The first day of the 2018 South Beach Symposium kicked off with two special programs in the morning: the Superficial Radiation Therapy and the Masters of Pediatric Dermatology Symposium. The late afternoon included sessions on the diagnosis, management and treatment of skin cancer as well as a special session on anti-aging for the dermatologist.
Masters of Pediatric Dermatology Symposium
Emerging Infections in Pediatric Skin
Lawrence F. Eichenfield, MD
Dr. Eichenfield began by emphasizing that although these infections may be rare, we must be able to recognize them, particularly as patients increasingly travel to endemic areas.
The first case was a four-day-old newborn who presented with superficial crusted erosions on the back. The infant was born premature at 24 weeks gestational age. This was a case of primary cutaneous aspergillosis, which has a typical clinical presentation of pustules, erosions, crusts, and ecchymoses. Risk factors for infection include immunosuppression due to prematurity, corticosteroids, broad-spectrum antibiotics, and primary immunodeficiency. Transmission could be due to hospital construction causing airborne mold and adhesive tape causing cutaneous trauma and subsequent wound contamination. The differential would include neonatal HSV, neonatal bullous pemphigoid, and other opportunistic fungi such as Rhizopus, Mucormycosis, Crytococcus, Histoplasmosis, Blastomycosis, Fusarium, Alternia, and Exserohilum rostratum.
Next, there was a discussion of Zika virus, a Flavirus transmitted by the Aedes aegypti mosquito. After a short incubation period of 3-8 days, patients can be asymptomatic or develop mild fever, mucocutaneous symtpoms, and arthralgias. The major association is fetal microcephaly, which seems to be due to a mutation of the prM protein in Zika virus causing apoptosis and neurotoxicity. Currently, all travel recommendations have been lifted from Miami-Dade County. However, there is still a burden on our system to be able to diagnose and treat Zika. PCR is very specific and has become standard for diagnosis.
Case three presented a previously healthy two-month-old with palmar and plantar erythema, fever, and irritability. PCR of CSF was positive for parechovirus, an emerging infection we need to be aware of. The clinical presentation is “hot, red, angry babies.” The differential of acral erythema includes Kawasaki disease, contact dermatitis, hand foot syndrome from Pseudomonas, parvovirus, other enteroviruses.
Case four was a 10-year-old patient with a two-day history of fever, joint pain, headache, and a red bumpy rash on the trunk who recently returned from a cruise. This was Chikungunya Virus, endemic to Africa, Asia, Europe, Indian/Pacific Ocean, and islands in the Caribbean. Acute symptoms include high fever, arthralgias, and a maculopapular rash. In neonates, there have been numerous reports of severe bullous lesions and SJS-like presentations.
The final case was a teen with a four-month history of non-healing bites after a trip to Israel. This was Leishmaniasis, an intracellular protozoan infection transmitted by the sand flea, with Old World variant (Phlebotomus genus; Mediterranean basin, Middle East, Asia, Africa) and New World variant (Lutzomyia genus, Central/South America).
Travel history is crucial in diagnosing these emerging emergent infections in pediatrics.
Psoriasis: Therapeutic Update in Children
Lawrence A. Schachner, MD
Up to one-third of psoriasis patients may develop skin lesions before the age of 18. While treatment is challenging, we now have the tools to defeat it! Dr. Schachner’s typical topical regimen for pediatric psoriasis consists of topical corticosteroids and/or vitamin D analogues every morning/night, 30 minutes of tar gel after school and 10 minutes of natural sunlight, home light box, or in-office NB-UVB or Excimer therapy. Anti-histamines can be added as an adjunctive therapy – non-sedating in morning/sedating at night. Of note, if long-term topical corticosteroid use in indicated, monitor with an 8 AM cortisol every 3-6 months.
Dr. Schachner’s typical MTX regimen is 0.3-0.6 mg/kg PO every week with folic acid 1 mg on non-treatment days. The MTX Polyglutamate assay demonstrates MTX efficacy, with research showing statistically significant lower MTX-p levels in patients not responding to MTX therapy – an indication for dose modification. Complications of MTX therapy include hepatotoxicity (montor LFTs, CBC q1-2 mo), anemia, mucocutaneous ulcerations, and immunosuppression (risk of live vaccines, possible long-term oncogenic risks).
