Brigham and Women's Hospitals

Immunosuppressed Patients

Updated: May 13, 2020

Oncology

  1. Data:
  1. Based on early descriptive studies from China, patients with cancer - particularly those on active treatment for cancer - appear to have a worse prognosis. This includes higher prevalence, higher risk of severe disease, and higher risk of death from COVID-19 in patients with cancer compared to those without. (WHO-China Joint Mission on COVID-19, Yu et al, JAMA Oncology 2020, anecdotal reports)
  1. Oncology Consultation/Coverage:
  1. For established DFCI patients, oncology consultation and guidance is provided by each patient’s primary oncologist (or coverage).
  2. Contact primary oncologist via page, not the general pager or fellow on call, to establish the best means of ongoing communication.
  1. Prognosis:
  1. Many patients have a reasonable or even good oncologic prognosis with current therapies. Do not assume an oncologic prognosis, even with metastatic disease: involve the primary oncologist.
  1. Meds:
  1. Check in Epic medications tab and in “Research: Active” tab to include experimental medications. Contact the primary oncologist with questions.
  1. Workup:
  1. Additional labs to standard workup:
  1. Weekly glucan/galactomannan in neutropenic/transplant patients.
  2. Specific patient populations may require additional monitoring (such as CMV, EBV monitoring in transplant patients – ask primary oncologist).
  1. Exam:
  1. Examine catheters (port, CVC, others) daily.
  2. Avoid rectal exams and any per-rectum therapies in neutropenic patients, but examine the perirectal area if symptoms or persistent fevers.
  3. In patients with heme malignancy or SCT: findings are more subtle or absent in neutropenic and immune suppressed patients.
  1. Pain management:
  1. Patients with cancer-related pain may have high opiate needs at baseline. Opiates should not be stopped but type may need to be adjusted in the setting of respiratory failure, renal injury, or liver injury.
  1. Consider Pain / Palliative Care consult
  1. Goals of Care:
  1. Involve primary oncologist whenever possible (recognizing that in critical/emergent situations, this may not be possible).
  1. Anticoagulation:
  1. Patients with solid tumors are at very high risk of thrombosis but at lower risk of infection than most heme malignancy patients.
  2. Thrombosis prophylaxis for all unless contraindicated
  1. Hold pharmacologic prophylaxis if platelet count < 30K, use pneumoboots
  2. Both COVID-19 infection and malignancy increase thrombotic risk, particularly with solid tumors.
  3. See “Thrombotic Disease” section for guidelines on both prophylactic and therapeutic anticoagulation.
  1. Transfusions:
  1. The BWH blood bank reviews orders and releases appropriate products (i.e., irradiated, leukoreduced, etc).
  2. See Blood Products section for transfusion thresholds of all patients - of note, the recommended RBC transfusion threshold for all patients, including oncology patients, is Hgb 7, Hct 21.

Febrile Neutropenia

  1. Definition:
  1. ANC < 500 cells/mm3 AND T ≥ 101F or T ≥ 100.5 for 1hr
  1. Workup:
  1. Blood cultures from peripheral (ideally two sets), and each lumen of central line (label clearly); UA/sed with urine culture (UA may not be as informative with neutropenia); glucan and galactomannan (if not checked recently), sputum if able; CXR
  1. Continue DAILY blood cultures while febrile.
  2. Monitor serum galactomannan and 1-3-beta glucan once weekly.
  3. Any positive glucan or galactomannan prompts ID consult.
  1. Initial Empiric Antibiotics:
  1. Cover GNRs in all patients: Ceftazidime 2g Q8h or Cefepime 2g Q8h
  1. Alternatives: Piperacillin-tazobactam (2nd line, high dose 4.5g Q6h) or meropenem (3rd line, 1g Q8h).
  1. GPCs: add Vancomycin if hemodynamically unstable, or if MRSA pneumonia or catheter-associated infection is suspected. Check dosing with pharmacy if able.
  1. Removal of lines:
  1. Catheter removal should be discussed if associated infection is suspected - involve primary oncologist and/or ID team to weigh risks and benefits, given that not all lines require removal.
  1. Persistent Neutropenic Fever:
  1. If fever persists x3 days despite antibiotics
  1. Add Micafungin 100mg IV daily
  2. Consideration of further imaging even if the patient appears stable (discuss with oncology / ID).
  1. Anti-infective course:
  1. Anti-Infectives should be continued until the patient has met all of these criteria:
  1. clinically improved, and
  2. has been afebrile for 48h, and
  3. has been non-neutropenic for 48h.

