Dr. Chheda’s Road to ME/CFS
I met Dr. Chheda of the Center for Complex Diseases at Ron Davis’s Working Group Meetings funded by the Open Medicine Foundation. She graciously agreed to talk more about how she approaches treating ME/CFS in her practice. I was particularly eager to talk to one of the younger and more recent ME/CFS experts to enter this field.
She and Dr. Kaufman, her partner at the Center for Complex Diseases, exemplify a curiosity and willingness to learn about this illness that is gratifying. Dr. Kaufman, for instance, played a critical role in Jeff’s ability to get diagnosed with craniocervical instability – a condition that an immune oriented doctor like himself – would hardly be expected to know anything about.
Dr. Bela Chheda went to medical school in India, and then, stimulated by the challenge the field presents, specialized at USC in infectious diseases. Infectious diseases are different than, say, heart disease, because they can affect any part of the body; a complexity that appealed to her. She’s Board Certified in both Internal Medicine and Infectious Diseases.
She worked in infectious diseases at the huge USC County Hospital in Los Angeles. Few Infectious Disease departments encounter more unusual diseases than County/USC, a large public health hospital serving the health needs of the most populous county in the U.S. From HIV to all sorts of tropical diseases in LA’s large immigrant population, Dr Chheda said LA County was a great training ground.
A couple of years ago she moved to the San Francisco Bay Area, worked with mostly geriatric patients for a time, and then started looking for an area she felt she could make more of a difference in.
Looking to go into preventative medicine, she shadowed a bunch of integrative and functional practitioners for over a year. While their integrative/functional practices were appealing, their tendency to drop a Western medicine approach was not.
Then she shadowed Dr. David Kaufman – a practitioner with a similar path. Kaufman, who has won many accolades for his work with HIV and other diseases, was Medical Director for one of the largest HIV Centers in New York and the Director for HIV Clinical Research at St. Vincent’s Hospital. In 2012, looking for new challenges, Kaufman moved out to the Bay Area and worked with the Open Medicine Clinic for several years.
After working on the front lines of the HIV epidemic for decades, Kaufman wasn’t about to drop a Western Medicine approach either. With Kaufman, Chheda found the blend of Western and Integrative medicine she was looking for. Four things made the difference with Kaufman for her: the comprehensive approach he took, his smarts, his compassionate and empathetic approach, and then there were his patients.
She’d stumbled onto a set of patients she’d never seen before – patients she could possibly make a real difference with. Plus, they presented complex, fascinating cases – the kind that stimulated her intellectually – while rocking her world a bit as well.
Kaufman’s ME/CFS patients were much sicker that the younger and healthier patients she’d seen while working with the functional doctors. In fact, even to this doctor who’d worked in one of the larger public health hospitals in the country, who’s probably seen it all – they were often appallingly ill. She said that even now she’s sometimes staggered by just how sick some of her ME/CFS patients are. She said she’d just had a patient who told her things were looking up – they had enough strength to brush their teeth every other day.
In 2017, Dr.Kaufman and Dr. Chheda opened the Center for Complex Diseases which focuses on treating people suffering from ME/CFS, dysautonomia, autoimmune diseases, small intestine bacterial overgrowth (SIBO) syndromes, mast cell activation syndrome (MCAS) and chronic infectious diseases including tick borne diseases.
The Center’s website states:
“At the Center for Complex Diseases, we believe in the need to understand the interplay of the immune system, and its effect on patient health. Our personalized, multifaceted treatment aims to understand the myriad factors responsible for chronic complex diseases and design treatment plans based on patient history, laboratory data, and differential diagnosis.”
I asked her if the kind of profound disability she sometimes sees in ME/CFS is found in other diseases or if it is more unique to ME/CFS. She said that when profound disability like that shows up, it is usually in the elderly, but when it shows up in younger patients, it’s in established autoimmune diseases and drugs can often help ward off the worst ravages of those diseases.