Cyclosporine is also exceedingly well-tolerated in children. Dr. Schachner has even been able to titrate doses to as few as two days per week – “weekend cyclosporine.” Monitoring should include monthly BP, Mg, and BUN/Cr. Systemic retinoids are typically administered at a dose of 0.5-1 mg/kg/day PO in divided doses. There are risks of skeletal growth interruption and Dr. Schachner recommends X-ray of L wrist, knee, and spine prior to treatment, then at 6 months and then every 1-2 years. Pregnancy should not occur for 2 years following discontinuation of therapy.
Erythromycin may be a secret weapon in the treatment of pediatric psoriasis. Erythromycin inhibits IL-6, IL-8, TNF-a, and chemotaxis of neutrophils. It also provides moderate strep coverage, which can be an inciting factor in pediatric psoriasis. The maximum dose is 1 mg/kg for one month only.
Apremilast is an oral PDE4 inhibitor. It is currently approved for adults with plaque psoriasis and psoriatic arthritis and is in Phase II trials for children ages 6-17 with moderate to severe psoriasis. Topically, crisaborole is a PDE4i currently approved for mild-mod atopic dermatitis in patients older than 2, and may be efficacious in the treatment of psoriasis.
The current biologics approved for the treatment of pediatric psoriasis are etanercept and ustekinumab. Etanercept is approved for ages 4-17 at a dose of 0.8 mg/kg/dose SQ once weekly. Ustekinumab was approved in Oct 2017 for ages 12-17 at a dose of 0.75mg/kg SQ (for patients less than 60 kg) at 0 and 4 weeks then every 12 weeks. Monitoring includes Quantiferon gold and hepatitis panel. Ixekizumab is currently in Phase III studies for approval in children ages 6-18, with expected approval in 2019.
Pediatric psoriasis patients should undergo appropriate screening for comorbidities with height/weight/BMI, vital signs, BMP, HbA1C, fasting lipid panel, strep test, and quality of life screening. There is evidence that the impact of psoriasis and AD in childhood on family and children’s QOL is greater than juvenile diabetes – because you can see it! There is a vicious cycle of psoriasis causing embarrassment leading to loss of self-esteem, social isolation and bullying, subsequently causing substance abuse, overeating, and obesity, and ultimately worsening psoriasis. Pediatric psoriasis should be a multi-disciplinary approach involving the dermatologist, pediatrician, nutritionist, physical therapist, and the patient.
Looking to the future, the ease of use, more favorable side effect profile, less lab monitoring, and more specific targeting may favor the use of biologics over older systemic therapies. There are new medication approvals on the horizon, including expansion of the JAK STAT inhibitors, PDE4i, IL-17 and IL-23 inhibitors.
Pediatric Atopic Dermatitis Symposium
Lawrence A. Schachner, MD and Lawrence F. Eichenfield, MD
Dr. Eichenfield started the symposium with a definition of atopic dermatitis as an inflammatory skin disease, starting in childhood with a chronic, intermittent or persistent course. He suggested that we avoid using the term eczema, and reviewed the nomenclature from around the world. Atopic dermatitis has a 10% prevalence in the United States, and overall 80% does not persist after the age of eight. Asthma and allergic conjunctivitis may also frequently be associated with atopic dermatitis. There are two major hypotheses in atopic dermatitis. First, the outside-inside view which is a primary defect in epithelial barrier leading to immune dysregulation and inflammation. The other main hypothesis in atopic dermatitis is the inside-outside view which begins as a primary immune dysfunction leading to secondary epithelial barrier disturbance.
Atopic dermatitis is a decrease of barrier function and is driven by Th2 inflammation. Th2 cytokines downregulate expression of proteins and thus play a significant role in atopic dermatitis. Dr. Eichenfield shared that Staphylococcus survival is increased in the skin of atopic dermatitis, and in both lesional and non-lesional skin antimicrobial function agains CoNS (Coagulase-negative staphylococci) is deficient. The disease burden of atopic dermatitis includes dermatitis symptoms, loss of work productivity, impaired quality of life, sleep disturbance, and numerous comorbidities. Dr. Eichenfield shared the results from a study where attention deficit hypersensitivity disorder is more common in association with atopic dermatitis. Also of note, infants with severe atopic dermatitis and egg allergy are at a risk for peanut allergy. These children should be exposed at an earlier age to foods containing peanuts, starting at 4-6 months as appropriate. However, this early addition of peanuts to the diet did not improve the atopic dermatitis.
