M.J.D. Goodfield

Psoriasis patients with nail disease have a greater magnitude of underlying systemic subclinical enthesopathy than those with normal nails

Objective Enthesopathy is a major feature of psoriatic arthritis (PsA), which is supported by imaging studies. Given that nail disease often predates PsA and that the nail is directly anchored to entheses, the authors asked whether nail involvement in psoriasis equates with a systemic enthesopathy. Methods Forty-six patients with psoriasis (31 with nail disease) and 21 matched healthy controls (HC) were recruited. 804 entheses of upper and lower limbs were scanned by an ultrasonographer blinded to clinical details. Results Psoriasis patients had higher enthesitis scores than HC (median (range) 21 (0–65) vs 11 (3–39), p=0.005). Enthesopathy scores were higher in patients with nail disease (23 (0–65)) than in patients without nail disease (15 (5–26), p=0.02) and HC (11 (3–39), p=0.003). Inflammation scores of patients with nail disease (13 (0–34)) were higher than patients without nail disease (8 (2–15), p=0.02) and HC (5 (0–19), p<0.001). Modified nail psoriasis severity index scores were correlated to both inflammation (r2=0.45, p=0.005) and chronicity scores (r2=0.35, p=0.04). No link between the psoriasis area and severity index and enthesitis was evident. Conclusion The link between nail disease and contemporaneous subclinical enthesopathy offers a novel anatomical basis for the predictive value of nail psoriasis for PsA evolution.

British Association of Dermatologists guidelines on the efficacy and use of acitretin in dermatology

This is a new set of guidelines prepared for the BAD Clinical Standards Unit, made up of the Therapy & Guidelines Subcommittee (T&G) and the Audit & Clinical Standards Subcommittee (A&CS). Members of the Clinical Standards Unit are: H.K. Bell (Chairman T&G), L.C. Fuller (Chairman A&CS), N.J. Levell, M.J. Tidman, P.D. Yesudian, J. Lear, J. Hughes, A.J. McDonagh, S. Punjabi, N. Morar, S. Wagle (British National Formulary), S.E. Hulley (British Dermatological Nursing Group), K.J. Lyons (BAD Scientific Administrator) and M.F. Mohd Mustapa (BAD Clinical Standards Manager).

Hydroxyurea in the management of therapy resistant psoriasis

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.

Advice on the safe introduction and continued use of isotretinoin in acne in the U.K. 2010

Department of Dermatology, Leeds General Infirmary, Leeds LS1 3EX, U.K. *Department of Dermatology, Cumberland Infirmary, Carlisle CA2 7HY, U.K. Independent Acne Patient Advisor, Belfast City Hospital, Belfast BT9 7AB, U.K. Department of Dermatology, Belfast City Hospital, Belfast BT9 7AB, U.K. §Department of Dermatology, The Park Hospital, Arnold, Nottingham NG5 5BX, U.K. –Department of Dermatology, Nuffield Health Newcastle upon Tyne Hospital, Newcastle upon Tyne NE2 1JP, U.K. **Department of Dermatology, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZN, U.K.

Treatment of dermatophyte infection of the finger‐ and toe‐nails with terbinafine (SF 86‐327, Lamisil), an orally active fungicidal agent

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.

Digital calcification in systemic sclerosis : effective treatment with good tissue preservation using the carbon dioxide laser

Summary Tissue calcification of the fingers associated with limited systemic sclerosis is a common problem and is the source of considerable morbidity as it may be extremely tender and cause considerable functional disability. The current treatment of digital calcification is unsatisfactory. We evaluated the use of the carbon dioxide (CO2) laser in the management of this condition in six patients with the limited form of systemic sclerosis. A total of 21 areas of symptomatic digital calcification ofthe fingers were treated. Complete resolution of symptoms occurred in 12, moderate response with partial improvement was seen in five, little improvement was observed in two, and recurrence of calcinosis was found in two. The patients average healing time was 6 weeks (range 4–10). The median duration of follow‐up was 20 months (range 12–40). Postoperative infection was seen in two patients, and resolved completely in both wilh the use of topical and oral antibiotics. We found the CO2 laser a simple and effective treatment for most of the symptomatic lesions of digital calcification, and it may obviate the need for deforming surgery in many cases.

Investigations of the ‘active’ edge of plaque psoriasis: vascular proliferation precedes changes in epidermal keratin

We have investigated markers of epidermal proliferation and differentiation in terms of keratin expression, the morphology of the cutaneous vasculature, and numbers of cutaneous mast cells, in patients with chronic plaque psoriasis. Using the phenomenon of the ‘active edge’, we have studied these features in the psoriatic plaque itself, and in the clinically normal active and inactive edges of the same plaque. Our results confirm the anticipated changes in keratin profiles, mast cell numbers and psoriatic morphology of the vasculature within the plaque itself. They further indicate that the vascular changes precede the epidermal and mast cell features at the active edge, and that the inactive edge is inactive for all of these variables. Mediators responsible for the vascular proliferation and elongation must be present in increased amounts at the active edge when compared with the inactive, and include locally produced and circulating factors.

