Women and Chronic Lyme Disease: Could Immune Responses Help Explain Persistent Symptoms?
Women were more frequently represented among patients diagnosed with chronic Lyme disease
Persistent immune activation may contribute to ongoing symptoms after treatment
CCL19 has been investigated as a possible risk marker for PTLDS
According to a study by Wormser and Shapiro from New York Medical College, “Patients with chronic Lyme disease were significantly more likely to be female than were patients diagnosed with either Lyme disease or with post-Lyme disease syndrome.”1
The authors proposed that conditions more common among women—including fibromyalgia, chronic fatigue syndrome, and depression—might sometimes be misdiagnosed as chronic Lyme disease.1
However, this observation does not establish why women were more frequently represented or prove that their symptoms resulted from misdiagnosis. Differences in immune responses, symptom patterns, healthcare experiences, and other biological or clinical factors may warrant further investigation.
In my clinical practice, I also see a substantial number of men with persistent, disabling symptoms following Lyme disease. The greater representation of women in this study should not be interpreted to mean that men are less likely to experience severe or prolonged illness.
Could Persistent Immune Activation Contribute to Ongoing Symptoms?
A separate study by Aucott and colleagues from Johns Hopkins University School of Medicine investigated CCL19, a chemokine involved in immune-cell trafficking and inflammatory signaling.2
The researchers reported that individuals treated for early Lyme disease had a greater than 12-fold increased risk of developing post-treatment Lyme disease syndrome (PTLDS) at six or twelve months when their CCL19 level remained above 111.67 pg/mL one month after treatment.2
Importantly, this CCL19 finding applied to the overall study cohort and was not reported as specific to women.
The authors proposed that elevated CCL19 might reflect an ongoing immune-driven response outside the lymphatic tissues. However, an association between elevated CCL19 and PTLDS does not establish the underlying cause of that immune activity.
Possible explanations discussed in the scientific literature include persistent inflammation, retained spirochetal antigens, immune dysregulation, or—in experimental animal models—the persistence of bacteria or bacterial material after antibiotic treatment.2 These possibilities have not been shown to explain persistent symptoms in every patient.
Is CCL19 Used to Diagnose or Treat PTLDS?
The study entitled CCL19 as a Chemokine Risk Factor for Post-Treatment Lyme Disease Syndrome: A Prospective Clinical Cohort Study identified CCL19 as a potential risk marker rather than a diagnostic test or treatment target.2
CCL19 testing is not currently an established clinical test for diagnosing PTLDS, proving persistent infection, or selecting treatment. Additional research is needed to determine whether this biomarker can reliably identify patients at risk or guide clinical care.
The authors also noted that short-term antibiotic retreatment during the early post-treatment period had not been formally tested, although it may occur in clinical practice.2 Their study did not determine whether retreatment based on an elevated CCL19 level improves patient outcomes.
Patients with persistent symptoms require an individualized evaluation that considers the original Lyme disease diagnosis, treatment history, possible coinfections, alternative diagnoses, and the severity and progression of symptoms.
Clinicians evaluating ongoing illness may also consider related discussions involving post-treatment Lyme disease syndrome, persistent Lyme disease mechanisms, and neuropsychiatric Lyme disease.
Frequently Asked Questions
Why might women experience different Lyme disease outcomes?
Researchers have proposed several possible explanations, including biological differences in immune and inflammatory responses, differences in symptom presentation, overlapping medical conditions, and diagnostic factors. The studies discussed here do not establish a single explanation.
What is CCL19 in Lyme disease?
CCL19 is a chemokine involved in immune signaling and immune-cell movement. In one prospective study, an elevated CCL19 level one month after treatment was associated with an increased risk of developing PTLDS.2
Was the CCL19 finding specific to women?
No. The CCL19 study evaluated a broader cohort of patients treated for early Lyme disease and did not establish that elevated CCL19 was specifically responsible for persistent symptoms in women.
Does an elevated CCL19 level prove persistent infection?
No. Elevated CCL19 may indicate ongoing immune activity, but it does not identify the cause of that activity or prove that viable bacteria remain after treatment.
Clinical Takeaway
Women were more frequently represented among patients given a chronic Lyme disease diagnosis in one study, but the reason for this difference remains uncertain.1
Research involving CCL19 suggests that persistent immune activation may help identify some patients at increased risk for ongoing symptoms after Lyme disease treatment. However, the CCL19 findings were not specific to women and do not prove persistent infection or establish a treatment strategy.
Related Articles
Post-Treatment Lyme Disease Syndrome
Persistent Lyme Disease Mechanisms
References
- Wormser GP, Shapiro ED. Implications of gender in chronic Lyme disease. J Womens Health (Larchmt). 2009;18(6):831–834.
- Aucott JN, Soloski MJ, Rebman AW, et al. CCL19 as a chemokine risk factor for post-treatment Lyme disease syndrome: a prospective clinical cohort study. Clin Vaccine Immunol. 2016;23(9):757–766.
Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.
Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention
I’ve been sick for 30 years. I’ve probably been bit 20 times at least. Even tho I had a rash my Dr denied me treatment a year ago. If this is immune caused why is there such a large reaction to die off and with repetitive rounds of treatment those die offs lesson. I also have 2 coinfections, Candida causing constant horrific rashes and HSV1 and sometimes 2, also systemic as well. I was given a bag of IVIG to up my platelets for cancer surgery. I have ITP, cause unknown or immune or microbe driven. These organisms have definite reproductive cycles with repeating symptoms. Of course I’ve never been told anything I have is autoimmune. I believe the bag of IVIG was contaminated with viruses not known to Americans. A shortage in the US caused my Dr to get it from China. I had so called aseptic (absurd) meningitis. I left the hospital almost catatonic and then had cancer surgery. I’m cancer free, the meningitis still present post infusion in 2010. Completely bedridden. Swamping sweats and nausea. This is autoimmune? sure feels like the worst flu or infection of my life. I’m 60 hrs old, I’ve given 29 of those to this dreaded disease. What will happen to me. They’re already talking nursing home. How about an intelligent, innovative Dr who doesn’t negate something’s existence because it can’t be cultured from blood, and thus must not exist quoted Eugene Shapiro, professor of epidemiology at Yale. That’s his theory. I cannot begin to explain the abuse I have received from these Yale egotists. Horrible insults about my weight caused by drugs they gave me like tricyclic antidepressants and neuronton. How about trying a bottle of antibiotics out antivirals dr, I screamed in my sleep. I’m so sick now i can barely sit up. Dysautonomia has appeared as my next adventure. I’m Afraid to take on biofilms by myself due to possible bleeding. IVIG was never supposed to be given to people with headaches, Black box warning everybody missed. I realize the original post is a bit old but I believe totally in Dr Horowitz’s description of MCIDS, Multiple systemic infectious disease syndrome..I don’t think I can even sit and wait for a Dr to hear me without gerting violently ill. Adding in esophageal motility issues, a hiatal hernia, bike reflux and a narrowed bowl have made treatment thru my GI track a nightmare. My husband is ill as well. He thankfully doesn’t get as sick as me though. And an article I read recently said Herpes feeds on probiotics and I think antivirals are murder weapons. Is there a way out for me. I’ve been to Hyde park before in my job as a sales rep for big pharma in Healthcare and infection control. Note I am a resistant infection host myself
I did a lousy job of getting the bugs out of me. Autoimmune?, Not feeling it. Even as a lowly med
tech I remember the symptoms of an infection. I think I’ve been chosen to be culled. No treatment, fill her with so many drugs she can’t think or remember and let her face away and die. I’m even to young to get Homecare from Medicare.
I need an LLMD but I’m on disability and insurance s don’t pay for long term Lyme treatments. They just give us the disease and abandon us. I wish I was dead every day but I won’t let whatever this is win. Any ideas?
Sheryl, please contact me if possible
The study by Aucott begs the question.
“Begging the question, sometimes known by its Latin name petitio principii (meaning assuming the initial point), is a logical fallacy in which the writer or speaker assumes the statement under examination to be true. In other words, begging the question involves using a premise to support itself.” grammarist.com
Aucott assumes the cytokine and chemokine changes cannot be due to chronic infection. His work is a disappointment.
Surely he must have observed that patients chronically ill with this disease report Jarisch-Hexheimer reactions when antibiotics are reintroduced. A Jarisch-Herxheimer reaction is driven by changes in cytokine levels associated with the lysis of certain kinds of microorganisms such as Borrelia.
The study that needs to be done that has not been done, in either animals or humans, is to compare pro-inflammatory cytokine levels in those with acute and chronic infection before, during, and after a period of antibiotic administration — and to compare this with a control group of those assumed not to be infected with any organism that would be predicted to cause a Jarisch-Herxheimer reaction (healthy controls).
In studies of human infection with Borrelia recurrentis, it has been shown that proinflammatory cytokines peak with antibiotic administration, driven by the lysis of the organism. There are several studies published in U.K. journals that show this very nicely, and how metapzinol, an opioid agonist-antagonist, inhibits pro-inflammatory cytokine release. The point of these studies was to find an intervention (here, metapzinol) that would depress the severe Jarisch-Herxheimer reaction associated with treatment of Borrelia recurrentis infections because treatment carried a high mortality rate due to the severity of the Jarisch-Hexheimer reaction. The Jarisch-Herxeimer reaction was so severe that physicians were scared to treat the patient due to the risk of death.
No studies have been done of the cytokine changes in the Jarisch-Herxheimer reaction in animals or humans associated with Borrelia burgdorferi infection. But the findings would be expected to be similar to what was reported with Borrelia recurrentis.
Then, one would design a study looking for the same pattern of proinflammatory cytokine release with the reintroduction of antibiotics in patients chronically ill with Lyme disease.
