MTC 7/29: Urine Trouble – Causes of RPGN

Rapidly progressive glomerulonephritis can be a confusing topic. Thankfully, Dr. Margaret Ivanov, one of our awesome nephrologists, dropped by our Hillcrest morning report today and offered some clinical pearls. We discussed the case of a middle-aged man with no history of renal disease who presented with an elevated serum creatinine to the mid-5’s. He has no significant medical history and takes no medications. His urinalysis revealed significant proteinuria and hematuria. Serum studies are positive for ANA and anti-dsDNA, and a renal biopsy showed thrombotic microangiopathy superimposed on a background of class IV lupus nephritis.

In a patient with new renal impairment, you should always ask about medication use, urinary symptoms, and other associated symptoms. Constitutional, mucosal, respiratory, GI, neurologic, hematologic, and dermatologic signs/symptoms may suggest the presence of an underlying disorder. Be sure to also do a good volume assessment to help determine if the patient requires diuresis and/or renal replacement therapy.

A urinalysis is an important first step in the evaluation of AKI. RPGN is a clinical syndrome characterized by rapid loss of renal function (over days or weeks) and a nephritic UA (hematuria with or without proteinuria). Urine microscopy will reveal RBC casts and dysmorphic RBCs. Dr. Ivanov pointed out that the automated process used to result UAs will not disclose the presence of RBC, WBC, and other casts and that urine microscopy will have to be done separately.

We then talked about the workup of RPGN (see below). These studies are typically sent in parallel because the etiology of RPGN cannot be reliably determined based on history and exam alone. (Many of these studies are send-outs and may take days to over a week to result.) Reasons to pursue a renal biopsy include unexplained AKI and an active urinary sediment. The classic pathologic finding in RPGN is crescentic glomerulonephritis. Light microscopy, electron microscopy, and immunofluorescence can help identify the cause of the RPGN. In some cases, multiple processes may be seen on renal biopsy. The biopsy also helps inform treatment and prognosis.

Key Learning Points:

  1. RPGN is a clinical syndrome characterized by a rapid loss of renal function (typically over days/weeks) and nephritic syndrome (hypertension, hematuria, variable proteinuria, dysmorphic RBCs, RBC casts).
  2. The classic pathologic finding is cellular crescent formation in the majority of examined glomeruli due to fibrin deposition and cell proliferation (“crescentic glomerulonephritis”).
  3. A renal biopsy is generally indicated in patients presenting with rapidly progressive glomerulonephritis to ascertain the etiology, determine its chronicity, and inform patient prognosis.

Thank you, Dr. Ivanov, for joining us today!

Medical Spanish Word of the Day: (el) análisis de orina = urinalysis

MTC 7/26: Don’t let your fear of syphilis management “spiro” out of control

Syphilis testing and management can be a confusing topic! That’s why we were lucky to have been joined by ID specialist extraordinaire, Dr. Amutha Rajagopal, this morning when we discussed a case of ocular and neurosyphilis. We reviewed the case of a middle-aged man who presented with subacute monocular vision loss and was found to have posterior placoid retinopathy consistent with ocular syphilis. CSF studies showed a lymphocyte-predominant pleocytosis and an elevated protein level. CSF VDRL was also reactive. He was treated with IV aqueous crystalline penicillin for 14 days.

Diagnosis: While darkfield microscopy is still the gold standard, it is rarely done in practice. Instead, a presumptive diagnosis can be made with a positive treponemal test AND a positive nontreponemal test. Treponemal tests (e.g., CIA/EIA, FTA-ABS, TP-PA) detect antibody response to Treponema pallidum and are nearly 100% specific; they are qualitative and usually remain positive for life after an infection. Nontreponemal tests (e.g., RPR, VDRL) detect antibody response to cellular fragments (e.g., cardiolipin) released as a result of cell damage from syphilis, so false positives are not uncommon. Nontreponemal tests are qualitative and can be used to track disease activity and treatment response. Due to the prevalence of HIV coinfection, don’t forget to test for HIV!

