DRESS Syndrome (or DIHS)

Today Dr. Kali Xu presented a riveting case of a middle-aged man with a history of gout on allopurinol who presented with a worsening, diffuse maculopapular rash with odynophagia, dysuria, and pain on defecation with eosinophilia, elevated ALT, and AKI.

Given the mucus membrane involvement, multiorgan dysfunction, diffuse rash, and recent allopurinol initiation, the group astutely narrowed the differential diagnosis to DRESS vs SJS/TEN, which was the same differential of the dermatology team came up with.

The following is a useful table we created when deciding between these two similar diagnoses.


Other useful clinical pearls from today’s noon report:

  • The most common triggers for DRESS: anti-epileptics and allopurinol
  • When dealing with anti-epileptic induced DRESS, many experts use valproic acid for seizure disorder treatment because it is least likely to cause DRESS
  • There is a trend toward calling DRESS syndrome DIHS (drug-induced hypersensitivity syndrome)
  • DRESS can involve any organ including liver, kidney, lungs, heart, GI, pancreas, thyroid, brain, muscles, nerves, and eyes
  • Treatment for DRESS consists of a long steroid taper, which usually required prophylaxis for osteoporosis and steroid-induced peptic ulcers with calcium-vitamin D supplementation and PPI
  • Thyroid function should be monitored 2-3 months after acute presentation because autoimmune thyroiditis can be a late presenting sequelae of DRESS

A case of psychosis with lymphocytic pleocytosis in CSF… Anti-NMDA Receptor Encephalitis!

Today we discussed a very interesting case of a young female who presented with 3 months of progressive behavioral disturbances, hallucinations, headache, insomnia, and a seizure. In young females with progressive symptoms and seizures, anti-NMDA receptor encephalitis is an important diagnostic consideration, although it is quite rare.

Illness Script for NMDA encephalitis:

  • occurs in young females with ovarian teratomas, but can be associated with other tumors as well and is sometimes seen in men and children
  • proposed association with a history of HSV encephalitis (in one study 20-30% of HSV encephalitis patients who didn’t have anti-NMDAR antibodies during their episode of encephalitis developed them later)
  • Clinical presentation: headache, fever, viral-like prodrome followed by multistage progressive symptoms:
    • psychiatric manifestations: anxiety, agitation, bizarre behavior, hallucinations, delusions, disorganized thinking
    • insomnia
    • memory deficits
    • language dysfunction: diminished language output, mutism, echolalia
    • seizures
    • decreased level of consciousness, stupor with catatonic features
    • dyskinesias: orofacial, choreoathetoid movements, dystonia, rigidity, opisthotonic postures
    • autonomic instability: hyperthermia, fluctuations of BP, tachycardia, bradycardia, cardiac pauses, hypoventilation
  • LP: can be initially negative or have lymphocytic pleocytosis or oligoclonal bands
  • EEG: Can have infrequent epileptiform activity, but frequently slow, disordganized activity that doesn’t correlate with patient’s abnormal movements
    • Unique pattern associated with prolonged illness: extreme delta brush
  • MRI: Usually normal, but can have transient FLAIR abnormalities
  • Diagnosis: CSF anti-GluN1 antibodies + clinical symptoms, abnormal EEG + oligoclonal bands, and reasonable exclusion of other disorders
  • Treatment:
    • Tumor resection when possible
    • Methylprednisolone 1g IV daily x5d
    • IVIG 400mg/kg IV daily x5d OR plasma exchange
    • If sypmtoms very severe, consider Rituximab

Acute Cholangitis without a Gallbladder

Today, Dr. Nakache presented a case of a 63yoF with a history of cirrhosis and cholecystectomy who presented with RUQ pain and sepsis with EColi bacteremia, found to have acute cholangitis.

