Screening for latent TB in patients with psoriasis
Doherty SD, Van Voorhees A, Lebwohl MG et al. J Am Acad Dermatol 2008; 59: 209-17
Latent TB is thought to be a significant problem in the US, affecting an estimated 9.6 million to 14.9 million individuals. Chronic immunosuppression is a known risk factor for reactivating latent TB.
The biologic TNF-alpha inhibitors are a promising new therapy in the treatment of psoriasis. However, TNF-alpha is also an important cytokine in preventing TB infection and keeping latent TB infection from reactivating. Therefore, the use of immunosuppressive and immunomodulatory therapies in the treatment of psoriasis has been associated with a risk of latent TB reactivation.
The aim of this US study was to try to reach a consensus on screening for latent TB in psoriasis patients receiving these therapies. Reports in the literature on immunosuppressive therapy and TB were reviewed.
The authors found few evidence-based studies on screening for latent TB in psoriasis patients who were about to receive immunosuppressive therapy. Screening patients before starting immunosuppressive (ciclosporin, methotrexate) or immunomodulatory (biologics) therapy is paramount. The current recommended method is a tuberculin skin test.
Positively identified patients need to be treated with a full course of latent TB infection prophylaxis, lasting nine months, before commencing their immunosuppressive or immunomodulatory therapy. However, many experts now believe that patients may be started on immunosuppressive or immunomodulatory therapy after one to two months if they require rapid control of their psoriasis and they are strictly adhering to the latent TB prophylactic regimen.
In conclusion, the authors recommended that all psoriasis patients who are about to have immunosuppressive or immunomodulatory therapy should be screened for latent TB with a tuberculin skin test before starting treatment. Positively identified patients should receive a full course of latent TB infection prophylaxis. Immunologic therapy should be delayed until the latent TB infection prophylaxis is completed. However, in patients requiring rapid control of their psoriasis, immunologic therapy could be started at one or two months, provided they adhere to the prophylactic regimen.
Dr Waseem Chaudhry is a GPSI in dermatology in Caerphilly.
Genetic variation in patients with psoriasis on methotrexate
Warren RB, Smith RL, Campalani E et al. J Invest Dermatol 2008; 128: 1925-9
Methotrexate is widely used as a systemic therapy for moderate to severe psoriasis, although its use can be limited by unpredictable efficacy and toxicity.
It is thought that single-nucleotide polymorphisms (SNPs) in methotrexate transmembrane transporters and adenosine receptors are associated with efficacy and toxicity of the drug.
This study aimed to test this hypothesis by examining the DNA of 374 patients with chronic plaque psoriasis. Phenotypic data on the efficacy and toxicity of methotrexate in these patients was collected. Using these data, the authors found that SNPs in certain methotrexate efflux genes were associated with an increased efficacy and toxicity. One of the gene SNPs was highly associated with toxicity to methotrexate.
The authors concluded that knowledge of genes relevant to methotrexate efflux could be relevant in selecting patients for this therapy. Although the research is in its early stages, the prospect of laboratory-based tests to identify patients susceptible to methotrexate toxicity and identifying those likely to benefit is a promising prospect. WC
Atopic dermatitis and serum IgE auto-antibodies
Altrichter S, Kriehuber E, Moser J et al. J Invest Dermatol 2008; 128: 2232-9
Atopic dermatitis (AD) is a common condition in which 80 per cent of those affected have elevated levels of IgE connected to the severity of the disease. A small proportion of patients with AD have been shown to have no detectable sensitivity to a broad panel of exoallergens, suggesting the existence of a non-immunological or an auto-reactive pathomechanism.
This study took the serum of 192 patients with AD and looked at their IgE to see if it was specifically targeted against the human epithelial cell line A431 and primary keratinocytes. Previous studies have shown that patients with AD have IgE targeted against self-proteins, supporting a theory of auto-reactivity, but none has looked specifically at this cell line and keratinocytes. As a control, the same studies were also performed on the serum of people without AD.
The study involved incubating normal skin with primary keratinocytes and analysing it by immunohistology, confocal laser microscopy and flow cytometry.
The results showed that 28 per cent of AD patients displayed serum IgE auto-reactivity by Western Blot analysis, but none in the control group, and the degree of auto-reactivity correlated with severity of disease. The researchers considered that the elevated IgE auto-antibodies were the result of repetitive and severe injury to the skin and found it conceivable that environmental exoallergens probably initiated the acute phase of the allergic cutaneous disease, leading to the destruction of keratinocytes and the release of auto-antigens into the circulation. IgE autoimmunity then contributes to the chronicity and severity of the continuing disease, even in the absence of further environmental allergens.
The IgE patterns pointed to the existence of unique and common specificities against epidermal or A431-derived proteins and immunostaining identified cytoplasmic and cell membrane associated targets for the auto-antibodies. In some, the surface staining patterns were higher at points of cellular contact.
Dr Nigel Stollery is a GP in Kibworth, Leicestershire, and clinical assistant in dermatology at Leicester Royal Infirmary
Antibiotic prescribing for skin and soft tissue infections
Hersh AL, Chambers HF, Maselli JH, Gonzales R. Arch Intern Med 2008; 168(14): 1585-91
In the past few years, the incidence of community-acquired MRSA skin and soft tissue infections has been steadily increasing. This study looks at the US, but similar trends are almost certainly the case in the UK and elsewhere.
As a result of these infections, prescribing trends and frequency of visits to the doctor have probably changed. This study was designed to find out if this is true and if so, how these trends have changed. In the US, data on visits and prescribing are available from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey from 1997 to 2005. These provide information about visits to primary care, the emergency department and hospital outpatient clinics.
The study looked at skin infections, soft tissue infections, cellulitis and abscesses. The results confirmed predictions, with an increase in the eight-year period from 32.1 to 48.1 visits per 1,000 population, equating to 14.2 million in 2005.
When these figures were broken down, it was revealed that 95 per cent of the change was attributable to cellulitis and abscesses, attendance rates for which increased from 17.3 to 32.5 visits per 1,000 population.
When location was reviewed, it was found that the largest increase in visits was to emergency departments, especially those in the south of the US and in safety net emergency departments (which provide care for the uninsured). It also revealed that the largest increase was seen in the black and under-18 populations. Along with an increase in the number of visits, antibiotic use also increased, from 7 to 28 per cent of visits. The predictors of this are age under 45 years, living in the south and presentation to an emergency department.
This study, although based on figures from at least three years ago, revealed that the incidence of community-acquired MRSA is on the increase and in the US, this increase is disproportionately high in certain groups and areas. It also indicated that there have been changes in prescribing habits and that at the time, there was room for modification of these trends, which almost certainly continues to be the case in 2008. NS.