Cardiac Sarcoidosis

Clinically manifest cardiac involvement occurs in approximately 5% of patients with sarcoidosis. While up to 25% of sarcoidosis patient will have silent disease involvement. The 3 principle manifestations include:

  1. Conduction abnormalities
  2. Ventricular arrhythmias (including sudden death)
  3. Heart Failure

Diagnosis:

The ECG is usually abnormal in patients with clinically manifest disease. Abnormalities include

  • various degrees of conduction block
  • QRS complex fragmentation
  • ST-T wave changes
  • Pathologic Q waves (pseudo-infarct pattern)
  • Epsilon Waves (small positive deflection occurring at the end of the QRS)

*Right bundle branch block typically predominates over left bundle branch blocks.

The Echocardiogram usually demonstrates non-specific abnormalities such as regional wall motion abnormalities not occurring in a non-coronary distribution, diastolic/systolic dysfunction, aneurysms. *The most specific finding is thinning of the interventricular septum.

Biomarkers such as Angiotensin-converting enzyme levels, troponins, and soluble interleukin-2 receptor levels are not sensitive or specific enough for clinical use.

Cardiac MRI: There is no specific pattern of late gadolinium enhancement on cMRI that is diagnostic for cardiac sarcoidosis, however it is usually patchy and multifocal with the endocardial sparing.

Cardiac PET: Patients must be fasting long enough to enter metabolic state where ketosis predominates (48 hours) in order to suppress physiologic FDG uptake in the cardiac muscle to help distinguish the areas of FDG-avidity signifying pro-inflammatory macrophages.

Endomyocardial Biopsy: Modality has a low sensitivity due to the focal nature of the disease. In order to increase diagnostic sensitivity some centers will utilize electrophysiological mapping or image-guided strategies for biopsy.

Clinical Situations Where Immunosuppression Should Be Considered in Patients with Cardiac Sarcoidosis

  • Mobitz II or 3rd degree heart block and evidence of myocardial inflammation
  • Frequent Ventricular ectopy or non-sustained arrhythmias and evidence of myocardial inflammation
  • Sustained ventricular arrhythmias and evidence of myocardial inflammation
  • Left ventricular dysfunction and evidence of myocardial inflammation

Treatment of Clinically Manifest Cardiac Sarcoidosis

  1. Prednisone 0.5 mg/kg/day for 3 months
  2. Repeat PET scan at 3 months
    1. If abnormal, FDG uptake present on PET add a methotrexate
    2. If normal, slowly taper corticosteroids over 9 months for a total treatment duration of 12 months.
      1. Repeat PET scan 3 months after cessation of treatment and reassess need for repeat treatment of relapsed disease (requires initiation of methotrexate

References:

  • Birnie D., Nery P.., Ha A., Beanlands R. Cardiac Sarcoidosis.J Am Coll Cardiol 2016;68:411–21

Approach to Cavitary Lung lesions

When presented with a cavitary lung lesion utilize the following approach:

Step 1: Review old images to determine chronicity of the lesion

Step 2: If the illness script and imaging suggest an acute or sub-acute duration (<12 weeks) evaluate for Acute Infection.

Step 2a: Assess the elements of the History and Physical to guide your further diagnostic evaluation (fever, chills, productive cough, aspiration risk, elevated WBC, elevated pro-calcitonin, Galactomannan and beta-D-Glucan levels, endemic fungal antigen)

Step 2b: Assess Non-contrasted CT Chest Features in the context of the clinical picture to identify possible etiology including:

  • Lung abscess
  • necrotizing pneumonia (typical and atypical bacteria)
  • septic emboli
  • fungal infection
  • Nocardia

Step 3: If the illness script and imaging suggest chronic duration (>12 weeks) evaluate for

Chronic Infections: Commonly featuring fevers, weight loss, chronic cough, hemoptysis, fatigue. These include:

  • Mycobacterial Tuberculosis
  • Non-tubercular Mycobacteria (e.g. MAI)
  • Fungal infection (aspergillosis and endemic fungi)
  • Human Papilloma Virus
  • Parasitic Disease (e.g. echinoccocus)

Malignancy: Cavities commonly encountered on Staging CT scans (up to 20% of lung malignancies)

Relative Frequency: Squamous histology > lymphoma>>>adenomatous histology/large cell/small cell histology

Autoimmune: Featuring history of rheumatologic disease, arthralgias, myalgias, positive serologic testing. These include:

  • Rheumatoid Arthritis
  • Granulomatosis with Polyangitis

References

  • Gafoor et al. Cavitary Lung Diseases: A Clinical-Radiologic Algorithmic Approach. CHEST 2018; 153(6):1443-1465.

