08/02/19 Immunizations

Pneumococcal vaccination

– Immunocompetent patients aged 19-65 years should receive PPSV23 (Pneumovax) if they have any of the following underlying medical conditions: chronic heart disease, chronic lung disease, diabetes mellitus, alcoholism, chronic liver disease, cigarette smoking, CSF leaks, cochlear implants)

– ACIP previously recommended that all patients aged 65 and older who have not previously been vaccinated should receive PCV13 (Prevnar), followed by a dose of PPSV23 1 year later 

           – The most recent recommendation (though technically not finalized) is to engage in shared decision making with your patients

– In immunocompetent adults aged 65 and older who have already received a dose of PPSV23, PCV13 should be administered no sooner than 1 year later

– In adults aged 19-64 years with high-risk conditions who require vaccination with both PCV13 and PPSV23 (sickle cell, asplenia, HIV, CKD, leukemia/lymphoma, generalized malignancy, iatrogenic immunosuppression, solid-organ transplant, multiple myeloma, inherited immunodeficiency, CSF leaks, cochlear implants) but have not yet received either, a single dose of PCV13 should be given first, followed by a single dose of PPSV23 given at least 8 weeks later

          – Those with high-risk conditions who have already received PPSV23 should be administered a single dose of PCV13 no sooner than 1  year after receiving the most recent PPSV23

          – In these high-risk patients, a second dose of PPSV23 should be administered 5 years after the first PPSV23 dose (except in those with CSF leaks or cochlear implants) 

Herpes zoster vaccination

– All adults aged 50 years and older (including those with a previous episode of zoster) should receive the shingles vaccine (preferably Shingrix).  If only Zostavax is available then vaccination is indicated for those aged 60 years and older

– Shingrix (recombinant vaccine) has demonstrated 97% efficacy in patients aged 50-69 years and 91% efficacy in those aged 70+.  It is administered in two doses 2-6 months apart and costs ~$400.  It is highly associated with a flu-like illness so be sure to warn your patients! 

– Zostavax (live attenuated vaccine) has approximately 50-60% efficacy and is administered in a single dose.  It costs ~$300.  It is recommended that patients who have been previously vaccinated with Zostavax should be re-vaccinated with Shingrix 

It is still appropriate for patients who have already had shingles to be immunized with either Shingrix or Zostavax as they still have a substantial risk for a future episode

Influenza vaccination

– There are four main ‘flavors’ of influenza vaccines: live attenuated (intra-nasal), trivalent, high-dose trivalent, and quadrivalent

– In general, give the quadrivalent to your patients <65 years and the high-dose trivalent to patients >65

– Patients with an egg allergy of any severity can receive any influenza vaccine formulation.  Those who previously developed symptoms of angioedema should have the vaccine administered in clinic (not at a pharmacy or flu-shot fair)

 

Author: Dr. Mark Robertshaw

Moderator: Dr. Larry Greenblatt

08/09/19: Colon, Breast, Lung, and Cervical Cancer Screening

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

– Patients with IBD should start colon cancer screening 8 years after diagnosis with biopsies every 1-2 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 (3-2-1-1 pattern) — three individuals affected, two successive generations, one before age 50, one 1st degree relative

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)

Lung cancer screening

– Age 55-80, 30 pack year history, quit in the last 15 years

Cervical cancer screening

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

– 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

 

Author: Dr. Mark Robertshaw

Moderator: Dr. Anne Phelps

July 25, 2019: Annual Exams

Annual Exam Practical Tips:

  • With every visit, it is helpful to spend 2-3 minutes connecting with the patient
  • Patient and provider have their own separate agenda, and you want to make sure you address the patient’s agenda to avoid hand in the doorknob syndrome
  • Use the annual exam as an opportunity to control/update the problem list (erase the clutter)
  • Make sure to ask social history (sex, etoh, tobacco, vaping, physical activity)
  • It is okay to “abort” wellness visit if patient has other active issues; ask patient to come back in a few weeks to focus on a “physical”
  • Physical exam does not need to be extensive, but should be thoughtful, if new murmur more thorough CV exam

Lecturer: Dr. Peyser

Author: Dr. Diana Mosquera

July 24, 2019: Eosinophilia

EOSINOPHILS

How do they develop? under the influence of IL-5, IL-3, and GM-CSF.

