Parapneumonic effusions

Thanks to Julie for presenting the case of a middle-aged man with recent CAP who presented with progressive SOB, pleuritic chest pain, weight loss, and anorexia, found to be septic with a large empyema, eventually requiring open decortication!

Clinical Pearls

  • Think of parapneumonic effusions in two broad categories: infected (complicated and empyema) and sterile (uncomplicated).
    • Infected (complicated and empyema) require chest tube placement and can be complicated by loculated effusions.
    • Uncomplicated resolve with the treatment of underlying pneumonia
  • Anaerobic organisms are a common cause of infected parapneumonic effusions.  Malodorous fluid at the time of thoracentesis is diagnostic!  But make sure to send anaerobic cultures to the lab to help with speciation.
  • pH of pleural fluid can be falsely elevated if not immediately stored on ice upon collection and processed in a blood gas analyzer.
  • Differential for pleural fluid that has low glucose/low pH is short: infection, TB, malignancy, rheumatoid pleurisy, and lupus pleuritis.
  • Remember that while ADA has high sensitivity (86%) and high specificity (87%) for TB, the study on which it is based was done in a high risk population so its utility in screening low risk patients is limited.

Parapneumonic effusions:

  • Form in 40% of bacterial pneumonia:
      • Uncomplicated: negative GS and Cx, pH>7.2, glucose >60, no loculations
      • Complicated: positive GS or Cx or pH <7.2, or glucose <60. LDH >1000 makes it more likely
      • Empyema: frank pus aspirated during thora, cell count with >50k WBCs

The latter two categories require chest tube placement to prevent formation of pleural “peels” that can lead to trapped lung and loss of lung function.

  • Imaging
    • Lateral decub or ultrasound, latter is more sensitive than CXR for diagnosing complicated parapneumonic effusions.
    • CT with contrast is the optimal imaging for empyema or loculated effusion
      • Look for the “split pleura sign”
  • Labs:
    • Serum procalcitonin >0.18 ng/mL is 83% sensitive and 81% specific for effusion having a bacterial infectious etiology
    • Bacteriology:
      • Anaerobic bugs are often the culprit!  So it is important to send pleural fluid for both aerobic and anaerobic cultures
      • Other bacteria: CAP organisms such as strep and staph as well as klebsiella in diabetic patients
      • Fungi
      • TB
  • Treatment:
    • Tube thoracostomy (chest tube): first intervention
      • CT within 24 hours to ensure correct positioning and adequate drainage, left in place until drainage is <50 cc/day
    • Fibrinolytic agents
      • DNA is a main contributor to viscosity of empyema fluid.  However, based on this trial published in NEJM in 2011, tPA and DNAase combined is associated with significant radiographic improvement of empyema, reduction in hospital stay, and lower number of surgical referrals.
    • VATS
    • Decortication
      • To remove the thickened fibrin layer covering the pleura.
    • Open thoracostomy
      • Rib resection and opening the chest wall at the inferior border of empyema to allow for ongoing drainage.  High risk of infection and complications.

Small cell bladder cancer and hematuria- 10/17/18

Thanks to Naina for presenting the case of an elderly man presenting with acute onset of n/v, and abdominal pain, found to have anemia and AKI, with work up revealing small cell cancer of the bladder causing ureteral obstruction with mets to the lymph nodes, liver, lung, and bone, hospitalization complicated by TLS prior to onset of chemo and contrast induced nephropathy.

Clinical Pearls

  • Bladder cancer is the most common malignancy of the urinary system and urothelial (transitional cell) carcinoma is the culprit >90% of the time.  Less common subtypes include squamous, adeno, small cell (our patient), and sarcoma.
  • Unexplained hematuria in anyone >40 years is bladder cancer until proven otherwise!
  • CT urography is the diagnostic imaging of choice in the work up of hematuria.
  • Diagnosis of bladder cancer is often delayed due to similarity of symptoms with other benign disorders.  However, majority of cases are still caught in stage 0-1 (muscle non-invasive disease) with overall good prognosis.

