Steroid, 5-FU, or Both: How Clinicians Actually Choose an Injection for Keloids

Ask a dermatologist how most keloids get treated and the answer usually involves a needle, not a scalpel. Intralesional injection, meaning medication delivered directly into the scar tissue itself, remains the first line approach for the majority of keloids because it targets the biology of the lesion without creating a new wound that could itself keloid. But the phrase "steroid shot" undersells what is actually a set of choices. The two most studied agents are triamcinolone acetonide, a corticosteroid, and 5-fluorouracil, a chemotherapy drug repurposed at low doses. Increasingly, clinicians mix them. Understanding why requires looking at what each drug does inside a keloid.

What triamcinolone does. A keloid is, at its core, a wound healing process that never received the stop signal. Fibroblasts in the scar keep producing collagen, particularly type I collagen, long after the skin has closed. Triamcinolone works on several fronts. It suppresses the inflammatory signaling that keeps fibroblasts activated, it reduces levels of transforming growth factor beta, a key driver of collagen production, and it increases collagenase activity, which breaks down the collagen already deposited. It also constricts the small blood vessels feeding the scar. The clinical result, when it works, is a keloid that softens, flattens, and stops itching over a series of treatments typically spaced four to six weeks apart.

What 5-fluorouracil does. 5-FU takes a different route. It is an antimetabolite that interferes with DNA synthesis, which means it preferentially affects cells that are dividing quickly. In a keloid, the fastest dividing cells are the overactive fibroblasts. 5-FU slows their proliferation and pushes some of them toward programmed cell death. It also appears to inhibit the same TGF beta pathway that triamcinolone targets, though through a different mechanism. Used at the low concentrations typical in scar treatment, usually 50 milligrams per milliliter, it does not cause the systemic effects associated with chemotherapy. The most common local side effects are pain during injection, temporary darkening at the site, and occasionally small ulcerations.

Why the combination has gained ground. Triamcinolone alone works, but it has two well documented problems. First, recurrence: reported recurrence rates after steroid monotherapy vary widely across studies, but figures of 30 to 50 percent within a few years appear regularly in the literature. Second, side effects: repeated steroid injections can cause skin atrophy, meaning thinning and depression of the tissue, telangiectasias, which are visible spidery blood vessels, and lightening of the skin, a particular concern for patients with darker skin tones, who are also the patients most likely to develop keloids in the first place.

Mixing 5-FU with triamcinolone, often in ratios that heavily favor the 5-FU component, allows clinicians to lower the total steroid dose while attacking the keloid through two mechanisms at once. Multiple randomized trials and meta-analyses have found that the combination produces greater flattening, better symptom relief, and fewer steroid related side effects than triamcinolone alone. Some head to head data also suggest lower recurrence with the combination, though follow up periods in many trials are short, and keloids are notorious for returning after the study ends.

Where each option still makes sense on its own. Triamcinolone monotherapy remains reasonable for smaller, newer, actively inflamed keloids, where the anti-inflammatory effect is doing most of the useful work. It is also the default when 5-FU is contraindicated, which includes pregnancy, breastfeeding, and certain blood disorders. 5-FU alone is sometimes chosen for patients who have already developed steroid side effects, or for scars where atrophy would be especially visible. The combination tends to be favored for older, firmer, treatment resistant keloids and for larger lesions where cumulative steroid dose becomes a concern.

What patients should realistically expect. No injection protocol dissolves a keloid in one visit. Most regimens involve three to six sessions at minimum, and improvement is usually measured in softening and flattening rather than complete disappearance. Pain during injection is real with both drugs, and many clinicians pretreat with topical anesthetic or add a small amount of lidocaine to the syringe. Itching and tenderness often improve before the visible bulk does, which is worth knowing, because symptom relief is a meaningful outcome in its own right.

The honest summary is this: intralesional therapy is not one treatment but a menu, and the evidence increasingly supports combining agents rather than escalating the dose of a single one. A patient whose keloid has stopped responding to steroid injections is not out of options. They may simply be a candidate for a different mixture in the same syringe, and that is a conversation worth having before considering surgery, radiation, or resignation.

Related reading: Steroid Shots vs 5-FU for Keloids: What the Injection Actually Does.