Many of the people with ME/CFS who come to her, on the other hand, have been misdiagnosed with depression, haven’t been treated properly, and, of course, drugs haven’t been developed for this disease.
I asked her how long it generally takes to know whether someone has ME/CFS or FM.
She answered that the first visit is really long. Two hours is what’s needed to dig deeply enough into the patient’s history to uncover leads or answers that have been buried by the passage of time. If her patients had gotten that kind of time with their prior doctors, at the very least she feels those doctors would have understood something was seriously wrong instead of dismissing them.
A great deal of blood is collected for testing. Panels examining metabolic disturbances, hormones, autoimmunity, thyroid, and pathogens, including tick-borne and vector borne diseases, are done.
The immune panel contains NK cell function, IgG subsets (she often finds them high or low), c-reactive protein (the highly sensitive test) and then there’s the SED or erythrocyte sedimentation rate (ESR).
Lab and insurance issues keep her from running two more general inflammatory markers (TGF-beta, C-4a) more often. (She doesn’t think TGF-beta is specific to mold as some do.)
Erythrocyte Sedimentation Rate (ESR)
As an infectious disease specialist, Dr. Chheda has run thousands of ESR or SED rates. (High ESR rates are typically found in bacterial infections.) The ESR rate refers to how quickly red blood cells fall to the bottom of a test tube. When the red blood cells clump together and rapidly fall to the bottom of the tube, ESR or SED rates are increased.
Moderately raised ESR rates can reflect many different states including pregnancy, anemia, inflammation, infection, cancer, diabetes, heart disease and collagen vascular diseases. Very high SED rates can be found in kidney disease, cancer and collagen vascular diseases.
Dr. Chheda, however, typically sees a low ESR rate (@2) in her ME/CFS patients. In fact, low ESR rates are so common in ME/CFS that when she gets a normal reading she wonders if the person has something else.
Low ESR rates do occur in some diseases, but they’re not well studied, and most medical websites only provide a value for high ESR rates. They could, however, reflect the problems with red blood cells that Ron Davis’s Open Medicine Foundation sponsored study is finding. We’ll have more on low ESR rates in an upcoming blog.
Mast Cell Activation Syndrome
Mast cell activation syndrome (MCAS) describes just what it is – an ongoing chronic activation of the mast cells in the body which is difficult to diagnose and which can cause an incredibly wide array of symptoms.
Dr. Chheda typically runs a mast cell panel (tryptase, chromogranin, histamine, prostaglandins, IgE). She’s mostly abandoned the 24-hour urine tests that other doctors run because she felt she was rarely getting valid results – perhaps because the urine had not been constantly chilled by the patient and/or the lab.
With regards to the mast cell results:
- Tryptase – a small percentage of people have elevated tryptase. When tryptase levels are elevated, they’re usually borderline elevated (13-20)
- Chromogranin – another small percentage of patients have high chromogranin. (She noted that low stomach acid can also cause elevated chromogranin).
- Prostaglandins – The two main MCAS markers she uses involve the prostaglandins. Prostaglandin D2 is the most helpful marker, but because it can have diurnal variations, it may take several tests to capture the elevation. F2 alpha – which is a breakdown product from other cells as well as mast cells – is moderately diagnostic.
- IgE is not diagnostic, but high IgE levels suggest that something may be going on with the mast cells.
Biopsies of the GI tract or from colonoscopies can provide another clue if they show high numbers of mast cells are present. If a patient has a biopsy, she tries to get it stained and counted for mast cells. While it’s not clear yet what constitutes an abnormal number of mast cells, in her experience >30 is probably abnormal.
With mast cell activation syndrome producing a wide variety of symptoms and diagnostic tests results that are open to substantial interpretation, it’s clear that quite a bit of gray area exists in MCAS diagnostics. Often a trial of MCAS medication – which is usually well tolerated – is called for.
