Consensus guidelines for diagnosis and management of anemia in epidermolysis bullosa.

BACKGROUND: Anemia is a common complication of severe forms of epidermolysis bullosa (EB). To date, there are no guidelines outlining best clinical practices to manage anemia in the EB population. The objective of this manuscript is to present the first consensus guidelines for the diagnosis and management of anemia in EB. RESULTS: Due to the lack of high-quality evidence, a consensus methodology was followed. An initial survey exploring patient preferences, concerns and symptoms related to anemia was sent to EB patients and their family members. A second survey was distributed to EB experts and focused on screening, diagnosis, monitoring and management of anemia in the different types of EB. Information from these surveys was collated and used by the panel to generate 26 consensus statements. Consensus statements were sent to healthcare providers that care for EB patients through EB-Clinet. Statements that received more than 70% approval (completely agree/agree) were adopted. CONCLUSIONS: The end result was a series of 6 recommendations which include 20 statements that will help guide management of anemia in EB patients. In patients with moderate to severe forms of EB, the minimum desirable level of Hb is 100 g/L. Treatment should be individualized. Dietary measures should be offered as part of management of anemia in all EB patients, oral iron supplementation should be used for mild anemia; while iron infusion is reserved for moderate to severe anemia, if Hb levels of > 80-100 g/L (8-10 g/dL) and symptomatic; and transfusion should be administered if Hb is < 80 g/L (8 g/dL) in adults and < 60 g/L (6 g/dL) in children.

Clinical Features, Prognostic Factors, and Treatment Interventions for Ulceration in Patients With Infantile Hemangioma.

Importance: Ulceration is a common complication of infantile hemangioma (IH), which leads to substantial morbidity. Ulceration in IH has not been systematically studied since the advent of ß-blocker therapy for IH. Objectives: To examine treatment interventions used for ulceration in IH and identify clinical prognostic indicators of healing time. Design, Setting, and Participants: A retrospective, multicenter cohort study was conducted on 436 consecutive patients with a clinical diagnosis of ulcerated IH and available clinical photographs. Patients receiving care at tertiary referral centers evaluated between 2012 and 2016 were included; statistical and data analysis were performed from February 7 to April 27, 2020. Exposures: Clinical characteristics, treatment interventions, course, complications, and resource use were analyzed. Treatment interventions for ulceration in IH included local (wound care, topical), systemic (ß-blocker, corticosteroids), and procedural (pulsed-dye laser). Main Outcomes and Measures: The primary end point was time to complete or nearly complete ulceration healing. Clinical characteristics were analyzed to determine the responses to most common interventions and prognostic factors for healing of ulceration. Results: Of the 436 patients included in the study, 327 were girls (75.0%); median age at ulceration was 13.7 weeks (interquartile range, 8.86-21.30 weeks). The median heal time was 4.79 weeks (95% CI, 3.71-5.86 weeks) with wound care alone, 5.14 weeks (95% CI, 4.57-6.00 weeks) with timolol, 6.36 weeks (95% CI, 5.57-8.00 weeks) with a systemic ß-blocker, and 7.71 weeks (95% CI, 6.71-10.14 weeks) with multimodal therapy. After adjusting for IH size, a dose of propranolol less than or equal to 1 mg/kg/d was associated with shorter healing time compared with higher propranolol doses (hazard ratio, 2.04; 95% CI, 1.11 to 3.73; P = .02). Size of the IH was identified as a significant prognostic factor for healing time in multivariable analysis. Increasing size of IH portends a proportionately longer time to heal of the ulceration. Conclusions and Relevance: Despite the use of ß-blockers, this cohort study found that a subset of patients with IH ulceration continued to experience prolonged IH healing times. Larger IH size appears to be a poor prognostic factor for time to heal. For patients requiring systemic therapy, initiation of propranolol at lower doses (≤1 mg/kg/d) should be considered.

Mechanisms of Cannabinoids and Potential Applicability to Skin Diseases.

