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REVIEW OF CURRENT LITERATURE
Year : 2019  |  Volume : 20  |  Issue : 4  |  Page : 315-319

Hot topics in paediatric dermatology


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

Date of Web Publication30-Sep-2019

Correspondence Address:
Dr 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_75_19

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How to cite this article:
Kamat D, Mahajan R. Hot topics in paediatric dermatology. Indian J Paediatr Dermatol 2019;20:315-9

How to cite this URL:
Kamat D, Mahajan R. Hot topics in paediatric dermatology. Indian J Paediatr Dermatol [serial online] 2019 [cited 2019 Nov 13];20:315-9. Available from: http://www.ijpd.in/text.asp?2019/20/4/315/268401




  Pulsed -Dye Laser Treatment Of Port-Wine Stains In Infancy Without The Need For General Anesthesia Top


We discuss a retrospective study conducted by Jeon et al.[1] where 197 infants with port-wine stains (PWS) were treated in infancy using 595 nm pulsed-dye laser (PDL) without any topical or general anesthesia. For periocular lesions, stainless steel corneal shields were used after topical anesthetic solution. Retrospective chart review over 17 years (2000–2017) was undertaken and included all infants with PWS treated before or at 1 year of age and excluded conditions such as nevus simplex. Data cutoff point was set at 1 year after initial treatment. Before and after photographs were analyzed by four different physicians and graded as per visual analog score. A total of 197 infants were included. The mean age at the time of the treatment was 3.38 months (range, 5–355 days), and the mean number of treatments was 9.8 (range, 2–23; median, 10). The recommended treatment interval was every 2–3 weeks, with longer intervals for patients with darker skin. Treatment settings using the PDL were 10–12 mm spot size, fluence of 6.5–9.0 J/cm2, and a pulse width of 0.45–1.5 ms. This, however, varied according to the size and location of the lesion. The majority (90.9%) of the infants had Fitzpatrick skin type between Type I and III. Overall 51 patients (25.9%) showed 100% clearance. The presence of a V1 lesion (in ophthalmic dermatome) was associated with a statistically significantly higher clearance rate (P< 0.001).


  Comments Top


The study is relevant as it discusses several important practical aspects of managing PWS. First, the timing of treating PWS has been long debated by clinicians. One school of thought is to treat early in infancy as the size of vessels, nodularity, and depth increases with age and makes it more difficult to treat.[1] However, one earlier prospective study did not show any significant difference in outcomes with respect to age of treatment initiation, although there were few differences in parameters such as spot size and fluence which may have affected the overall efficacy.[2] Second, a major concern is giving general anesthesia to an infant being treated with PDL. A recent survey among laser users in the UK showed that 81% of the practitioners used general anesthesia while treating children with PWS.[3] This may be important in a country like India where availability of both the PDL and the pediatric anesthetists may be limited to few centers and may discourage dermatologists to treat PWS at an early age.

In this retrospective study, PWS was found both safe and effective in infants treated without general or topical anesthesia. The exclusion of nevus simplex has made the results more reliable. The favorable outcome of V1 dermatome was significant even on adjusting for the size of the lesion which may help the physicians to explain the prognosis to the parents with greater confidence. Although the side effects noted have not been detailed in the results, it was mentioned that none of the infants suffered from pigmentary changes or scarring. However, postlaser management of pain, purpura, and edema should have been mentioned as this may be a cause of apprehension among parents after the procedure. In addition to the study being a retrospective chart review, the main limitation as highlighted was the period to follow-up which was taken as 1 year and would probably not account for the recurrences. However, considering the large sample size evaluated, the study gives encouraging results to initiate PDL early in infancy for PWS without the need for anesthesia.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

  1. Jeon H, Bernstein LJ, Belkin DA, Ghalili S, Geronemus RG. Pulsed dye laser treatment of port-wine stains in infancy without the need for general anesthesia. JAMA Dermatol 2019;155:435.
  2. van der Horst CM, Koster PH, de Borgie CA, Bossuyt PM, van Gemert MJ. Effect of the timing of treatment of port-wine stains with the flash-lamp-pumped pulsed-dye laser. N Engl J Med 1998;338:1028-33.
  3. Mahendran R, Sheehan-Dare RA. Survey of the practices of laser users in the UK in the treatment of port wine stains. J Dermatolog Treat 2004;15:112-7.