Here at UCSD, we use the “reverse algorithm”: we screen using a treponemal test (chemiluminescence assay), and positive tests are reflexed to a nontreponemal test (RPR). Discordant results (i.e., reactive CIA and nonreactive RPR) requires adjudication with a different treponemal test (e.g., TP-PA). Using the results of these tests and a thorough history and exam (see below), the patient’s infection status can be ascertained.

Treatment: Treatment of syphilis depends on the stage. Primary, secondary, and early latent syphilis (i.e., infection generally acquired in the past year) are treated with a single dose of IM benzathine penicillin G 2.4 million units. Late latent and tertiary syphilis (i.e., infection acquired >1 year ago or duration of infection unknown) are treated with 3 weekly doses of IM benzathine penicillin G 2.4 million units. Neurosyphilis, ocular syphilis, and otosyphilis can occur at any time and are treated with IV aqueous crystalline penicillin G 3-4 million units every 4 hours for 10-14 days.

Remember: CSF VDRL is poorly sensitive (as low as 27%), so a negative test does not exclude neurosyphilis! If the clinical syndrome and CSF studies are otherwise compatible with neurosyphilis, treat with IV penicillin!

Key Learning Points:

  1. To diagnose syphilis, treponemal and nontreponemal tests must both be reactive.
  2. Neurosyphilis can occur at any time and is treated with IV penicillin for 10-14 days.
  3. A negative CSF VDRL does NOT rule out neurosyphilis. Use the patient’s clinical syndrome and the results of other CSF studies to guide you.
  4. HIV coinfection is common in individuals diagnosed with syphilis.

Helpful Link: 2021 STI Treatment Guidelines (CDC, released 7/23/21)

Thank you so much to Dr. Rajagopal for being part of this awesome morning report!

Medical Spanish Word of the Day: la sífilis = syphilis

MTC 7/19: “Leuk” out for these causes of an elevated white count!

Today, at our inaugural Hillcrest Primary Care Morning Report, we discussed the case of an elderly woman who presented with night sweats and splenomegaly and was found to have a significant leukocytosis. A peripheral blood smear revealed increased bands, metamyelocytes, myelocytes, and basophils. A BCR/ABL1 PCR was sent and returned positive, confirming the diagnosis of chronic myelogenous leukemia. She improved with initiation of imatinib.

With the help of our primary care expert, Dr. Lawrence Ma, a proud alumnus of the residency program, we talked about the most common etiologies of leukocytosis in the outpatient setting. Non-malignant causes of leukocytosis include stress (e.g., trauma), exercise, smoking, medications, acute/chronic infection, chronic inflammation, bone marrow activation, and asplenia. Malignant causes of leukocytosis include chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), other myeloproliferative/lymphoproliferative disorders, and various solid tumors.

The peripheral blood smear can offer important diagnostic clues. At UCSD and the VA, you can digitally view blood smears using CellaVision. The appearance of blasts should raise concern for an acute leukemia, whereas an increase in more mature blood cells of the myeloid or lymphoid lineage could signal the presence of CML or CLL, respectively. As Dr. Ma pointed out, the decision to refer a patient to Hematology/Oncology is contingent upon a number of factors, including severity/duration of leukocytosis, B symptoms (fevers, night sweats, weight loss), hepatosplenomegaly, lymphadenopathy, bleeding, bruising, and petechiae. Presence of blasts, other immature forms, increased basophils, monomorphic lymphocytosis, and other cell line abnormalities are all suggestive of a hematologic disorder.

Remember, CML is a diagnosis that any primary care physician can make! Classified as a myeloproliferative neoplasm, CML is associated with the t(9;22) translocation (Philadelphia chromosome) and BCR/ABL1 fusion. Diagnosis is confirmed by FISH (for the translocation) and/or PCR (for the BCR/ABL1 fusion transcript). Treatment is with BCR/ABL1-specific tyrosine kinase inhibitors, which include imatinib and dasatinib.

