Jeff is a 23-year-old male with a history of juvenile rheumatoid arthritis symptoms. Because of their progression and a clinical diagnosis, he was placed on Etanercept in 2011. This significantly improved his joint function and he was able to work on cars for the first time in several years.

At the beginning of November he was changing the spark plugs on his car when he scraped his hand on some metal. He did not think much about it at the time. A couple days later his hand was swollen and tender. It was a Saturday and he decided to wait to see his family doctor on Monday. By Sunday night his hand and forearm were red, tender, and swollen. He had a fever and started to feel dizzy and had a sense of impending doom.

His wife took him to the local hospital’s Emergency Department where he was admitted to the medicine service for cellulitis and possible sepsis. Blood and wound cultures isolated Staphylococcus aureus but it was not methicillin resistant (MRSA). He was started on intravenous antibiotics.

He was evaluated the next day by an orthopedic surgeon who decided to incise and drain an area with loculated pus.  The medicine service was very busy and under pressure from the charge nurse, the attending requested the patient be transferred to the orthopedic service because of the need for repeated debridements.

A series of several debridements and several days of antibiotics were required to get the infection under control. Jeff was scheduled to be discharged with daily IV antibiotics administered via a peripherally inserted central catheter (PICC line) with the help of a home health agency. During his admission, his surgeon did not consult his rheumatologist (who did not have privileges at this hospital).  The rheumatologist was not aware of Jeff’s hospitalization. Jeff continued to have pain and the surgeon suggested an NSAID for pain control prior to discharge. The patient’s discharge medication reconciliation included the NSAID as well as continuation of his current rheumatologic treatment.

10 days later Jeff returned to the ED very pale and weak. His stools had been black for a couple days. He was readmitted and a peptic ulcer was diagnosed. He received four units of blood and was stabilized. He was discharged a couple days later. He was hoping that once he got better that he could take a vacation and try to forget about his recent illnesses.

Case Discussion

In the discussion below, we suggest medical algorithms and calculators that can assist physicians in the diagnosis, assessment, and management of juvenile rheumatoid arthritis and the complications experienced by the patient in this case study.

Juvenile Rheumatoid Arthritis (JRA) and the Need for Targeted Therapy

Juvenile Rheumatoid Arthritis (JRA), also known as juvenile idiopathic arthritis (JIA), is a form of arthritis that starts before 17 years of age and affects 1 or more joints.  It may be limited to a few joints (pauciarticular), many joints (polyarticular) or be associated with systemic symptoms (systemic). The diagnosis requires exclusion of other disorders such as Lyme disease.

Severe diseases can result in deformity and disability which can severely affect the patient’s adult life. Early control of the inflammatory response can result in less deformity and a better functional outcome.

Targeted therapies involve development of an antibody against an effector molecular or a receptor, then “humanizing” it by attaching it to a portion of a human immunoglobulin. These antibodies inhibit the action of the target molecule and can significantly reduce inflammation for long periods without the adverse side effects of standard disease modifying regimens. One such therapy is Etanercept (Enbrel®), which is antibody against tumor necrosis factor alpha (TNF-alpha).

Adverse Effects of TNF-Inhibitors

Unfortunately TNF-inhibitors can have adverse side effects. Injection-site reactions are common with TNF-alpha inhibitors such as Etanercept, but these are usually minor and rarely result in discontinuation of medications. Infusion reactions may also occur with other TNF-alpha inhibitors and in some cases can be more severe.

TNF-alpha is key component of the immune system and its inhibition can leave patients susceptible to serious infection. TNF-alpha is important for macrophage activation and granuloma formation and inhibition can leave patients especially susceptible to infections that are sequestered within granulomas.  These can include Mycobacterium, Staphylococcus aureus, Toxoplasma and fungi such as Histoplasma, Cryptococcus, and Candida. Patients should be screened for tuberculosis prior to treatment with TNF-alpha inhibitors due to risk of reactivation of latent tuberculosis. Those who test positive for tuberculosis should undergo treatment before initiating Etanercept.

Staphylococcus aureus Sepsis

Infection with Staphylococcus aureus may be complicated by sepsis. Sepsis is defined as a systemic inflammatory response syndrome to an infection. Severe sepsis occurs when sepsis is complicated by end organ dysfunction and septic shock occurs when sepsis is complicated by hypotension that is refractory to intravenous fluids. Risk factors for sepsis encompass both a patient’s risk for infection as well as their predisposition for organ failure once an infection develops. Patients with chronic disease or those on immunosuppressive medications are at increased risk.

The latest treatment in sepsis is based on clinical guidelines established by the Surviving Sepsis Campaign and focus on initial management to provide cardio pulmonary resuscitation and treatment of infection. Empirical antibiotic therapy should be started [within 3 hours] after obtaining blood cultures based on suspected site of infection.

NSAIDS for Pain Control

Although non-steroidal anti-inflammatory drugs (NSAIDS) are effective in control of many kinds of pain, the also have a wide range of adverse side effects. These tend to occur when used in high doses or for long periods of time. Patients with chronic pain conditions such as juvenile rheumatoid arthritis are at increased risk because of often continued use. These drugs can cause a wide range of adverse effects on the gastrointestinal tract, including ulceration and hemorrhage.

Take Home Points

  • Targeted therapy for an autoimmune disease blocks key pathways in the immune response but in doing so make the patient susceptible to overwhelming infections.
  • A patient with autoimmune disorders who presents with infection needs to be asked if she or he is taking a targeted therapy.  A patient on a targeted therapy who develops an infection is at risk for a fulminant course.
  • The rheumatologist, infectious disease specialist, and other providers need to communicate and to coordinate care, especially when prescribing medications.
  • Combining medical training with powerful, evidence-based algorithms can help physicians diagnose, assess, and manage diseases.

About the Authors

Adam Vohra is a Health Innovation Fellow at Apervita. He is currently a dual-degree MD/MBA student in his final year at The University of Chicago Pritzker School of Medicine and Booth School of Business. He plans to pursue a residency in internal medicine next year. Adam is interested in issues related to health care quality and delivery and has published research on predictors of intensive care unit admission for pneumonia. He is currently working on research to create analytics to predict heart failure readmissions. Adam is also involved heavily in health care policy and currently serves on the Board of Trustees of the Illinois State Medical Society as the sole medical student member. In the past, Adam has also represented medical students in the American Medical Association House of Delegates. Prior to coming to The University of Chicago, Adam completed his undergraduate studies at Northwestern University where he studied biology and political science.

Dr. Chad Rudnick, MD, FAAP is a board-certified pediatrician in Boca Raton, FL. He is the Medical Director of The Medical Algorithms Company. A proponent of incorporating medical technology into his practice, Dr. Rudnick uses telemedicine and medical algorithms from The Medical Algorithms Company in his daily practice to better serve his patients and their families. An accomplished medical writer, he maintains a popular pediatric blog, All Things Pediatric, and has written for numerous online and print publications including

John Svirbely, MD is a founder and Chief Medical Officer of The Medical Algorithms Company and the primary author of its medical algorithms. John is a co-founder of the Medical Algorithms Project and has developed its medical content for nearly 20 years. He has a BA degree from the Johns Hopkins University and his MD from the University of Maryland. He is a board-certified pathologist with a fellowship in medical microbiology and biomedical computing at Ohio State University. Currently he is in private practice in Cincinnati, Ohio. He has authored multiple books and articles on medical algorithms.