Today at report we were joined by radiology to review some cases with interesting imaging. Here are some clinical pearls we discussed related to a couple of the cases:
Cystic Lung Disease
True cystic lung disease is rare! Other pathologic processes that may resemble cystic lung disease on imaging include:
- emphysema, particularly bullous disease
- cavitary lesions
Below are some key identifying characteristics of four relatively more common cystic lung diseases:
- Lymphangioleiomyomatosis (LAM)
- seen almost exclusively in females; there have been case reports in males with tuberous sclerosis complex (TSC)
- symptom onset usually age 20s-30s
- can be associated with TSC; signs/symptoms include cutaneous angiofibromas, intellectual disability, seizures, ash-leaf spots, and shagreen patches
- angioleiomyomas are also commonly found in kidneys
- may be associated with chylous effusions (pleural effusion with most cystic lung diseases is rare)
- radiology findings include diffuse homogenous cysts
- Pulmonary Langerhan’s Cell Histiocytosis (LCH)
- slight female predominance, symptom onset usually age 20s-40s
- seen almost exclusively in current or former smokers
- extrapulmonary manifestations are present in approximately 20% and include DI and cystic bone lesions
- radiology findings progress from nodules to uneven and bizarrely shaped cysts with sparing of the costophrenic angles
- Birt-Hogg-Dube Syndrome
- autosomal dominant inheritance, symptom onset usually age 30s-40s
- cutaneous fibrofolliculomas, common in midface
- associated with renal neoplasms
- radiology findings include lentiform/elliptical cysts especially basilar and abutting the mediastinum and pleura
- Lymphoid Interstitial Pneumonia (LIP)
- associated with auto-immune diseases or immunodeficiency; most strongly associated with Sjogren’s disease (present in 25-50%)
- radiology findings include few thin-walled cysts in areas of ground glass opacity, may have internal septae or nodules
A pneumo ex-vacuo is a air between the parietal and visceral pleura that is present when a lung cannot expand to fill this space following thoracentesis. This may happen for one of two reasons:
- Lung entrapment: the lung cannot expand due to active disease that restricts the intrinsic elastic recoil of the lung or visceral pleura. This can occur due to malignancy, infection, or inflammatory processes.
- Trapped lung: the visceral pleura can develop collagenous or fibrous rind (scar) from a remote or chronic inflammatory process that “traps” the lung and prevents it from expanding. This can occur due to history of inflammatory insult to the pleural such as infection, hemothorax, thoracic surgery or can result from chronic pleural effusion.
The VA team conquered an interesting case of a 22 yo F who presented to the outpatient setting with chronic urticaria and “recurrent anaphylaxis.” She was a distance runner participating in multiple marathons. After a 13 mile run she developed SOB, hives, diarrhea and was rushed to the hospital for treatment.
We reviewed anaphylaxis how to clinically diagnose anaphylaxis:
2+ organ systems involved post exposure – skin/mucosa, respiratory, hypotension, GI
Hypotension (as defined as SBP<90 or >30% decrease in SBP) following exposure to a KNOWN allergen
We also discussed the initial treatment algorithm including IM epi, benadryl, ranitidine, steroids — stressing the importance that only IM epinephrine has mortality benefit.
Our patient has resolution of the anaphylactic episode which was the second she’d had that year, but had persistent recurrence hives over the last year.
We discussed the difference in differential between urticaria + angioedema and angioedema ALONE — if angioedema WITHOUT urticaria and reviewed the work up for chronic urticaria (lasting >6 weeks) including: CBC, ESR/CRP, TSH and ANA (2). We also discussed that lesions lasting for >48 hours require biopsy. We reviewed an approach to chronic urticaria as outlined in the imaging below.
After extensive testing, including inducing her hives with an exercise tolerance test, our patient was found to have exercise induced anaphylaxis NOT associated with food. We discussed overall treatment of urticaria with ceterizine, avoidance of NSAIDs/ASA, H2 blocker, and avoidance of her triggers. Because exercise induced anaphylaxis can be triggered by various amounts of exertion, she was counseled to always have her IM Epi on hand and to only exercise with a friend (3).
- Hosey RG, Carek PJ, Goo A. Exercise Induced Anaphylaxis and Urticaria. AAFP 2001;64 (8):1367-1372.
- Berstein, JA et al. The diagnosisand management of acute and chronic urticaria: 2014 update. AAAAI 2014;133(5):1270-1277.
- Barg W et al. Exercise Induced Anaphylaxis: An Update on Diagnosis and Treatment. Curr Allergy Asthma Rep (2011) 11:45-51.
Emily Kossow presented a cool case of a young cement cutter who presented with dyspnea and cough and was found to have miliary nodules on chest CT, now felt to be atypical sarcoid vs silicosis!
There are three different patterns that nodules can take on chest CT:
Source: Radiology Assistant
To understand why certain diseases may show up as one pattern, you have to understand the anatomy of the pulmonary lobule
So it makes sense that diseases that spread through the airways (ex: antigens in hypersensitivity pneumonitis) may present with centrilobular nodules, while others that move via the lymphatics (ex: sarcoid, lymphangitic spread of tumor) will dot the pleura and secondary pulmonary lobule.
