J.-H. Saurat

The Association of the Two Antimalarials Chloroquine and Quinacrine for Treatment-Resistant Chronic and Subacute Cutaneous Lupus erythematosus

Antimalarials are the first line in the treatment of chronic and subacute cutaneous lupus erythematosus (LE). However, some patients show either no or only minor improvement on antimalarial monotherapy. We treated 14 patients (9 with chronic LE and 5 with subacute cutaneous LE) who had poorly responded to chloroquine or hydroxychloroquine with an association of chloroquine and quinacrine. The initial dose was: chloroquine 100 mg 3x/day and quinacrine 65 mg 3x/day. The skin lesions improved significantly or cleared totally in 5 of the 9 patients with chronic LE and in all the 5 patients with subacute cutaneous LE. These findings suggest that a chloroquine-quinacrine combination may sometimes be superior to the usual antimalarial monotherapy, especially for subacute LE. If chloroquine or hydroxychloroquine fails to control chronic or subacute cutaneous LE, chloroquine-quinacrine is worthy to be tried.

Intralesional and intravenous treatment of cutaneous B-cell lymphomas with the monoclonal anti-CD20 antibody rituximab: report and follow-up of eight cases

Background  Rituximab (MabThera®; Roche, Basel, Switzerland; an anti‐CD20 chimeric monoclonal antibody) has been shown to have significant activity in nodal B‐cell lymphomas, with few associated adverse effects. Its efficacy and safety were first demonstrated in the treatment of systemic B‐cell lymphomas. Intravenous and subsequently intralesional administration of rituximab have also been reported to be effective and well tolerated in cutaneous B‐cell lymphoma (CBCL). The comparative efficacy of intravenous vs. intralesional rituximab in CBCL is not known.

Dermoscopy for the in vivo Detection of Sarcoptes scabiei

We report the case of an 80-year-old patient who had intense pruritus which did not respond to a 3-month treatment with topical corticosteroids. On dermoscopy examination of the excoriations, we found the typical dermoscopic aspect of the scabies mite at a distance. Dermoscopy allows identifying a triangular structure which corresponds to the anterior section of the mite including the mouth part and the 2 pairs of front legs. This aspect has been described as resembling a jetliner with its trail, a delta glider or a spermatozoid. Traditional diagnostic methods for scabies failed in this case because the mites were at a distance from the burrows. This was due to the fact that the reaction to the mite was less pronounced and the diagnosis is frequently missed. Dermoscopy is a useful tool for the diagnosis of scabies either as a diagnostic test or to guide the traditional diagnostic tests.

Skin and nail responses after 1 year of infliximab therapy in patients with moderate-to-severe psoriasis: a retrospective analysis of the EXPRESS Trial.

Background: The EXPRESS study demonstrated the initial efficacy of infliximab in psoriasis affecting the skin and nails. Objective: To further assess how patients with a positive initial response to infliximab respond to 1 year of continuous infliximab treatment. Methods: A retrospective analysis of patients with moderate-to-severe plaque and nail psoriasis who initiated and continued infliximab treatment up to week 46 was conducted. Results: Among all nail psoriasis patients receiving 1 year of infliximab (n = 186), 74.6 and 54.1% achieved at least 75 or 90% improvement in the Psoriasis Area and Severity Index (PASI) at week 50. These PASI-75 (n = 138) and PASI-90 (n = 100) responders had respective mean improvements from baseline to week 50 of 93.6 and 97.3% for the PASI, 90.6 and 94.1% for the Dermatology Life Quality Index (DLQI) and 78.2 and 80.3% for the Nail Psoriasis Severity Index (NAPSI). Conclusions: Infliximab treatment for 1 year produced sustained improvement in PASI, DLQI and NAPSI scores.