Immune Checkpoint Inhibitors

  1. Overview
  1. Immune Checkpoint Inhibitors (ICIs) are not immunosuppressive when used alone, but the steroid dosages used to treat immune toxicities are often immunosuppressive.
  2. Most common ICIs are CTLA-4 inhibitor (ipilimumab) and PD-1/PD-L1 inhibitors (pembrolizumab, nivolumab, durvalumab, atezolizumab and avelumab).
  1. Immune toxicity
  1. If patient develops organ dysfunction, it may be due to immune toxicity
  1. Consult the service team of the involved organ system and inform primary oncologist.
  1. Common immune toxicities include pneumonitis / respiratory failure (may be difficult to distinguish between COVID19 disease or may be aggravated by COVID19 infection), colitis, endocrine dysfunction (thyroid, pituitary / hypothalamic, adrenal), nephritis. Less common hepatitis, meningitis, dermatitis.
  1. Check TSH, ACTH, cortisol if hypotension or concern for endocrine dysfunction.
  2. Check T-spot, HIV, HBV, HCV serologies if immune toxicity is suspected, in case additional immunosuppression (particularly TNF-alpha blockade) is required.
  1. Immune toxicities are usually treated with high dose steroids
  1. risks and benefits must be weighed immediately with primary oncologist and ID consult teams if immune toxicity is suspected concurrent with COVID19 infection.
  1. BWH/DFCI iTox guidelines can be found here (Partners login required)

Patients on Immunosuppressants

Immunosuppressant medications and risk of infection

  1. This section is in development

Rheumatology

  1. This section is in development

Neurology

  1. This section is in development

Gastroenterology

  1. This section is in development

Dermatology

  1. Management of the dermatologic patient on immunosuppressive therapy
  1. Immunosuppressive agents:
  1. Biologics and targeted small molecule inhibitors
  1. TNF-a inhibitors: most immunosuppressive of biologic class, increased risk of serious infection (Kalb et al JAMA Dermatol 2015) and upper respiratory tract infections (Lebwohl et al JAAD 2020)
  2. IL-12/23, IL-23, IL-17 inhibitors: theoretical risk of infection but has not been demonstrated in most studies (Lebwohl et al JAAD 2020)
  3. JAK Inhibitors: increased risk of herpes zoster virus compared to placebo (Winthrop JAAD 2017), risk of other viruses unknown
  4. Dupilumab: no increased risk of infection
  5. Apremilast: no increased risk of infection
  1. Conventional disease modifying agents
  1. Systemic corticosteroids: dose dependent increased risk of infections, worse outcomes in MERS (Hui et al. Am J Respir Crit Care Med 2018)
  2. Methotrexate (MTX): no to mild increased risk of infection compared to reference agent (Schneeweiss JAAD 2019) and placebo (Solomon Ann Intern Med 2020) at dermatologic dosing
  3. Mycophenolate mofetil / Azathioprine / Cyclosporine: increased risk of infections compared to reference agent (Schneeweiss JAAD 2019)
  1. Renal Transplant patients on these medications had worse COVID-19 outcomes (Akalin NEJM 2020)
  1. Hydroxychloroquine (HCQ): no increased risk of infection
  1. COVID-19 outcomes in patients with immune mediated inflammatory disease similar to general population in NYC (Haberman NEJM 2020) n= 86 (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, IBD), similar hospitalization rates to general population (11 v 26%). Higher chronic prednisone, HCQ, MTX use in hospitalized compared to ambulatory patients
  2. Management Recommendations
  1. Asymptomatic patients / COVID-19 negative on immunosuppressive agents:
  1. Do not stop agent
  2. Avoid high dose steroids when possible
  3. If high risk of COVID-19 related complications, shared decision making based on 1. Condition being treated, 2. Level of immunosuppression (see above), 3. Need for monitoring, 4. Comorbidities
  1. Symptomatic patients / COVID-19 positive on immunosuppressive agents:
  1. Stop agent
  2. Resume when fully recovered and no sooner than end of isolation
  3. Unclear potential benefit from remaining on immunosuppressive agents regarding COVID-19 therapeutics
  1. Resources: Immunosuppression Guidelines by Society
  1. American Academy of Dermatology Guidelines
  2. American College of Rheumatology (ACR) Guidelines
  3. National Psoriasis Foundation Guidelines
  4. British Association of Dermatologists Guidelines

Transplant

  1. This section is under development
  2. See also cardiac transplant section