 2013, her UPCR was
0.37 and her albumin had normalized.
She was started on azathioprine
50 mg BID as maintenance treatment
while the prednisone was tapered to
5 mg/day. Warfarin was discontinued
without recurrent thrombosis. Her
antiphospholipid antibodies, including
lupus anticoagulant, have remained
negative. The patient was able to go back
to her job full-time.
Discussion
We have described a complex case of
lupus with active disease in several
organs and excellent response to prompt
and aggressive management. The
patient first presented with nephrosis
and secondary DVT-PE. Then she
developed pleuropericarditis and, finally,
neuropsychiatric (NP) SLE with bipolar
symptoms, psychosis and catatonia.
Although glucocorticoids may cause
psychosis, it was unlikely they were the
culprit here, as they had been tolerated
well. The patient’s NP symptoms occurred
concurrently with disease activity in
other organs. Catatonia is a rare NP
manifestation of SLE, often associated
with an underlying bipolar disorder. [1]
It may be triggered by antipsychotics
like haloperidol and often responds to
lorazepam, as in our case. Treatment of
lupus with glucocorticoids, IVCY and/or
plasma exchange is also effective. [1]
Pure membranous lupus nephritis,
when accompanied by nephrotic range
proteinuria, is also a severe manifestation
of SLE and demands treatment with
MMF, IVCY or cyclosporine. [2, 3] We added
rituximab, as it is often effective in severe
lupus as well as NPSLE. [4]
References
1. Grover S, Parakh P, Sharma A et al. Catatonia
in systemic lupus erythematosus: a case
report and review of literature. Lupus 2013;
22: 634–8.
2. Austin HA, 3rd, Illei GG, Braun MJ, Balow JE.
Randomized, controlled trial of prednisone,
cyclophosphamide, and cyclosporine in
lupus membranous nephropathy. J Am Soc
Nephrol 2009; 20: 901–11.
3. Radhakrishnan J, Moutzouris DA, Ginzler EM
et al. Mycophenolate mofetil and intravenous
cyclophosphamide are similar as induction
therapy for class V lupus nephritis. Kidney Int
2010; 77: 152–60.
4. Tokunaga M, Saito K, Kawabata D et al.
Efficacy of rituximab (anti-CD20) for
refractory systemic lupus erythematosus
involving the central nervous system. Ann
Rheum Dis 2007; 66: 470–5.
Author Disclosures
Dr. Naveed Chaudhry does not have a financial
interest or relationship with the manufacturers
of products or services.
Dr. Kyriakos A. Kirou does not have a financial
interest or relationship with the manufacturers
of products or services.
Dr. Steven P. Salvatore does not have a financial
interest or relationship with the manufacturers
of products or services.
Figure 1: C3 staining by immunofluorescence
microscopy showing global 3+ capillary wall
deposits (40x).
Figure 2: Electron microscopy revealing global
subepithelial electron dense deposits (arrows).

22
Division of Rheumatology
Case 4 presented by Alana B. Levine, MD
Subacute Bacterial
Endocarditis Masquerading
as Polymyalgia Rheumatica
Case Report
A 70-year-old woman was referred to the
HSS Division of Rheumatology for a second
opinion regarding polymyalgia rheumatica
(PMR). She had been diagnosed with PMR
at another hospital eight months prior
to presentation based on fatigue and an
elevated ESR. Her fatigue resolved rapidly
after starting prednisone 20 mg daily,
which was tapered off over the course
of two months. Fatigue recurred after
discontinuing steroids and the patient was
restarted on prednisone and, eventually,
methotrexate.
One month prior to presentation at HSS,
the patient developed a new non-painful,
non-pruritic leg rash. Skin biopsy revealed
leukocytoclastic vasculitis. At the time, she
was taking prednisone 5 mg daily, which
was increased to 40 mg daily, and the
rash resolved.
On presentation to HSS, the patient
complained of severe fatigue, nocturnal
fevers to 101°F, night sweats and anorexia
with a 20-pound weight loss.
