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REVIEW OF CURRENT LITERATURE
Year : 2018  |  Volume : 19  |  Issue : 4  |  Page : 375-379

Hot topics in pediatric dermatology


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

Date of Web Publication28-Sep-2018

Correspondence Address:
Dr. Dipankar De
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_101_18

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How to cite this article:
Thakur V, Dipankar De. Hot topics in pediatric dermatology. Indian J Paediatr Dermatol 2018;19:375-9

How to cite this URL:
Thakur V, Dipankar De. Hot topics in pediatric dermatology. Indian J Paediatr Dermatol [serial online] 2018 [cited 2020 Sep 21];19:375-9. Available from: http://www.ijpd.in/text.asp?2018/19/4/375/242403




  Allergic Contact Dermatitis and Polysensitization in Atopic Dermatitis: Impact on Course of Disease Top


We discuss a recent study by Boonstra et al.[1] that investigated the occurrence of allergic contact dermatitis (ACD) and rate of polysensitization in difficult-to-treat atopic dermatitis (AD). This was a retrospective study analyzing patch test results of 48 patients of AD unresponsive to conventional treatments. The aim of the study was to assess the rate of ACD and rate of polysensitization and to identify the common allergens. Furthermore, dynamic patch test analysis was done to differentiate between true allergic and irritative properties of the allergens. Of total 48 patients, 75% had positive patch test to one allergen and 39% were polysensitized, i.e., an allergic reaction to three or more different group of allergens. The most common allergens were wool alcohols, bichromate, nickel, surfactants cocamidopropyl betaine (CABP) and dimethylaminopropylamine (DMAPA), and fragrance mix I. Most of the reactions were allergic on dynamic pattern analysis. Based on these results, the authors concluded that difficult-to-treat AD patients suffered from multiple concomitant contact allergies and proposed this as a reason for AD becoming difficult-to-treat.

Comments

This study showed a very high prevalence of ACD in difficult-to-treat AD in contrast with the previous studies. In a study by Lubbes et al., the prevalence of contact sensitization in AD patients was 48% as compared to 47% in non-AD patients.[2] In another study by Simonsen et al., 30% of AD patients had at least one positive patch test reaction and 17% with at least one contact allergy relevant to skin symptoms.[3] The severity of the disease correlated with the risk of contact sensitization. The reason for high prevalence as stated by the authors is the selected difficult-to-treat AD patients based on the eczema area and severity index (EASI) >25, but EASI score was available in only 54% patients and was determined in retrospect by experienced observers. The rate of polysensitization in difficult-to-treat AD was also higher (39%) in this study as compared to ACD patients (14%–16%).[4] However, AD is a known risk factor for polysensitization and impaired skin barrier in AD patients facilitates penetration of allergens increasing chances of sensitization. Most common allergens were wool alcohols and other surfactants such as CABP and DMAPA, fragrance mix I, and bichromate. These hydrophilic surfactants' permeability is increased because of impaired lipid organization of stratum corneum in AD patients. Impaired skin barrier leading to penetration of the allergens such as wool alcohols present in the emollients and therapeutic ointments may elicit ACD and cause a flare of eczema leading to vicious cycle of more dermatitis-more treatment, causing difficult-to-treat AD. However, other causes of difficult-to-treat AD such as lack of compliance, secondary infections, and other triggers such as food and psychosocial factors were not explored in this study. This study showed true allergic nature of wool alcohols and CAPB/DMAPA in dynamic pattern analysis which has been earlier debated to have irritant properties only. Patch test is an important tool in the diagnostic workup of AD patients but is uncommonly undertaken due to practical difficulty in performing patch test because of active dermatitis and immunosuppressive treatment. The authors suggest that treatment with emollients, anti-inflammatory ointments free of allergens such as wool alcohols, surfactants, and fragrance mix, and regular bleach baths are usually effective and patch test can be done subsequently. The strengths of the study are systematic establishment of relevance of positive patch test. Although nickel and cobalt were found to be common sensitizers, they were seldom of current relevance. The main limitations of this study were its retrospective nature and small sample size. AD has increased rates of concomitant ACD and polysensitization contributing to persistence of skin symptoms, and these may be even higher in difficult-to-treat AD patients. Further research on ACD to wool alcohols generally contained in skin care products for the management of AD is warranted, particularly pertaining to their role in polysensitization and difficult-to-treat status.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

