Pediatric Pearls Restrung (Part 1)

 

Sheila Friedlander, MD and Ilona Frieden, MD

What’s really new in pediatric dermatology?  In this presentation, Drs. Friedlander and Frieden discussed the latest and greatest in pediatric dermatology.

Beta Blockers & Hemangiomas

Do hemangiomas go away?  Before 2008 and to this day, many treatments can provide modest efficacy, and are best used in growth phase. These treatments include corticosteroids: systemic, intralesional and topical; other systemic agents such as interferon alpha and vincristine; pulsed dye laser and other treatments such as cryotherapy and imiquimod.

A somewhat recent breakthrough was the discovery of the use of propranolol for the treatment of hemangiomas. These data were published in 2008 in The New England Journal of Medicine.  The general consensus among pediatric dermatologists is that this truly is a breakthrough, along the lines of isotretinoin for severe acne and other major treatment breakthroughs.

Propranolol Q & As

Does it work?

There are more than 75 articles published since original report. It has impressive efficacy with more shrinkage of Infantile Hemangiomas (IH) than with prior treatments

Does it ever not work?

Occasionally; Based on the literature, there seems to be about a 5 to 10% failure rate

What is the usual dose?

1-3 mg/k/day divided BID or TID usually 6-12 months

What is the duration of treatment?

That depends on many factors – usually 6-12 months, sometimes longer

Can rebound occur?

YES!  Literature says about 20-25% of time

Can it be efficacious in older children with a fully-grown hemangioma?

There is some evidence for efficacy in older children up to age 3 to 4

What about for other vascular tumors or malformations (Kasabach-Merritt, Lymphatic Malformations)?

Probably NOT

Safety

Regarding the safety of propranolol, there are potential effects on cardiovascular system but bradycardia and hypotension are usually not an issue. There have been some reports of hypoglycemia, which can happen after weeks to months, mostly in the setting of decreased eating/fasting (anticipatory guidance), this is truly a risk that needs to be monitored. Nightmares, GI upset, asthma exacerbation have also been reported. There is a special concern for children with PHACE syndrome regarding arteriopathy/ “demand related potential ischemia”, which could cause a stroke.

There is really no consensus regarding how to best monitor patients on propranolol; however, there is a randomized control trial underway (sponsored by Pierre Favre). Here is how propranolol is used in Dr. Frieden’s practice at UCSF:

How does Propranolol work?

CD34+ EPCs in proliferative stage express angiotensin converting enzyme and angiotensin II receptor-2. An explant model shows EPCs form proliferative blast-like structures in the presence of angiotensin II. The authors hypothesize that the renin-angiotensin system may account for the response to propranolol. (Itinteang et al. J Plast Reconstr Aesthetic Surg 2010; Online early)

Topical Beta Blockers

There are three recent articles regarding the use of Timolol 0.5%. Timolol Gel-Forming Solution BID may be helpful for some superficial IH.  (Pope E, Chakkittakandiyil A. Topical timolol gel for infantile hemangiomas: a pilot study. Arch Dermatol. 2010 May;146:564-5.; Guo S, Ni N. Topical treatment for capillary hemangioma of the eyelid using beta-blocker solution. Arch Ophthalmol. 2010 Feb;128:255-6.; Khunger N,  Pahwa M. Dramatic response of a large hemifacial infantile hemangioma associated with PHACE syndrome to timolol lotion. Br J Dermatol Dec 15, 2010) The use of topical Timolol can be monitored by looking at systemic effects and the heart rate.

Treating Hemangiomas Current Status

Warts and Molluscum

Warts and molluscum can be seen as a very important part of the dermatology practice as they are both extremely common. They are often physically benign; however, they can be extremely psychologically debilitating. Parents may become overly invested in a “clean slate”, and parents can really do damage to the child because of the messages they are giving. You, as the dermatologist, must act as the child’s advocate, as not all warts need to be treated because the risk of the treatment may be worse than the psychological damage that it is going on. It is important to consider what the parent feels because that is what the child is hearing.

