Dermatologic Drug Therapy in Children

Topical Therapy

Many dermatoses in pediatric patients are managed with topical therapy, and familiarity and comfort with use of a range of topical agents and combination therapy can maximize results and reduce adverse effects (AE). The disease being treated, its severity, sites of involvement, total body surface area (BSA) of involvement, speed of progression, age of the child, and associated symptoms, such as itch or pain, should factor into the choice of topical therapies. Medication potency (especially topical corticosteroids [TCS]) and the delivery vehicle (ointment, cream, solution, oil, gel, foam, spray, etc.) should be carefully considered to optimize efficacy, patient acceptance, and compliance. In addition to choosing the most suitable vehicle for the site and age of the patient, allowing older children and adolescents to express vehicle preferences, such as cream versus ointment, will result in “buy-in” and promote treatment adherence. In general, try to avoid overly complicated regimens, write out detailed instructions, and keep it simple and manageable.

Q70.1 Dosing topical medications requires special consideration in infants and young children because they have a relatively high BSA-to-body volume ratio. This increases the risk of systemic AE caused by absorption, when topicals are applied to widespread areas. For example, topical medications containing salicylic acid could potentially result in salicylate toxicity, if applied frequently and to large areas of skin in young children. Measurable serum levels of corticosteroids (CS) and immunomodulators have been reported after topical application and may result in systemic complications in patients who have impaired skin barrier function or other comorbid conditions. To avoid AE from topically applied medications, take caution in selection of drug potency, delivery vehicle, area of application, frequency of application, anticipated occlusion, and quantity prescribed because all of these characteristics impact absorption (see Chapter 1 ).

Systemic Therapy

Most systemic medications prescribed to children are dosed based on body weight until approximately adolescence or age 14 years, above which, in otherwise healthy children of normal weight, many medications are dosed similarly to adults. Because of the large range of weights, heights, and corresponding ages, it is important to calculate each patient’s individual dosage according to their current weight. Some drugs, such as chemotherapeutics, some immunomodulators, and at times high-dose CS, are dosed according to BSA and expressed as mg/m . BSA, which is different than body mass index (BMI), measures the total surface area of the body. Drugs prescribed by BSA usually have a narrow margin between therapeutic and toxic blood concentrations (‘narrow therapeutic index’). If it is necessary to calculate drug dosage based on BSA, this website provides a user-friendly calculator to determine a patient’s BSA: http://www.pediatriconcall.com/fordoctor/pedcalc/body_surface_area.aspx .

The dose range for a number of medications commonly used for dermatologic conditions in children are listed in Table 70.1 .

Q70.2 Barriers to compliance with/adherence to medication regimens in pediatric patients include refusal to take medication because of the route of administration or the taste of the drug. Prescribe tablet and capsule formulations when available to children who can swallow pills (unless there is a specific reason not to, such as the preference for intramuscular methotrexate (MTX) for morphea, where it may have less gastrointestinal [GI] AE and be more efficacious). Liquid formulations are often more expensive, less palatable at higher volumes, and may be less readily available than pill formulations for certain drugs. If there is a choice between two or more liquid formulations, clinicians should prescribe the product that is more palatable (example, generic versions of prednisolone can be quite unpalatable, whereas branded Orapred is usually well tolerated). Many pharmacies will either compound a medication with their own flavoring regimen, or use a medication flavoring system, such as FlavoRx ( https://www.flavorx.com/ ) to enhance the taste. For infants, medications that are less palatable can be given shortly after starting a feed, when the baby is hungry, followed immediately by resuming the feeding. If medications are stable enough to be mixed with milk, juice, pudding, applesauce, or ice cream, offer that option to parents, but first be sure to double check a drug’s stability and absorption in the presence of foods with the pharmacist.

Dose medication at the minimum acceptable frequency to ease the burden on families (once-daily dosing of prednisone instead of twice-daily dosing) and prescribe the optimal concentration of a liquid medicine to reduce the total volume required (one teaspoon of cephalexin 250 mg/5 mL concentration may be easier to administer than 2 teaspoons of the 125 mg/5 mL concentration).

Topical Anesthetics

Topical anesthetics are sufficient for pain control, in some cases, or as ‘preanesthetics’ in others. For example, a topical anesthetic may be used before laser therapy or as a preliminary intervention before lidocaine injection or venipuncture.

Liposome-encapsulated lidocaine cream (LMX) 4 and LMX 5 (formerly ELA-Max; 4% or 5% lidocaine encapsulated in a liposomal vehicle) are over-the-counter (OTC) options for topical anesthesia approved for use in children 2 years of age and older. Application of a thick layer of LMX 4 with occlusion (to limit area of medication) will achieve superficial anesthesia in 30 minutes with a duration of action of approximately 60 minutes.

