Kara N. Shah

The Diagnostic and Clinical Significance of Café-au-lait Macules

Café-au-lait, also referred to as café-au-lait spots or café-au-lait macules, present as well-circumscribed, evenly pigmented macules and patches that range in size from 1 to 2 mm to greater than 20 cm in greatest diameter. Café-au-lait are common in children. Although most café-au-lait present as 1 or 2 spots in an otherwise healthy child, the presence of multiple café-au-lait, large segmental café-au-lait, associated facial dysmorphism, other cutaneous anomalies, or unusual findings on physical examination should suggest the possibility of an associated syndrome. While neurofibromatosis type 1 is the most common syndrome seen in children with multiple café-au-lait, other syndromes associated with one or more café-au-lait include McCune-Albright syndrome, Legius syndrome, Noonan syndrome and other neuro-cardio-facialcutaneous syndromes, ring chromosome syndromes, and constitutional mismatch repair deficiency syndrome.

“Urticaria Multiforme”: A Case Series and Review of Acute Annular Urticarial Hypersensitivity Syndromes in Children

Acute annular urticaria is a common and benign cutaneous hypersensitivity reaction seen in children that manifests with characteristic annular, arcuate, and polycyclic urticarial lesions in association with acral edema. It is mistaken most often for erythema multiforme and, occasionally, for a serum-sickness–like reaction. Although these 3 entities may present in a similar manner, specific clinical features help to distinguish them, and it is important for the clinician to be able to differentiate among them. We present herein a series of 18 patients who were given a diagnosis of acute annular urticaria and review the clinical distinctions between acute annular urticaria, serum-sickness–like reactions, and erythema multiforme. Because of the frequency of its clinical confusion with erythema multiforme, we propose the term “urticaria multiforme” as a more apt description to highlight the distinctive clinical features of this urticaria variant.

Combined Immune Deficiency in a Patient with a Novel NFKB2 Mutation

NFKB2 encodes the p100/p52 protein, a critical mediator of the canonical and noncanonical NFkB signaling pathways. Here we report the comprehensive immune evaluation of a child with a novel NFKB2 mutation and provide evidence that aberrant NFKB2 signaling not only causes humoral immune deficiency, but also interferes with the TCR-mediated proliferation of T cells. These observations expand the known phenotype associated with NFKB2 mutations.

Medallion-like dermal dendrocyte hamartoma.

Abstract:  Medallion‐like dermal dendrocyte hamartomas are rare congenital cutaneous lesions, with only three occurrences reported in the English language literature. They present at birth as asymptomatic circular, oval, or triangular well‐circumscribed, atrophic patches. Typically, they have an erythematous or yellow‐brown hue and a characteristic pliable, wrinkled surface; subtle telangiectases may also be appreciated. They may be misdiagnosed as atrophoderma, cutis aplasia, or anetoderma. All reported patients have been female. Characteristic histologic findings include epidermal atrophy and the presence of a CD34‐positive spindle cell proliferation in the dermis. This spindle cell proliferation represents a population of dermal dendrocytes, which are bone marrow‐derived cells that are believed to function as antigen‐presenting cells that contribute to the function of the skin immune system. Little is known about the pathophysiology of medallion‐like dermal dendrocyte hamartomas. We present a patient with this entity and review similar presentations reported in the literature.

Diagnosis and Treatment of Pediatric Psoriasis: Current and Future

Psoriasis is a common yet complex inflammatory dermatosis that may be seen in infants, children, and adolescents. The clinical presentation and course may be quite variable, and while patients with mild disease are often easily managed, those with recalcitrant or more severe disease often present a therapeutic dilemma given the number of therapies available and the relative lack of data on the efficacy and safety of use of these therapies in children. This review presents the reader with an overview of the current understanding of the pathophysiology, diagnosis, and treatment of pediatric psoriasis, with an emphasis on the available data in the literature that pertains to the use in children of currently available topical and systemic therapies, including topical corticosteroids, vitamin D analogs, phototherapy, systemic immunosuppressive medications, and biologic agents.

From the Medical Board of the National Psoriasis Foundation: Treatment targets for plaque psoriasis

Background: An urgent need exists in the United States to establish treatment goals in psoriasis. Objective: We aim to establish defined treatment targets toward which clinicians and patients with psoriasis can strive to inform treatment decisions, reduce disease burden, and improve outcomes in practice. Methods: The National Psoriasis Foundation conducted a consensus‐building study among psoriasis experts using the Delphi method. The process consisted of: (1) literature review, (2) pre‐Delphi question selection and input from general dermatologists and patients, and (3) 4 Delphi rounds. Results: A total of 25 psoriasis experts participated in the Delphi process. The most preferred instrument was body surface area (BSA). The most preferred time for evaluating patient response after starting new therapies was at 3 months. The acceptable response at 3 months postinitiation was either BSA 3% or less or BSA improvement 75% or more from baseline. The target response at 3 months postinitiation was BSA 1% or less. During the maintenance period, evaluation every 6 months was most preferred. The target response at every 6 months maintenance evaluation is BSA 1% or less. Limitations: Although BSA is feasible in practice, it does not encompass health‐related quality of life, costs, and risks of side effects. Conclusion: With defined treatment targets, clinicians and patients can regularly evaluate treatment responses and perform benefit‐risk assessments of therapeutic options individualized to the patient.

