Michel Heenen

Apoptosis in Established and Healing Psoriasis

Background: Previous studies have described apoptosis in the stratum granulosum and in the stratum corneum, but not in the germinative compartment in normal skin. In psoriasis, an increased epidermal apoptosis has been observed in the differentiated compartment, suggesting that apoptosis has a key role in the pathogenesis of psoriasis, as a counteracting factor to the overproduction of cells. Little is known on apoptosis in the germinative compartment. Methods: Apoptosis was studied on biopsies of normal skin, established lesions of psoriasis and PUVA-treated psoriasis using the transferase-mediated uridine nick end labelling method, which detects fragmented DNA, and electron microscopy. Counting of apoptotic cells was restricted to the germinative compartment as defined by Mib1 staining to evaluate the impact of cell loss on cell production and tissue architecture. Results: The apoptotic index was 0.12% in normal epidermis, 0.035% in established psoriasis and 0.31% in regressive psoriasis. Conclusion: These results have three implications: (1) they show the physiological presence of apoptosis in the germinative compartment in normal epidermis; (2) they suggest that induction of apoptosis is involved in the regression of psoriatic hyperplasia after PUVA therapy; (3) the decrease of physiological apoptosis in the psoriatic lesion suggests that this phenomenon could play a role in the induction of psoriatic hyperplasia.

Clinical efficacy and safety comparison of adapalene gel and tretinoin gel in the treatment of acne vulgaris: Europe and U.S. multicenter trials

BACKGROUND Adapalene is a new chemical entity that exhibits tretinoin-like activities in the terminal differentiation process. OBJECTIVE We evaluated a dose range effect of two concentrations of adapalene gel as acne treatment and compared adapalene 0.1% gel with tretinoin 0.025% gel in the treatment of acne patients in two large multicenter studies. METHODS Multicenter, investigator-masked, parallel group studies including 89 acne patients in the dose range study and 591 patients in the concurrent controlled studies were conducted. RESULTS Adapalene gel 0.1% was significantly more effective in treating acne lesions than 0.03% adapalene gel. Adapalene gel 0.1% was significantly more effective than 0.025% or tretinoin gel in one study and of the same effectiveness in the other study. Adapalene gel was always better tolerated than tretinoin gel. CONCLUSION Adapalene 0.1% gel is a safe and effective treatment of acne vulgaris.

Methotrexate induces apoptotic cell death in human keratinocytes

Abstract The mechanism by which low doses of methotrexate act in psoriasis to restore a clinically normal skin is poorly understood. Apoptosis is a programmed cell death activated when cell removal is needed. The purpose of the present work was to examine using an organotypical model of keratinocyte culture, the possibility that low doses of methotrexate can induce apoptosis of keratinocytes. Epidermal explants were cultivated on dead deepidermized dermis under air-exposed conditions. After 10 days, methotrexate (10 –7 M ) was added. After a further 5 days, one part of each culture was fixed and submitted to routine histology, DNA nick end labelling (TUNEL) to detect DNA fragmentation (a molecular marker of apoptotic cell death) and immunohistochemical detection of p53 (a protein involved in apoptosis induced by DNA-damaging agents). The other part of each culture was processed for electron microscopy. A significant proportion of keratinocytes (1%) were damaged and exhibited the morphological features of apoptotic cell death. Immunohistochemical overexpression of p53 was detected in the basal layer of the cultures treated with methotrexate. Low doses of methotrexate induce apoptosis. This mode of action could explain the reduction in epidermal hyperplasia during treatment of psoriasis with methotrexate.

High serum galectin-3 in advanced melanoma: preliminary results

Background.  Galectin‐3 (Gal‐3) is a member of the family of β‐galactoside‐binding mammalian lectins, and has been implicated in tumour invasion and metastatic process in vitro and in vivo.

Anti-tumor necrosis factor alpha-induced psoriasiform eruptions: three further cases and current overview.

The increasing use of anti-TNF-α agents led to a better knowledge of their side effects. Among the cutaneous reactions, psoriasiform eruptions are increasingly described. We encountered 3 further psoriasiform eruptions during anti-TNF-α treatment for rheumatologic conditions and review the literature in order to identify the common characteristics of these cases. We found 30 case reports by using a comprehensive search of the 1966–2005 Medline database with a wild variety concerning the psoriasis type of eruption, the anti-TNF-α agent, the treatment duration and the presence or absence of a personal or familial history of psoriasis. We conclude that a psoriasiform eruption during anti-TNF-α treat- ment seems to be a class effect, without any as yet known identified predisposing factors, but it is more often self-limited and does not require treatment discontinuation.

Value of Standard Laboratory Tests for the Early Recognition of Group A β-Hemolytic Streptococcal Necrotizing Fasciitis

The laboratory data for 17 patients with group A beta-hemolytic streptococcal necrotizing fasciitis (GAS NF) were compared with data for 145 patients hospitalized for cellulitis during the same period. Admission values of C-reactive protein and creatine kinase were higher for patients in the group with GAS NF than for patients in the group with cellulitis (P<.001), suggesting that standard laboratory tests may be useful for the early differential diagnosis of GAS NF and cellulitis.

