The Side Effect She Was Too Embarrassed to Mention

When your MS treatment causes a problem your neurologist wasn't trained to find

Recently, I was wrapping up a routine visit with a patient I have known for a long time. Her MS was doing beautifully: no relapses, no worsening, MRI stable. She’d been on ocrelizumab for six years, and was living a very healthy life. But as I reached for the door handle, she said: “Can I ask you something? It’s probably not related to any of this. But I value your opinion and I am lost.”

She’d been dealing with a persistent vaginal discharge for over a year. Yellowish, heavy, relentless, with pain, particularly during sex. It had affected her marriage. She felt, in her words, dirty. She’d seen her OB-GYN multiple times. First she was told it was a yeast infection. Treated with no improvement. Then bacterial vaginosis. She was given multiple courses of antibiotics, again with no real improvement. Nothing worked. The cultures kept coming back unremarkable. Her OB was running out of ideas and she was running out of hope.

She hadn’t mentioned it to me because she assumed it had nothing to do with her MS. What she didn’t know was that I had heard similar complaints from a handful of patients over the past year, and I had started looking into a possible connection.

The condition no one talks about

What my patient has is called desquamative inflammatory vaginitis, or DIV. It is an uncommon but real chronic inflammatory condition of the vagina. The lining of the vagina becomes red, swollen, and sore, and it sheds its surface cells faster than normal. This causes a heavy yellow or greenish discharge, burning, soreness, and often pain with sex. It occurs more often in perimenopausal women, and it is routinely misdiagnosed.

The reason it gets missed is that it looks like something else. The discharge often first gets blamed on yeast. When antifungals fail, clinicians pivot to bacterial vaginosis (BV) and prescribe metronidazole. When that fails too, and it will, because DIV does not respond to this kind of antibiotic, women enter a frustrating cycle of repeat visits, repeat antibiotics, and mounting demoralization.

DIV is not a simple infection. No single germ has been found to cause it, and it is not passed from person to person through sex. What happens is that the normal balance of bacteria in the vagina gets disrupted (an imbalance called dysbiosis). The helpful bacteria (lactobacilli) that usually keep the vagina healthy disappear, and other everyday bacteria, the kinds normally found on skin or in the bowel, take their place. The body’s immune system reacts in the vaginal lining, but whether the change in bacteria is part of the cause or a result of the inflammation, or both, remains unclear.

There is no single blood test to diagnose DIV. The diagnosis is made by ruling out other causes of discharge, such as yeast, trichomonas, or bacterial vaginosis, and by looking at a sample of vaginal fluid under a microscope in the office. A clinician looks for:

• Lots of white blood cells: the body’s inflammatory cells, which show that the tissue is irritated.

• Immature surface cells (or parabasal cells): young, round cells from the deeper layers of the vaginal lining. Finding these means the lining is shedding faster than it can mature. This is the hallmark finding in DIV.

• Missing good bacteria: the normal rod-shaped lactobacilli are gone and replaced by other bacteria.

• A higher-than-normal pH: the vagina is less acidic than it should be (typically around 6, where normal is below 4.5).

• No fishy odor test result and no “clue cells”: these are features of BV, and their absence helps separate the two.

• On examination, the vaginal walls often look red and inflamed, sometimes with tiny red spots or small raw areas. A biopsy is typically not needed. It is reserved for cases where a different skin or immune condition needs to be ruled out, particularly if symptoms do not improve with treatment.

• A key clinical clue, emphasized in a major NEJM review of the condition: when a patient diagnosed with BV fails metronidazole, DIV should be on the differential.

So why is a neuroimmunologist writing about a vaginal condition?

Because the immune system doesn’t stop at the blood-brain barrier

DIV has always been suspected to have an immune-mediated component. The condition responds to anti-inflammatory treatment, topical clindamycin and intravaginal hydrocortisone, far better than to antibiotics. Its pathogenesis appears to involve not just dysbiosis but a breakdown in the mucosal immune environment that normally helps keep the vaginal flora in check.

And here’s where it becomes very much a neuroimmunologist’s problem.

