Corticosteroids in Dermatology: What's Old Is new

Corticosteroids have long been used in medical practice for the management of inflammation. In dermatology, they play a pivotal role in interventions for various conditions, such as atopic dermatitis and psoriasis. And yet, despite their status as a mainstay treatment, steroids in general have certain baggage, due in part to public perception with the name to their clinical use in therapy for nearly six decades. According to James Dinulos, MD, who practices at Dermatology and Skin Health in Dover, NH and is Clinical Assistant Professor of Dermatology at the University of Connecticut, despite some advances in the research and treatment of various diseases in recent decades, corticosteroids remain essential to the treatment of many dermatologic conditions. Ahead, Dr. Dinulos discusses the latest trends and advances regarding corticosteroids.

There has been some research suggesting a high prevalence of corticosteroid “phobia.” What do you make of the report and do they influence your practice?

“There is no doubt that ‘steroid phobia’ exists,” notes Dr. Dinulos. Smaller children may be too young to be fearful of certain agents, but Dr. Dinulos points out that older kids as well as their parents often have a phobia toward steroids. “Given that parents tend to be the ones applying the medications in many of our pediatric patients, most of our interaction about the safety of steroids will likely be with parents,” he continues.

Addressing “steroid phobia” can be a challenge with some particularly resistant parents, but Dr. Dinulos observes that setting the appropriate context is key toward helping them understand the adverse event profile of steroids. “I usually tell the patient or parent that these agents have been used for roughly 60 years and that just by sheer numbers and time we know that they are safe,” says Dr. Dinulos. But just like any other medicine, there are potential side effects when steroids are not used appropriately, and Dr. Dinulos stresses the importance of discussing these in a fair manner, as well. “Often when patients think about side effects of medications, they’re not weighing the risks of potential side effects against the risks of non-treatment,” he notes. “The adverse effects of unopposed inflammation in dermatologic conditions such as atopic dermatitis or psoriasis can be devastating,” he says. When patients or parents refuse to treat one of these conditions because of concern about systemic absorption, Dr. Dinulos emphasizes the consequences of uncontrolled inflammation and it's impact on overall health.

“Studies have been done on heart disease showing that psoriatic patients, for example, are at increased risk for myocardial infarction, presumably from uncontrolled inflammation,” he continues. That’s why it is important to control inflammation, he stresses. “Whenever I talk about a side effect of a medication, especially steroids, I try to make sure it’s a balanced discussion of risks and benefits. Patients are more likely to be hyper-aware of the steroidal side effects but may not be as aware of the consequences of not treating inflammation,” observes Dr. Dinulos.

Has “steroid phobia” affected how clinicians themselves may be treating inflammation, perhaps in cases of particularly resistant patients/ parents?

For dermatologists, the notion of “steroid phobia” is well accepted, says Dr. Dinulos. How to talk to parents who are treating their children that want to know more about adverse events can be a challenge, however. “Truth be told, treating the inflammatory response with glucocorticoids can improve barrier function and diminish the risk for secondary bacterial infection.” This also applies for emollients, observes Dr. Dinulos, but improving barrier function with emollients alone is not realistic. At the same time, Dr. Dinulos explains, “There is a tipping point with steroid use, where the AD or psoriasis may resolve but you get a negative impact from diminished collagen production. The art of medicine comes in with how we can judge a patient’s response and tailor a therapeutic regimen that minimizes risks while maximizing efficacy of the agents.”

Perhaps a symptom of “steroid phobia” is what Dr. Dinulos calls the unwritten “two-week rule” of steroid treatment. “Some clinicians will stop glucocorticoid treatment after two weeks as a general rule, perhaps to avoid side effects,” he says. The problem with this logic, Dr. Dinulos suggests, is that it doesn’t focus enough on the patient’s clinical response. “The impact of a given agent, both from the standpoint of safety and efficacy, should be weighed by its impact on the disease state,” he notes. Many inflammatory conditions are not curable, he argues. “Steroidal agents are effective at controlling these disease states. Patients cannot be on them all the time, but their time on them should depend on response and disease state rather than on an arbitrary duration,” says Dr. Dinulos.

Dr. Dinulos points out that clinicians can get creative with incorporating agents such as calcipotriene to limit the amount of steroids used. “This is called ‘chronic long-term flare maintenance,’ which basically holds that you use higher potency glucocorticoids for flares and then maintain response and limit the severity of the glucocorticoid and increase time between flares with agents such as tacrolimus and pimecrolimus, or even ceramide-based creams.” This model has been studied and proven successful, says Dr. Dinulos. “By being disease-state oriented, we can limit exposure to all of these medications,” he observes.

Finally, in terms of compromising with resistant parents, Dr. Dinulos imparts that it is important to treat a disease within the context of a patient or parent’s own belief systems. This may not always result in the most optimal treatment, but it is more important to have patients agree to some kind of intervention rather than nothing at all. That doesn’t mean that a parent cannot be swayed, however, if you provide enough reason within that belief system, says Dr. Dinulos. “Some parents want only natural treatments for their children and consider steroids to be unnatural. In these cases, sometimes a compromise is not possible. However, that can present a pathway to discussing the effects of uncontrolled inflammation, but perhaps from another perspective. You can perhaps discuss how a child at one year old may be discouraged to learn and explore as they should when they are constantly scratching and itching. If you explain to a parent that not treating a child’s inflammation can negatively impact a child’s cognitive and motor development, the parent may be more receptive to the notion of steroids,” notes Dr. Dinulos.

