CASE STUDY: RHEUMATOID ARTHRITIS

M.L. is a 50-year-old white female who has been working in the front office of a medical clinic for the
past five years. She has made an appointment to see her primary care provider because she has been
feeling very tired for the past month and has also been suffering from stiffness, pain, and swelling in
multiple joints. “I ache all over,” she told her PCP, “and I have pain in different places all the time. One
day it is in my right shoulder, the next day in my right wrist, and the following day in my left wrist. I’m
stiff everywhere when I get up in the morning or if I sit for any length of time. And I feel so tired, like I
have a case of the flu that won’t go away.” The patient is allergic to IV iron dextran from which she has
developed shortness of breath. She rarely uses alcohol and does not smoke. She is taking an over-the-
counter calcium supplement, levothyroxine sodium, and venlafaxine. There is no family history of
rheumatoid arthritis.

Patient Case Question 1

Which of the vital signs above is consistent with a diagnosis of rheumatoid arthritis and why?

A temperature of 100.0° F which is considered as a low-grade fever. Rheumatoid arthritis is a

chronic, systemic, inflammatory disease that affects connective tissue. A fever is a systemic sign
of an ongoing inflammation in the body and is consistent with a diagnosis of RA.

References:

 Evans, S. S., Repasky, E. A., & Fisher, D. T. (2016). Fever and the thermal regulation of immunity:
The immune system feels the heat. Nature Reviews Immunology.
 Heidari, B. (2011). Caspian Journal of Internal Medicine. Rheumatoid Arthritis: Early diagnosis
and treatment outcomes.
 Rheumatoid Arthritis. Retrieved April 26, 2020 from https://www.mayoclinic.org/diseases-
conditions/rheumatoid-arthritis/symptoms-causes/syc-20353648
 Wolff, D. (2008). XPharm: The Comprehensive Pharmacology Reference. Rheumatoid Arthritis.

Patient Case Question 2

List two conditions for which the drug venlafaxine is often prescribed.

Venlafaxine (Effexor) is a bicyclic antidepressant and is categorized as a serotonin-

norepinephrine reuptake inhibitor (SNRI). It can be used to treat a number of psychiatric
disorders, including unipolar major depressive disorder and panic disorder.
Off-label, venlafaxine can be used for attention deficit disorder, fibromyalgia, and diabetic
neuropathy.

References:
 Chew et al. (2017). What Your Patients Need to Know About Psychiatric Medications (3 rd Ed).
Venlafaxine, pp 152. American Psychiatric Association Publishing.
 Schatzberg, A.F., & Nemeroff, C.B. (2009). The American Psychiatric Publishing Textbook of
Psychopharmacology (4th Ed). Chapter 22 Venlafaxine and Desvenlafaxine, pp 441. American
Psychiatric Publishing Inc.
 Venlafaxine. Retrieved April 26, 2020 from https://pubchem.ncbi.nlm.nih.gov/compound/
Patient Case Question 3
Identify two abnormal findings from the physical exam above that are consistent with rheumatoid
arthritis.

Patient M.L. “appears very tired”. Fatigue and malaise are common symptoms of RA. Studies
show that up to 80% of people with RA have at least some sense of feeling run down, and more
than 50% have high levels of fatigue.
Mild lymphadenopathy. More than 50% of patients with rheumatoid arthritis (RA) exhibit
lymphadenopathy and reactive follicular hyperplasia. Lymphadenopathy can occur in the nodes
near the affected joints.

References:

 Hsi, E.D. (2012). Hematopathology. Reactive lymph nodes chapter 4, pp 136. Elsevier Inc.
 RA and Fatigue. Retrieved April 26, 2020 from https://www.webmd.com/rheumatoid-
arthritis/ra-fight-fatigue#1
 Saito et al. (2014). Hindawi Journals. A Case of Rheumatoid Arthritis.

Patient Case Question 4

What is the association between the “fixed nodule(s) at pressure point(s)” on the left wrist/right elbow
and a diagnosis of rheumatoid arthritis?

