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GPs with an interest in dermatology review the latest papers of significance from research teams across the world

Methotrexate and ciclosporin in the treatment of psoriasis
Topical treatments in mild to moderate facial acne vulgaris
Combination therapy in acne
Allopurinol, SJS and toxic epidermal necrolysis
Insulin resistance, psoriasis, CVD and diabetes mellitus
Infant haemangioma and the possible risk of ulceration
Predicting acne relapse and second doses of isotretinoin
Targeted immune modulators for severe psoriasis vulgaris
Etanercept for plaque psoriasis in children and adolescents
Alcohol and psychological distress in psoriasis patients
Azathioprine v mycophenolate mofetil in bullous pemphigoid

Methotrexate and ciclosporin in the treatment of psoriasis
Flytström I, Stenberg B, Svensson Å, Bergbrant I-M. Br J Dermatol 2008; 158: 116-21

This was the first study to compare methotrexate with ciclosporin in the treatment of moderate-to-severe plaque psoriasis. It aimed to compare effectiveness, quality of life and side-effects in the context of a normal clinical setting.
The study involved 84 patients, all with moderate-to-severe plaque psoriasis. They were randomised to treatment with either methotrexate or ciclosporin for a 12-week period.
The Psoriasis Severity and Area Index (PASI) was used to assess effectiveness, while quality of life was assessed with the Dermatology Life Quality Index (DLQI) and the 36-item Short Form Health Survey (SF-36).
Of the 84 patients in the study, 68 undertook treatment, with drop-out higher in the ciclosporin group. The mean change in the PASI score from baseline to 12 weeks was 58 per cent in the methotrexate group and 72 per cent in the ciclosporin group, showing ciclosporin to be the more effective of the two treatments. Methotrexate showed a better improvement in the SF-36 scoring, although there was no significant difference in the DLQI score.
The study showed that both treatments effectively controlled plaque psoriasis over a 12-week period, but ciclosporin was significantly more effective than methotrexate.
- Dr Nigel Stollery is a GP in Kibworth, Leicestershire, and clinical assistant in dermatology at Leicester Royal Infirmary

Topical treatments in mild to moderate facial acne vulgaris
Langner A, Chu A, Goulden V, Ambroziak M. Br J Dermatol 2008; 158: 122-9

This randomised single blind comparison study was undertaken in two centres, in Poland and the UK. It set out to compare two popular topical treatments for acne vulgaris.
Clindamycin plus benzoyl peroxide (CDP/BPO) was compared with the retinoid monotherapy adapalene. The study was small, involving 65 patients in each group, with an age range of 12–39 years. All of these patients had mild-to-moderate facial acne, with at least 15 lesions at the outset.
The study involved avoidance of ultraviolet light (sunbeds) and the application of one of the treatments once a day for 12 weeks.
Outcome was determined by lesion counts, acne grading and global improvements at one, two, four, eight and 12 weeks. The results showed an earlier onset of action with CDP/BPO, with a faster significant reduction in inflammatory and total lesions. This was significant from week one onwards. The CDP/BPO group also reported better tolerability throughout the study, with fewer side-effects, such as dry skin. NS

Combination therapy in acne
Krunic A, Ciurea A, Scheman A. J Am Acad Dermatol 2008; 58(1): 60-2

The aim of this study was to look at the efficacy and safety of treating acne using spironolactone and drospirenone in combination. In the study, 27 women were included with either severe papular acne or nodulocystic acne.
Treatment included the oral contraceptive Yasmin, which contains 30 microgram ethinyl oestradiol and 3mg drospirenone, and a 100mg daily dose of spironolactone. Potassium levels were checked at the outset and around week five. Any side-effects were also recorded.
Although the numbers included were only small, the results were impressive, with 85 per cent of subjects being entirely clear of acne lesions or reporting excellent improvement at six months (7.4 per cent reported only mild improvement and 7.4 per cent, no improvement). There was also no significant elevation in potassium levels and no side-effects severe enough to warrant stopping the treatment.
It is important to note that the numbers included in this study were only small, but it suggests that further studies are required in this therapeutic area. NS

Allopurinol, SJS and toxic epidermal necrolysis
Halvey S, Ghislain PD, Mockenhaupt M et al. J Am Acad Dermatol 2008; 58(1): 25-32

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, life-threatening cutaneous reactions associated with a number of drugs. One of these is allopurinol, a xanthine oxidase inhibitor.
This study recruited 379 patients with severe cutaneous adverse reactions and 1,505 matched hospitalised controls. Analysis of the drugs to which these patients were most recently exposed revealed that 66 of the affected group had recently taken allopurinol (17.4 per cent), compared with 28 of the control group (1.9 per cent).
Further analysis revealed that daily doses of more than 200mg were associated with a higher risk, but this risk was not increased further by the co-prescribing of other medications and was also restricted to short-term use of up to eight weeks. The study concluded that allopurinol is the drug most commonly associated with SJS or TEN and this risk is dose-dependent.
It also revealed that in approximately 86 per cent of cases, allopurinol was prescribed inappropriately, suggesting that many of the cases of SJS and TEN were preventable. NS

