Faculty Bibliography

Mastocytosis is a clinically heterogenous disease characterized by mast cell hyperplasia in skin, bone marrow and/or visceral organs. Cutaneous mastocytosis is more frequently observed in children, whereas indolent systemic mastocytosis is more commonly observed in adults. Aggressive systemic presentation, particularly of the neonate, is exceptionally rare. We present a rare case of congenital aggressive systemic mastocytosis. The patient was a 37-week-old male, born by caesarean section owing to hepatosplenomegaly and ascites diagnosed in utero, who exhibited extensive cutaneous and systemic manifestations of mastocytosis at birth. Mutation analysis of c-KIT identified D816V mutation in exon 17. Although initial bilateral bone marrow aspirates demonstrated no mast-cell infiltrates or haematological neoplasm, subsequent bone-marrow biopsies postmortem exhibited multifocal mast-cell aggregates. Clinical course was complicated by bacteraemia and cardiorespiratory failure, leading to death at 10 weeks.

Therapeutic regimens for the treatment and long-term management of AD traditionally had a two-fold objective of decreasing skin inflammation and repairing the defective skin barrier. Essential treatments for AD in children should include topical moisturizers for skin hydration and prevention of flares, topical anti-inflammatory medications (e.g. corticosteroids, calcineurin inhibitors, PDE4 inhibitor), allergen/irritant avoidance, and treatment of skin infections. Treatment regimens should be severity-based, and implemented in a stepwise approach tailored to the individual patient. This stepwise approach includes initial use of emollients, gentle skin care, and escalating to more potent anti-inflammatory treatments as the disease severity increases. Currently available systemic medications should be reserved for the presence of recalcitrance to topical therapies due to associated toxicities. We believe that early treatment of AD is not only essential in treating the skin disease, but also in preventing the development of additional atopic diseases, such as food allergy, asthma and allergic rhinitis. The defective skin barrier of AD permits a route of entry for food and environmental allergens, and upon exposure, keratinocytes secrete TSLP, which activates the T_H2 pathway. This T_H2 differentiation sets off the atopic march and the subsequent diseases that are seen. This review highlights treatment options and strategies in pediatric AD therapy with an emphasis on early therapy. Supporting evidence on the efficacy and safety of each intervention will be discussed.

Patients with HIV and AIDS are living longer because of advancements in antiretroviral therapy. These patients are often susceptible to debilitating inflammatory disorders that are refractory to standard treatment. We discuss the relationship of tumor necrosis factor-alpha and HIV and then review 27 published cases of patients with HIV being treated with tumor necrosis factor-alpha inhibitors. This review is limited because no randomized controlled trials have been performed with this patient population. Regardless, we propose that reliable seropositive patients, who are adherent to medication regimens and frequent monitoring and have failed other treatment modalities, should be considered for treatment with tumor necrosis factor-alpha inhibitors.

INTRODUCTION/BACKGROUND:Atopic dermatitis (AD) is the most common inflammatory skin disease in the general population. There are different endophenotypes of AD that likely have a unique immune and molecular basis, such as those who are predisposed to eczema herpeticum, or Staphylococcus aureus infections. AREAS COVERED/METHODS:In this review, we highlight the endophenotypes of AD where reduced interferon gamma expression may be playing a role. Additionally, we review the potential role of recombinant interferon gamma therapy in the treatment of atopic dermatitis and the particular phenotypes that may benefit from this treatment. EXPERT OPINION/CONCLUSIONS:Recombinant interferon gamma treatment will likely benefit the pediatric population with AD, as well as those with susceptibilities for skin infections. Future studies are needed to elucidate whether IFN-γ may reduce the prevalence of skin infection in AD.