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  1. https://doi.org/10.1016/j.amsu.2021.102978Get rights and content Under a Creative Commons license open access Highlights • Cushing syndrome is an abnormality resulting from high level of blood glucocorticoids. • Iatrogenic Cushing syndrome due to the overuse of topical corticosteroids is rarely reported. • This report presents a case of topical corticosteroid induced iatrogenic Cushing syndrome in an infant. Abstract Introduction Cushing syndrome (CS) is an endocrinological abnormality that results from a high level of glucocorticoids in the blood. Iatrogenic CS due to the overuse of topical corticosteroids is rarely reported. The current study aims to present a rare case of topical corticosteroid induced iatrogenic CS in an infant. Case presentation A 4-month-old female infant presented with an insidious onset of face puffiness that progressed over a 2-month period. The mother reported to have used a cream containing Betamethasone corticosteroid 5–8 times a day for a duration of 3 months to treat diaper dermatitis. Laboratory findings revealed low levels of adrenocorticotrophic hormone (ACTH) and serum. Abdominal ultrasound showed normal adrenal glands. The topical corticosteroid was halted and physiologic topical hydrocortisone doses were administered. Clinical discussion Infants are more likely to acquire topical corticosteroid induced iatrogenic CS due to their thin and absorptive skin, higher body surface area, and the high prevalence of conditions that necessitates the use of these medications. Most iatrogenic CS cases following topical steroid application have been reported in infants with diaper dermatitis that are most commonly treated with Clobetasol and Bethamethasone. Conclusion Infants are susceptible to develop CS due to topical corticosteroid overuse. Hence, physicians need to consider this in infantile CS cases, and take appropriate measures to avoid their occurrence. Previous article in issue Next article in issue Keywords Cushing syndrome Infant Iatrogenic Topical corticosteroid 1. Introduction Cushing syndrome (CS) is a reversible endocrinological abnormality that results from high level of cortisol or other glucocorticoids in the blood [1]. It can be caused by either endogenous factors such as excess steroid production and secretion due to adrenal or pituitary tumors, or exogenously through prolonged use of corticosteroid medications resulting in iatrogenic CS [2]. Iatrogenic CS due to the overuse of oral or parenteral corticosteroids is common, however, while topical corticosteroids are one of the most widely prescribed medications by dermatologists, they are less frequently reported to cause iatrogenic CS [3,4]. Even though CS is very rare in the pediatric population with an annual incidence of only 5 cases per million, children of the pediatric age have a higher risk of developing iatrogenic CS, which is likely due to the high prevalence of conditions that necessitates the use of topical corticosteroids and the thinness of their skin that can more easily absorb the steroid [5,6]. The aim of the current study is to present a rare case of topical corticosteroid induced iatrogenic CS in an infant. SCARE guidelines are considered in writing this report [7]. 2. Case presentation 2.1. Patient information A 4-month-old female infant presented with an insidious onset of puffiness of the face; the swelling progressed over a period of 2 months without any other associated symptoms. The infant's prenatal, developmental, and family history were insignificant, and she was born full term to consanguineous parents via caesarian delivery. After delivery she did not require neonatal intense care unit (NICU) and was discharged in good health. She has been given both bottle and breastfeeding every one to two hrs, and she has received all the required vaccinations at their proper times. The mother reported to have used a topical corticosteroid cream (Optizol-B cream; a combination of Clotrimazole and Betamethasone) for a period of 3 months with a dose of 5–8 times a day to treat diaper dermatitis of the infant. 2.2. Clinical findings The infant's physical examination revealed facial puffiness (Moon face) with no body edema, and cutaneous examination showed the diaper rash without any other cutaneous manifestations. The infant was vitally stable with no dysmorphic features and no skeletal deformities. Her growth parameters were within normal limits, and her systemic examination was unremarkable. 