Thank you, Dr. Ma, for everything you do for your patients and for being part of UCSDIM history!

Medical Spanish Word of the Day: el bazo = spleen

MTC 7/12: Don’t be pH’ooled by a normal bicarb!

Today during Hillcrest morning report, Dr. Randall Blankers, one of our phenomenal PGY-2’s, shared the case of a middle-aged man with uncontrolled type 2 diabetes on insulin and SGLT-2 inhibitors who presented with acute onset of vomiting and diffuse abdominal pain. He was found to have mild hyperglycemia, a combined ketoacidosis and metabolic alkalosis, and an acute kidney injury and was ultimately diagnosed with euglycemic diabetic ketoacidosis (eDKA). Because of the patient’s combined ketoacidosis and metabolic alkalosis from profuse vomiting, his serum bicarbonate and venous pH were both within normal limits, which initially obfuscated the patient’s underlying diagnosis.

With the help of our amazing endocrinologist, Dr. Kristen Kulasa, we discussed the pathophysiology of eDKA in the setting of SGLT-2 inhibitor use, which involves glycosuria, decreased insulin secretion, increased counterregulatory hormones, and increased ketogenesis. We also reviewed other benefits and complications of SGLT-2 inhibitor use. Patients on SGLT-2 inhibitors should be counseled on “sick day” rules, or when their SGLT-2 inhibitor should be held.

Thank you, Dr. Kulasa and Dr. Blankers, for sharing this illuminating case!

Medical Spanish Word of the Day: el goteo (o la infusión) de insulina = insulin drip

MTC 7/8: Mixing things up with some hematology

All hematology cases are exciting, but this morning at Hillcrest, we talked about an EXTRA fascinating case of an elderly gentleman who presented with large intramuscular hematomas and was found to have factor VIII inhibitors.

Our amazing hematologist, Dr. Jenny Zhou, joined us remotely from the UCSD Hemophilia and Thrombosis Treatment Center. We used this case to discuss important historical and exam features that help distinguish thrombocytopenia (or platelet dysfunction) from coagulopathy (clotting factor deficiency or inhibitor formation). Personal and family history of bleeding are important clues that help determine whether the disorder is inherited or acquired. We concluded that platelet problems are prone to producing petechiae and mucocutaneous bleeding, whereas coagulopathies can cause considerable bleeding into deep tissues (e.g., muscles, joints). We took a moment to review the coagulation cascade. The differential for bleeding diathesis will depend on whether PT/INR, PTT, or both are elevated (see Slide 2). We also discussed the role of a mixing study, which helps us distinguish between factor deficiency and inhibitor activity.

Finally, we would like to remind everyone that much of the information we covered today is also available in your handbook. You can find an UPDATED version of the handbook here. For instance, some useful diagrams related to today’s topic can be found on pages 118-119 of the updated handbook. Thank you, Dr. Zhou, for joining us today!

Medical Spanish Word of the Day: la hemorragia, el sangrado = bleeding

MTC 6/28: SIADH – When they (serum Na/Osm) go low, U (Na/Osm) go high

During the new interns’ very first Hillcrest morning report today, we covered the quintessential medicine topic of hyponatremia. We shared the case of a frail elderly woman with a history of diffuse large B-cell lymphoma who presented with hyponatremia of subacute onset, down to a sodium of 122. She had nausea, vomiting, and generalized weakness and was admitted for treatment of her hyponatremia. Laboratory studies–including a low serum osmolality, a high urine sodium, and a urine sodium–were consistent with SIADH (syndrome of inappropriate antidiuretic hormone secretion). She was ultimately found to have a recurrence of her lymphoma affecting the hypothalamus, thought to be the cause of her SIADH. She was started on fluid restriction and urea.

