A recording of this presentation is available HERE.
Ehlers-Danlos Syndrome, Dysautonomia, and MCAS: Diagnosis and Management in Primary Care (Ohringer, 9/3/25)
A recording of this presentation is available HERE.
This week's Grand Rounds, by Dr. Alison Ohringer, was so phenomenal that I have literally been thinking about it nonstop since she finished. The topic-- Ehlers-Danlos Syndrome, Dysautonomia, and MCAS-- doesn't exactly sound titillating, but after years in primary care taking care of patients with chronic symptoms that I don't always know what to do with -- I had a serious physician "AHA moment".
Dr. Ohringer started with a silly meme that has now become an earworm for me: "If you cannot connect the issues, think connective tissues."
I have long thought of rheumatology and/or autoimmunity as a linking factor for non-specific symptoms in patients, particularly in women with fatigue, dizziness, and other systemic malfunctions. I also have long dreamed of studying how our enteric nervous system interacts with the central nervous system (leading to diarrhea, constipation, and anxiety), but I cannot say I had specifically tied in connective tissues to the issues-- until yesterday.
If you are a primary care provider, I definitely recommend watching this one! If you just want my notes, here goes. . .
Hypermobility= the ability of a joint to move beyond the normal range (can be isolated and/or benign (e.g. gymnasts) or generalized and/or symptomatic, impacting multiple joints and leading to pain, fatigue and can be associated with other symptoms)
Spectrum of severity of hypermobility:
Ehlers-Danlos Syndrome (EDS): a group of conditions characterized by one or more of several common features: skin hyperextensibility, joint hypermobility, and tissue fragility, with subtypes distinguished by family history, clinical criteria, and oftentimes genetic testing.
Hypermobile Ehlers-Danlos Syndrome (hEDS), previously referred to as EDS type III, the most common subtype, is diagnosed by hx and clinical criteria. There is no genetic test. Many experience symptoms of Mast Cell Activation Syndrome (MCAS), Postural Orthostatic Tachycardia Syndrome (POTS) and related dysautonomia, small fiber neuropathy, and migraine
Hypermobility Spectrum Disorder (HSD) is diagnosed by history and clinical criteria, on a spectrum ranging from asymptomatic to chronic pain. Some may have some of the hEDS comorbidities, though they may be less severe
Prevalence:
- EDS 1/20-40,000 (vascular EDS 1/100K)
- hEDS 1/3000-5000
- HSD: ~1/500
This schematic below depicts Dr. Ohringer's explanation for the relationships between the issues. Note that MCAD=Mast cell activation disorders.
Symptoms of mast cell activation include a variety of organ systems, including not only allergy, but also cardiologic (hypotension, tachycardia), GI (diarrhea, cramping), and constitutional (fatigue and even memory/concentration problems).
MCAS (mast cell activation syndrome) = MCAD + abnormal labs
Dysautonomia and POTS:
Dysautonomia: all disorders of the autonomic nervous system resulting from imbalanced sympathetic/parasympathetic activation - can be a clinical diagnosis, can be diagnosed with certain tests
POTS: a form of dysautonomia meeting 2 specific diagnostic criteria: - History of orthostatic intolerance with or without systemic symptoms - Correlation of symptoms with a sustained increase in upright HR by at least 30 bpm (40 bpm if pt <20yo) within 10 minutes of standing or head-up tilt, without orthostatic hypotension
Common symptoms in patients with MCAD and POTS/dysautonomia
General: fatigue, night sweats, anaphylaxis, weight changes
HEENT: itchy/watery eyes, nasal congestion, itchy throat
Cardiac: light headedness, pre-syncope, palpitations, tachycardia, labile BP
Pulm: shortness of breath, wheeze, cough
GI: refractory acid reflux, intermittent abdominal pain, nausea, vomiting, diarrhea
GU: bladder irritability and frequent voiding, uterine cramps, heavy menstrual bleeding
Derm: hives, itch, flushing, rash MSK: long bone pain
Neuro: LH/dizziness, brain fog, neuropathy
Diagnosis and Evaluation:
- Assess for hypermobility using the Beighton Score (score results dependent on puberty and age)
- Assess for EDS "red flags" (screening for vascular EDS and risk for ruptures, see image below)
- Eval for hEDS then possibly for HSD once the red flags for the high-risk, genetic EDS subtypes have been ruled out
- Eval for comorbid dysautonomia and/or MCAD
- Rule out mimics (e.g. iron-deficiency, vit D deficiency, allergy, GERD, etc)
Management
This was my favorite part of the presentation-- for a cohort of patients that almost feel untreatable, Dr. Ohlinger gave us SO many ways to consider treating these patients. The general idea is outlined again on her schematic in green (details below). Trigger avoidance, mast cell stabilizers, Autonomic Nervous System regulation, and H1/H2 blockers.
