New forum - latest research

Incidence of early melanoma and skin biopsy rates
The use of sunscreen products in post-transplant patients
URTI increase in acne patients
Venous insufficiency
BCCs: How close can you go?
Skin problems in wet hands
Development of sarcoidosis in cosmetic tattoos
Helping parents of infants with atopic eczema
Perinatal problems and atopic disease in childhood
Breastfeeding reduces the risk of childhood eczema

Incidence of early melanoma and skin biopsy rates
BMJ 2005; 331:481

In this study from the US, the authors are trying to discover if the apparent increase in incidence of early melanoma is a real increase, or simply the results of increased scrutiny, biopsy and diagnosis. From available data, there does appear to have been a six-fold increase in the incidence of melanoma from 1950 to 2002.

To do this, they looked at Medicare data from nine areas in the US, from 1986 to 2001, which was available for the over-65 population only. From this, they were able to extract information regarding melanoma diagnosis, which appeared to have increased 2.4-fold (45 to 108 per 100,000 population).

Closer inspection revealed that the increase was for in situ and localised disease only, with minimal increase for wider-spread and distant disease and more importantly, a minimal increase in mortality rates.

They then went on to look at available data for skin biopsy rates and found a similar increase of 2.5-fold (2,847 to 7,222 per 100,000 population) over the same period. The problem here was that from the available data, they were unable to differentiate between biopsies where there was a suspicion of the lesion being a melanoma, and all skin biopsies, including those for skin lesions associated with systemic disease.

Also, early stage disease had risen in incidence while the incidence for late stage disease and mortality stayed the same. From careful analysis of the data, the researchers came to the conclusion that the apparent increase was actually an increase in diagnosis, rather than a true increase in incidence of the disease.

This is all well and good, except for a number of important key points regarding melanoma. This is, in many cases, a disease of the younger to middle-aged population. The median age at diagnosis is 53 and it is the most common cancer in the female 25-year-old to 29-year-old population.

Other forms of skin cancer, especially BCCs and squamous cell carcinoma (SCC), tend to affect the older population more, requiring more biopsies in that age group. It is good to see that mortality and diagnosis of advanced disease is static in the over-65s, and that they feel the apparent rise in numbers for early disease is merely over-diagnosis, but what of younger people? Comparing the incidence of disease against all biopsies does not offer much and from that viewpoint, the study appears flawed.

They do mention the fact that there have always been questions as to the accuracy of diagnosis in the early stages from histological examination, with dermatologists arguing that some lesions appearing malignant to pathologists are biologically benign. This, again, will undoubtedly throw up questions.

What would be more useful to know is whether biopsy rates for lesions where there is a suspicion of melanoma have increased and how this correlates with an increase in incidence of the disease, but more importantly to know about biopsy rates and incidence in the younger and more relevant population.

With any study looking at mortality, it is useful to remember that this sort of data often relies on information extracted from death certificates, which we know are usually poor in their relation to actual causes of death. Most physicians have no formal training in completing such documents and with extensive co-morbidity being the norm in the elderly population, their accuracy often needs to be questioned.

In conclusion, all that this study essentially tells us is that the diagnosis of in situ and localised melanoma is increasing among older Americans and the number of total skin biopsies for the same population is also increasing. As the authors state, this is not very useful data and in essence, is not much different from correlating melanoma diagnosis with prostate biopsies.
- Dr Nigel Stollery is a GP in Kibworth, Leicestershire, and clinical assistant in dermatology at Leicester Royal Infirmary

The use of sunscreen products in post-transplant patients
Arch Dermatol 2005; 141:978-82

Triple immunosupressive therapy with cyclosporin, azathioprine and prednisolone used in transplant patients is known to increase the risk of developing non-melanoma skin cancer 100-fold.

This study from the Beaumont Hospital in Dublin sets out to determine which patients are most at risk and why some people are more likely to develop skin cancers than others.

The study involved 270 patients, 56 of whom went on to develop 100 tumours; 76 squamous cell carcinoma (SCC) and 24 basal cell carcinoma (BCC). The researchers concluded that those most at risk are male, over 50, with outdoor jobs and hobbies, and that the risk increases with the duration of suppression. In the case of BCCs, short periods of intense sun exposure were significant, whereas with SCCs, it was a cumulative effect of total sun exposure.

Of the 100 tumours, 93.5 per cent were on sun-exposed areas, with 80 per cent of those affected admitting to never using sun protection. Perhaps unsurprisingly, those under the age of 50 were more likely to use sun protection both before and after the transplant, as were female patients before transplantation.