  1. 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.
  2. Lubbes S, Rustemeyer T, Sillevis Smitt JH, Schuttelaar ML, Middelkamp-Hup MA. Contact sensitization in Dutch children and adolescents with and without atopic dermatitis – –Contacective analysis. Contact Dermatitis 2017;76:151-9.
  3. Simonsen AB, Johansen JD, Deleuran M, Mortz CG, Skov L, Sommerlund M, et al. Children with atopic dermatitis may have unacknowledged contact allergies contributing to their skin symptoms. J Eur Acad Dermatol Venereol 2018;32:428-36.
  4. Belhadjali H, Mohamed M, Youssef M, Mandhouj S, Chakroun M, Zili J, et al. Contact sensitization in atopic dermatitis: Results of a prospective study of 89 cases in Tunisia. Contact Dermatitis 2008;58:188-9.



  Methotrexate and Cyclosporine as First-Line Immunosuppressive Agents in Atopic Dermatitis: A Comparison of Treatment Profile Top


The next study we discuss is by Law Ping Man et al.[1] which has compared two first-line immunosuppressive agents, methotrexate and cyclosporine in atopic dermatitis (AD) using drug survival and postdrug survival analyses. This was a retrospective study of 56 moderate-to-severe AD patients treated with one of the two first-line agents, methotrexate or cyclosporine. Drug survival was defined as duration on treatment with either methotrexate or cyclosporine and postdrug survival as interval between stopping either of these two first-line agents and initiation of second-line agents such as mycophenolate mofetil, azathioprine, intravenous immunoglobulin and omalizumab. The results of the study showed that 89% of patients had childhood onset of AD, and among 56 patients, 25 (44.6%) and 31 (55.4%) patients received cyclosporine and methotrexate as the first-line immunosuppressive agent, respectively. A higher number of patients had discontinued treatment with cyclosporine (20/26; 76.9%) as compared to methotrexate (18/31; 58%) at the end of study period due to disease control, failure of therapy, or side effects. Disease control was more in patients treated with methotrexate while failure to therapy and side effects were seen more commonly in patients treated with cyclosporine. The median drug survival for methotrexate and cyclosporine was 23 and 8 months, respectively, indicating shorter treatment duration and rapid clearance of disease with cyclosporine. The median duration of postdrug survival for methotrexate and cyclosporine was 12 and 2 months, respectively. After 6 months of discontinuation of treatment, the second-line treatment was needed in 28% and 75% of the patients with methotrexate and cyclosporine, respectively. Thus, the authors concluded that the methotrexate may provide a better treatment profile than cyclosporine for long-term management of moderate-to-severe AD.

Comments

Drug survival studies have recently emerged in the field of dermatology, mostly limited to biologics in psoriasis and have been proven quite informative in real-life settings. There have been clinical trials comparing the efficacy and safety of methotrexate and cyclosporine in moderate-to-severe AD, but the results of these trials are difficult to generalize in real-life settings. This was the first comparative study in daily practice between methotrexate and cyclosporine using drug survival and postdrug survival analyses. In previous studies using drug survival for methotrexate and cyclosporine individually, duration of treatment was consistent with the results of this study.[2],[3] Shorter drug survival with cyclosporine may be explained by its rapid efficacy in AD and safety concerns about nephrotoxicity and carcinogenesis. In this study, the use of postdrug survival analysis in AD was a new tool providing the information about drug-free interval, which is a major concern for patients and physicians. Postdrug survival for cyclosporine was shorter than methotrexate suggesting inability of cyclosporine to maintain remission and pointing toward probable immunomodulatory effects of methotrexate. Furthermore, drug survival analysis can provide information about reasons for discontinuation of treatment. More such studies are coming up in the field of management of chronic diseases and estimation of postdrug survival can be an additional tool for the assessment of drug-free period and can help in developing strategies for long-term management of chronic skin diseases with immunosuppressive agents.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