Trigger Avoidance:
Low-Histamine Diet
AVOID • Aged cheeses/Cured meats
• Fermented foods (sauerkraut, kimchi, yogurt)
• Alcohol (especially red wine)
• Vinegar-containing foods (pickles, soy sauce)
• Certain fish (tuna, mackerel, sardines)
• Leftover meats and fish
• High histamine fruits: strawberries, citrus fruits,
bananas, pineapples, papayas, plums, etc.
• High histamine vegetables: spinach, eggplant,
avocado, tomatoes, pumpkin, etc.
INCLUDE: Foods that are generally safe include:
• Fresh meat and freshly caught fish
• Fresh fruits (excluding those listed above)
• Fresh vegetables (excluding those listed above)
• Dairy substitutes (rice milk, coconut milk)
GOOD Eating Habits
• Eat fresh, home-cooked meals.
• Freeze leftovers immediately to prevent
histamine formation.
• Limit processed and packaged foods
Mast Cell Stabilizers:
Autonomic Nervous System Regulation
- Systemic symptoms: Glycemic control [1st line], Duloxetine or venlafaxine [1st line]
- Compression: Compression socks (ideally to thigh) [1st line] Abdominal binder IF no pelvic floor dysfunction [2nd line]
- Electrolyte repletion: Daily oral rehydration solution [1st line] • Normalyte powder, or LMNT powder, or DIY with ¾ tsp table salt, 2 tsp powdered sugar, ¼ tsp cream of tartar, squeeze of lemon for taste, all in 750 mL water 1-2x/day
- Autonomic nervous system retraining: Vagal tone exercises [1st line] see image below
- Symptomatic orthostatic tachycardia from POTS: Cardio-selective beta blocker (or propranolol if no asthma/resp sx) [1st line] Ivabradine (Corlanor) 5mg bid [2nd line] Fludrocortisone [3rd line] Midodrine [4th line]
H1/H2 Blockade
H1: allegra, loratadine, etc
H2: high dose famotidine
Pro Tips:
1) IF you cannot get a patient in with a genetic counselor, primary care CAN order an Invitae Genetic Panel
• Iron repletion for goal ferritin >50 (or >100 if baseline inflammation)
2) Low hanging fruit for everyone:
• Ferrous sulfate or iron bisglycinate M/W/F (Pure Encapsulations OptiFerin-C) if GI sx from other iron
• Vitamin D repletion for goal vitamin D >30
• Magnesium glycinate before bed is good for everyone who doesn't have diarrhea
I particularly appreciated how Dr. Ohlinger finished off her talk: with primary care strategies for managing what is a patient population that has often been dismissed, stigmatized, mislabeled, and struggled with a undeniably fragmented system. . .
Validate lived experiences: “Your symptoms are real and recognized.”
- Lean in to the "I don't know" with a commitment to find solutions together.
- Use structured frameworks (Beighton, consensus criteria) when possible to guide workup.
- Document functional impact clearly to support referrals and accommodations
Cirrhosis and MASLD (Santana, 8/6/2025)
A recording of this presentation is available HERE.
***
Thanks to Dr. Noemi Santana, R3 for kicking off the Senior Resident Grand Rounds series this past week. She gave a sweeping presentation this week on one of my favorite topics, Cirrhosis. See my highlights below.
