Erythroderma (exfoliative dermatitis). Part 1: underlying causes, clinical presentation and pathogenesis.

Erythroderma (exfoliative dermatitis), first described by Von Hebra in 1868, manifests as a cutaneous inflammatory state, with associated skin barrier and metabolic dysfunctions. The annual incidence of erythroderma is estimated to be 1-2 per 100 000 population in Europe with a male preponderance. Erythroderma may present at birth, or may develop acutely or insidiously (due to progression of an underlying primary pathology, including malignancy). Although there is a broad range of diseases that associate with erythroderma, the vast majority of cases result from pre-existing and chronic dermatoses. In the first part of this two-part concise review, we explore the underlying causes, clinical presentation, pathogenesis and investigation of erythroderma, and suggest potential treatment targets for erythroderma with unknown causes.

Erythroderma (exfoliative dermatitis). Part 2: energy homeostasis and dietetic management strategies.

Erythroderma (exfoliative dermatitis) is associated with important metabolic changes that include an enhancement in energy expenditure. The key components to total energy expenditure (TEE) include basal metabolic rate (~68% of TEE), physical activity (~22% of TEE) and thermic effect of food (~10% of TEE). In the erythrodermic state, there are likely multiple contributors to the increase in basal metabolic rate, such as 'caloric drain' resulting from increased evaporation of water from enhanced transepidermal water loss, increased activity of the cardiovascular system (including high-output cardiac failure), increased nonshivering thermogenesis and hormonal changes such as hypercortisolaemia. A change in the patient's level of physical activity and appetite as a result of ill health status may further impact on their TEE and energy consumption. In Part 2 of this two-part concise review, we explore the key constituents of energy homeostasis and the potential mechanisms influencing energy homeostasis in erythroderma, and suggest much-needed dietetic management strategies for this important condition.

Genotype-phenotype correlation in a large English cohort of patients with autosomal recessive ichthyosis.

BACKGROUND: Recessive forms of congenital ichthyosis encompass a group of rare inherited disorders of keratinization leading to dry, scaly skin. So far, 13 genes have been implicated, but there is a paucity of data on genotype-phenotype correlation in some populations. OBJECTIVES: We compiled an English cohort of 146 individuals with recessive ichthyosis and assessed genotype-phenotype correlation. METHODS: Deep phenotyping was undertaken by history-taking and clinical examination. DNA was screened for mutations using a next-generation sequencing ichthyosis gene panel and Sanger sequencing. RESULTS: Cases were recruited from 13 National Health Service sites in England, with 65% of patients aged < 16 years at enrolment. Pathogenic biallelic mutations were found in 83% of cases, with the candidate gene spread as follows: TGM1 29%, NIPAL4 12%, ABCA12 12%, ALOX12B 9%, ALOXE3 7%, SLC27A4 5%, CERS3 3%, CYP4F22 3%, PNPLA1 2%, SDR9C7 1%. Clinically, a new sign, an anteriorly overfolded ear at birth, was noted in 43% of patients with ALOX12B mutations. The need for intensive care stay (P = 0·004), and hand deformities (P < 0·001), were associated with ABCA12 mutations. Self-improving collodion ichthyosis occurred in 8% of the cases (mostly TGM1 and ALOX12B mutations) but could not be predicted precisely from neonatal phenotype or genotype. CONCLUSIONS: These data refine genotype-phenotype correlation for recessive forms of ichthyosis in England, demonstrating the spectrum of disease features and comorbidities, as well as the gene pathologies therein. Collectively, the data from these patients provide a valuable resource for further clinical assessment, improving clinical care and the possibility of future stratified management. What's already known about this topic? Recessive forms of ichthyosis are rare but often difficult to diagnose. Mutations in 13 genes are known to cause recessive forms of ichthyosis: ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, LIPN, NIPAL4, PNPLA1, SDR9C7, SLC27A4, SULT2B1, ST14 and TGM1. Some phenotypic features may associate with certain gene mutations, but paradigms for genotype-phenotype correlation need refining. What does this study add? The genotypic spectrum of recessive ichthyosis in England (based on 146 cases) comprises TGM1 (29%), NIPAL4 (12%), ABCA12 (12%), ALOX12B (9%), ALOXE3 (7%), SLC27A4 (5%), CERS3 (3%), CYP4F22 (3%), PNPLA1 (2%) and SDR9C7 (1%). New or particular phenotypic clues were defined for mutations in ALOX12B, ABCA12, CYP4F22, NIPAL4, SDR9C7 and TGM1, either in neonates or in later life, which allow for greater diagnostic precision. In around 17% of cases, the molecular basis of recessive ichthyosis remains unknown.

Decline of dermatological publications in the UK: truth or myth?

