Today’s intern morning report involved 93 year old woman who presented with altered mental status and syncope, found to have MRSA in her urine as well as blood and eventually diagnosed with MRSA endocarditis.

Important teach points regarding endocarditis:
-MRSA is NOT a usual organism found in the urine, even in the presence of an indwelling foley catheter. Anybody with staph aureus bacteriuria needs further work-up for another source, and bacteremia/endocarditis always needs to be evaluated.
-The sensitivity of TTE for detecting endocarditis is <80%, therefore if suspicion is high (especially in the case of MRSA bacteremia), a TEE is indicated.

Diagnosis of endocarditis is based upon the Duke criteria (2 major, 1 major + 3 minor or 5 minor):
Major- 1. Positive blood cultures (typical organism from 2 separate cultures or 3 cultures with a common skin contaminant organism) 2. Evidence of vegetation, abscess or prosthetic valve dehiscence or new valve regurgitation (change in murmur not sufficient)
Minor- 1. Risk factors (IVDU, prosthetic valve) 2. Fever ≥38 deg C 3. Vascular phenomena (septic emboli, pulmonary infarct, Janeway lesion, mycotic aneurysm) 4. Immunologic phenomena (+Rheumatoid factor, glomerulonephritis, osler nodes, roth spots) 5. Positive blood cultures not meeting major criteria or serologic evidence of infection

-Empiric therapy while awaiting cultures is vancomycin, gentamicin is not indicated. Rifampin can be added in the setting of prosthetic valve endocarditis.

For additional information, see the infective endocarditis handout, which is also posted under “Quick References”.

Thank you Edward Lin for teaching us all about endocarditis!

PGY3 Chris Foss presenting a very interesting case of a 34 year old male with no PMH who presented with fevers, vague GI symptoms and acute encephalopathy who was found to have fevers, pancytopenia, elevated liver enzymes and elevated ferritin. CT C/A/P revealed hepatosplenomegaly and diffuse lymphadenopathy concerning for lymphoma. Bone marrow biopsy did not show malignancy or evidence of hemophagocytosis. Rheumatologic and infectious work-up were negative, other than positive EBV DNA PCR. Based on patient’s clinical and laboratory findings there was high suspicion for Hemophagocytic Lymphohistiocytosis (HLH) and empiric treatment was initiated. The patient is currently pending a quantitative EBV DNA level and lymph node biopsy to determine his trigger for HLH.

HLH is a syndrome of excess immune activation and can be triggered by various events including infection, neoplasms and autoimmune diseases. It is a life-threatening condition and requires prompt recognition and initiation of therapy.

Diagnosis of HLH requires identification of an HLH associated gene mutation or five of eight of the following:
1. Fever
2. Splenomegaly
3. Peripheral blood cytopenias (at least two of: Hgb<9, Plt<100, ANC<1000)
4. Hypertriglyceridemia (Fasting>265) and/or hypofibrinogenemia (<150)
5. Evidence of hemophagocytosis (bone marrow, LN, liver)
6. Low/abset NK cell activity
7. Ferritin >500
8. Elevated soluble CD25

Pearls:
-A negative bone marrow biopsy does not rule out HLH. Studies have shown that marrow histologic findings do not reliably predict the probability of HLH.
-Important triggers for HLH include infections (viral infections more common such as EBV, CMV, HSV, HIV), malignancy (lymphomas/leukemias), and rheumatologic disorders.

Thank you Chris for doing a great job with such a complex patient and teaching us all about HLH!

Sherrie Yu presented an interesting case of PTHrP secreting squamous cell lung cancer! The patient presented with diffuse bone pain, leg weakness and constipation.

– When working up hypercalcemia, always check an albumin level. Ionized calcium level should be checked in specific conditions such as multiple myeloma.
– The first step in work up should include a PTH value to determine if the hypercalcemia is PTH mediated. PTH mediated processes include hyperparathyroidism and rarely ectopic PTH production (ovarian cancer). **Remember that familial hypocalciuric hypercalcemia can present with normal/high PTH as well.
– If PTH is low, need to consider checking PTHrP, 1,25-dihydroxyvitamin D, 25-hydroxyvitamin. 1,25-dihydroxyvitamin D can be elevated in granulomatous diseases such as sarcoidosis, tuberculosis as well as lymphomas.
– Hypercalcemia due to malignancy is due to PTHrP secretion, osteolytic metastases, 1,25-dihydroxyvitamin D, and ectopic PTH production.

Below is a flowchart to help you work up your hypercalcemic patients!