  Severity of Disease and Quality of Life in Parents of Children with Alopecia Areata, Totalis, and Universalis: A Prospective, Cross-sectional Study Top


We discuss a study by Putterman et al.[1] which studied caregiver-oriented quality of life (QoL) parameters in parents of children affected with all types of alopecia areata. This study was the of its kind where parent-tailored QoL survey was correlated with the Severity of Alopecia Tool (SALT) scores. This was a cross-sectional study that included all types of alopecia areata. SALT scores were recorded at baseline. Two surveys were conducted for one parent per patient: the Quality of Life in a Child's Chronic Disease Questionnaire (QLCCDQ), which measures QoL in parents of children with general chronic disease, and the Family Dermatology Life Quality Index (FDLQI), a dermatology-specific QoL index. Scores on the QLCCDQ are reported as an average per item (0–7 points) as well as averages (0–7) for each domain. Lower QLCCDQ scores represent a greater impairment in QoL. The FDLQI is a well-validated 10-item questionnaire measuring the impact of skin diseases on families of affected patients. The FDLQI is reported as a total out of 30 possible points, with higher scores representing greater impairment in QoL. Children >7 years of age also completed the Children's Dermatology Life Quality Index. The authors found no significant correlation between the duration of disease and overall parental QoL. They found that the overall parental QoL negatively correlated with the child's age. The emotional component of QLCCDQ was significantly related to the severity of the disease (P< 0.001). The emotional domain of QoL might be more closely related to the severity of disease than either age of the child or duration of disease.


  Comment Top


This cross-sectional study provides a more targeted assessment of the parents than family members in general. The FDLQI is intended for broad use in any -degree relative of affected patients. Both the QoL questionnaires chosen were validated with robust internal consistency, reliability, and reproducibility. The strength of this study, when compared to previous studies, is the recruitment was in a clinical setting rather than support groups, thus reducing the bias. Successful treatment of dermatological conditions affecting the pediatric population requires caregiver-oriented patient care. It is imperative to include parental counseling in routine practice which can prevent anxious parents from overtreating common dermatoses. This study provides insight into parental QoL impairment which is often not routinely addressed during counseling and can be used to help set realistic expectation goals. Parental QoL-centered studies are now being increasingly done in chronic dermatoses such as pediatric atopic dermatitis and pediatric psoriasis.[2],[3]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

  1. Putterman E, Patel DP, Andrade G, Harfmann KL, Hogeling M, Cheng CE, et al. Severity of disease and quality of life in parents of children with alopecia areata, totalis, and universalis: A prospective, cross-sectional study. J Am Acad Dermatol 2019;80:1389-94.
  2. Jang HJ, Hwang S, Ahn Y, Lim DH, Sohn M, Kim JH, et al. Family quality of life among families of children with atopic dermatitis. Asia Pac Allergy 2016;6:213-9.
  3. Tollefson MM, Finnie DM, Schoch JJ, Eton DT. Impact of childhood psoriasis on parents of affected children. J Am Acad Dermatol 2017;76:286-9.e5.



  Sirolimus for Treatment of Verrucous Venous Malformation: A Retrospective Cohort Study Top


We discuss this study by Zhang et al.[1] where oral sirolimus was used to treat verrucous venous malformations in a cohort of 10 patients. The mean age was 17 ± standard deviation months, and six of these patients had received earlier treatments with frequent relapses. Sirolimus was initiated at dose of 0.8 mg/m2 administered twice daily. The random serum levels of sirolimus ranged from 6 to 15 ng/mL. To measure overall treatment response, volume reduction ratio (VRR) was used. Kaplan–Meier survival curves were used to calculate effective response time (assessed as a VRR >90%) of sirolimus. The median effective response time was 25 months, and all patients achieved visible improvement. None had any serious adverse effects.


  Comment Top


Although limited by its small sample size, this study shows that sirolimus can be safely used even for a long term in children affected with venous malformations. The rationale behind using sirolimus was a demonstration of somatic mutation in MAP3K3 in verrucous venous malformation which is an upstream target in the rapamycin-signaling pathway.[2] The other concern regarding recurrence is still not addressed in this study as no standard guidelines are recommending the optimal duration of therapy. Encouraging results have been seen with sirolimus used for lymphatic malformations as well with a significant response (clinical and radiological) being seen as early as in 3 months. The most common side effect noted was mild dyslipidemia.[3] Sirolimus has been used in various low-flow malformations and complicated vascular malformations. Long-term prospective studies in a larger cohort are required to further guide treatment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

  1. Zhang G, Chen H, Zhen Z, Chen J, Zhang S, Qin Q, et al. Sirolimus for treatment of verrucous venous malformation: A retrospective cohort study. J Am Acad Dermatol 2019;80:556-8.
  2. Couto JA, Vivero MP, Kozakewich HP, Taghinia AH, Mulliken JB, Warman ML, et al. Asomatic MAP3K3 mutation is associated with verrucous venous malformation. Am J Hum Genet 2015;96:480-6.
  3. Wiegand S, Wichmann G, Dietz A. Treatment of lymphatic malformations with the mTOR inhibitor sirolimus: A systematic review. Lymphat Res Biol 2018;16:330-9.



