COMMENTARY

Those Pesky Rashes: Critical Dermatology Issues in Primary Care

An Update on Everyday Rashes

Charles P. Vega, MD; Graeme M. Lipper, MD

Disclosures

October 29, 2015

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Editor's Note:
Part 2 of this 2-part discussion will be live in mid-November.

Dermatology Update for the PCP

Charles P. Vega, MD: Hello. Welcome to Medscape's series on critical issues. Today we're going to be covering critical issues in dermatology. I'm Chuck Vega, a clinical professor of family medicine here at the University of California at Irvine. I'm very excited to be joined by Dr Graeme Lipper, who is a partner at the Advanced DermCare practice in Danbury, Connecticut and an assistant clinical professor of dermatology at the University of Vermont. Graeme, welcome.

Graeme M. Lipper, MD: Thanks for having me.

Dr Vega: As Graeme and I have discussed a little bit previously, we're going to be doing a two-part series for you. The first is focused on some very common yet critically important dermatologic conditions that have some updates in terms of diagnosis and management that translate very well into the primary care practice. We want to really emphasize the need for coordination between dermatology and primary care.

The second part of our talk should be a little bit fun because there is going to be a quiz component to it, which should allow for some active learning. Graeme is going to be talking about some cases using some pictures. It will be "Identify the Rash" time for me, and I'll be put on the spot a little bit. Hopefully, it's a lot of fun for you, too. I would encourage you to play along at home and see what you think about the diagnoses as we go.

Psoriasis

To get underway, we have some common dermatologic conditions that I think need attention. I'm going to lead off with psoriasis. Psoriasis affects 7.4 million adults in the United States.[1] The total cost of psoriasis per annum in the United States exceeds $30 billion.[2] Most of that is actually due to disability and health-related quality-of-life issues. In addition, we know that a lot of that disability is due to psoriatic arthritis. Rates of psoriatic arthritis prevalence within the disorder of psoriasis vary pretty greatly, anywhere from 6% to 42%.[3] It depends on how the diagnosis of psoriatic arthritis is made. We do know that it takes a severe toll on patients. Moreover, it reflects systemic inflammation, which is a hallmark of psoriasis. Graeme, I know the link between psoriasis and other disorders is a topic of interest to you and one that merits further attention.

Dr Lipper: This area has been incredibly exciting to treat and manage as a dermatologist. When I started out as a resident 13-15 years ago, we really didn't have a whole lot to offer our patients. We obviously had the typical topical treatments, like corticosteroids, and phototherapy. Other options were cumbersome and tedious. In the best of scenarios, if we had someone with moderate-to-severe psoriasis, we could improve their quality of life, but—and there were studies that showed this—most patients were not satisfied with the care we were giving them.

Then came a whole slew of highly effective treatments, starting with the tumor necrosis factor (TNF)-alpha inhibitors (infliximab and adalimumab) and a whole bunch of monoclonal antibodies (and TNF blockers) like etanercept. They really revolutionized the way we manage this disease. Instead of talking about controlling people's symptoms and having them apply topicals ad infinitum for the rest of their lives, we could start to look at people and say, "Yes, we can help you. We can clear you."

If I had to emphasize the two main paradigm shifts that have happened over the past decade or so in psoriasis, one is that our goal is now to clear people, to have them not look like they have even a speck of psoriasis. We've gone from a goal of Psoriasis Area and Severity Index (PASI) 25 to PASI 50, which is basically clearing 50% of disease. Now we're talking about PASI 100, which wasn't even a concept when I was a resident. In other words, no visible disease. This has been possible because of some tremendous bursts in research and understanding of the immunophysiology of psoriasis. Whereas initial treatments targeted less specific inflammatory signals—primarily TNF-alpha—we've moved on to interleukin (IL)-12/23 inhibitors and, most recently, IL-17 inhibitors. Not only are these treatments more and more selective toward skin immunity, but they also deliver incredible PASI scores. We don't really talk about improving psoriasis anymore. We want to clear people.

The second thing would be that we used to think of psoriasis as a skin disorder. Now, we really think of it as a systemic inflammatory disease akin to lupus and dermatomyositis. You wouldn't look at a malar rash and say, "That's a skin problem." And you wouldn't look at Gottron papules and say, "Oh, that's just a skin problem." I think we have to treat psoriasis the same way. If someone has cutaneous manifestations of a systemic disease, we have to manage the joint disease and any associated cardiovascular complications. Psoriasis has been associated with metabolic syndrome, diabetes, obesity, cardiovascular disease, hypertension, and stroke in addition to psoriatic arthritis. This condition can severely shorten a person's life span if we don't treat it adequately.