Dr. Chheda referred to a recent patient with a classic case of ME/CFS who did not appear at first blush to have MCAS. An antihistamine trial told the tale, though; while neither 1-2 antihistamines a day made a difference, adding a third one did – it completely removed the patient’s anxiety!
Dr. Chheda suggests starting with non-sedating antihistamines such as Claritin or Allegra. (She doesn’t recommend patients trying more than 2 antihistamines at a time on their own without supervision.) She also can use the herbal mast cell stabilizer called quercetin (500 mg twice a day). Ketotifen, she said, is a compounded antihistamine that is also a mast cell stabilizer.
If someone thinks they may have MCAS, she recommends reading Dr. Afrin’s book – Never Bet Against Occam.
Dr. Chedda usually runs a large autoimmune panel, which includes ANA, autoantibodies to thyroid, celiac proteins, rheumatoid factor, Sjogren’s Syndrome (SS), and early Sjogren’s antibodies. While noting that it’s not clear that a positive test indicates that early SS is present, she believes it suggests a problem with some type of systemic autoimmunity may be present.
Dr. Schofield found that 76% of patients with “refractory autoimmune disease” (most of whom had postural orthostatic tachycardia syndrome (POTS)) had antiphospholipid antibodies and 42% had novel Sjögren antibodies. (Several studies have found higher rates of these novel antibodies in Sjogren’s patients than the traditional antibodies tested for in the disease.) Thirty-two percent of the participants also tested positive for one or more thyroid antibodies. Very few tested positive on the Mayo Clinic’s autoimmune dysautonomia panel.
- Check out Lauren Stiles, the leader of Dysautonomia International, on the early Sjogren’s antibody tests here.
She runs an antiphospholipid panel (anti cardiolipin, beta2 glycoprotein, antiphosphatidylserine, prothrombin) in patients with a history of Raynaud’s, discoloration of upper or lower extremities, history of migraines (due to sludging of the blood), or history of stroke.
Cost considerations do play a factor in how many panels Dr. Chheda runs. She would run the Cell Trend autoantibody panel on everyone if it were not so costly. She’s found that most people test out in the low to moderate range, but it’s the very high or very low readings on that panel that are the most helpful to her diagnostically.
Very low readings suggest that any dysautonomia present is probably not autoimmune driven, while high readings provide a data point which could suggest autoimmunity is present and is playing a major role in the illness.
Cost precludes running the Cunningham panel on everyone as well. The Cam kinase results, in particular, can suggest an inflammatory process is going on.
Small Intestine Bowel Overgrowth (SIBO)
If Dr. Chheda finds evidence of autoimmunity, one of the first places she looks at and tries to fix is the gut, and that means testing for small intestinal bowel overgrowth (SIBO). SIBO refers to an overgrowth of bacteria in the small intestine which causes symptoms similar to irritable bowel syndrome including bloating, diarrhea or constipation, stomach pain, leaky gut, and immune issues.
Noting that the hydrogen/methane SIBO tests can have false negative results (i.e. may miss SIBO – when slow motility is also present), Dr. Chheda stated that she always runs the test and finds it positive 2/3 to maybe 3/4 of the time. If GI symptoms are present, Dr. Chheda thinks SIBO is probably present, even if the test is negative.
She aggressively treats SIBO, and sometimes that alone helps to shift the disease. She will use either a two-week course of Xafaxin, an antibiotic which is absorbed mostly in the gut, doesn’t impact other flora and is well tolerated – or a combination of antibiotics ( Xifaxin with flagyl or neomycin if methane is present) or herbs. Xafaxin has the advantage of quickly giving her information about the gut, while herbs, which can be effective, take 2-3 months to work and the change is more gradual.
Getting GI tract motility back to normal is critical as the SIBO will probably come back if it’s not fixed. (Motility refers to the speed at which food moves through the gut. Too high motility results in diarrhea, low motility results in constipation. Different stomach bacteria dominate in low or high GI motility states.)
