Chiefs’ Inquiry Corner – 3/28/22

March 28, 2022

Chief residents of the NYU Langone Internal Medicine Residency give quick-and-easy, evidence-based answers to interesting questions posed by house staff, both in their clinics and on the wards.

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 We typically think of ordering a B12 level as an evaluation for vitamin B12 deficiency, but incidental elevations can also be detected. Elevated B12 is typically defined as >1000 ng/L, and it has been associated with various diseases – including liver pathology, myeloid blood malignancies, chronic renal failure, and inflammatory diseases. Population-based studies have shown an association between elevated B12 and solid organ malignancy as well. One study recently looked at individuals with elevated B12 levels at baseline (excluding those who had another likely etiology, such as those mentioned above). They followed these individuals over time, measuring a second B12 level and observing cancer-free survival between groups that had either the presence or absence of persistently elevated levels at the second measurement. They found that a persistently elevated B12 >1000 was associated with occurrence of a solid cancer (HR 5.90) during their 60 month follow-up. Incident diagnoses of chronic liver disease and myeloid blood malignancies were also made. These findings all raise questions regarding clinical surveillance of these individuals and further reflex screening studies if patients have observed persistently elevated levels in our clinical practice. The mechanism itself is not yet understood – some have suggested the development of solid cancer may be secondary to the elevated B12, though most feel that the cancers are either directly or indirectly responsible for the elevated levels. Proposed mechanisms include secretion of a tumor mediator that increases bioavailability to promote nucleic acid synthesis by cancer cells or release of haptocorrins (transcobalamins that bind B12) by cells involved in the anti-tumor response.

References: Persistent elevation of plasma vitamin B12 is strongly associated with solid cancer
 Patients with a clinical syndrome compatible with GAS pharyngitis who lack symptoms of a respiratory viral syndrome should have microbiologic testing. We assess the pre-test probability of GAS in algorithmic fashion using the Centor criteria: 1) presence of tonsillar exudates, 2) presence of tender anterior cervical lymphadenopathy, 3) fever, and 4) absence of cough. We then test further using a sensitive rapid antigen detection test (RADT) in patients with ≥3 Centor criteria. For most adults with suspected GAS pharyngitis, RADT alone is sufficient for diagnosis, and follow-up throat culture is not needed. If the RADT is positive, antibiotic treatment is recommended. The specificity of most available RADTs is high, ranging from approximately 88 to 99 percent. Thus, in patients with suspected GAS pharyngitis, false positives are uncommon. If the RADT is negative, for most adults additional GAS testing isn’t needed and patients can remain untreated; though with a test sensitivity ranging from 77-92%, this can lead to some false negatives without confirmatory throat culture. Studies have shown that the incidence of complications, such as acute rheumatic fever, is generally low in adults and observational data suggest that using an RADT without culture confirmation is not associated with increased complications. How do we generally approach this in our own practice settings? Typically, it’s easy to swab someone and collect both specimens concurrently. But if a patient comes in from an outside setting having 4/4 Centor criteria and only a negative RADT, consider getting ordering a throat culture particularly if they have any of the following features: 1. higher risk for severe infection or complications from GAS pharyngitis (eg, patients with a history of acute rheumatic fever or immunocompromising conditions 2. close contact with individuals at high risk for complications (eg, patients caring for infants or living with immunocompromised individuals) 3. young adult patients living in college dormitories or other settings where the prevalence of GAS pharyngitis is higher than in the general adult population 4. lives in areas where acute rheumatic fever is endemic or where there are active acute rheumatic fever epidemics. Culture generally takes about 24 to 48 hours. The sensitivity of throat culture is between 90 and 95 percent, and specificity is between 95 and 99 percent. You can wait for the culture to result without treating empirically as short delays have not been shown to lead to higher rates of complication.

References: Rapid antigen detection test for group A streptococcus in children with pharyngitis
 Consideration of splenectomy is usually limited to patients who do not have a response to or cannot receive standard medical therapies because of side effects and in whom at least a year has passed since diagnosis (to allow for remission to occur). The frequency of splenectomy has decreased substantially during the past two decades. Laparoscopic splenectomy is associated with lower postoperative mortality and morbidity and a shorter recovery time than open splenectomy. Partial splenic artery embolization appears to be an area of interest, though studies have been emerging over the last few years and it is not yet the standard of care. Initial data seems to suggest this may offer long-term, durable response at 1 year in some patient populations.

References: Long-term efficacy of partial splenic embolization for the treatment of steroid-resistant chronic immune thrombocytopenia