Normal levels: 0 to 500/microL (<0.5 x 109/L) is typically considered normal.

Mechanisms of eosinophilia:

  1. Overproduction of IL-5 stimulating eosinophil production: usually seen in helminthic infections, allergen exposure, EGPA, adenocarcniomas which produce IL-5, tc cell or hodgkin’s lymphomas
  2. Clonal expansion: less common but due to acute or chronic eosinophilic leukemia

Peripheral eosinophilia cannot be used to accurately predict risk of organ damage.

How do eosinophils damage tissue?

  • Release of toxic granule products (major basic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, or eosinophil cationic protein
  • Production of lipid mediators, such as sulfidopeptide leukotrienes and platelet activating factor, which mediate smooth muscle contraction and recruitment of inflammatory cells.
  • Release of cytokines such as GM-CSF, transforming growth factors (TGF)-alpha and -beta, and interleukins, which may be involved in tissue remodeling and fibrosis.

Causes: NAACP

Neoplasms, Addison’s disease, Allergic diseases, Collagen vascular diseases, and Parasitic diseases.

Degree of eosinophilia is not very useful other than at the extremes (very low is likely allergic v.s very high is likely myeloproliferative)

Neoplastic causes:

  • Primary hypereosinophilic syndrome (HES): FIP1L1, PDGFRA, PDGFRB, FGFR1
  • Acute eosinophilic leukemia (FAB M4Eo): usually present with S/S of pancytopenias (fatigue, infection, bleeding)
  • Chronic eosinophilic leukemia: can be asymptomatic or have constitutional symptoms
  • Other MPNs: JAK2 (P. vera), CML
  • Lymphomas
  • Sezary syndrome: cutaneous lymphoma with eosinophilia and erythroderma.
  • Pre-B ALL: Acute ALL with 5;14 translocation
  • Systemic mastocytosis: present w/urticaria pigmentosa

Parasites to consider:

  • Strongyloidiasis: endemic in hot, humid climate (Southeastern US and southern Europe): can have latecy of years between initial exposure and development of symptoms. Think of it if people were given systemic glucocorticoids for COPD or rheumatologic conditions.
  • Toxocariasis: Can be ingested with soil/food contaminated by dog or cat feces
  • Trichinellosis: Ingestion of uncooked meat, especially prok
  • Hook work (Ancylostoma duodenale): Can present with rash, cough, GI symptoms

Non helminthic infections:

  • Scabies
  • Aspergillus infections
  • Retroviral infections

Drug reactions:

  • DRESS: REGISCAR Criteria, drug initiation 6-8 weeks prior, morbilliform rash that becomes confluent, liver/kidney involvement

Connective tissue/rheumatologic disorders

  • Eosinophilic  granulomatosis with polyangitis (formerly Churg Strauss)
  • Toxic oil syndrome
  • Eosiniophilic fasciitis

Immunologic causes:

  • Hyperimmunoglobulin E syndrome (Job syndrome): recurrent bacterial infections, elevated IgE, chronic dermatitis
  • Others: Omenn syndrome, IPEX, ZAP-70

Author: Madhu Eluri

References:

July 18, 2019: ANCA Vasculitis

ANCA associated Vasculitis

Definition: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is necrotizing vasculitis affecting small blood vessels that does not involve deposition of immune complexes.

Associated with ANCA specific for myeloperoxidase (MPO-ANCA) or Proteinase 3 (PR3-ANCA)

  • Encompasses granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis

Notable presenting symptoms of GPA/MPA:

  • ENT: Things like sinusitis, otitis media, bloody nasal discharge, nasal/oral ulcerations much more common in GPA than MPA (90 vs 35%)
  • Lower respiratory tract: Chronic cough, hemoptysis, stridor, wheezing, pleuritic chest pain.
    • On radiography, can see nodules, patchy or diffuse opacities, and hilar adenopathy
  • Renal: Hematuria, subnephrotic proteinuria, renal failure (even RPGN)

 

Notable Presenting symptoms of EGPA:

  • Typically have chronic rhinosinusitis, asthma, and eosinophilia

Diagnosis:

