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REVIEW OF CURRENT LITERATURE
Year : 2018  |  Volume : 19  |  Issue : 3  |  Page : 280-284

Hot topics in pediatric dermatology


Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Web Publication28-Jun-2018

Correspondence Address:
Rahul Mahajan
Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpd.IJPD_64_18

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How to cite this article:
Bhattacharjee R, Mahajan R. Hot topics in pediatric dermatology. Indian J Paediatr Dermatol 2018;19:280-4

How to cite this URL:
Bhattacharjee R, Mahajan R. Hot topics in pediatric dermatology. Indian J Paediatr Dermatol [serial online] 2018 [cited 2019 Dec 9];19:280-4. Available from: http://www.ijpd.in/text.asp?2018/19/3/280/235497



Effect of Mixture of Oral Probiotic Strains in Moderate Atopic Dermatitis

We discuss a recent study by Lopez et al. that assessed the effect of probiotics in reducing SCORing Atopic Dermatitis (SCORAD) severity index and the use of topical corticosteroids in 50 children aged between 4–17 years with moderate atopic dermatitis (AD) over a 12-week study period.[1] A mixture of different strains of probiotics, namely Bifidobacterium lactis CECT 8145, Bifidobacterium longum CECT 7347, and Lactobacillus casei CECT 9104, was used with maltodextrin as a carrier. The placebo group received maltodextrin-only capsules. The two groups were stratified and blocked randomized according to sex, age, and age of onset. Patients with a history of systemic immunosuppressive drugs in the previous 3 months or antibiotics in the previous 2 weeks or concomitant diagnosis of intestinal bowel disease or signs of bacterial infection were excluded. The main outcomes analyzed were SCORAD index score and days of topical steroid use. The authors observed a significant reduction in the SCORAD and use of topical steroids to treat flares in the probiotic arm compared with the control arm. Based on these results, they concluded that this particular probiotic mixture is an effective and safe adjuvant in the treatment of AD.

Comments

The results of the study are very interesting as the evidence so far on the effectiveness of probiotics in AD is not very robust and is equivocal. The present study was a well-designed, double-blinded, parallel arm, placebo-controlled, randomized trial which adhered to the CONSORT guidelines for reporting randomized controlled trials (RCTs). Furthermore, the authors rationalize their use of the new probiotic formulation based on the different mechanisms of action of the different components of the combination; namely strain B. lactis CECT 8145 provides antioxidant properties, strain B. longum CECT 7347 has anti-inflammatory properties, and strain L. casei CECT 9104 acts again certain gut pathogens. Moderate AD is the main group requiring topical corticosteroids, so the results of the study affect a sizable proportion of patients with AD. The study included objective parameters as well as subjective symptoms. In addition, the authors measured the effect of the probiotic formulation on Th2 cytokines.

However, the parameters studied in this study have been assessed by prior RCTs, so the results are not entirely novel, barring the use of combined probiotic formulation. A meta-analysis of RCTs has also commented on the use of a mixture of probiotics versus a single strain and found that the greatest effect observed in studies using a mixture of different bacterial species, followed by Lactobacillus species alone.[2] Another review of 13 studies found a significantly reduced cumulative incidence of AD among children in the probiotic group compared to the placebo group, with a significantly reduced risk of having moderate AD among infants supplemented with probiotics, including infants without a family history of atopy.[3] However, none of the mentioned studies compared probiotics mix with single strain. The main drawback of the study is the low power of the study as the sample size of 50 children may be too small to extrapolate the results to the general population. Participants were required to be currently consuming a high-quality Mediterranean diet with a Mediterranean Diet Quality Index score >7 which itself may have some effect on atopic symptoms. Hence, the extrapolation of results may be difficult to children of different geographical areas and different eating habits. The study period of 12 weeks is short to draw any definitive conclusions regarding the sustainability of probiotics in reducing SCORAD or the use of topical steroids which are the mainstay of the treatment of AD. The question of applicability of the results to children with mild and severe AD, as well as adults with AD, which constitute a sizable proportion of people suffering from AD, is not answered in this RCT. Other aspects that may be important are the availability, dose, and duration of probiotic formulation. According to a meta-analysis on the use of probiotics in AD, comparative analysis of the effect of placebo using prebiotics such as maltodextrin, cellulose, and fructooligosaccharide versus a nonprebiotic placebo shows that the studies using a nonprebiotic placebo showed greater mean differences in SCORAD value changes. Hence, whether the use of a different placebo could alter the effectiveness will be an interesting question for the future RCTs. The study also does not address the aspect regarding the use of topical tacrolimus in AD which is the mainstay of long-term maintenance therapy. The definition of flare of AD requiring the use of topical corticosteroids is arbitrary. There was no statistically significant difference in subjective symptoms, which constitute a significant component of morbidity in these patients. Overall, despite certain limitations, the results of the RCT are very encouraging and should be reproduced in the future RCTs.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