The patient’s past medical history was
significant for mitral valve prolapse and
osteopenia. She had dental work one
month prior to the PMR diagnosis and had
two caesarian sections in the past. Her
medications included methylprednisolone
4 mg daily, rabeprazole 20 mg daily, and
calcium supplementation.
On physical examination, the patient was in
no acute distress. Her blood pressure was
110/65 mm Hg, pulse 112, and temperature
100.2°F. She weighed 104 pounds and was
62 inches tall. Her exam was remarkable for
a loud systolic murmur, heard throughout
the precordium but most pronounced at
the apex. She had fingernail clubbing and
several non-blanching 2-mm palpable
purpuric lesions over the shins. Her lung
exam was unremarkable, pulses were
strong throughout and without bruits,
and she had no synovitis. The differential
diagnosis at that time included systemic
vasculitis, malignancy and endocarditis.
Labs were significant for hemoglobin
8.7 g/dL, serum creatinine 2.2 mg/dL
(0.9 mg/dL one month prior), rheumatoid
factor 222 IU/mL, ESR 53 mm/hr, CRP
125 mg/L, C3 31 mg/dL, and C4 7 mg/dL.
Urinalysis showed 2+ protein, 3+ blood,
>30 WBC/hpf and >30 RBC/hpf.
Antinuclear antibodies, double-stranded
DNA antibodies, extractable nuclear
antigens, and anti-CCP antibodies
were negative.
The patient was admitted for evaluation of
acute renal failure. Multiple sets of blood
cultures were drawn and held for slowgrowing
organisms, and the patient was
started on broad-spectrum antibiotics.
A renal ultrasound was unremarkable. A
transthoracic echocardiogram showed
severe mitral regurgitation with a
1.9 x 1.8 cm vegetation on the posterior
mitral leaflet. Blood cultures grew
gram-variable rods, which were later
speciated as Suttonella indologenes.
Due to the size of the vegetation and
severe mitral regurgitation, the patient
was recommended for mitral valve
replacement surgery.
Discussion
Subacute bacterial endocarditis may cause
a constellation of symptoms, including
fatigue and malaise, fevers, valvular
dysfunction, renal failure secondary to
glomerulonephritis, and leukocytoclastic
vasculitis. Suttonella indologenes is a
gram-negative, rod-shaped bacterium
found in normal respiratory tract flora, but it
[1, 2]
has been known to cause endocarditis.
References
1. Ozcan F, Yildiz A, Ozlu MF, et al. A case of fatal
endocarditis due to Suttonella indologenes.
Anadolu Kardiyol Derg 2011;11:85–7.
2. Yang EH, Poon K, Pillutla P, Budoff MJ, Chung
J. Pulmonary embolus caused by Suttonella
indologenes prosthetic endocarditis
in a pulmonary homograft. J Am Soc
Echocardiogr 2011;24:592 e1–3.
Author Disclosures
Dr. Alana B. Levine does not have a financial
interest or relationship with the manufacturers
of products or services.
Figure 1: Transthoracic echocardiogram showing
1.9 x 1.8 cm vegetation on the mitral valve.
Figure 2: Transesophageal echocardiogram
showing vegetation and flail posterior
mitral leaflet.
Figure 3: Transesophageal echocardiogram
showing severe mitral regurgitation and
perforation of the posterior mitral leaflet.

Hospital for Special Surgery 23
Case 5 presented by Danielle Ramsden-Stein, MD, Sonali Narain MD, MPH, and
Michael D. Lockshin, MD
Retiform Purpura Initially
Concerning for Granulomatosis
with Polyangiitis
Case Report
A 47-year-old woman with recurrent
sinusitis and bronchitis, intermittent febrile
rashes and depression presented to an
outside hospital with rapidly progressing
skin rash after eating at a seafood
restaurant. She had bruises on her left
shoulder, left thigh and under her left
breast accompanied by fever to 102°F,
arthralgias and fatigue. The rash worsened
within 24 hours to involve her upper and
lower extremities, cheeks, ears, breasts
and abdomen. She denied trauma, toxic
exposures, new medications, sick contacts,
or recent travel.
