PracticeUpdate: Dermatology & Rheumatology

SUMMER AAD 2016 19

We anxiously await the results of the paediatric trials. Crisaborole ointment 2% is a topical option for AD. Crisaborole ointment is a boron-based PDE4 inhibitor that has been studied in both adults and paediatric patients. A recent study of 31 children published in Pediatric Dermatology documented both minimal absorption of the drug via pharmacokinetic evaluation, as well as significant improvement in participants’ eczema severity scores ( Pediatr Dermatol 2016;33:380-387.). We are certainly in need of new, effective non-steroid topicals! Infantile haemangioma Another area of therapeutic interest in paediatric dermatology concerns the treatment of infantile haemangiomas and the efficacy of propranolol. Infantile haemangiomas are vascular lesions that can be associated with significant functional impairment as well as cosmetic deformity. Hundreds of publications have documented the efficacy of propranolol for the treatment of problematic lesions. However, many lesions do not need to be treated, and other, smaller lesions will do well with topical timolol therapy. Candidates for systemic propranolol therapy include healthy children with significant lesions who are free of cardiac and pulmonary conditions. Very young (<5 weeks) or premature infants under 45 weeks’ post- menstrual age usually require admission. Children with large facial haemangiomas >5 cm should be evaluated for PHACE syndrome before undergoing treatment. Families must be counselled about the risk of hypoglycaemia and the need to feed the infant frequently and to withhold the drug if vomiting or decreased feeding occurs. Baseline pulse and blood pressure measurement, repeated after each significant change in dose, is recommended. One propranolol dosing regimen for outpatient treatment is 0.5 mg/kg twice daily, with blood pressure and pulse check 1 to 1.5 hours after the first dose. The following week the dose is usually increased to 1 mg/kg twice daily, again taking blood pressure and pulse following the dose. Many children will show good response at 2 mg/kg per day in two divided doses. Patients should be re- evaluated 1 week after starting this dose, and maintained on this dose unless response is suboptimal. If needed, the dose can be increased to 2.5 to 3 mg/kg daily in divided doses. Concerns regarding adverse effects have been mostly allayed. It is not necessary to obtain ECG or cardiac evaluation in an otherwise normal infant. Sleep disturbance and acral mottling (cold peripheries) are the most common side effects; bradycardia, cardiac complications, and hypoglycaemia are rare in healthy babies ( Br J Dermatol 2016;174:594-601). Premature infants may be more susceptible to adverse effects, and some very small infants are started on lower doses of the drug. Propranolol does cross the blood-brain barrier, and concerns regarding developmental side effects have been raised. A recent prospective study evaluating 82 children who were followed and evaluated at 4 years of age failed to detect any evidence of developmental or growth abnormalities ( J Am Acad Dermatol 2016;75:59-63.e1). Treatment must be continued for a prolonged period, as those infants who receive less than 9 months of therapy are more likely to relapse. One study showed that children were less likely to rebound if they were treated until at least 16 months of age ( Br J Dermatol 2016;174:594-601); however, most experts counsel families that therapy will likely take at least 12 months. In summary, those infants who are properly screened are likely to do well on propranolol therapy, but prolonged treatment is required.

Dr Misha Rosenbach on advanced systemic therapeutics – systemic treatment of granulomatous diseases

Misha Rosenbach MD is an Assistant Professor of Dermatology and Internal Medicine at the Perelman School of Medicine at the University of Pennsylvania. SYM S001 – advanced systemic therapeutics

Noninfectious granulomatous skin diseases represent a spectrum of cutaneous reactions which can challenge any dermatologist. First and foremost, some granulomatous reactions may represent a skin sign of systemic disease, warranting thorough workup, with treatment focused on the underlying systemic process. Second, granulomatous reactions may themselves cause significant morbidity to patients and warrant treatment – often with little high-quality evidence to guide the clinician. In the Advanced Systemic Therapeutics session devoted to granulomatous diseases, we reviewed the data and presented some algorithmic approaches to managing these entities. Treatment options generally include topical therapies, phototherapy, immunomodulatory/anti-inflammatory agents, and immunosuppressive agents. Topical steroids can be beneficial in some cases (such as fine papular granuloma annulare or thin patches of necrobiosis lipoidica). Intralesional triamcinolone can be quite helpful in treating isolated lesions. Phototherapy can be particularly helpful in widespread granuloma annulare (while there is more evidence for PUVA, narrowband UVB can be helpful and may be a simpler starting point). Immunomodulatory/ anti-inflammatory agents include tetracycline class antibiotics (minocycline being the most effective), antimalarial agents (with more data for chloroquine, but hydroxychloroquine being easier to obtain and administer), and phosphodiesterase inhibitors (pentoxiphylline or apremilast). Immunosuppressive agents (particularly corticosteroids and methotrexate) are quite effective in treating most granulomatous reactions. Finally, the TNF inhibitors are rapidly coming to the fore as some of the most effective anti-granulomatous agents in our arsenal. Focusing on granuloma annulare, while intralesional injections can help when there are limited, localised lesions, most widespread cases warrant consideration for systemic treatment. The best data available is for PUVA or chloroquine; we suggest starting with either narrowband UVB or hydroxychloroquine for ease of use and fewer side effects. Antimalarials in particular seem to be highly effective, with some of the best available data. When those agents fail, treatment decisions are based on isolated case reports for the most part. Tetracycline class antibiotics, retinoids, dapsone, or even methotrexate may be considered; but, in severe, recalcitrant cases, there are emerging reports demonstrating efficacy with a number of TNF inhibitors. One critical point to keep in mind is that granulomatous inflammation is slow; slow to develop, and slow to resolve. All therapies take months to demonstrate efficacy, and patience is essential – which should be carefully explained to patients, less the lack of patience from impatient patients leads you to abandon a treatment before it has a chance to work.

DECEMBER 2016