Dr. Schachner continued the atopic dermatitis symposium by reminding us that atopic dermatitis is a disease of the whole family, and that every patient should receive a handout before leaving the office. One key in the management of atopic dermatitis to consider is that if your atopic patient is flaring, you think about staphylococcus infection. Other infections to consider in the atopic dermatitis patient include tinea, and herpes simplex. Topical calcineurin inhibitors remain a very good option in the therapeutic approach to atopic dermatitis in both safety and efficacy. Post market registry of topical calcineurin inhibitors also have shown no increased risk of malignancies and lymphoma. And in fact, these risks may be lower than the general population. Dr. Schachner reminds us to give adequate volumes of medications, to consider patch testing in atopic dermatitis patients, and remember the impact on the whole family.
In patient education handouts for atopic dermatitis, recommendations for short baths and cotton clothing, along with gentle laundry detergent, antibacterial soaps should be included. These recommendations are in addition to the use of topical products. Emollients should be advised to the entire body after every bath and a simple sliding scale should be provided for parents of atopic dermatitis children to use at home. Dr. Schachner explained that he will educated parents about flared areas of atopic dermatitis that are red or pink and which products to apply to these areas. Other instructions to include on patient handouts are oral antibiotics, oral antihistamines, and scalp care. According to Dr. Schachner, the secret weapon for atopic dermatitis is doxepin for five days, which can help with sleep.
Topical corticosteroids and topical calcineurin inhibitors are first line treatments for atopic dermatitis. If these options do not work, cyclosporine can improve atopic dermatitis in approximately two weeks. At baseline and monthly Dr. Schachner recommends to check blood pressure, renal function, and magnesium levels. In patients that improve on cyclosporine, a weekend only dosing regimen can be utilized to maintain improvement over longer courses of therapy. Alternative therapies, such as massage therapy and melatonin supplements, were also discussed to improve atopic dermatitis.
The pediatric atopic dermatitis symposium concluded with a question and answer session. The panel discussed the use of emollients starting at birth, which can contribute to a sustained normal skin flora. Due to the high prevalence of atopic dermatitis, the recommendation for this practice could be recommended in the future. Also, the early introduction of fish into the diet of pediatric patients was advised.
Superficial Radiation Therapy for Dermatology:
Appropriate Pathology of Non-Melanoma Skin Cancer and Scars for SRT
Clay Cockerell, MD
Dr. Cockerell introduced his lecture by noting the importance of properly diagnosing skin lesions in order to select appropriate treatment. The overall goal is to eradicate cancer and minimize side effects, which can be achieved by SRT. He reiterates to treat appropriate lesions and ensure the neoplasms are encompassed in the field of therapy. Dr. Cockerell continues by reviewing histopathologic and clinical photos of challenging cases:
Clinically appearing nodular BCC. On histopathology (low power) basaloid appearing tumor islands; however on higher magnification noted to be Merkel Cell Carcinoma; which is not appropriate for SRT.
Biopsied lesion diagnosed as SCC, subsequently treated by excision and found to have areas consistent with BCC on histology – Combined SCC and BCC. Remember patients have considerable sun damage and field effect is a common phenomenon. Recurrence can have squamous or sclerosing morphology and are more aggressive lesions. Dermatologists must also consider variants of BCC which are metatypical and can still be treated by SRT. In contrast to spindle cell SCC, other spindle cell neoplasms I.e. carcinosarcoma, AFX, melanoma, leiomyosarcoma will not respond to SRT and are best treated by Mohs surgery.
Dr. Cockerall notes superficial biopsies can lead to Tip of the Iceberg Effect, resulting in misdiagnosis of aggressive NMSK. If planning to perform SRT, clinicians may consider performing punch or saucerization biopsies to minimize this effect. The reverse is also true in that overcall of benign lesions occurs and can lead to the inappropriate use of SRT. He emphasized to always correlate clinically.
Dr. Cockerall then discusses treatment of keloids with SRT. Keloids are very responsive to SRT. Consider biopsy of keloids if multi-nodular component is present to rule out other soft tissue neoplasms not amenable to SRT (i.e. DFSP). Other entities which can be treated with SRT include Kaposi Sarcoma (patch, plaque stage), Cutaneous B cell Lymphoma, and Mycosis Fungoides.