As was mentioned at our liver transplant GR just a few weeks ago, the liver is responsible for many physiologic activities of the body, including detoxifying the blood, protein synthesis and hormone production.
Metabolic associated steatotic liver disease (MASLD) is currently defined as hepatic steatosis with at least 1/5 of the following cardiometabolic risk factors:
- obesity
- hypertension
- elevated triglycerides
- decreased HDL
- elevated blood sugars
In the next 20-30 years, MASLD will be the primary indication for liver transplant.
80-90% of people with MASLD are overweight
50-60% have DM2
Many have atherosclerosis, and CKD
There are population differences with regards to additional risk factors including alcohol use (for white), HCV (for African American) and _____________ for Japanese/American Native/Hawaiian, and Latinos.
MASLD is chronically underdiagnosed due to its generally asymptomatic course>> 40% of people with MASLD are diagnosed at their first hospitalization for decompensated cirrhosis. There are currently no standard screening for MASLD, but clinicians should consider risk-based screening for those demonstrating risk factors.
Screening for cirrhosis
- FIB-4 has high NPV (96%) but low PPV (63%) for cirrhosis
- Imaging modalities to assess for cirrhosis
- ultrasound: low sensitivity in early cirrhosis
- Fibro scan (ultrasound w/elastography), MR-E: can be inaccurate in ascites and obesity
- MRI/CT: best for HCC, varices, thrombosis
- Liver biopsy is still considered gold standard but often reserved for people with unclear etiology
Physical exam in cirrhosis:
- Terry nails (see image)
- gynecomastia
- caput medusae (see image)
- facial telangiectasia (see image)
- palmar erythema
- decreased body hair
- testicular atrophy
- jaundice
Decompensated Cirrhosis
some clinical pearls on common manifestations of decompensate cirrhosis:
- Ascites: be careful with salt restriction as it limits people's diet and may not have enough impact to be indicated, fluid restriction is not indicated unless Na<125
- SBP: defined as >250 PMNs in ascitic fluid
- Varices: >10 mmHg in portal vein is defined as portal hypertension; non-selective beta blockers (nadolol, propranolol) decrease risk of decompensation. Carvedilol is recommended as first line but can decreases MAP
- Hepatic Encephalopathy: consider outpatient use of psychometric HE score, which looks at subtle changes in cognitive capabilities
- HRS/AKI: hepatorenal syndrome defined as SCr not responsive to 2 days of volume expansion; renal injury in cirrhosis portends increased mortality
- Malnutrition and Micronutrient Deficiencies
- pts with cirrhosis need ~0.35 kcal/kg/day (calories) including 1.2-1.5gm/kg/day of protein
- good idea to recommend a late evening protein-rick snack
- screen for deficiencies including Vitamins D/E/B, zinc, and selenium
Emerging therapies for cirrhosis
- Early TIPS: a good discussion here
- Biomarkers (e.g. urine NGAL for AKI in cirrhosis), e.g. a recent paper https://pubmed.ncbi.nlm.nih.gov/33979307/
- Microbiome role in cirrhosis and mitigating disease progression: e.g. https://pmc.ncbi.nlm.nih.gov/articles/PMC7796381/
- Acute on chronic liver disease risk score: CLIF C, used to assess severity of A/CLF
Common Ground Society (O'Leary and King, 8/30/2025)
A recording of this presentation is available HERE.
***
Larkin O'Leary and Emily King presented this week as leaders of the Common Ground Society, a local non-profit offering support to "families who receive any life changing diagnosis for their child." Examples of life-changing diagnoses include Down Syndrome, Autism, and birth complications, but also rare genetic diseases.
They vulnerably shared their own stories as parents of children with special needs, and they challenged us to rethink how we speak to parents about their children's conditions, to debunk disability stereotypes, and to remember to listen to parents.
Some important takeaways and some possible ways to say things:
- "Congratulations on your beautiful baby!" are ALWAYS the appropriate first words for any new parent, despite any differences noted before, at, or around birth.
- Being clear is kind.
- Be careful with "maybe we will just watch that" without clarifying exactly what it is we are "watching".
- Avoid "your child is not normal". Try instead "this is unexpected".
