11/28 HUP Report: Hemoptysis due to ABPA

Thank you Dr. Dine for coming to report to discuss a case of Allergic BronchoPulmonary Aspergillosis (ABPA for short!). The patient we talked about today was a young female who had a history of asthma diagnosed in childhood who presented with a subacute history of cough and subjective fevers, with recent recurrent non-massive hemoptysis.

We discussed important characteristics of hemoptysis to gather information about during a history, including volume, appearance, color, rate and any associated symptoms or triggers. The lungs receive a dual blood supply – the bronchial artery usually arises from the aorta and has a relatively small circulating blood volume at high pressure, while the pulmonary circulation is at lower pressure and involves almost the entire blood volume. Usually, massive hemoptysis arises from bronchial arteries due to their higher pressure and the fact that they supply the airways and airway lesions. It is important to remember that in a minority of patients a spinal artery can originate from the bronchial artery, so a potential rare but serious complication of embolizing the bronchial artery can be paralysis in these patients. Diagram below is from Netter’s Anatomy.

ABPA1.pngThis patient’s imaging was notable for bronchiectasis and mucus plugging, and her workup showed elevated total IgE, eosinophilia, and positive aspergillus skin test. She was diagnosed with ABPA. In this disease, the airways are colonized with aspergillus and a hypersensitivity reaction causes inflammation –it is important to realize that the pathology here is not due to fungal infection, but rather an inflammatory response to fungal colonization. There are differing guidelines for diagnostic criteria; below is the set proposed by the International Society for Human and Animal Mycology (patient must have predisposing condition and both obligatory criteria plus two other criteria; non-CF bronchiectasis patients can also get ABPA).

ABPA2Glucocorticoids are the cornerstone of therapy for ABPA. There are differing perspectives on antifungal therapy – some physicians use antifungal therapy only if patients fail glucocorticoid therapy, and some physicians use antifungal therapy in all patients with this diagnosis. There are studies looking into use of monoclonal antibodies for treatment (omalizumab) – stay tuned for more data!

 

 

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11/21 Presby report: pulmonary complications of cocaine, cavitary lung lesions

Thanks to Robin Mansour for presenting a great case of a middle aged woman who presented with a cough, chest pain and a 90 lb (!) weight loss, who was found to have several cavitary chest masses

We talked about some of the pulmonary complications of cocaine use:

Screen Shot 2017-11-21 at 10.19.35 AM.png

Restrepo et al. RSNA Radiographics 2007

 

Crack lung is a specific term for an acute hemorrhagic alveolitis after crack inhalation, characterized by cough, SOB, hypoxia, fever, bronchospasm and even hemoptysis and focal infiltrates (and diffuse alveolar damage, microscopically)

Remember that cocaine can be adulterated with substances that can cause a variety of toxic effects in and of themselves:

  • Levamisole (a veterinary antihelminthic): can cause P- and C-ANCA+ leukocytoclastic vasculitis
  • Clenbuterol (beta agonist) that can cause hyperglycemia, hypokalemia, tachycardia (which cocaine can also cause)
  • Other ‘cutting’ agents like talc or baking soda can lodge in the pulmonary microcirculation and cause a local granulomatous reaction

What’s the difference between a cavity and a cyst?

  • Cavities tend to be thicker walled: generally we call something with a wall >5mm a cavity, while <5mm is called a cyst
  • Cavity wall thickness can help with figuring out etiology
    • in one study, cavities w/ max wall thickness >15mm were 90% malignant while those <4mm were 95% nonmalignant

Here’s a framework for thinking about cavitary lung lesions:

Screen Shot 2017-11-21 at 11.32.10 AM.png

Derived from Gadkowski et al, Clin Microbio Rev 2008

Lastly, a differential for skin lesions involving tattoos:

  • Sarcoidosis
  • Nontuberculous mycobacteria
  • Discoid lupus
  • Local foreign-body granulomatous skin reaction

References

  1. Restrepo et al. Pulmonary Complications from Cocaine and Cocaine-based Substances: Imaging Manifestations. RSNA 2007.
  2. Gadkowski et al. Cavitary Pulmonary Disease. Clin Microbio Rev 2008.

11/9 Presby report: a moste curious case of metformin-associated lactic acidosis

Late post because I’m on service (sorry!).

A huge thanks to recent Penn IM alum Geoff Bass for giving a great talk on a middle-aged diabetic man who came in with abdominal pain and was found to have metformin-associated lactic acidosis (MALA).