The legalisation of cannabis in a growing number of jurisdictions has led to increasing interest in its potential therapeutic effects in a range of disorders, including cutaneous conditions. Cannabinoids have been used as natural medicines for centuries; however, their biological activity in the skin is a new area of study. Recent data suggest that cannabinoids are involved in neuro-immuno-endocrine modulation of skin functioning, yet their effect on the features of dermatologic conditions is unclear. This article sought to review the mechanisms by which cannabinoids regulate skin functioning through the lens of relevance to treatment of dermatologic diseases looking at the effects of cannabinoids on a range of cellular activities and dermatologic conditions both in vitro and in vivo. We identified studies demonstrating an inhibitory effect of cannabinoids on skin inflammation, proliferation, fibrosis, pain, and itch-biological mechanisms involved in the pathogenesis of many dermatologic conditions. Cannabinoids have the potential to expand the therapeutic repertoire of a wide spectrum of skin disorders. Given their widespread unregulated use by the general public, basic and clinical studies are required to elucidate the effectiveness and long-term effects of topical and systemic cannabinoids in cutaneous disorders.

Vitamin D Level and Supplementation in Pediatric Atopic Dermatitis: A Randomized Controlled Trial.

BACKGROUND:: Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by a pruritic eczematous rash. Evidence surrounding the role of serum vitamin D (VD) in modifying disease severity is inconsistent. OBJECTIVES:: To determine whether VD levels are correlated with AD severity and the effects of VD supplementation on disease modification. METHODS:: This was a 2-phase study, using a cross-sectional design to evaluate the relationship between VD level and severity, as well as a double-blinded, randomized control trial to elucidate the effects of VD supplementation. Patients aged 0 to 18 years with AD were included in phase 1, and disease severity and serum VD levels were determined. Those with renal, liver, or other dermatologic conditions were excluded. Patients with abnormal (<72.7 nmol/L) VD levels were eligible for phase 2 and to be randomized to either VD supplementation of 2000 IU/d or placebo. VD level and severity were assessed at baseline and 3 months. RESULTS:: The 77 patients included in phase 1 had a mean (SD) age of 7.4 (4.5) years, and 45.5% (33/77) were female. Increased severity was significantly correlated with lower VD levels ( P = .015). Of the 45 patients included in phase 2, 21 and 24 were assigned to the supplementation and placebo arm, respectively. The mean (SD) change in severity did not differ significantly between the supplementation (15.35 [9.71]) and placebo (15.13 [8.97]) groups after 3 months of intervention ( P = .7). CONCLUSION:: Although VD levels correlated with AD severity, VD supplementation did not significantly improve disease severity.

Sinecatechins ointment for the treatment of warts in children.

BACKGROUND: Sinecatechins ointment, a green tea derivative, is a novel agent approved for the treatment of anogenital warts in immunocompetent adults and has been reported to be effective in treating extragenital warts as well. Data are lacking in children. We sought to determine the efficacy and tolerability of sinecatechins ointment for treating warts in children. METHODS: A retrospective cohort study was conducted of children with anogenital and/or extragenital warts treated with sinecatechins ointment for at least 1 month. The primary outcome was frequency of complete response (total resolution of warts at follow-up). Secondary outcomes included frequency of partial response (reduction in number and/or size of warts) and adverse events. There was no control group for comparison. RESULTS: Of 24 patients who met the inclusion criteria, 14 (58.3%) had anogenital warts, 7 (29.2%) had extragenital warts, and 3 (12.5%) had both anogenital and extragenital warts. Mean age at treatment initiation was 8.0 years (SD = 3.9). Median duration of warts at treatment initiation was 1.2 years (range 0.09-12.62). Sixteen patients (66.7%) experienced a reduction in the number and/or size of the warts. Four patients (16.7%) had complete resolution. Median treatment duration was 4.5 months (range 0.6-21.8) overall. Median time to complete resolution was 2.9 months (range 1.3-7.7). Fifty-four percent of patients used sinecatechins ointment as prescribed. Adverse events were limited to mild local irritation (7 patients; 29.2%). CONCLUSION: Sinecatechins ointment is a promising therapy for warts in children, and its use should be evaluated in prospective controlled clinical trials.

