Screening labs, complacency, and the ABCDEs of pediatric melanoma

In part three of our discussion about pediatric dermatology, Kelly Cordoro, M.D., associate professor of dermatology and pediatrics at the University of California in San Francisco, discusses screening labs, avoiding complacency, and the ABCDEs of melanoma with Dermatology Times editorial advisor, Elaine Siegfried, M.D.

Dr. Siegfried: You wrote a great paper about screening labs and the relative value of screening labs when using systemic agents for kids with psoriasis. Given whatever your favorite drug is, which labs do you routinely check and how often?

Dr. Cordoro: Thank you. I really wanted to research more about these drugs and what are the differences. We get most of our information on screening from other subspecialties: We borrow from the rheumatology literature; we borrow from the hematology-oncology literature; we borrow from the gastrointestinal literature. We don’t have our own data-driven evidence for kids with psoriasis specifically, or for kids with atopic dermatitis specifically to really answer these questions. So my approach is very clinically driven.

Check out part 1 of this three part series: Clinical pearls in pediatric dermatology

I start out very conservatively. I will check labs at baseline and fairly frequently early in the course of therapy. And the specific labs and frequency differ depending upon the specific agent used.  

We know for cyclosporine, we have to be more aware of checking blood pressures, electrolyte levels and kidney function. With methotrexate, we have to be more aware about testing liver function and so forth.

Over the course of therapy and depending on the patient’s individual situation, their response to disease and lab results, I’ll check more or less frequently. Even though we have published recommendations, your clinical experience and the individual patient will prompt a variable approach. I will liberalize or tighten the lab monitoring as the clinical course evolves.

In developing the AAD’s clinical guidelines for management and treatment of atopic dermatitis with phototherapy and systemic agents, we agreed on recommendations for monitoring. Those were derived based on available evidence and expert consensus.[i] There are charts in the manuscript detailing the dosing and recommendations, and I follow those pretty closely.

For psoriasis, my approach is similar. It’s really a more aggressive approach upfront and then adjustments over time based on individual factors. My recommendations around that can be found in an article that Anne Marqueling, M.D., our former pediatric dermatology fellow who is now faculty at Stanford, and I wrote called “Systemic Treatments for Severe Pediatric Psoriasis: A Practical Approach.” This contains straightforward and clinically driven suggestions for baseline and then ongoing monitoring.[ii]

NEXT: Avoiding complacency

Avoiding complacency

Dr. Siegfried: It is an advantage and a disadvantage that we don’t have a lot of high-tier, evidence-based medicine, and so we have the privilege of customizing treatment for our patients. Patients aren’t templates; they all have unique issues that impact the best treatment choice. What advice would you give to new clinicians about this?

Dr. Cordoro: Well said. I think my advice to very junior clinicians is to start by the textbooks, go by what’s been written by those with more knowledge and experience. In general we tend to be more cautious with monitoring at first and then over time, the approach may evolve.

However, I will say this: I am constantly humbled by these medications-both conventional systemic therapies and biologics.  We have to be careful as we are modifying and customizing that we don’t become complacent and say, ‘I’ve been doing this for so many years, we don’t have to check that anymore.’ Because as soon as we let our guard down, we can get burned. So the right answer is somewhere between being cost-effective and not over-monitoring, but not getting too comfortable either.

Dr. Siegfried: Do you check all kids that you are going to put on any kind of immunomodulating therapy for TB risk?

Dr. Cordoro: I do because I live in a high-prevalence area in the San Francisco Bay area. When I practiced in Virginia, I did not. I would routinely do it for TNF inhibitors, I routinely did it for methotrexate; and, right or wrong, I did not do it for some of the other systemic agents. Now of course I am doing it for everybody and maybe everybody should be doing it for every patient with all of these medications.

Dr. Siegfried: Are you doing purified protein derivative (PPD) or QuantiFERON (Cellestis)?

Dr. Cordoro: I am doing PPD (purified protein derivative) for the most part. I think it’s the most cost-effective screen. If we are not guaranteed that they will follow up on their PPD and we can’t reach their pediatrician, then we will do a QuantiFERON. However, data on performance are scant in the pediatric age group. The Centers for Disease Control and Prevention cautions use in patients less than 17, and in particular in kids less than 5 years old.

Check out part two of this three part series: Pediatric psoriasis, eczema:Triggers and therapies

Dr. Siegfried: What biologics have you used?

Dr. Cordoro: Well, as you well know, all biologic treatments for dermatologic use in kids are off-label, as are all systemic medications for psoriasis and atopic dermatitis. So yes, I’m always prescribing off-label and I use the TNF inhibitors the most. I use this for recalcitrant plaque and pustular psoriasis. I tend to prescribe etanercept initially, because it has the most data for kids. There has been a randomized, controlled trial, as you know, spearheaded by [Dr.] Amy Paller.³ However, its efficacy often wanes over time and may require a transition to other TNF agents or a class change.

I would say that I have the most experience with TNF inhibitors. I don’t use them as much as I do systemic therapies. I am still in the “drugs I know and can monitor” phase of my career. I have some concerns about the lack of knowledge about long-term risks of some of these agents. For example, I do not have a vast experience with ustekinumab yet. I have prescribed it only one time to a teenager with severe psoriasis who failed anti-TNF.

For generalized pustular psoriasis, my drug of choice is infliximab if I need to achieve really rapid control. I often accompany that by small doses of methotrexate to block human antichimeric antibodies, which overtime can lead to loss of efficacy and increased infusion reactions. I have not used a biologic agent for the treatment of atopic dermatitis.

NEXT: ABCDEs of melanoma

ABCDEs of melanoma

Dr. Siegfried: Your publications have been very diverse including a couple of really great articles. Can you talk about what inspired the ABCDEs for pediatric melanoma and the seminal article on eczema coxsackium?

