Evidence-based treatment of atopic eczema in general practice

No Abstract

Intravenous glutathione for skin lightening: Inadequate safety data

Background. Glutathione (GSH) is the most abundant naturally occurring non-protein thiol that protects mammalian cells from oxidative stress. Intravenous (IV) GSH for skin lightening is advertised by clinics in South Africa and internationally online, yet to date no published review on the subject exists.Methods. We conducted a MEDLINE search (to 30 September 2015) of GSH use for skin lightening and of all indications in medicine, to evaluate its safety.Results. Two controlled clinical trials (GSH capsules: 60 patients; 2% glutathione disulphide lotion: 30 patients) and a case series (GSH lozenges: 30 patients)  reported a significantly decreased melanin index. A case series (GSH soap: 15  patients) reported skin lightening based on photography. Two systematic reviews of IV GSH for preventing chemo-induced toxicity and a third review of adjuvant therapy for Parkinson’s disease altogether included 10 trials. Most trials reported either no or minimal GSH adverse effects, but all had treatment durations of a few doses (IV) or 4 - 12 weeks. No study reported long-term IV GSH use.Conclusion. In spite of widespread reported use, there are no studies of IV GSH use for skin lightening or of its safety for chronic use (for any indication). The switch from brown to red melanin production may increase the risk of sun-induced skin  cancers in previously protected individuals. Regulatory assessment of systemic GSH administration for cosmetic use by the Medicines Control Council seems urgently warranted to protect consumers from potential side-effects and from  complications of IV infusions. This is especially concerning because of reports of GSH bought online. Effective topical GSH may be useful for hyperpigmented skin disorders, but this requires scientific scrutiny. The debate on the merits of cosmetic skin lightening is best handled by multidisciplinary teams

Affordable moisturisers are effective in atopic eczema: A randomised controlled trial

Background. Many patients depend on moisturisers issued by public health services in the management of atopic dermatitis (AD).Methods. In a randomised controlled trial of patients with mild to moderate AD, aged 1 - 12 years, study 1 compared aqueous cream v. liquid paraffin (fragrance-free baby oil) as a soap substitute, all patients using emulsifying ointment as moisturiser, and study 2 compared four moisturisers, emulsifying ointment, cetomacrogol, white petroleum jelly and glycerine/petroleum (proportion 1:2; ‘the 1:2  moisturiser’), all using fragrance-free baby oil as soap substitute. Assessments were one quality of life and three AD severity scores, at baseline and weeks 4, 8 and 12. Differences were compared using repeated measures of analysis of variance.Results. In both studies (120 children randomised, 20 in each group of the two trials) disease severity scores declined with time. The only significant difference was in one AD severity score (SCORing Atopic Dermatitis) in study 1, both at baseline and over time (p=0.042 and p=0.022). The groups did not differ with regard to topical steroid use or side-effects. Itching from baby oil applied as soap was reported by four patients in the two studies, the petroleum jelly group had more dropouts than the 1:2 moisturiser group, although this was not statistically significant, and 110 patients (91.7%) completed the trial.Conclusions. The small sample limits generalisability, but the duration was longer than in most AD moisturiser studies. Fragrance-free baby oil as a soap substitute may be better tolerated (if irritation occurs) as a bath additive. The 1:2 moisturiser may be preferable to white petroleum jelly, but both are equivalent to cetomacrogol and emulsifying ointment. Use of accessible moisturisers could reduce the cost of managing mild to moderate AD

Health Diplomacy the Adaptation of Global Health Interventions to Local Needs in sub-Saharan Africa and Thailand: Evaluating Findings from Project Accept (HPTN 043).

Study-based global health interventions, especially those that are conducted on an international or multi-site basis, frequently require site-specific adaptations in order to (1) respond to socio-cultural differences in risk determinants, (2) to make interventions more relevant to target population needs, and (3) in recognition of 'global health diplomacy' issues. We report on the adaptations development, approval and implementation process from the Project Accept voluntary counseling and testing, community mobilization and post-test support services intervention. We reviewed all relevant documentation collected during the study intervention period (e.g. monthly progress reports; bi-annual steering committee presentations) and conducted a series of semi-structured interviews with project directors and between 12 and 23 field staff at each study site in South Africa, Zimbabwe, Thailand and Tanzania during 2009. Respondents were asked to describe (1) the adaptations development and approval process and (2) the most successful site-specific adaptations from the perspective of facilitating intervention implementation. Across sites, proposed adaptations were identified by field staff and submitted to project directors for review on a formally planned basis. The cross-site intervention sub-committee then ensured fidelity to the study protocol before approval. Successfully-implemented adaptations included: intervention delivery adaptations (e.g. development of tailored counseling messages for immigrant labour groups in South Africa) political, environmental and infrastructural adaptations (e.g. use of local community centers as VCT venues in Zimbabwe); religious adaptations (e.g. dividing clients by gender in Muslim areas of Tanzania); economic adaptations (e.g. co-provision of income generating skills classes in Zimbabwe); epidemiological adaptations (e.g. provision of 'youth-friendly' services in South Africa, Zimbabwe and Tanzania), and social adaptations (e.g. modification of terminology to local dialects in Thailand: and adjustment of service delivery schedules to suit seasonal and daily work schedules across sites). Adaptation selection, development and approval during multi-site global health research studies should be a planned process that maintains fidelity to the study protocol. The successful implementation of appropriate site-specific adaptations may have important implications for intervention implementation, from both a service uptake and a global health diplomacy perspective

Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to <i>FAM111B </i>mutations

BACKGROUND: Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. METHODS: Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected. RESULTS: Key features consist of: (i) early-onset poikiloderma, hypotrichosis and hypohidrosis; (ii) multiple contractures, in particular triceps surae muscle contractures; (iii) diffuse progressive muscular weakness; (iv) pulmonary fibrosis in adulthood and (v) other features including exocrine pancreatic insufficiency, liver impairment and growth retardation. Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration. Microscopy of the skin showed a scleroderma-like aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two recurrent mutations were found respectively in three and four independent families). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain-of-function or dominant-negative mutations resulting in FAM111B enzymatic activity changes. CONCLUSIONS: HFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder

Apparent fragility of African hair is unrelated to the cystine-rich protein distribution: a cytochemical electron microscopic study.

A feature of black African hair is an apparent increased fragility of the hair shaft compared to other ethnic groups (as measured by the tensile force needed to break the hair fibre). This has certain similarities to that reported for trichorrhexis nodosa (weathering secondary to physical damage) and trichothiodystrophy [a genetic disorder associated with reduced cystine (sulphur)-rich proteins and increased fragility]. In the present study, the distribution of the cystine-rich proteins in the hair of black Africans was compared to that of Caucasian and Asian volunteers, plus patients with trichorrhexis nodosa and trichothiodystrophy, using transmission electron microscopy and specific silver stains. It was found that the silver staining pattern of the hair shafts of black Africans was similar to that observed for Caucasians, Asians and also patients with trichorrhexis nodosa. The cuticular cells exhibited an electron dense A layer and exocuticle, and in the cortex the microfibrils forming the macrofibres were outlined by electron-dense material. This contrasts with the abnormal distribution of the cystine-rich proteins seen in trichothiodystrophy. This study is the first formal comparison of the cystine-rich proteins in the various racial groups and shows that there is no abnormality in their distribution in black African hair shafts compared to the other ethnic groups. Therefore, the excessive structural damage observed in the African hair shafts is consistent with physical trauma (resulting from grooming) rather than an inherent weakness due to any structural abnormality

What is normal black African hair? A light and scanning electron-microscopic study.

BACKGROUND: The hair of normal black Africans forms a mat of tightly interwoven hair shafts. The effect of this on the structure of the hair shaft and the response to grooming is unknown. OBJECTIVE: Our purpose was to use light and scanning electron microscopy (SEM) to examine the structure of Negroid-type hairs and effects of combing in black African volunteers. METHODS: Hair samples were collected, by combing, from Africans and compared with those from Caucasian and Asian volunteers. The volunteers had never used chemical treatments. Their hair had not been cut for at least 1 year and grooming had been limited to shampooing, drying, and combing. RESULTS: More than 2000 hairs in 12 African volunteers were examined by light microscopy. The hairs appear as a tight coiled springlike structure. Many shafts exhibited knots (10%-16% vs 0.15%) and appear broken compared with hair shafts from other ethnic groups. SEM of African hairs showed features consistent with repeated breaks of the shaft. Examination of hairs in situ showed interlocking of hair shafts. CONCLUSION: These observations provide an understanding of the physical nature of, and effect of combing on, black African hair

A systematic review of treatments for bullous pemphigoid.

OBJECTIVE: To assess the effectiveness of treatments for bullous pemphigoid. METHODS: The Cochrane Library search strategy was used to identify randomized controlled trials from MEDLINE and EMBASE, from their inception to September 30, 2001. All randomized controlled trials on interventions for bullous pemphigoid, confirmed by immunofluorescence studies, were included. RESULTS: We found 6 randomized controlled trials with a total of 293 patients. Two trials, one comparing prednisolone, 0.75 mg/kg per day, with prednisolone, 1.25 mg/kg per day, and the other comparing methylprednisolone with prednisolone, did not find any significant difference in effectiveness. The higher dose of prednisolone, however, was associated with more severe adverse effects. Combination treatments of prednisone with azathioprine in one trial and of prednisolone with plasma exchange in another were useful in halving the corticosteroid dose required (mean +/- SD, 0.52 +/- 0.28 mg/kg in the plasma exchange-treated group vs 0.97 +/- 0.33 mg/kg in the prednisolone only-treated group). However, a fifth trial, including all 3 treatment groups (prednisolone alone, prednisolone and azathioprine, and prednisolone and plasma exchange), failed to confirm the benefit of combination treatment over prednisolone alone. A trial of 20 patients, comparing prednisone with tetracycline and niacinamide, found no statistically significant difference in response between the 2 groups, but the prednisone-treated group had more serious adverse effects. CONCLUSIONS: There is inadequate evidence for a recommendation of a specific treatment for bullous pemphigoid, and there is a need for larger randomized controlled trials with adequate power. Starting doses of prednisolone greater than 0.75 mg/kg per day do not seem to give additional benefit, and it seems that lower doses may be adequate for disease control. The effectiveness of the addition of plasma exchange or azathioprine to corticosteroids has not been established. Combination treatment with tetracycline and niacinamide seems useful, although this needs further validation

Bullous pemphigoid in pregnancy: contrasting behaviour in two patients.

Bullous pemphigoid (BP) is an increasingly common immunobullous disease of the elderly, and, due to the late age of onset, is rarely seen in women of fertile age. Consequently, to the best of our knowledge no cases of BP in pregnancy have been described. We present two cases of BP that have differed in disease behaviour during pregnancy