  1. Navarro-López V, Ramírez-Boscá A, Ramón-Vidal D, Ruzafa-Costas B, Genovés-Martínez S, Chenoll-Cuadros E, et al. Effect of oral administration of a mixture of probiotic strains on SCORAD index and use of topical steroids in young patients with moderate atopic dermatitis: A randomized clinical trial. JAMA Dermatol 2018;154:37-43.
  2. Kim SO, Ah YM, Yu YM, Choi KH, Shin WG, Lee JY, et al. Effects of probiotics for the treatment of atopic dermatitis: A meta-analysis of randomized controlled trials. Ann Allergy Asthma Immunol 2014;113:217-26.
  3. Foolad N, Armstrong AW. Prebiotics and probiotics: The prevention and reduction in severity of atopic dermatitis in children. Benef Microbes 2014;5:151-60.



  Childhood Psoriasis and Comorbidities: A Real Concern? Top


Here, we discuss the study by Tollefson et al. on the association of metabolic syndrome and associated comorbidities in pediatric psoriasis.[1] This was a retrospective cohort study of 29,957 children diagnosed with psoriasis over a 10-year period (affected children) and an age-, sex-, and race-matched comparator cohort of 29,957 children without psoriasis divided into four groups: (1) nonobese without psoriasis (reference cohort); (2) nonobese with psoriasis; (3) obese without psoriasis; and (4) obese with psoriasis. The aim of this study was to determine the risk of dyslipidemia, hypertension, metabolic syndrome, polycystic ovarian syndrome, diabetes, nonalcoholic liver disease, and elevated liver enzyme levels in children with and without psoriasis and the relative contribution of obesity to the risk of development of these comorbidities in children with and without psoriasis. It was found that psoriasis itself increased the risk of developing these conditions even in nonobese children with psoriasis, making it an independent risk factor in addition to obesity. Studies analyzing the prevalence of comorbidities including metabolic syndrome in pediatric psoriasis patients are relatively scarce. The results contrast with another cross-sectional, multicenter study from France that found childhood-onset psoriasis not to be an additional risk factor for higher frequencies of cardiovascular and metabolic comorbidities during adulthood.[2]

Comments

The strength of the study lies in its huge sample size with an equal number of matched controls, making the data very robust. Psoriasis was evaluated independent of obesity as a risk factor for the development of comorbidities, in addition to studying their additive effect. The entire spectrum of metabolic syndrome was studied in childhood psoriasis, of which there are not much data of this magnitude and period. In addition to metabolic syndrome, many novel parameters such as polycystic ovarian syndrome, nonalcoholic liver disease, and elevated liver enzyme levels have been analyzed in this study.

Despite its novelty, the study has few limitations such as its retrospective study design and the accompanying bias. The diagnosis of psoriasis was not uniform and not verified by a dermatologist. All laboratory values were not uniform and were not measured at the same laboratory, thereby leading to potential nonuniformity. The effect and potential alterations by ongoing treatment on the studied parameters were not taken into account. However, the study does offer some interesting insights into the comorbidities associated with pediatric psoriasis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

  1. Tollefson MM, Van Houten HK, Asante D, Yao X, Maradit Kremers H. Association of psoriasis with comorbidity development in children with psoriasis. JAMA Dermatol 2018;154:286-92.
  2. Mahé E, Maccari F, Beauchet A, Lahfa M, Barthelemy H, Reguiaï Z, et al. Childhood-onset psoriasis: Association with future cardiovascular and metabolic comorbidities. Br J Dermatol 2013;169:889-95.