Bladder cancers:

  • Epidemiology
    • Most common malignancy of the urinary system, 3-4 x more common in men but women are usually diagnosed with more advanced disease and have a higher mortality rate.
    • Median age at diagnosis is ~70
    • Incidence has increased by more than 50% during the past 20-30 years.
  • Types:
    • Urothelial (transitional cell) carcinoma is the predominant histologic subtype in the US and Europe (>90% of all bladder cancers) and can arise in renal pelvis, ureter, or urethra
    • Other: squamous, adeno, small cell, sarcoma
  • Degree of invasion:
    • Superficial (non-muscle-invasive)
    • Muscle-invasive
    • Metastatic
  • Clinical presentation
    • Painless hematuria
    • Irritative voiding symptoms (frequency, urgency, dysuria) – only in 30% of patients
    • Sometimes metastases cause the initial symptoms that lead to diagnosis (as in our patient)
    • Most cancers eventually become symptomatic
  • Diagnosis: often delayed due to similarity of symptoms to other benign d/o
    • Urine cytology >98% specific, 12-64% sensitive based on grade of tumor
    • Imaging
      • CT favored over IVP
    • TURBT done for diagnosis and staging
    • DDx
      • Hematuria from enlarged prostate
      • Pregnancy
      • Cystitis
      • Prostatitis
      • Passage of renal calculi

Staging bladder cancer

Source: Nature Outlook.


  • Management
    • Over 50% of people diagnosed with non-invasive disease develop recurrence
    • Assess performance status with Karnofsky or Eastern Cooperative Oncology Group scales for older patients before deciding on chemotherapy
    • Chemo regimens are often cisplatin-based which carry the side effects of nephrotoxicity, ototoxicity, and neuropathy

treatmetn of bladder cancer

Source: Nature Outlook


Refer to this thorough algorithm on UpToDate.

  • Incidence of malignancy in microscopic hematuria is ~2-5%
  • Incidence of malignancy in macroscopic hematuria is ~20%

Extra pearls on onset of hematuria during voiding:

  • Occurs at the beginning? Urethral source
  • Discharge noted between voidings or stain on undergarment? Urethral meatus or anterior urethra
  • Terminal hematuria? Bladder neck or prostatic urethra
  • Throughout voiding? Anywhere in the GU tract

Hepatopulmonary Syndrome 10/10/2018

A 67 year old man with history of cirrhosis secondary to Hepatitis C and alcohol, hepatocellular carcinoma with recent TACE, presented with worsening dyspnea on exertion and positional shortness of breath. His breathing was worse when he sat upright, and better when he was supine. What’s going on?

Just to go over some terms:

  • Orthodoxia: Drop in PaO2 by 5mmHg or O2sat by 5% when moving from supine to upright.
  • Platypnea: Dyspnea that is induced by moving to an upright position, relieves when supine.

Hepatopulmonary syndrome


  • Chronic liver disease or portal hypertension
  • Intrapulmonary vascular dilations (IPVD)
  • Impaired oxygenation


Up to 25% of patients with chronic liver disease will have some degree of shunting, can occur at any stage (mild or severe)


  • Not well understood but the theory is due to increased nitric oxide production and reduced NO clearance, resulting in pulmonary vasodilation (IPVDs) mostly concentrated at the lung bases.
  • When upright, blood preferentially perfuse the lower lung  zones due to gravity.
  • Vasodilation leads to poor gas exchange.


  • This leads to a VQ mismatch


  • CXR: Not helpful, might show e/o interstitial lung markings.
  • CT: Can reveal IPVDs
    • Dilated peripheral pulmonary vessels
    • Inc pulmonary artery to bronchus ratios
  • PFT: Not helpful
  • Transthoracic contrast echo (TTCE): Can be used to demonstrate presence of intrapulmonary shunts supportive of presences of IPVDs
    • Concept of bubble study: Shooting agitated saline (with bubbles into the vasculature
    • Bubbles visible in the R heart chambers, should not be visible in the left heart chambers.
    • If presence of bubbles in the left: This is indicative of a shunt:
      • Intracardiac shunt: bubbles seen within 1 beat
      • Intrapulmonary shunts: bubbles seen after 3-8 beats.


Normal Echo: Notice how the agitated saline bubbles remain on the right side of circulation and do not cross over. The bubbles were filtered out by the pulmonary vasculature.

