Anti-tumour necrosis factor alpha therapy and increased risk of de novo psoriasis: is it really a paradoxical side effect?

OBJECTIVES: Tumour necrosis factor (TNF) alpha inhibitors (infliximab, etanercept, adalimumab) revolutionised the treatment of autoimmune diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD) and plaque psoriasis. During these treatments, cutaneous adverse effects may occur like eczema, lupus, alopecia areata or psoriasis, which represents a paradoxical adverse effect. The aim of this study was to collect and to analyse characteristics and outcomes of psoriasis induced by anti-TNF alpha treatments. METHODS: A search in the French Pharmacovigilance Database was performed between January 2002 and September 2009 using the following terms 'infliximab', 'etanercept', 'adalimumab' combined with the term 'psoriasis'. A literature review was performed utilising PubMed Database and Google scholar using permutations of the following terms 'infliximab', 'etanercept', 'adalimumab', 'tumour necrosis factor-α inhibitor' combined with 'psoriasis', 'palmoplantar pustular psoriasis', palmoplantar pustulosis'. Certolizumab pegol and golimumab were approved only recently and so were not included in the search. RESULTS: We found 57 cases in the French Pharmacovigilance Database and 184 cases in the literature. It appeared that the eruptions are most often pustular lesions and occur mainly on palms and/or soles (33.3% in the French Pharmacovigilance Database and 42.9% in the literature), while palmoplantar pustular psoriasis represents only 1.7% of the psoriatic patients. The three anti-TNF-alpha are involved in the psoriasis induction. Half the cases appeared with infliximab. The patients affected by this adverse effect are mostly women aged between 40-50 years old. The time of onset of psoriasis is highly variable. Those patients treated for their psoriasis with TNF-alpha inhibitor developed a psoriasis induced by the treatment with a different localisation and a different morphology from the initial psoriasis while other patients had a recurrence of this side effect with two different TNF-alpha antagonists, then the psoriasis developed with the 2nd anti-TNF alpha is of the same type as the psoriasis developed with the first molecule. CONCLUSIONS: This suggests that psoriasis occurring during anti-TNF alpha therapy are de novo psoriasis and not an aggravation of a pre-existing psoriasis. To this day several hypotheses have been proposed to explain the mechanism of action. The occurrence of this adverse effect may call into question the continuation of the treatment which is nevertheless effective.

Ketamine in chronic pain: A Delphi survey.

BACKGROUND: There is no recommendation in Europe for the use of ketamine in patients with chronic pain. The heterogeneity of practice highlights the need to seek the advice of experts in order to establish a national consensus. This Delphi survey aimed to reach a national consensus on the use of ketamine in chronic pain in Pain clinics. METHODS: A collaborative four-round internet-based questionnaire was used. It was created after literature search on ketamine administration in chronic pain and included about 96 items. It discussed utility and advantages, adverse events and deleterious aspects, methods of administration, concomitant treatments and assessment of results. RESULTS: Twenty-eight experts completed all rounds of the survey with a total of 81.3% items reaching a consensual answer. Neuropathic pain represents the first indication to use ketamine, followed, with a good to moderate utility, by other situations (fibromyalgia, complex regional pain syndrome, central neuropathic pain, peripheral neuropathic pain, nociceptive pain, sensitization, opioid withdrawal, palliative care, depression). Experts agreed on the rare occurrence of adverse events. Concerning routes of administration, intravenous infusion with doses of 0.5-0.9 mg/kg/d for 4 days of treatment is preferred. Place of care is hospital, as in- or out-patient, with a quarterly administration of ketamine. Finally, ketamine effectiveness is assessed 1 month after infusion, and experts encourage combination with non-pharmacological treatment. CONCLUSIONS: This Delphi survey established a consensus of pain specialists on the use of ketamine in refractory chronic pain, thus providing a basis for future comparative trials. SIGNIFICANCE: This Delphi survey in chronic pain reached agreement on four main aspects: (1) Priority to treat neuropathic pain with evaluation of effectiveness at 1 month; (2) No deleterious effects in the majority of listed diseases/situations with the absence or <3% of suggested adverse events; (3) 0.5-0.9 mg/kg/d IV infusion; (4) Combination with non-pharmacological treatment.

The Value of High-Frequency Repetitive Transcranial Magnetic Stimulation of the Motor Cortex to Treat Central Pain Sensitization Associated With Knee Osteoarthritis.

AIM: Chronic pain associated with knee osteoarthritis may develop in connection with a maladaptive process of pain sensitization in the central nervous system. Repetitive transcranial magnetic stimulation (rTMS) has been proposed to treat various pain syndromes related to central sensitization phenomenon, but was never applied in the context of knee osteoarthritis. METHODS: A 71-year-old woman presenting clinical evidence of central sensitization of pain associated with left knee osteoarthritis underwent monthly sessions of rTMS delivered at 10 Hz over the right motor cortex. RESULTS: From the week following the third session, she began to improve on various clinical aspects, including pain. After 10 sessions (i.e., almost one year of follow-up), pain was reduced by 67%, especially regarding neuropathic components, while sleep disorders and fatigue also improved by 57-67%. The central sensitization inventory (CSI) score was reduced by 70%. CONCLUSION: This observation suggests that high-frequency motor cortex rTMS could be a therapeutic option to treat neuropathic pain and psychological symptoms associated with central sensitization developing in the context of chronic osteoarthritis of the knee joint.

Treatment of refractory headache secondary to intracranial endovascular procedure by transcutaneous electrical nerve stimulation of the occipital nerve.

This pilot study aimed at assessing the effect of transcutaneous electrical nerve stimulation (TENS) of the occipital nerve (ON) to treat chronic refractory headache secondary to intracranial endovascular procedures (iEVP) in 4 patients. The duration of ON-TENS therapy was only 1 month (n=2) or longer than 4 months (n=2). Overall, pain intensity decreased from 7.8 (on a 0-10 scale) at baseline to 0.8 at 6 months after ON-TENS therapy initiation (-90%), while drug treatment was reduced from 34.3 to 0.8 (-98%) on the medication quantification scale. ON-TENS is a simple technique that may benefit patients with post-iEVP refractory headache.