Indian Journal of Paediatric Dermatology

REVIEW OF CURRENT LITERATURE
Year
: 2019  |  Volume : 20  |  Issue : 2  |  Page : 117--121

Hot Topics in Paediatric Dermatology


Vishal Thakur, Dipankar De 
 Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Correspondence Address:
Dr. Dipankar De
Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012
India




How to cite this article:
Thakur V, De D. Hot Topics in Paediatric Dermatology.Indian J Paediatr Dermatol 2019;20:117-121


How to cite this URL:
Thakur V, De D. Hot Topics in Paediatric Dermatology. Indian J Paediatr Dermatol [serial online] 2019 [cited 2019 Jun 25 ];20:117-121
Available from: http://www.ijpd.in/text.asp?2019/20/2/117/255198


Full Text



 Factors Predicting the Course of Atopic Dermatitis Through Childhood



Recently, in a study by Thorsteinsdottir et al., genetic, clinical, and environmental factors associated with the persistence of atopic dermatitis (AD) in children up to the age of 13 years were studied.[1] The study cohort included 411 children with a maternal history of asthma and were followed up till the age of 13 years. AD was diagnosed by Hanifin and Rajka's criteria and graded with the SCORAD index. Persistent AD was defined as ongoing disease at the age of 13 years, whereas no clinical symptoms without the use of topical anti-inflammatory treatment for 1 year was defined as remission. Of the 411 children, AD was diagnosed in 186 children from birth till 13 years of age and 166 of them were included in the final study group. Mothers with AD and less use of antibiotics during pregnancy and fathers with allergic rhinitis/asthma were seen more in the children in AD group. At the age of 13 years, 24% had persistent AD. The prevalence of AD was highest at the age of 2 years which declined to 11% at 13 years of age. Among heritable factors, paternal asthma and AD were significantly associated with persistent AD. However, no statistically significant association was found between persistent AD and maternal asthma and AD and allergic rhinitis and paternal allergic rhinitis. This heritage pattern can be explained by the at-risk nature of the cohort. All mothers had asthma as per the inclusion criteria and therefore, were more likely to have AD and allergic rhinitis. A significant association was observed between filaggrin mutation and persistent AD. Higher socioeconomic status and maternal education and increasing maternal age were associated with persistent AD. However, other factors such as maternal smoking, cord blood Vitamin D levels, season of birth, mode of delivery, and exposure to pets were not significantly associated with persistent AD. No associations were found between early allergic sensitization and persistent AD. Several features including Dennie–Morgan folds, anterior neck folds, white dermographism, food intolerance, and allergy were seen to be more prevalent in children with persistent AD. However, in this study, persistent AD had higher SCORAD index than AD in remission, but the difference was not statistically significant. Based on these findings, the authors concluded that an AD genetic risk score, selected minor features of Hanifin and Rajka's criteria, and social factors are risk factors for persistent AD through childhood and can help predict the disease course.

Comments

AD is a pruritic, chronic inflammatory relapsing skin condition beginning most often in infancy. Risk factors associated with AD have been described in literature, but the factors leading to the persistence of AD through childhood and beyond that are yet to be elucidated. Identification of such factors would be important in clinical practice to guide both clinicians and parents. In a recent meta-analysis, persistent AD after the age of 8 years was found in one-fifth of children with AD and was found to be associated with late onset of AD, longer duration, and severe disease.[2] However, in this study, persistent AD had higher SCORAD index than AD in remission, but without any statistical difference between the two groups. In another study, filaggrin mutations were more common in persistent AD, similar to the observation in this study, and were associated with nonuniform response to treatment.[3] AD has been reported more commonly in children in higher socioeconomic groups. This study finds higher socioeconomic status as a risk factor for persistent AD. Contact sensitization has been previously reported as a factor for persistent and difficult-to-treat disease.[4] Impaired skin barrier leads to the increased penetration of the allergens and may elicit allergic contact dermatitis leading to flare of eczema and may cause persistence of AD. However, allergic sensitization, along with asthma and rhinitis, was not found to be a significant risk factor for persistent AD. This aspect needs to be further explored. Few selected minor diagnostic features of Hanifin and Rajka's criteria were more commonly associated with persistent disease, which have not been studied previously. Knowledge about these factors along with disease severity and genetic assessment may help in predicting the course of the disease. The findings of this study require further validation as the selection of mothers with asthma for the study is the major limitation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

