Cytokine release syndrome:

Cytokine release syndrome is an acute systemic inflammatory syndrome characterized by collection of symptoms that vary from fever to vomiting. These symptoms occur when the immune system becomes activated and releases massive amount of inflammatory cytokines in a short time period.

Symptoms of Cytokine release syndrome:

Constitutional: Fever, chills, myalgia and skin rash

Gastrointestinal: Nausea/Anorexia, diarrhea

Cardiac dysfunction: Tachycardia, Hypotension, diminished cardiac output, Arrhythmias

Respiratory: Tachypnea, Dyspnea, and Hypoxemia

Renal and Hepatic dysfunction: Acute kidney injury, Transaminitis, Hyperbilirubinemia

Coagulopathy: Elevated D-dimer, Low fibrinogen, disseminated intravascular coagulation.

Neurologic: Headache, Aphasia, Seizures, coma

Causes of Cytokine release syndrome:

CRS can occur due to infection or as a result of any medical treatments. It has recently become more formally associated with T-cell engaging immunotherapies such as Blinatumomab and chimeric antigen receptor CAR-T cell therapy.

Currently the US Food and Drug Administration (FDA) have approved two CAR-T cell therapies:

Tisagenlecleucel (Kymriah): It is a CAR T-cell immunotherapy. It works by engineering T cells to have special receptors called chimeric antigen receptors (CARs). These receptors help T cells recognize and attack cancer cells. This approved immunotherapy medicine is used to treat a certain type of acute lymphoblastic leukemia in people who are up to 25 years old. It is also used to treat certain adult patients with large B-cell lymphoma.

Axicabtagene ciloleucel: It is an immunotherapy medicine used to treat large B-cell lymphoma in adults. Axicabtagene ciloleucel is given after at least two other treatments have failed.

New subcategory for “Cytokine release syndrome”: D89.83

A new subcategory is introduced for “cytokine release syndrome” in 2021 ICD-10 CM code changes. It is further expanded to six new codes to report the appropriate grade of the syndrome. Also you have the instructional notes “code first” to report the underlying cause and “use additional” codes to identify any associated manifestations.

Grading of Cytokine release syndrome:

There are many new systems developed to define and grade CRS events and are used in different CART-T therapy clinical trials. Below is the list of few grading scales and their key differences:

Penn scale: It defines CRS as a single event and frames CRS severity in terms of hypotension and fluid and/or pressor requirements used for CRS management.

Lee scale: It provides definitions of mild, moderate, and severe CRS with additional attention to single-organ toxicities. It also outlines detailed CRS management recommendations, including use of tocilizumab and anti-cytokine therapy.

ASTCT (American Society for Transplantation and Cellular Therapy): It simplifies the CRS grading scale, focusing on fever, hypotension and hypoxia and symptoms that occur primarily within 14 days of CAR-T infusion. The FY 2021 IPPS Proposed Rule also includes new ICD-10-CM codes for Cytokine Release Syndrome (CRS) based on the current grading system established by the American Society for Transplantation and Cellular Therapy (ASTCT). It is also accepted by the CAR-T providers for its use in medical documentation.

Based on the toxicity descriptions found in the ASTCT CRS Grading system, grades 3, 4 and 5 are assigned to unstable patients requiring hospitalization to arrest further deterioration. Assignment of ICD-10-CM codes D89.833, D89.834 and D89.835 would indicate that the provider is treating a complicated patient with major comorbid conditions that require high resource use.

New codes for Cytokine release syndrome:

  • D89.831 Cytokine release syndrome, grade 1
  • D89.832 Cytokine release syndrome, grade 2
  • D89.833 Cytokine release syndrome, grade 3
  • D89.834 Cytokine release syndrome, grade 4
  • D89.835 Cytokine release syndrome, grade 5
  • D89.839 Cytokine release syndrome, grade unspecified

Happy learning! Happy coding!


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