Biomedical subjects
Publications and source records attributed to A M Layton.
The following article reviews treatment for acne vulgaris. Selection of therapy should be based on clinical appearance taking into account lesion type and severity, as well as identification of acne scarring and the psychosocial disability caused by the disease.
Since the introduction of generic oral isotretinoin there have been discussions around harmonizing the summary of product characteristics of each formulation. As a result of these discussions, a European Directive concerned with the prescribing of oral isotretinoin has been introduced and the FDA (Food and Drugs Administration) has recently implemented new regulations. The aims of this article are to summarize the history of the processes involved, outline the new recommendations and discuss the impact of these changes in clinical practice.
BACKGROUND: Many patients with inflammatory acne suffer from significant scarring, which is disfiguring and difficult to treat. A cell-mediated immune response is considered to be involved in the pathogenesis of acne, although the extent of this response has been found to differ among patients. OBJECTIVE: To assess whether there were differences in the cell-mediated immune responses at different time points in inflamed lesion development and resolution in patients who were prone (S patients) and those with the same degree of inflamed acne who were not prone (NS patients) to develop scarring. METHODS: Cellular and vascular markers were investigated using standard immunohistochemical techniques on biopsies of inflamed lesions of known duration, i.e. < 6 h (n = 14), 24 h (n = 14), 48 h (n = 10), 72 h (n = 10) and 6-7 days (n = 11) from the backs of acne patients. RESULTS: In early lesions from NS patients there was a large influx of CD4+ T cells, macrophages and Langerhans cells with a high number of cells expressing HLA-DR. Also there was significant angiogenesis and vascular adhesion molecule expression. Cell recruitment peaked in 48 h lesions, after which leucocyte numbers decreased and vascular activity returned to normal. Of the T cells, only 50% were memory/effector (CD45RO+) and naive (CD45RA+) cells, while the remainder were unclassified (CD45RO-, CD45RA-). In early lesions from S patients, CD4+ T cell numbers were smaller, although a high proportion were skin homing memory/effector cells. Langerhans cell numbers and cellular HLA-DR expression were low, while numbers of macrophages, blood vessels and vascular adhesion molecules were high. In resolving lesions angiogenesis remained high, with a further influx of macrophages and skin homing memory/effector cells and increased cellular HLA-DR expression. CONCLUSIONS: The cellular infiltrate was large and active with a greater nonspecific response (few memory T cells) in early lesions of NS patients, which subsided in resolution. In contrast, a predominantly specific immune response was present in S patients, which was initially smaller and ineffective, but was increased and activated in resolving lesions. Such excessive inflammation in healing tissue is conducive to scarring and suggests that the use of topical anti-inflammatory treatments would be appropriate for these patients.
BACKGROUND: Staphylococcus aureus has a role in the pathophysiology of atopic eczema. Topical fusidic acid is widely used in its treatment. There is concern that topical use of fusidic acid may be driving the selection and dissemination of fusidic acid-resistant (FusR) S. aureus. OBJECTIVES: To test the hypothesis that treatment of atopic eczema for 2 weeks with topical fusidic acid/steroid combination can increase carriage of FusRS. aureus. METHODS: Forty-six patients with atopic eczema were allocated randomly to one of two treatment groups. Group 1 (28 patients) were treated with topical 2% fusidic acid plus 0.1% betamethasone cream, and group 2 (18 patients) with topical 2% mupirocin and 0.1% betamethasone cream. The clinical response and nasal and skin colonization with S. aureus were recorded before treatment and after 1 and 2 weeks of therapy. RESULTS: Baseline samples from the site of worst eczema showed S. aureus (sensitive and resistant) in 76% of patients, and FusRS. aureus in 26%, with no significant difference between treatment groups. After 1 and 2 weeks, both groups showed similar significant clinical improvement. The overall median clinical improvement was paralleled by a reduction in prevalence and population density of S. aureus (sensitive and resistant) at the worst eczema site (P < 0.0001). However, for FusRS. aureus there was no significant change in the prevalence of carriage, or population density in either group compared to baseline. Over 50% of patients carried S. aureus in the nerves and over 20% carried FusRS. aureus. Neither regimen affected either the prevalence or population density of S. aureus or FusRS. aureus in the nerves. CONCLUSIONS: In this small study there is no evidence to support the hypothesis that short-term treatment of atopic eczema with fusidic acid/steroid combination increases fusidic acid resistant S. aureus during a 2-week period.
