Thanks to Tom Franzon and Ben Manning for presenting two (different) patients who presented with subacute shortness of breath and were found to have diffuse groundglass opacities (GGOs) on chest CT and were ultimately diagnosed with HIV for the first time.
Along the way, we went through a diagnostic approach for diffuse ground glass opacities. Developing a differential for just ‘GGOs’ is a Herculean task, but creating a differential for diffuse GGOs (as opposed to scattered GGOs, particularly in association with some other consolidation) is actually much easier to do.
Here’s a table from a paper by Penn radiologist/wizard Wally Miller:
This man was ultimately diagnosed with PCP pneumonia.
A few key points about diagnostic testing related to HIV and opportunistic infections:
Beta-D-glucan has excellent sensitivity (~95%) and specificity (~70-80%) for the diagnosis of PCP; in a patient who truly has PCP, BDG levels will likely be >400-500
CD4 counts can decrease with periods of acute/critical illness, so the CD4% may be a more stable marker to follow in someone with HIV, as it shouldn’t change all that much
An absolute CD4 count >500 corresponds to a CD4% of >30%
An absolute CD4 count between 200-500 corresponds to a CD4% of 15 to 30%
An absolute CD4 count <200 cells/microL corresponds to a CD4% of <15%
Most of the time, non-HIV related low CD4 counts don’t predispose to opportunistic infections, with the exception of idiopathic CD4+ lymphopenia— patients with this condition behave similarly to HIV+ patients with low CD4 counts in terms of OI susceptibility, except that they don’t have HIV!
Legionella urine antigen tests only for Legionella pneumophila serovar 1, so as a whole it has about a 70% sensitivity
The histoplasma urine antigen is best in HIV+ patients with disseminated disease (95% sens); sensitivity is probably similar in non-HIV patients
It’s really not a great test for less severe pulmonary histo or chronic cavitary histo, especially in non-AIDS patients
It can be false positive with other endemic fungi (Blasto, coccidio, etc)
A brief note on IRIS
It represents ‘unmasking’ of an underlying, unrecognized infection as the immune system ‘reconstitutes’ itself while on ART
Many pathogens (TB, NTBMB, PCP, HBV, crypto) have been associated with IRIS, while others (ex: toxo) are rarely associated with it
Generally develops when pre-ART CD4 nadir <100, and generally develop within one week to a few months after initiation of ART (depending on the kind of infection, host characteristics, etc)
Thank you, Jesse Platt, for walking us through the complicated case of a 66 year old man with months of worsening dyspnea and hypoxia of unclear origin who was diagnosed with (very) severe pulmonary hypertension, and is thought to have either PVOD or pulmonary capillary hemangiomatosis (PCH)!
We went through the classification of pulmonary hypertension:
Suggested approach to etiologic workup of PH
Physical exam (look for clubbing, parasternal heave, S2, crackles on lung exam, signs of cirrhosis, etc)
Chest X-ray (look for venous congestion, prominent PA, ILD)
CT chest (looking for ILD, parenchymal lung disease, nodules, mosaic attenuation (what is that?) which may suggest areas of heterogenous blood flow or air trapping)
Transthoracic echo (with bubble/contrast): looking for intracardiac (early bubbles) or intrapulmonary (late bubbles), estimate of RV and PA pressures, signs of RV dilation or volume/pressure overload
Ventilation/perfusion (V/Q) scan: this is the gold standard for ruling out CTEPH. Remember that CTEPH doesn’t require a history of repeated PEs; it really represents a dysregulated healing response to vasoactive cytokines from even a single PE in the past!
Consider PFTs and nocturnal polysomnography (to rule out OSA)
Consider ABG (to confirm hypoxia, and also if concern for shunt physiology)
Consider blood testing for other causes of PH (HIV, ANA [only send dsDNA, RNP if ANA+ ), RF, ANCA)
Right heart catheterization: gold standard for diagnosing/confirming PH (defined as a mean PA pressure >25mm Hg)
Ultimately, this patient’s testing (RHC w/ severe pHTN, TTE w/ LVEF 60% but moderate RV dilation and late bubbles suggestive of pulmonary AVMs, CT chest w/ scattered basilar nodules with diffuse mosaic attenuation) suggested a diagnosis of PVOD vs PCH as the diagnosis.