Are rheumatoid nodules, lesions containing lymphocytes and dead cell debris that are
characteristic of rheumatoid arthritis. Rheumatoid nodules are firm, noticeable lumps that form
underneath the skin of some rheumatoid arthritis patients. They generally form on or near the
base of the arthritic joints. They are a symptom that is unique to rheumatoid arthritis.
The nodules can be present in the acute and chronic stages of the disease. Most commonly,
rheumatoid nodules develop in patients already living with rheumatoid arthritis for some time.

References:

 Ezerioha, M. (2018). Rheumatoid Nodules: Are Rheumatoid Nodules Dangerous. Retrieved from
https://www.rheumatoidarthritis.org/ra/symptoms/rheumatoid-nodules/
 Villines, Z. (2017). What are rheumatoid nodules? Retrieved April 27, 2020 from
https://www.medicalnewstoday.com/articles/319839

Patient Case Question 5

Why is it reasonable that this patient has no stiffness, pain, or swelling in the DIP joints of the fingers?

The distal interphalangeal (DIP) joints are generally spared in Rheumatoid arthritis, this is a
distinguishing characteristic that helps to differentiate RA from osteoarthritis. It is more
common for DIP joints to be affected by osteoarthritis than by RA.
The joints involved most frequently are the proximal interphalangeal (PIP) and
metacarpophalangeal (MCP) joints of the hands, the wrists, and small joints of the feet including
the metatarsophalangeal (MTP) joints. The shoulders, elbows, knees, and ankles are also
affected in many patients.
References:

 Nietto, A. (2015). Arthritis-Health Article. Hand Pain and Rheumatoid Arthritis

 Rheumatoid Arthritis Signs and Symptoms. Retrieved April 26, 2020 from
https://www.hopkinsarthritis.org/arthritis-info/rheumatoid-arthritis/ra-symptoms/

Patient Case Question 6

Identify three abnormal laboratory tests in Table 1 that are consistent with a diagnosis of rheumatoid
arthritis.

Elevated Erythrocyte Sedimentation Rate (ESR)

 The patient has an ESR of 38mm/hr
 The normal reference range for ESR results is 1–20 mm/hr for females. High ESR is an
indication of inflammatory conditions like RA.
+ Rheumatoid factor
 High levels of rheumatoid factor in the blood are most often associated with
autoimmune diseases, such as rheumatoid arthritis
Elevated White Blood Cell (WBC)
 The patient has a WBC of 15,100/mm3 which is above the normal range of 5,000 to
10,000/mm3.
 A high white blood cell count could mean there is inflammation (swelling), which can be
caused by rheumatoid arthritis (RA).

References:

 Medlineplus. Retrieved April 26, 2020 from https://medlineplus.gov/lab-tests/erythrocyte-

sedimentation-rate-esr/
 Murrell, D. (2018). Medical News Today. What does it mean if your ESR is high? From
https://www.medicalnewstoday.com/articles/
 Mayoclinic. Retrieved April 26, 2020 from https://www.mayoclinic.org/tests-
procedures/rheumatoid-factor/about/pac-20384800
 Richey, M. (2018). Hospital for special surgery. Understanding Rheumatoid Arthritis Lab Tests
and Results.
 White Cell Count. Retrieved April 26, 2020 from https://www.urmc.rochester.edu/encyclopedia

Patient Case Question 7

Why is it entirely appropriate that the PCP has ordered a TSH test for this patient?

Patient M.L. is taking levothyroxine. Levothyroxine used to treat thyroid hormone deficiency.
Because the patient has symptoms of fatigue and malaise, it is appropriate to determine her
serum TSH in order to attribute these symptoms to thyroid dysfunction or possibly another
condition, such as RA.
TSH concentration aids in differentiating hypothyroidism. A TSH test is also used to find out how
well the thyroid is working. This test would be considered appropriate given the symptoms.