- Perilymphatic: sarcoidosis, lymphangitic carcinomatosis, amyloidosis (rare), silicosis (rare), LIP (rare)
- Centrilobular: bronchiolitis (infectious/inflammatory), hypersensitivity pneumonitis, endobronchial spread of TB, pneumoconiosis, endobronchial spread of tumor (BAC), vasculitis, pulmonary capillary hemangiomatosis, Langerhans cell histiocytosis (+cysts)
- Random: hematogenous metastases, miliary TB, disseminated endemic fungi, sarcoid (rare)
Today we discussed a middle aged woman with factor V Leiden who came in with dyspnea and was found to have a monster (seriously) saddle PE. We had the pleasure of having Dr. Jay Giri talk to us today about the evolving evidence in submassive PE management and the PE response team.
There was way too much discussed to put in one post, but I’ll try to distill the essentials.
PE risk stratification
- Low risk PEs (those with none of the features above) can be treated with just anticoagulation (and may not even need admission, depending on the situation)
- High risk (‘massive’) PEs should usually be treated with fibrinolytics because they will otherwise almost certainly progress to death; uncontrolled bleeding is the main contraindication
- Intermediate risk (‘submassive’) PEs are where the opportunity is ripe to prevent morbidity and mortality
Options for treating intermediate risk PE
- Anticoagulation + systemic thrombolysis
- Catheter directed intervention (thrombolysis, vacuum aspiration)
- (much less commonly) surgical embolectomy
While it’s well-accepted that thrombolysis is the best option for massive PEs, the use of thrombolytics for submassive PEs has been the subject of intense study. Several trials and meta-analyses have looked at this question, so I’ll highlight a few:
- PEITHO: anticoagulation + tenecteplase vs anticoagulation alone in patients with submassive PE. The study confirmed that fibrinolytics decreased the risk of hemodynamic decompensation
- This study was not powered to detect differences in mortality
- The bleeding rate was ~2% in the lytic group; in subgroup analyses a lot of that was driven by patients >75 (see plot below)
Meyer et al. NEJM 2014
- This 2014 JAMA meta-analysis looked at prospective randomized trials of thrombolysis in >2000 patients with submassive or massive PE
- Thrombolysis reduced all-cause mortality by 44% with a NNT of 59 (p=0.01), an effect also seen among the subgroup with submassive PE
- Also note (table below) that the NNH is only 18 for major bleeding (but NNH = 176 in patients <75!)
Chatterjee et al. JAMA 2014
Overall, clinicians who deal with this frequently find themselves in the position of having to decide which patients with submassive PE might benefit from thrombolysis. Right now it’s a decision made without clear guidance, but younger age and fewer comorbidities (and patient preference) are likely to play big roles.
A few other pearls from today’s talk
- Why do older patients do so much more poorly with lytics? Many possibilities: underlying amyloid angiopathy, prior strokes (whether recognized or not), possible old unrecognized ICHs
- Lytic therapy is known to decrease PA systolic pressures much more rapidly than just anticoagulation, but there may be a ‘catch up’ phenomenon, such that months after the incident PE, PASPs are approximately equivalent in patients treated with lysis vs just anticoagulation; this suggests that A/C works, just slower
- Transthoracic echo is decent at estimating RV and PA pressures (as compared to RHC), but that close concordance falls apart at very high PA pressures (approximately >60)
- If someone codes and you suspect it’s due to a massive PE, you could consider giving them emergent lytics, but those people rarely survive given the attendant high bleeding risks with CPR, anoxic brain injury, etc. The better thing may be to crash them on to VA ECMO, which in some series confers a higher survival rate
- Some (albeit shaky) data exists that lower doses of tPA (50mg instead of 100mg) may be equivalent, since the entirety of the cardiac output flows through the pulmonary vasculature
- Catheter directed lysis theoretically has a lower risk of major bleeding since the tPA dose (typically 8-24mg) is much lower than systemic lytic doses, but that lower bleeding risk hasn’t actually been proven
Finally, consider activating the PE response team for any patient who has a submassive or massive PE; the attending or fellow on-call can always be found on Penn Medicine on Call (UPHS homepage).
- Meyer et al. Recent advances in the management of pulmonary embolism: focus on the critically ill patient. Ann Intensive Care 2016.
- Piazza et al. Management of submassive pulmonary embolism. Circulation 2010.
- Submassive PE: are we treating it backwards? Pulmcrit/EMCrit.
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.
Diffuse GGOs in a patient with methotrexate pneumonitis. AJR 2005.
Here’s a table from a paper by Penn radiologist/wizard Wally Miller:
Miller and Shah, AJR 2005
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)
- Miller, Wally Jr and Shah, Rosita. Isolated Diffuse Ground-Glass Opacity in Thoracic CT: Causes and Clinical Presentations. AJR 2005.
- Kauffman, C. Histoplasmosis: a clinical and laboratory update. 2007.
- Murdoch et al. Immune Reconstitution Inflammatory Syndrome (IRIS): review of common infectious manifestations and treatment options. 2007.
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:
Simonneau et al. JACC 2013.
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)
- Ginns et al. Pulmonary Capillary Hemangiomatosis With Atypical Endotheliomatosis: Successful Antiangiogenic Therapy With Doxycycline. Chest 2003.
- Chaisson et al. Pulmonary Capillary Hemangiomatosis and Pulmonary Veno-occlusive Disease. Clinics in Chest Medicine 2016.
- Simonneau et al. Updated clinical classification of pulmonary hypertension. JACC 2013.
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