The reasons given were cost, lack of knowledge, forgetfulness, unacceptable cosmetic appearance and in some cases, the misconception that their skin could tolerate the sun.

Although this study looked at transplant patients, the findings are relevant to the population as a whole. The results of this work illustrate the aetiological significance of sun exposure in the development of skin cancer. NS

URTI increase in acne patients
Arch Dermatol 2005; 141 (9): 1132-6

Acne patients taking long-term antibiotics are at significantly increased risk of upper respiratory tract infection (URTI). The odds of URTI were 2.15 greater than those not receiving treatment. The risk of urinary tract infection (UTI) was not increased. This was a sound cohort study, using a large sample of more than 118,000 patients from the GP research database .

Antibiotic use was for more than six weeks and mainly a combination of topical and oral. Follow-up was for one year. The authors controlled for several confounding factors to minimise the bias inherent to retrospective studies. The increased association of URTI with acne antibiotic use was shown not to be simply due to an increased frequency of visits to the doctor.

No explanation was given for why URTI increased, while UTI did not. The authors acknowledge that the study does not establish a causal association. A very useful editorial in the same issue, by Drs Chan and Shaw,1 discusses methodological considerations, as well as biological plausibility, including the possibility that antibiotic-induced alteration of resident flora might influence risk for URTI, as might possible immunomodulatory effects of antibiotics. This study is likely to arouse concern, particularly among patient support groups. The research is not enough on its own to change practice, but GPs may find themselves having to discuss the question with their patients.
- Dr Evanthia Frangos is a GPSI in dermatology in London

1 Editorial. Acne, Antibiotics, and Upper Respiratory Tract Infections. Chan A-W, Shaw JC. Arch Dermatol 2005; 141 (9): 1157

Venous insufficiency
J Am Acad Dermatol 2005; 53(3):504-8

Patients with poor venous circulation in their legs often complain of irritation, and scratching can damage associated varicose veins and produce significant bleeding. So I was surprised that no work had been carried out on the prevalence of such symptoms.

Here, itch, pain and burning sensation symptoms were assessed in 100 patients with mild to moderate chronic venous insufficiency, using a questionnaire. The prevalence of itching was high, at no less than 66 per cent of patients. Itch with burning and pain were found in 47 per cent and 44 per cent respectively. Surprisingly, there was no correlation between severity of symptoms and degree of venous insufficiency.

The study also found that itch, in particular, had a negative impact on quality of life. What we need now is a study to tell us which is the best, safest, long-term treatment.
-Dr Jane Barnard is a GP in Yateley, Hampshire

BCCs: How close can you go?
J Am Acad Dermatol 2005; 53: 464-8

Many GPs practise minor surgery, and the more experienced ones may often remove a small basal cell carcinoma (BCC) from the face. The problem is that because of cosmetic or functional concerns, the recommended 4mm skin margin is not always feasible. In such cases, the appropriate margin is often determined by the doctor on the basis of the clinical features of the tumour. This well-conducted study shows that this is not a wise compromise. More than 130 small (less than 1cm), well-demarcated nodular BCCs on the face were studied. The surgeon decided on a suitable margin, with the elliptical excisions having a range of margins from 1mm to 3mm. Frozen sections were examined to check the histology of the margin.

More than 20 per cent of the samples had histologically positive margins, with almost as many positives in the 3mm margin specimens as in the 1mm ones, and most (24 per cent) occurring within the 2mm margin range. Neither tumour size nor location appeared to be relevant. So take note, any tumour margin of less than 4mm runs the risk of incomplete excision, recurrence and further surgery. If in doubt, referral for Mohs’ micrographic surgery might be best. JB

Skin problems in wet hands
Int Arch Occup Environ Health 2005; DOI: 10.1007/ s00420-005-0016-0

As you read the abstract of this study and reach the part about swine slaughterhouses, its relevance to general practice may seem obscure. But put simply, the researchers were trying to find out if a properly implemented evidence-based skin protection programme might help to reduce the incidence of skin problems in workers in an environment that kept their skin wet and where there was risk of infection. This randomised control intervention study involves just six departments, so is clearly a small study.

Management and workers were involved in the strategy, with a safety representative and an education programme. Managers’ intervention alone did not make much difference, but team efforts produced significant reduction in skin problems. JB

Development of sarcoidosis in cosmetic tattoos
Arch Dermatol 2005; 141:869-872

Sarcoidosis is a granulomatous disease of unknown aetiology affecting multiple organs. The skin is involved in about one-third of cases. The characteristic histological finding in sarcoidosis is non-caseating granulomas.

