This morning we were lucky to be joined by Dr. Darcy Wooten, an amazing HIV Medicine attending and APD of the Infectious Disease Fellowship, to discuss one of her Owen clinic patients.
The 30-year old man with newly diagnosed HIV presented to our hospital with cough, fevers, chills, night sweats, decreased appetite, and recent weight loss. On admission, the patient had a CD4 count of 102 cell/uL and viral load of 185,000 copies/mL. The CXR revealed a diffuse micronodular/miliary pattern and CT showed upper lobe predominant diffuse ground glass opacities. Initially concerning for TB, the patient’s work-up was significant for elevated serum Coccidiodes IgG antibodies, positive cocci complement fixation with a 1:512 titer, and negative bone scan and spine computerized tomography. The patient was diagnosed with severe pulmonary coccidioidomycosis with presumed dissemination (based on the high titer).
The patient was treated with amphotericin B for severe cocci and discharged on fluconazole therapy (along with antiretroviral therapy and Bactrim prophylaxis). He could not tolerate the fluconazole and was switched to Posaconazole. The patient subsequently developed severe hypertension refractive to amlodipine, lisinopril, and hydrochlorothiazide. Work up demonstrated low levels of potassium, renin, and aldosterone. The patient was diagnosed with pseudohyperaldosteronism, taken off Posaconazole, and placed on itraconazole and spironolactone, leading to a resolution side effects. The mechanism behind pseudohyperaldosteronism is similar to that of licorice root extract, where steroid synthesis products directly activate mineralocorticoid receptors. Treatment is focused on cessation of Posaconazole and antagonism of the mineralocorticoid receptor with spironolactone.
This morning we discussed a case of 42-year-old man who presented to UCSD Hillcrest with a history of subacute cough and shortness of breath. Review of systems was additionally notable for subacute fevers and chills, night sweats, weight loss, and progressive generalized weakness. His sexual history was suspicious for potential undiagnosed HIV infection, and we created a differential of possible pulmonary disease in HIV+ patients by CD4 count. His CXR and elevated LDH and beta-D glucan (sensitive although not specific) were suspicious for PJP. The diagnosis was ultimately diagnosed by sputum silver stain, and we discussed the frequent need for bronchoscopy with BAL to obtain adequate sample. After initiation of treatment with TMP-SMX, the patient’s respiratory condition worsened, and we discussed the role of systemic steroids in PJP treatment. Thank you to Dr. Darcy Wooten from Infectious Disease, who guided us through the differential diagnosis and provided many relevant clinical pearls.
Today our amazing Med/Peds PGY3, Jack Strutner, led us through a case he saw in Mozambique at his time at Maputo General Hospital. His patient was a young man with HIV who came in with subacute diarrhea with profuse bloody bowel movements and a fever. He was found to be severely volume depleted and with an AKI on exam. We worked through our diagnostic schema and work-up of diarrhea in an HIV patient, focusing on infectious etiologies. Our expert discussant from Infectious Diseases, Dr. Stephen Rawlings, helped further flesh out our differential for these patients and discussed ARV side effects. We then discussed the differences in work-up approaches for patients in resource poor settings vs here in the US, with the main difference being more focus on stabilization and resuscitation with empiric antibiotics and less so on diagnostic tests. The patient unfortunately passed which we discovered is sadly a common scenario on a global scale, highlighting the importance of ongoing global efforts to improve water supply and sanitation in disease prevention.
Take away points:
1) Remember to take a thorough history regarding diarrhea onset, characteristics (volume, content, frequency) and associated symptoms
2) ARVs, particularly protease inhibitors, integrase inhibitors and Zidovudine (causing acute pancreatitis) may be the cause of diarrhea in some HIV patients
3) Diarrheal illness is still a leading cause of death worldwide, particularly in resource poor nations
Thank you again to Dr. Strutner for a thought provoking case, and to Dr. Rawlings for always providing great teaching! We hope to hear from our colleagues in Maputo sometime again soon!
Today at Owen conference, we dove into the primary literature by reading the ATLAS and FLAIR trials that just came out last week in the New England Journal of Medicine. These trials examined the efficacy of monthly injectable injections of cabotegravir/rilpivirine for treatment naïve patients (FLAIR) and patients already on ARVs (ATLAS), with both showing non-inferiority compared with a standard oral regimen. Our residents also learned about the concept of the “visual abstract”, which they then utilized beautifully to synthesize and demonstrate their understanding of the two trials! Dr. Daniel Lee provided us with insight about the novelty of the 2-drug regimen, anticipated challenges in implementation, and what we might expect to see in the near future.
Thanks Dr. Lee for his insights and to our residents for their creativity!
Take away points:
1) ARV regimens are trending toward two-drug regimens rather than the traditional three drug regimen (2 NRTIs + another ARV class).
2) The long-acting injectable regimen cabotegravir/rilpivirine has shown non-inferior efficacy compared with standard oral regimens. It requires viral suppression with an oral regimen first. The regimen is promising in its potential to improve medication adherence but presents logistical challenges in terms of readjusting clinic infrastructure and work-flow to optimize delivery.