We discussed one diagnostic algorithm for hyponatremia. The first step is to confirm that the hyponatremia is hypotonic (by measuring the serum osmolality) and not related to a laboratory error/artifact or the presence of another osmolyte (classically glucose). Then, measure the urine osmolality to determine whether ADH is the cause of hyponatremia. If urine osmolality is low (typically below 100-200), the process is ADH-independent; otherwise, the process is ADH-dependent (see diagram below). When the volume status is not apparent, the urine sodium can be used as a guide to determine whether the effective circulating volume is reduced (as in hypovolemic and most hypervolemic states), but keep in mind that diuretics can elevate the urine sodium and cloud the picture.

Our stellar nephrologist, Dr. Tyler Woodell, then talked us through the management of SIADH. If hyponatremia is severe and associated with significant symptoms, hypertonic saline (e.g., 100-150 mL of 3% NaCl repeated up to 2-3 times) can be given. Recall that isotonic fluids can in fact worsen hyponatremia in the setting of SIADH. Fluid restriction is the mainstay of SIADH treatment, but in some cases, additional solutes, in the form of salt tablets or urea packets, may be required. Our patient improved with treatment and was discharged with plans for outpatient treatment of her lymphoma.

Thank you to Dr. Woodell for being part of this memorable morning report!

Medical Spanish Word of the Day: el sodio = sodium

(Bonus: el potasio = potassium, el calcio = calcium, el magnesio = magnesium)

MTC 6/24: Take your VITAMINS to ward off dementia!

Dr. Priya Sharma, one of our phenomenal senior residents, presented a “hot case” this morning: a middle-aged man with rapidly progressive dementia characterized by language deficits, behavioral changes, paranoia/obsessions, and tremors that evolved over the course of several months. After a initial workup ruled out reversible medical etiologies, the patient was ultimately transferred to the Neurology service for further workup.

We were incredibly fortunate to have been joined by Dr. David Coughlin, our movement disorder specialist extraordinaire, who reviewed key historical features and exam findings while evaluating a rapidly progressive dementia syndrome. It is important to obtain collateral information, assess the patient’s psychosocial milieu, and rule out any contribution from delirium. The differential diagnosis for rapidly progressive dementia is quite broad and includes vascular, infectious, toxic-metabolic, autoimmune, malignant, iatrogenic, neurodegenerative, and systemic/structural/seizure-related causes. If initial laboratory and imaging studies fail to disclose an etiology, additional serum/CSF, advanced imaging, and electrographic studies should be considered.

Several studies are still outstanding for our patient. The working differential includes Creutzfeldt-Jakob disease, autoimmune encephalitis (e.g., limbic encephalitis, anti-LGI1 encephalitis), and an atypical presentation of frontotemporal dementia. We anticipate some of these studies will return in the next few weeks. Stay tuned for an update!

Thank you to Dr. David Coughlin and the Neurology team for participating in this multidisciplinary morning report and for taking wonderful care of this patient.

Medical Spanish Word of the Day: el cerebro = brain

MTC 6/21: When stones have the gall to attack

This morning, Dr. Lainey Flatow-Trujillo, one of our amazing R2s, shared with us the case of a young woman with a history of biliary colic who presented with 5 days of epigastric pain radiating to the back and an initial lipase > 3000. The group quickly arrived at the diagnosis of gallstone pancreatitis.

We then spent some time delving into the management of acute pancreatitis. Because gallstones are the most common cause, an abdominal US is required. Patients in whom the diagnosis is unclear or whose symptoms persist may benefit from a CT with contrast. In patients without gallstones or heavy alcohol use, other etiologies, such as hypertriglyceridemia, hypercalcemia, and medications, should be investigated. Other less common causes include post-ERCP, traumatic, infectious, and autoimmune pancreatitis.

The key to management is aggressive hydration (e.g., 4 liters in the first 24 hours). Patients are often volume-depleted, so a bolus followed by a continuous infusion (e.g., 2 L up front followed by 100 mL/hr for 20 hr) is reasonable. IV analgesics are indicated. Oral (or at least parenteral) feeding should be started as soon as the patient is able to tolerate it, as this has been shown to decrease the risk of complications such as infection.