In summary, Dr. Cockerall reiterates sampling the entire extent and depth of lesion. Non-invasive technology is on the horizon to aid in achieving better mapping including skin ultrasound and confocal microscopy. Dr. Cockerall concluded by discussing the challenges of utilizing SRT: reimbursement issues, turf wars between radiation oncologists and dermatologists, inappropriate use, inadequate training and supervision. He closed by stating dermatologists are skin cancer specialists and should have every treatment armamentarium available.
Use of Superficial Radiation Therapy in Treatment of Non-Melanoma Skin Cancer: Consensus Guidelines
David J. Goldberg, MD, JD
Dr. Goldberg indicated the focus of his presentation – to review the consensus guidelines of SRT for NMSC. SRT is another form of electromagnetic radiation and is simple to use. It utilizes low photon X-ray energy and gives a calibrated dose delivery with accurate internal filtration technology. The unit automatically stops when cumulative amount of radiation is delivered.
SRT treats lesions effectively and penetrates about five mm in depth, and thus is appropriate for NMSC (FDA-approved). It is most commonly used for BCC and SCC and ideal for achieving great cosmetic result, particularly for scalp, eyelid, nasal ala, and external ear lesions. SRT is also beneficial for treating lower extremity NMSC. There is a minority view of concern in regards to treating legs of individuals suffering with edema, however, with fractionation over 14-16 treatments, SRT proves a slow, gentle treatment. Dr. Goldberg further presents a study indicating the cure rate for 1715 primary nonaggressive NMSC treated with SRT-100 was found to be 98%.
Dr. Goldberg states there is confusion regarding the differences between radiation therapies. SRT uses more energy and penetrates deeper than Grenz Rays. Electron beam therapy uses medical linear accelerators and is intended to treat deep tumors, thus cure rate for NMC is not as high vs. SRT. Brachytherapy uses radioactive source within or adjacent to it. Overall SRT is a simpler option.
Energy is tightly delivered with only one mm lateral edge drop off and the field beyond obvious skin cancer will be small (penumbra). SRT treatment margins for BCC (8-10 mm) and SCC (10 mm) are based on estimated surgical margins.
SRT does not require patients to stop anticoagulants and is best for those who cannot perform wound care, and those with fear of scarring. It can safely be used in patients with poor circulation. Contraindications are few but include patients with pacemaker or defibrillator in treatment area or previous radiation therapy to area. In cases of skin cancer recurrence, Mohs surgery is recommended.
Complications of SRT include temporary erythema related to dose of radiation, hyperpigmentation (most common in Fitzpatrick V-VI skin types), and radiation dermatitis. Radiation dermatitis is very mild partly because SRT dosage is small and localized, with fractionated energy delivered over time.
Dr. Goldberg concluded by stating SRT is superior compared to other forms of radiation therapy for the treatment of NMSC and keloid scars
Diagnosis, Management and Treatment of Skin Cancer
New AAD NMSC Guidelines
Suzanne Olbricht, MD
The 2018 Guidelines for management of non-melanoma skin cancers were published in the January issue of the Journal of the American Academy of Dermatology. Dr. Olbricht explained that guidelines are in place for clinical decision making support, as well as to make official recommendations and for use in patient advocacy. The process to establish guidelines is lengthy and does not allow for industry sponsorship. Dr. Olbrich, current President of the American Academy of Dermatology, reviewed the new guidelines released this year.
For basal cell carcinoma, there is no formal staging system. 188 articles pertaining to non-melanoma skin cancer were reviewed and the evidence stratified into low risk and high risk groups. Low risk basal cell carcinomas are primary lesions with a well defined border without perineural invasion. No single optimal biopsy technique was recommended for basal cell carcinoma according to current guidelines. Surgical excision and Moh’s are acceptable treatment options for basal cell carcinoma. Curettage and electrodessication can be considered for low risk tumors in non hair bearing sites according to the current guidelines. Nonsurgical therapy options for basal cell carcinoma include cryosurgery for low risk BCCs, and other topical treatments such as 5-FU and imiquimod can be used as well. Dr. Olbricht shared that the time to recurrence according to the current guidelines is about 5 years. Also, for metastatic or locally advanced basal cell carcinomas the current guidelines recommend a multidisciplinary approach as systemic chemotherapy may be indicated. Annual skin examinations are recommended for patients with a history of basal cell carcinoma according to current guidelines.
