Pediatric dermatology: advancement in management and targeted therapy

Teng, Joyce M.C.

doi: 10.1097/MOP.0000000000000385
DERMATOLOGY: Edited by Joyce M.C. Teng

Department of Dermatology, Stanford University, Palo Alto, California, USA

Correspondence to Joyce M.C. Teng, MD, PhD, 700 Welch Road; Suite 301G, Palo Alto, CA 94304, USA. Tel: +1 650 723 6493; e-mail: jteng3@stanford.edu

Article Outline

The topics chosen for the dermatology section in this issue of Current Opinion in Pediatrics encompass a broad range of cutaneous inflammatory skin diseases and hereditary disorders that are difficult to diagnose or manage. Atopic dermatitis is one of the most common inflammatory skin diseases, affecting more than 10% of children in the USA. Despite the prevalence of this condition, the pathogenesis of the disease has recently been elucidated further. The article by Dr Leung (pp. 456–462) has highlighted our recent understanding about the interplay between epithelial skin barrier and cutaneous immune responses that may have contributed to the complex clinical phenotypes of atopic dermatitis. The disrupted skin barrier may have resulted in systemic sensitization and altered cytokine balance in atopic dermatitis. Therefore skin-directed therapy to maintain its normal barrier function and targeted treatment to mitigate polarization of immune response are the cornerstone in management of atopic dermatitis.

There has been a significant advancement in understanding the genetics of autoimmune disorders during the past several years. Alopecia areata and vitiligo are common autoimmune skin conditions that are seen in ambulatory clinics. In addition to associated risks of systemic autoimmune diseases, these conditions can be disfiguring, therefore have significant psychosocial impact. For decades, nonspecific immune suppressive treatments have been used to manage alopecia areata and vitiligo. However, clinicians often struggle to balance the risks and benefits of long-term treatment especially in children. This issue of Current Opinion in Pediatrics includes a comprehensive review by Dr Rork et al. (pp. 463–469) that discussed the shared, novel mechanisms between alopecia areata and vitiligo, which inform the development of future targeted treatments. Genome-wide association studies have implicated risk alleles that influence both innate and adaptive immunity in vitiligo and alopecia areata. Animal studies have indicated IFNγ-driven immune response as the main drivers of disease pathogenesis. Several proof-of-concept clinical studies targeting signaling pathways implicated using biologics have shown promising results. Another article in this issue by Dr Hersh (pp. 470–475) has compared recent discoveries about the genetics of systemic and cutaneous lupus erythematosus (SLE and CLE) that are multifactorial diseases. Both major histocompatibility complex (MHC) and non-MHC genetic polymorphisms have been identified which may contribute to the similar cutaneous manifestations of SLE and CLE. Despite the similarities, there appear to be unique genetic factors specifically associated with CLE. Improved understanding of the genetics of CLE will help to guide the development of new therapies that will improve the patient's clinical outcome.

Congenital melanocytic nevus (CMN) is the result of postzygotic somatic mutations involving key proteins in the mitogen-activated protein kinases pathway, primarily neuroblastoma RAS and BRAF. Dr Price et al. (pp. 476–482) has reviewed the indications of recent genetic discoveries on nevogenesis, malignant potential, and possible therapeutic targets. The two most devastating complications of CMN include neuromelanosis and the development of melanoma. This review detailed practical guideline in regard to the complex management of patients with CMN as well as potential genetically targeted therapies for patients with complications.

Despite the prevalence of common skin conditions such as hair loss, wart, and molluscum contagiosum, there has been a lack of high quality clinical trials to investigate the efficacy of different treatment modalities available. Hair loss particularly on the scalp can affect all ages and impact patients socially as well as emotionally. Here Dr Castelo-Soccio (pp. 483–489) has reviewed common causes of hair loss in children that are related to infection, autoimmune conditions, nutrition, trauma/traction, or underlying genetic disorders. Careful physical examination of the hair, scalp, skin, and nails coupled with dermoscopy and/or trichoscopy can yield accurate diagnosis in a timely manner that is essential for best management plans. The majority of hair loss in children is nonscarring and biopsy is rarely needed. Another article in this issue by Dr Sterling (pp. 490–499) has provided a comprehensive review of evidence-based treatment for warts and molluscum. The two most commonly used treatments for warts are salicylic acid and cryotherapy; whereas for molluscum contagiosum, there is growing evidence for the use of irritants. Despite the lack of strong evidence for common treatments used in clinical practice, there are emerging studies that help to delineate the efficacy of these therapies including immunological approach to the management of warts and molluscum.

We have the last section of this issue dedicated to review the emerging therapies in the care of epidermolysis bullosa, a rare yet challenging multisystem genetic skin disorder. The disease usually presents with blistering at birth. For newborns with blistering, many differential diagnoses should be considered. Dr Murrell (pp. 500–506) has recommended a systemic approach that should be taken to rule out potential infection, autoimmune, or other congenital blistering disorders. Dr Cohn et al. (pp. 507–516) have discussed epidermolysis bullosa as a multisystem genetic skin disorder which requires multidisciplinary care. The review has Summarized the recent advancement in supportive care of epidermolysis bullosa and listed cutting edge clinical trials and treatments, including protein, cell, and gene therapy that will soon have the potential of changing the clinical practice for the care of these patients.

We are greatly indebted to all the contributing authors. We hope the readers recognize the great value of genetic evaluation and targeted approach to treatment of complex skin disorders. In addition we hope the readers find these up-to-date reviews valuable in diagnosis and management of children with various cutaneous disorders as detailed above.

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Acknowledgements

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Conflicts of interest

There are no conflicts of interest.

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