Dr Vega: That's a great point, Graeme. Thanks for sharing that. I agree that it's amazing to hear the idea of a PASI 100. I know that leads to a lot of improvement in quality of life for our patients. You do have to pay attention to metabolism, too. A systematic review[4] of 33 studies showed that having psoriasis was associated with a 25% increase in the risk for myocardial infarction and psoriatic arthritis with a 57% increase, with lesser increases in the risk for stroke. Some limited evidence shows that treating psoriasis with disease-modifying agents can actually bend back that risk. But it's going to take not just treatment with disease-modifying agents but also with statins, aspirin, lifestyle changes, and all the treatments that we normally think of for metabolic risk factors for cardiovascular disease.

Dr Lipper: Absolutely. I would also add the psychiatric impact of psoriasis. There is depression. Suicide rates are significantly higher in people with moderate-to-severe psoriasis, as is the incidence of depression and alcoholism. There are lifestyle interventions that can affect the disease. For instance, palmar and plantar pustular psoriasis is quite heavily correlated with smoking. If we can encourage smoking cessation, we can significantly improve that condition. Conversely, if we manage people with systemic therapy but fail to get them on a smoking cessation program, they may be refractory to all of our efforts. It's really an "all-hands-on-deck" approach, treating risk factors as well as lifestyle factors.

Acne, Rosacea, and Perioral Dermatitis

Dr Vega: Let's pivot to another common skin disorder. I don't think it carries the consequence that psoriasis might, but it's still very common and can be very troubling for patients, and that is acne and rosacea. You wanted to comment on the diagnosis and differential between acne and rosacea, giving primary care physicians a leg up on making that diagnosis.

Dr Lipper: Acne is one of the most deceptively complicated conditions to manage as a dermatologist. A patient with acne is not a 2-minute or a 5-minute visit. It can be a very involved consultation, and there's a good reason for that. If you see an acne patient, say a 16-year-old teenager with comedonal acne with some cysts, and you say, "Here are a bunch of creams. Use them. Goodbye," then I would say that your chance of success is very low. First of all, it's a teenager. You've told them nothing about what to expect. Adults, also. Everyone. You're not providing context, and without context, patients are not going to know how to manage their condition. When I look at facial papular and pustular disorders, I like to broadly divide them into acne, rosacea, and an orphan cousin of rosacea, perioral dermatitis, which we see often misdiagnosed by primary care providers. I definitely think it's worth mentioning.

Acne. If you think one size fits all for acne, you're definitely mistaken. When you look at a patient with acne, you have to assess a lot of factors. What is the severity of their acne? Are they developing cysts with scarring? Is this primarily comedonal acne with a lot of blocked pores, as you might see with a young teenager, and the sebum isn't really revving up and fueling the process? Are you dealing with a 40-year-old woman who is coming in with what we consider hormonally distributed acne, with periodic, often quite painful, cysts in the jawline and hairline in the so-called U distribution? She may have very sensitive skin as opposed to the oilier, tough skin of a teenager. All of these different types of acne would need to be managed very differently.

Whenever you see a patient with acne, you always have to manage expectations. Explain that a lot of our treatments take time to work. Especially if there's a lot of comedonal acne, we need to work on opening up blocked pores with topical retinoids. I like to review how to apply these and the importance of using good moisturizers and emollients. I also like to explain that the best approach to treating acne is through targeting at multiple levels. There is a pretty good consensus that if you want to manage acne, using an oral antibiotic as monotherapy would be inappropriate. You might get some initial improvement in the first month or two as you cut down on the Propionibacterium acnes colonization. But then you'll hit a wall, and the acne will start to recur as resistance develops, and it will be a total treatment failure. Plus, you've encouraged and developed resistance for the lifetime of that patient.

You want to start someone on a simple acne regimen that would typically involve a topical retinoid to address the comedonal components. Obviously, in a 45-year-old woman without as many comedones, that might not be as important. You want something to cut down on bacterial loads, so an oral antibiotic along with topical benzoyl peroxide would be appropriate. Whenever I use a systemic antibiotic, I always use a topical benzoyl peroxide or other topic agent to reduce the incidence of resistance. Then, if you're dealing with a lot of cystic acne and scarring, you may need to go with more powerful weapons such as systemic isotretinoin.