Causes of Acute Cholangitis: Stones, strictures, malignancy, stent occlusion, s/p ERCP, postoperative (Whipple, gastric bypass, etc), or extrinsic compression (Lemme’s syndrome, acute pancreatitis, Mirizzi syndrome), parasites (liver flukes or ascaris)


Charcot’s triad: Fever, jaundice, abdominal pain (only 50-75% have this triad)

Reynold’s pentad for severe cholangitis: Charcot’s triad + hypotension and AMS

Complications: septic shock, hepatic abscess, multiple organ dysfunction

Labs: Leukocytosis/evidence of infection, Cholestatic LFTs, although can also get transaminitis if hepatocyte necrosis (high 2000s, consider liver abscess)


Must meet all criteria:

  1. Evidence of systemic inflammation: Fever, shaking chills, leukocytosis, elevated CRP
  2. Evidence of cholestasis (Tbili >= 2, elevated LFTs 1.5x ULN)
  3. Imaging with biliary dilation OR evidence of cause (stones, stricture, etc.

Choice of Imaging:

Start with abd US. If negative but still very high clinical suspicion, get abd CT. If negative, but still very high clinical suspicion, get MRCP. These tests get more expensive, more time consuming, and more sensitive as you go down the list.

Caveat #1: If the patient’s is s/p cholecystectomy, abdominal ultrasound may be too nonspecific due to normal postoperative biliary dilation. Visualization of the distal CBD is also particularly poor on ultrasound.


  1. Supportive care (fluids, electrolyte repletion, analgesia)
  2. Antibiotics
  3. Biliary drainage via ERCP, which is successful 90-95% of cases
  4. Address the cause (consider cholecystectomy if 2/2 stones, consider stenting if due to malignancy)

Antibiotic treatment:

If infection is community acquired without risk factors for antibiotic resistance, use one of the following regimens:

– Zosyn

– Cephalosporin + Flagyl

– Cipro or Levofloxacin + Flagyl

If the patient shows signs of end-organ damage, is in septic shock, OR there are risk factors for antibiotic resistance (recent travel to Asia, Africa, or Middle East, known colonization with antibiotic resistant organisms, or healthcare-acquired infection), use one of the following regimens:

– Zosyn

– Carbapenem: Meropenem or Imipenem + cilastatin or Doripenem

– Cefepime or ceftazidime + Flagyl

Duration of Therapy:

Continue antibiotics until 4-5 days after source control.

Timing of ERCP:

70-80% of cholangitis patients respond to initial therapy and ERCP can be done nonemergently within 24-48 hours.

If they shows signs of end organ damage, are in septic shock, or do not respond to 24 hours of antimicrobial therapy and supportive care, they should get ERCP emergently within 24 hours.

It’s Not Lupus…Except When It Is!

After a week-long hiatus we are back folks!

Yesterday we presented a case of a patient with untreated SLE who presented with the following:

  1. Diffuse joint pain and swelling, that were non-erosive on x-ray
  2. DAT+, IgG+ anemia
  3. ANA 1:640!
  4. +anti-dsDNA/+anticardiolipin screen
  5. UPCR of >13g/day with an AKI
  6. Pleuritic chest pain, likely representing serositis

Taken together, she meet at least 6/11 criteria for lupus by ACR (only 4/11) are needed), which we briefly reviewed:


We then reviewed the ISN/RPS histological classification of lupus nephritis and while it is full of technical language, we simplified it greatly as the following:

  • Class 1&2 – mesangial disease
    • conservative treatment with ACE-i
  • Class 3&4 – proliferative disease
    • treat with steroids + (mycophenolate OR cyclophosphamide)
  • Class 5 – membranous lupus nephritis (AKA membranous nepropathy-like with significant proteinuria
    • treat similarly to proliferative disease, though some experts also consider involving use of a calcineurin inhibtor, extrapolating its benefit from idiopathic membranous nephropathy
    • important to recognize that these classes are not stages, and you can have combined class 3 and class 5 disease OR you can have isolated class 5 disease for example that converts later to combined class 4 and 5 disease – illustrating the importance of a repeat biopsy in situations of acute decline in eGFR or increase in proteinuria
  • Class 6 – advanced sclerosing lupus nephritis
    • >90% of glomeruli on LM are globally sclerosed with no residual activity
    • conservative therapy until RRT needed

For a further review of lupus nephritis, please see the previous, excellent post:


A Teetering Submassive PE

Today we discussed a case of an unfortunate young man who presented with chest tightness and syncope who later was found to have a massive PE.