Effects of Vitamin D levels and supplementation on atopic dermatitis: A systematic review.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin condition affecting 5%-20% of children worldwide. Studies suggested both a correlation between serum vitamin D (VD) levels and AD severity and a therapeutic potential role for VD supplementation. OBJECTIVES: To determine whether serum VD levels correlate with AD severity and the effects of supplementation for disease improvement in children. DATA SOURCES: Ovid MEDLINE, EMBASE, and Cochrane Library databases were searched. STUDY SELECTION: Publications with children 0-18 years old with AD and data evaluating effects of VD levels or supplementation on AD severity were included. DATA EXTRACTION: Author, year, inclusion criteria, study design, location, age, VD levels, VD supplementation regimens, and baseline and final disease severities were extracted. RESULTS: Of the 21 included publications, 15, 5, and 1 evaluated VD level, VD supplementation, and both factors with disease severity, respectively. There were 4 randomized control trials (RCTs), 5 cohort, 6 case-control, and 6 cross-sectional studies. A significant inverse correlation between VD level and severity was described in 62.5% (10/16) of studies. There were 67% (4/6) that reported a significant improvement in AD severity with supplementation. LIMITATIONS: Studies meeting inclusion criteria were limited. Furthermore, papers were heterogeneous in terms of location, season, and VD supplementation regimen. Language and publication bias was another potential limitation. CONCLUSION: In children, the majority of existing literature confirmed a link between serum VD levels and AD severity. Weak evidence was found supporting improvement of AD with VD supplementation. Future large-scale studies are needed to support our findings.

Evaluation of Treatments for Pruritus in Epidermolysis Bullosa.

Pruritus is a common complication in patients with epidermolysis bullosa (EB). There is limited published data about the treatments that individuals with EB use for pruritus. The objective of the current study was to determine quantitatively which treatments individuals with EB have used for pruritus and to evaluate the perceived effectiveness of these treatments in pruritus relief. A questionnaire was developed to evaluate the treatments and therapies used for pruritus in patients of all ages and for all types of EB. Questions about bathing products, moisturizers, topical products, oral medications, dressings, and alternative therapies were included. A 5-point Likert scale (-2 = relieves itch a lot, -1 = relieves itch a little, 0 = no change, 1 = increases itch a little, 2 = increases itch a lot) was used to evaluate perceived effectiveness. Patients from seven North American EB centers were invited to participate. Greasy ointments (53.4%), lotions (45.2%), creams (40.4%), and oral hydroxyzine (39.0%) were the most frequently used treatments for pruritus. Treatments that were used frequently and perceived to be the most effective included creams (mean = -1.1), topical prescription corticosteroids (mean = -1.0), oils (mean = -0.9), oral hydroxyzine (mean = -0.9), topical diphenhydramine (mean = -0.9), and vaporizing rub (menthol, camphor, eucalyptus) (mean = -0.9). Systemic opioids (mean = 0.3), adherent bandages (mean = 0.3), and bleach baths (mean = 0.2) slightly increased pruritus. Randomized controlled trials of therapies will be necessary to develop evidence-based recommendations for control of pruritus in individuals with EB.

Childhood mycosis fungoides: experience of 28 patients and response to phototherapy.

Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma (CTCL), is rare in childhood. The prognosis and response to treatment are poorly described in children. The objective of the current study was to evaluate the response to phototherapy in a pediatric cohort. A retrospective cohort study of all patients diagnosed with MF before the age of 18 years and referred to the regional CTCL phototherapy service was performed between January 1990 and April 2012. Twenty-eight patients were identified (13 boys, 15 girls). The mean age at presentation was 11.6 ± 3.9 years. The hypopigmented variant was noted in 79% of patients. All patients had stage I disease (IA = 10, IB = 17, unknown = 1). The median follow-up after diagnosis was 43 months (range 6-274 mos). Narrowband ultraviolet B (NbUVB; 311 nm) was used as first-line phototherapy in 18 patients and psoralen (bath) plus ultraviolet A (PUVA) was used in 8 patients. Complete or partial response was observed in 19 of 22 patients (86%). A further course of phototherapy was required in 7 of 12 patients (58%) treated with NbUVB after a median of 4 months (range 4-29 mos). A further course of phototherapy was required in four of eight patients (50%) successfully treated with PUVA after a median of 45.5 months (range 30-87 mos). No disease progression was noted over the follow-up (median 43 mos). The majority of patients in our cohort had hypopigmented MF. Phototherapy offers an effective option for treatment of childhood MF, although the period of remission may be greater in patients treated with PUVA.