Erosive pustular dermatosis of the leg: report of three cases

Summary Erosive pustular dermatosis of the leg is a distinct form of spongiform amicrobial pustulosis. The disorder typically affects the lower limbs of elderly patients presenting with chronic venous insufficiency and stasis dermatitis, and has a chronic course. Three elderly patients with chronic venous ulcers are described, who developed pustules and moist eroded lesions on the leg. The clinical and histological features were typical for erosive pustular dermatosis. The lesions rapidly responded to topical treatment with either tacrolimus or corticosteroids. Of note, this condition was associated with a diverticular disease in two patients, while in another patient an epidermoid carcinoma of the tongue was present. Erosive pustular dermatosis of the leg is an uncommon but distinct skin disorder typically associated with trophic changes of the lower limbs. Our observations raise the question of the relation of erosive pustular dermatosis of the leg with the group of neutrophilic dermatoses. Topical immunotherapy with tacrolimus may constitute a novel therapeutic option for this frequently recalcitrant condition.

The antibacterial activity of topical retinoids: the case of retinaldehyde.

Background: Retinoids such as retinoic acid (RA), retinol (ROL) and retinaldehyde (RAL) are currently used in many formulations and indications ranging form acne to skin aging. Most if not all their pharmacological activities occur through binding to nuclear receptors with subsequent modulation of the activities of several genes. Little attention has been given to the many other potential actions on the surface of the skin. Aim: To analyse the potential anti-infective activities of topical ROL, RAL and RA. Methods: Microbial minimal inhibitory concentrations (MIC) of ROL, RAL and RA were determined by a microdilution method on reference strains including Staphylococcus aureus, Staphylococcus epidermidis, Micrococcus flavus, Propionibacterium acnes, Micrococcus luteus, Enterococcus faecium,Staphylococcus hominis, Escherichia coli, Pseudomonas aeruginosa, Candida albicans and 133 clinical strains including methicillin-resistant S. aureus, methicillin-sensitive S. aureus, coagulase-negative Staphylococcus, Streptococcus group B, Enterococcus faecalis, vancomycin-resitant E. faecalis, vancomycin-resistant E. faecium and Pseudomonas/Klebsiella. In two clinical trials in healthy human volunteers, skin bacterial densities were evaluated in samples obtained with the cylinder scrub method: (1) 2 and 5 h after a single application of 0.05% RAL or vehicle on the forearm and (2) in a single-blind randomized study where 0.05% RAL or vehicle were applied daily for 2 weeks on the forehead of 22 volunteers. Paired results from treated (or vehicle) and untreated areas were analysed. Results: Of the three retinoids tested, only RAL showed a significant in vitro antibacterial activity; this activity was found against reference strains of gram-positive bacteria like S. aeureus, Micrococcus spp. or P. acnes. No activity was found against gram-negative bacteria. These results on reference strains were confirmed on 133 clinical isolates. MIC50 and MIC90 values for RAL were 8 and 16 mg/l, respectively, for methicillin-sensitive S. aureus and 4 and 8 mg/l for methicillin-resistant S. aureus. The two in vivo studies showed that areas treated with RAL had a significant decrease in the bacterial counts. In the forehead study, the median decrease was 102 log/cm2 for P. acnes and 101.8 log/cm2 for staphylococci. No resistant bacteria were found after 2 weeks of topical use. Preliminary results suggest that the antibacterial effect of RAL is due, in part, to the aldehyde group in the lateral chain, since non-retinoid pseudo-analogues of the chain, like citral and hexenal, showed a similar antibacterial activity. Conclusion: We have shown that RAL differs from parent natural retinoids such as ROL and RA in demonstrating significant antibacterial activities upon topical use. This activity is likely due to the aldehyde group in the isoprenoic lateral chain, which illustrates the potential bifunctional properties of some retinoids.