Thorsteinsdottir S, Stokholm J, Thyssen JP, Nørgaard S, Thorsen J, Chawes BL, et al. Genetic, clinical, and environmental factors associated with persistent atopic dermatitis in childhood. JAMA Dermatol 2019;155:50-7.Kim JP, Chao LX, Simpson EL, Silverberg JI. Persistence of atopic dermatitis (AD): A systematic review and meta-analysis. J Am Acad Dermatol 2016;75:681-7.e11.Margolis DJ, Apter AJ, Gupta J, Hoffstad O, Papadopoulos M, Campbell LE, et al. The persistence of atopic dermatitis and filaggrin (FLG) mutations in a US longitudinal cohort. J Allergy Clin Immunol 2012;130:912-7.Boonstra M, Rustemeyer T, Middelkamp-Hup MA. Both children and adult patients with difficult-to-treat atopic dermatitis have high prevalences of concomitant allergic contact dermatitis and are frequently polysensitized. J Eur Acad Dermatol Venereol 2018;32:1554-61.

 PHACE Syndrome and Ocular Complications



Our next study of interest is by Samuelov et al.,[1] which aimed to characterize the risk of negative ocular findings associated with PHACE syndrome (P – posterior fossa anomalies; H – hemangioma; A – arterial; C – cardiac; and E – eye abnormalities) by evaluating the clinical features and complete ophthalmological examination of patients with PHACE syndrome, with special emphasis on the ocular manifestations particularly associated with PHACE syndrome. This was a retrospective study of thirty patients aged 18 years or younger over a period of 15 years. All patients diagnosed as PHACE syndrome were evaluated by an ophthalmologist and were reviewed for ocular manifestations. The ocular findings were divided into complications specifically associated with PHACE syndrome or with periorbital distribution of hemangioma. Of the 30 patients, 28 had segmental distribution, with S2 segment of face being involved in 64% of patients and periorbital hemangioma in 70% (21) of patients. Only two patients had symptomatic ocular involvement, excessive tearing, and abnormal eye movements in one patient each. Nine patients had ocular complications related to periorbital distribution of hemangioma such as mild ptosis, nasolacrimal duct obstruction, astigmatism, and amblyopia, whereas only 1 patient had ophthalmological anomalies specifically associated with PHACE syndrome, i.e., Horner syndrome. No ocular complication was observed in patients with PHACE syndrome without periorbital hemangioma. The authors concluded that PHACE syndrome has a low incidence of ocular complications related specifically to the syndrome. However, periorbital hemangiomas require a complete ophthalmological examination owing to the complications associated with periocular location.

Comments

PHACE syndrome is a rare neurocutaneous syndrome characterized by infantile hemangioma and other abnormalities involving the central nervous system, cardiovascular system, and eye. The incidence of ocular abnormalities associated with PHACE syndrome has been reported as high as 10%.[2] However, results of this study showed that the ocular complications in patients with PHACE syndrome were mainly due to the periorbital location of the infantile hemangioma and the abnormality specifically associated with PHACE syndrome, i.e., Horner syndrome was seen in one patient only. Another highlight of this study was that, despite having 50% of hemangiomas in S1 segment which is reported to be most predictive of cerebrovascular and ocular involvement, only one patient had specific ocular anomaly of PHACE syndrome. This is in contrast with the previous reports which have documented higher incidences of specific ocular anomalies. Thus, patients with PHACE syndrome require full ophthalmological evaluation as the risks of ocular complications are significant due to the periocular location of hemangiomas. A previous study by the same authors has already highlighted the need for a thorough ophthalmological examination in patients with large periorbital hemangioma as direct compression on the globe by hemangioma or obstruction of visual axis due to ptosis may lead to permanent visual dysfunction.[3] Ophthalmological evaluation in patients with PHACE syndrome without a periocular hemangioma may not reveal significant anomalies. Although ocular complications are usually diagnosed by full clinical ophthalmic evaluation, MRI which is routinely done for the detection of brain and arterial anomalies in PHACE syndrome may serve as a useful adjunct in diagnosing ocular anomalies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