The Safety and Efficacy of Pimecrolimus, 1%, Cream for the Treatment of Netherton Syndrome: Results From an Exploratory Study

BACKGROUND Impaired skin integrity in patients with Netherton syndrome (NS) results in significant systemic absorption of topically applied medications. Some have advocated the administration of pimecrolimus, 1%, topical cream for the treatment of patients with NS. Insufficient data exist with regard to its safety, systemic absorption, and efficacy. OBSERVATIONS An exploratory study was conducted involving 3 children with NS who received twice-daily application of pimecrolimus, 1%, cream over 18 months. There were no notable abnormalities in hematologic or chemistry profiles. Blood levels of pimecrolimus ranged from 0.625 to 7.08 ng/mL, with peak levels reached during the first month in all 3 patients. Dramatic reductions were observed in the Netherton Area and Severity Assessment, Eczema Area and Severity Index, Investigator Global Evaluation of Disease, and pruritus scores compared with baseline levels. CONCLUSIONS Use of pimecrolimus, 1%, cream was well tolerated and demonstrated marked improvements in nearly all of the parameters evaluated. Patients treated with pimecrolimus responded rapidly, within the first month of treatment, and improvement persisted throughout the study period. In adult patients receiving oral pimecrolimus, blood levels as high as 54 ng/mL for 3 months have not shown clinically significant immunosuppression. Absorption of pimecrolimus, 1%, cream was detectable, but levels were much lower than expected even when applied to 50% of total body surface area. Larger studies are warranted to determine the safety and efficacy of pimecrolimus, 1%, cream in the treatment of NS. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00208026.

Obesity and the metabolic syndrome in pediatric psoriasis

Psoriasis is a common, chronic inflammatory dermatosis that often has its onset during childhood. There is increasing evidence that psoriasis in adults is associated with obesity, the metabolic syndrome, and associated comorbidities, including insulin resistance/type 2 diabetes, dyslipidemia, hypertension, and cardiovascular disease. This association is postulated to arise, at least in part, as a result of a systemic proinflammatory state that is mediated by adipose tissue. Several recent observational studies suggest that children and adolescents with psoriasis may be at increased risk of being overweight and obese as well as having an increased risk for features of the metabolic syndrome. Such an association raises concern with regards to the long-term health implications for children and adolescents with psoriasis and suggests that better awareness, evaluation, and management of overweight and obese patients and associated metabolic disease are warranted in this population.

Factitial dermatoses in children.

Purpose of review Factitial skin diseases are characterized by unusual patterns of skin lesions that do not conform to any known dermatologic condition and that are consciously or subconsciously fabricated by the patient. This review summarizes the current literature regarding the diagnosis and management of factitial dermatoses in children. Recent findings Neurotic excoriations, acne excoriee and trichotillomania are the most common factitial skin diseases seen in children. Dermatitis artefacta is also seen in children, but is less common. In many cases, the development of factitial skin disease is associated with a comorbid psychiatric condition or identifiable psychosocial stressor. With regard to the management of factitial dermatoses in children, it is of paramount importance for the clinician to establish an appropriate physician–patient–family relationship. Although controlled studies in children are lacking, pharmacologic and/or nonpharmacologic adjunctive therapy can be helpful in the treatment of these difficult conditions. Summary The diagnosis and management of factitial skin diseases in children is a challenge. Clinicians caring for children should be able to recognize the common factitial dermatoses that are seen in the pediatric population. The conveyance of support and acceptance by the physician is essential to the treatment process. Both psychotherapy and psychopharmacology can be important adjunctive treatments.

Biologic Response Modifiers and Pediatric Psoriasis

The efficacy and safety of biologic response modifiers such as etanercept, adalimumab, infliximab, and ustekinumab have been demonstrated in the treatment of psoriasis in adults, but none are currently approved for the treatment of psoriasis in children in the United States, and only etanercept is approved for the treatment of psoriasis in children in the European Union. Through case reports, case series, and a large clinical trial of the use of etanercept, the literature supports the use of these agents to treat psoriasis in children. Data on the use of the tumor necrosis factor‐α antagonists etanercept, adalimumab, and infliximab in the treatment of other inflammatory diseases in children—namely Crohns disease, juvenile arthritis, and uveitis—support their safety profile in children.