References:

 Levothyroxine. Retrieved April 27, 2020 from https://www.drugs.com/levothyroxine.html

  Pagana, K.D., & Pagana, T.J. (2014). Mosby's Manual of Diagnostic and Laboratory Tests. Thyroid
Stimulating Hormone pp 487. Elsevier Inc.
 TSH (Thyroid-stimulating hormone) Test. Retrieved April 27, 2020 from
https://medlineplus.gov/lab-tests/tsh-thyroid-stimulating-hormone-test/

Patient Case Question 8

Provide a reasonable explanation for the serum uric acid test result shown in Table 1.

The reason for the testing of the uric acid is to rule out other conditions which present with
similar clinical manifestations as RA, like gouty arthritis. Elevated serum levels of uric acid are
consistent with a diagnosis of gouty arthritis. Patient M.L. has 2.9 mg/dL of uric acid level and
it’s within the normal limits of 2.5 to 7.5 mg/dL for females.

References:

 American college of physicians. (2008). MKSAP for Students 4: Medical Knowledge Self-
assessment Program.
 Brown, J. (2018). Gout vs. Rheumatoid Arthritis. Retrieved from
https://creakyjoints.org/symptoms/gout-vs-rheumatoid-arthritis/
 Gabbey, A.E., & Nall, R. (2017). Uric Acid Test (Blood Analysis). Retrieved from
https://www.healthline.com/health/uric-acid-blood

Patient Case Question 9

What is probably the first class of drugs that the PCP will prescribe for this patient?

With the main goal to reduce the inflammation and pain while preserving joint function and
preventing deformities, the first class of drugs for RA is NSAID. NSAIDs work to reduce the levels
of inflammation in the joints, thus relieving pain and restoring mobility. Examples of NSAIDs
commonly used are ibuprofen and naproxen, prescription NSAIDs like celecoxib may also be
prescribed as they offer a higher dose with longer-lasting results and require fewer doses
throughout the day.
For severe joint damage, disease-modifying antirheumatic drugs (DMARDs) like methotrexate
are used. DMARDs interfere with the autoimmune attacks occurring in rheumatoid arthritis
patients, these medications also aim to preserve the joint structure and reduce the progression
of early rheumatoid arthritis.

References:

 Duckworth, H. (2018). RA Medications: Are NSAIDs or DMARDs Better for Pain? Retrieved from
https://www.rheumatoidarthritis.org/treatment/medications/nsaids-vs-dmards/
 Lemke, T.L., & Williams, D.A. (2008). Foye's Principles of Medicinal Chemistry. Chapter 36:
Nonsteroidal Anti-inflammatory Drugs pp 989. Lippincott Williams & Wilkins.
 Rheumatoid Arthritis Drug Guide. Retrieved April 27, 2020 from
https://www.webmd.com/rheumatoid-arthritis/rheumatoid-arthritis-medications#1
 Understanding Rheumatoid Arthritis – Treatment. Retrieved April 27, 2020 from
https://www.webmd.com/rheumatoid-arthritis/understanding-rheumatoid-arthritis-
treatment#1
Patient Case Question 10
In terms of the progression of the disease, what do the results of the hand x-ray suggest?

The earliest sign of RA is a periarticular soft-tissue swelling. As seen in the hand x-ray of the
patient, soft tissue swelling and bone demineralization are present. This suggests that the
patient has had RA for more than 6 months’ time but has not had the condition long enough to
cause significant radiographic changes associated with RA along with the evidence that there’s
still no erosion in the bones.
Bone erosion happens in stage 3 of rheumatoid arthritis.

References:

 Freeman, J. (2018). RA Progression: What are the Signs of Rheumatoid Arthritis Progression?
Retrieved April 27, 2020 from https://www.rheumatoidarthritis.org/ra/symptoms/progression/
 Lovering, C. (2019). Four Stages and Progression of Rheumatoid Arthritis. Retrieved April 27,
2020 from https://www.healthline.com/health/rheumatoid-arthritis/stages-and-progression.
 Newman, E.D., & Matzko, C. (2008). Rheumatoid Arthritis FAQs. Geisinger Clinic and Decker Inc.
 Tsou, I.Y. (2019). Rheumatoid Arthritis Hand Imaging. Medscape Articles.