Legionnaires’ Disease

Legionnaire’s disease

Discovery: First outbreak in 1976 in Philadelphia. Case fatality rate 29/182 (16%). Largely due to intracellular bacteria’s resistance to beta-lactams.

Clinical manifestations:

Atypical pneumonia that may resemble typical pneumonia. May account for 2-9% of CAP.

Prodrome: headache, myalgias, anorexia. Fever is accompanied by relative bradycardia (Faget Sign).  The presence of GI (N/V, diarrhea) and neurological symptoms (AMS, seizures, AMS, focal neurologic symptoms).

Labs: non-specific hyponatremia, hypophosphatemia, CK elevation, leukocytosis with relative lymphopenia.

Imaging: Most commonly patchy, unilobar infiltrate progressing to consolidation, but all patterns are seen. Up to 50% have pleural effusions. Immunosuppressed individuals can have nodules and cavitation.

Risk Factors: Underlying pulmonary disease, smokers, Age >50, Steroids, hematologic malignancies. Unclear whether HIV is a risk factor for Legionnaires’ disease.

Diagnosis: urine antigen testing is first line. It is limited to detection of only certain legionella sp. Test sensitivity is 56-99%. The ISDSA and ATS guidelines recommend urine antigen testing in CAP patients 1) not responding to outpatient antibiotic therapy, severe pneumonia such as those requiring ICU, immunocompromised individuals, excessive alcohol use history, travel within past 2 weeks, age >50.

Antimicrobial therapy: Most macrolides, ketolides, quinolones are effective. Beta lactams and aminoglycosides should be avoided.  No RCT has compared outcomes between levofloxacin versus azithromycin.  The British recommend a fluoroquinolone in the setting of severe disease (limited supporting data).

Reference: Cunha B, Burillo A, Bouza E. Legionnaires’ disease. Lancet 2016; 387: 376–85.

PMID: 26231463

Vaping Induced Lung Injury

Think your young patient has a vaping induced lung injury (VAPI)?

Suspicion should be high in young, otherwise healthy adults who use e-cigarettes or THC products. Clinical features include a sub-acute bilateral interstitial pneumonitis. CT chest will often demonstrate sub-pleural sparing.

Here are the CDC Case Confirmation Criteria:

  1. Use of e cigarette or dabbing in 90 days prior and pulmonary infiltrate
  2. Absence of pulmonary infection on initial work up.
  3. No evidence in medical record of alternative plausible diagnoses (e.g. cardiac, rheumatologic, neoplastic)

Minimal criteria include: negative RVP/influenza, urine antigen for strep pneumonia and legionella, sputum culture if productive cough, blood culture, negative HIV and HIV-related opportunistic infection.

 

PA Week

National Physician Assistant Week 10/6-10/12

History of a Profession

The origin of the PA profession began with Dr. Charles L Hudson, MD an internist from Cleveland, Ohio who recognized a growing gap between the demand for medical care and the existing supply in the post-WWII era. During his service in WWII, he saw first-hand how individuals without formal medical training could quickly be trained to assist physicians. In 1961 he first proposed to the AMA the creation of what we now consider the PA profession. He suggested trainees could undergo two years of undergraduate coursework followed by 2 years of medical education. Dr. Eugene Stead of Duke was one of the first three physicians to answer the call in 1965. The first pool of trainees were largely comprised of former military corpsmen. However, Dr. Stead was an advocate for women trainees with Duke’s first female graduate in 1970. The program was the first to graduate an African American student in 1968.  At the time the US government was discharging approximately 30,000 medics from the military and only one third were entering the civilian health care service. Since the tax payers had already spent ~$25,000 dollars to train each medic, it made financial sense for the government to finance PA training.

 

 

 

Hemolytic Anemia with Mitral Valve Repair

From Dr. Elliott’s presentation of a patient with new onset hemolysis that likely originated from a recent MVR: Thanks to Dr. Narcisse for his overview of the case!

A gentlemen presented with fatigue and chest pain however the chest pain was a red herring from a recent MVC that was unrelated to presentation. He had mitral valve repair with ring annuloplasty the year prior.  On lab work, he was found to have new anemia (trickling down from prior baseline) and lab work consistent with hemolysis along with schistocytes on blood film. TTE with mild to moderate MR. Hematology and cardiology were consulted and workup was otherwise unrevealing of a diagnosis. Presumably related to mitral valve repair however unable to confirm.