OTC topical anesthetics containing benzocaine have been marketed for soothing gums during periods of teething. However, in 2018 the FDA issued a warning that benzocaine-containing topicals used in children younger than 2 years of age was associated with a high risk of methohemoglobinemia and now are contraindicated in this age group and should be used with caution in older children.

Injectable Anesthetics

Pediatric dosing is based on a patient’s age and weight to avoid systemic toxicities of excessive lidocaine absorption, including tinnitus, perioral numbness, seizures and potentially life-threatening cardiac arrhythmias. The maximum recommended dose of injectable subcutaneous lidocaine is 4.5 mg/kg and 7 mg/kg, if the lidocaine contains the local vasoconstrictor, epinephrine.

The injection of anesthetics, particularly lidocaine with epinephrine, is associated with an uncomfortable burning sensation when injected. The buffering of these anesthetics with sodium bicarbonate has been shown to be effective in reducing this burning sensation. Reduction in the burning sensation is attributed to the neutralization of pH. One may buffer the lidocaine by adding 1 mL of 8.4% sodium bicarbonate to each 10 mL of lidocaine with epinephrine. This buffering slightly reduces the epinephrine concentration below 1:100,000. However, adequate vasoconstrictive effects may still be found when the concentration falls by as much as half to 1:200,000, thus the addition of 1 mL of sodium bicarbonate should have minimal interference with epinephrine effects. Finally, epinephrine in the presence of sodium bicarbonate slowly deteriorates. It is recommended that the buffered lidocaine with epinephrine be kept no longer than 1 week, given that epinephrine can maintain at least 75% of its pharmacologic effect for this duration.

General Principles

Systemic CS delivered orally, intravenously, or intramuscularly are prescribed in a variety of clinical contexts within pediatric dermatology, from relatively short-term use for severe allergic contact dermatitis to potentially prolonged use for rheumatologic conditions. The decision to treat with systemic CS should involve careful consideration of the benefits versus the risks of therapy, as well as a plan for transition to ‘steroid-sparing’ drugs, if possible and as needed, for chronic conditions. In general, it is best to avoid oral CS in chronic inflammatory disorders, such as atopic dermatitis and psoriasis, where their use will be initially beneficial but likely to be followed upon their discontinuation by rebound flares and increasingly difficult to control disease. Systemic CS should be tapered and stopped as soon as possible for acute conditions. For complex inflammatory, autoimmune and other chronic conditions where long-term treatment is anticipated, interdisciplinary management of dosing, stress-dosing, tapering, and discontinuing systemic CS with specialists such as rheumatologists and endocrinologists is preferable. Importantly, not all systemic steroid preparations are bioequivalent, and differences in absorption and metabolism of corticovarious formulations should be kept in mind. Prednisone and prednisolone formulations commercially available in the United States should be bioequivalent, but this is not the case for other preparations. Refer to equivalency guides when selecting specific formulations. For children who cannot swallow pills, oral prednisone liquid in concentrations of 5 mg/5 mL and prednisolone at 5 mg/mL are both effective; however, the branded version of prednisolone, Orapred (15 mg/5 mL) is much more palatable.

Adverse Effects and Preventive Strategies

There are many potential AE associated with systemic CS, some more serious and long-lasting than others ( Box 70.1 ). Once-daily morning dosing of systemic CS will help maintain the physiologic diurnal variation of cortisol and reduce the likelihood of HPA axis suppression. Alternate-day dosing further reduces some AE, such as growth retardation and weight gain. When pharmacologic doses of CS are taken for more than 4 weeks, there will be an increased risk of systemic complications, such as hyperglycemia, hypertension, linear growth retardation, weight gain, decreased bone mineral density, glaucoma, and cataracts. Avascular osteonecrosis (AVN) is one of the most worrying and unpredictable AE of systemic CS and is often irreversible. Long-term use of oral CS is thought to contribute to AVN. A more detailed discussion of the pathogenesis of corticosteroid-induced AVN can be found in Chapter 13 . Most of the literature on pediatric cases of AVN cites children treated with CS for acute lymphocytic leukemia and juvenile rheumatoid arthritis Although hard to know if this is able to be extrapolated to pediatric dermatologic use, awareness of this potential complication and early detection, through close surveillance for focal joint (one or more sites) or bone pain, a limp with walking, or decreased activity because of pain. Hip joints are most commonly affected, but other joints may also be affected. If suspicion arises, immediate referral for further clinical and radiologic evaluation is warranted. Only through early detection of AVN can the affected joint be salvaged.