Biomedical subjects
Publications and source records attributed to M J Goodfield.
Dermatofibromata are common benign dermal tumours of unknown aetiology. They usually present as a single lesion on the limbs of young adults. Multiple dermatofibromata have been reported occurring in patients with autoimmune disease, who were receiving immunosuppressive treatment. A 25-year-old female is reported who developed multiple dermatofibromata during her first pregnancy, a state of altered immunity.
We have investigated the systemic effect of local treatment with dithranol for one week in psoriasis by a combination of subjective assessment of the severity of individual plaques and more objective assessment of blood flow (measured by laser-Doppler flowmetry) of the centre of the plaque, and at the active edge of the plaque. There is both subjective and objective evidence of an improvement in untreated plaques of psoriasis when dithranol is used on plaques elsewhere on the body. Blood flow falls at the active edge and at the centre of the plaques that are untreated. These findings indicate a systemic effect of local treatment that is more likely to be due to circulating factors, possibly T cells, rather than a direct effect of circulating dithranol. They also suggest that within patient comparisons of topical treatment in psoriasis may be inaccurate.
It is unclear whether the changes in platelet function which are observed in systemic sclerosis are a primary characteristic of this disease or whether they occur secondary to vascular changes. Whole blood platelet aggregation was studied in 26 patients with systemic sclerosis, normal subjects matched for age, sex and secondary characteristics, 19 patients with Raynaud's disease and 19 patients with systemic lupus erythematosus. Plasma levels of fibrinogen, von Willebrand factor antigen and factor VIII:C were also measured. Systemic sclerosis was associated with a significant (P > 0.001) enhancement of the sensitivity of platelets to collagen. In contrast, significant enhancement of the response to either ADP or adrenaline was not observed. Enhanced sensitivity to collagen was not associated with the presence of either Raynaud's disease or systemic lupus erythematosus. Systemic sclerosis was associated with significantly raised levels of von Willebrand factor antigen and fibrinogen. On an individual patient basis, von Willebrand factor antigen was related to the severity of the disease whereas platelet sensitivity to collagen was not. In conclusion, this study suggests that the enhanced sensitivity to collagen which occurs in systemic sclerosis is due to a primary change in the platelet and that this change can combine with elevated levels of adhesive proteins.
Acne can affect unusual sites and occur at unusual ages with little involvement of the commonly affected sites. Discrete areas can be affected by acne which has been reported to occur in a naevoid form. We report a patient who developed an acneiform rash in the site of a previous herpes zoster infection.
A case of chilblain lupus erythematosus during pregnancy is described in a 28-year-old woman. Symptoms and signs were present by 8 weeks of her first pregnancy and had resolved by 10 days after delivery. The condition is discussed with particular emphasis on the relationship with pregnancy.
OBJECTIVE: To evaluate the effect of short term treatment with terbinafine on dermatophytosis. DESIGN: Multicentre, randomised, double blind placebo controlled trial of 250 mg/day terbinafine for 12 weeks in dermatophyte onychomycosis. SETTING: Eight dermatology centres in the United Kingdom. PATIENTS: 112 patients (mean age 44, range 19-78), 99 with mycologically proved toenail infections and 13 with fingernail infections, of whom eight were subsequently excluded and 19 failed to complete the study. INTERVENTION: Terbinafine 250 mg daily or placebo for 12 weeks. Follow up for 36 weeks after stopping treatment. MAIN OUTCOME MEASURES: Mycological cure (negative results on microscopy and culture) and clinical cure at the end of follow up, adverse events, and biochemical and haematological variables at monthly intervals during treatment. RESULTS: After follow up 82% (37/45) (95% confidence interval 68% to 92%) mycological cure and 69% clinical cure were recorded for evaluable patients treated with terbinafine for toenail infection and 71% (5/7) (30% to 96%) mycological cure and clinical cure for those treated for fingernail infection. The corresponding values for those treated with placebo were 12% (3% to 31%) mycological cure and no clinical cure for toenail infections and 33% (1% to 91%) mycological cure and no clinical cure for fingernail infections. On an intention to treat basis for toenail infections the figures were 73% (38/52) (58% to 85%) mycological cure for terbinafine compared with 6% (0% to 30%) for placebo (p less than 0.007). Two withdrawals were related to adverse events with terbinafine, and there were no significant abnormal laboratory test results. CONCLUSION: 12 weeks' terbinafine is effective and safe treatment for nail dermatophytosis.