  The Effects of Melatonin Administration on Disease Severity and Sleep Quality in Children with Atopic Dermatitis: A Randomized, Double-blinded, Placebo-controlled Trial Top


We discuss a study by Taghavi Ardakani et al.[1] which studies the effects of oral melatonin on disease severity and sleep quality in pediatric atopic dermatitis. Children diagnosed with atopic dermatitis with no other chronic illness were recruited in the study matched for disease severity, age, and degree of sleep disturbance. This was a placebo-controlled trial in which the intervention group received 6 mg of melatonin at bedtime for 6 weeks. Uniform and standard treatment for atopic dermatitis was administered to both treatment groups. The primary outcome was the Scoring Atopic Dermatitis (SCORAD) index (the change in SCORAD overtime) which was used to evaluate the severity of atopic dermatitis (AD). The secondary outcomes were parameters related to sleep quality, serum total IgE levels, and serum high-sensitivity C-reactive protein. Sleep quality was evaluated using the Children's Sleep Habits Questionnaire (CSHQ). Intention to treat analysis was applied to all the recruited patients. After 6 weeks, it was found that melatonin supplementation significantly improved SCORAD index (P = 0.007), objective SCORAD index (P = 0.001), serum total IgE levels (P = 0.005), and total CSHQ scores (P = 0.006). A trend toward a greater reduction in sleep-onset latency (P = 0.09) and a greater increase in total sleep time (P = 0.07) was observed in the melatonin group. In the melatonin group, the total sleep time increased from 404.5 ± 75 at baseline to 420.7 ± 83.0 (min/night) at the end of 6 weeks of melatonin intake.


  Comments Top


The strengths of this study were it was a well-designed, double-blinded, parallel-arm, placebo-controlled, randomized trial which adhered to the CONSORT guidelines for reporting randomized controlled trials. Randomization and allocation concealment for both the researchers and participants were carried out by trained staff. Hence; it is very interesting to note that the administration of melatonin could improve disease severity. Whether this beneficial effect is due to its central nervous system effects or anti-inflammatory effects on skin needs to be explored further. In addition, while the effect of melatonin on improving sleep quality appears to be promising, the current study was not adequately powered to answer this question since it was a secondary objective. The role of melatonin in sleep disturbance had been long debated; however, a recent meta-analysis showed that melatonin had a significant effect on sleep onset, efficiency, and latency.[2] However, results of the impact on sleep disturbances were generated using a questionnaire rather than objective noninvasive sleep monitoring methods. The period of the intervention of 6 weeks was too less to convincingly study the impact on disease severity. Although melatonin was found to be favorable for sleep quality, it had no significant change in pruritus scores which is a major concern in pediatric atopic dermatitis which is often resistant to -generation antihistaminics as well. In a similar study, 3 mg/day of melatonin was administered and it was found that it improved the sleep-onset latency and disease severity in pediatric AD.[3] Another aspect needs to be highlighted in the frequency of night awakenings which may be equally important as sleep duration in impairing the sleep quality. Further studies with melatonin are required which should be aimed at assessing its impact on the inflammatory markers of atopic dermatitis. Further, drug tolerance is another concern with melatonin which should be addressed in long-term studies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

  1. Taghavi Ardakani A, Farrehi M, Sharif MR, Ostadmohammadi V, Mirhosseini N, Kheirkhah D, et al. The effects of melatonin administration on disease severity and sleep quality in children with atopic dermatitis: A randomized, double-blinded, placebo-controlled trial. Pediatr Allergy Immunol 2018;29:834-40.
  2. Brzezinski A, Vangel MG, Wurtman RJ, Norrie G, Zhdanova I, Ben-Shushan A, et al. Effects of exogenous melatonin on sleep: A meta-analysis. Sleep Med Rev 2005;9:41-50.
  3. Chang YS, Lin MH, Lee JH, Lee PL, Dai YS, Chu KH, et al. Melatonin supplementation for children with atopic dermatitis and sleep disturbance: A randomized clinical trial. JAMA Pediatr 2016;170:35-42.