Normal Echo


Echo demonstrating intrapulmonary shunting (see bubbles crossing over from the right to the left)




  • Supplemental O2 indicated if O2 sats < 88%, PaO2 < 55mmHg
  • Mild to moderate: Monitor Q6-12 months
  • Severe to very severe: Referral for liver transplant
  • Insufficient data on other treatment options (garlic, pentoxifylline, NO synthase inhibitors, IPVD embolization, plasma exchange, oxtreotide).


Image adapted from Uptodate

Check out this article if you’re interested in the data behind pentoxifylline!

On rhabdo and myopathies – 10/9/18

Thanks to Cameron and Adam for presenting the case of a middle aged man with no significant PMH who presented with diffuse myalgias and chronic progressive proximal muscle weakness, found to have a CK >12k and EMG findings concerning for an inflammatory myopathy, awaiting muscle bx for diagnosis.

Clinical Pearls

  • Rhabdomyolysis literally means dissolution of skeletal muscle and has a broad differential outside of the typical traumatic or exertional processes associated with it see below).
  • The four main inflammatory myopathies are dermatomyositis, polymyositis, inclusion body myositis, and necrotizing autoimmune myositis.
  • Polymyositis is rare and a diagnosis of exclusion after the other three main inflammatory myopathies have been investigated.
  • Overall, the prognosis of inflammatory myopathies is good with appropriate treatment.  The exception is inclusion body myositis which is a progressive disorder without any effective therapy.
  • Pigment nephropathy can occur with rhabdo regardless of the underlying etiology especially in patients with CK >5000.  Aggressive IV hydration to lower CK levels is important to reduce the risk of kidney injury.



  • Traumatic
    • Crush injuries, surgery, prolonged compression from immobility or coma
  • Non-traumatic
    • Exertional:
      • Normal muscle: strenuous exercise, heat stroke, seizures, hyperkinetic states
      • Abnormal muscle: metabolic myopathies, mitochondrial myopathies, malignant hyperthermia, NMS
    • Non-exertional
      • Alcoholism
      • Drugs and toxins: lipid-lowering drugs (fibrates, statins), alcohol, heroin, cocaine, meth, colchicine
      • Infections: influenza, coxsackie, EBV, HIV, legionella
      • Electrolyte abnormalities: hypokalemia, hypophosphatemia, hypocalcemia
      • Endocrinopathies: DKA, HHS, hypothyroidism, vitamin D deficiency
      • Inflammatory myopathies (rare)
      • Paraneoplastic
      • Miscellaneous

Inflammatory myopathies

Largest group of potentially treatable myopathies in children and adults.

  • Four subtypes: distinguishing which process is important because each subtype has a different prognosis and response to therapy
    • DM
      • Anti-Mi-2, anti-MDA-5, anti-TIF-1, anti-NXP-2
    • PM
      • Rare, often misdiagnosed
      • Dx of exclusion
    • Necrotizing autoimmune myositis
      • More common than PM
      • Occurs alone or after viral infections or in association with cancer, CTD, or post-statin
      • Anti-SRP or anti-HMGCR
      • Highest CK level
    • Inclusion body myositis
      • Most common in people >50
      • 7.9 cases/million in the US
      • Distal muscles impacted first
      • Facial muscles impacted
      • Muscle atrophy occurs earlier than in others
      • Extramuscular manifestations are uncommon
      • Dysphagia occurs in >50%
      • Muscle atrophy is common
      • Lowest CK level
  • Up to 30% of patients with DM or PM have a constellation of clinical findings termed “antisynthetase syndrome”
    • Acute disease onset
    • Constitutional symptoms (fever, weight loss)
    • Myositis
    • Raynaud’s
    • Mechanic’s hands
    • Non-erosive arthritis
    • ILD
    • Labs show antibodies to tRNA synthetase enzymes (anti-Jo-1)
  • Extramuscular manifestations
    • systemic symptoms
    • cardiac arrhythmias or ventricular dysfunction
    • pulmonary complications (ILD)


Table above adapted from this and this review article by NEJM.

Lymphocytic hypophysitis – 10/3/18

Thanks to Sahar for presenting the interesting case of a middle-aged woman with metastatic melanoma recently started on ipilimumab who presented with a headache and fatigue, found to have hypothyroidism and adrenal insufficiency with work up consistent with hypopituitarism related to an adverse effect of ipilimumab: lymphocytic hypophysitis!