On examination, she had saddle nose
deformity and necrotizing purpura
with bullae developing over the
dependent areas. She had proteinuria
and pancytopenia. Lumbar puncture
was negative, but chest X-ray showed
left lower lobe consolidation. She was
started on ceftriaxone/vancomycin. She
developed a cough with blood-tinged
sputum and gross hematuria. Head CT
scan showed pansinusitis. Intravenous
methylprednisolone 40 mg every six hours
was prescribed. The lesions progressed
from pruritic to tender, with darkening of
color to purple, peaking on the third day
of hospitalization, affecting approximately
70 percent of her body surface area.
Biopsy revealed leukocytoclastic
vasculitis, and the patient requested
transfer for further management.
On admission, corticosteroid was
continued, since new onset granulomatosis
with polyangiitis (Wegener’s) was
suggested by the rash, nose deformity,
proteinuria and recurrent sinusitis.
Antibody to proteinase 3 was strongly
positive. Review of her pathology
slides deemed the underlying process
to be classic for a cocaine-induced
vasculitis. After an initial dose of pulse
methylprednisolone, the patient was
started on oral prednisone 1 mg/kg dose
tapered over a 20-day period. There was
very slow improvement in the cutaneous
lesions, and she eventually underwent
multiple sessions of skin grafting. At the
time of discharge, there was marked
improvement with mild scarring. Despite
repeated questioning, the patient did not
admit to cocaine use.
Discussion
Although we were unable to confirm that
the presentation of this rash in our patient
was related to cocaine use, the pathology
report prompted us to understand the
pathophysiology of cocaine-induced
vasculitis. Unlike granulomatosis with
polyangiitis, cocaine-induced vasculitis
is less commonly a true vasculitis but
rather a vasculopathy with thrombosis. Its
occurrence is associated with cocaine that
has been contaminated with levamisole,
a veterinary antihelminthic agent, although
recently it has been hypothesized that
cocaine itself may enhance complement
synthesis and trigger the formation of
C5b-9, resulting in endothelial cell injury.
While levamisole has been acknowledged as
possessing immunomodulatory properties
since the 1960s, the mechanism is not
well understood. It reportedly potentiates
the psychotropic effects of cocaine and
therefore makes it highly desirable to
manufacturers of illegal cocaine. Reports
consistently state that it is added to
approximately 70 percent of cocaine
available in the United States.
In cocaine-induced disease, the classic
skin finding is that of retiform purpura, a
net-like pattern of irregular nonblanching,
violaceous plaques. Skin biopsy shows a
very distinctive intravascular occlusion
without vasculitis, termed vasculopathy,
primarily targeting capillaries and
venules. Gross et al. found, in 16 patients,
that 13 percent had a pure small vessel
vasculitis, 40 percent thrombotic
vasculopathy, and 47 percent vasculitis
and thrombosis. [1]
While ANCA positivity has been
documented with both cocaine use
and with levamisole use individually,
normalization of ANCA and APL antibodies
after levamisole exposure tended to take
place within 2–14 months in Rongioletti’s
study. [2] Given this patient’s history,
repeat serologies at 6–12 months will
be useful.
References
1. Gross RL, et al. A novel cutaneous
vasculitis syndrome induced by levamisolecontaminated
cocaine. ClinRheumatol 2011;
30(10):1385.
2. Rongioletti F, et al. Purpura of the ears: a
distinctive vasculopathy with circulating
autoantibodies complicating long-term
treatment with levamisole in children. Br J
Dermatol 1999;140:948–951.
Author Disclosures
Dr. Danielle Ramsden-Stein does not have
a financial interest or relationship with the
manufacturers of products or services.
Dr. Sonali Narain does not have a financial
interest or relationship with the manufacturers
of products or services.
Dr. Michael D. Lockshin does not have a financial
interest or relationship with the manufacturers
of products or services.
Figure 1: Extensive retiform purpuric lesions on
patient’s bilateral lower extremities, Day 5.