  Topical Timolol in Infantile Hemangioma: The New Favorite on the Block? Top


Here, we discuss and review a systematic review and meta-analysis by Zheng et al. on the use of topical timolol in infantile hemangioma.[1] The present study assessed the response rate and adverse events of topical timolol in the treatment of infantile hemangioma. Ten studies, comprising 887 infants with hemangioma, met the inclusion criteria for the evaluation in this systematic review. These trials included topical timolol as one arm with the comparator arm being laser, observation, placebo, or propranolol. The study populations in these trials were significantly heterogeneous which makes the meta-analysis difficult to interpret. The difference in the response rate was significant while comparing topical timolol with controls but not propranolol. The difference in the adverse events was significant when timolol was compared to controls. This meta-analysis concluded that topical timolol alone was more beneficial on response rate and adverse event than laser, placebo, and observation. However, the response rate did not differ significantly when compared to propranolol.

Comments

The systematic review and meta-analysis follow a good methodology adhering to the PRISMA guidelines. The literature search and filtering of articles were extensive. The reference lists of all retrieved studies and published reviews were manually searched and included. Five randomized controlled trials (RCTs), three prospective cohort studies, and two retrospective cohort studies were included. The various kinds of bias identified in each RCT were adequately summarized in risk of bias table. The meta-analysis included a total of 887 infants included which increases the power of the results. The quality of the cohort studies included in the meta-analysis was high. Although the studies were heterogeneous in terms of evaluation of efficacy, the authors employed random effect models to counter this. The studies were quite homogenous while reporting adverse effects and favored timolol consistently.

This is not the first meta-analysis on the use of topical timolol in infantile hemangiomas. Another recent systematic review and meta-analysis including 31 studies and 10 studies, respectively, found a 91% resolution rate in pooled meta-analysis with the degree of resolution significantly greater in the treatment than in the nontreatment group. The number of RCTs included in both the meta-analyses was few, which in turn depicts the need for high-quality RCTs comparing topical timolol with other treatment modalities such as oral beta-blockers.[2]

Although the current meta-analysis under review concludes topical timolol to be better than placebo, laser, and no treatment in terms of effectiveness and adverse effect profile, the confidence intervals were wide which again points toward the needs for more well-designed trials. Concluding, this excellent-quality systematic review provides evidence in favor of the use of topical timolol in infantile hemangioma.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

  1. Zheng L, Li Y. Effect of topical timolol on response rate and adverse events in infantile hemangioma: A meta-analysis. Arch Dermatol Res 2018;310:261-9.
  2. Khan M, Boyce A, Prieto-Merino D, Svensson Å, Wedgeworth E, Flohr C, et al. The role of topical timolol in the treatment of infantile hemangiomas: A Systematic review and meta-analysis. Acta Derm Venereol 2017;97:1167-71.





  Pediatric Recurrent Erythema Multiforme: Review on a Lesser Recognized Entity Top


Our fourth study of interest is by Heinze et al. reviewing their experience on pediatric erythema multiforme (EM).[1] The study is a retrospective chart review of 26 patients to characterize the clinical features, laboratory findings, and treatment responses of pediatric recurrent EM, including clinical characteristics, causes, and response to treatment. Inclusion criterion was a diagnosis before the age of 18 years with recurrent EM, defined as a symmetrically distributed, fixed eruption, including target lesions, with or without mucous membrane involvement, occurring on at least three occasions. The median age of onset was 9.1 years; two-thirds of these were boys. Herpes simplex virus (HSV) testing was positive in only 52.9% (9 out of 17) of patients. Remission was achieved in 31% of patients while taking suppressive antivirals. Eight patients received continuous anti-inflammatory treatment, of which two (25%) experienced remission.