Terbinafine, an orally active antifungal agent, is effective in the treatment of dermatophyte onychomycosis when given for 12 months in the case of toenail infection (TN) and 6 months for fingernail infection (FN). The rapid response and short mycological cure time indicate a potential for a reduced treatment duration. In this multicentre double-blind placebo-controlled trial, 112 patients with mycologically proven dermatophyte onychomycosis were given 250 mg/day of terbinafine for 3 months. Twenty-seven patients were excluded, leaving 85 fully evaluable [average age 44 (range 19-78) years; 55 men; 75 TN, 10 FN]. Forty-nine of the TN patients and seven of the FN patients received terbinafine. At the end of the follow-up period, the TN mycological cure rate with active treatment was 82% (37/45), but no patient taking placebo maintained mycological cure (P less than 0.001). Of the FN patients treated with active drug, 71% (5/7) achieved mycological cure at the end of follow-up. Minor side-effects occurred in 41% of the placebo-treated group compared with 33% of those taking terbinafine. These adverse events were mainly gastrointestinal. Two patients taking terbinafine discontinued treatment--one with tonsillitis and another with diarrhoea. In conclusion, 3-month treatment with terbinafine is effective, well tolerated and safe in dermatophyte onychomycosis. Short-duration therapy for this indication represents a major therapeutic advance.
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Fifty patients with psoriasis undergoing a standard Ingram regime were entered into a double-blind comparison of oral indomethacin and placebo. No significant differences were observed between the two groups in respect of disease activity or dithranol tolerance after 6 weeks.
The yeast Pityrosporum orbiculare is thought to cause the folliculitis associated with seborrheic eczema. However, a combination of mechanical and microbiological factors may be involved, with follicular occlusion leading to yeast overgrowth and folliculitis. Scanning electron microscopy was used to investigate this hypothesis. Skin biopsy specimens obtained from patients with Pityrosporum folliculitis were examined by scanning electron microscopy before and after oral ketoconazole therapy. Patients with active disease showed occlusion of noninflamed follicles, which resolved after ketoconazole treatment. Follicular occlusion was not present in biopsy specimens obtained from unaffected controls nor was it related to the presence of P orbiculare. These findings suggest that follicular occlusion may be a primary event in the development of this folliculitis, with yeast overgrowth a secondary occurrence. The beneficial effect of ketoconazole in this disease may be due to direct effects on the follicle.
The acute effects of smoking a single cigarette on peripheral blood flow were investigated by laser-Doppler flowmetry in nine patients with Raynaud's phenomenon and 12 normal controls. In regular smokers, a marked fall in finger blood flow was demonstrated, but this was not present in non- or irregular smokers. In addition, no effect on capillary blood flow was found. There was no difference between subjects with and without Raynaud's phenomenon. In five normal, non-smoking volunteers, 2.4 g of aspirin for 3 days resulted in a similar fall in blood flow due to a single cigarette. These results suggest that regular smoking sensitizes the peripheral vasculature to the vasoconstricting effects of the next cigarette, and that at least part of this sensitization is mediated by the inhibition of endothelial prostacyclin synthesis. Patients with Raynaud's phenomenon, either primary or secondary, are no more sensitive than normal subjects, but should nevertheless avoid cigarette smoking.
It is unclear whether an abnormal vascular response to temperature change, independent of central sympathetic control, exists in Raynaud's phenomenon. We investigated this using the hyperaemic response to localized heating of dorsal foot skin, recorded by laser Doppler flowmetry. Fifteen normal adults, nine patients with primary, and seven with secondary Raynaud's phenomenon were studied. On warming, blood flow normally increases gradually at first, followed by rapid vasodilatation at temperatures above 33 degrees C. Normal geometric mean (95% confidence interval) blood flows at 33 degrees C and 36 degrees C were 0.19 (0.16-0.22) and 0.39 (0.29-0.53) arbitrary units respectively. In primary Raynaud's phenomenon, blood flows were 0.53 (0.44-0.62) and 1.07 (0.86-1.35) arbitrary units respectively (P less than 0.01 compared to normal subjects), showing early vasodilatation. Normal women have an intermediate response between men and primary Raynaud's patients. Responses in secondary Raynaud's phenomenon widely overlap the other groups. We conclude that an abnormal peripheral vascular response to temperature change exists in primary Raynaud's phenomenon.