We first discussed that the PE risk stratification is, by no means standardized and that every single society guideline differs slightly. Furthermore, an algorithmic approach is never 100% sensitive and an overall gestalt is valuable.

A. Risk Stratification per ACP from their clinical guidelines, published in 2015 in Annals


B. Once a PE is diagnosed, we emphasized the need to classify patients based on the following framework:

  • Massive PE
    • Hypotension is defined as a systolic blood pressure <90 mmHg or a drop in systolic blood pressure of ≥40 mmHg from baseline for a period >15 minutes or hypotension that requires vasopressors or inotropic support and is not explained by other causes
  • Submassive PE
    • Electrocardiographic Signs of Right Heart Strain
    • Echocardiographic Signs of Right Heart Strain
    • Biomarkers of Heart Strain
  • Nonmassive PE

Remember, the anatomic location of the embolus does not relate to the above classification (i.e in a saddle embolus, a retrospective analysis found that only ~22% of such patients had hemodynamic instability)

B. Treatment of PEs

  • Nonmassive PEs will be anticoagulated
  • Regarding massive PEs, treatment patterns vary depending on the institution – but generally speaking –thrombolytics are first line. Depending on the patient and expertise, mechanical thrombectomy and catheter-directed lysis are also possibilities
  • The controversial area is the submassive PE
  • There is no standardized approach to submassive PEs, and even more complicated is that there is no consensus on what exactly is submassive. As Dr. Gohil said, there is submassive and there is submassive. Our goal as internists is to identify patients on teethering death. See this phenomenal PulmCrit post regarding this concept: https://emcrit.org/pulmcrit/submassive-pe-peitho/

C. Treatment of Submassive PEs

  • For years the prevailing dogma is that in submassive PE, thrombolysis fixes the numbers but does nothing to improve clinically meaningful outcomes. The relatively low NNH due to ICH and other clinically significant extracranial bleeding was further evidence for skeptics that we really should not be doing this
  • The heterogeneity of studies has muddled meta-analysis and yet still, the 2014 (somewhat controversial) Chaterjee paper found a mortality benefit to a preemptive thrombolysis approach in submassive patients, muted of course by the increased incidence of bleeding. It is important to note that that has never been an individual RCT that has shown a mortality benefit in lysing submassive patients
  • In the view of experts, what is likely is that in acute, high risk submassive PE patients, thrombolysis may acutely drive the PA pressure down enough to prevent hemodynamic collapse and when done at a reduced dose (50mg/2hrs of tPA) likely does not confer a clinically increased risk of major bleeding
  • The question of course is who are these patients who would benefit from lysis? This requires expertise and early consultation with your specialists. Some experts have advocated for the following patients to be closely examined for thrombolysis


  • Elevated shock index (HR/BP)
  • Syncope or presyncope
  • High Endogenous Stress
    • Lactic acidosis
    • Severely “ill appearing” or decompensating


  • Severe hypoxemia
  • Severe right ventricular dysfunction
  • Extensive clot burden

The reason we lyse these patients is improvement of PA pressures just enough that it prevents hemodynamic compromise and a PEA arrest. The 2017 update to the PEITHO study quite convincingly shows that the long-term morbidity with regards to prevention of RV dysfunction and CTEPH, is likely not different, when compared to patients who were just anticoagulated.

D. Summary of Treatment Considerations (No Consensus and Must be Individualized!)

  • Use a clinical decision rule to help guide your pre-test probability and management for suspected PE
  • Attempt to identify high-risk submassive patients
  • Obtain studies & interventions quickly with the early assistance of consultants (pulmonary, IR, cards)
  • Thrombolysis in submassive patients should be restricted to patients at the greatest risk of death. In other words, it is likely most efficacious in acute, high risk submassive PE, not patients with stable subacute to chronic symptoms
  • Reduced dose of thrombolytics are likely just as efficacious as the full dose, with clearly reduced risk of clinically significant and intracranial bleeding
  • All of the above is not supported by any guidelines and for test question purposes, unless the patient is hypotensive, thrombolysis is probably not the right answer!
  • Other Considerations
    • Avoid volume loading an already dilated RV and if hypotensive, focus on norepinephrine
    • Avoid intubation unless absolutely essential (attempt HFNC first if possible)
    • iNO may have a role