An uncommon cause of hemolysis can be seen after  mitral valve repair and replacements (whether surgical or trans catheter) due to paravalvular leak (PVL). PVL is most commonly related to the disruption of sewing ring sutures that result in incomplete apposition of the valvular structure against the annulus leading to the formation of single or multiple jets. Often it can be mild and cause no symptoms, but some leaks can lead to heart failure, hemolytic anemia, or endocarditis. PVL can sometimes be under appreciated on TTE, and TEE as we said is more useful  in evaluating the shape and significance of PVL. Repair of the valve often resolves the hemolytic anemia.

In line with our discussion of etiologies of mitral valve regurgitation, MR is common in HOCM/septal enlargement due to distortion of the mitral valve apparatus from systolic anterior motion secondary to LVOT obstruction. Anterior displacement of the anterolateral papillary muscle is a common pathogenic abnormality. In most cases, intrinsic mitral valve disease is not present and MR is most often relieved with surgical septal myectomy alone without the need for additional mitral valve intervention.

Matt Carlisle

Cancer Screening

Thanks to Mike Noujaim for his outpatient cancer screening overview!

Cervical cancer screening

– For patients aged 21-29, get a pap smear alone every 3 years (don’t forget screening for gc/chlamydia in all women until age 24)

– Starting at age 30 and until age 65, you can back off screening to co-testing (cytology + HPV) every 5 years, cytology every 3 years, or just HPV every 5 years

– Must follow any abnormal screening test for at least 20 years

– It is okay to discontinue screening at at age 65 IF there are two or more negative pap smears in the past 10 years with the last one being within 5 years. You can also discontinue if a patient had a low risk hysterectomy; however, if patient had hysterectomy for cervical cancer you have to continue screening the vaginal tissue.

Colon cancer screening

– For the general population, start screening for colon cancer at age 50

– In patients with a first-degree relative who was diagnosed with colon cancer, start screening 10 years before the age when the relative was diagnosed or at age 40, whichever is earlier. The guidelines state that if you have a FH of colon ca in a first-degree relative diagnosed at age 60 or greater, then the screening intervals don’t change.

– Patients with IBD should start colon cancer screening 8 years after diagnosis with biopsies every 1-2 years

– In patients with a personal history of colon cancer you screen at 1 year; if normal then at 3 years and if that is normal then at 5 years.

– It can be challenging to remember the appropriate follow up intervals for each of the different polyp types, but here is a basic summary:

– 10 year follow up — hyperplastic polyps <10 mm

– 5 year follow up — sessile serrated polyp <10 mm, fewer than 3 tubular adenomas

– 3 year follow up — any polyp >10 mm, 3 or more tubular adenomas, any villous polyps

– If a first-degree relative was diagnosed before age 60 then screening should continue every 5 years regardless of the findings (unless it finds cancer, obviously)

– Don’t forget about Lynch syndrome Amsterdam II Criteria (3-2-1-1 pattern) — three individuals affected, two successive generations, one before age 50, one 1st degree relative

– Remember start screening at age 45 for African Americans as they can potentially develop colon cancer earlier

– You can do annual FIT testing for patients who refuse colonoscopy. However, remember to discuss that the next step will have to be colonoscopy if FIT testing is positive. Medicare will pay for FIT-DNA (Cologuard) every 1-3 years up to age 85.

Breast cancer screening

– In general, the boards will only cover guidelines that overlap between USPFTF and ACS recommendations

– You should be screening for breast cancer every 1-2 years from ages 50-74.  You can consider starting at age 40 after having a discussion of the risks/benefits with the patient

– Per the boards, high breast density alone does not necessitate adjunctive breast imaging (though you can consider adding tomosynthesis in real practice)

– If there is a 20% lifetime risk of breast cancer, order breast MRI and mammogram (calculate risk with Gail model)

– Remember the sensitivity for mammogram alone is only 60%; the false positive rate is 10%. Mammogram + US is 80%. Mammogram + MRI is greater than 90%.

AAA Screening

-Screen once for patients 60 or older who have a smoking history of 100 cigarettes or more.

Lung cancer screening

– Annual low dose CT chest for patients age 55-80, 30 pack year history, quit in the last 15 years

– For ground-glass nodules you have to follow those for 5 years because they can be slow-growing adenocarcinomas

Matt Carlisle

 

Minimal Change Disease

Thanks to James Helzberg for an excellent report on nephrotic syndrome and Minimal Change Disease!