  Biological Treatments for Pediatric Psoriasis: A Retrospective Observational Study on Biological Drug Survival in Daily Practice in Childhood Psoriasis Top


We discuss a study by Phan et al.[1] which evaluated the survival rates of biological therapies in children with psoriasis in real-life conditions. This was an observational retrospective record review. Clinical records of 134 children reviewed. Kaplan–Meier estimates were used to analyze overall drug survival and in subgroups such as plaque psoriasis, bio-naïve, and nonnaïve patients. One hundred and eighty-four treatment courses were analyzed: 70 with etanercept, 68 with adalimumab, and 46 with ustekinumab. Factors associated with the choice of the -line biological agent were the age at initiation (younger for adalimumab, P < 0.0001), age at onset of psoriasis (younger for adalimumab and etanercept, P = 0.03), and baseline PASI (psoriasis area severity index) and PGA (physician global assessment) (both higher for adalimumab, P < 0.001). Overall drug survival rates were higher for ustekinumab than for adalimumab and etanercept (P< 0.0001) and in subgroups for all psoriasis types (P = 0.0003). Drug survival rates were higher among bio-naïve patients (P = 0.0007) than among patients who had previously failed therapy with one or more biological agents (P = 0.007). Severe adverse effects were noted in eight treatment courses. All serious adverse effects occurred in patients on tumor necrosis factor (TNF) inhibitors, and none occurred with ustekinumab-treated patients. For -line biological agents, loss of efficacy (19.2%) and primary inefficacy (8.9%) were the most common causes of discontinuation. Discontinuation because of loss of efficacy was significantly more frequent with etanercept (34.9%) than with adalimumab (9.1%) and ustekinumab (0%).


  Comment Top


Drug survival is defined as the time from initiation to discontinuation (stop/switch) of biologic therapy on a registry. It is a marker for treatment sustainability in chronic diseases such as psoriasis.[2] The strength of this study is the exclusion of cases which were part of clinical trials, which gives a more reliable real-life assessment. Being a multicentric study, the data are more uniform and reliable. Of all the currently available biological agents, maximum data concerning its efficacy and safety in pediatric psoriasis are available for etanercept as it was the to be licensed for use in pediatric psoriasis in 2008. The findings of this study are in concordance with findings in the adult population; the drug survival rates of ustekinumab were better than TNF alpha-blockers, and the drug survival rates were higher for bionaïve population. Either primary inefficacy or loss of efficacy was the most frequent reason to switch biological as in the adult population. The biologic agents currently available for the treatment of psoriasis have been approved for continuous and indefinite use. The failure of one biologic agent often leads to switching to another, which involves an induction regimen that is significantly more expensive than a maintenance regimen.[3] This study in corroboration with similar studies in adults confirms the long drug survival rates and lower rates of adverse effects seen with ustekinumab. These data coupled with the easy scheduling of ustekinumab dosing would make it the preferred biologic agent for pediatric and adult psoriasis of all types.

Apart from the study's merits, it is very interesting to note the ever-increasing publication of the “drug survival studies” concerning the use of biologics not only in psoriasis (adults and children) but also in rheumatoid arthritis. One of the basic premises of evaluating the need of drug survival is that these drugs can be used for continuous indefinite periods in psoriasis to achieve remission and to maintain it. For a chronic disease like psoriasis which shows remissions and relapses (sometimes spontaneous remissions in summer season in tropical countries such as India), the use for continuous indefinite periods requires more debate. Another aspect to be studied is the economic costs of persistent use. While many of the pharmaceutical-funded studies on this aspect emphasize that there is no significant economic difference between patients who persist with biologics and those who discontinue it[4] (and may even be more cost-effective due to their benefit on co-morbidities, decrease in antidepressants/anxiolytic use, etc.), few other nonfunded-studied studies suggest a more cautious approach – “biologics are less effective than what physicians have been led to believe in a real-life, nonselected population.”[5]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

  1. Phan C, Beauchet A, Burztejn AC, Severino-Freire M, Barbarot S, Girard C, et al. Biological treatments for paediatric psoriasis: A retrospective observational study on biological drug survival in daily practice in childhood psoriasis. J Eur Acad Dermatol Venereol 2019. doi: 10.1111/jdv.15579.
  2. Menter A, Papp KA, Gooderham M, Pariser DM, Augustin M, Kerdel FA, et al. Drug survival of biologic therapy in a large, disease-based registry of patients with psoriasis: Results from the psoriasis longitudinal assessment and registry (PSOLAR). J Eur Acad Dermatol Venereol 2016;30:1148-58.
  3. Carrascosa JM, Notario J. Drug survival in biologic therapy. Do we know what it means? Can we calculate it? Actas Dermosifiliogr 2014;105:729-33.
  4. Lee S, Xie L, Wang Y, Vaidya N, Baser O. Evaluating the effect of treatment persistence on the economic burden of moderate to severe psoriasis and/or psoriatic arthritis patients in the U.S. department of defense population. J Manag Care Spec Pharm 2018;24:654-63.
  5. Sbidian E, Mezzarobba M, Weill A, Coste J, Rudant J. Persistence of treatment with biologics for patients with psoriasis: A real-world analysis of 16 545 biologic-naïve patients from the French national health insurance database (SNIIRAM). Br J Dermatol 2019;180:86-93.







 

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