Figure 2: Saddle nose deformity. Resolving
retiform purpura on cheeks.
Figure 3: Skin biopsy shows a very distinctive
intravascular occlusion without vasculitis primarily
targeting capillaries and venules.

24
Division of Rheumatology
HSS staff members, including Jillian Rose, LCSW, MPH, Director of Community Engagement, Diversity and
Research (center), and Lillian Mendez, Program Associate, Charla de Lupus (Lupus Chat®) (second from right),
with members of Charla de Lupus (Lupus Chat®) during the “Walk With Us to Cure Lupus” fundraiser, which
benefits the Lupus Research Alliance.
Empowering Patients Through
Support and Education Programs
At HSS, providing patient
support and education is a key
part of our mission to deliver
the highest quality care. We
offer a variety of services
for patients with rheumatic
diseases; in fact, we provide
more support and education
programs for lupus patients
than any other hospital in the
country. “Not only do we have
the most programs, but we’ve
been doing this the longest—for
over 25 years,” says Stephen
A. Paget, MD, Attending
Physician and Physician-in-
Chief Emeritus.
HSS patients can learn more
about their conditions in
several different ways. Our
physicians educate patients
through Facebook Live events,
video chats and in-person
support group meetings.
In addition, several of our
Centers of Excellence offer
webinars. Over the past year,
the Inflammatory Arthritis
Center of Excellence developed
three educational webinars
for patients in collaboration
with the HSS Department of
Social Work Programs, the HSS
Education Institute, the Arthritis
Foundation and the Spondylitis
Association of America. The
Scleroderma, Vasculitis &
Myositis Center of Excellence
at HSS delivers a monthly email
news blast to patients, and
the HSS Division of Pediatric
Rheumatology has developed
patient education materials in
multiple languages.
Patient support and education
programs are integral to the
mission of the Department
of Social Work Programs
at HSS. “Our department
partners with HSS physicians
and healthcare teams to help
support, empower and enhance
the quality of life for people
with rheumatologic conditions,”
says Roberta Horton, LCSW,
ACSW, Assistant Vice President,
Department of Social Work
Programs. HSS offers programs
for patients with specific
rheumatologic conditions,
including the following:

Hospital for Special Surgery 25
Lupus
SLE Workshop
This support and education program for lupus
patients and their families and friends has been
ongoing since 1985. Lupus care experts give
lectures, which are followed by informal discussions.
LANtern® (Lupus Asian Network)
LANtern is the only national, hospital-based
bilingual support and education program
dedicated to serving Asian Americans with lupus
and their families. Asians are more likely to develop
lupus than Caucasian people, and their illness
may be more severe. LANtern offers a bilingual,
toll-free telephone support line of peer educators.
These trained volunteers—either Asian Americans
with lupus or Asian Americans who have family
members with lupus—can help callers better
understand their condition, address any concerns,
and offer advice on how to work effectively with
their physicians.
Charla de Lupus (Lupus Chat®)
This unique national program provides peer
support and education to English- and Spanishspeaking
people with lupus. It includes the Charla
Line, a toll-free support and education helpline
that screens and matches callers with peers.
In addition, the program offers peer support at
several rheumatology clinics in New York City.
“Since 1988, we’ve trained lupus patients to
provide specific support to families while they
are sitting in the waiting room,” says Jillian Rose,
LCSW, MPH, Director of Community Engagement,
Diversity and Research. Program staff members
conduct more than 30 community and professional
presentations annually to raise awareness of lupus
and provide access to educational resources.
Additional programs offer support to teens and
their parents.
Rheumatoid Arthritis
Living with Rheumatoid Arthritis provides
monthly education and support for patients with
moderate to severe rheumatoid arthritis (RA) and
their families. RA care experts give lectures, which
are followed by a discussion facilitated by a clinical
social worker and rheumatology nurse.
The Early RA Support and Education Program was
developed for people who were recently diagnosed
with RA. Participants meet for a free, four-session
workshop series, which provides tips on how to
communicate with their physician about RA and
manage activities of daily living.