  • ANCA
    • 82-94% of GPA or MPA have + ANCA
    • Only 40% of EGPA have + ANCA
    • GPA: Mostly PR3-ANCA
    • MPA: Most commonly MPO-ANCA
    • 20% of MPA or GPA have opposite ANCA
    • EGPA: Usually MPO-ANCA
  • Leuckocytosis, thrombocytosis, elevated inflammatory markers also seen
  • Eosinophilia in EGPA
  • UA
    • Usually with active sediment
  • Biopsy (almost always needed)
    • Typically the skin or the kidney
      • Skin shows leukocytoclastic vasculitis without complement (or minimal) and immunoglobulin
      • Kidney biopsy typically shows pauci-immune glomerulonephritis
    • Occasionally, a lung biopsy can be done as well (usually thorascopic)
    • For EGPA, biopsy often show eosinophilic infiltration

 

Treatment:

  • Aggressive immunosuppression is warranted in almost all patients
  • Two main phases
    • Initial treatment
      • Regimen depends on presence of organ or life threatening manifestations (renal failure, cerebral involvement, pulm hemorrhage, etc)
      • Methotrexate, rituximab, or cyclophosphamide combined with steroids most frequently
      • EGPA is typically steroids +/- cyclophosphamide
    • Maintenance
      • EGPA
        • MTX or azathioprine + steroid taper
      • PR3-ANCA positive
        • MTX, axathioprine, or rituximab + steroid taper
      • MPO-ANCA positive
        • Azathioprine or MTX + steroid taper

Authors:

Dr. Nicholas Koutlas

Dr. Anish Badjatiya

July 19, 2019: Hypertension outpatient management

Hypertension Morning report

  • In 2017, ACC/AHA released their HTN guidelines which updated the HTN goals (previously established by JNC8-2014)
      1. Normal” is < 120 and < 80, an “elevated BP” is 120-129 systolic and <80 diastolic
      2. Hypertension stage 1 is 130-139 systolic or 80-89 diastolic
      3. Hypertension stage 2 is a SBP >140 or DBP >90
  • White Coat Hypertension is an intermediate risk group that many studies (not all) have identified a minimal increase in risk of CVD complications or all-cause mortality when compare to normotensive patients1
  • BP goal: ACC/AHA advocate for 130/80 goal for everyone (SPRINT trial, though it excluded DM patients)
  • ACC/AHA guidelines also take into account the ASCVD risk when deciding management of new stage 1 HTN (if ASCVD risk>10, medication usually indicated, if ASCVD risk< 10, can start with lifestyle modifications)
  • Lifestyle modifications
    • Smoking cessation
    • DASH diet (diet rich in fruits, vegetables, legumes, and low-fat dairy products and low in snacks, sweets, meats, and saturated and total fat)
    • Aerobic exercise
  • Also do not forget to evaluate for secondary causes of hypertension if indicated
      1. OSA (most common)
      2. Renal artery stenosis (CTA or MRA, can consider Renal Doppler US but mainly useful if positive)
        1. Controversial whether beneficial (ASTRAL did not include patients most likely to need it) but may be worth evaluating patients for it, especially those with resistant hypertension (more than 3 drugs at max doses
      3. Hyperaldosteronism
      4. Pheochromocytoma (uncommon)
      5. Cushing’s
      6. Aortic Coarctation

