GPA

Today, we had an interesting case of an older lady who presented with vague fatigue and mouth sores, found to have AKI, RBCs in urine, and bilateral patchy opacities which progressed to frank hemoptysis and hypoxemia. Ultimately she was diagnosed with granulomatosis with polyangiitis!

GPA.png

Learning Points: Today we focused a lot on DDx...

  1. DDx oral ulcers -- Infections (HSV, VZV, HIV, coxsackie, syphilis), autoimmune diseases (SLE, Behcet's, vasculitis, bullous pemphigoid, pemphigus vulgaris), drugs.
  2. DDx hemoptysis -- Airway diseases (bronchitis, mets, foreign body), pulmonary parenchymal diseases (infections like TB, rheumatic disease), pulmonary vascular diseases (CHD, PE, HF, MS, endocarditis), disorders of coagulation (DIC, ITP/TTP/HUS, von Willebrand, platelet dysfunction), iatrogenic injuries, drugs/toxins.
  3. Ultimately, our patient was diagnosed with presumed diffuse alveolar hemmorhage secondary to GPA. We discussed options for diagnosis of DAH including bronch with BAL with lavage aliquots showing progressively more hemorrhage as well as hemosiderin-laden macrophages on Prussian blue staining. Our patient had such classic findings of GPA coupled with hypoxia, bilateral patchy infiltrates and hemoptysis that no further diagnostics were explored before starting treatment.

EBV Negative PTLD

kidney1.jpg

Today Dr. Bien presented an interesting case of abdominal pain, subjective fevers and diarrhea in an immunosuppressed post-solid organ transplant (kidney and liver) patient.

This was a refresher from a Noon Report case on June 28th. Remember, these presentations may be subtle. You should ask about:

  • timing from the transplant?
  • surgical complications?
  • immunosuppression? (any dose changes, the duration)
  • prophylaxis? (any dose changes, the duration)
  • environemental exposures?

One framework for fever in a post solid organ transplant patient is based on the time they are out from the transplant.

  • Early Period (Less than 1 Month): surgical complications (wound infection, line infection, anastomotic leaks); hospital acquired infections (CDiff); donor-derived infections (uncommon with currently testing but include HSV, rabies and West Nile); recipient-derived infections (mainly colonization, ex. Aspergillus and Pseudomonas post-lung transplant)
  • Mid Period (1-6 Months): activation of latent infections or relapsed residual infections (CMV, HCV, BK virus, TB); opportunistic infections (Listeria, Nocardia, Legionella, Toxoplasma, Strongyloides, Leishamnia, Trypanosoma cruzi, endemic fungal infections, PJP); anastamotic complications (stenosis, thrombosis or leak); acute rejection (typically within the first 90 days)
  • Late Period (After 6 Months): community acquired infections (Asperigillus, endemic infections, Nocardia, Listeria CAP); late viral reactivation (VZV, BK virus, CMV); PTLD (may or may not be from EBV)

Post-Transplant Lymphoproliferative Disorder (PTLD) is the second most common malignancy in solid organ transplant patients after skin cancer. It has been historically linked to EBV. However, the further away from the transplant it occurs, the more likely it is to be EBV negative. A case series was reported of EBV negative PTLD in the Journal of Clinical Oncology in 1998. It is quite heterogenous but typically presents with fever and lymphadenopathy or more commonly extranodal disease. Treatment typically includes the following in a step-wise approach:

  • reduction in immunosuppression
  • Rituximab if CD-20+
  • Chemotherapy (CHOP)

For additional information on post-liver transplant patient management, please see the following article from the Cleveland Clinic.

Nephrotic syndrome (aka totality of proteinuria)

Thanks Curtis for presenting an excellent case! Also many thanks to Robert Rope for attending and his knowledge bombs on nephrotic syndrome. This was a case of a patient with soft tissue sarcoma on chemotherapy with gemcitabine, well-controlled diabetes, presenting with subacute progressive bilateral lower extremity swelling found to have nephrotic syndrome thought due to membranous nephropathy vs minimal change disease secondary to the patient’s malignancy.

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(Img: N Engl J Med 2013; 368:956-958)

Main points:

  • 1) Bilateral lower extremity edema is most commonly secondary to heart failure, liver failure, or renal failure/ nephrotic syndrome.
  • 2) Nephrotic syndrome is defined as the triad of (1) nephrotic range proteinuria (>3.5g/day), (2) hypoalbuminemia (serum albumin < 3) and (3) edema
  • 3) A complication of nephrotic syndrome is thromboembolism so if there is any suspicion for renal vein thrombosis, get a renal ultrasound with dopplers!

Want to learn more?