Rosacea. Rosacea is a totally different story. Rosacea isn't due to an overgrowth of Propionibacterium or comedones. The primary lesion in rosacea is a papule or pustule without a comedone, usually in the centrofacial area. It also depends on what type of rosacea you're dealing with. The first stage of rosacea is centrofacial redness and flushing. With phase 2, you tend to get pimples and pustules, and then as it progresses in a small percentage of cases, you can actually get some swelling and scarring, the phymatous changes of rosacea.

We like to tailor our treatment of rosacea based on what we're looking at clinically. Initially, I like to tell my patients that papules and pustules are a lot easier to manage than the background erythema. If someone is flaring with severe rosacea, we will typically add an oral tetracycline antibiotic to get them under control, usually combined with a topical antibiotic with anti-inflammatory activity such as metronidazole or one of the new kids on the block, topical ivermectin, which has also been quite effective.

Perioral dermatitis. I suspect that many clinicians see patients with perioral dermatitis but probably don't realize it. While we sometimes see this condition in men, it's much more common in women and children. It's a monomorphic inflammatory papular eruption that tends to flare periorally, around the nasal alar region, and often around the eyes. This can often be triggered by topical corticosteroids or cosmetic use.

An important take-home point here is that this is more of an irritant reaction. If you try to manage this with a topical retinoid or benzoyl peroxide, you're actually going to make it worse. So when you see that fine papular rash, almost like a combination of eczema and maybe a hint of seborrhea, with flaking and redness, and you find papules around the mouth and eyes and nose, that typically needs to be managed with a 4- to 6-week course of an oral tetracycline such as doxycycline. It can also be managed quite effectively with topical metronidazole. Some people have been using topical ivermectin off-label for this. If it's very inflammatory, topical pimecrolimus or tacrolimus are quite helpful in reducing inflammation, especially if the patient has gotten dependent on topical steroids with significant flares whenever they stop the steroid.

The New Kid on the Block: Ivermectin

Dr Vega: I do think that it's worth mentioning ivermectin just because it is a new kid on the block and maybe more so for those of us in primary care. I don't think I was quite as aware of its efficacy until I did a little bit more research on it. It was approved by the US Food and Drug Administration (FDA) for the treatment of rosacea in late 2014 and has three clinical trials. They were all 12-16 weeks in duration. Two of the trials compared ivermectin with placebo,[5] and one had an active comparator, topical metronidazole.[6] Overall, efficacy was very good with 38%-40% of patients in the two placebo-controlled trials[5] either cleared or almost cleared of their rosacea. Treatment satisfaction exceeded two thirds of the combined study cohort. Health-related quality of life also improved. One of the trials was extended to 52 weeks. Clearance or near clearance occurred in 70% of patients who continued to use ivermectin. So, it is a strong rate of improvement overall.

In the head-to-head comparison trial with metronidazole,[6] the ivermectin was superior in terms of lesion count, treatment satisfaction, and health-related quality of life. I should mention that it has a tolerability profile similar to placebo. Ivermectin does seem to be an effective treatment option for patients with rosacea, based on the research.

Atopic Dermatitis

Dr Vega: Let's move on to our last common dermatologic condition that has affected millions of people in the United States: atopic dermatitis. Atopic dermatitis affects 12.5% of all children.[7] Of note, I found a study[8] that showed that although two thirds of these patients have mild disease, 85% of them are referred from pediatric offices to dermatology practices like yours, Graeme. The authors suggested that there may be difficulty in applying some of the basic principles of atopic dermatitis management, which includes avoiding triggers, the religious application of emollients, and use of no soap or only mild soap. I can tell you that with my young kids, that's the one thing they can get behind: no soap or mild soap. Otherwise, it's me chasing them around with emollients, literally up and around the house, and there are emollients everywhere because it's a mess. But it's a battle worth fighting because it's the simple things that go a long way. Trust me, I know how hard it could be in terms of practical application.

Something that people are very interested in—I think partly because it can be so difficult just to grind through those preventive measures on a regular basis—is the use of prebiotics and probiotics to either prevent or treat atopic dermatitis. A recent systematic review[9] published in 2013 found that probiotics were effective in preventing atopic dermatitis in 11 of 17 included studies and reduced the severity of atopic dermatitis in 5 of 6 studies. Previous reviews weren't that positive, but more recent research in the last 3 years emphasized that probiotics, in particular, can be effective. The one probiotic that comes up again and again is Lactobacillus rhamnosus GG. It might be an option for parents who are really struggling and whose kids are facing more severe illness despite the application of those routine methods.

