Good afternoon to Doctor Constantino, Doctor Fundimera, our resident doctors and colleagues!

We are Team C of the group 4 and we will be presenting our case entitled “Sus-Rheuma-
ryosep! A Case of Rheumatoid Vasculitis”. // Presenting will be yours truly, PGI Hayase, with me
are PGIs Ingan, Lumidao, and Malana.//

To get things started, our objectives are:

 To discuss a case of Rheumatoid Vasculitis as one of the most common extra-articular

manifestation of Rheumatoid vasculitis.
 To discuss the diffferential diagnosis of Rheumatoid vasculitis.
 To discuss the pathophysiology and treatment of Rheumatoid vasculitis.//

And now, I will be introducing our patient. Patient S.D. is a 34-year-old female, single, filipino,
Roman Catholic, Vendor, born on Aug 12, 1989, lives in Sangandaan, Quezon City, and was
admitted at QCGH on Feb. 2, 2024 // with a chief complaint of black discoloration of the
fingertips and finger toes, or “nangingitim ang mga daliri sa kamay at paa”.

Our Patient was apparently well until 22 days prior to admission, when the patient started to
have sudden swelling, and redness of distal phalanges of the 4th digit of her right hand
associated with tenderness described as pricking pain, non-radiating, 9/10 in the pain scale,
aggravated by cold weather and movement, and alleviated by taking a pain reliever, specifically
Diclofenac 75 mg/tab. It is worthy to note that the patient also had Prednisone 20 mg/tab every
12 hours as her maintenance as the patient is a known case of Rheumatoid arthritis, however
she is not compliant to the maintenance. No other associated symptoms such as fever, malaise,
fatigue, weight loss, night sweats, pallor, numbness, morning stiffness, hand deformities or
limitation of movements. Patient did not seek consultation at the time. //

–slide– This slide illustrates the affected areas at the moment //

Moving on, 19 days PTA, still with the pricking pain on the distal phalanges of the 4th
digit of her right hand but now the patient presented with swelling of the 3rd and 5th digits of the
right hand associated with the same character of tenderness mentioned above. This was now
aggravated by cold temperature and limitation of movement and tenderness which prompted
consultation at QCGH-OPD in the Family Medicine department. Still no other associated
symptoms such as edema, pallor, morning stiffness and claudication were noted. Work-up was
advised to be done and the patient was prescribed with Losartan 50 mg/tab, 1 tab to be taken
once a day, Amlodipine 10 mg/tab, 1 tab to be taken once a day, Prednisone 20 mg/tab, 1 tab to
be taken twice a day, and Celecoxib 200 mg/cap, 1 cap to be taken twice a day. No relief of
symptoms were noted at the time. //

–slide– This slide illustrates the progression of the symptoms. //

In the interim, still with intermittent episodes of tenderness on 3rd-5th digits of her right
hand now with noted blackish discoloration of the said digits. During this time, 2nd-4th digits of
the left hand were also now noted to be swollen with blackish discoloration of the 4th digit, left
hand. There was no limitation in motion but there was presence of intermittent pain at the
time. //
–slide– This slide illustrates the involvement of the left hand during the interim. //

And now, Four days prior to admission, still with the mentioned symptoms, but with
noted swelling and tenderness of the 1st-2nd distal phalanges of right foot and 2nd distal
phalanx of left foot. There was still no limitation in motion but there was presence of intermittent
pain. Furthermore, the patient noted no associated symptoms such as pallor, paralysis, or
paresthesia. Patient consulted back to QCGH-FM OPD and came with the following laboratory
results: FBS: 5.15, Creatinine: 66.16, and a high CRP at 8.41. The patient was then referred to
our service for further evaluation and comanagement wherein the patient was then referred to
IM-Rheumatology service and was advised for admission, hence admitted. //

–slide– This slide illustrates the symptoms of the patient upon admission //

Past Medical History

Patient is a known hypertensive which was diagnosed this year in January 2024 and
was maintained on Amlodipine 5 mg/tab and Losartan 50 mg/tab. Moreover, the patient was
also diagnosed with Rheumatoid Arthritis since 2021 maintained by Prednisone 20 mg/tab BID -
non compliant. Patient has no allergies from any food, medications, or any other environmental
allergens, no previous hospitalizations or surgeries. No history of other diseases such as
Diabetes Mellitus, other Rheumatoid diseases (e.g SLE), blood dyscrasias and malignancies
that runs in the family.//