Clinical Pearls

  • Remember that adrenal insufficiency and hypothyroidism are causes of elevated ADH levels.
  • Red flags for obtaining head imaging for headache include age >55, sudden onset, positional, onset after trauma or exercise, fever, focal neuro findings, and immunosuppression.
  • Pituitary adenomas can have three manifestations: mass effect, hormonal hypersecretion, and hypopituitarism.  When imaging shows a pituitary mass, your work up should address each of these categories.
  • The most sensitive test to assess hypothalamic-pituitary access function is LH/FSH!
  • Immunotherapies are commonly associated with a flare of autoimmune diseases.  A more rare side effect of CTLA-4 inhibitors (like ipilimumab) is lymphocytic hypophysitis (inflammation of the pituitary gland)
    • This condition commonly presents with headache out of proportion to neurologic findings and preferential decline in ACTH and TSH though other hormones can also be impacted.
  • For hypopituitarism, remember to always treat adrenal insufficiency first before replacing thyroid hormone.  Failure to do so can precipitate adrenal crisis!

Indications for imaging a patient with headache:

  • Age >55
  • Sudden onset
  • Worse with lying down or wakes patient from sleep
  • Rapid onset after trauma or exercise
  • Fever
  • Focal neurologic findings
  • New headache in immunosuppressed patient

Pituitary adenoma:

  • Evaluate for the following
    • Mass effect: visual field deficit, headache
    • Hormonal hypersecretion
      • Prolactin ⇒ galactorrhea, amenorrhea, infertility
      • GH ⇒ Acromegaly
      • TSH ⇒ hyperthyroidism
      • ACTH ⇒ Cushing disease
      • ADH ⇒ SIADH
    • Hyposecretion:



  • Inflammation of the pituitary
  • Four categories based on histologic findings:
    • Lymphocytic
      • Most common form
      • Seen in late pregnancy and post-partum period
      • Also associated with ipilimumab as our patient here!
    • Granulomatous
      • Idiopathic or secondary to GPA, sarcoid, TB
    • Plasmacytic (IgG4-related)
    • Xanthomatous (most rare)
  • Clinical presentation
    • Headache out of proportion to exam findings
    • Preferential decrease in ACTH and TSH ⇒ adrenal insufficiency and hypothyroidism
  • Prognosis:
    • Pituitary size eventually normalizes but pituitary loss of function is often permanent.


Lastly, refer to this algorithm from our recent morning report to help you think through hyponatremia.

Acute pancreatitis – 10/2/18

Thanks to Tiffany for presenting the case of a middle-aged man presenting with acute onset of epigastric abdominal pain and nausea/vomiting, found to have a normal lipase initially which jumped up to 1150 48 hours later consistent with acute pancreatitis.

Clinical Pearls

  • Gallstones and ETOH account for the majority of cases of acute pancreatitis.
  • Up to 30% of cases of acute pancreatitis are idiopathic!  This is a diagnosis of exclusion.
  • Lipase typically rises within 4-8 hours after the onset of pancreatitis and lasts for >8 days as opposed to amylase (6-12 hours, lasts for 3-5 days).  Lipase is also more sensitive and specific than amylase.
  • Common electrolyte abnormalities associated with pancreatitis are hyperglycemia and hypocalcemia.
  • BISAP, Ranson’s, and APACHE II scores are useful for prognostication
  • In a patient with history of recurrent pancreatitis presenting with acute GI bleed, think hemosuccus pancreaticus (pseudoaneurysm between the splenic artery and pancreatic duct) which requires IR or surgical intervention.