The vagina, like the mouth, gut, and airways, is lined with a moist surface called a mucous membrane. These surfaces are home to large numbers of harmless bacteria, and the body has ways of keeping that community in balance. Part of that system involves antibodies, which are proteins made by immune cells that recognize and stick to bacteria. Two types, called IgA and IgG, are found in vaginal fluid. When an antibody sticks to a bacterium, it is described as “coating” it. Coating can help clump bacteria together, keep them away from the tissue lining, and make it easier for the body to clear them. Interestingly, the vagina handles antibodies differently from the gut. The gut has large numbers of resident antibody-producing cells built into its lining; the vagina has relatively few. Instead, antibody-producing cells appear to travel in from the bloodstream when needed.

B-cell depleting therapies, such as rituximab, ocrelizumab (Ocrevus), ofatumumab (Kesimpta) or ublituximab (Briumvi) have become the backbone of modern MS treatment and are remarkably effective at preventing relapses and new MRI lesions. These drugs attach to a marker called CD20 that sits on the surface of B-cells, and cause those cells to be destroyed. This is intentional and is how the drug treats the disease. Mature plasma cells, the antibody producing cells that develop from B lymphocytes, do not carry the CD20 marker, so they are not directly killed by these drugs. Some plasma cells are long-lived and can survive in the bone marrow for years without needing replacement, which is why many patients maintain adequate antibody levels on treatment. But others are short-lived and depend on a steady supply of new B cells to replenish them. When the B-cell supply is cut off, that replenishment stops, and over time antibody levels can gradually fall, particularly in patients treated for longer periods or over repeated cycles

Low antibody levels after B-cell depleting treatment are common and well documented. Some people recover normal levels once B cells return, which usually takes about 6 to 9 months. In others, low levels persist for years. This is why doctors check antibody (IgG) levels before treatment and periodically afterward, and why some patients receive antibody replacement infusions.

No study has proven that B-cell depleting therapies cause DIV. But the biology makes the connection plausible. The proposed chain of reasoning is: fewer B cells → fewer antibodies reaching the vaginal surface → less antibody coating of bacteria → the normal bacterial community shifts → the tissue becomes inflamed and starts shedding cells, which is what DIV looks like. However, it is worth noting that the exact cause of DIV remains unknown and may represent a primary inflammatory syndrome rather than purely a consequence of microbiome disruption.

The emerging evidence

In 2021, a team from Massachusetts General Hospital published a retrospective study in *BMC Women’s Health* examining women on long-term rituximab for autoimmune conditions. They identified 16 cases of inflammatory vaginitis, a prevalence of approximately 3.5% among women treated with rituximab. All reported copious vaginal discharge. Seventy-five percent reported pain with sex. Most were initially misdiagnosed.

But the most telling finding was what happened when B cells came back. Among the nine women whose circulating B cells recovered to above 10 cells/μL, every single one improved: five completely, four significantly. The temporal association between B-cell reconstitution and symptom resolution was hard to ignore.

Then, in 2024, Libby Levine and Claire Riley at Columbia published a case series of four women with MS on B-cell suppressing therapies who developed inflammatory vaginitis. Ages ranged from 27 to 41. All presented with the classic triad: discharge, irritation, dyspareunia. Again, B-cell reconstitution was temporally associated with improvement of inflammatory vaginitis symptoms. The paper called for “further investigation and vigilance for this potential treatment-emergent adverse event affecting sexual and reproductive health of women with MS.”

And just this year, a review from Riley Bove’s group at UCSF, published in Multiple Sclerosis Journal, made the broader case that gynecological health is “a missing link in comprehensive treatment monitoring for multiple sclerosis.” The review highlighted three categories of gynecological complications in women on DMTs: HPV-related cervical disease, herpesvirus infections, and inflammatory and infectious vaginitis.

So what am I seeing in my own practice? Like most MS specialists today, I prescribe B-cell therapies frequently, across the lifespan. I would say I am very experienced with these treatments. Inflammatory vaginitis doesn’t appear to be common affecting fewer than 5% of women, but I am seeing it frequently enough that I am noticing the signal. And I wonder how many suffer in silence. I have cared for several women like the one in this case and have seen their distress firsthand. All spent months without a clear diagnosis. But when properly diagnosed, most achieved some form of remission with DIV treatment, though they frequently required ongoing maintenance therapy. The majority have chosen to stay on B-cell therapy which is reassuring because these treatments are highly effective. Only one of my patients has discontinued B-cell treatment (for a variety of reasons, including DIV) and saw her vaginal symptoms resolve once B-cells fully repopulated.