2.3. Diagnostic approach Laboratory findings revealed low adrenocorticotropic hormone (ACTH) level in the blood measuring 5.9 p.m./l, a serum cortisol level of 24 nmol/l, and normal serum sodium and potassium levels of 144 mEq/l and 4.8 mmol/l, respectively. Abdominal ultrasonography (US) showed normal adrenal glands. 2.4. Therapeutic intervention The topical corticosteroid cream that contained Bethamethasone was halted and oral hydrocortisone was given (10 mg/m2) tapered over one month. The patient was given a card addressing Cushing syndrome to inform the health care providers in case of emergency situation or unexpected surgical intervention. 2.5. Follow-up and outcome The infant's facial puffiness was significantly improved after 7-month follow-up of the patient. 3. Discussion CS is an endocrinological disorder resulting from high glucocorticoid level in the blood, it is categorized into ACTH dependent (due to pituitary tumors or excess ACTH administration) or ACTH independent CS (due to adrenal neoplasms or excessive glucocorticoid intake) [8,9]. Under normal circumstances, ACTH is secreted by the pituitary gland which in turn stimulates the secretion of cortisol by the adrenal glands [10]. Prolonged exogenous corticosteroid administration can lead to a number of adverse effects based on potency and duration of the treatment, including the suppression of hypothalamic-pituitary-adrenal (HPA) axis and iatrogenic CS, severe infections, and failure to thrive [11]. While iatrogenic CS is frequent with prolonged administration of oral or parenteral corticosteroids, it is occurrence due to topical corticosteroids have rarely been reported [12]. Multiple factors can increase the probability of acquiring the condition, such as corticosteroid potency, amount and frequency of application, age, skin quality, presence of occlusion, and duration of application [4]. In general, infants are more likely to develop topical corticosteroid induced iatrogenic CS, this is due to their thin and absorptive skin, higher body surface area, underdeveloped skin barrier, and the high prevalence of conditions that necessitates the use of these medications [5,6]. Most iatrogenic CS cases following topical steroid application have been reported in infants with diaper dermatitis [8]. This was also the case in this study. This is likely because the diaper area provides occlusion, the perineal skin has intrinsically absorptive properties, the steroid causes local skin atrophy, and percutaneous absorption is even more increased as the result of skin inflammation [13]. The most frequently used corticosteroid for the treatment of diaper dermatitis is reported to be Clobetasol followed by Bethamethasone, with a mean application duration of 2.75 (1–17) months to induce cortisol and ACTH levels suppression [4]. Typical clinical manifestations of CS include facial puffiness (Moon face), generalized body edema and obesity, hirsutism, buffalo hump, hypertension, skin fragility, and purple striae [3,5]. The causative corticosteroid in the current case was Bethamethasone that only resulted in facial puffiness (Moon face) without generalized body edema. A specific and definitive diagnostic approach for iatrogenic CS is currently lacking [5]. However, prolonged exogenously administered glucocorticoids can suppress ACTH secretion which results in dismissing the need for proper endogenous production of cortisol [14]. Hence, almost all iatrogenic CS cases are associated with low ACTH and cortisol levels which can aid in the diagnosis of the condition [8]. Same findings were observed in this case. According to multiple studies, exogenous corticosteroid administration can often lead to HPA axis suppression alongside CS [15,16]. However, topical corticosteroid induced iatrogenic CS has been reported without HPA axis suppression [8]. The management of these cases start with the cessation of the causative corticosteroid medication and administration of physiologic topical hydrocortisone [5]. The same approach was followed in this study. In order to prevent the development of this condition in the first-place; clinicians should avoid prescribing high potency corticosteroids in the treatment of infantile dermatological disorders and instead choose low potency topical steroids, and also parents should be advised not to overuse these medications and only apply a thin layer to the affected area [6]. In conclusion, even though iatrogenic CS in infants is rare, overuse of topical corticosteroids can lead to their occurrence. Hence, physicians need to consider extensive steroid use as a causative agent of infantile