Patient Case Question 11

Which findings in the examination of the synovial fluid are consistent with a diagnosis of rheumatoid
arthritis?

7.4 mL volume of synovial fluid aspirated from the patient.

 Healthy joints contain just 0.15 to 4.0 mL of synovial fluid, too much fluid indicates
inflammation.
The color and clarity of the synovial fluid is cloudy and yellow in appearance
 Normal synovial fluid is clear.
 Abnormal fluid may look cloudy
14,000 WBC/mm3
 In RA, aspirate from an affected knee joint has a WBC count that exceeds 3,000 and has
more than half of differential being neutrophils and macrophages.
Glucose 60 mg/dL in aspirate, 94 mg/dL in serum.
 The glucose level in the aspirate is less than the patient’s serum glucose concentration.
 Glucose levels of synovial fluids (as well as pleural and pericardial fluids) in patients with
RA are often low compared with serum glucose levels.

References:

 Cole, J.D. (2014). Diagnosis through Synovial Fluid Analysis. Retrieved April 27, 2020 from
https://www.arthritis-health.com/treatment/joint-aspiration/diagnosis-through-synovial-fluid-
analysis
 Faryna, A., & Goldenberg, K. (1990). Clinical Methods: The History, Physical, and Laboratory
Examinations. (3rd Ed.). Chapter 166 Joint Fluid. Boston.
 Smith, H.R. (2020). Rheumatoid Arthritis (RA) Workup. Retrieved April 27, 2020 from
https://emedicine.medscape.com/article/331715-workup#c11

Patient Case Question 12

What causes limitation of joint motion that occurs early in the clinical course of rheumatoid arthritis?

In the early course of RA, joint mobility is reduced due to the initial inflammatory response. The
inflammatory response includes vasodilation in the tissues of the affected joint in response to
the production of histamine, prostaglandins and other cytokines. Vasodilation increases blood
flow, causes the symptoms of warmth and redness while swelling is caused by increased
capillary permeability that accompanies inflammation and vasodilation. The swelling of the joint
is the initial cause of loss of joint mobility. The inflammatory response eventually goes on to
erode bone and cartilage and destroy the joint.

References:

 Heidari, B. (2011). Caspian Journal of Internal Medicine. Rheumatoid Arthritis: Early diagnosis
and treatment outcomes.
 Kandola, A. (2018). Rheumatoid arthritis (RA): Prognosis. Retrieved from
https://www.medicalnewstoday.com/articles/323631

Patient Case Question 13

What causes limitation of joint motion that occurs late in the clinical course of rheumatoid arthritis?

Limitation of motion occurs as a result of articular surface damage, joint and tendon sheath
swelling, or alteration of joint supporting structures. Effusion may limit joint motion through
pain or by causing sufficient tightness of the joint capsule to impede joint mobility. Fibrosis
involving tendons and muscles may limit normal joint motion and result in flexion contractures.
In the later course of RA, significant inflammation causes small blood vessels to become
obstructed with microthrombi composed of fibrin and platelets. The body tries to compensate
for the compromised blood flow by creating a new network of blood vessels in the synovial
membranes. This tissue is known as pannus, the formation of pannus is a characteristic feature
of RA that distinguishes it from other forms of arthritis. The pannus extends from the synovium
to the unprotected bone and leads to the formation of scar tissue within the joint space. Scar
tissue ultimately reduces joint motion and leads to joint immobilization.

References:

 Reynolds, W.E. (1995). Medical Clinics of North America. The Clinical Manifestations of
Rheumatoid Arthritis, Volume 39, Issue 2, March 1955, Pages 365-377.
https://doi.org/10.1016/S0025-7125(16)34694-6
 Smith, H.R. (2020). Rheumatoid Arthritis (RA) Clinical Presentation. Retrieved from
https://emedicine.medscape.com/article/331715-clinical#b4
 Xiu, P. (2012). Crash Course Pathology (4th Ed). Elsevier Inc.