MOC August 2014: IRIS

History

It's the season of sub-zero weather when you (and your parka) meet an ambulance coming in. 

Patient is a pleasant 50-year-old female with a pertinent past medical history that includes breast cancer, history of prosthestic heart valve (on Coumadin), mitral regurgitation, and SVT who presents to the emergency department today for evaluation of shortness of breath. She is currently on chemotherapy for breast cancer and her last treatment was 6 days ago. She is actually discontinuing treatments due to adverse reactions.

No history of HIV.  Denies associated symptoms such as fever, chills, cough, chest pain, nausea, vomiting, abdominal pain.  No urinary symptoms.  No headache or neck pain.

Of note, patient was recently in the ED (3 days ago) for evaluation of SVT and had an ablation at that time.

Social History

Single, part time caregiver.  Has never smoked.  Drinks approximately 8 beverage of hard alcohol per week.  Denies illicit drug use.

Allergies

Bactrim; Mold extracts; and Pollen extracts

Medications

Reviewed and non-contributory with exception of chemotherapy agents and Coumadin.

Physical Exam

Vital Signs: Temp 97.9°F, HR 78, BP 113/65, SpO2 100% on room air, Wt: 95 kg, Ht 167 cm

Patient is alert and oriented x3.  She has a mechanical heart sound, but no murmur.  Has mild respiratory distress, speaking in 3 word phrases.  No wheezes or crackles.  No pedal edema.  Abdomen is soft and nontender.  Port-a-cath in place in right upper chest.  Remainder of exam is unremarkable.

Differential diagnosis

CHF, SIRS, Sepsis, Pneumonia, COPD, ACS, PE, others.

Diagnostic Testing

EKG

HR 107

Sinus Tachycardia

Otherwise unremarkable

Chest X-ray

No acute consolidations.  Prosthetic cardiac valve and Port-A-Cath visualized.  Pulmonary vasculature within normal limits. 

Labs

CBC - WBC 13.7, Hgb 8.4, Plt 179; elevated bands

BMP remarkable only for creatinine of 2.13 (new from previous labs)

BNP 1748

INR 4.6

Troponin 0.899

Urine negative

Lactate pending

Updates

You are notified that the patient’s temperature is now 104.6°F.  Lactate is ordered and elevated at 2.6.

Next steps

What are you thinking – update to differential?

            Add: IRIS, endocarditis.

Any treatments you would start immediately in the ED at this point?

            Antibiotics?  Lasix?  Heparin?  Steroids?

What is your plan?

            Admit and let the hospitalist deal with it!

What is IRIS?

"Immune Reconstitution Inflammatory Syndrome"

This is a syndrome in which there is paradoxical worsening of pre-existing infections in certain situations - namely initiation of HAART therapy for HIV.  This can also happen with corticosteroid withdrawal, chemotherapy discontinuation, recovery of neutropenia after cytotoxic chemotherapy, and other situations.  The most common and definition of the syndrome is when HAART is initiated in HIV infected patients that have an opportunistic infection that they are being treated for, such as CMV, Pneumocystis, cryptococcal, or others.

Basically what happens is that the immune function improves too rapidly, causing systemic (or local) inflammatory reactions.  This reaction can range from self-limited (most of the time) to fatal.

Diagnostic Criteria

•   Presence of AIDS with low pretreatment CD4 count.

•   Positive virologic and immunologic response to HAART.

•   Absence of evidence of drug-resistant infection, bacterial superinfection, drug allergy or adverse reaction, patient non-compliance, or reduced drug levels.

•   Presence of clinical manifestations consistent with an inflammatory condition.

•   Association between HAART initiation (or recovery of neutropenia after chemotherapy in our case) and onset of clinical features of illness.

•   It is a diagnosis of exclusion.

Leading pathogens: Mycobacterium tuberculosis or avium, cytomegalovirus, cryptococcus, pneumocystis, herpes simplex, hepatitis B, human herpes virus 8.

Clinical Manifestations

Vary widely.  Only about 50% of patients will develop fever.  Often related to whatever the underlying infection is.  Onset is typically 12-45 days after initiation of HAART.

Management

Treat the infection, but recognizing that the timing is related to HAART, chemo, or other cause is key to management for the future.  There really is no prevention.  Anti-inflammatory agents such as corticosteroids or NSAIDs can be helpful in decreasing symptoms.

Outcome

Our patient ended up being diagnosed with severe sepsis caused by probable endocarditis.  Blood cultures grew out staph aureus.  She had a normal Echocardiogram 7 days before admission, and the day of admission had a thickened mechanical valve (no gross vegetation).  She may not have actually had IRIS, but I had discussed the patient with the hospitalist, who asked me then to call cardiology and infectious disease and he was the one who brought up the possibility.  I had never heard of it so I looked it up.  Patient was given antibiotics in the ED. She was admitted to the ICU and had a 7 day hospital stay and was discharged to a TCU.

Questions

1. What does IRIS stand for?

a.    Irritational Radiation Idiopathic Syndrome

b.    Immune Reconstitution Inflammatory Syndrome

c.    It Rules In Sepsis

d.    Immunologic Restoration  Iatrogenic Syndrome

      2. Which of the following is another example of a situation in which a patient can develop IRIS when not on HAART or HIV positive?

a.    Recovery of neutropenia after cytotoxic chemotherapy

b.    Initiation of corticosteroid therapy

c.    Bacterial superinfection

d.    Initiation of therapy for Hepatitis C

      3. Which of the following is NOT a sign or symptom of bacterial endocarditis?

a.    New Murmur

b.    Petechiae

c.    Koplik Spots

d.    Splinter Hemorrhages

      4. What percentage of patients develop fever with IRIS?

a.    5%

b.    25%

c.    50%

d.    80%

      5. Which of the following is NOT one of the diagnostic criteria for IRIS?

a.    Presence of clinical manifestations consistent with an inflammatory condition.

b.    Absence of drug-resistent infection, bacterial superinfection, drug allergy or adverse reaction, patient non-compliance, or reduced drug levels.

c.    Association between HAART initiation and onset of clinical features of illness.

d.    Positive IRIS antigen

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Answers

     B

     A

     C

     C

     D