  1. Law Ping Man S, Bouzillé G, Beneton N, Safa G, Dupuy A, Droitcourt C, et al. Drug survival and postdrug survival of first-line immunosuppressive treatments for atopic dermatitis: Comparison between methotrexate and cyclosporine. J Eur Acad Dermatol Venereol 2018. doi: 10.1111/jdv.14880.
  2. van der Schaft J, Politiek K, van den Reek JM, Christoffers WA, Kievit W, de Jong EM, et al. Drug survival for ciclosporin A in a long-term daily practice cohort of adult patients with atopic dermatitis. Br J Dermatol 2015;172:1621-7.
  3. Politiek K, van der Schaft J, Coenraads PJ, de Bruin-Weller MS, Schuttelaar ML. Drug survival for methotrexate in a daily practice cohort of adult patients with severe atopic dermatitis. Br J Dermatol 2016;174:201-3.



  Association of Pediatric Morphea with Inflammatory Arthritis: Implications on Management Top


Our next study of interest is by Kashem et al.,[1] who investigated the association of pediatric morphea with inflammatory arthritis. In this study, a retrospective review of 53 pediatric morphea patients was done with respect to subtype of morphea, joint involvement, immunologic findings, and treatment modalities. The results of the study showed that 20.8% of patients predominantly in girls with type I & II skin with generalized or linear subtype of morphea had inflammatory arthritis, mostly polyarthritis. However, there was no correlation between the site of joint involvement and the site of morphea lesions. Inflammatory markers were not elevated in patients with arthritis. However, antinuclear antibody (ANA) positivity was significantly higher (80%) in these patients as compared to morphea patients without arthritis (38%). All of those with arthritis received methotrexate, in combination with other modalities for treatment. Use of mycophenolate mofetil, hydroxychloroquine and phototherapy was significantly more frequent in those with arthritis. While there was improvement in morphea after treatment in majority, a few patients with inflammatory arthritis did not respond to immunosuppressive medications. The authors concluded that both morphea and inflammatory arthritis may be a manifestation of ongoing systemic inflammatory process and the association may have implications on the management of these patients.

Comments

Morphea (localized scleroderma) was thought to be confined to the skin without any internal organ involvement. However, studies in the recent past have shown extracutaneous involvement in approximately one-fourth of morphea patients.[2] These include musculoskeletal, neurologic, vascular, gastrointestinal, and ocular manifestations. Approximately 25% of patients with morphea have joint involvement in the form of arthralgias, arthritis, joint contractures, and decreased mobility.[2] Extent of joint involvement is more in generalized morphea. However, the site of joint involvement is not related to the site of cutaneous involvement. In this study, arthritis was found in 20.8% of patients and was more common in linear and generalized subtypes. Inflammatory arthritis at distant sites from morphea plaques suggests systemic inflammatory process rather than a local mechanism. Furthermore, a higher proportion of morphea patients with inflammatory arthritis having ANA positivity support this hypothesis. In a study by Torok et al., levels of circulating interferon gamma and interleukin 17 were found significantly higher in pediatric morphea patients as compared to controls.[3] These cytokines have also been implicated in the pathogenesis of inflammatory arthritis in various studies. Thus, possibility of shared immunopathology between morphea and inflammatory arthritis should be further explored and may allow management of these with more targeted biological therapies in addition to immunosuppressive agents. Based on the findings of this study, systematic evaluation and careful monitoring of all pediatric morphea patients for inflammatory arthritis should be carried out, especially in patients with linear and generalized morphea.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

  1. Kashem SW, Correll CK, Vehe RK, Hobday PM, Binstadt BA, Maguiness SM, et al. Inflammatory arthritis in pediatric patients with morphea. J Am Acad Dermatol 2018;79:47-51.
  2. Zulian F, Vallongo C, Woo P, Russo R, Ruperto N, Harper J, et al. Localized scleroderma in childhood is not just a skin disease. Arthritis Rheum 2005;52:2873-81.
  3. Torok KS, Kurzinski K, Kelsey C, Yabes J, Magee K, Vallejo AN, et al. Peripheral blood cytokine and chemokine profiles in juvenile localized scleroderma: T-helper cell-associated cytokine profiles. Semin Arthritis Rheum 2015;45:284-93.