What are important steps for minimizing risks of common adverse events? When adverse events do occur, are there common contributory factors?

The first thing that clinicians should do to minimize adverse events, according to Dr. Dinulos, is to select an agent with the least likelihood of side effects for patients. “Particularly in pediatric patients, realizing that there are other factors, such as increased absorption from diapers are important and should be considered,” he adds. After agent selection, you want to treat at appropriate strength, which will vary based on the specific circumstances of each case, Dr. Dinulos reminds.

Another crucial element to reducing any unwanted effects from treatment and for maximizing efficacy is to provide careful instruction on how to apply steroids. “Sometimes you have to demonstrate how to apply the cream and then watch the parent do it,” says Dr. Dinulos. How an agent is applied—either by dabbing or rubbing— can affect the dosage of the drug the patient is actually receiving. “If a lower-strength steroid is not working, you must first determine if the steroid has been applied appropriately before changing the course of treatment,” notes Dr. Dinulos. Again, this will depend on how well you know the patient and their compliance patterns.

When side effects do occur, it’s usually from clinicians who inadvertently use a super potent corticosteroid in a child, says Dr. Dinulos. “The most common side effect we see in pediatrics is skin thinning and epidermal atrophy, which thankfully most of the time resolves in pediatric patients.” They also improve with time in older patients, but at a slower rate, Dr. Dinulos explains. Another potential side effect can occur when using steroid around the eyes. “Patients can get glaucoma and cataracts with long-term use of steroids near the eyes, but thankfully this is fairly rare.” Nevertheless, it’s a severe potential side effect, and clinicians should exercise restraint in these areas. Another side effect Dr. Dinulos sees more in girls than boys is stria formation. “This has likely to do with periods in a person’s life when the hormonal status is changing,” he says. As with any other stretch mark, stria formations improve with time but are permanent.

There is also some research about corticosteroids impairing barrier function and possibly having a negative effect on collagen production. Could you offer some clinical context for these findings?

“There has been a lot of relevant research over the last 10 years roughly that’s looked at lipid biosynthesis and the lipid content of the epidermis. This has led to a greater emphasis on ceramides, which has translated into newer creams, often called ‘barrier repair agents,’” Dr. Dinulos explains. Barrier repair products have taken two approaches, notes Dr. Dinulos. “The first is to be approved as a medical device, with ceramides dispersed in the appropriate ratios.” Among these products are Epiceram (Promius), Mimyx (Stiefel/GSK), Hylatopic Plus (Onset Dermatologics), Atopiclair (Sinclair), and Eletone (Mission Pharmacal). “The other path is the more commercial route, with agents such as CeraVe (Valeant) and Restoraderm (Galderma) that incorporate lipids into moisturizers,” says Dr. Dinulos.

While these agents can be exploited to the benefit of patients and physicians, Dr. Dinulos sees barrier repair agents as complimentary to steroids, rather than displacing them. “In chronic long-term flare maintenance, barrier creams represent a way to help diminish inflammation in the skin and thereby serve a potential function as part of a long-term regimen,” he says.

There has been some discussion about pediatric labeling for corticosteroids. Can you clarify the issue from a technical standpoint? Is this clinically relevant?

Dr. Dinulos believes that pediatric labeling is important for one critical reason. “We all know that with many of the medications that we’re using, the vast majority have not been studied in the pediatric population,” he notes. Thus, with almost any medication you choose, you’re going off-label. “With a drug that has been studied and approved, it becomes extremely relevant to study with further trials, for these reasons.” Dr. Dinulos notes that fluticasone has been studied in three month olds, and it is likely to be used more readily in this population than those that have not been studied.

Given that pediatric studies are not as feasible for many manufacturers, Dr. Dinulos recommends that clinicians be mindful when administering any medication—dermatologic or otherwise—to an infant. “Kids are not little adults, and that’s why pediatric labeling for steroids is probably a benefit to both patients and physicians,” he observes. It may also help to curb the problem of under-treatment of infants, he adds. “Perhaps because of a lack of pediatric indications, many infants suffer and go without treatment, so pediatric labeling may help to prevent this, as well,” says Dr. Dinulos.

What is your take-away message about the status and importance of corticosteroids in the realm of managing inflammatory dermatological conditions?

Sometimes keeping things simple is the best approach for a given condition. “Steroids are still the standard of care in many conditions,” says Dr. Dinulos. “Other than trying to manipulate or combining steroids with steroid-sparing agents or tweaking the vehicle, we haven’t had many new molecules for topical application in dermatology for roughly a decade.” However, he continues, “though there is little that’s ‘new,’ on the other hand, if we stick to the basics of talking to our patients about the importance of managing inflammation, we can continue to control these conditions,” he observes. So in a sense, he notes, “what’s old is new again.”