Samuelov L, Kinori M, Mancini AJ, Kruse LL, Wagner A, Yoon H, et al. Ocular complications in PHACE syndrome: A true association or a coincidence? J Pediatr 2019;204:214-8.e2.Metry D, Heyer G, Hess C, Garzon M, Haggstrom A, Frommelt P, et al. Consensus statement on diagnostic criteria for PHACE syndrome. Pediatrics 2009;124:1447-56.Samuelov L, Kinori M, Rychlik K, Konanur M, Chamlin SL, Rahmani B, et al. Risk factors for ocular complications in periocular infantile hemangiomas. Pediatr Dermatol 2018;35:458-62.

 Assessment of Major Clinical Events in Epidermolysis Bullosa: Impact on the Course of Disease



Our next study of interest is by Feinstein et al.,[1] in which the “milestone events” in the clinical course of epidermolysis bullosa (EB) were described. Milestone events were defined as major diagnostic and clinical events and outcomes in a child with EB. These included the timing of the clinical and molecular diagnosis of disease and other objective assessments such as time of hand surgery and gastrostomy tube placement for esophageal dilatation. This multicentric study included 644 EB patients with four subtypes, i.e., recessive dystrophic EB (RDEB), EB simplex (EBS), junctional EB (JEB), and dominant dystrophic EB. The percentage of patients in the respective groups was 43.9%, 30.1%, 9.8%, and 16.2%. The genders were equally distributed in these subtypes. Clinical symptoms at birth were present in the majority of patients in all subtypes except EBS. The highest incidence of aplasia cutis was seen in patients with RDEB. Most of the patients received a clinical diagnosis of EB within the 1st year of life, whereas a small number of patients remained undiagnosed. Confirmatory testing for EB such as electron microscopy, immunofluorescent microscopy, and genetic analysis was performed in most of the patients, with the highest rates in JEB and the lowest in EBS. Genetic analyses were performed mostly before 10 years of age in all subtypes except EBS. Age at major milestone events in the form of initial esophageal dilatation, hand surgery, development of squamous cell carcinoma (SCC), and death in patients of RDEB was 6.6 years (occurred in 37%), 8.1 years (in 22%), and 22.6 years (SCC in 6% and death in 7%), respectively. The authors concluded that assessment of these clinical events in patients with EB may lead to improved characterizations, clinical care, and better outcomes of these patients.

Comments

EB, a rare genetic disorder, has significant negative impact on the quality of life of a patient and his/her parents owing to the devastating complications associated with certain subtypes of EB. Because of its rarity, enough evidence to guide the optimal care of these patients is still lacking. Trials on emerging disease-modifying therapies or cure are going on, but seem futuristic. This study highlights an important issue about the lag period between the clinical diagnosis and the confirmatory molecular testing for EB, which may have a significant impact in modifying the course of disease by early identification and prevention of complications. Furthermore, early confirmatory testing by genetic analysis of EB plays an important role in counseling for planning further pregnancies. Reason for this lag as mentioned in the study may be unavailability of genetic analysis at certain places at a particular time and cost. However, availability of newer genetic testing panels for the diagnosis of EB may overcome these factors. The notion of this study, i.e., assessment of these events in patients with EB, is novel and encouraging as these events may improve the understanding of the clinical course. Furthermore, anticipation of the timing of complications in these patients by creating more evidence through such studies will help in modifying the disease course.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Reference

Feinstein JA, Jambal P, Peoples K, Lucky AW, Khuu P, Tang JY, et al. Assessment of the timing of milestone clinical events in patients with epidermolysis bullosa from North America. 2018. doi: 10.1001/jamadermatol.2018.4673.