Insulin resistance, psoriasis, CVD and diabetes mellitus
Boehncke S, Thaci D, Beschmann H et al. Br J Dermatol 2007; 157: 1249-51(10): 898-911

The aim of this small study was to investigate the metabolic state of patients with psoriasis and establish whether insulin resistance could be the link between psoriasis, cardiovascular disease and diabetes mellitus.
It recruited 39 consecutive patients attending a dermatology unit with moderate-to-severe plaque-type psoriasis. Data collection involved recording the severity of the psoriasis, using the Psoriasis Area and Severity Index (PASI), BMI, smoking habits and medication, and blood tests for lipids, markers of inflammation and multiple cytokines.
In addition, an oral glucose tolerance test was performed to calculate the homeostasis model assessment of insulin resistance (HOMA). The intima-media thickness of the carotid artery was also measured using ultrasound.
The results showed that the cohort of psoriasis patients were overweight to obese. They confirmed the well-established correlations between BMI and HOMA, and BMI and vessel wall thickness. They also revealed a significant correlation between the PASI score and insulin secretion, and the PASI was positively correlated with serum resistin levels – a cytokine known to be increased in insulin resistance. Lastly, measurements indicative of insulin resistance were found to be significantly correlated with psoriasis severity.
These findings support the concept that insulin resistance could be a consequence of the chronic inflammation seen in psoriasis and this could be the possible pathogenic cause for the comorbidities known to be associated with psoriasis.
Perhaps while we await larger, more robust studies, we should encourage our psoriasis patients to minimise their risk by addressing modifiable risk factors, such as weight and smoking.
- Dr Jane Barnard is a GP with an interest in dermatology in Yateley, Hampshire

Infant haemangioma and the possible risk of ulceration
Chamlin SL, Haggstrom AN, Drolet BA et al. J Pediatr 2007; 151: 684-9

This research was carried out as a cross-sectional analysis within a large prospective cohort study. The cohort study involved 1,096 children with haemangiomas of infancy.
The cohort was designed to characterise demographic, prenatal and perinatal risk factors for the development of infantile haemangiomas and to determine patient or haemangioma characteristics which predispose to complications or need for treatment.
Within the cohort study, haemangiomas were more common in fair-skinned, premature, female infants, who were more likely to be born as a product of multiple gestations. Their mothers were of higher maternal age and more likely to have had multiple-gestation pregnancies.
The cross-sectional study looked at ulcerating haemangiomas and whether there was any relationship between patient or haemangioma characteristics and the risk of ulceration. It found that of the 1,096 patients, ulceration occurred in nearly 16 per cent. No patient, maternal or pregnancy characteristics were statistically associated with the complication of ulceration, but the haemangioma characteristics were important.
Ulceration was statistically more likely in haemangiomas located on the lower lip, neck and anogenital region. Ulceration was also statistically more likely in larger haemangiomas of mixed (superficial and deep) clinical type and segmental morphologic type.
Ulceration occurred at a median age of four months, when the haemangioma is most likely to be in its proliferative phase. Bleeding occurred in 41 per cent and infection in 16 per cent, and most ulcerated haemangiomas required treatment. JB

Predicting acne relapse and second doses of isotretinoin
Azoulay L, Oraichi D, Bérard A. Br J Dermatol 2007; 157: 1240-8

This study from Canada aimed to identify and quantify predictors of acne relapse and of receiving a second dose of isotretinoin.
At first glance, it appeared to be a well-constructed, large study (17,351 patients) performed over a period of 19 years. However, further reading highlighted a number of flaws.
The researchers performed a nested case-control analysis of patients, with the results demonstrating a 41 per cent relapse rate. The main predictors of relapse were being male and under 16 years of age, and living in an urban area in Canada.
This paper is rather confusing; the summary states that isotretinoin doses >2,450mg and treatment longer than 121 days were statistically associated with acne relapse, whereas in the paper itself, it says that these two factors were less likely to lead to further anti-acne medication.
The authors mention several weaknesses in the study, which seemed quite significant. An administrative database was used, so only those patients who used their prescriptions were recorded. No record was made of three important groups: patients who had a relapse but did not consult a physician, those who had a relapse but did not use their prescription and those who used OTC preparations for relapses.
The urban/rural findings could also be questioned because patients in urban areas of Canada had much better access to a physician and were more likely to consult. The researchers also state that they could not adjust for acne severity or site because the database used the ICD-9 classification. They conclude that their data could be of prognostic value to clinicians treating acne sufferers; I think you need to draw your own conclusion. JB