Pneumocystis Jirovecii Pneumonia in untreated HIV infection

Thanks to Dr. Michael Chung for presenting today’s case about a young transgender woman with a history of untreated HIV who presented with gradual onset fever, cough, and acute hypoxic respiratory failure with a high A-a gradient, found to have PJP pneumonia on induced sputum. A special thanks to Dr. Kirsch for attending morning report and giving us stellar clinical pearls.

The differential for pulmonary symptoms in an HIV patient is broad, including typical viral, bacterial, and fungal etiologies with the addition of PJP, TB, MAC, toxo (other parasites including strongyloides, microsporidium, and crypto), lymphoma, Kaposi’s sarcoma, and immune reconstitution syndrome (if ART has been recently started).


Basics: HIV and severely immunocompromised

PJP is the most common AIDS-defining opportunistic infection in the US. It affects severely immunocompromised patients including HIV with CD4<200, hematologic malignancies, transplant patients, chronic steroids, and severe malnutrition. Risk factors that should raise your clinical suspicion for PJP are history of previous PJP or recurrent bacterial pneumonia, high viral loads, unintentional weight loss, or presence of oral thrush.

Clinical Presentation:

Basics: 3 weeks of nonproductive cough, dyspnea, and constitutional symptoms, now with hypoxic respiratory failure

HIV patients with PJP typically present with gradual worsening of symptoms over days to weeks (average 3 weeks): nonproductive cough (95%), fever (80-100%), and dyspnea (95%). Chills, chest pain, and unintentional weight loss are also commonly present. Physical exam usually reveals tachypnea and desaturations, but lung exam can be clear in 50% of patients.

Lab Evaluation:

Basics: LDH and B-D Glucan are sensitive, but nonspecific indicators of PJP that can help you decide to treat empirically if confirming the diagnosis in a timely manner is impractical. 

LDH is nonspecific, but very sensitive (elevated in >90% of HIV patients with PJP). LDH has been proposed as a prognostic marker in PJP pneumonia as those who do not survive PJP despite treatment were observed to have higher initial LDH levels than those who did survive. LDH can also be trended throughout treatment to evaluate response and prognosis. B-D-glucan, a component of fungal cell walls, is also nonspecific, but is elevated in PJP pneumonia. Due to the high mortality of untreated PJP pneumonia in HIV patients, these lab tests can raise your clinical suspicion for the disease and help you decide to treat empirically in the absence of confirmed diagnosis.

It is necessary to get an ABG in all patients with suspected PJP pneumonia to calculate the Alveolar-arterial oxygen gradient. This indicates severity of disease and will be useful in deciding on whether to give steroids with your antibiotics.

A-a gradient at sea level on room air= [150- PaCO2/0.8] – PaO2. Normal is <10 but increases with age.


Basics: PJP can cause almost any presentation on CXR/CT but diffuse bilateral infiltrates is most common. CXR is not sensitive so get a CT if clinical suspicion is high. 

25% of chest XRs of HIV patients with PJP are normal. The most common manifestations is diffuse bilateral infiltrates, but PJP can present in almost any way. CT scan is 100% sensitive for PJP in HIV patients.


Basics: Don’t delay treatment for diagnosis. Induced sputum first, then BAL if negative. 

If clinical suspicion is high, diagnosis should not delay treatment. Treat empirically in these cases. Diagnosis can be made with sputum induction (variable sensitivity 50s%-90% depending on patient characteristics, sputum characteristics, and skill of RT/lab/pathologist). If negative, proceed to bronchoscopy with BAL (sensitivity up to 90%). If clinical suspicion is extremely high, but these tests are negative, lung biopsy with PCR can be done, but is very rarely indicated and very invasive. Usually it is only done when lung biopsy is needed to diagnose other pathology concurrently. Silver stain with cysts or trophozoites is the typical method of detection for board exams.