  Periorbital Infantile Hemangioma – Factors Associated with Ocular Morbidity Top


Here, we discuss a study by Samuelov et al.[1] assessing the clinical features of periorbital infantile hemangioma (IH) associated with adverse ocular outcomes. This study was a retrospective analysis of 96 patients seen by both pediatric dermatologist and ophthalmologist with periocular IHs over a 21-year period, defined as hemangiomas involving eyelids, canthi, glabella, lower forehead, eyebrows, and temples. Involuted hemangiomas were excluded from the study. Large hemangiomas were defined as diameter >1 cm, 1 cm cut-off was taken as this corresponds to horizontal approximate diameter of the cornea in the newborn. Ptosis was present in 35% patients and was found significantly associated with large hemangiomas, deeper involvement, and upper eyelid involvement. Amblyogenic astigmatism and amblyopia were found in 16% and 10% of patients, respectively and were significantly associated with larger hemangiomas, deeper involvement, and upper eyelid involvement. No patient with size of hemangioma < 1 cm developed amblyopia. Out of these, most significant predictive factor was size of the hemangiomas. Patients with large hemangiomas were found to have 21 times higher risk of developing amblyopia. Authors concluded that patients with these features should be promptly referred to a pediatric ophthalmologist and treated to prevent permanent functional impairment. Lower eyelid and involvement of canthi were not associated with any adverse ocular outcome.

Comments

IHs are the most common benign vascular tumors of infancy, mostly having spontaneous resolution without any sequelae. Periocular IHs may result in astigmatism, refractive errors, strabismus, leading to amblyopia and visual impairment. This study characterized clinical features of periocular hemangiomas associated with ocular complications. Amblyopia was found in 10% of patients with periocular hemangioma which was lower as compared to rates described in previous studies conducted by ophthalmologists. The reason for this may be overreporting of amblyopia as only severe cases are referred to ophthalmologists. However, in this study, all periocular hemangiomas were evaluated by ophthalmologists reflecting actual rates of amblyopia in this population. In a study by Alniemi et al.,[2] amblyopia was found in 19% patients with similar risk factors associated with ocular complications. A study by Schwartz et al.[3] also showed clear relationship of amblyopia with size of the lesion and upper eyelid location. Upper eyelid hemangiomas may cause a direct compression on the globe, leading to the distortion of cornea and astigmatism, and astigmatism was found to be the cause of amblyopia in 60% of patients. Other mechanism causing amblyopia is blockage of visual axis due to ptosis leading to deprivation amblyopia. Other refractive errors associated were hyperopia and myopia in 20% of patients with amblyopia. Hemangiomas located nasally can also cause ptosis, proptosis, globe displacement, or strabismus and amblyopia. In this study, most patients with astigmatism were diagnosed at the first eye examination and few of them had already developed amblyopia, possibly due to lag between development of IH and examination of the eyes. Thus, all patients with periocular hemangiomas require ophthalmological examination and those with larger hemangiomas and with other predictive risk factors for amblyopia should be evaluated early, thoroughly and monitored closely with serial visual acuity examination to prevent permanent functional impairment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

  1. 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.
  2. Alniemi ST, Griepentrog GJ, Diehl N, Mohney BG. Rate of amblyopia in periocular infantile hemangiomas. Arch Ophthalmol 2012;130:943-4.
  3. Schwartz SR, Blei F, Ceisler E, Steele M, Furlan L, Kodsi S, et al. Risk factors for amblyopia in children with capillary hemangiomas of the eyelids and orbit. J AAPOS 2006;10:262-8.