Acne vulgaris is one of the most common inflammatory dermatoses and is seen in both the hospital setting and in general practice. Multiple factors are involved in the pathophysiology of acne, including: an alteration in the pattern of keratinization within the pilosebaceous follicles resulting in comedone formation; an increase in sebum production which is influenced by androgens; the proliferation of Propionibacterium acnes; and the production of perifollicular inflammation. Genetic and hormonal factors may also contribute to acne. Better understanding of the pathophysiology of the disease has led to the development of novel therapies which are directed at one or more of the implicated etiologic factors. Systemic antibiotics for acne have been the mainstay of treatment for many years. The main cause for concern following the use of systemic antibiotics is the emergence of antibiotic-resistant strains of P. acnes. Concomitant use of non-antibiotic therapies such as benzoyl peroxide helps to decrease the occurrence of resistance and can be effective in the treatment of resistant and nonresistant propionibacterial strains. However, no one agent is able to eradicate resistant strains completely and as resistant strains correlate to poor clinical response to therapy, prescribing strategies are required to minimize the occurrence of resistance to P. acnes. When assessing acne it is important to take an all embracing approach and to examine carefully for both the clinical and psychologic effects of the disease process. There are numerous forms of acne scarring and it is important to be aware of these as patients who are developing scarring merit early effective therapy. Some patients with acne will develop psychologic problems as a consequence of their condition. Even mild to moderate disease can be associated with significant depression and suicidal ideation and psychologic change does not necessarily correlate with disease severity. Acne scars themselves have been shown to produce significant psychopathology. When initiating treatment it is important to consider the aims of therapy. Treatment should be aimed at achieving clearance of acne, prevention of scarring and, where necessary, relief from any psychologic stress resulting from the acne. Therapy should be commenced early in the disease process in order to prevent scarring and it is important to select appropriate therapies according to the clinical signs and psychologic disability. It is also important to ensure that the patient is able to comply with therapy and clear guidelines regarding treatment, possible adverse effects and realistic expectations should be provided.
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The mechanisms involved in the development of inflammation in acne vulgaris have yet to be elucidated. Previous studies have shown that the initial cellular infiltrate in early inflammatory lesions is mononuclear, predominantly CD4 positive T cells. The aims of this study were to investigate the pattern of expression of adhesion molecules and HLA-DR in evolving acne lesions. Forty-nine patients with moderate to severe acne were biopsied following lesion mapping. Lesions were classified according to their duration of inflammation as up to 6 h, from 6 to 24 h, from 24 to 48 h and from 48 to 72 h. The cellular infiltrate was determined using monoclonal antibodies to CDI, CD3, CD4 and CD8. The expression of ICAM-1, E-selectin. VCAM-1 and HLA-DR was determined. Early (6 h) lesions had perivascular CD3 positive T-cell infiltrates which were predominantly CD4 positive. This was associated with vascular expression of ICAM-1, E-selectin, VCAM-1 and HLA-DR. Periductal infiltrates were present in 70% of the early lesions (up to 6 h). The cells were predominantly CD4 positive and associated with a high level of HLA-DR and ICAM-1 expression. Periductal infiltration increased with time and persisted to 72 h. ICAM-1 and HLA-DR were expressed epidermally in early and late lesions. CD1 positive cells were a minor, but consistent element in the perivascular and periductal infiltrates of early and late lesions. There was no statistically significant difference in the levels of expression of E-selectin, VCAM-1, ICAM-1 or HLA-DR for lesions of different duration. The pattern of HLA-DR and adhesion molecule expression plus the nature of the cellular infiltrate supports the hypothesis that inflammation in acne is mediated by CD4 positive T cells.