Family History
The patient’s father is known hypertensive and her sister is known to have bronchial
asthma. Moreover, the patient noted that there were cases of arthritis on both her paternal and
maternal sides. Otherwise, the patient has no knowledge of other heredofamilial diseases, such
as Diabetes Mellitus, other Rheumatoid diseases (e.g SLE), blood dyscrasias and malignancies
that runs in the family.//

Personal and Social History

Patient is a worker at a joint burger stall. Patient is also a known smoker for 9 pack
years, an occasional alcoholic beverage drinker. Moreover, the patient was previously a
marijuana user for 6 years wherein she consumes ½ - 1 stick, twice a week, however, the
patient mentioned that she stopped in 2018. These informations are worthy to note as these are
paramount in determining our differential diagnoses.//

OB-Gyne History
Patient is a G3P3 (3003) with no history of abortion. Patient had her menarche at 10
years old with regular intervals, lasting for 4 days, using 5 pads per day with no symptoms. Also,
the patient noted no history of contraceptive use. //

Our Review of Systems was unremarkable. //

Upon physical examination, patient was conscious, coherent, and not in cardiorespiratory
distress with stable vital signs of 130/90, 99, 20, 37.0 C, and 99% O2 saturation. Examination of
the head, eyes, ears, nose, throat, chest and lungs, heart, and abdomen were unremarkable. //

However, the examination of the extremities reveal pain on passive external rotation of bilateral
shoulder joints, // pain on passive flexion and extension of the right elbow joint, // pain on
palpation of the PIP at the 4th digit of the right hand with swelling on the distal phalanges of the
3rd-5th digits of the right hand with dark discoloration on the palmar surface, // swelling on the
distal phalanges of the 2nd-4th digits of the left hand with dark discoloration on the distal 2nd
digit of left hand, dorsal surface, // swelling on the 4th-5th digits of the right foot and distal
phalanges of the 2nd and 5th digit of the left foot, and dark discoloration of the 2nd digit of
bilateral foot. //

Salient features //

With these presentations, we will proceed to discuss our differential diagnosis. // To begin, with
the patient's medical history, it is important to consider rheumatoid vasculitis as a possible
diagnosis, particularly given its higher incidence in middle-aged women. Studies suggest that
smoking can exacerbate vasculitis in RA patients. Inflammation of the small blood vessels can
lead to ischemia, resulting in discomfort and necrosis, which can cause discoloration in the
affected area - in this case, the patient's fingertips. However, the diagnosis is less likely as the
patient did not report experiencing morning stiffness or constitutional symptoms like fatigue,
weight loss, and night sweats. Additionally, the patient does not exhibit joint deformities, resting
pain, and DIP joints are rarely affected in RA. However, we cannot dismiss the possibility
entirely, as the patient's condition still bears some resemblance to that of rheumatoid vasculitis.
Additionally, high inflammatory markers like CRP strengthen our evidence that this may be a
case of autoimmune vasculitis secondary to rheumatoid arthritis. //

To further elaborate, Vasculitides are a rare group of autoimmune diseases that can have
devastating consequences. They cause inflammation of the blood vessels, which can lead to
ischemia, necrosis, and hemorrhage, resulting in damage to vital organs. These diseases can
be primary or secondary to another disease, and in this case, it is likely secondary to RA, an
autoimmune disease. The immune system mistakenly attacks healthy tissues, and that
confusion leads to vasculitis. It is crucial to understand the underlying causes of these diseases
to provide the right treatment and avoid further complications. By identifying the root cause and
working to treat it, we can help manage the symptoms and improve the quality of life for patients
with vasculitis. //

Based on the 2012 Chapel Hill Consensus Nomenclature, the classification of vasculitis is
based on the size of the vessel predominantly affected which is categorized to Large, Medium,
Small (ANCA or non-ANCA associated) or Variable vasculitis. Our patients’ clinical presentation
means that she is having a small vessel vasculitis. //

Rheumatoid vasculitis is an unusual complication of longstanding, severe rheumatoid arthritis

(RA). Rheumatoid vasculitis occurs in approximately 2 to 5% of patients who have RA.
Rheumatoid vasculitis is a skin condition that is a typical feature of RA, presenting as peripheral
vascular lesions that are localized (purpura, cutaneous ulceration, and gangrene of the distal
parts of the extremities). The cause of RV is unknown, but given the prominence of immune
components and the pathologic changes in involved blood vessels, an autoimmune process is
suggested. //