At SCVMC, induced sputum to diagnose PJP requires a pulmonology consult due to the specialized nature of the induction procedure and patient selection and possibility of bronchoscopy.


Basics: Treat with Bactrim. Use adjunctive steroids if significant hypoxia. Things will get worse before they get better. 

Treat with Bactrim 15-20mg/kg PO or IV (equal bioavailability) x 21 days. If sulfa allergy, desensitize in the MICU and treat. If SJS or TEN with sulfa drugs, consider alternative regimens (clinda + primaquine, trimethoprim + dapsone, atovaquone, pentamidine). Always check for G6PD deficiency before starting primaquine or dapsone. Keep in mind that pentamidine is rarely used due to severe side effects: hypotension, hypoglycemia, nephrotoxicity, pancreatitis. It is often necessary to monitor these patients in the ICU for treatment due to the propensity of respiratory failure to initially worsen with treatment before getting better.

Give adjunctive steroids if PaO2 <= 70 or A-a gradient >= 35 or hypoxemia on pulse ox. Steroids have been shown to decrease mortality in these patients without an increase in other opportunistic infections.


Key Points:

  • HIV (CD4<200) and severely immunocompromised get PJP
  • Presents with 3 weeks of nonproductive cough, dyspnea, and constitutional symptoms, now with hypoxic respiratory failure
  • LDH and B-D Glucan are sensitive, but nonspecific indicators of PJP that can help you decide to treat empirically if confirming the diagnosis in a timely manner is impractica
  • PJP can cause almost any presentation on CXR/CT but diffuse bilateral infiltrates is most common. CXR is not sensitive so get a CT if clinical suspicion is high. 
  • Don’t delay treatment for diagnosis. Induced sputum first, then BAL if negative. 
  • Treat with Bactrim. Use adjunctive steroids if significant hypoxia. Things will get worse before they get better.

HTG-Panc – Don’t Pan(i)c!

Today we discussed a case of hypertriglyceridemia-induced pancreatitis (TG >4k). We first utilized this case as an opportunity to provide a comprehensive overview of acute and chronic pancreatitis:


We then discussed the management strategy:

General Pancreatitis Management

  1. Assess severity of pancreatitis with SIRS
  • Mild – absence of organ failure and local systemic complications
  • moderate – local complications and +/- transient organ failure (<48hrs)
  • Severe – persistent organ failure (>48hrs)
  1. Aggressive hydration at 5-10mls/kg/hr
  • Adjust based on vital signs, exam, urine output BUN, HCT
  1. Pain Control
  2. Nutrition
  • Mild
    • initiate PO intake within 48 hours (based on symptoms, NOT lipase reduction)
    • Go straight to low residue, low fat, soft diet
  • Moderate – Severe
    • If unable to tolerate PO, consider NJ vs. NG tube after 3-4 days
  • Enteral nutrition >>> parenteral nutrition
  1. Antibiotics?
  • not recommended regardless of pancreatitis severity or type (i.e interstitial or necrotitizing) unless extrapancreatic infection suspected (blood stream, PNA, UTI etc.) OR necrotizing fluid collection suspected to be secondarily infected (systemic infection OR radiographic evidence of infection)

HTG-Pancreatitis Management

  • Insulin Therapy
  • Lipid Lowering Therapy
  • Plasmapheresis (controversial)
    • invasive
    • expensive
    • requires AC
    • Despite that – UTD recommends apheresis in patients with any of the following (hypocalcemia, lactic acidosis, two or more signs of worsening inflammation, worsening organ dysfunction)
    • Two studies of note that discuss this
      • 1) Head-to-head RCT showed quicker time to TG reduction compared to insulin but worse clinical outcomes
      • 2) Addition of apheresis to patients already receiving insulin showed no clinically significant differences in outcome
    • Bottom Line: based on the limited data above, some experts favor an insulin only approach
    • For an in-depth analysis of this topic – please see this fantastic PulmCrit blog post: https://emcrit.org/pulmcrit/hypertriglyceridemic-pancreatitis/