3) Visual abstracts provide a visual summary of an article’s key findings in a shorter format. It can be a great way to improve exposure to a publication and invite individuals to read the full article!
Today, med/peds PGY-3 Kevin Yang presented a great case of a patient with subacute fatigue & weakness and recent falls found to have hyponatremia and relative hyperkalemia in the setting of vomiting. In the setting of HIV/AIDS (CD4 58, VL 10k), we acknowledged that the differential is very broad. However, the presentation suggested possible adrenal insufficiency, and the patient was quickly diagnosed with an AM cortisol <0.2. This allowed us the opportunity to review differentiation, between primary, secondary, and tertiary adrenal insufficiency, diagnostic work-up and next steps for this patient. Furthermore, his HIV/AIDS diagnosis prompted us to discuss adrenal dysfunction in this particular patient population. Adrenal insufficiency has historically been known as the most common endocrinopathy associated with HIV/AIDS, usually in the context of an opportunistic infection such as CMV or MAC. Patients with HIV/AIDS typically have higher cortisol levels than patients without HIV/AIDS, though many have subclinical adrenal dysfunction and lower reserve. Thank you to Dr. Gigi Blanchard for her insights into the case!
Don’t forget about non-HIV/AIDS diagnoses in patients with AIDS.
Use the cosyntropin test and ACTH level to diagnose and differentiate between primary and secondary adrenal insufficiency which have different etiologies and treatment.
Be aware of the effects of ARVs, particularly protease inhibitors, have on exogenous steroid use (even inhaled or nasal steroids!) and other metabolic processes leading to lipodystrophy, hyperglycemia, etc.
Today our excellent R2, Dr. Kevin Wang, presented a case of a middle aged transwoman who presented with lower extremity swelling and L groin pain who was found to have new onset heart failure and also generalized lymphadenopathy. We used this case to discuss a few issues surrounding HIV patients:
a) Heart failure: patients with HIV are more likely now to suffer and pass away from chronic medical conditions such as heart failure than from complications of HIV given the success of current anti-retroviral therapies. Patients with HIV have about a 3 fold increase risk of developing CAD and also heart failure, due to the pro-inflammatory state of their HIV, their increased likelihood of co-morbid tobacco and stimulant abuse, and the side effects of older ART, specifically protease inhibitors.
b) We were able to break into groups and then go over possible differentials for generalized lymphadenopathy, using the MIAMI mnemonic (provided by the AAFP, see figure above from 2016 article on work-up of generalized lymphadenopathy) as one diagnostic schema. Our patient was ultimately diagnosed with having DLBCL and had to get modified DA-R-EPOCH regimen given she could not get doxirubicin due to her pre-existing heart failure.
c) We also spent some time discussing the nuances of caring for our transgender patients and how we can work to create a welcoming, inclusive environment that would best build a therapeutic relationship.
Special thanks to our expert discussant, Infectious Disease fellow, Dr. Stephen Rawlings for sharing his expertise on these topics!
Transgender HIV patients are at greater risk of med nonadherence and inability to achieve viral suppression due to a number of psycho-social barriers and stigmas they face in the health care setting. To better understand their needs please read the following NEJM article: https://www.nejm.org/doi/full/10.1056/NEJMcp1903650
DLBCL is one of the most prevalent malignancies in HIV patients as HIV infection can lead to chronic antigen stimulation and polyclonal B-call expansion, promoting emergence of monclonal B-cell lines. Remember to get excisional biopsies if possible (or multiple cores) in order to best preserve the lymph node architecture.
Today, RACE track superstar Masha Barsky presented a fascinating case of a patient in their 40s with newly diagnosed HIV/AIDS (CD4 27, VL 126K) who had 2 weeks of dry cough and progressive shortness of breath. We went through a great diagnostic schema of approaching respiratory disease in an HIV/AIDS patient, including both HIV/AIDS-specific diagnoses and diagnoses pertinent to immunocompetent and immunocompromised patients. The patient underwent a multitude of tests which revealed a positive AFB sputum and MTB-PCR, as well as chest imaging concerning for miliary TB! We then reviewed miliary TB, including distinctions between pulmonary vs miliary (disseminated) TB and additional work-up needed to evaluate for extrapulmonary involvement. Thank you to our expert discussant, Dr. Jocelyn Keehner, for her insights!
Use a diagnostic schema for an HIV patient with respiratory symptoms that includes bacterial/fungal/parasitic/viral infectious causes as well as several non-infectious causes – consider HIV/AIDS-specific diagnoses and the CD4 counts associated with them, but don’t forget diagnoses that can occur in anyone as well!
Evaluate carefully for extra-pulmonary involvement in miliary TB, including dedicated imaging for any suspected organ abnormality and a lumbar puncture for any neurologic symptoms.
Pulmonary TB can occur in HIV/AIDS patients with any CD4 count, while miliary TB is more likely to occur in HIV/AIDS patients with CD4 count <100-200.
