Steroid Cream Not Working — Is It Resistance? Five Things to Check

Three-Line Summary

• What is commonly called resistance is a mix of true resistance, the body's adaptation (a dulled response) and pseudo-resistance. When a steroid cream feels as if it is not working, it is often pseudo-resistance, which arises when the amount, frequency or duration of application, or the way it is applied, falls short.
• The most common reason is that the amount, frequency or duration of application falls short, and the next is a mismatch between the stage of the condition and the strength or formulation of the medication. A changed diagnosis or an added infection, and the stretch where improvement slows down, are also easy to mistake for resistance.
• In a 1999 study, when 32 patients with psoriasis were treated continuously for 12 weeks, no change that could be regarded as resistance was observed, and a 2013 literature review also concluded that a meaningful dulling of the effect with repeated use had not been identified in clinical trials. The right order is to check how you are using the medication and discuss it in clinic, rather than stopping or switching it on your own.

The Word "Resistance" Mixes Three Things

When patients say in clinic that they have "built up resistance", that phrase mixes three phenomena that are medically distinct.

• True resistance — bacteria or tumor cells change genetically and become able to withstand the drug.
• Adaptation or dulling (tolerance) — the body's response to a drug gradually lessens while the drug is used repeatedly.
• Pseudo-resistance — a situation in which the medication does not work, as though resistance had developed, because the amount, frequency, duration or method of application falls short.

In dermatology, true resistance is rarer than you might think. When patients say "the medication isn't working for me", it often falls into the third category, pseudo-resistance. So before concluding that it is resistance and giving up on treatment, it is first necessary to work out which of the three the current situation falls under.

When True Resistance Is the Issue — Antibiotics and Botulinum Toxin

Before turning to steroid creams, let us first note the cases where true resistance does matter. In dermatology, two are relatively clear: antibiotic resistance and neutralizing antibodies to botulinum toxin. The principles of antibiotic use below reflect the position as of January 2026.

Topical Antibiotics — For Wounds and for Acne

When antibiotics are used for a long time and often, resistant bacteria can emerge. That is true of oral and topical antibiotics alike, and it is a prime reason antibiotics should not be overused. In dermatology, the places where this is easy to notice are antibiotic ointments applied to wounds and topical antibiotics applied for acne. Fusidic acid, for example, is an ingredient for which resistance is often raised as a concern, so in dermatology mupirocin is often used as the wound ointment.

With topical antibiotics for acne such as clindamycin or erythromycin, the risk of resistance rises when they are used alone for a long time. So the principle that is stressed is to use them briefly, only for as long as needed, and where possible together with benzoyl peroxide (BPO) or as a combination product. Using topical antibiotics together with benzoyl peroxide or a retinoid is the key point in managing resistance. The evidence for benzoyl peroxide and how to use it are set out separately in our article on over-the-counter acne treatments.

Oral Antibiotics — Set the Duration and Plan the Next Step at the Same Time

In acne, oral antibiotics such as doxycycline or minocycline are used not only to reduce bacteria but also to calm inflammation. That is why they are sometimes used for longer periods. The problem of resistance is clearly there, however, and what matters is that this resistance does not stop at acne bacteria. With long exposure to antibiotics, the bacteria that normally live in and on the body (the normal flora) change, and this can affect the treatment of other infections as well.

So with oral antibiotics, the key is to use them for a set period, not to keep starting and stopping, and, once things improve, to carry on with maintenance treatment using a non-antibiotic medication such as a retinoid or benzoyl peroxide. There are cases where this is hard to do, though, so the specific duration and plan are decided in clinic.

Botulinum Toxin — Neutralizing Antibodies

With botulinum toxin injections, having them too often and at high doses can, in rare cases, lead to neutralizing antibodies and a weaker effect. The feeling that "it doesn't smooth things out the way it used to", however, is more often explained by the treatment interval, an insufficient dose, or changes in the muscles of facial expression and their compensation than by resistance, and the rate of actual resistance is known to be very low. We cover this topic in detail in our article on botulinum toxin resistance.

Five Reasons a Steroid Cream Can Seem Not to Be Working

When it feels like "the cream isn't helping even though I'm using it" or "I think I've built up resistance", the actual cause is often one of the five below.

1. Too Little Is Applied

This is the most common reason. The gap between the amount a patient means by "I applied it" and the sufficient amount the doctor expects is larger than you might think. If you are worried about steroids and squeeze out an amount no bigger than a grain of rice, then spread it over a wide area, it is less that the medication is weak than that not enough of the medication has reached the lesion.

2. It Is Applied for Too Short a Time

Inflammatory skin conditions have ups and downs, improving and then flaring again. If it flares again after three days of application, that cannot be taken straight away as resistance. It may be because the time that condition needs to settle is longer than that to begin with.

The leaflet that comes with a cream sometimes says not to use it for 2 weeks or more. But not every skin condition settles within 2 weeks. What the leaflet says and the length of treatment actually needed can differ, so how long to apply it should be decided in clinic, as the condition of the skin is followed, not lengthened or shortened on your own.

3. The Strength and Formulation Do Not Suit the Current State

A steroid is not so much a medication to be stepped up because resistance has developed as one where the expected response comes more easily if you start, from the outset, at a strength that suits the thickness of the lesion and the degree of inflammation. Topical steroids come in several levels of strength, and in dermatology the level is chosen and prescribed to suit the condition. So a cream you used before, on a different area or for a different condition, may not suit the lesion you have now.

The same goes for formulation. Examples are applying only a thin lotion to a thickened, lichenified lesion, or covering an oozing lesion in the acute phase with a greasy ointment.