BACKGROUND: For some time, there has been a suspicion that the number of articles published by UK-based authors in dermatology has declined. This probably reflects a reduction in the publication output of dermatology departments generally. METHODS: We identified articles with British authorship in the British Journal of Dermatology between 1970 and the present date, and compared the journal with the three most commonly cited dermatological journals: Archives of Dermatology, Journal of Investigative Dermatology and Journal of the American Academy of Dermatology. Later, we expanded this search to include a further 33 dermatological journals. RESULTS: Despite an increase in the total number of published papers by the British Journal of Dermatology, there was a decline in the number of British-authored papers, from 97 (57%) in 1970 to 80 (22%) in 2005. The trend was also seen in the Journal of the American Academy of Dermatology, with 16 papers (5%) in 1989 and 7 (2%) in 2005. In Journal of Investigative Dermatology, British papers increased from 10 papers in 1975 to 17 in 2005, with a percentage decrease from 7% to 4%. Overall, despite an increase in the total number of publications in dermatological journals from 2745 in 1985-5034 in 2005, British publications increased from 271 in 1989 to only 289 in 2005, which represents a percentage decrease from 10% to 6%. CONCLUSIONS: Despite a three-fold increase in dermatology consultants and registrars in UK, a three-fold increase in dermatological journals and a four-fold increase in dermatological papers published, the overall number of British papers has remained static over the years.

Sulfamethoxypyridazine-responsive pemphigoid nodularis: a report of two cases.

Pemphigoid nodularis is a chronic and uncommon variant of bullous pemphigoid. The condition is characterized by the presence of prurigo nodularis-like lesions, possible history of blistering, and immunohistochemical findings of bullous pemphigoid. These patients are often unresponsive to conventional therapy with potent topical and systemic steroids and different immunosuppressive agents used alone or in combination. We describe two cases of pemphigoid nodularis treated successfully with sulfamethoxypyridazine without any adverse effects.

Raised epidermal phospholipase A2 activity in rheumatoid arthritis.

Epidermal phospholipase A2 (PLA2) in RA patients was significantly higher than in normals (p less than 0.0001) but lower than in psoriatic patients (p less than 0.05). No relationship was observed between PLA2 activity and commonly used measures of rheumatoid disease activity in a cross-sectional study. However, in a longitudinal study change in PLA2 activity correlated strongly with changes in disease activity.

Cyclosporin in childhood psoriasis.

BACKGROUND: Cyclosporin is known to be highly effective in the treatment of psoriasis in adults. It has also proved effective and well tolerated in the treatment of severe childhood atopic dermatitis. Psoriasis in childhood is relatively unusual but by no means rare and on occasions the disease can be very difficult to control in this age group. The use of cyclosporin for psoriasis in childhood has received scarcely any attention and in the few cases that have been reported the results have been inconsistent. Three children aged from 7 to 11 years with severe psoriasis resistant to topical agents were treated with cyclosporin. The highest dose required was 3.5 mg/kg per day. The duration of treatment ranged from 6 weeks to 4 months. Cyclosporin was effective and generally well tolerated. Treatment was interrupted in one case due to nausea and diarrhoea. None of the patients developed hypertension or renal impairment. The potential role of cyclosporin in severe childhood psoriasis is discussed.

Erythropoietic protoporphyria presenting in an adult.

Erythropoietic protoporphyria is an inherited disorder of porphyrin metabolism, in which reduced activity of the enzyme ferrochelatase leads to accumulation of protoporphyrins in erythrocytes. Protoporphyrins are photoactivated by ultra-violet light causing tissue damage by release of free oxygen radicals, which manifests as photosensitivity. The majority of cases of erythropoietic protoporphyria present in childhood although sometimes symptoms are delayed until the second decade. We report here a case presenting in adulthood and discuss the risk of liver disease in the condition.

Folic acid supplementation during treatment of psoriasis with methotrexate: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: The value of folate supplementation in methotrexate (MTX)-treated patients remains controversial. OBJECTIVES: To determine the effect of folic acid (FA) on the efficacy of MTX and the frequency of side-effects associated with MTX therapy. METHODS: A 12-week double-blind clinical trial was conducted in patients with psoriasis stable on their long-term MTX doses but not receiving FA. They were randomized into two arms of either FA 5 mg or placebo daily. MTX doses were not changed throughout the study. Patients were monitored every 3 weeks by the same observer. Assessments included Psoriasis Area and Severity Index (PASI), a visual analogue scale (VAS) of patients' perception of their psoriasis severity and the Dermatology Life Quality Index (DLQI). Adverse events were systematically recorded. Haematological and biochemical monitoring was performed. RESULTS: Twenty-two patients with psoriasis were recruited. Age, sex and weekly MTX doses were similar in both groups. All 22 patients completed the study. The mean PASI in the FA group increased from 6.4 at baseline to 10.8 at 12 weeks. In the placebo group the mean PASI fell from 9.8 at baseline to 9.2 at 12 weeks. The mean change from baseline in the FA group was 4.4 vs. -0.6 in the placebo group (P < 0.05). Similar trends were observed in the changes in VAS and in the DLQI and differences between the groups were significant for both these parameters (P < 0.05). Few adverse effects were reported. CONCLUSIONS: This study suggests that supplementation with FA during long-term MTX treatment reduces the efficacy of MTX in the control of psoriasis. Due to the relatively small sample size and short duration of this study, no conclusions can be drawn regarding the possibility that FA may reduce the side-effects of MTX.