The Surprising Side Effect She Didn’t Dare Talk About

MS Care and Unexpected Challenges

However, Commorbidities can complicate this issue your neurologist wasn’t trained to find.

Lenora Freeman, MD, PhD

Aug 07, 2026

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. It was 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.

Then bacterial vaginosis was diagnosed. 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. 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 is lined with a moist surface called a mucous membrane. The mouth, gut, and airways share this feature. These surfaces host many harmless bacteria. The body has ways to keep this balance. Part of that system involves antibodies. They 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. It keeps them away from the tissue lining and helps the body 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. Vagina has relatively few. Instead, antibody-producing cells appear to travel in from the bloodstream when needed.

These therapies deplete B cells, including rituximab, ocrelizumab (Ocrevus), ofatumumab (Kesimpta), and ublituximab (Briumvi).

They have become the backbone of modern MS treatment.

They are remarkably effective at preventing relapses and new MRI lesions.

These drugs attach to the CD20 marker on B-cell surfaces.

This binding leads to the destruction of those B-cells.

Mature plasma cells, which produce antibodies, do not carry CD20.

Therefore they are not directly killed by these drugs.

Some plasma cells are long-lived and can survive in the bone marrow for years.

Others are short-lived and depend on a steady supply of new B cells.

When the B-cell supply is cut off, replenishment stops, and antibody levels can gradually fall.

This occurs particularly in patients treated for longer periods or in 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

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