Interferon alpha as adjuvant postsurgical treatment of melanoma: a meta-analysis

Background: The literature on the benefit of α-interferon (IFN-α) as adjuvant postsurgical treatment of melanoma reports discordant results. Objective: With the published data so far, we performed a meta-analysis in order to evaluate the effect of IFN-α on the relapse rate (RR) and the overall survival (OS). Methods: Published randomised trials were identified by Medline search. Stage IV melanoma was not considered. Results: Nine published studies were included, with a total of 2,880 patients. Both the per protocol and the intention-to-treat analysis show that IFN-α significantly decreased the RR (OR = 0.74; 95% CI = 0.64–0.86). Subgroup analyses show that, for all stages, high and low doses decreased the RR (OR = 0.71, 95% CI = 0.54–0.92, and OR = 0.76, 95% CI = 0.63–0.91, respectively). No difference has been evidenced on OS. Conclusions: High and low doses of IFN-α significantly decrease the RR, but the OS does not seem to be improved.

Evaluation of the prognostic significance of serum galectin-3 in American Joint Committee on Cancer stage Iii and stage Iv melanoma patients

Galectin-3 (Gal-3) is a member of the &bgr;-galactoside-binding lectins family and has been implicated in angiogenesis, tumor invasion, and metastatic process in vitro and in vivo. As we showed recently that advanced melanoma patients presented high serum level of Gal-3, we investigated the association of this protein with the outcome of melanoma patients. Whether this protein could be a biomarker has not been assessed, and we compared the prognostic value of serum Gal-3 in multivariate analysis with lactate dehydrogenase, C-reactive protein and S100B. We conclude that Gal-3 could be of prognostic value in melanoma patients; more precisely, this protein has a strong independent prognostic signification with a cut-off value of 10 ng/ml. After these data, we believe that serum Gal-3 measurement can have an important role in the follow-up and management of advanced American Joint Commission on Cancer stage III and stage IV melanoma patients. Further studies will uncover whether Gal-3 will be able to open new therapeutic perspectives.

Cyclosporin in atopic dermatitis: review of the literature and outline of a Belgian consensus.

This paper reflects the consensus reached among Belgian professors of dermatology on the place of cyclosporin (CsA) in the treatment of atopic dermatitis (AD). Existing therapeutic modalities and ways to evaluate efficacy of treatment are reviewed briefly. Based on data from the literature and personal experience, guidelines for the use of CsA in AD are proposed. CsA can be prescribed in recalcitrant cases of AD on a short-term basis, both in adults and children. Long-term treatment, up to 1 year, should be considered only in exceptional cases that cannot be controlled by short-time therapy. Contraindications, drug interactions and necessary controls during treatment are also discussed.

Treatment of Plantar Hyperhidrosis with Dermojet Injections of Botulinum Toxin

Focal axillary, palmar or plantar hyperhidrosis is a chronic, distressing and sometimes disabling disorder that often responds poorly to conventional therapies. Surgical procedures are performed in severely affected patients. Intraor subcutaneous injections of botulinum toxin are a novel, effective and safe alternative therapeutic modality in the management of focal hyperhidrosis [1–6]. Its benefits may last as long as 14 months [1, 2]. However, the series of injections through the densely innervated skin of the palms and soles are often rated as not acceptable by the patients. Injections with a Dermojet have been used for palmar hyperhidrosis to reduce injection pain [6]. This technique is however not recommended because of possible injury to the superficial palmar nerves or vessels. A safer technique is the regional block of the ulnar and median nerves at the wrist level with 1% lignocaine [6]. However, anesthesia of the soles cannot be achieved with such a regional block so that plantar hyperhidrosis remains a therapeutic challenge. Since the plantar nerves are deeper than their palmar homologues, we considered the efficacy and safety of injections with a Dermojet for plantar hyperhidrosis. We treated 3 patients with plantar hyperhidrosis with botulinum toxin type A injections. A total dose of 100 mouse units botulinum toxin (Botox, Allergan, Irvine, Calif., USA)/5 ml 0.9% NaCl was distributed over both soles with the Dermojet technique. Informed consent was obtained from each patient. Evaluation of the hyperhidrosis was performed by the ‘iodine-starch’ test, as previously described [2]. Patients were then followed up every 2 months with serial ‘iodinestarch’ records. Pain injection was rated as acceptable. There were neither paresthesias nor other side effects. In each of the 3 patients, hyperhidrosis improved after 1 week and this effect was still present after respectively 10, 8 and 6 months. These results suggest that injections of botulinum toxin with a Dermojet may be an effective and comfortable technique for the treatment of plantar hyperhidrosis. Because of the deeper location of the plantar nerves, it is likely that this technique is safer and more appropriate for plantar than for palmar hyperhidrosis.