Comments

This is the first study on recurrent EM in children. Prior studies have addressed pediatric EM, and there are a plethora of studies on recurrent EM, but those that have been restricted to the adult population only. The study evaluates a moderately substantial number of patients at two major pediatric centers over a long-term period of 15 and 25 years. Detailed work-up including biochemical as well as microbiological evaluation (ELISA, polymerase chain reaction [PCR], and HSV serology) was done. The study provides clinical experience on a relatively less well-described entity along with an in-depth review of literature.

However, the study does not mention a detailed drug history. PCR for HSV was not performed in all the children (17 out of 26). There was no age- and sex-matched control arm to establish the incidence of HSV in the control population. It is not clear whether HSV is responsible for EM or HSV infection is secondary to steroid/immunosuppressive therapy administered to these patients for the recurrent episodes of EM.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

  1. Heinze A, Tollefson M, Holland KE, Chiu YE. Characteristics of pediatric recurrent erythema multiforme. Pediatr Dermatol 2018;35:97-103.





  New Insight into the Association of Atopic Dermatitis in Children with Central Obesity and High Blood Pressure Top


Our final study once again focuses on associated comorbidities, but this time with pediatric atopic dermatitis (AD), authored by Silverberg et al.[1] This study was a prospective, clinical, US multicenter, cross-sectional study that addressed whether AD is associated with central obesity and elevated blood pressure (BP) in childhood AD. Moderate-to-severe AD was found to be associated with body mass index for age and sex of 97th percentile or greater, waist circumference in the 85th percentile or greater, and waist-to-height ratio of 0.5 or greater. AD was associated with higher BP for age, sex, and height percentiles, particularly a systolic BP in the 90th percentile or higher, and with higher systolic BP in Hispanics/Latinos and Asians. Severe-to-very severe AD was associated with systolic BP in the 90th percentile or higher. AD was associated with a family history of hypertension and type 2 diabetes mellitus, but not obesity or hyperlipidemia. The conclusion drawn was that moderate-to-severe pediatric AD may be associated with central obesity and increased systolic BP.

Comments

This multicenter study was conducted on 132 children and 143 controls, making sample size adequate, the data robust, and increasing the power of the study. The study specifically addressed central obesity in AD which is an important parameter of metabolic syndrome. An exhaustive analysis of obesity and systolic and diastolic BP with severity of AD was done. The data collection was prospective, which is another plus point. An interesting observation of the present study was an association between AD and hypertension after controlling for other variables such as body mass index, waist circumference, and use of drugs such as cyclosporine/corticosteroids. This was partly attributable to genetics (with hypertension more frequent in families of children with AD) but is important as hypertension may be the important factor in persistence of low degree of inflammation in AD and may also be a precursor of cardiovascular events later in life.

Since the assessment was done cross-sectionally, the conclusions drawn need to be further consolidated in the future longitudinal studies. The cases were significantly younger than the controls, so age-related variations in the anthropometric parameters might have confounded the final results of the study. The severity of AD was assessed using the investigator's global assessment, which is less standardized than other AD scoring systems such as Eczema Area and Severity Index. BP was measured at a single recording and could have been spuriously elevated. Other criteria for metabolic syndrome such as lipid profile could also be analyzed.

While no other study has addressed the prevalence of high BP in children with AD, a recent systematic review of observational studies has concluded overweight/obesity to be associated with an increased risk of AD, though the incorporated studies had a lot of discrepancy in the observations with more recent prospective studies reporting a positive association, not observed in older cross-sectional studies.[2] Hence, large prospective cohort studies are required to confirm the association between AD and childhood obesity and high BP to consolidate the findings of this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

  1. Silverberg JI, Becker L, Kwasny M, Menter A, Cordoro KM, Paller AS, et al. Central obesity and high blood pressure in pediatric patients with atopic dermatitis. JAMA Dermatol 2015;151:144-52.
  2. Ali Z, Suppli Ulrik C, Agner T, Thomsen SF. Is atopic dermatitis associated with obesity? A systematic review of observational studies. J Eur Acad Dermatol Venereol 2018. doi: 10.1111/jdv.14879. [Epub ahead of print].







 

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