Approach to bilateral lower extremity edema

  • 1) Most common causes: heart failure, liver failure, or renal failure/ nephrotic syndrome
  • 2) Less common/ don’t miss: hypoalbuminemia (2/2 malnutrition/ malabsorption), venous stasis, thromboembolism, refeeding syndrome, hypothyroidism, vasodilated state (sepsis, burns, severe allergic reaction), medications (anti-hypertensives, NSAIDs, vasodilators, steroids)

Approach to nephrotic syndrome

Nephrotic syndrome can be thought of as a primary condition or secondary to systemic disease. Rob Rope suggested a brief 5-item differential of: FSGS, membranous, minimal change, inflammatory (infection, malignancy, autoimmune) and meds. See this excellent former chief resident blog post on a more detailed approach to nephrotic syndrome.

Given this workup, consider ordering the following labs: A1C, lipid panel (HLD/lipiduria is common complication), coags, ANA, complements, SPEP/SFLC/UPEP, HIV, Hepatitis B and C Abs, RPR, renal ultrasound with dopplers… and don’t forget that usually you will need a kidney biopsy to make the definitive diagnosis!

Mini EBM: Nephrotic syndrome and cancer mortality

Curtis found a retrospective cohort study out of a National Danish registry of ~4000 patients with nephrotic syndrome as per ICD coding from 1980-2010. Of these, ~300 were diagnosed with cancer subsequently. This study tried to address whether the patients with nephrotic syndrome with subsequent cancer had an increased 5-year mortality as compared to those without nephrotic syndrome and cancer. It identified a comparison cohort from a Danish cancer registry of patients with cancer. The study used a cox regression adjustment for age, gender and comorbidity. It did not pre-define its endpoints, adjust for multiple hypothesis testing, propensity score match, or perform sensitivity analysis. At 5 years, 69% of patients with prior nephrotic syndrome died whereas 63% of patients without prior nephrotic syndrome died. It concluded that the adjusted hazard ratio was 1.20 for 5 year mortality (95% CI 1.02-1.42).

Sarcoidosis...?

Today, Dr. Amrock presented an interesting case presentation with a diffuse HPI and poorly localizing signs and symptoms for which the diagnostic concern centered around evidence of granulomatous inflammation, hilar lymphadenopathy, uveitis, and possible infiltrative cardiomyopathy concerning for sarcoidosis. The patient underwent BAL with testing sent for analysis of the CD103/CD8 ratio that was potentially suggestive of pulmonary sarcoidosis. Some takeaways:

  • The published sensitivity and specificity of the CD103/CD8 ratio in BAL washings for the diagnosis of sarcoidosis was 81% and 78% respectively, which gives a +LR of 3.68 and 0.24 respectively. Which means the positive test should raise our pretest probability of the diagnosis of sarcoidosis ~20-25% (link to my favorite sensitivity/specifity to likelihood ratio converter).
  • Sarcoidosis is a multisystem disorder of unknown etiology that is characterized pathologically by the presence of noncaseating granulomas in involved organs
  • A definitive diagnostic test does not exist. The diagnosis of sarcoidosis requires three elements: 1) Compatible clinical and radiographic manifestations 2) Exclusion of other diseases that may present similarly 3) Histopathologic detection of noncaseating granulomas.

Syncope secondary to torsades de pointes

Today we reviewed a case of an elderly gentleman with a complex cardiac history who presented with a witnessed syncopal episode, found to have recurrent inpatient syncopal episodes with telemetry evidence of torsades de pointes. Ultimately, he required isoproterenol and eventually overdriving pacing to maintain his normal rhythm.

Learning points:

  1. We reviewed the differential diagnosis of syncope early in the report to help guide our history taking and broke the categories down into neurally mediated, orthostatic hypotension, cardiovascular (arrhythmia, mechnical) and neurogenic.
  2. We asked targeted questions including onset of syncope, position of patient, provocative factors, associated symptoms before and after the event, pre-existing conditions and reviewed his medication list.
  3. As we all strive for high value and cost conscious care, we reviewed the cost of common diagnostic tests for syncope in a fun "Price is Right" game. A retrospective study by Mendu is an excellent resource to review a cost-effective approach to evaluating syncope.
  4. Dr. Purtell provided an excellent overview of drug-induced QT prolongation and torsades de pointes including factors to consider (medications, organic heart disease, metabolic derangements, bradycardia, AV and SA blocks, female gender). Here is the link to his PICO question article examining azithromycin and the risk of cardiovascular death published by Ray in the NEJM.

Horner syndrome & Diffuse large B-cell lymphoma

Thanks Aya for presenting an excellent case! Also many thanks to Vinay Prasad for attending and shedding wisdom on the history and diagnosis of lymphoma. This was a case of a patient presenting with recurrent syncope, found on exam to have Horner syndrome and diagnosed with pancoast tumor on biopsy found to be consistent with "double-hit" diffuse large B cell lymphoma. The patient was found to not be in tumor lysis and was started on R-EPOCH to treat lymphoma.

horner

(Img: UtD)

Main points:

  • 1) The sympathetic trunk spans the area of the hypothalamus down to approximately the T2 spinal cord level and normally innervates muscles of the eyelid (superior tarsal muscle), pupil (pupillary dilator muscle) and sweat glands. Horner syndrome consists of the triad of “ptosis, miosis and anhidrosis” and is caused by damage along any portion of the sympathetic trunk.