For squamous cell carcinoma, Dr. Olbricht shared that there are 3 formal staging systems, and that NCCN risk stratification is clinically useful. The current non-melanoma skin cancer guidelines include features that should be mentioned in a in pathology report such as tumor depth, differentiation, and perineural invation. The current margin recommendation for squamous cell carcinoma 4-6mm for low risk tumors, which is a change from the previous recommendation of 4mm. Surgical excision, Moh’s, radiation and cryosurgery are all acceptable treatment options for low risk squamous cell carcinoma according to current guidelines. In contrast to basal cell carcinoma, topical 5-FU is not recommended for squamous cell carcinoma treatment. In solid organ transplant recipients, acitretin can be a useful therapeutic option for squamous cell carcinoma. Dr. Olbricht concluded the review of current guidelines by reminding the audience that these can be found online and in print for further review.
Panel Discussion: What to Do with Dysplastic Nevi
Moderator: Darrell S. Rigel;
Panelists: Neal Bhatia, MD, Suzanna Olbricht, MD, David J. Goldberg, MD, JD
The panel discussion about the dilemma in treating dysplastic nevi started with a review of a previous survey of dermatologists. Dr. Rigel shared the trends among dermatologists responding to these surveys. In regard to the management of dysplastic nevi, 78% believed patients with a personal history of dysplastic nevi are at increased risk for melanoma overall. In addition 97% of surveyed dermatologist agreed that they would re-excise a severely dysplastic nevi if the biopsy margin was positive. Also in the same group of dermatologists, 50% would excise a severely dysplastic nevi if the biopsy margins were negative. According to the survey, 77% of US dermatologists use dermoscopy in evaluating dysplastic nevi, but 89% do not use other technologies such as MelaFind or confocal microscopy.
The panel continued the discussion of dysplastic nevi with a discussion of mild, moderate and severe pathologies. The panel agreed that a trusted relationship with your dermatopathologist is key in evaluating dysplastic nevi. Also, the panel unanimously agreed that severely dysplastic nevi should always be excised with a clear margin. The discussion of management of moderately dysplastic nevi was left up to the practitioner. From a medical legal standpoint, a dermatologist may choose to excise all dysplastic nevi regardless of atypia. The panel discussed that from a utilization perspective, most moderate and all severely dysplastic nevi should be excised with clear margins.
Special Session on Anti-aging for the Dermatologist
Introduction to Bioidentical Hormone Replacement:
What the Dermatologist Needs to Know
Andrew Heyman, MD
Dr. Heyman started the discussion for hormone replacement therapy (HRT) by reviewing the function of hormones, which are biochemical messengers that affect growth, immune system regulation, and mood. For aging women, estrogen and progesterone decline over time and there is a subsequent decline in bone density, skin elasticity, and memory. Conventional hormone replacement agents include estradiol, estrone, and estriol. Conjugated equine estrogen should not be included in hormone replacement therapy due to its carcinogenic properties.
Estradiol (E2) is the most common formulation included in HRT. Transdermal estrogen does not adversely affect inflammatory markers, unlike oral estrogen therapy. Transdermal dosing avoids first pass metabolism, and is the preferred method of delivery in HRT. Synthetic progesterones increase breast proliferation, however the micronized progesterone form does not carry this risk may have cardioprotective and neuroprotective effects.
The original data against the use of HRT was the Womens Health Initiative study, which concluded that estrogen only therapy had an increased risk of breast cancer and other negative effects. Dr. Heyman shared that since that time, numerous benefits of combination HRT have been proposed, including decreased CV risk. HRT can be formulated into creams, gels, pellets for topical use and troches and pills for oral use. Common HRT medications include synthetic micronized progesterone, estradiol, estriol, testosterone. Dr. Heyman also discussed the possible negative outcomes from delayed initiation of HRT in the perimenopausal time period. Dr. Heyman explained that the most benefit from HRT is within seen when therapy is initiated within the first 10 years after menopause, and these include decreased vasomotor symptoms, improved mood and cognition, improved libido, and improved quality of sleep. In addition, HRT can have positive outcomes on atherosclerosis, risk for stroke, lipid profile, and risk for Alzheimer’s disease. According to Dr. Heyman, bioidentical HRT appears to be more efficacious in symptom relief than non-bioidentical hormone replacement therapy.