In brief, PVOD is characterized by smooth muscle hypertrophy within pulmonary veins and venules, whereas PCH is marked by atypical capillary proliferation; both cause pulmonary hypertension, and can be difficult to differentiate from PH of other causes.
We learned that severe hypoxia (10L O2 in this case) is uncommon with most causes of PH, and should make you think of:
Large intracardiac/intrapulmonary shunt
See this table to see a comparison of PH, PVOD and PH:
Two final pearls
PVOD and PCH patients are at a higher risk of pulmonary edema with vasodilator therapy given their capillary hemodynamics
PASPs from echos are derived from the maximum tricuspid valve velocity; but this is reliant on good views on echo, and varies based on underlying comorbidities, etc. Generally TTE PASPs are thought to be off from RHC PASPs by about 10mm Hg (want more info?)
There are case reports of PCH being treated with doxycycline, which apparently has anti-angiogenic properties! (see #1 below)
Many thanks to Will Levine for walking us through an interesting case of a 58 year old woman with several days of chest tightness who was incidentally found to have multiple pulmonary nodules.
Along the way, we talked about the PERC (pulmonary embolism ruleout criteria), which can help rule out PE in low risk populations (ie populations with a low prevalence of PE, felt to be <15%).
The rule is really only validated for the ED (where the incidence of PE is likely low), but not the inpatient settings in which we usually practice.
We then got into a discussion of pulmonary nodules, and how several key features of them can help figure out the cause.
Metastases tend to favor the lower lobes (since they’re often hematogenously disseminated, and blood flow is greatest in gravity dependent areas)
Diseases like TB and certain pneumoconioses may favor the upper lobes (due to inhalation of the agent)
Perilymphatic or centrilobular distribution?
Large nodules (>~1cm) are more likely to be malignant
Most solid tumor metastases tend to be well demarcated, with the exception of those that tend to bleed (melanoma, thyroid, Kaposi’s and other vascular tumors, RCC, choriocarcinoma)
Fungal nodules are more likely to bleed and may have fuzzy borders (‘halo sign’)
Here’s a differential for multiple pulmonary nodules
And for those of you that were wondering about what the deal is with necrobiotic lung nodules in IBD, this may shed some light (or at least a faint glow).
Also thanks to James Chen (IR fellow) for speaking to us at intern report about some IR basics. Quick pearls:
Tunneled catheters (like a small bore central catheter, which is really just a PICC that’s tunneled) can be pulled at the bedside as long as they’re uncuffed. The cuff is a little band of material around the catheter which stimulates scar formation by the body and thus holds the catheter in place without needing sutures etc; if a catheter is cuffed, IR must be the one to pull it.
If you run into bleeding around a tunneled catheter, hold pressure at both the skin entry site AND the venotomy site (where the catheter actually enters the vein; see below)
Easy trick to figure out on CXR whether a catheter is tunneled or not: if it courses above the clavicle, it means it’s a tunneled line; if not, it’s non-tunneled
Singh B et al. Pulmonary embolism rule-out criteria (PERC) in pulmonary embolism–revisited: a systematic review and meta-analysis. Emerg Med J 2012. PMID 23038695
Hi everyone- we’re really happy to have a little topical guest contribution from recent Penn graduate Bill Fuller, who’s now living the primary care life in NYC. Take a look at his post about the new Lancet trial that studies the role of azithromycin in asthma, and check out his blog!
Azithromycin — it’s not just for chlamydia! Shockingly, the good people at Pfizer rejected my suggested slogan, but hey, their loss. Macrolide antibiotics have always occupied an odd spot in medicine, as anything that is killed by macrolides is also killed by strong language or an exceptionally stern glare. What I’m saying is, they’re not exactly the backbone of modern antimicrobial therapy.
But something weird and kind of wonderful has happens when you give them to patients with chronic obstructive pulmonary disease (COPD), and they have fewer exacerbations. Perhaps due to non-antibiotic effects, chronic daily azithro has been an approved treatment for severe COPD since a 2011 randomized controlled trial (RCT) demonstrated its ability to reduce the number of COPD exacerbations compared to placebo. While there have been a few trials of daily azithro in severe asthma previously, they have been mostly small and short-term, and have failed to demonstrate…