 Contact Immunotherapy in Pediatric Alopecia Areata



Our next study is by Wu et al.[1] which studied the efficacy and safety of topical anthralin on alopecia areata (AA) in children. In this retrospective analysis of 37 children with AA, the mean duration of topical anthralin application was 9 months in patchy AA (65%), ophiasis pattern (5%), and alopecia totalis or universalis (30%). Most of the patients (89%) had received other treatments prior to the initiation of topical anthralin and were on concomitant therapy with topical and intralesional corticosteroids and minoxidil. The mean follow-up duration was 2.5 years, with 70% of patients having the follow-up duration of at least 6 months. Thirty-two percent of the patients had complete regrowth and 68% of the patients had more than 50% regrowth. The mean time for the earliest response and maximum response was 3.4 months and 15 months, respectively. Limited scalp involvement, i.e., patchy alopecia, showed better response than alopecia totalis or universalis. Response to topical anthralin was not associated with the age at initiation of treatment. All initially treatment-naïve patients had more than 50% regrowth, but none of the two patients on anthralin monotherapy achieved more than 50% response. Of 25 patients achieving response more than 50%, 64% of the patients had relapse of alopecia. Thus, the authors concluded that topical anthralin may be an effective therapy without significant systemic adverse effects. However, longer treatment duration is needed to achieve maximum efficacy and may be limited by high rates of relapse and cutaneous adverse effects.

Comments

AA is a chronic relapsing autoimmune disorder causing nonscarring hair loss. Contact immunotherapy is one of the treatment options for AA, apart from corticosteroids (systemic, topical, and intralesional) and other immunosuppressive agents. The most commonly used contact allergens are diphenylcyclopropenone (DPCP) and squaric acid dibutyl ester (SADBE). Topical anthralin has also been used as a contact sensitizer in different concentrations. Several studies using contact immunotherapy have shown variable success rates ranging from 4% to 81%.[2] These variations may be due to the differences in the study populations and criteria for classification and treatment regimens used in individual study. A recent meta-analysis which assessed DPCP and SADBE as contact immunotherapeutic agents reported mean success rate of 24.9%–74.6%.[2] Severe disease, longer duration of disease, atopy, and nail involvement were significantly associated with poor response.[2] Topical anthralin has shown its efficacy in severe refractory disease, achieving partial or complete growth in 70% of patients in a recent randomized controlled trial.[3] In the retrospective analysis discussed above, response more than 50% was seen in 68% of patients, but most of these patients were on other treatment modalities along with topical anthralin which might have significantly altered the outcome in this study. Another limitation of this study was the use of different anthralin concentrations, frequency, and duration of application. Another retrospective study showed the efficacy of anthralin in AA, in which the combination of DPCP and anthralin was found more effective than DPCP alone. A shorter duration of treatment with the combination of DPCP and anthralin was required.[4] Contact immunotherapy with anthralin is an effective modality for the treatment of AA. Significant adverse effects associated with its use such as eczematous reactions, blistering, lymphadenopathy, and pigmentary changes in addition to high rate of relapse after treatment discontinuation are limitations. Emphasis on proper counseling and education about disease course and prognosis is required to improve patients' adherence to treatment and clinical outcome.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

Wu SZ, Wang S, Ratnaparkhi R, Bergfeld WF. Treatment of pediatric alopecia areata with anthralin: A retrospective study of 37 patients. Pediatr Dermatol 2018;35:817-20.Lee S, Kim BJ, Lee YB, Lee WS. Hair regrowth outcomes of contact immunotherapy for patients with alopecia areata: A systematic review and meta-analysis. JAMA Dermatol 2018;154:1145-51.Özdemir M, Balevi A. Bilateral half-head comparison of 1% anthralin ointment in children with alopecia areata. Pediatr Dermatol 2017;34:128-32.Durdu M, Ozcan D, Baba M, Seckin D. Efficacy and safety of diphenylcyclopropenone alone or in combination with anthralin in the treatment of chronic extensive alopecia areata: A retrospective case series. J Am Acad Dermatol 2015;72:640-50.