  • 2) When Horner syndrome is present on exam, consider cross sectional imaging of the neck AND chest given the location of the sympathetic trunk.

  • 3) Diffuse large B-cell lymphoma can be an aggressive disease and oncologic emergencies to consider evaluating for include tumor lysis syndrome (hydrate and trend TLS labs) as well as evaluating for airway compromise (ENT consult) and cord compression (neurosurgery consult) if suspected.


Want to learn more?

Framework for Horner syndrome

One approach to Horner syndrome can be to think about ipsilateral CNS vs pre/postganglionic lesions. As pictured above, the first order neurons start in the hypothalamus and terminate at C8-T2, the preganglionic neurons terminate at the superior cervical ganglion and postganglionic neurons terminate at the site of innervation.

  • Central Nervous System

    • Any lesions of the hypothalamus, brainstem and spinal cord (eg demyelination from multiple sclerosis, vascular abnormalities, tumors, vertebral stroke eg. Wallenberg / lateral medullary syndrome)
  • Peripheral Nervous System (preganglionic and postganglionic)

    • Neck/ cervical roots – cervical rib, aortic aneurysm, surgery/ trauma
    • Apical lung disease – Pancoast tumor (which can also associated with shoulder/arm symptoms and voice changes from compression of brachial plexus, SVC, and recurrent laryngeal nerve and usually is 2/2 lung cancer but can be any malignancy that occurs at the lung apex and includes infections such as TB and pneumonia)
    • Internal carotid artery – eg dissection (which can present with headache, blurry vision, pulsatile tinnitus in a patient who has had trauma to the neck/ or risk factors such as collagen vascular disease)
    • Middle ear disease
    • Cavernous sinus disease
    • Skull base lesions
    • Thyroid cancer
    • Headache syndrome such as cluster headaches

Diffuse large B-cell lymphoma

Workup of diffuse large B-cell lymphoma includes biopsy (FNA although excisional or core usually needs to be performed to get more tissue) to be sent for IHC and flow cytometry, serum LDH (IPI prognostic score), tumor lysis labs (patients at risk), PET-CT (staging) as well as HIV, hepatitis B, TTE, and fertility/ sperm banking prior to starting therapy with combination cytotoxic chemotherapy and rituximab.

Since we see this diagnosis fairly often as it is the most common lymphoma in the Western world, here is an an excellent review article on diffuse large B-cell lymphoma from Annals of Oncology that goes through diagnosis, staging (including review of double-hit vs double-expressor), and current treatment options for patients with this disease. The standard of care in most cases is R-CHOP.

rchop

(Img: http://www.nejm.org/doi/pdf/10.1056/NEJMct1114348 )

Here are some additional papers that Aya identified regarding how aggressive to be in treatment of double-hit lymphoma given its poor prognosis:

  • 2014 Blood paper: non-randomized retrospective study of patients with double-hit lymphoma showed daEPOCH-R had the highest response rate, but insignificant overall survival benefit
  • 2014 British Journal of Haematology paper: retrospective study of patients with double-hit lymphoma showing better 2-year event-free survival (EFS) in the R-EPOCH group
  • 2016 ASH presentation: randomized phase III of patients with advanced DLBCL found no difference in EFS in patients treated with R-EPOCH in comparison to R-CHOP, although the n for double-hit lymphoma is likely too small to draw conclusions

Vertebral Osteomyelitis Causing Diffuse Abdominal Pain

Thank you to Dr. Cohen for a very interesting case of a woman presenting with "30/10" abdominal and back pain with initial concern for symptomatic choledocholithiasis found to have vertebral osteomyelitis. A few key learning points from today's case:

  1. Not all "abdominal pain" is from the abdomen. If the description does not fit your illness script, then start to think about other causes. For example, bilateral "band-like" abdominal pain does not fit the classic description of choledocholithiasis but could fit with pain radiating from the vertebra (think osteo or compression fracture, etc).
  2. Post-cholecystectomy common bile duct (CBD) dilatation can be normal and asymtomatic generally up to 10mm according to a 1-year prospective study out of Korea. Additionally, methadone maintenance therapy can increase the CBD diameter an average of 2.39mm according to a study out of Boston.
  3. Don't forget to review the primary data yourself! On outside hospital transfers, have the images pushed to our system and review them yourself and/or with Radiology. Some findings can be missed and the clinical history may change when you see them prompting evaluation of different features.
  4. In a clinically stable individual with vertebral osteomyelitis, obtain blood cultures, ESR, CRP, consider an Echo (especially if there is a new murmur) and consult your surgical colleagues to obtain tissue before starting antimicrobials.
  5. Be leary of the spinal cord stimulator. Look out for complications which include hardware malfunction such as lead migration or fracture, infection or tolerance. For more information on spinal cord stimulators, please refer to the systematic review and meta-regression analysis in Pain Practice.