Why did Eczema get worse on LDN?

Im curious! My eczema worsened since I started LDN. But I do think Ive had fewer allergic reactions (I can swell up from unknown causes, usually when I ate something odd or sleep in another place so maybe laundry detergent or house mites?). Why would my eczema get worse though?

First, what does LDN do?

LDN is thought to modulate the immune system, mostly by:

• Blocking opioid receptors briefly, which leads to a rebound increase in endogenous endorphins.

• Modulating microglial cells in the central nervous system (reducing neuroinflammation).

• Altering T-regulatory (Treg) cell function, helping balance overactive immune responses.

So in theory, it should help with autoimmune or inflammatory conditions — including allergies and eczema. But paradoxical reactions can happen.

Why could your eczema get worse?

Here are some possible reasons:

1. Immune System Rebalancing

LDN may be shifting your immune response — sometimes this initial rebalancing flares up existing conditions before they improve. Think of it like “unmasking” inflammation that was being suppressed in another way.

2. Th1/Th2 Immune Shift

LDN may shift the immune response from Th2-dominant to a more Th1-balanced profile. Eczema is typically Th2-mediated, so this shift can initially aggravate it — before calming down later on. Meanwhile, allergic responses (like your swelling episodes) might improve with this Th2 dampening, which fits what you're describing.

3. Endorphin/Opioid Receptor Effects on the Skin

LDN increases endorphins, and skin has opioid receptors. There’s some evidence that these can influence itch perception, inflammation, and barrier function. You might be unusually sensitive to these changes, especially if you already have thin or inflamed skin.

4. Histamine Sensitivity

LDN doesn’t directly block histamine, but immune modulation might change how your body responds to histamine triggers (dust mites, detergents, food additives). It’s possible your threshold for skin irritation went down temporarily.

The improvement in allergic-type reactions makes sense

LDN seems to be reducing your hypersensitivity to environmental allergens, likely through Treg and Th2 modulation — a very good sign.

What to Do

• Track eczema symptoms over weeks/months — it might worsen before it gets better.

• Use gentle, fragrance-free skin care and minimize new exposures (detergents, clothing, etc.).

• Ask your doctor about:

  • Antihistamines or barrier creams during the adjustment period - in my practice LDN + Ketotifen (compounded) + Methylene Blue can be helpful.

  • If the flare is severe, possibly adjusting the LDN dose or temporarily pausing it.

• Consider checking for secondary skin infections (eczema herpeticum, staph, etc.) if the flare is intense.