Topical Colchicine Therapy for Actinic Keratoses

Background: The beneficial effect of topical colchicine therapy for actinic keratoses has already been described in 1968. Objective: To confirm that the application of a 1% colchicine gel is a safe and effective treatment for actinic keratoses. Methods: Twenty patients were included in a double-blinded protocol. They all had actinic keratoses on the scalp, most of which had been previously treated with 5-fluorouracil or cryotherapy. Ten patients applied twice daily on the forehead a hydrophilic gel (placebo group), while the other 10 where treated with the same gel containing 1% of colchicine (colchicine group). Erythema and efficacy were evaluated at each control on days 7, 30 and 60, with repetitive blood tests to exclude a possible systemic absorption. Results: A complete healing of the solar keratoses was observed in 7 out of the 10 patients treated with 1% colchicine gel; these showed no recurrence after 2 months of follow-up. Burning and itching occurred only in the colchicine group after 2 or 3 days of application, with an inflammatory reaction on the areas where the gel was applied, while pustules and crusts were located specifically on the actinic keratoses. Repeated blood controls showed that there was no systemic absorption. Conclusions: This double-blind placebo-controlled study confirms the activity of colchicine for the treatment of actinic keratosis. A comparison with other topical treatments in terms of efficacy and practicability is needed.

Eccrine syringofibroadenoma in a patient with erosive palmoplantar lichen planus.

We report the case of an 82-year-old woman with a 6-year history of erosive palmoplantar lichen planus associated with eccrine syringofibroadenoma (ESFA). Examination revealed a well-demarcated patche writish of reticulated whitish papular lesions in skin of otherwise normal appearance at the border of erosive lichen planus plaques. These lesions had the histological appearance of ESFA. We suggest that these lesions are induced by the inflammatory remodelling associated with erosive lichen planus and propose to consider ESFA in the context of skin tissue remodelling as a new subtype of ESFA.

Takayasu Arteritis and Cutaneous Necrotizing Vasculitis

Takayasu arteritis (TA) is an inflammatory arteriopathy involving predominantly the aorta and its main branches. The disease evolves in two phases: a first, nonspecific inflammatory stage and a late ‘pulseless’ stage, in which complications related to arterial stenosis and aneurysm formation predominate. In both phases, skin manifestations, such as inflammatory nodules, erythema-nodosum- and pyoderma-gangrenosum-like ulcers, have been described. We report 2 patients with TA, who had cutaneous necrotizing vasculitis as presenting manifestation of the disease. A review of the literature revealed 8 similar cases. TA does not only involve large arteries, but also small blood vessels. The observation that in TA the inflammatory process of the large arteries affects regions of the walls supplied by the vasa vasorum, the anatomy of which bears resemblance to the cutaneous vessel system, suggests that primary involvement of small vessels contributes to the development of the clinicopathological features of TA. Knowledge of the skin manifestations associated with TA remains important for its diagnosis and prompt instauration of life-saving treatment.

How best to halt and/or revert UV-induced skin ageing: strategies, facts and fiction

Abstract:  Once considered mainly a cosmetic issue, photoageing research has long moved to the forefront of investigative dermatology. Besides obvious market pressures, increasing insight into the mechanistic overlap between UV‐induced skin cancer and UV‐induced skin ageing has contributed to this development. Also, as strategies that work to antagonize intrinsic skin ageing/senescence may also be exploited against photoageing (and vice versa!), it has become an important skin research challenge to dissect both the differences and the overlap mechanisms between these interwined, yet distinct phenomena. Finally, the current surge in putative ‘antiageing’ products, devices, and strategies – too many of which boldly promise to fight and/or repair the perils that come along with a lifetime spent in the sun in the absence of convincing evidence of efficacy – makes it particularly pertinent to critically review the available evidence to support often made antiageing claims. The current CONTROVERSIES feature, therefore, aimed to provide both guidance through, and critical voices in, the antiageing circus. Here, a panel of experts defines relevant key problems, points the uninaugurated to intriguing aspects of photoageing that one may not have considered before, highlights promising strategies for how best to halt and/or revert it, and spiritedly debates some controversially discussed approaches.