ERCP, a therapeutic procedure, is indicated when there is concern for ascending cholangitis or persistent obstruction. Otherwise, MRCP or EUS can be considered (not required for mild episodes). Laparoscopic cholecystectomy is recommended during the same admission to reduce the risk of recurrence for mild cases of gallstone pancreatitis. Debridement of necrosis, if present, should be avoided unless the patient is unstable.

Thank you to Dr. Wilson Kwong, our expert discussant, for offering his clinical pearls!

Medical Spanish Word of the Day: la piedra (colloquial), el cálculo (formal) = stone

Tuesday Owen Report at Hillcrest

Today at Owen Report, one of our stellar R2’s, Anna Ter-Zakarian, presented a case of a patient she recently cared for in the ICU. He had advanced HIV with a CD 4 count of 3 (!) and presented with acute shortness of breath, tachypnea and hypoxemia requiring 60 L of 100% oxygen. Chest radiograph revealed diffuse opacifications and blood gas had markedly elevated A-a gradient. A broad infectious work-up was sent and the patient ended up having both Pneumocystis Jiroveci and Cryptococcal pneumonias. 

Due to the patient’s acute symptoms onset (rather than subacute and gradual as would be expected with these organisms), and recent re-initiation of ART, there was high concern for Immune Reconstitution Inflammatory Syndrome (IRIS). We discussed how IRIS “unmasks” occult and asymptomatic opportunistic infections and why it is important to rule out cryptococcal meningitis. We also discussed that some patients may present with “paradoxical” worsening of inflammatory symptoms even as their OIs are being treated. We also learned that IRIS can unmask undiagnosed autoimmune conditions. Risk factors for IRIS include low CD4 count and high viral loads. The treatment includes steroids as well as ongoing treatment of any underlying OIs and (usually) continuation of ART. 

Thank you to Dr. Laura Bamford for being our expert discussant and sharing many valuable pearls with our audience!  

VA Morning Report 4/27 – Cold Agglutinin Disease in B-cell ALL

This morning at the VA our stellar Med/Peds senior, Dr. Alexis Quade, presented a case of a 40-year-old man who came into the hospital with subacute fatigue, weakness and dyspnea. The most striking finding on his initial work up was the CBC: Hgb 4.2, Plts 116, and WBC 45 with 88% lymphocytes on his differential. He discussed further work-up of his acute anemia, including studies to evaluate hemolysis. The patient’s peripheral smear had marked red blood cell agglutination into irregular clumps. The blood bank then called the team with an urgent finding: the patient’s Direct Coombs test was C3 positive, IgG negate. He discussed the difference between “warm” (IgG) and “cold” (IgM-complement) autoimmune hemolytic anemia. We were lucky to have our expert discussant, Dr. Soo Park from hematology/oncology, on site to help us navigate testing and its implications. Some of the key take home points about cold agglutinin disease:

  • Causes autoimmune hemolytic anemia when IgM recognize antigens on RBCs at temps below normal core body temp cause agglutination and extravascular, complement-mediated hemolysis
  • Can be secondary to underlying disease (e.g. infection, malignancy)
  • Treatment: transfusion (warmed), avoid cold environment, treat underlying disease, plasmapheresis (severe disease)

Additional work up with flow cytometry and bone marrow biopsy revealed that the patient had acute B-cell lymphoblastic leukemia. This disease has a bimodal distribution and usually presents in children or those over 60 years old. It is important to test for the Philadelphia chromosome translocation as this has major impact on the treatment regimen. Unfortunately, our patient was Ph – and therefore not a candidate for tyrosine kinase inhibitor therapy. He is instead being treated with CALGB chemo regimen, including intrathecal methotrexate and cytarabine. We discussed the role of pre-treatment sperm banking prior to initiation for fertility presentation, as well as the need for intrathecal prophylaxis.

Thank you to Dr. Park for all her clinical pearls as we worked through this complex and interesting case.