Causes of pancreatitis: GET SMASHED

  • Gallstones
  • EtOH
  • Trauma
  • Scorpion bite (and Gila monster!)
  • Mumps, Malignancy (pancreatic adenocarcinoma)
  • Autoimmune (seen in IgG4 related disease and celiac)
  • Steroids
  • Hypertriglyceridemia and Hypercalcemia (unclear mechanism)
  • ERCP
  • Drugs (sulfas, thiazides, ACEi, lasix, ARVs are most common)

If you have ruled out the above etiologies, here is a more thorough list to sift through:

  • Infections
    • Viruses: coxsackie, CMV, HIV, VZV, HBV, HSV
    • Bacteria: salmonella, legionella, mycoplasma, leptospira
    • Fungi: aspergillus
    • Parasites: toxo, crypto, ascaris
  • Hypotension
  • Atheroembolism
  • Vasculitis (SLE or PAN)
  • Hereditary mutations
  • Cystic fibrosis

Work up for pancreatitis without identifiable cause:

  • EUS with bile sampling for microlithiasis
  • If EUS is negative or unavailable, then MRCP with secretin administration to evaluate dynamic obstruction or early chronic pancreatitis



For a very thorough review of pancreatitis, please see this prior blog post.

GPA – 10/1/18

Yours truly presented a case of a middle-aged woman with a recent history of otitis, sore throat, conjunctivitis, photophobia, and arthralgias who presented with chronic and progressive decline in functional status and AMS, found to be uremic with work up revealing c-ANCA associated ESRD.

Clinical Pearls

  • Remember that oval fat bodies are specific for glomerular pathology (more commonly nephrotic syndrome but can be seen in nephritic disease as well).
  • ANCA-associated vasculitides include GPA, MPA, eGPA (and renal-limited vasculitis).
  • All have similar features on renal histology (focal necrotizing, crescentic, pauci-immune glomerulonephritis).
  • They can affect multiple organ systems (see breakdown below) which makes their clinical diagnosis challenging apart from the following differences:
    • c-ANCA is associated with GPA, p-ANCA is seen in MPA and eGPA
    • Granulomas are seen in GPA and eGPA
    • Eosinophilia and asthma are associated with eGPA

ANCA-associated vasculitides


Chart above adapted from this paper by Koldingsnes et al.

Granulomatosis with polyangiitis (GPA)

Diagnostic criteria (two or more has 88% sensitivity and 92% specificity):

  • Nasal or oral inflammation (painful/painless oral ulcers, or purulent or bloody nasal discharge)
  • Abnormal chest radiograph showing nodules, fixed infiltrates, or cavities
  • Abnormal urinary sediment (microscopic hematuria w/w/o red cell casts)
  • Granulomatous inflammation on bx of artery or perivascular area

Clinical presentation:

  • Most commonly in older adults, M=F
  • More common among white individuals (~89%)
  • S/s
    • Fatigue, fever, weight loss, arthralgias, rhinosinusitis, cough, dyspnea, urinary abnormalities, purpura, and neurologic dysfunction.
    • ENT
      • 90% of GPA cases, only 35% of MPA
      • Nasal crusting, sinusitis, otitis media, earache, polychondritis, ulcers, discharge
      • Conductive and/or sensorineural hearing loss
      • Saddle nose deformity
    • Tracheal and pulmonary disease
      • Airways or parenchyma
    • Renal
      • ~18% at presentation but subsequently develops in 77-85% of patients within the first 2 years of disease onset
      • High risk of progression to ESRD
      • Asymptomatic hematuria
      • Subnephrotic range proteinuria
      • Rapidly progressive GN
    • Cutaneous
      • ~50% of patients
      • Leukocytoclastic angiitis is most common which causes purpura of lower extremities
      • Other findings: urticarial, livedo reticularis, nodules, erythema nodosum, pyoderma gangrenosum, and Sweet syndrome
    • Ophthalmic/orbital
      • Conjunctivitis, corneal ulcers, episcleritis/scleritis, optic neuropathy, retinal vasculitis, and uveitis.
    • Other organs
      • CNS: neuropathy, CN abnormalities, mass lesions, hearing loss, granulomatous inflammation of the CNS
      • GI tract, heart, lower GU, parotids, thyroid, liver, or breast
      • High incidence of DVT (unclear mechanism)
    • Can progress slowly over months or explosively over days
    • Relapses can manifest differently than original presentation

Diagnosis requires biopsy!


  • Prompt initiation of therapy can be life and organ sparing
  • Induction therapy: Steroids +-Cyclophosphamide +-Rituximab
  • Maintenance therapy: multiple options-Azathioprine, MTX, Rituximab, Leflunomide