Leena Patel

Hypothalamic-pituitary-adrenal function and glucocorticoid sensitivity in atopic dermatitis.

Objectives. Topical glucocorticoids (GCs) fail to produce a clinical response in some children with atopic dermatitis (AD), suggesting that GC resistance may be present. To determine whether such resistance is generalized or specific to diseased skin, hypothalamic-pituitary-adrenal (HPA) axis function has been assessed in children with moderate to severe AD, who showed a variable response to treatment with topical GC. Study Design. Thirty-five patients (.7–18.7 years old; median: 9.3 years) with AD requiring topical GCs from infancy underwent a low-dose adrenocorticotrophin hormone (ACTH; Synacthen) test (LDST) (500 ng/1.73 m2 ACTH). Groups 1 (7 patients), 2 (17 patients), and 3 (4 patients) used mild, moderate, or potent/very potent topical preparations, respectively. Group 4 (7 boys with severe, treatment-resistant disease) had received GC in at least 1 form (inhaled ± intranasal ± oral) in addition to varying potencies of topical GC. Fourteen healthy subjects (3.8–17.3 years old) served as control subjects. Group 4 patients had a daytime plasma cortisol profile and 08.00 hours measurement of plasma ACTH and its precursors. Results. The response to ACTH for groups 1 and 2 did not differ from that of control subjects. Group 3 had lower peak, increment, and area under curve cortisol responses than those in controls, whereas group 4 had lower baseline, peak, and area under curve cortisol responses. Eight patients failed the LDST (peak cortisol <500 nmol/L and increment <200 nmol/L): controls = 0/14, group 1 = 0/7, group 2 = 1/17, group 3 = 4/4, and group 4 = 3/7. Treatment score (based on GC potency, area treated, and duration) was the only factor to influence peak cortisol response on LDST (r 2 = 24%). In group 4, only 1 of 7 patients had a cortisol profile within the normal range but he failed the LDST. In the 5 subjects with an 08.00 hours cortisol <300 nmol/L, the matched ACTH level was inappropriately low. Conclusions. HPA suppression was rarely found in children or adolescents with moderate to severe AD who used mild or moderately potent topical GCs over many years. However, HPA suppression was common in those receiving potent topical GC preparations or a combination of GC routes of administration. In those with severe AD, evidence of HPA suppression but lack of clinical response to GC treatment excluded significant generalized GC resistance. This would suggest that localized resistance to GCs within the diseased skin may be part of the aetiopathogenesis of severe AD.

Atopic eczema is associated with delayed maturation of the antibody response to Pneumococcal vaccine

The aim of this study was to investigate a previously undocumented observation, that children with atopic eczema under 9 years of age tended to have a poor antibody response to Pneumococcal vaccination. Thirty‐five children (mean age 8·8 years, range 3–16 years) with moderate to severe atopic eczema but no history of systemic infection were studied retrospectively. Pneumococcal antibody responses after immunization with Pneumovax II were compared with a hospital control group consisting of 36 children (mean age 6·0 years, range 3–16 years) with recurrent upper respiratory tract infections. Only 17% of children with atopic eczema aged 3–8 years responded to Pneumovax. This response was significantly poorer than that of the controls (57%) (odds ratio 0·20, 95% confidence interval (CI) 0·05–0·84, P = 0·03). There were no significant differences in the levels of total IgG2, the component of IgG associated with protective antibody responses to Pneumococcus between the two groups. Delay in maturation of the total IgG and IgG2 antibody response to Pneumococcus is a feature in this group of children with moderately severe atopic eczema.

Adrenal function following topical steroid treatment in children with atopic dermatitis

Summary Adrenal suppression is a potential complication of topical corticosteroid treatment in atopic dermatitis. We used a low‐dose adrenocorticotrophic hormone (ACTH) test (500 ng/1.73 m2) to detect subtle changes in adrenal glucocorticoid function in 14 prepubertal children with moderate or severe atopic dermatitis affecting 16–90% (median 58%) of the body surface area. All had received regular treatment with mild potency BNF (British National Formulary) classification topical corticosteroid ointments (hydrocortisone 48.7–223.2 mg/m2 body surface area/day; median 134.2) for 3–10 years (median 6.5 years). Nine children had also intermittently used moderate potency preparations. However, none had been treated with corticosteroids by any other route in the preceding 6 months. Fourteen prepubertal children with constitutional short stature, without atopic disease, served as controls.