Topical Corticosteroids and Calcineurin Inhibitors

Another way that we treat atopic dermatitis—certainly in clinical care—involves the application of corticosteroids or topical calcineurin inhibitors. I'm always concerned with the potential side effects of topical corticosteroids. I think the choice is clear if you're talking about sensitive areas such as the face. What is your experience as a dermatologist? I see high-potency steroids used over time for very mild conditions, and I'm sensitive to that, particularly among children, because their skin is different from those of adults. I see it across the age range. How much damage are we doing to our patients with the routine application of too much steroids or maybe not the right indications?

Dr Lipper: That is a very good question. I think topical corticosteroid application is one of those situations where using the right product for the right amount of time in the appropriate location can be a lifesaver. There's nothing better at controlling acute flaring atopic dermatitis than an appropriate-strength topical corticosteroid.

I would say that there is not much of a role for ultrapotent or fluorinated corticosteroids, Class 1 or Class 2 potency, at least in my practice, in managing atopic dermatitis in children. Certainly, the only place I would use them in adults is in lichenified, thickened, or chronic lesions on the extremities. If you use a lower-potency—Class 5, 6, or 7—topical corticosteroid for a very finite period of time (7- to 14-day pulses), even with facial use, there have been very reassuring data over time that this doesn't suppress the hypothalamic-pituitary-adrenal axis and doesn't induce the skin changes that we try to avoid such as atrophy or steroid-induced acne. There are some very good studies out of Europe that showed that even chronic, periodic use of lower-potency steroids around the eyes does not increase the risk for glaucoma or cataracts.[10]

I try to steer away from using ultrapotent topical steroids in skin folds and flexures of the face. I also stress that the time period should be limited to periods of 7-10 days. If someone is using steroids more frequently than that, then they are what we would call steroid-dependent. They really need to be on an alternative. In that context, topical calcineurin inhibitors, either tacrolimus ointment or pimecrolimus, are usually what I turn to. As I'm sure that people are aware, there is an FDA warning—a black box warning—on the labeling of these agents, and I'm not going to question the reason that it's there. It's there, and we're stuck with it. It was based on some animal data that showed some concerns with chronic exposure. There have been excellent long-term follow-up data.[11] In fact, there are better safety data for these drugs than there are for topical corticosteroids, and our initial concerns about malignancy, especially with lymphoma,[12] were not borne out by 10+ years of follow-up data.

Very recently, some follow-up data on pimecrolimus came out. The Pediatric Eczema Elective Registry (PEER) study[13] of eczema in children and young adults using pimecrolimus showed no elevation in the malignancy risk associated with this drug, including lymphoma. So I am very comfortable using it, and I think it should be used as an alternative to topical corticosteroids as a steroid-sparing agent.

Plus, you don't want to forget the importance of topical emollients and gentle skin care. If you're throwing lavender body wash on a child while you're trying to manage them with topical steroids, you are basically pouring gas on a fire that you're trying to put out. It's not going to work. Good care for eczema-prone skin requires taking time to educate patients. That's really the cornerstone you need to build on.

Dr Vega: Yes, absolutely. I think that as soon as we get to the point of good skin care, you can see the difference, but it does take a little bit of persistence. As clinicians, we can understand just how difficult it is to get a 4-year-old to comply with some of these things. It is certainly a challenge we all face.

Dr Lipper: You mentioned the probiotic Lactobacillus. I tell my patients that the verdict is still out.[14] There are some encouraging data. As long as something is harmless, I think it's reasonable to try. We would love a pill or something simple to manage atopic dermatitis. As I've said, I'm encouraged and happy about all of the developments in psoriasis. The flip side of that is that we really haven't come very far with managing atopic dermatitis, unfortunately. That's an area where we really need some new safe therapeutic options that we just don't have.

Dr Vega: Well, you just described a few options, and I think if you throw probiotics in the mix, you're creating a spectrum of different treatments that patients can pick and choose from depending on which are working for them and which are working for their kids. I think it's always a positive thing to have more in the armamentarium. But as you said, hopefully there is more to come to really raise us to a different level of care in preventing some of the complications associated with atopic dermatitis.

Dr Lipper: Absolutely.

Dr Vega: That's all we have time for today. Graeme, I'd like to thank you again for your great input and responses. We're going to be moving on to the case study part of our discussion. I look forward to seeing you there.

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