Steroid Shots Alone or Steroid Plus 5-FU: What the Evidence Says About Injecting Keloids

Ask most dermatologists how they treat a keloid that is too large to ignore but too risky to cut out, and the answer usually starts with a needle. Intralesional triamcinolone acetonide, a corticosteroid injected directly into the scar, has been the workhorse of keloid care since the 1960s. But over the past fifteen years, a second drug has steadily moved from oncology wards into scar clinics: 5-fluorouracil, or 5-FU. Increasingly, the question patients face is not whether to inject, but what to inject.

How triamcinolone works, and where it falls short

Keloids are essentially fibroblasts that never received the signal to stop. These cells keep producing collagen long after a wound has closed, driven in part by an overactive TGF-beta signaling pathway. Triamcinolone attacks this on several fronts. It suppresses inflammation, reduces fibroblast proliferation, and increases the activity of collagenase, the enzyme that breaks down excess collagen. The clinical result, when it works, is a scar that softens, flattens, and itches less over a series of injections spaced roughly three to six weeks apart.

The limitations are well documented. Response rates for triamcinolone alone are typically reported in the range of 50 to 70 percent, and recurrence after apparent success is common, with some studies citing rates above 30 percent within a year. Side effects are the other problem. Because steroids thin tissue indiscriminately, repeated injections can cause skin atrophy, visible surface blood vessels called telangiectasias, and hypopigmentation, which is especially noticeable and distressing in darker skin tones, the same populations most prone to keloids in the first place.

What 5-FU adds to the picture

5-FU is a chemotherapy agent, but the doses used in scar treatment are a small fraction of oncologic doses and act locally rather than systemically. Its mechanism is complementary to steroids rather than redundant. 5-FU interferes with DNA synthesis in rapidly dividing cells, which selectively slows the hyperactive fibroblasts inside a keloid. It also appears to inhibit TGF-beta driven collagen production more directly than steroids do.

Most clinicians who use 5-FU for keloids do not use it alone. The common protocol mixes 5-FU with a small amount of triamcinolone, often in a ratio around 9 to 1, injected into the scar at similar intervals to steroid monotherapy. The logic is that the steroid quiets inflammation while the 5-FU suppresses fibroblast activity, and the reduced steroid dose lowers the risk of atrophy and pigment loss.

What comparative studies show

Multiple randomized trials and several meta-analyses have compared triamcinolone alone against the combination. The consistent findings, in plain terms, are these. First, the combination tends to flatten keloids faster and more completely, with pooled analyses generally showing higher rates of good to excellent response. Second, recurrence rates appear lower with the combination, though follow-up periods in most trials are short, often twelve months or less, which matters because keloids can recur years later. Third, the side effect profiles differ rather than one being clearly safer. Combination therapy produces less skin atrophy and hypopigmentation, but 5-FU brings its own issues: injection site pain, temporary darkening of the treated area, and occasionally small ulcerations that heal but are unpleasant.

One practical caveat: 5-FU is generally avoided in pregnancy, in patients with significant anemia or bone marrow suppression, and in anyone with a known sensitivity to the drug. A brief medical history matters before the first injection.

Why neither option is a cure

It is worth being blunt about what injections can and cannot do. Both regimens are best understood as suppression, not eradication. A keloid is not a foreign object that can be dissolved; it is the patient's own tissue behaving abnormally, and the underlying tendency remains after treatment. This is why clinicians increasingly frame keloids as a chronic condition requiring maintenance, similar in spirit to managing eczema or acne, rather than a one-time fix.

It also explains why injections are frequently combined with other modalities. After surgical removal of a large keloid, for example, injections or radiotherapy are often used to keep the fresh wound from regrowing into a bigger scar than the original. Silicone sheeting and pressure therapy address mechanical tension, another driver of keloid growth, and can extend the results of injection therapy.

The practical takeaway

For small to moderate keloids, injection therapy remains the reasonable first step, and the evidence now tilts toward the triamcinolone plus 5-FU combination for most adults, particularly those with darker skin who face higher risks of steroid-induced pigment changes. Triamcinolone alone still has a place: it is cheaper, more widely available, and appropriate when 5-FU is contraindicated. Either way, patients should expect a series of treatments rather than a single visit, honest counseling about recurrence, and a maintenance mindset. The needle is a tool, not a cure, and the best outcomes come from clinicians and patients who both understand that from the start.

Further reading: Analysis of Therapeutic Interventions for Hypertrophic and Keloid Scarring: A Systematic Review (J Drugs Dermatol 2025); Keloid management: a review of treatment modalities (Ital J Dermatol Venerol 2025); Pathogenesis, attenuation, and treatment strategies for keloid management (Tissue Cell 2025).