Today one of our amazing Resident as Clinician Educator (RACE) track residents Dr. Maggie Kozman led us through a fascinating case of a young woman with HIV and priorly diagnosed disseminated MAC affecting the liver who presents with diffuse abdominal pain and fevers after restarting ARVs for 6 weeks. We learned that she had markedly elevated alkaline phosphatase and GGT levels and diffuse abdominal and pelvic lymphadenopathy.
Dr. Kozman lead us through a diagnostic schema for an HIV patient coming in with fever and abdominal pain, with the help of our expert Owen discussant, Dr. Jill Blumenthal and taught us about HIV cholangiopathy. Ultimately, we learned that the patient had likely IRIS from MAC infection in the setting of her recently restarted ARVs, as her CD4 count had a marked recovery with a corresponding significant drop in the viral load.
Thank Dr. Kozman for that interesting case and excellent teaching, and Dr. Blumenthal for your additional clinical pearls!
1) When thinking of the differential for fever and focal infectious symptoms consider the categories of 1) common infections 2) opportunistic infectious and 3) IRIS.
2) HIV/AIDs cholangiopathy is a cause of secondary biliary sclerosis in HIV patients. Patients who have had infections with cryptosporium or CMV may be more at risk. They can present with fever, RUQ pain and diarrhea and can have a markedly elevated AP and ggt, as well as biliary strictures visualized on MRCP.
3) IRIS or immune reconstitution syndrome is a diagnosis of exclusion in HIV patients presenting with fever, particularly those with an initial low CD4 count and high VL who have a significant response and immune recovery after restarting ARVs. Infectious etiologies should be ruled out prior to patients being diagnosed with IRIS and getting treated with steroids.
Today our excellent R2 Dr. Mia Awan lead us through an interesting case of a middle aged man with HIV/AIDS who presented with pain with swallowing. We first went through the differential of what that might mean in terms of odynophagia at the oropharygeal level vs esophageal level, how it is important to distinguish that from the discomfort from dysphagia. We then learned that this patient had thrush that he was being treated for but despite this had worsening pain eating solids and then liquid and had lost 30 lbs in the last month. He was ultimately found to have refractory candidiasis with concern for esophagitis but also on blood cultures and throat swabs to have disseminated gonococcal infection! Special thanks to our expert discussant, Owen attending Dr. Amutha Rajagopal for your additional insight!
Teaching Points: 1. Don’t forget to be systematic when evaluating the complain of pain while eating. Make sure you consider both oropharyngeal and esophageal causes, including infections (dental abscesses, HSV, EBV, CMV, gc/chlamydia, HPV, trauma, malignancy, autoimmune/inflammatory processes). 2. Remember to triple site swab for gonorrhea and chlamydia in individuals who engage in oral, penetrative and receptive anal sex. 3. Disseminated gonorrhea may present asymptomatically, as a triad of cutaneous lesions, polyathralgias and tenosynovitis, or as septic/purulent arthritis. Treat disseminated gonorrhea with IM or IV ceftriaxone for about 7 days, extending the course up to 14 days for purulent arthritis. You should empirically treat for chlamydia as well in high risk patients with 1 gm of azithromycin.
Today stellar R2 Sai Vanam walked us through a case of a young woman with untreated HIV who has had recurrent admissions for multiple opportunistic infections. She unfortunately had not been started out of worries of med non-adherence given her homelessness, untreated mental health conditions and ongoing substance use and lack of outpatient follow-up. We used this as a launching point for discussing these barriers our patients may encounter to adherence on antiretroviral therapy and how we can try and address them. Our expert discussant from the UCSD Owen team, Dr. Maile Young-Karris informed us of the resources we have available and upcoming advancements that may be help address some of these barriers.
We next learned that our patient had a history of reportedly treated TB, and had been prescribed medications during her last hospitalization empirically for PJP and also for disseminated cryptoccoccus. We then discussed when to be concerned about immune reconstitution syndrome, which infections may put you more at risk, and the pathophysiologic mechanism involved.
We also highlighted what pulmonary cryptoccocus infection might appear like and why this patient’s chest x-ray and symptoms were not as suggestive. Remember that like most fungal infections, you might expect more nodular/focal opacities and lymphadenopathy on exam. You should also rule out CNS involvement for any immunocompromised patient with cryptoccocemia. This patient ultimately got continued on empiric PJP treatment as well as for cryptococcemia, as well as CAP.
Remember to assess for barriers to drug adherence such as drug costs, patient’s understanding of their disease process and desire to start treatment, concomitant untreated mental health or substance abuse conditions, and homelessness when initiating ARVs so that patients may be adequately connected to resources.
IRIS is more likely to occur in patients with very high HIV viral burden and extremely suppressed immune systems prior to initiating ARVs. It’s time frame is variable from 1 week to up to a year depending on the rate of immune recovery and presence of infections that are more likely to trigger a response. Be wary of initiating ARV in patients with meningitis as the degree of inflammation may dangerously cause cerebral edema and raise ICPs.
Patients with HIV are just as likely to get infections from organisms such as strep/staph causing CAP so keep those on your differential in addition to the rarer opportunistic infections.
Thank you Sai for a thought-provoking case, and to Dr. Young, for your insight into caring for our HIV patients!