Nephrotic Syndrome

Definition: Nephrotic range proteinuria (>3.5 g daily) with hypoalbuminemia and peripheral edema.

Other Common Features: Hyperlipidemia (hypertriglyceridemia & hypercholesterolemia), and lipiduria

Epidemiology: 2008 BMJ review article quoted 3 new cases per 100,000 each year in adults

Workup:

  1. Spot urine protein/creatinine ratio
  2. Things to think about before labs: DM, SLE, HIV infection, NSAID use, Interferon treatment, bisphosphonates, lithium, gold Penacillamine
  3. HbA1c, HIV, ANA, C3/C4, Serum free light chains, SPEP, UPEP & immunofixation, syphilis serologies, HBV & HCV serologies, cryoglobulins
  4. Anti-PLA2R antibody screen
  5. Renal Biopsy

Common Glomerular Nephrotic Syndromes and Associations:

Minimal Change Disease (MCD): Glomeruli appear normal on light microscopy. Retraction, widening, and shortening of foot processes seen on EM. Most common form of nephrotic syndrome in children. About 16% of nephrotic syndrome cases in adults. Associations include NSAID use, paraneoplastic effect 2/2 malignancy – most often Hodgkin’s Lymphoma

FSGS: Segmental areas of mesangial collapse and sclerosis seen on LM. Most common form of nephrotic syndrome in adults. Associations include HIV, reflux nephropathy, massive obesity, interferon treatment, heroin abuse. Primary (idiopathic) disease is usually acute onset, secondary disorders are generally more insidious.

Membranous:  BM thickening seen on LM with electron dense deposits across the glomerular membrane on EM (“spike and dome”). Most commonly idiopathic (antibodies to PLA2-R). Secondary causes are HBV, HCV, syphilis, autoimmune diseases, thyroiditis, solid tumors, and drugs (NSAIDs, penicillamine, gold, captopril).

Amyloidosis: Congo red stain shows apple green birefringence on biopsy. Monoclonal paraprotein usually detected in serum or urine.

Diabetic GN: Kimmelsteil-Wilson lesions on LM. Most common cause of ESRD in US.

Complications: Protein malnutrition, hypovolemia, AKI, Thromboembolism, infection (cellulitis)

Treatment: Diuresis, Sodium restriction, ACE or ARB long term, Immunosuppression

Matt Carlisle

 

 

Pulmonary Embolism

Thanks to Dr. Talal Dahhan for a great overview of pulmonary embolism management! Below is a brief overview of some of the discussion.

Pulmonary Embolism – Overview on Management.

  • From Risk Stratification Standpoint:
    • Low Risk PE: Most of cases. Normal BP and HR. sPESI score is zero —-> can go home once started on anticoagulation option with follow up with Hematology/Anticoagulation clinic and their PCP. Preferably and recommended to use a DOAC.
    • Intermediate Risk PE: Some of them. Aka Submassive. SBP > 90 mmHg. Usually will be admitted to step down. Unless ProBNP is more than 1000 (BNP > 500) and have relative hypotension with slight upward trending on HR, then needs an ICU admission or transfer with a PERT discussion. All need follow up with Hem/AC, PVD and PCP.
    • High Risk PE: aka massive. SBP < 90 despite some resuscitation. Needs admission to ICU. PERT discussion is needed for a primary reperfusion intervention ASAP (tPA vs CDT vs Surgery). May need a temporary IVC filter if huge DVTs are still there following tPA by US Doppler assessment. Likely a week of hospital stay. Should see PVD, Hem/Anticoagulation and PCP for follow up.
  • When they visit PVD clinic, we determine:
    • Resolution of submassive, massive or significant clot burden PEs (that can be low risk but we need to make sure it dissolves): repeating VQ scan within 6 months. Typically within 3 months.
    • Resolution of RV dysfunction seen on Echo/CT scan on presentation with a follow up Echo.
    • Assure absence of high risk patients to progress to CTEPH from Piazza et al Table.
    • Assure adherence and availability of anticoagulants.
    • Follow up on: Factor VIII level, D-Dimer and ProBNP. First two preferably in clinic and when not sick as they could rise in acute illness. They are considered acute phase reactants.
    • Duke PE Management Algorithm: Please note it is an interactive chart to make it less busy. So click on Yes/No as fits your case.
    • Please note that HsTnT was removed on the algorithm as no data exist for its usefulness in risk stratification.
    • Please consult PVDC when needed. Preferably when suggested on the algorithm.
    • We sometimes need PERT consult rather than PVDC one.