Dilated cardiomyopathy in epidermolysis bullosa: a retrospective, multicenter study.

Dilated cardiomyopathy (DC) has been reported in severe epidermolysis bullosa (EB) subtypes. Poor nutritional status, low carnitine levels, selenium deficiency, chronic iron overload, drugs and viral etiology have been proposed as potential contributors. This was a retrospective, descriptive, multicenter study describing EB patients that developed DC, and determining potential pre-disposing risk factors. Fifteen patients were enrolled in the study; 11 of them were male subjects (73%). Eighty-seven per cent of the participants had dystrophic EB and 13% had junctional EB. Mean age at diagnosis of DC was 12.18 +/- 4.99 years. Chronic anemia was diagnosed in 13 of 15 patients (86.7%). Sixty per cent of patients had prior red blood cell transfusions. At diagnosis, selenium levels were low in 55% of the patients (n = 11) and total carnitine levels were low in 45% of the patients (n = 11). Systolic function was moderately impaired, with a mean shortening fraction of 19.38% (SD = 5.04, n = 8). After a mean follow-up period of 6.3 +/- 4.8 years, six patients were alive without being on any medications (40.0%), two were alive on medications (13.3%) and seven had died (46.7%). Limitations of the study was that it was a retrospective chart review with relatively small sample size. Retrospective chart review, relatively small sample size. This study substantiates the association between DC and EB. Currently, there is no single risk factor identified in EB patients that leads to DC. Further prospective studies are needed.

Dilated cardiomyopathy in epidermolysis bullosa.

Dilated cardiomyopathy (DC) is a rare but potentially fatal complication of epidermolysis bullosa. No clear cause for it has been identified, but iron overload, low carnitine, low selenium, concomitant viral illness, chronic anemia, and medications have been proposed as possible contributors to the development of DC in reported cases. Early detection allows for medical treatment that delays clinical progression and prolongs survival.

Mycosis fungoides in the pediatric population: report from an international Childhood Registry of Cutaneous Lymphoma.

BACKGROUND/OBJECTIVES: There are limited data on the clinical presentation and progression of pediatric cutaneous lymphoma. This study focuses on the clinical characteristics of pediatric patients with mycosis fungoides (MF). MATERIALS AND METHODS: This descriptive study presents clinical characteristics of 22 pediatric patients with MF, enrolled in the international Childhood Registry for Cutaneous Lymphomas (CRCL). RESULTS: The mean ages at onset and at diagnosis were 7.5 (SD 3.8 years) years and 9.9 (SD 3.4) years, respectively. The most common MF presentation was patch stage (68%), followed by hypopigmentation (59%) and plaque stage disease (50%). Epidermotropism and lymphocytic atypia were the most common pathologic features, found in 89% and 85%, respectively. Cerebriform nuclei were noted in 42%, and Pautrier microabscesses were seen in 16% of cases. A cytotoxic pattern was more commonly seen (67% vs 33%), and clonality was detected in 21% (3 of 14) of patients. All patients presented with early-stage disease and received skin-directed therapy (topical steroids, 73%; light therapy, 54%; or combination therapy, 35%). CONCLUSIONS: Pediatric patients with MF present in the first decade of life, with early-stage disease and unusual forms such as hypopigmented variant. Further patient enrollment will provide information regarding natural history, treatment response, and overall prognosis of pediatric cutaneous T-cell lymphoma (CTCL).