Algorithm to Approaching Warts

It is important to provide a handout for these patients detailing a clear description of the products and an explanation as to how to apply the products. It is important to be sure that patients/parents get the sequence right and that they are warned of any potential adverse effects, i.e. blisters, ring wart, scarring, and terror upon your entering the room.

What else can be done?

Other Potential Treatments

According to Dr. Friedlander, Cimetidine can be used to buy you some time. There are some positive reports regarding the use of cimetidine. It appears to work better in children, atopics and in conjunction with topicals. The maximum dose is not really known, Dr. Friedlander generally uses up to 1200 mg, occasionally 1600 mg. It is very important to be aware of drug interactions and parents need to be aware of any other therapies that the child is on or prescribed. Some children don’t like the taste of cimetidine and others have experienced nausea while on the therapy. Dr. Friedlander has found that cimetidine works in about 30% of patients.

Candida, the mighty antigen, is currently a favorite. Candida is a highly immunogenic antigen. It augments the immune response and there is empiric and academic data supporting its use (note that in the first studies many of the patients were also on interferon and; therefore, some patients got sick). Candida is used in a variety of ways; many of the experts adhere to the following:

Candida does have an effect and it is important to beware of the “painful purple digit”. Do not overdo the injections in the periungual distal finger area.  Candin® the brand name for a candida antigen suspension may be obtained from Allermed Laboratories and a generic Candida antigen is also available.

Molluscum

Molluscum is a large brick-shaped virus. A renewed interest in the virus was came about recently due to the threats of biological warfare. The molluscipoxvirus belongs to the group of Poxviruses. It shares with the true Smallpox virus part of its genome, its specific pathogenicity to humans and its classic “brick-shape”. However, the Molluscipoxvirus is strictly localized to the epidermis and invokes a weak immune response compared to the deadly potential of the Orthopoxvirus.

Who gets molluscum?

The vast majority of people who have molluscum in the pediatric dermatology office are less than eight years of age. Most kids will have less than fifteen lesions, generally on the trunk extremities. A question remains as to whether atopic dermatitis patients have more trouble getting rid of the virus…

We know that molluscum will eventually go away, so why would we treat? There are occasional studies in the literature of molluscum spreading in pools and waterparks, so many physicians advise parents not to let their patients bathe with other children. Spread is a big issue. With molluscum, often times you can see infection and pseudo-infection, along with social stigma so there is a problem in having this disease; therefore, it should be treated.

Options for Treatment of Molluscum

Physical treatment includes curettage (mainly in Canada), cryotherapy and the use of keratolytic agents like salicylic acid. Immunotherapy includes candida, imiquimod, cimetidine and cantharidin. Cantharidin is referred to as “a blistering defense of an ancient medicine.”  It used to be a “Beetle-extract” vesicant and can cause intra-epidermal acantholysis.  Lesions treated with cantharidin heal without scarring and the treatment  is mostly painless. There has been a long history in both folk and traditional medicine regarding its use. In 1962, cantharidin lost FDA approval due to failure of its manufacturers to submit data attesting to its efficacy. The FDA interim policy: Cantharidin on “Bulk Substances List” most commonly used as 0.7% proprietary formulation: ‘topical use in the professional office setting only’

It is also important to conduct test sites and be sure that the family is aware of the blistering. Do not use cantharidin on the face.

A retrospective study on cantharidin looked at 537 children with MCV. Cantharidin treatment was used in 300 children with a follow-up phone interview. The results showed 90% clearing and 8% improvement. The average number of treatments was 2.1. There were blistering sites in 92% of the patients. Temporary burning, pain, erythema, and pruritus were seen in 6-37%. Overall, 95% of the parents reported that they would proceed with the treatment again.

Cantharidin is an excellent treatment for molluscum, but usually needs to be purchased from Canada. (www.ABCpharmacy.com)

Summary Warts & Molluscum