If there is NO ACTIVE INFECTION, one would not expect to see increases in proinflammatory cytokines with antibiotic administration. Nor would you expect patients to report that they experience symptoms of a Jarisch-Herxheimer reaction — but we all know this exists. Twenty years post acute infection, patients will report Jarisch-Herxheimer reactions with antibiotic administration. This is EVIDENCE OF CHRONIC INFECTION.
Clinicians with Lyme disease practices could do a simple case report using patients from their practices. It does not require a big federal grant to begin to demonstrate this finding. All one needs is access to a blood draw station that can competently collect samples to send to reference labs. Because cytokines degrade quickly, the collection process must be done properly and specimens sent on dry ice.
So why has this not been studied? It is the obvious study to do.
It seems to me that studies which beg the question are not unimportant, although they disappoint. Don’t they sometimes beg the question which needs to be asked NEXT?
Dr. Cameron and/or Dr. Shepler…. Is there a way that you can facilitate this study, or initiate it somewhere that could do it – a graduate student in need of a study, perhaps? I’m not a scientist and so get lost in a lot of the language, but I am a female patient who suffered greately, who endured 9 years of treatment (off and on, mostly ON because I could never get beyond a six month remission), who was misdiagnosed and tested for everything BUT Lyme disease – until finally I pushed and pushed for (and paid dearly for) better tests. My husband, who is a scientist, can’t stop wondering why some of us just get caught in this pattern of failed remissions… my term, because that’s how I see my journey. I used to consider myself a treatment failure but I’m now refusing that – it’s my remissions that keep failing, but why? Maybe this. Maybe this study mentioned by Dr. Shepler would help so many of us. Maybe not.
I was diagnosed with Lymes three weeks ago and am almost crippled by the end of the day, unable to bend, stretch or raise my arms. Have been on a Course of Doxycycline which does not seem to be doing much. Only relief is from NSAIDS which a I am now not supposed to touch because of Covid.
Any light at the end of the tunnel?
Thank you for this rebuttal! I appreciate your expression of knowledge. I can attest firsthand to the involvement of “herxes” as a chronic Lyme and co-infections “model”.
Could that be the base cause of my Ankylosing Spondylitis? I do have the HLA-B27 gene. I grew up in Minnesota and Wisconsin, and was well known for having wood ticks. I don’t remember deer ticks at all, but I didn’t see all the ones Ma took off me. What do I need to look for or be tested for? I’m in Utah now, and am 56 yrs old, in constant pain.
It doesn’t hurt to look a second time at diseases that overlap with Lyme disease
Again all Lyme patients are immunosuppressed, not just woman.
http://www.truthcures.org
The immune system is rather complex. The Aucott study demonstrated markedly elevate chemokines levels. It is helpful to drill down
As a male, I have a very pronounced 28 day cycle in my symptoms, post treatment. This seems more like active infection, as autoimmunity doesn’t really make sense. Another way it’s harder for women, because they are fobbed off by telling them it’s hormones.
Hi
Can it trigger scleroderma,systemic?
There are overlapping findings for most rheumatologic conditions. There has not been much written on the scleroderma.
In my experience Lyme and Co is the main trigger of autoimmune response, in my case it tries to trigger scleroderma, but Im treating Lyme and it keeps autoimmunity at bay. I plan to win Lyme with essential oils (natural antibiotics). Antibiotics didnt do much for my chronic and advanced Lyme.
So sorry to hear all that are suffering.i had Lyme Disease in 1989-90-91.
Luckily, I was under the care of Dr Derek Desilva. A specialist in NJ.
He put me on 4500mg of Amoxicillin,and 1500mg of Probenicid daily, for 91 days. It knocked out most of the symptoms, and then I continued to heal for another 2 1/2 years. I was active and extremely healthy for many years.However he did warn of a complication, which was Arthritis, in my later years. He was so right. No arthritis in my large extended family on either side, but I’ve got it. And it’s almost debilitating. The Rheumatologist that I go to put me on Prednisone and that has been giving me great relief. I can’t even walk without it. I’m not big on meds, but if it helps me to function, I will take them. Use them if you must. It’s better than being half alive.
I had to be on doxy for 9 months. Make sure you have a Lyme literate doc.https://www.lymedisease.org/find-lyme-literate-doctors/
I had to wait 4 months to see my dr but it was worth it. It was a tough road. But I made it. Don’t give up.
I’ve been on antibiotics 20 years..now my liver is messing up. Any ideas on safe things to take to kill bartonella babesia and lyme?
Sorry to hear you are still ill. It can be difficult for all doctors involved.
“This finding,” says Wormser, “suggests that illnesses with a female preponderance, such as fibromyalgia, chronic fatigue syndrome, or depression, may be misdiagnosed as chronic Lyme disease.” [1]
This is wrong and reversed. LYME DISEASE is misdiagnosed as fibromyalgia, chronic fatigue syndrome, and depression. DO NOT devalue the damage that Lyme disease can cause. There is a way to heal from Lyme disease, the other conditions are idiopathic.
Insightful article presenting important health information in an easy-to-understand way. Thank you for raising awareness about chronic Lyme disease and its potential effects.