Myositis
HSS sponsors a Myositis Support Group, and meetings are generally held once a month at the
Hospital. During the first hour, speakers such as myositis specialists, social workers and patients give
presentations on topics as varied as managing your medical team, fatigue, and current research and
treatments. During the second hour, members are able to share their thoughts and feelings about
the illness.
Scleroderma
HSS hosts a monthly scleroderma support group sponsored by the Tri-State Chapter of the Scleroderma
Foundation. In addition, the Scleroderma, Vasculitis & Myositis Center of Excellence hosts two
Scleroderma Foundation patient forums every year.
For more information on these programs, visit hss.edu/support-programs
Using technology to assist lupus patients
In 2017, HSS launched LupusMinder, a mobile app designed to help lupus patients track medications,
daily symptoms and appointments. Unlike other apps, this one was created with significant input from
lupus patients themselves. The app enables users to take photos of their symptoms to share with their
physician and chart daily symptoms, such as pain.

26
Division of Rheumatology
Rheumatology
Leaders
of the Future
Bella Mehta, MBBS, MD
Iris Navarro-Millán, MD, MSPH
Medha Barbhaiya, MD, MPH
Rheumatology has always attracted physicians who
enjoy problem solving and managing some of the most
complex cases in medicine. This is especially evident
among the newest rheumatologists at HSS, who are
committed to performing cutting-edge research and
revolutionizing patient care. Here are their hopes for
the future of the field.
David R. Fernandez, MD, PhD

Hospital for Special Surgery 27
Medha Barbhaiya, MD, MPH
Medha Barbhaiya, MD, MPH, Assistant Attending Physician, is developing
new classification criteria for APS and researching environmental risk
factors for lupus.
Medha Barbhaiya, MD, MPH,
Assistant Attending Physician,
is poised to become a leading
researcher on lupus and
Antiphospholipid Syndrome
(APS). In 2015, Dr. Barbhaiya
received the Rheumatology
Research Scientist Development
Award to study environmental
risk factors for lupus. “One of
the biggest mysteries is why
lupus seems to affect young,
previously healthy patients,”
she says. “Some patients may
have an underlying genetic
predisposition, but we hope
to identify additional factors
that contribute to their risk of
developing lupus.” Dr. Barbhaiya
studies lupus risk factors in
over 230,000 participants in
the Nurses’ Health Study and
59,000 participants in the
Black Women’s Health Study.
She is examining the role of
smoking, alcohol intake, diet
(including the Mediterranean,
Alternative Healthy Eating
Index, and Inflammatory diets),
UV light exposure, and even
psychological factors, such
as child abuse. In a study
published in 2018 in Annals
of the Rheumatic Diseases,
Dr. Barbhaiya found that while
cigarette smoking was not
associated with a greater risk
of developing lupus overall,
it was for a subset of lupus
patients who had a specific
type of antibody known as antidouble
stranded DNA (dsDNA).
In another study published in
August 2018 in Arthritis Care
& Research, she demonstrated
that while smoking slightly
elevated the risk of developing
lupus, moderate alcohol
intake seemed protective. “In
moderate amounts, alcohol
may have an anti-inflammatory
effect,” she says.
In addition to her ongoing
lupus-related research studies,
Dr. Barbhaiya has been involved
in APS research since medical
school. She received a “Young
Scholar” award from the APS
Alliance for Clinical Trials
and International Networking
(APS ACTION) in 2014. In
2018, she was the recipient
of an Investigator Award from
the Rheumatology Research
Foundation to support her
APS research. Currently, she
is investigating risk factors
for the development of
thrombosis in APS in a spinoff
study of an ACR/EULARsupported
multidisciplinary
effort to develop new APS
classification criteria, for which
she is one of the core planning
group members. Studies of
APS have been limited by
small sample sizes, varying
definitions of the disease,
and laboratory tests that are
not standardized. “There’s an
urgent need for rigorous, highperforming
APS classification
criteria,” says Dr. Barbhaiya.