Adult height in patients with childhood onset atopic dermatitis

Cross sectional studies have reported impaired growth in children with atopic dermatitis. If this growth impairment is irreversible, it would be expected to adversely influence final height attainment. The standing heights and other anthropometric parameters were assessed in 35 adults with onset of atopic dermatitis before 5 years of age and a control group of 35 adults with adult onset contact dermatitis or psoriasis.  There was no significant difference in the standing height SD score, mid-parental height SD score, sitting height SD score, subischial leg length SD score, nor body mass index between the atopic dermatitis and control groups. The standing height SD score was not significantly different among: (a) patients with atopic dermatitis affecting less than 50% of their body surface area and those with greater than 50% affected; (b) patients using the four different potency topical corticosteroids; and (c) patients with atopic dermatitis without asthma and those with coexisting asthma.  It is concluded that short stature is not a feature of our group of adult patients with onset of atopic dermatitis before 5 years of age, continuing into adulthood, and severe enough to require specialist care. This suggests that if growth impairment occurs in childhood, it is likely to be temporary and reversible. Key messages • Severe childhood atopic dermatitis does not impair final height attained • Any growth impairment from atopic dermatitis in childhood is likely to be temporary • Individual susceptibility to growth impairment from topical corticosteroid treatment may vary • Children treated with topical corticosteroids need careful growth monitoring

Persistent Müllerian duct syndrome: lessons learned from managing a series of eight patients over a 10‐year period and review of literature regarding malignant risk from the Müllerian remnants

Study Type – Therapy (case series)

Abnormal Neurodevelopmental Outcomes are Common in Children with Transient Congenital Hyperinsulinism

Introduction: Neuroglycopenia is recognized to be associated with abnormal neurodevelopmental outcomes in 26–44% of children with persistent congenital hyperinsulinism (P-CHI). The prevalence of abnormal neurodevelopment in transient CHI (T-CHI) is not known. We have aimed to investigate abnormal neurodevelopment and associated factors in T-CHI and P-CHI. Materials and Methods: A cohort of children with CHI (n = 67, age 2.5–5 years) was assessed at follow-up review and noted to have normal or abnormal (mild or severe) neurodevelopmental outcomes for the domains of speech and language, motor, and vision. Children were classified as P-CHI (n = 33), if they had undergone surgery or remained on medical therapy, or T-CHI (n = 34), if medical treatment for hypoglycemia was stopped. Results: Overall, abnormal neurodevelopment was present in 26 (39%) children with CHI, of whom 18 (69%) were severe. Importantly, the incidence of abnormal neurodevelopment in T-CHI was similar to that in P-CHI (30 vs. 47% respectively, p = 0.16). The prevalence of severe abnormal neurodevelopment in speech, motor, and vision domains was similar in both T-CHI and P-CHI children. For this cohort, we found that the severity of disease [based upon maximal diazoxide dose (odds ratio 95% confidence intervals) 1.3 (1.1; 1.5), p = 0.03], and early presentation of CHI <7 days following birth [5.9 (1.3; 27.8), p = 0.02] were significantly associated with abnormal neurodevelopment. There was no significant association with gender, genotype, or the histopathological basis of CHI. Conclusion: Abnormal neurodevelopment was evident in one third of children with both T-CHI and P-CHI, early presentation and severe CHI being risk factors. Early recognition and rapid correction of hypoglycemia are advocated to avoid abnormal neurodevelopment in children with CHI.

A pilot study to evaluate gene expression profiles in peripheral blood mononuclear cells (PBMCs) from children with GH deficiency and Turner syndrome in response to GH treatment

Response to GH treatment is variable and dependent on diagnosis and dose. We used a pharmacogenomic approach to assess whether this variability is reflected in patterns of GH‐induced gene expression in peripheral blood mononuclear cells (PBMCs) taken from three children with GH deficiency (GHD) and three girls with Turner syndrome (TS).

Problem-based learning as an alternative to lecture-based continuing medical education.

Do you pick up most of your new information in the lecture theatre? Do you believe that all-day pressure on the gluteus maximus whilst accumulating continuing medical education (CME) points is the best way to keep up to date? Do you think that Royal Colleges know best? If your answers to these questions are all yes, then this article is not for you. If, on the other hand, your experience is that there is little connection between sitting in lectures and improving knowledge and skills, and that lecture-based CME is largely a waste of time, then this article may be of interest.

Pattern of growth and adiposity from infancy to adulthood in atopic dermatitis.

Background  Impaired linear growth has been reported in children with atopic dermatitis (AD) but the pattern of growth in height and weight through childhood and adolescence has not been described.

Suppression of puberty with long‐acting goserelin (Zoladex‐LA): effect on gonadotrophin response to GnRH in the first treatment cycle

background and objectives Depot GnRH analogues are widely used in the treatment of precocious puberty, or suppression of relatively early puberty where growth or psychosocial well‐being may be compromised. One example is Zoladex (Z goserelin 3·6 mg), which can be given every 4 weeks. This injection frequency may not always achieve adequate suppression of pubertal signs. A long‐acting form, Zoladex‐LA 10·8 mg, has now been introduced with a potential duration of action of 12 weeks. In order to assess the efficacy of Zoladex‐LA in gonadotrophin suppression we have measured LH and FSH responses to GnRH at diagnosis and 8 and 12 weeks after injection in a group of children treated with Zoladex‐LA for central precocious or early puberty.