Screen Shot 2017-11-13 at 2.18.09 PM.png

Lactate metabolism is intertwined with that of glucose and pyruvate

Hyperlactatemia occurs via one of four mechanisms:

  • Tissue hypoxia
  • Aerobic glycosis (aka glycolysis that depends on factors other than tissue hypoxia (think high-epinephrine states)
    • Sepsis
    • Severe asthma + beta-agonist use
    • Cardiogenic or hemorrhagic shock
    • Pheochromocytoma, cocaine
  • Impaired oxidative phosphorylation
    • Drugs: ARVs, propofol (PRIS), metformin, toxic alcohols, salicylates, cyanide
  • Liver dysfunction
    • the liver normally clears ~70% of whole body lactate, so acute liver dysfunction can lead to elevated serum lactate; but chronic liver disease (ie cirrhosis) usually doesn’t (in the absence of sepsis or some other driver)

Metformin toxicity is generally rare, and usually only occurs in the context of other predisposing conditions: AKI/CKD, liver disease, alcohol use, concurrent critical illness, heart failure

It is a clinical diagnosis, as there is no one test that confirms the diagnosis; you can send off a metformin level, but it takes a while to come back and is generally unhelpful unless it’s totally negative (in which case you should look for other causes)

MALA is mostly treated with conservative measures:

  • Gastric decontamination
  • Supportive care
  • Hemodialysis
    • Consider if lactate >15-20, pH <7.1, or other conditions such as shock, renal failure, etc

References

  1. DeFonzo R, Fleming GA, Chen K, et al. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism, 2016 Feb; 65(2): 20-29.

  2. Kraut JA, Madias NE. Lactic Acidosis. NEJM,  2014 Dec 11;371(24):2309-19.

10/23 VA Report: Pleural Effusions with Lymphocytosis

Today’s report focused in on a patient with a history of adenocarcinoma of the lung s/p Chemo/XRT/surgical resection and who lived in South East Asia for 10 years who presented with hemoptysis, chronic cough and a new pleural effusion.

We re-reviewed Light’s Criteria — acknowledging that we sacrifice specificity for sensitivity by pooling the three criteria — with a reported ~97% sensitivity and ~80% specificity.

Our patient had an effusion demonstrating >95% lymphs on diff — creating a nice tidy differential to work with — TB, malignancy, sarcoidosis, chronic rheumatoid pleurisy, yellow nail syndrome or chylothorax. We followed his work up narrowing the differential down to TB vs. malignancy.

In doing so we discussed the use of ADA and the proper time to send it — distinguishing between malignant and TB pleurisy with an exudative effusion that is lymphocytic AND has initial cytology and smear and culture negative for TB. We discussed that in patients with a lymphocytic:neutrophil radio >0.75 and ADA >40 empiric treatment for TB is reasonable — with pleural biopsy as a confirmatory test if either of those two criteria are not met. We discussed the diagnostic accuracy of the ADA in reviewing this paper. 

In the end our patient had an ADA <1.6 and is awaiting biopsy for continued malignancy work up.

References:

  1. Liang QL, Shi HZ, Wang K, Qin SM, Qin XJ. Diagnositc Accuracy of adenosine deaminase in tuberculous pleurisy: a meta-analysis. Respir Med. 2008 May; 102(5): 744-54. PMID: 18222681

 

 

9/20 HUP Report: Cystic Lung Disease, Pneumothorax ex-vacuo

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
  • honeycombing
  • bronchiectasis
  • pneumatocele

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

 

Pneumothorax Ex-Vacuo

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.

References:

https://www.uptodate.com/contents/diagnostic-approach-to-the-adult-with-cystic-lung-disease?source=search_result&search=cystic%20lung%20disease&selectedTitle=1~150

https://www.uptodate.com/contents/diagnosis-and-management-of-pleural-causes-of-unexpandable-lung?source=search_result&search=trapped%20lung&selectedTitle=1~46

9/13 VA Report: Chronic Urticaria

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

OR

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.

IMG_0034

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).

References:

  1. Hosey RG, Carek PJ, Goo A. Exercise Induced Anaphylaxis and Urticaria. AAFP 2001;64 (8):1367-1372.
  2. Berstein, JA et al. The diagnosisand management of acute and chronic urticaria: 2014 update. AAAAI 2014;133(5):1270-1277.
  3. Barg W et al. Exercise Induced Anaphylaxis: An Update on Diagnosis and Treatment. Curr Allergy Asthma Rep (2011) 11:45-51.

8/31 (HUP): miliary pulmonary nodules

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:

Screen Shot 2017-08-31 at 11.25.08 AM.png

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)