As part of the classification
criteria development efforts,
Dr. Barbhaiya has been working
with a large, international group
of APS researchers, including
other specialists, such as
hematologists, pathologists and
dermatologists. She plans to
use international, multicenter
patient data to investigate
associations between potentially
modifiable environmental
factors and the risk of
developing APS. Ultimately,
she hopes that identifying risk
factors will lead to improved
prevention strategies.
“For lupus and APS, there are so
many unanswered questions,”
says Dr. Barbhaiya. “Hopefully,
I can help answer some of
these questions and see the
impact of my research on my
patients’ care.” There is no
better institution to support
this work than HSS, since
the Hospital takes a multidisciplinary
approach to lupus
and APS, says Dr. Barbhaiya.
“There’s a lot of camaraderie
and synergy between clinicians
and researchers,” she says.
“There’s also a tremendous
amount of support for junior
faculty. We are given time to
perform research while serving
as clinicians.”

28
Division of Rheumatology
David R. Fernandez, MD, PhD
David R. Fernandez, MD, PhD, Assistant Attending Physician, aims to study the molecular mechanisms that
drive myositis to develop better treatments.
David R. Fernandez, MD, PhD,
Assistant Attending Physician,
has dedicated his career to
researching and caring for
patients with myositis. While he
has successfully treated many,
he’s haunted by thoughts of
those who haven’t responded to
treatment. “This provides strong
motivation to try to help patients
further,” says Dr. Fernandez,
who is researching the causes
and treatment of myositis.
“Uncommon disorders like these
could use more support, and
HSS is in a great position to
provide that.”
Dr. Fernandez is creating a
registry of myositis patients to
study the natural history of the
disease. “At HSS, we see a high
volume of patients, which helps
to inform research and move the
field forward,” he says. Currently,
Dr. Fernandez is collecting blood
samples to determine whether
T cells and B cells in myositis
patients have some of the
same abnormalities commonly
found in lupus patients. “There
are a lot of clinical similarities
between the two diseases, so
we’re hoping we may be able
to confirm that on a molecular
level,” he explains. Dr. Fernandez
is also participating in a clinical
trial focusing on the effects
of the lupus drug belimumab
to treat dermatomyositis and
polymyositis. He is studying the
protein mTOR, which is altered
in people with lupus. “One recent
clinical trial found that a drug
that targeted mTOR showed
some benefit in lupus patients,
so we’d like to see if this protein
is also affected in myositis,
which may indicate similar
therapies might help some of our
myositis patients,” he explains.
Dr. Fernandez is the physician
advisor to the HSS Myositis
Support and Education Program.
He attends support group
meetings and speaks to patients
about the latest advances in
treatment and research. “I spend
80 percent of my time doing
research, but the 20 percent
of time spent with patients is
invaluable,” he says. “It reminds
me of the acuity of these
illnesses and how important it
is to move the field forward. It
also benefits me as a researcher
because it helps me understand
how much these diseases can
vary from person to person.”
Ultimately, Dr. Fernandez
hopes to run his own myositis
laboratory at HSS, which would
allow him to study the molecular
mechanisms that drive the
disease. “I have many colleagues
with expertise in different
diseases,” he says. “If I’m having
trouble with a case history or
designing a study protocol,
they’re just down the hall. I can’t
imagine a better environment to
do research and treat patients.”

Hospital for Special Surgery 29
Bella Mehta, MBBS, MD
Bella Mehta, MBBS, MD,
Assistant Attending Physician,
became interested in the
field of rheumatology when
she came to HSS in 2010 as
a visiting medical student
from India. One of her first
cases involved diagnosing a
patient who had suffered from
persistent, unexplained fevers
for many years. It took multiple
specialists to come up with a
diagnosis: adult-onset Still’s
disease, a rare autoimmune
disorder. “Rheumatology cases
are never straightforward
and simple,” says Dr. Mehta.
“There’s something very
satisfying about making the
right diagnosis.”