Moving forward, Thromboangiitis obliterans, also known as Buerger disease, is a disease that
causes inflammation and blockage of small and medium-sized blood vessels in the extremities.
It is commonly found in individuals with a history of tobacco consumption, such as smoking,
chewing, or vaping. Symptoms of the disease include intermittent claudication, Raynaud
phenomenon, and migratory superficial thrombophlebitis, which can ultimately lead to critical
limb ischemia, rest pain, absent pulse in the extremities, and/or digital ulcerations. However, in
our patient, only Raynaud phenomenon and digital ulceration are present. Additionally, the
patient's high inflammatory marker (CRP) rules out vasculitis and confirms the diagnosis of
Buerger's disease, hence, this disease is less likely to be the diagnosis. //

Additionally, progression of symptoms despite having stopped smoking for 8 years also made
us rule this out as a research conducted by Seebald and Gritters showed that smoking is the
only complete cessation of tobacco consumption in any form and is the single most effective
therapeutic measure for Buerger's disease. //

We have also considered Systemic lupus erythematosus, or SLE due to its risk factors of being
a middle-aged, smoking female, as our patient. Patient also presented with swelling and rubor
on bilateral DIP joints with arthralgia in both hands, along with the presence of periungual skin
manifestations which strengthens the diagnosis of SLE. However, since the patient is a known
case of RA with no history of abortion, does not complain of photosensitivity, fatigue, anorexia,
intractable headaches, seizures, febrile episodes, malar rashes, oral ulcers, and alopecia, the
diagnosis of SLE can be ruled out. //

Our final differential diagnosis is Secondary Reynaud’s phenomenon. This disease occurs more
commonly in female with known case of arthritis, and presents with skin color changes starting
at painful DIP joints which are not aggravated by cold temperatures. All of which along with the
presentation on the distal phalanges of the patient makes this diagnosis more likely. However,
since the patient has no known history of Reynaud’s disease in the family and symptoms are
not relieved by rewarming, we can rule out this diagnosis. //

APPROACH TO MSK //

RA is a clinical diagnosis. Our patient is presented with chronic joint pain in bilateral hands PIP
and DIP, accompanied by inflammation (swelling, tenderness, high marker: CRP). Clinical
presentation is positive for Rheumatoid arthritis.//

The majority of individuals with musculoskeletal complaints can be diagnosed with a thorough
history and a comprehensive physical and musculoskeletal examination. Based on our patients
history and PE, she experienced chronic polyarticular joint pain with associated swelling
involving the distal phalanges of 3rd-5th digits of right hand; 2nd-4th digits of Left hand; 2nd and
4th digit, left foot; 4th and 5th digits, right foot and tenderness in PIP 4th digit, right hand. //

We classify our patient for as Chronic inflammatory polyarthritis due to presence of symmetrical
soft tissue swelling to the distal 3rd-5th digits of right hand; 2nd-4th digits of Left hand; 2nd and
4th digit, left foot; 4th and 5th digits, right foot and a high CRP value. //

Since distal phalanges of 3rd-5th digits of right hand; 2nd-4th digits of Left hand; 2nd and 4th
digit, left foot; 4th and 5th digits, right foot our patient then fit for the criteria of Rheumatoid
arthritis. //

To elaborate, Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory autoimmune

disorder that primarily affects the joints (e.g., causes pain, swelling, synovial destruction,
deformities), but may also manifest with extraarticular features (e.g., rheumatoid nodules,
pulmonary fibrosis, vasculitis). The risk of RA increases with age, and the disease
predominantly affects women. The diagnosis is clinical and may be supported by laboratory
tests (e.g., rheumatoid factor, anticitrullinated peptide antibodies) and imaging studies (e.g., the
presence of synovitis on ultrasound and, later in the disease course, bone erosions and/or joint
space narrowing on x-rays). There is no curative therapy for RA but early intervention with
disease-modifying antirheumatic drugs (DMARDs) using a treat-to-target strategy can prevent
disease progression and RA-related disability. //

Vasculitides are a rare group of autoimmune diseases that can have devastating
consequences. They cause inflammation of the blood vessels, which can lead to ischemia,
necrosis, and hemorrhage, resulting in damage to vital organs. These diseases can be primary
or secondary to another disease, and in this case, it is likely secondary to RA, an autoimmune
disease. The immune system mistakenly attacks healthy tissues, and that confusion leads to
vasculitis. It is crucial to understand the underlying causes of these diseases to provide the right
treatment and avoid further complications. By identifying the root cause and working to treat it,
we can help manage the symptoms and improve the quality of life for patients with vasculitis. //