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Acne vulgaris is a common inflammatory dermatosis capable of producing significant psychological and physical scarring. The following work describes the benefit of using a questionnaire as a clinical tool to identify acne patients who have developed psychological sequelae as a result of the disease process. In addition, the benefit of isotretinoin on psychological impact has also been highlighted by this work. A prospective clinical study examines the early use of isotretinoin in acne and demonstrates the beneficial effect of early therapy in minimising acne scarring. In summary, oral isotretinoin (Roaccutane/Accutane) provides a very effective therapy to prevent acne patients being 'scarred for life'!
BACKGROUND: Oral isotretinoin (Roaccutane) revolutionized the treatment of acne when it was introduced in 1982. METHODS: Twelve dermatologists from several countries with a special interest in acne treatment met to formally review the survey of their last 100 acne patients treated with oral isotretinoin. The primary purpose of the survey was to identify the types of acne patients who were prescribed oral isotretinoin and how the patients were managed. RESULTS: Of the 1,000 patients reviewed, 55% of those who received oral isotretinoin had those indications treated historically, i.e. severe nodular cystic acne or severe inflammatory acne, not responding to conventional treatment. Forty-five percent of patients who were prescribed oral isotretinoin however had either moderate or mild acne. Most patients in this group had moderate acne (85%). However, 7.3% had mild acne on physical examination. The criteria for prescribing oral isotretinoin in this less severe group of patients included acne that improves < 50% after 6 months of conventional oral antibiotic and topical combination therapy, acne that scars, acne that induces psychological distress and acne that significantly relapses during or quickly after conventional therapy. Treatment is usually initiated at daily doses of 0.5 mg/kg (but may be higher) and is increased to 1.0 mg/kg. Most of the physicians aimed to achieve a cumulative dose of > 100-120 mg/kg. Mucocutaneous side-effects occur frequently but are manageable while severe systemic side-effects are rarely problematic (2%). The teratogenicity of oral isotretinoin demands responsible consideration by both female patients and their physicians. Significant cost savings when treating acne patients with oral isotretinoin as compared to other treatment modalities were further proven in this study. CONCLUSIONS: Our recommendation is that oral isotretinoin should be prescribed not only to patients with severe disease but also to patients with less severe acne, especially if there is scarring and significant psychological stress associated with their disease. Acne patients should, where appropriate, be prescribed isotretinoin sooner rather than later.
Systemic sclerosis is a multi system disorder, for which there is no satisfactory treatment. Theoretically, dietary supplementation with essential fatty acids may lead to an increase in their derivatives, the vasoactive prostaglandins, which benefit the acute and chronic ischaemic lesions of this disease. We assessed the value of concentrated essential fatty acids in patients with systemic sclerosis, concentrating particularly on vascular symptoms and objective tests of vascular reactivity. Twenty-five patients with systemic sclerosis were randomised to receive concentrated essential fatty acids or placebo, for 6 months in a double-blind parallel group study. There was no significant difference between the active and placebo groups in terms of maximum blood flow after warming, minimum blood flow after cooling or the recovery time after cooling. There were no significant differences between the groups in the other parameters measured. Dietary essential fatty acids have no role in the treatment of vascular symptoms in established systemic sclerosis.
The relationship between hidradenitis suppurativa (HS) and hyperandrogenism is largely based on the finding of an increased free androgen index due to a low sex hormone binding globulin (SHBG). As SHBG is now believed to be regulated by factors that influence body weight, and previous studies were not controlled for body weight, we have re-evaluated the androgen status of female patients with HS. We have studied the endocrine status of 66 women with HS. Twenty-three had acne, and 23 were significantly obese (body mass index: BMI > 30). There was no relationship between obesity and disease duration. Nineteen of 56 women were hirsute. A premenstrual flare in disease activity was reported by 32 women, but this was not related to menstrual disturbances. No consistent relationship was reported with pregnancy. Eight women with HS were menopausal at presentation, and one developed her disease 6 years after the menopause. Plasma androgens in women with HS were compared with controls matched for BMI and hirsuties. There was no difference between HS and controls. Testosterone and dehydroepiandrosterone sulphate were normal in all subjects with HS. In obese subjects, SHBG was reduced, consistent with BMI-matched controls. We have found no supporting evidence for biochemical hyperandrogenism in women with HS when compared with age-, weight- and hirsuties-matched controls. We report the continuation and primary development of HS in postmenopausal women.