Dr. Cordoro: Thank you for the compliment. My articles have been driven by my passion for dermatology and the confusion that arises when caring for complex patients.  My patient care practice really dominates the questions that I have asked.

The ABCDE story for pediatric melanoma really began in my pediatric dermatology fellowship. As I mentioned earlier, I transitioned from being an adult dermatologist to pediatric dermatology, and it was profound for me when I realized how differently melanoma can present in children and that it could be missed a large part of the time because of the different clinical presentation.

READ: Melanoma rates rise in Hispanics

I remember saying to my fellowship director and mentor, [Dr.] Ilona Frieden, while caring for a young girl with amelanotic melanoma, ‘The ABCDEs do not always apply to pediatric melanoma. These kids are at risk for very late detection. I want to write this up.”  This was in 2007. She said, “Why don’t you collect data and see if it supports your notion?” So, the idea was born in 2007 and resulted in a paper that was published in 2013.⁴ In reviewing the literature on childhood melanoma, I realized the paucity of clinical information-in particular, the original appearance of the melanoma-provided in published series.  We reviewed the details of every melanoma diagnosed before the age of 18 at UCSF, and our data together with other published series allowed us to make some clinically important observations.

One of the things we learned is that E is the most predictive criterion. Persistent lesions that are evolving or changing should be approached with a higher degree of suspicion. The study supported the need for raised awareness for melanoma in children with lesions that are amelanotic, or bleeding, and even those that are uniform in color and of small diameter [<6mm]. 

NEXT: More on ABCDEs of melanoma

The most important lesson we learned in that study was that the presentations of melanoma are vastly different in prepubertal patients. That age group requires a higher index of suspicion for lesions with these atypical presentations.

As far as the eczema coxsackium paper⁵, I have to give 100% of the credit to my colleague and friend [Dr.] Erin Mathes, who is a pediatric dermatologist at UCSF. Dr. Mathes, one of our fellows Dr. Vikash Oza, and Dr. Frieden really spearheaded that work. We were observing these variant hand-foot-mouth disease (HFMD) presentations and there had been some reports coming out of other countries around the same time. I take really little to no credit for that paper other than contributing a few cases, reviewing, and helping to edit the final product. I think it was a very important paper that we all learned from. The CVA6-associated enterovirus outbreak was responsible for an exanthem potentially more widespread, severe, and varied than classic HFMD that could be confused with bullous impetigo, eczema herpeticum, vasculitis, and primary immunobullous disease.

Dr. Siegfried: What do you enjoy the most, what takes most of your time? Is it patient care, teaching, research?

Dr. Cordoro: I love that you asked me that question. It’s patient care. I am first and foremost a clinician, and I’m happiest when I am behind a closed door with a complicated patient. The bonus is, I’m in an academic environment where my passion for teaching is married to patient care. Every patient I see presents a learning opportunity for our trainees and for me.

Dr. Siegfried: I know you’re working a lot on psoriasis. Is there anything else that’s really exciting you and making you enthusiastic?

Dr. Cordoro: Psoriasis is probably my favorite disease. I am working with the Pediatric Dermatology Research Alliance (PeDRA). We have a psoriasis investigator group, and we’re composing a survey to determine current management patterns for pediatric psoriasis in the United States [The MAPP US Study: Management Approaches to Pediatric Psoriasis in the United States], because we assume that there’s a huge divergence in the way patients are approached in this country and among clinicians in other countries. We’ll extend the survey to Canada as well. We’re trying to gather data to inform future research and move us closer to achieving consensus in the area of management and risk stratification for purposes of evaluating children with psoriasis for comorbidities.

READ: Intralesional therapy for metastatic melanoma

Of course psoriasis projects are always hot on the front burner. Other projects at the moment include a study exploring refractory pediatric lupus panniculitis (LEP). Most of the published articles about lupus panniculitis indicate that pediatric patients get better with hydroxychloroquine (Plaquenil), rarely requiring additional medications. My experience with three or four patients with severe, refractory, disfiguring disease on massive systemic immunosuppression prompted further investigation. Other than those cases ultimately diagnosed with subcutaneous panniculitis-like T cell lymphoma, there is not much published about refractory LEP. 

My other passion is procedural dermatology. I enjoy an active laser practice and we are putting together our experience using the long-pulsed Nd:YAG laser to treat pediatric vascular malformations such as glomuvenous and venous malformations.  There are gaps in the pediatric procedural literature and based on years of practice, we are looking forward to being able to make a contribution in this area.

In case you missed it

Check out part two of this three part series: Pediatric psoriasis, eczema:Triggers and therapies

Check out part one of this three part series: Clinical pearls in pediatric dermatology

References

1. Sidbury R, Davis DM, Cohen DE, et al. Guidelines of care for the management of atopic dermatitis: section

3. Management and treatment with phototherapy and systemic agents. J Am Acad Dermatol. 2014;71(2):327-49. https://www.aad.org/education/clinical-guidelines

2. Marqueling AL, Cordoro KM. Systemic treatments for severe pediatric psoriasis: a practical approach. Dermatol Clin. 2013;31(2):267-88.

3. Paller AS, Siegfried EC, Langley RG, et al. Etanercept treatment for children and adolescents with plaque psoriasis. N Engl J Med. 2008;358(3):241-51.

4. Cordoro KM, Gupta D, Frieden IJ, Mccalmont T, Kashani-sabet M. Pediatric melanoma: results of a large cohort study and proposal for modified ABCD detection criteria for children. J Am Acad Dermatol. 2013;68(6):913-25.

5. Mathes EF, Oza V, Frieden IJ, et al. "Eczema coxsackium" and unusual cutaneous findings in an enterovirus outbreak. Pediatrics. 2013;132(1):e149-57.