What my patient needed to hear

My patient was formally diagnosed only after I reached out to her OB and asked her to specifically evaluate for DIV based on case reports in women treated with B-cell therapies. The wet mount confirmed it.

I had told her three things.

First: this is not your fault, and you are not dirty. You have a real medical condition with a name and a known mechanism.

Second: your MS treatment may have contributed to this. Not your MS itself, but the therapy we use to treat it. The evidence is still early, but the connection is likely enough to take seriously.

Third: there is treatment. Topical 2% clindamycin or 10% hydrocortisone intravaginally works in roughly 86% of patients within three weeks. The catch is relapse. About a third of patients relapse within six weeks of stopping therapy, and many need long-term maintenance, often weekly or twice-weekly clindamycin. This number may be higher in women on B-cell therapy. In perimenopausal or postmenopausal women, adding intravaginal estrogen can help restore the vaginal lining, though estrogen alone is not sufficient.

She teared up when I shared this with her, because for the first time in over a year, someone had connected the dots. And she felt she had a plan.

This is why I am writing this post today. Because if you are the woman in this case, I want you to have a plan.

The bigger lesson

We have gotten very good at monitoring the things we were trained to monitor. MRI lesions. Relapse rates. EDSS scores. Lymphocyte counts. JCV antibody titers. We check labs, we order scans, we track disability, and this is all of the utmost importance.

But the woman sitting across from us is not just a brain. She has a body. She has mucosal surfaces. She has a vaginal microbiome that her immune system, the same immune system we are deliberately suppressing, helps support.

When we put someone on a B-cell depleting therapy and they develop refractory vaginal symptoms, we need to consider that there may be a link between the two. And we need to be the ones to recognize it, because their OB-GYN may not know to look for it, and the patient herself may be too embarrassed to bring it up or too convinced it has nothing to do with “her MS.”

If you are a clinician reading this: ask the women in your clinic who are on B-cell therapies about vaginal symptoms. Proactively. Don’t wait for them to mention it on the way out the door. And if they report persistent discharge that hasn’t responded to standard treatment, think DIV. Ask their OB/GYN to do a wet mount and look for parabasal cells and inflammatory cells, and an elevated pH.

If you are a woman living with MS reading this, and you have vaginal symptoms that keep coming back, it’s worth asking for a look under the microscope rather than being treated for yeast again and again. You are allowed to bring this up. Your neurologist needs to know.

In your corner,

Dr. Freeman

References

1. Paavonen J, Brunham RC. Bacterial Vaginosis and Desquamative Inflammatory Vaginitis. N Engl J Med. 2018 Dec 6;379(23):2246-2254. doi: 10.1056/NEJMra1808418. PMID: 30575452.

2. Sobel JD. Desquamative inflammatory vaginitis: a new subgroup of purulent vaginitis responsive to topical 2% clindamycin therapy. Am J Obstet Gynecol. 1994 Nov;171(5):1215-20. doi: 10.1016/0002-9378(94)90135-x. PMID: 7977522.

3. Sobel JD, Reichman O, Misra D, Yoo W. Prognosis and treatment of desquamative inflammatory vaginitis. Obstet Gynecol. 2011 Apr;117(4):850-855. doi: 10.1097/AOG.0b013e3182117c9e. PMID: 21422855.

4. Yockey L, Dowst S, Zonozi R, Huizenga N, Murphy P, Laliberte K, Rosenthal J, Niles JL, Mitchell CM. Inflammatory vaginitis in women on long-term rituximab treatment for autoimmune disorders. BMC Womens Health. 2021 Aug 5;21(1):285. doi: 10.1186/s12905-021-01423-0. PMID: 34353326; PMCID: PMC8340364.

5. Levine L, Son J, Yu A, Wesley S, De Jager PL, Moynihan E, Farber RS, Rosser M, Haque H, Riley CS. Inflammatory vaginitis in four B-cell suppressed women with Multiple Sclerosis. Mult Scler Relat Disord. 2024 Feb;82:105387. doi: 10.1016/j.msard.2023.105387. Epub 2023 Dec 16. PMID: 38134606.

6. Arab Bafrani M, Rios V, Kim MJ, Balan A, Bove R. Gynecological health: A missing link in comprehensive treatment monitoring for multiple sclerosis. Mult Scler. 2025 Aug;31(9):1023-1031. doi: 10.1177/13524585251346371. Epub 2025 Jun 18. PMID: 40528461; PMCID: PMC12357974.