Dr Christian Derancourt
On Saturday morning, 4 speakers gave an excellent round-up of the various aspects of viral STIs. Here is a broad look at the most important points:
- the now well-proven link (systematic review and meta-analyses) between HCV infection and lichen planus, as well as PCT, nodular prurigo; the variable frequency of related cryoglobulinemia, of poor prognosis (particularly high in France: 55%); the change in the prognosis for the infection with the new treatments
- the increase in the incidence of Kaposi's disease over the last 10 years in sub-Saharan Africa but also in the USA among patients infected with HIV (whether the infection is controlled or not); in San Francisco 30% of Kaposi's sarcomas have occurred in the last 3 years among the HIV-negative gay population. For HIV patients, the primary treatments are still: radiotherapy, alitretinoin, and intralesional chemotherapy. The PD-1 receptor pathway is another treatment option, as for melanoma!
- HPV infection and how it is changing; in particular the oral infection rate (10% in men and 3.6% in women), the higher risk with cunnilingus than fellatio; the treatment of condyloma with specific reference to sinecatechins (green tea leaf extracts) available in a 15% concentration in the USA and 10% in Europe and Canada...
The Cleveland (poster 2800) authors offered guidelines for carrying out additional examinations in dermatomyositis, depending on the increased risk (OR) for each cancer, and its frequency. For all patients (symptomatic or not), chest scan for lung cancer (OR=15-19.7), colonoscopy for colon cancer (OR=4), CA 125 and endovaginal ultrasound for ovarian cancer (OR=5.4), breast exam and mammogram after age 30 for breast cancer (OR=3.5), cervical smear up to age 80 for cervical cancer. For other types of cancer examinations are only suggested when there are even more symptoms or risk factors (oesophagus, pancreas, kidneys, bladder, cancer of the naso-pharynx, haematological cancers). During follow-up, questioning and clinical examinations associated with the same screening tests as for the general population are recommended, and further examinations if there is the slightest clinical doubt... Other authors from the same city (poster 2799) tried to establish a score for the neoplasia risk associated with DM (after 28 patients with cancer out of 242); the initial results were presented and the score needs to undergo external validation, the variables are however already interesting: males, the oldest subjects, presence of Gottron's papules, "mechanic's hands", and the existence of arthralgias.
Dr Rémi Maghia
New treatments for rosacea
Two alpha adrenergic agonists: brimonidine gel 0.33% (alpha2-adrenergic receptor agonist) and oxymetazoline hydrochloride cream (alpha1- and alpha2-adrenergic receptor agonist) were tested. For brimonidine, phase II trials in erythematous rosacea showed a significant improvement in facial erythema for eight to twelve hours, compared to placebo, with a favourable tolerance profile. For oxymetazoline two conclusive phase III trials made it possible to obtain FDA pre-approval, expected in 2016.
Azelaic acid foam 15% for treating papulo-pustular rosacea.
A randomised double-blind trial against its vehicle was carried out at twenty sites in the USA. Patients aged 19 and over with a moderate to severe clinical IGA score received either the active ingredient as a topical foam or the vehicle, twice a day for 12 weeks. For the IGA score the criterion "completely or almost clear" was significantly achieved in comparison to the vehicle, at 12 and 16 weeks respectively, for about one-third of the patients. The side effects, which were expected, were notably tingling and itching sensations. FDA approval was obtained in August 2015 in light of two phase II studies conducted in parallel.
What about the long-term efficacy of ivermectin in cream form?
The IGA criterion "completely or almost clear" climbed from less than 30% at week 12 to about 70%, increasing over time, at week 40. (Stein Gold et al. study J Drugs Dermatol.2014).
The Taïeb study in BJD 2014 showed that the median time for a relapse in rosacea after treatment was 115 days with ivermectin 1% applied topically once a day, versus 85 days with topical metronidazole 0,75% once a day. The no relapse rate was 37.3% for ivermectin.
Prof Frédéric Caux
Treatment of pemphigus vulgaris is currently based on generalised corticosteroid treatment. However, new treatments, notably rituximab, have been tested in humans to prevent the side effects with oral corticoids. Rituximab, which binds to the CD20 receptor of the lymphocytes, induces B lymphopenia and reduced production of the pathogenic antibodies that target desmogleins 1 and 3. A poster (P3530) introduces a new treatment targeting the B lymphocytes which was tested in a canine model of pemphigus foliaceus. It is a Bruton's tyrosine kinase inhibitor, PRN473, which leads to a reduction in the signalling downstream from the lymphocyte B and receptor and from the receptor at the Fcg, resulting in less inflammation caused by these receptors. Seven dogs suffering from spontaneous pemphigus received PRN473 alone or in combination with an immunosuppressant. An improvement in the clinical lesions was observed in all the dogs but with early relapse for 2 dogs and a complete improvement for 4 dogs. When taken again during a relapse, PTN473 was effective once more. This molecule is also effective in a different autoimmune disease, collagen-induced arthritis. A phase II study using a different Bruton's tyrosine kinase inhibitor, PRN1008, was started among humans with an indication of pemphigus vulgaris.
A poster (P3516) showed the results, after 4 years, of the effect of everolimus on the skin lesions of patients who were tuberous sclerosis complex carriers. These patients received everolimus due to subependymal giant cell astrocytomas or renal angiomyolipomas (EXIST-1 and EXIST-2 trials). The analysis of the skin lesions was a secondary assessment criterion in these trials. 212 patients where included and the clinical assessment was carried out on a scale of the overall opinion of the doctor. A complete response to the skin lesions was observed in 4.7% of the patients with 58.5% experiencing a partial response. Side effects were common with about 40% of the patients developing stomatitis. The photographs on this poster did not show the clear efficacy of everolimus on facial angiofibromas. Therefore everolimus does not seem to offer a significant reduction in skin lesions for this genetic disease. However, it would be worthwhile to supplement this work with a trial centred on the dermatological aspect of the disease with a standardised assessment of the angiofibromas.