Dr. Chheda noted that high levels of methane indicate the problem is not bacterial, and that some believe statins are the way to go. She’s cautious about that but noted that statins could be the future for the harder to treat methane associated SIBO.
- Check out a SIBO protocol (not examined or assessed by Dr. Chheda) – SIBO – Route-to-resolution
Craniocervical instability (CCI)
Craniocervical instability (CCI) occurs when lax ligaments that are no longer able to hold the head properly above the body cause the head to compress the brainstem, producing potentially a wide variety of symptoms. Spinal surgery enabled both Jeff and Jen Brea to recover from what had been diagnosed as severe cases of ME/CFS.
Dr. Chheda regularly tries a poor man’s office test to assess the possibility that CCI is present: when the patient is lying on the table she lifts the head up off the body (cervical traction) to see if symptoms are relieved. If they are and CCI is a possibility, she has an MRI done.
Cerebral spinal fluid leaks
If a person is hypermobile and has headaches that consistently get better when lying down and worse sitting up, Dr. Chedda suspects a cerebral spinal fluid leak may be present. If a leak is suspected, she uses a test that Dr. Carroll of Stanford recommends: she has a person lie flat for 48 hours and then stand up and see if their symptoms reappear. Leaks, she noted, show up more often in more hypermobile patients.
She occasionally sees indications of high intracranial pressure (intracranial hypertension) on lumbar puncture (LP), but noted that most of her patients have either not had LP’s done, or if they were done, the opening pressure was not measured – something she finds quite frustrating. Finding intracranial hypertension puts an extra focus on checking for CCI/AAI. She has tried acetozolamide and has seen it help, but only rarely.
General Treatment Plan
Newbies are generally easier to diagnose and treat. If a close examination of a patient’s history indicates that everything started with a tick or cat bite, everything may fall quickly into place. Wait ten years, though, as the memory fades and autoimmunity and other issues may have been added to the mix, and things get more complicated. (It’s clearly a good idea to take good notes and maintain a good history of your illness.)
Dr. Chheda takes a multiple pronged approach and likes to try to hit everything at once. Everyone gets a shot at low dose naltrexone (LDN). Almost everyone gets treated for SIBO and many people try histamine blockers for a couple of weeks. Dysautonomia, when present, is treated from a GI motility and POTS perspective.
Low Dose Naltrexone
About half her patients respond positively to LDN. Those that don’t respond to it but can tolerate it (most do) she keeps on the drug because of the many studies that suggest it is helpful. If people can’t tolerate the normal low starting dose (1.5 mgs), she titrates downwards. Some people start off on as low a dose as 0.1 mgs/day. Side effects usually pass within 2 weeks.
This drug does so many good things that she wants her patients taking the highest tolerated dose, up to 4.5 mg, even if they aren’t noticing a difference.
Check out many resources on LDN at Health Rising’s FM and ME/CFS LDN Resource Center
If the autoimmune panels suggest autoimmunity is present, the gut is given a strong emphasis. With regard to drugs, plaquenil has been a good drug that is generally well tolerated but can take up to 6-12 months to work. (Plaquenil or hydroxychloroquine was first used to treat malaria but is also used in autoimmune diseases such as rheumatoid arthritis and lupus.) Other autoimmune drugs can be tried, but she emphasized that they are not risk free.
IVIG consists of antibodies drawn from thousands of healthy people which is used to treat a variety of immune disorders and sometimes disorders which fail to respond to other treatment. It’s very difficult to get insurance companies to approve this very expensive drug, but when available, Dr. Chheda has found it to be helpful, particularly with the autoimmune dysautonomia she sometimes finds. She does extensive autoimmune antibody testing and small fiber neuropathy testing to help support a request for IVIG.
She generally uses the subcutaneous (instead of the infused) form of IVIG and weekly dosing (instead of once a month). She’s found this approach cheaper and better tolerated, and while it can take a while to show benefits, it works as well in the long run.
If after a few months to six months good improvement is not seen, she drops the drug. If she sees partial improvement, she’ll either try to increase the dose or think of other drugs.