Liver fibrosis in patients with psoriasis and psoriatic arthritis on long-term, high cumulative dose methotrexate therapy

OBJECTIVES Dermatologists and rheumatologists have differed in their use of serial liver biopsy and liver function tests (LFT) to monitor the risk of hepatic fibrosis in long-term MTX therapy. It is judged safe to monitor LFT only in RA. Whilst there are few studies in PsA to justify this approach, it is widely used in rheumatology practice. The study aimed to assess prevalence of hepatic fibrosis in both psoriasis and PsA patients on long-term MTX therapy. METHODS A prospective study of 54 patients with psoriatic disease had a liver biopsy according to dermatology guidelines on long-term MTX treatment with full assessment of risk factors. Previously, monitoring these patients was in accordance with ACR guidelines with 3-monthly LFT. RESULTS MTX treatment duration was a mean of 6.9 years, with a mean cumulative dose of 4396 mg. There were no cases of advanced fibrosis or of cirrhosis and mild early fibrosis in 11 (22%) patients. The presence of early mild changes was related to the number of risk factors that the patient had for hepatic fibrosis [also the risk factors for non-alcoholic steatohepatitis (NASH)]. Pro-collagen 3 N-terminal peptide (PIIINP) was unhelpful in PsA and frequently elevated despite normal liver biopsy. CONCLUSIONS Despite other risk factors for NASH, monitoring for hepatic fibrosis using serial liver function and ACR guidelines tests alone as in RA appears safe in psoriasis and PsA. Liver biopsy ought to be considered to assess the liver if LFT are persistently elevated. PIIINP is misleading in active PsA.

The link between enthesitis and arthritis in psoriatic arthritis: a switch to a vascular phenotype at insertions may play a role in arthritis development

Objective Subclinical enthesopathy is recognised in both psoriasis and psoriatic arthritis (PsA). This study used ultrasonography with power Doppler (PD) to test the hypothesis that subclinical enthesopathy in PsA was associated with an ‘inflammatory’ or vascular phenotype compared to that seen in psoriasis. Methods 100 patients with a mean age of 46.3 years (SD 15) (42 with psoriasis and 58 with PsA) and 23 matched healthy controls (HC) from two centres were included. 1230 lower limb entheses were scanned by ultrasonographers blinded to clinical details. Both inflammatory and chronic features of enthesopathy were scored. Results Psoriasis patients (with or without arthritis) were more likely to express a vascular phenotype, with higher inflammation-related enthesopathy scores than HC (for inflammation p<0.0001, for chronicity p=0.02, for total ultrasound scores p<0.0001). The PsA patients had higher ultrasound enthesopathy scores than psoriasis patients (inflammation p=0.04, chronicity p=0.02) and HC (inflammation p<0.0001, chronicity p=0.003). When symptomatic entheses were excluded, PsA patients still had higher PD scores than psoriasis patients (p=0.003). Doppler positivity in at least one entheseal site was observed more frequently in PsA (21/58, 36.2%) versus psoriasis (4/42, 9.5%; p=0.002). Conclusions This study shows that the ultrasound appearances of subclinical enthesitis in psoriasis differ from the subclinical enthesitis in PsA, with PsA patients having more PD. This is suggestive of a more inflammatory or vascular process in PsA, and offers potentially novel insights into the progression from skin to joint disease in psoriasis.

Clinical and Pharmacogenetic Influences on Response to Hydroxychloroquine in Discoid Lupus Erythematosus: A Retrospective Cohort Study

The recommended systemic therapy of choice for discoid lupus erythematosus (DLE) is the 4-aminoquinolone antimalarial hydroxychloroquine. There is limited published information on the likelihood of clinical response and, in particular, what factors influence outcome. We conducted a multicenter observational and pharmacogenetic study of 200 patients with DLE treated with hydroxychloroquine. The primary outcome was clinical response to hydroxychloroquine. We investigated the effects of disease attributes and metabolizing cytochrome P450 (CYP) polymorphisms on clinical outcome. Although the majority of patients responded to hydroxychloroquine, a significant proportion (39%) either failed to respond or was intolerant of the drug. Cigarette smoking and CYP genotype did not have any significant influence on response to hydroxychloroquine. Moreover, multivariate analysis indicated that disseminated disease (odds ratio (OR): 0.21; 95% confidence interval (CI): 0.08-0.52; P<0.001) and concomitant systemic lupus erythematosus (SLE; OR: 0.06; 95% CI: 0.01-0.49; P = 0.009) were significantly associated with lack of response to hydroxychloroquine. These findings suggest that baseline lupus severity and SLE are predictors of response to hydroxychloroquine. A prospective study is now required to further investigate the relationship between disease activity and response to hydroxychloroquine. This will have the potential to further inform the clinical management of this disfiguring photosensitive disease.