Today, Dr. Mehta is putting her
sleuthing skills to good use,
analyzing HSS registries and large
data sets to address important
questions about healthcare
disparities and outcomes for
patients with arthritis. Using
geospatial epidemiology, she
and several colleagues, including
Susan M. Goodman, MD, Director
of the Integrative Rheumatology
and Orthopedic Center of
Excellence and Attending
Physician, investigated how
neighborhood characteristics—
specifically the proportion
of impoverished people and
immigrants—influence outcomes
after joint replacement surgery at
HSS. “Geospatial epidemiology is
usually thought of as a marketing
tool (businesses use it in different
neighborhoods to figure out what
types of food residents eat),
but it can help us understand
how where a person lives affects
health outcomes.”
While pain and function scores
after total hip replacement
were similar for blacks
and whites in middle-class
or affluent communities,
Bella Mehta, MBBS, MD, Assistant Attending Physician, is investigating
disparities in healthcare among arthritis patients.
Dr. Mehta found that blacks
in poorer neighborhoods
fared significantly worse than
their white counterparts. In
other research, Dr. Mehta
discovered that education can
help mitigate the effects of
these outcomes. “In poorer
communities, those who have
some college education have
significantly better pain and
function scores than those who
don’t,” she says. These findings
suggest that patients without
a college education who live in
economically disadvantaged
neighborhoods should be
targeted for preoperative and
postoperative interventions,
including being encouraged
to have procedures like joint
replacement earlier to achieve
better outcomes.
In 2017, Dr. Mehta’s work on
epidemiology and rheumatology
outcomes was selected as one
of the top three research studies
at the American College of
Rheumatology annual meeting.
Dr. Mehta’s goal is to decrease
disparities, reduce disability and
improve outcomes in arthritis
patients. “It’s a different level
of disparity than what I was
used to in India, where many
impoverished people simply go
without health care because
resources such as Medicare aren’t
available,” she says. “In the U.S.,
even if someone has Medicare
or Medicaid, they still might not
have surgery or see their primary
care physician. The question
becomes, what other factors are
holding people back, and why?”
Dr. Mehta is confident she will be
able to answer these questions at
HSS. “The intellectual stimulation
here is so energizing,” she says.
“We have some of the greatest
minds in medicine here.”

30
Division of Rheumatology
Iris Navarro-Millán, MD, MSPH
Iris Navarro-Millán, MD, MSPH, Assistant Attending Physician, is
studying the prevalence and incidence of cardiovascular risk factors
among patients with psoriatic and rheumatoid arthritis.
For more than half a century,
research has shown that
rheumatoid arthritis (RA)
raises the risk of developing
cardiovascular disease (CVD).
Despite this, many physicians
and patients are unaware of
the connection: One recent
study found that about half of
all patients with RA and their
primary care providers were
unaware of the link and were
not taking steps to implement
preventive care. Iris Navarro-
Millán, MD, MSPH, Assistant
Attending Physician, is
attempting to close that gap.
Over the last few years, she has
been studying the prevalence
and incidence of cardiovascular
risk factors—high blood
pressure, elevated cholesterol
levels, obesity and Type 2
diabetes—among patients
with psoriatic and rheumatoid
arthritis. She published a study
in Annals of the Rheumatic
Diseases highlighting the
association of high levels of
inflammatory markers, such as
C-reactive protein (CRP) and
erythrocyte sedimentation rate
(ESR), with an increased risk of
heart attack and stroke among
veterans with RA. “Our research
shows that this inflammation
is driving the increase in
cardiovascular disease among
people with rheumatoid
arthritis,” she explains.
Managing cardiovascular
risk factors in RA patients
is key, yet a study published
by Dr. Navarro-Millán in the
Journal of International Medical
Research in 2018 found that
patients with inflammatory
arthritis (rheumatoid arthritis,
psoriatic arthritis and ankylosing
spondylitis) were no more
likely to be treated for high
cholesterol than people without
any cardiovascular risk factors.