Check out Health Rising’s IVIG Series:
- An IVIG Chronic Fatigue Syndrome (ME/CFS) / POTS Treatment Success Story: IVIG#1
- Are Chronic Fatigue Syndrome, POTS and Fibromyalgia Autoimmune Dysautonomias? IVIG #2
- The Case for IVIG Treatment in Chronic Fatigue Syndrome (ME/CFS), Fibromyalgia, Small Fiber Neuropathy, and POTS: IVIG#3
Ehlers Danlos Syndrome, Hypermobility and Spinal Issue and Others
The Beighton Test is a self-questionnaire that is often used to assess whether hypermobility is present. Dr. Chedda noted, though, that people who don’t score positive on the Beighton Test or who don’t fit the criteria for Ehlers Danlos Syndrome (EDS) may still be hypermobile. She recently had a patient who scored low on the Beighton Test and seemed perfectly normal except she was able to pop her shoulder and hip in and out – which she promptly demonstrated.
Hypermobility puts people at an increased risk of craniocervical instability and cerebral spinal fluid leaks. Dr. Chheda noted that if you go deep enough into a person’s history, you will sometimes find some very odd types of hypermobility as well as a history of physical trauma such as whiplash or other kind of head injury. For a person who is hypermobile, she said, it doesn’t take much trauma to cause craniocervical instability (CCI) or a spinal fluid leak.
She guessed that more than half of her patients have some kind of hypermobility: whether that consists of stretchy skin, the ability to pop their joints in and out or some other type of hyperflexibility.
For some people, hypermobility is the starting point of their disease. For others, the hypermobility comes on later – perhaps as a side-effect of mast cell activation.
Other problematic conditions, such as median arcuate ligament syndrome (MALS), can be present. MALS occurs when the median arcuate ligament under the diaphragm compresses the autonomic center in the abdomen (celiac ganglia) and the celiac artery, causing pain and gut issues. It can be resolved surgically but is difficult to diagnose and treat.
Subsets or a Spectrum Disorder?
Dr. Chheda doesn’t think in terms of subsets. Instead, she believes that all these illnesses (MCAS, POTS, EDS, FM, ME/CFS) – are likely interrelated. They probably constitute a kind of vast, multi-dimensional spectrum disorder.
She visualizes the issues in her patients in terms of Venn diagrams. Hypermobility, MCAS, SIBO, pathogens, dysautonomia, autoimmunity, craniocervical instability, unusual sensitivities, etc. – each occupy a circle in these Venn diagrams – with each person having their own unique assemblage of circles – some larger than others.
Testing will reveal that one group of patients, for instance, will have tick-borne, vector-borne (insect-borne) diseases or herpesvirus reactivation. The pathogen circle in their unique Venn diagram will be larger than those without that issue.
Dr. Chheda had some good news about the future. The next ten years, she thinks, are going to be huge – not just for people with ME/CFS, but for ill people in general.
The medical field, she reported, is undergoing an explosion in multiple areas. It’s ever advancing ability to mine huge amounts of data is going to be increasingly helpful in correctly matching the right treatments with a person’s unique physiological and genetic makeup.
Immune therapies are going to become more powerful – and more commonly used – as the medical field learns how to pull out immune cells and target the specific immune issues present in a person’s illness.
Developing better means of drug delivery may not sound exciting but will have a major impact as drug companies produce drugs able to get right to the source of the problem, thus reducing their side effects and boosting their potency.
In short, ten years, Dr. Chheda believes, will bring us much more effective medicines. Nobody wants to be sick, but if you’re going to be sick, she said, 2019 is not a bad time to be ill. She encourages everyone to keep their hopes up and stick around.
She also invited physicians to come shadow her and Dr. Kaufman’s work and enter a fascinating field.
- Coming up shortly – the researcher you’ve never heard of who’s devoted the last four years of her life to understanding ME/CFS.
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