An increased rate of venous ulcer healing with the use of oral enteric-coated aspirin (300 mg) daily has been reported. Whether the effect of aspirin in this condition is related to its action on the haemostatic mechanism is unclear, and therefore this study aimed to assess the effect of aspirin on some haemostatic parameters in patients with chronic venous leg ulcers. A double-blind, randomized, placebo-controlled, parallel-group study of haemostatic activity and the effect of aspirin was implemented over a 4-month period. Twenty patients with venous leg ulcers, and 20 age- and sex-matched controls were studied. Patients received enteric-coated aspirin (300 mg) or placebo (one tablet) daily for 4 months, in addition to standardized local compressive bandaging (Setopress). Assessments made at recruitment, and at 2 and 4 months, included measurement of total ulcer surface area, haematological and biochemical screening, measurement of coagulation times, coagulation factor VIII:C (FVIII:C) and von Willebrand factor (vWF), and plasminogen activator inhibitor-1 (PAI-1) levels. Procoagulant activity was assessed by a computer-assisted technique, to determine the rate of thrombin production in vitro. Patients with venous ulcers had increased levels of fibrinogen (P < 0.01), FVIII:C (P < 0.05), vWF (P < 0.05) and PAI-1 antigen (P < 0.01) compared with controls. Shortening of the coagulation rate, shown by a reduction of the time to generate 50% maximal thrombin activity in seconds (T50), was seen in patients, in comparison with control subjects (P < 0.05). T50 was longer in patients receiving aspirin than those receiving placebo, reflecting prolongation of coagulation rate in the aspirin-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)
A 53-year-old woman presented with erosive pustular dermatosis of the scalp 6 weeks after a bifrontal skin flap and right frontal craniotomy had been performed for removal of a suprasellar meningioma. Although some authors consider that acute local trauma is a precipitating factor for this condition, we believe that this is the first reported case following a neurosurgical procedure.
Papuloerythroderma has been described as a distinct clinical entity. It is characterized by pruritus, red flat-topped papules with skin crease sparing, blood eosinophilia and lymphopenia. It has been described almost exclusively in elderly men. We report a case of cutaneous T-cell lymphoma which, at presentation, was indistinguishable from papuloerythroderma, in a 79-year-old male. An excellent clinical response to low dose oral corticosteroids and photochemotherapy was observed. There have only been two previous reports linking papuloerythroderma with T-cell lymphoma. This patient is in keeping with the two previously reported cases and would support the view that papuloerythroderma may predispose to, or in fact represent, an early form of cutaneous T-cell lymphoma.
BACKGROUND: There is at present little published information on the current indications for isotretinoin as a treatment of acne vulgaris. OBJECTIVES: To investigate the factors which influence our current prescribing of isotretinoin: acne severity, response to previous therapy, scarring and psychological effect. METHODS: Data on the factors influencing treatment of 200 patients with isotretinoin between January 1993 and May 1994 were examined. RESULTS: 41% of patients were prescribed isotretinoin for partial response to previous therapy, 26% for partial therapy and scarring and 17% for partial response to treatment and psychological disturbance. Only 16 patients received isotretinoin for severe acne. CONCLUSION: Patients who show only partial response to conventional antibiotic therapy should be prescribed isotretinoin in order to minimize scarring and significant psychological disturbance, independently of the severity of the acne.
The effect of oral aspirin on the healing rate of chronic venous leg ulcers was compared with that of placebo in a double-blind randomised trial. 20 subjects with chronic venous leg ulcers were randomised to daily enteric-coated aspirin 300 mg or placebo, and standardised compression bandaging. 4 months of treatment achieved ulcer healing in 38% of the patients receiving aspirin compared with 0% of those receiving placebo (p < 0.007). 52% of the aspirin-treated group showed significant reduction in ulcer size compared with 26% of placebo recipients (p < 0.007). Reduction in ulcer surface area was significantly better in the aspirin-treated group at 2 (p < 0.01) and 4 months (p < 0.002) compared with that in the placebo group.