4. The Diagnosis Has Changed, or Another Problem Has Been Added

This is when a cream was applied on the assumption that the problem was eczema, but it was in fact a fungal infection, or when it was understood to be atopic dermatitis, but a secondary bacterial infection is present as well. In these cases, it is not that the medication is not working; what needs to be treated has changed, so the diagnosis needs to be made again.

5. The Stretch Where Improvement Slows Down

With a steroid cream, the skin improves quickly at first, and then, from some point, there comes a stretch where the pace slows. This stretch is easy to mistake for resistance. Often, though, it is not resistance but the point at which the goals and strategy of treatment need adjusting, and decisions such as whether to move on to maintenance therapy belong here.

The Five Reasons at a Glance

How Has Research Viewed Steroid Resistance?

What is spoken of in clinic as steroid resistance is commonly described in research papers as tachyphylaxis, that is, a response that dulls quickly with repeated use. As of January 2026, however, in clinical trials there is no clear evidence that the treatment effect falls meaningfully over time.

Doctors' Perception and the Actual Result — The 1999 Study

In a study that Miller and colleagues published in the Journal of the American Academy of Dermatology in 1999, 57% of dermatologists felt that resistance develops after about 8 weeks. Yet when 32 patients with psoriasis were actually treated continuously for 12 weeks, none showed a change that could be regarded as resistance.

The 2013 Literature Review

A literature review that Taheri and colleagues published in the Dermatology Online Journal in 2013 points in the same direction. It concluded that clinically significant tachyphylaxis had not been identified in clinical trials.

Acute Tolerance Observed in the Laboratory

There is also data pointing in a different direction. A classic study that du Vivier and Stoughton published in the Archives of Dermatology in 1975 observed acute tolerance in the vasoconstriction test, that is, a test that looks at the blanching of the skin. It is hard, though, to carry this result straight over to the conclusion that "the inflammation cannot be brought under control", in other words, resistance.

How Far Has This Been Confirmed?

To sum up, when a medication seems not to be working, it is more often pseudo-resistance, such as the amount, frequency or duration of application, a mismatch in strength or formulation, or a changed diagnosis, than resistance. The 1999 study, however, followed 32 patients with psoriasis for 12 weeks, and the conclusion of the literature review is likewise that it "has not been identified in clinical trials". This does not mean it has been proven never to occur under any circumstances.

If You Cut Back or Stop on Your Own for Fear of Resistance

Some patients tell us, "I applied it every other day because I was afraid of building up resistance", or "It got a bit better, so I stopped." In many chronic skin conditions, however, what actually causes trouble is not resistance but a vicious circle like the following.

1. The medication is applied irregularly.
2. The lesion comes back.
3. Treatment starts again from the beginning.
4. In the end, the total amount used goes up.

If anything, using enough of a medication at a strength that suits the condition, settling the inflammation in a short period and then finishing, as decided in clinic, can be a way to reduce total steroid exposure. When to cut back or stop is also better decided together in clinic than on your own.

What to Check First When a Medication Seems Not to Be Working

Before you go in for an appointment, or before the medication is changed, it is worth checking three things first.

• How much (amount) — whether you applied enough for the area being treated, using one finger segment's length of cream (a fingertip unit, FTU) as the yardstick
• How often (frequency) — whether you kept exactly to the number of applications prescribed
• How long (duration) — whether you judged it after applying it for just two or three days

On top of these, look at two more things.

• Whether the lesion has spread from where you were applying the medication to other areas
• Whether anything has changed in your daily life, such as alcohol, stress, sleep or a cosmetic product you have just started using

Simply noting these points down and bringing them with you makes it much easier to find a way forward in clinic. This check is not for changing or stopping the medication yourself; it is a process of gathering the material for the decision to be made in clinic.

Would Switching to a Stronger One Solve It?

The principle is not to go stronger regardless, but to use a strength that suits the lesion as it is now. It is the same logic as a large fire being hard to put out with one bucket of water. Topical medication alone is also often not enough, so whether to raise the strength or add another treatment is decided in clinic.

Before Changing the Medication

In many cases, the skin responds to the same medication again once the amount, frequency and duration of application are corrected. So when a medication feels as if it is not working, checking how it is being used comes before changing it.

Summing Up — What to Keep in Mind

What is commonly called resistance in dermatology is often less a problem with the medication itself than a situation in which usage, strength, diagnosis and condition are out of line with one another. When it feels more and more as if resistance has developed, keeping a record, checking, and realigning the treatment strategy resolves it in quite a few cases.

• Decisions belong in clinic — please do not stop or change your medication while worrying about it on your own; talk it over with a board-certified dermatologist and work out where things have slipped out of line. This article is a general explanation and does not replace an individual diagnosis.
• Individual variation — the strength and formulation that suit, and the duration needed, differ according to the type of condition and the state of the lesion.
• Scope and date of the evidence — the sources cited in this article are a 1975 laboratory study, a 1999 study in which 32 patients with psoriasis were treated for 12 weeks, and a 2013 literature review. The content of this article is as of January 2026, and the explanation may change with later research and clinical guidelines.

References

1. Miller JJ, Roling D, Margolis D, Guzzo C. Failure to demonstrate therapeutic tachyphylaxis to topically applied steroids in patients with psoriasis. J Am Acad Dermatol. 1999;41(4):546-549. doi:10.1016/S0190-9622(99)80050-4
2. Taheri A, Cantrell J, Feldman SR. Tachyphylaxis to topical glucocorticoids; what is the evidence? Dermatol Online J. 2013;19(7):18954.
3. du Vivier A, Stoughton RB. Tachyphylaxis to the action of topically applied corticosteroids. Arch Dermatol. 1975;111:581-583.