 Risk Factors of Late Growth of Infantile Hemangioma



Our next study of interest is by O'Brien et al.,[1] which analyzed the clinicodemographic characteristics of children with infantile hemangioma (IH) showing growth after 3 years of age. In this retrospective study, 59 children with late growth, i.e., after 36 months of age, were reviewed for patient demographics, clinical characteristics of hemangioma, previous treatment, and associated anomalies. The study cohort showed a female preponderance and segmental hemangiomas in 38/59 (64%) patients, with S3 segment of face being the most common location. Multisegmental hemangiomas were present in 17/38 (45%) patients. Large hemangiomas, i.e., >10 cm2, were present in 45/59 (76%) patients and >100 cm2 in 26/59 (44%) patients. In 93% of the patients, regrowth of IH was seen in the head-and-neck region and 88% of them had deep or mixed hemangiomas. PHACE syndrome (P – posterior fossa anomalies; H – hemangioma; A – arterial; C – cardiac; and E – eye abnormalities) was seen in 20/38 (53%) patients with segmental hemangioma. The clinical features of late growth included increase in redness and discoloration in 42 (71%) patients, increase in volume in 42 (71%) patients, and increase in telangiectasia in 4 (7%) patients. Propranolol alone or propranolol with systemic steroids were given to 50 (84%) patients during the initial growth phase, out of which 41 (84%) patients reported rebound after the discontinuation of propranolol. Late growth of hemangiomas was reported till 8.5 years of age. To summarize, late growth of IH was associated with large hemangiomas, segmental hemangiomas involving the head-and-neck region, deep or mixed component, and associated PHACE syndrome.

Comments

IHs are the most common benign vascular tumors of infancy completing proliferative phase by 9 months of age followed by spontaneous resolution by the age of 3 years in most of the cases. Regrowth after initial regression has been observed but less commonly. Few studies in literature have tried to characterize IHs associated with regrowth after initial resolution. The age of late growth has not been defined yet. However, regrowth after 3 years is unusual; thus, the criteria for late growth used in this study seem to be acceptable. Similar factors as reported in this study have been found to be associated with late growth in previous studies by Brandling-Bennett et al.[2] and Phillips et al.[3] The reasons for late growth of IHs have been hypothesized to their origin from fetal mesenchymal cells[4] and retention of stem cell properties even after involution; persistence of growth hormone receptors' positive hemangioma stem cells and their response to endogenous growth hormone during growth spurts in childhood;[5] and systemic therapy such as propranolol decreasing endothelial cell proliferation without altering stem cell reservoir,[6] leading to rebound after the stoppage of therapy. However, more research is needed to further confirm these speculative mechanisms associated with late growth and guide the clinicians regarding the course of IHs.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

O'Brien KF, Shah SD, Pope E, Phillips RJ, Blei F, Baselga E, et al. Late growth of infantile hemangiomas in children >3 years of age: A retrospective study. J Am Acad Dermatol 2019;80:493-9.Brandling-Bennett HA, Metry DW, Baselga E, Lucky AW, Adams DM, Cordisco MR, et al. Infantile hemangiomas with unusually prolonged growth phase: A case series. Arch Dermatol 2008;144:1632-7.Phillips RJ, Crock CM, Penington AJ, Bekhor PS. Prolonged tumour growth after treatment of infantile haemangioma with propranolol. Med J Aust 2017;206:131.Huang L, Nakayama H, Klagsbrun M, Mulliken JB, Bischoff J. Glucose transporter 1-positive endothelial cells in infantile hemangioma exhibit features of facultative stem cells. Stem Cells 2015;33:133-45.Munabi NC, Tan QK, Garzon MC, Behr GG, Shawber CJ, Wu JK. Growth hormone induces recurrence of infantile hemangiomas after apparent involution: Evidence of growth hormone receptors in infantile hemangioma. Pediatr Dermatol 2015;32:539-43.Lee D, Boscolo E, Durham JT, Mulliken JB, Herman IM, Bischoff J. Propranolol targets the contractility of infantile haemangioma-derived pericytes. Br J Dermatol 2014;171:1129-37.