CS. Appropriate measures need to be taken to avoid their occurrence by prescribing less potent steroids, limiting the use of high potent steroids, and informing parents about adverse effects of steroid overuse in infants. Source of funding None is found. Author statement Soran Mohammed Ahmed: physician managing the case, follow up the patient, and final approval of the manuscript. Shaho F. Ahmed, Snur Othman, Berwn A. Abdulla, Shvan M.Hussein, Abdulwahid M.Salih, and Fahmi H. Kakamad: literature review, writing the manuscript, final approval of the manuscript. Patient consent Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request. Provenance and peer review Not commissioned, externally peer-reviewed. Guarantor Fahmi Hussein Kakamad. Declaration of competing interest None to be declared. References [1] A. Tiwari, M. Goel, P. Pal, P. Gohiya Syndrome in the pediatric age group: a rare case report Indian journal of endocrinology and metabolism, 17 (1) (2013), pp. S257-S258 View Record in ScopusGoogle Scholar [2] R.R. Lonser, L. Nieman, E.H. Oldfield Cushing's disease: pathobiology, diagnosis, and management J. Neurosurg., 126 (2) (2017), pp. 404-417 View PDF View Record in ScopusGoogle Scholar [3] A. Ozdemir, V.N. Bas Iatrogenic Cushing's syndrome due to overuse of topical steroid in the diaper area J. Trop. Pediatr., 60 (5) (2014), pp. 404-406 View PDF CrossRefView Record in ScopusGoogle Scholar [4] T. Tempark, V. Phatarakijnirund, S. Chatproedprai, S. Watcharasindhu, V. Supornsilchai, S. Wananukul Exogenous Cushing's syndrome due to topical corticosteroid application: case report and review literature Endocrine, 38 (3) (2010), pp. 328-334 View PDF CrossRefView Record in ScopusGoogle Scholar [5] L. Alkhuder, H. Mawlawi Infantile iatrogenic cushing syndrome due to topical steroids Case reports in pediatrics, 9 (1) (2019), pp. 1-4 View PDF CrossRefView Record in ScopusGoogle Scholar [6] C.W. Ho, K.Y. Loke, Y.Y. Lim, Y.S. Lee Exogenous Cushing syndrome: a lesson of diaper rash cream Hormone research in paediatrics, 82 (6) (2014), pp. 415-418 View PDF CrossRefView Record in ScopusGoogle Scholar [7] R.A. Agha, T. Franchi, C. Sohrabi, G. Mathew, A. Kerwan, A. Thoma, et al. The SCARE 2020 guideline: updating consensus Surgical CAse REport (SCARE) guidelines Int. J. Surg., 84 (2020), pp. 226-230 ArticleDownload PDFView Record in ScopusGoogle Scholar [8] F. Özgüç Çömlek, S. Örüm, S. Aydın, F. Tütüncüler Exogenous Cushing syndrome due to misuse of potent topical steroid Pediatr. Dermatol., 35 (2) (2018), pp. e121-e123 View PDF CrossRefView Record in ScopusGoogle Scholar [9] A. Rustowska, A. Wilkowska, R. Nowicki Iatrogenic Cushing syndrome due to topical glicocorticosteroid therapy Dermatol. Online J., 4 (4) (2013), pp. 503-505 View PDF CrossRefView Record in ScopusGoogle Scholar [10] C.A. Stratakis Diagnosis and clinical genetics of Cushing syndrome in pediatrics Endocrinol. Metabol. Clin, 45 (2) (2016), pp. 311-328 ArticleDownload PDFView Record in ScopusGoogle Scholar [11] M.K. George, A. James, S. Reddy, B. Yasaswini, T.R. Ak, T. Sivakumar Topical steroid induced iatrogenic cushing syndrome in young adult age group: a case report Indian Journal of Pharmacy Practice, 8 (2) (2015), pp. 87-88 View PDF CrossRefView Record in ScopusGoogle Scholar [12] Z. Şiklar, İ. Bostanci, Ö. Atli, Y. Dallar An infantile Cushing syndrome due to misuse of topical steroid Pediatr. Dermatol., 21 (5) (2004), pp. 561-563 View PDF CrossRefView Record in ScopusGoogle Scholar [13] O. Taylor, J.D. Mejia‐Otero, G.M. Tannin, K. Gordon Topical triamcinolone induced Cushing syndrome: a case report Pediatr. Dermatol., 37 (3) (2020), pp. 582-584 View PDF CrossRefView Record in ScopusGoogle Scholar [14] A.W. Root, D.I. Shulman Clinical adrenal disorders Pediatric Endocrinology, Mechanisms, Manifestations, and Management, Lippincott Williams & Wilkins, Philadelphia (2004), pp. 568-600 Google Scholar [15] A. Güven, Ö. Gülümser, T. Özgen Cushing's syndrome and adrenocortical insufficiency caused by topical steroids: misuse or abuse? J. Pediatr. Endocrinol. Metab., 20 (11) (2007), pp. 1173-1182 View Record in ScopusGoogle Scholar [16] F. Tütüncüler, M. Tekin, D. Balci, Ö. Şahaloğlu Iatrogenic Cushing syndrome due to topical steroid administration in an infant Balkan Med. J., 27 (1) (2010), pp. 95-97 View PDF View Record in ScopusGoogle Scholar © 2021 The Authors. Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd. From https://www.sciencedirect.com/science/article/pii/S2049080121009286?via%3Dihub
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