  Topical Sirolimus for the Treatment of Vascular Anomalies: Is it Universally Effective? Top


Recently, Le Sage et al.[1] assessed the efficacy and systemic toxicity of topical sirolimus in treating vascular anomalies. This was a case series of six pediatric patients aged 2–17 years with extratruncular lymphatic malformations in three patients and verrucous venous malformation, infantile hemangioma, and truncular lymphatic malformation in one patient each. One patient was treated with compounded preparation of sirolimus ointment 0.05% while others were treated with commercial oral sirolimus solution 0.1% applied topically twice daily. Sirolimus plasma levels were measured after 1 week, 1 and 3 months. A rapid and early response was seen in all three patients with extratruncular lymphatic malformations, while the patients with other three vascular anomalies did not respond to topical sirolimus. Sirolimus levels in blood were undetectable and minor adverse effects such as irritation at application site were seen. These side effects were easily managed. Thus, authors concluded that topical sirolimus is an effective treatment option for extratruncular lymphatic malformation without any systemic toxicity.

Comments

Vascular anomalies are a heterogeneous group of disorders comprising vascular tumors and vascular malformations. Various treatment modalities such as oral steroids, beta-blockers, vincristine, sclerotherapy, and debulking have been used in the past. Sirolimus is being increasingly used in vascular anomalies recently. Sirolimus was initially used successfully in Kaposiform hemangioendothelioma (KHE). The basis for its use in KHE was the lymphatic component of tumor and the activation of the PI3K/AKT/mTOR pathway in lymphangiogenesis.[2] Topical sirolimus has previously been used successfully in the treatment of lymphatic malformations, but literature supporting its use in other vascular anomalies is very sparse. In a study by Rössler et al.,[3] oral sirolimus was effective in decreasing lymphatic leakage from microcystic lymphatic malformations, but recurrence was noted after stopping treatment. In this study also, there was significant improvement in extratruncular lymphatic malformation with respect to decreased leakage and size of superficial blebs, although there was no improvement in verrucous venous malformation, truncular lymphatic malformation and infantile hemangioma. Ineffectiveness of sirolimus in these anomalies may be due to lack of lymphatic component, but studies with larger sample size are needed to establish its efficacy in other vascular anomalies. Adverse effects of oral sirolimus include mucositis, headaches, gastrointestinal effects, peripheral edema, renal dysfunction, hematological (thrombocytopenia, leukopenia, and anemia) and metabolic effects (hyperlipidemia, hyperglycemia, and hypokalemia).[4] In this study, topical sirolimus was associated with minimal adverse effects which was limited to local irritation in only one patient and blood levels of topical sirolimus were also undetectable, suggesting better safety of topical sirolimus compared to systemic therapy. Thus, topical sirolimus can be used as an alternative or an adjunct to systemic therapy in view of better safety profile as compared to oral sirolimus.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

  1. Le Sage S, David M, Dubois J, Powell J, McCuaig CC, Théorêt Y, et al. Efficacy and absorption of topical sirolimus for the treatment of vascular anomalies in children: A case series. Pediatr Dermatol 2018;35:472-7.
  2. Hammill AM, Wentzel M, Gupta A, Nelson S, Lucky A, Elluru R, et al. Sirolimus for the treatment of complicated vascular anomalies in children. Pediatr Blood Cancer 2011;57:1018-24.
  3. Rössler J, Geiger J, Földi E, Adams DM, Niemeyer CM. Sirolimus is highly effective for lymph leakage in microcystic lymphatic malformations with skin involvement. Int J Dermatol 2017;56:e72-5.
  4. Nadal M, Giraudeau B, Tavernier E, Jonville-Bera AP, Lorette G, Maruani A, et al. Efficacy and safety of mammalian target of rapamycin inhibitors in vascular anomalies: A systematic review. Acta Derm Venereol 2016;96:448-52.







 

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