Author: Diana Mosquera

July 17, 2019: IgG4-related disease

IgG4-Related Disease

Definition: Tumefactive lesions consisting of IgG4-positive plasma cells, storiform fibrosis, and sometimes elevated serum IgG4 that can involve any organ system
What is IgG4? Accounts for <5% of total IgG in healthy people. IgG4 can be produce by Th2-cell mediated immune reaction which produce Interleukin 10 –> increases IgG4
  • IgG4 is thought to play a role in pemphigus vulgaris, idiopathic membranous GN, and TTP
Since it’s discovery in 2003, IgG4-related disease has been adopted to replace other conditions that were previously thought to be separate entities: Riedel’s thyroiditis, mediastinal fibrosis etc (see Table 1 in NEJM article)
Clinical Manifestations:
  • pancreatitis
  • Aortitis –> aneurysms/aortic dissection
  • Cholangitis –> which if untreated can lead to hepatic failure in months
  • Siladenitis
  • Orbital structure involvement
  • Retroperitoneal fibrosis
  • Atopy such as bronchial asthma or chronic sinusitis
Diagnosis:
  • Biopsy w/histopathology findings of lympoplasmocytic infiltrate w/IgG4-positive plasma cells, storiform fibrosis (matted and irregularly whorled pattern), and obliterative phlebitis. can also see mild-to-moderate eosinophilic infiltrate. Usually peri-ductal infiltration in glandular organs.
  • Increased serum IgG4 is seen in ~40-70% of patients, but can be nonspecific as it can also be seen in GPA, bronchiectasis etc
Treatment: Treatment response depends on degree of fibrosis that is already in place. Patients who are still in the lymphoplasmocytic inflammatory phase tend to respond better to therapy vs. those with well-established fibrosis.
  • Prednisone: 0.6mg/kg x 2-4 weeks followed byslow taper
  • Azathioprine, mycophenolate mofetil, methotrexate
  • Refratory or recurrent disease: Rituximab
Reference:
Stone et al. N Engl J Med. 2012; 366:539-551

July 7, 2019: Adrenal incidentalomas

Adrenal incidentalomas

Definition: an adrenal mass generally 1cm or more in diameter that is found incidentally on radiology performed for another reason
Differential: benign adrenocortical adenoma, cortisol-secreting adrenocortical adenoma, pheochromocytoma, adrenocortical carcinoma and metastatic carcinoma
 
General approach to incidentalomas:
  • Lab workup: 1mg overnight dexamethaxone suppression test, 24-hr urine fractionated metanephrines and catecholamines, +/- plasma renin/aldosterone if hypertensive
  • Imaging with CT abdomen with and without contrast (consider MRI, PET or SPECT based on clinical suspicion for metastatic disease)
  • If the above findings are normal, repeat imaging at 6, 12 and 24 months and repeat hormonal evaluation yearly for 4 years
  • Consider adrenalectomy if adrenal mass is >4cm, enlarges by >1cm during surveillance period of if hormonal evaluation changes
Other considerations:
  1. CT scan findings for carcinoma: >4cm, heterogenous enhancement, irregular margins, calcifications, necrosis, density >10 HU, contrast washout <50% in 10 minutes. on MRI- hyperintensity on T2
  2. Cancers that metastasize to adrenals: lymphoma, melanoma, lung
  3. If you suspect that it is an adrenocortical carcinoma, it needs to be removed (b/c biopsy can’t distinguish from hyperplasia)

Author: Dr. Madhu Eluri

References:

  1. Young WF Jr. Clinical practice. The incidentally discovered adrenal mass. N Engl J Med 2007; 356:601.
  2. Young et al. The adrenal incidentaloma. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com (Accessed on July 07, 2019.)

 

July 11th, 2019: Cancer Screening

Cancer Screening

– Only two cancers have grade A for asymptomatic screening Colon cancer and cervical cancer

– Most other screening cancer guidelines have grade B or C due to adverse effects of working up the cancer and complications of therapy alone (ie lung cancer, breast cancer, etc)
– How to determine what disease are worth screening for?
  • There is an effective screening test, that is affordable
  • Asymptomatic but detectable period
  • High prevalence of disease
  • Early diagnosis lead to improved outcomes (ie mortality)

– Be aware of systematic biases with screening tests

  • Lead time bias- Identifying the disease earlier, does not necessarily mean survival time is improved (you just caught it earlier)
  • Length time bias- Indolent disease is more likely to be found by screening, but miss more aggressive (faster progressing) disease, thus also appearing to improve survival when you truly have not
Prostate Cancer
-It’s prevalent, 5th leading cause of cancer death in 2018
-USPTF recommends shared decision making, which has a grade C
  • PSA specificity depends on cut off used
  • Positive test likely leads to biopsy (invasive)
  • Early diagnosis does appear to lead to improved outcomes
  • Surgery, radiation, and hormonal therapy have adverse effects (ED and incontinence are the most common ones)

Author: Dr. Diana Mosquera Aguirre

Faculty preceptor: Dr. David Edelman