- Consider "We are about to go on a journey. . .there will be lots of questions, and I am here to help and to ride with you on this journey".
- Look to the family for guidance, consider "What do you think is going on, mom?"
- Be careful with handing out the standard "milestones sheets" at Well Child Checks
- Talk to kids with disabilities in an age-appropriate manner (e.g. don't talk to a teenager with DS as if they were a toddler, use age appropriate language). Consider: "I am Dr. V. I am going to ask your mom some questions."
- Remember parents are doing their best.
- Be a kind human.
- Remember, this is your job, but this is their whole life.
Liver Transplant (Wakil 7/23/25)
A recording of this presentation is available HERE .
***
Thank you to Dr. Adil Wakil, CPMC liver transplant hepatologist, who kicked off Grand Rounds this year with a presentation on Liver Transplant.
He reminded us that the liver is the largest internal organ vital for metabolism, responsible for a plethora of functions including:
- energy metabolism
- protein metabolism
- bile production
- alpha 1 antitrypsin production
- immune function (with innate immune cells)
- lipoprotein metabolism (including converting LDL)
In addition, the liver receives "secondary wastewater" from the body, receiving 80% of portal vein flow as well as gut flow (from the SMA, splenic vein, IMA, etc).
Elevations of AST/ALT > 1000 occur in only three conditions: viral hepatitis, toxin-induced, and shock liver (i.e. ischemic)
Lab abnormalities provide us clues about the type of hepatic injury:
- hepatocellular injury: AST/ALT/LDH
- cholestatic injury: ALK Phos, GGT, Bilirubin
- synthetic capacity: INR/albumin and prealbumin/lipoproteins
**INR is best predictor of prognosis
Chronic vs. Acute Liver Disease
Chronic: long course (years), portal hypertension, encephalopathy, sometimes irreversible (though new evidence showing remodeling is possible)
- alcohol,
- metabolic dysfunction (MASLD)
- High fructose corn syrup has lead to huge increases in obesity in America (since the 1980s), combination of addiction and epigenetics)
Acute: short course (< 8 weeks), rare to see portal hypertension & encephalopathy, commonly see acute cerebral edema, often reversible
- HAV, HBV, toxin-induced, HCV (now most commonly seen in prison population)
Liver Failure
parenchymal: cholestatic changes, jaundice, weakness, fatigue, coagulopathy, HCC
portal hypertension: splenomegaly, GIB, ascites/SBP, encephalopathy, hepatopulmonary
Assessing for Decompensated Cirrhosis
Child's Criteria (CTP score: https://www.hepatitis.va.gov/cirrhosis/background/child-pugh-calculator.asp)
CTP A: 5-6 points
CTP B and C >7 points denotes decompensated cirrhosis>> transplant referral
MELD 3.0 (https://optn.transplant.hrsa.gov/data/allocation-calculators/meld-calculator/) is used to predict 90 day mortality, revised 2023 to correct for inequities in organ assignments for for female patients). MELD max score is 40. A MELD of >15 predicts that risk of surgery for transplant is smaller than the risk of dying from liver disease.
Liver transplant began in the US in the 1960s
Now >11,000 Liver Transplants/year in the US
Survival rates: 96% @ 1 year, 88% @ 5 year, 71% @ 10 year
Much of improved survival is attributable to immunosuppressant therapies, especially Tacrolimus
Patients with alcoholic liver disease (ALD) are not excluded from assessment for liver transplantation but most demonstrate (1) insight into their disorder (2) a period of prolonged abstinence (not quantified).
Artificial Intelligence: Best Practices in Primary Care to Achieve the Quintuple Aim (Toub, 5/28/25)
A recording of this presentation is available HERE.
Pathologizing Queer Patients (Harlow, 5/14/2025)
A recording of this presentation is available HERE.
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Great thanks to Dr. Jose Maldonado, a Stanford psychiatrist and neuropsychiatrist, who literally wrote the benzodiazepine-sparing alcohol wi... -
Artificial Intelligence: Best Practices in Primary Care to Achieve the Quintuple Aim (Toub, 5/28/25)A recording of this presentation is available HERE .