In her most recent study, she
found that only 37 percent of
patients with RA are screened
for hyperlipidemia. This article
was published in November 2018
in Arthritis Care and Research,
and it was highlighted as one
of the must-read articles for
the first week of December by
Rheumatology News Clinical
Edge. As a result, Dr. Navarro-
Millán is currently developing
an intervention to address the
gaps in patient care. “We’re
focusing mainly on improving
screening and management
of hyperlipidemia among
patients with RA,” she says.
“We’re developing a series of
brief videos for patients that
explain the short- and long-term
effects of RA and medications.
The videos will also cover the
importance of screening and
management of cholesterol
levels as a way of decreasing
their risk of complications.” The
videos will be available online
for patients to watch on their
own, but they can also receive
the assistance of a peer coach
to guide them. Peer coaches
are individuals who have RA
and have received training to
provide guidance regarding the
video content and support. “We
do not anticipate that everyone
with RA will need a peer coach,
but this option will be available
for those individuals who have
limited experience navigating
the healthcare system and may
need guidance and support to
understand the importance of
CVD risk as part of having RA,”
says Dr. Navarro-Millán. “We
aim to make these resources
accessible to everyone in
this country.”
Dr. Navarro-Millán is confident
that the community of physicianresearchers
at HSS will help her
achieve her goal of improving
the care of RA patients. “Having
such a diverse cadre of clinicians
to collaborate with and to help
me generate questions I can
develop into meaningful clinical
research studies is, for me, the
biggest asset of working at HSS,”
she says.

Hospital for Special Surgery 31
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About Hospital for Special Surgery
Founded in 1863, Hospital for Special Surgery (HSS) is a world leader in orthopaedics, rheumatology and rehabilitation.
HSS is ranked #1 in the U.S. for Orthopaedics and #3 for Rheumatology by U.S. News & World Report “Best Hospitals”
(2018–2019 rankings). It is also ranked Best in New York City for Pediatric Orthopaedics and #21 nationally by U.S.
News & World Report “Best Hospitals” (2018–2019 rankings). It is the first hospital in New York State to receive the
Magnet® designation for Excellence in Nursing Service from the American Nurses Credentialing Center four consecutive
times. Located in New York City, HSS also serves patients in the regional area with outpatient centers in Westchester
County, New York; Connecticut; New Jersey; Long Island and Queens. In 2019, there will be a new HSS location in West
Palm Beach, FL. Patients choose to come to HSS from across the U.S. and from around the world. HSS has one of the
lowest infection rates in the country. The Hospital’s Research Institute is internationally recognized as a leader in the
investigation of musculoskeletal and autoimmune diseases. To learn more, please visit hss.edu.
Attributions
The HSS Division of Rheumatology Annual Report is published by the Communications Department, Hospital for Special
Surgery, 535 East 70th Street, New York, NY 10021. 866-976-1196
Hospital for Special Surgery is an affiliate of Weill Cornell Medical College.
©2018 Hospital for Special Surgery. All rights reserved.
Officers
Co-Chairs
Thomas Lister
Robert K. Steel
Vice Chair
Michael Esposito
President and
Chief Executive Officer
Louis A. Shapiro
Surgeon-In-Chief and
Medical Director
Todd J. Albert, MD
Executive Vice President and
Chief Operating Officer
Lisa A. Goldstein
Executive Vice President and
Chief Financial Officer
Stacey L. Malakoff
Executive Vice President,
Chief Legal Officer and Secretary
Irene Koch, Esq.
Chairmen Emeriti
Winfield P. Jones
Richard L. Menschel
Aldo Papone
Kendrick R. Wilson III
Credits
Executive Editorial Board
Todd Albert, MD
Mary K. Crow, MD
John Englehart
Lionel Ivashkiv, MD
Louis A. Shapiro
Executive Editor
Rachel Sheehan, MA, MBA
Editor-in-Chief
Deborah Pike Olsen
Writers
Stacey Colino
Beth Howard
Hallie Levine
Design
Suka Creative
Photo Editor
Deborah Garcia
Printing
Earth Color
Photography
John Abbott
Robert Essel

HOSPITAL FOR SPECIAL SURGERY
535 East 70th Street
New York, NY 10021
212-606-1000
hss.edu