Targeted immune modulators for severe psoriasis vulgaris
Canadian Agency for Drugs and Technologies in Health

This review aimed to investigate the use and impact of targeted immune modulators (TIMs). It looked at adalimumab, alefacept (not available in the UK), efalizumab, etanercept and infliximab.
The authors addressed four issues – clinical benefit and long-term harm, optimal dosages, comparative cost-effectiveness and the potential budgetary impact of prescribing TIMs.
TIMs were found to be far superior to placebo in treating chronic plaque psoriasis. They led to a physical improvement in psoriasis and in patient-related quality of life questionnaires.
The authors were unable to draw any conclusions about long-term side-effects because all of the trials lasted less than 12 months. They also found little evidence regarding optimum dosages. However, there was some evidence that continuing maintenance therapy for etanercept and infliximab was more effective in maintaining remission than ‘as needed’ therapy.
No comparative trials have been performed to suggest any one TIM is more efficacious. The authors estimated the cost of treating severe chronic plaque psoriasis with TIMs at about Can$30 million (£15.2 million) per year. However, this does not take into account the need to keep increasing the dose to maintain the same beneficial effect.
- Dr Waseem Chaudhry is a GPSI in dermatology in Caerphilly

Etanercept for plaque psoriasis in children and adolescents
Paller AS, Siegfried EC, Langley RG et al. N Engl J Med 2008; 358: 241-51

This US study, a double blind multicentre randomised control trial of 211 patients (aged four to 17) looked at using etanercept in children and adolescents with psoriasis.
Patients were randomised to active or placebo treatment for 12 weeks, followed by 24 weeks of open treatment for all and finally, a further randomisation to active and placebo treatment to investigate the effects of withdrawal and retreatment.
They were assessed using the Psoriasis Area and Severity Index (PASI). PASI scores of 50 and 75 denote improvement of 50 and 75 per cent from baseline, respectively. A PASI score of 75 was used as the primary endpoint for this study. The results showed a significant improvement with active treatment in the initial 12-week period, compared with placebo; 75 per cent of the patients on etanercept had a PASI score of 50, compared with 23 per cent on placebo. A PASI score of 75 was achieved in 57 per cent of the patients on etanercept, compared with 11 per cent on placebo. Adverse effects were rare.
These results suggest etanercept is a relatively safe treatment that can significantly reduce disease severity in children and adolescents with psoriasis. WC

Alcohol and psychological distress in psoriasis patients
Kirby B, Richards HL, Mason DL et al. Br J Dermatol 2008; 158; 138-40

This study investigated whether increased alcohol consumption is linked to increased levels of psychological distress in patients with psoriasis. Ninety-five patients with chronic plaque psoriasis attending a specialist outpatient clinic were assessed, using questionnaires.
Clinical severity was assessed with the Self-Administered Psoriasis and Severity Index and psychological distress with the Psoriasis Disability Index, the Hospital Anxiety and Depression Scale and the Penn State Worry Questionnaire. Alcohol consumption was assessed using alcohol subscales of the Health Screening Survey and the Michigan Alcohol Screening Test.
Results showed that 17–30 per cent of patients reported alcohol problems (depending on screening tool). A modest but significant association between psychological distress and increased alcohol use was demonstrated. Patients with increased alcohol use were shown to have increased levels of anxiety, depression and psoriasis-associated disability. Finally, a small but significant association between alcohol use and psoriasis severity was found. These results show that a significant minority of patients with psoriasis have increased alcohol intake and problems with psychological distress. Screening in clinics for alcohol-related problems could help to identify and manage these patients. WC

Azathioprine v mycophenolate mofetil in bullous pemphigoid
Beissert S. Arch Dermatol 2007; 143: 1536

Remission in bullous pemphigoid is effectively obtained with oral corticosteroids. However, side-effects are common, so steroid-sparing agents are often used as maintenance therapy.
Traditionally, azathioprine has been used, although mycophenolate mofetil has been suggested as an alternative. This study compared azathioprine and mycophenolate mofetil plus systemic corticosteroids for bullous pemphigoid.
Seventy-three patients in Germany were randomised to receive azathioprine and methylprednisolone or mycophenolate mofetil and methylprednisolone. Once blister formation had stopped, the steroid was tapered and discontinued.
Results showed no significant statistical difference in the two groups in the time needed to achieve total blister healing. Cumulative doses of steroids were also similar in both groups. The two groups had a similar number of adverse events (including infections), except for an increased number of abnormal LFTs in the azathioprine group.
The results show that in treating bullous pemphigoid, mycophenolate mofetil is as effective as azathioprine, with less hepatotoxicity. However, mycophenolate mofetil is much more expensive than azathioprine, which may limit its use. WC

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