This study challenges the commonly held belief that foreign material within non-caseating granulomas is incompatible with the diagnosis of sarcoidosis. The authors report the first case of systemic sarcoidosis presenting with sarcoidal granuloma formation in cosmetic tattooing.

Their patient, a 41-year-old woman, presented with nodular lesions in cosmetic tattoos along her lips and eyebrows, with associated shortness of breath. Histopathological analysis of the nodules showed sarcoidal granulomas associated with foreign body material. Subsequent chest X-ray confirmed hilar lymphadenopathy consistent with sarcoidosis.

After four months of therapy with topical steroids and doxycycline 100mg twice daily, her skin lesions and breathlessness fully resolved. A repeat chest X-ray showed resolution of the hilar lymphadenopathy. After stopping therapy, an eight-month follow-up showed no signs of relapse.

This case highlights the need to investigate for systemic sarcoidosis in any patients who present with skin nodules showing histopathological finding of non-caseating granulomas, even in the presence of foreign body material. It also confirms previous reports of successful treatment of cutaneous sarcoid with oral tetracylines.
-Dr Waseem Chaudhry is a GPSI in dermatology in Caerphilly

Helping parents of infants with atopic eczema
Pediatr Allergy Immunol 2005; 16(6):527-33

Atopic eczema usually develops in infancy or early childhood, with considerable impact on patients’ and parents’ quality of life. This randomised double-blind study compared the efficacy of pimecrolimus 1% cream against base vehicle in nearly 200 infants with mild to severe eczema.

The response was measured using the questionnaire Quality of life for the parents of children with atopic dermatitis. This measures factors such as psychosomatic well-being, effects on social life, confidence in medical treatment, emotional coping and acceptance of disease. The findings showed that pimecrolimus 1% cream was more effective than vehicle alone in improving quality of life scores.

Although this study shows the superior efficacy of pimecrolimus 1% cream compared with vehicle, it does not address the issue of the efficacy of the cream compared with conventional treatments for atopic eczema, such as topical steroids. Also, the patients had a wide range of disease, from mild to severe eczema. This study does not show if pimecrolimus had an equal benefit in all severities of atopic eczema. WC

Perinatal problems and atopic disease in childhood
Clin Exp Allergy 2005; 35(9):1135-40

Previous work looking at the link between atopic disease, foetal development and obstetric complications has given equivocal results. This was a retrospective study looking at 700 families in the Netherlands who had children between 1988 and 1990. Data were collated from neonatal and birth records, and health surveys at the age of six years.

The results showed that gestational age was inversely related to risk of developing asthma and low birthweight was associated with a lower risk of developing allergy (although this was not statistically significant). The ratio of neonatal head circumference to birth weight was positively associated with the risk of atopic disorders, especially asthma, while vacuum extraction was a risk factor for allergy, but not asthma.

Induced labour was positively associated with the risk of inhalant allergy and asthma (to a lesser extent), but no relationship with either forceps delivery, or caesarean section and atopy, was shown by the study.

The results from this survey were rather confusing and in some cases, surprising; for example, low birthweight being associated with the risk of developing allergy. Other results were more in keeping with current beliefs, such as prematurity being a risk factor for the development of asthma.

Overall, the results were interesting, but the relationship between atopic disease, foetal development and obstetric complications remains equivocal. WC

Breastfeeding reduces the risk of childhood eczema
J Allergy Clin Immunol 2005; 116(3):657-61

The issue of breastfeeding being a ‘preventative’ measure for atopy has been an attractive notion for some time, but the theory has always been controversial.

This was a prospective study of a birth cohort of more than 4,000 children in Sweden. Data were collected via parental questionnaires at two months and one, two and four years of age on breastfeeding, allergic symptoms and confounding factors. Blood specific IgE was analysed at the age of four as a measure of atopy. Children who developed symptoms of atopy during the period of breastfeeding were excluded, to avoid disease-related modification of exposure.

The results of the study showed that breastfeeding for a period of four months or more was associated with a reduced risk of developing eczema at the age of four years. This was found to be the case irrespective of combination with asthma, sensitisation to common allergens, or parental allergic disease.

The decreased risk was most notable in early onset eczema (before age two) persisting to four years. This study supports the belief that breastfeeding for more than four months can help lower the risk of eczema at the age of four years. WC

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