Pulmonary Hypertension – Brief Review on Definitions

Based on the last WSPH criteria

    • mPAP > 20 mmHg is considered now pulmonary hypertension, with only consideration to have treatment considered if above 25 mmHg unless SSc related.
    • CO or Cardiac Index (CI) is the most important (< 2 L/min —> serious disease!).
    • PCWP (or PAOP) > 15 indicates high filling pressure or Pulmonary venous hypertension or Group II patients, while less than 12-15 is more in favor of pre-capillary disease (Groups I, III, IV and V)
  • Additional tools to help differentiating different groups:
    • Transpulmonary Gradient (TPG) = mean Pulmonary Artery Pressure – PAOP. Difference of more than 15 may indicate possible PAH on top of PH processes (mixed disease).
    • Diastolic Pulmonary Gradient = diastolic pulmonary pressure – PAOP or wedge pressure. Difference more than 5-7 mmHg may further prove PAH in these patients is more valuable [JACC Heart Fail. 2015 May;3(5):424-5 ].
    • A rise in PAOP after a 7 ml/Kg fluid bolus to above 15 mmHg gets a better chance to identify group II patients[ CHEST 2017; 151(1):119-126 ]
    • Exercise RHC can unmask precapillary disease better but cannot be obtained anywhere [ Circ Heart Fail. 2010;3:588-595 ].
  • When to refer a PH patient to clinic ?
    • Sure about Group I, or IV possibility
    • Preferably to have mostly a precapillary involvement
    • Echo is your best screening tool, and you need to see one of these three findings in the absence of acute or critical illness and perhaps better to have the echo done as outpatient:
      • RVSP > 60 mmHg
      • RV dilation
      • RV hypokinesis (without ischemic heart disease history)
  • General Management options we need to consider in ALL groups of PH. Please consider initiating management in that direction when you suspect PH clinically
  • Cardiopulmonary rehabilitation: slow-paced respiration therapy is feasible in patients with PAH and may improve symptoms and lower IL-6. Therefore, patients need to be referred to pulmonary rehab [Heart Lung 2017 Jan – Feb;46(1):7-13].
  • Salt and fluid restriction, extrapolated for management of heart failure [Circulation. 2013;128(16):e240].
  • Diuretics: They diminish hepatic congestion, peripheral edema, and pleural effusions and may be of particular benefit in those in whom interventricular sepal deviation from elevated RV pressure impairs left ventricle output. Has clinical benefit to avoid end organ damage from PH [Eur Heart J. 2016;37(1):67].
  • Anticoagulation: might be favored in CCB responders’ Group I and Patients on maximum combination therapy Unless Connective Tissue Disease associated patients.
  • Avoid or Correct Anemia: can cause RV ischemia which leads to worsening disease.

 

Matt Carlisle

 

Ocular Candidiasis

The rate of Candida fungemia has increased over the past several decades while the rate of ocular involvement has decreased. Ophthalmologic evaluation and timing is often a question that arises after diagnosis of Candida fungemia. There are differing views on the utility and timing of the dilated retinal exam, in part because of the low-quality of evidence regarding these patients. The current IDSA guidelines (2016 Update) recommend a dilated retinal exam within the first week of therapy in nonneutropenic patients. Findings such as choroidal and vitreal infection are minimal until resolution of neutropenia so it is recommended to delay the exam until recovery of neutrophil counts in neutropenic patients. Both of these are strong recommendations with a low-quality of evidence. A retrospective study (Khalid et al, PMID: 25484895) evaluated patients from 2000-2010 who were diagnosed with Candida fungemia who underwent fundoscopic evaluation to assess the burden of ocular involvement. 283 patients with Candida fungemia were assessed in the study with 144 (51%) undergoing fundoscopic evaluation. The mean time from collection of positive blood cultures to fundoscopic evaluation was 5.8 days. 18 patients (12.5% of those evaluated) had chorioretinitis while only 2 patients had endophthalmitis. Based off the current IDSA guidelines ophthalmologic evaluation should be obtained in all patients within 7 days of diagnosis of fungemia. There is not sufficient current evidence to forego a formal exam based off lack of ocular symptoms.


References

https://www.idsociety.org/practice-guideline/candidiasis/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248481/

Matthew Carlisle