Based on the 2012 Chapel Hill Consensus Nomenclature, the classification of vasculitis is
based on the size of the vessel predominantly affected which is categorized to Large, Medium,
Small (ANCA or non-ANCA associated) or Variable vasculitis. Our patients’ clinical presentation
means that she is having a small vessel vasculitis. //

Presented here is a retrospective cohort of Mayo Clinic, written by Makol et al., among the
patients with RV which determine the clinical correlates and its predictors. It was proven that
cutaneous vasculitis followed by vasculitic neuropathy are the most common manifestation of
rheumatoid vasculitis for 58% of women who has long standing RA. Risk factors for RV were
younger age at RA diagnosis, smoking and having vascular disease.

LABS, XRAYS and ECG //

PATHOPHY

Presented here is the overview of the pathophysiology of vascular inflammation. //

In rheumatoid arthritis, 40% of patients develop extra-articular manifestations. Among these is

systemic rheumatoid vasculitis. Clinical manifestations of rheumatoid vasculitis may involve
many of the body’s different organ systems, including but not limited to the skin, peripheral
nervous system, eyes with scleritis, and arteries of the fingers and toes causing digital ischemia,
as was seen in our patient. //

Digital ischemia occurs when there is blood flow deficiency in the tip of the finger caused by an
obstruction of the digital artery. This may have been caused by vascular inflammation which
fosters a local prothrombotic state, leading to vasoocclusion and then microabcess formation.
Subacutely, granulomatous inflammation develops, and the thrombus is reorganized and
recanalized. As the thrombus matures chronically, vascular fibrosis ensues, leaving a stenotic
arterial lumen. //

Factors that may have contributed to vascular inflammation include the history of the
patient having RA, genetic predisposition, and environmental factors such as tobacco smoking.
Our patient is also a 9 pack-year smoker. Tobacco smoking triggers an inflammatory response
in susceptible individuals leading to progressive thrombosis and fibrosis of small and medium-
sized vessels. This leads to luminal stenosis and location-dependent symptoms of tissue
ischemia. While tobacco exposure is central to disease onset and continuation, the precise
mechanisms of disease initiation remain unknown. //

Generally, most of the vasculitic syndromes are assumed to be mediated at least in part
by immunopathogenic mechanisms that occur in response to certain antigenic stimuli. As was
seen in this selected area. //

Another cause of vascular inflammation is the involvement of antineutrophil cytoplasmic

antibodies. ANCA are antibodies directed against certain proteins in the cytoplasmic granules of
neutrophils and monocytes. The activation of the antibodies eventually degranulate neutrophils
and produce reactive oxygen species that can cause tissue damage. //

This part illustrates the process where vascular endothelial cells expresses human
leukocyte antigen molecules which is followed by activation of cytokines than eventually lead to
the enhancement of the adhesion of leukocytes to endothelial cells in the blood vessel wall,
hence, inflammation of the vessels. //

TREATMENT
This flow shows the flow of treatment in RA. Disease-modifying antirheumatic drugs
(DMARDs) are immunosuppressive and immunomodulatory agents and are classified as either
conventional DMARDs or biologic DMARDs. Although many medications can be used in the
treatment of RA, methotrexate is the most commonly used agent as an initial treatment.

Each DMARD has a unique mechanism of action, ultimately interfering with critical
pathways in the inflammatory cascade. Other medications in this class serve to inhibit
proliferation or cause dysfunction of lymphocytes. Leflunomide inhibits dihydroorotate
dehydrogenase resulting in inhibition of pyrimidine synthesis hence blocking lymphocyte
proliferation. Sulfasalazine mediates its anti-inflammatory effects by preventing oxidative,
nitrative, and nitrosative damage. On the other hand, hydroxychloroquine is a very mild
immunomodulatory agent that inhibits intracellular toll-like receptor TLR9.

Biologics, on the other hand, are very selective in their mechanism of action. The
overarching functions of biologics include (1) interfering with cytokine function or production, (2)
inhibiting the “second signal” required for T-cell activation, or (3) depleting B-cells or inhibiting
factors that activate B-cells. Tofacitinib is a small molecule inhibitor of JAK, a protein tyrosine
kinase involved in mediating cytokine signaling //