Two patients, one with Sézary syndrome and one with mycosis fungoides are described, in whom lesions on the palms and soles were associated with extensive ulceration and gave rise to diagnostic difficulty. Extensive ulceration of the palms and soles is uncommon; its presence should alert clinicians to the possibility of cutaneous T-cell lymphoma.
The therapeutic efficacy of conventional superficial radiotherapy and topical psoralen photochemotherapy (topical PUVA) administered over a 6 week period was compared in a double-blind study of 21 patients with chronic bilateral constitutional hand eczema. One hand was treated with conventional superficial radiotherapy and the other with topical 8-methoxy-psoralen and long-wave ultraviolet light (topical PUVA). Significantly better clinical improvement was seen in superficial radiotherapy treated hands over topical PUVA treated hands after 6 weeks of treatment, but this difference was not maintained at 9 or 18 weeks. There was no significant difference in symptom severity between the two treatments after 6 weeks, but superficial radiotherapy produced significantly more symptomatic improvement at 9 and 18 weeks. Superficial radiotherapy is a less time consuming procedure than topical PUVA and leads to more rapid improvement.
Eighty-five patients with extensive chronic plaque psoriasis, unresponsive to conventional topical therapy, were treated with long-term hydroxyurea in a dose of 0.5-1.5 g daily. Fifty-two (61%) had a satisfactory remission during treatment without significant adverse effects. Treatment was discontinued in 33 patients (39%), due to an inadequate response or significant relapse during treatment and because of adverse reactions (19%). Four (4.7%) patients on hydroxyurea developed actinic psoriasis. Significant haematological abnormalities occurred in 30 patients (35%), but these became normal following a reduction in the dose of hydroxyurea or temporarily stopping the drug. In only six was it considered necessary to discontinue treatment because of bone marrow suppression. Our experience suggests that hydroxyurea is an effective long-term treatment for psoriasis that is refractory to conventional topical therapy and that the incidence of serious adverse effects compares favourably with other cytotoxic drugs.
We report on the use of a new orally active fungicidal agent, terbinafine (SF 86-327, Lamisil) in the treatment of patients with dermatophyte onychomycosis. Twenty patients with toe-nail, and 10 with finger-nail infection received 250 mg of terbinafine daily: finger-nail infections were treated for 6 months and toe-nail infections for 12 months. All 24 patients who completed the course of therapy achieved mycological cure, as did two subjects who dropped out of the trial. All but two patients had clinically normal nails at the end of the study period. The mean time for mycological cure was 12.5 weeks for finger-nail infection, and 24 weeks for toe-nail infections. The time for a clinical cure with normal nails was 20.5 weeks for finger-nail infection, and 44 weeks for toe-nail infection. An exacerbation of pre-existing dyspepsia occurred in three of the six patients who did not complete the trial but there were no other significant adverse reactions.
Vascular problems are very common in systemic sclerosis with 95% of patients suffering with Raynaud's phenomenon at some stage in their illness. Acute ischaemic lesions are much less common, but when they occur are a serious complication, and are often difficult to treat. Many drugs have been used in this situation, including both oral and intravenous vaso-dilators and low molecular weight dextran, each with varying degrees of success. The phospho-diesterase inhibitor, pentoxifylline, is reported to be useful in peripheral vascular disease, and in Raynaud's phenomenon, and the intravenous form is indicated for acute peripheral ischaemia, though its use in the context of connective tissue disease has not so far been reported. We now report the use of intravenous pentoxifylline in two patients with acute peripheral gangrene due to systemic sclerosis.
A 20 year old Caucasian woman with Crohn's disease is described in whom axillary artery occlusion due to arteritis dominated the clinical picture. This case demonstrates that isolated large vessel arteritis can be an unusual feature of Crohn's disease. Crohn's disease should be considered in any patient presenting with a large vessel arteritis.