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Familial hidradenitis suppurativa: evidence in favour of single gene transmission.

The three English families in this report have a total of 21 members (16 females and five males) suffering from chronic hidradenitis suppurativa. In family A the condition is associated with acne conglobata and there is vertical transmission of the disorder through three generations. In the others there is no associated cystic acne, but all those affected had a history of acne vulgaris with comedone formation, and the condition has been confirmed in two generations. It is likely that a male in an earlier generation in family B suffered from the disease and affected sibs in family C were born to different fathers. The familial aggregation and number of affected subjects suggests a single gene disorder and the pattern of transmission is consistent with autosomal dominant inheritance. Males and females are affected in successive generations and there is the anticipated variation in clinical severity in those suffering from the condition.

Adolescent↗

Modelling the infundibulum in acne.

The human sebaceous-pilosebaceous infundibulum was isolated and maintained for 7 days. Infundibular viability was maintained over 7 days in this medium. The addition of 1 ng/ml interleukin 1 alpha (IL-1 alpha) caused hypercornification of the infundibulum similar to that seen in comedones which could be blocked by 1,000 ng/ml IL-1 receptor antagonist. However, in contrast to interferon gamma 1, IL-1 alpha had no effect on the expression of intercellular adhesion molecule or human leucocyte antigen type DR in infundibular keratinocytes. The addition of 5 ng/ml epidermal growth factor or 5 ng/ml transforming growth factor alpha to the medium caused a disorganization of the keratinocytes of the infundibulum. We are now, therefore, able to model histologically the major infundibular changes in acne. Furthermore, we suggest that IL-1 alpha causes the scaling seen in many inflammatory skin diseases.

Antigens, CD↗

The possible role of reactive oxygen species generated by neutrophils in mediating acne inflammation.

The purpose of this study was to investigate the possible role of reactive oxygen species (ROS) generated by neutrophils in mediating acne inflammation. Antibiotics used for the treatment of acne significantly inhibited ROS generated by neutrophils, when compared to other antibiotics. Metronidazole, which is effective in the treatment of acne, markedly inhibited ROS generated by neutrophils. The drug is known to have no significant effect on the growth of Propionibacterium acnes. The proportion of linoleic acid is markedly decreased in acne comedones. Linoleic acid significantly suppressed ROS generated by neutrophils. The ability of neutrophils to produce ROS was significantly increased in patients with acne inflammation. These results seem to reveal the involvement of ROS generated by neutrophils in the disruption of the integrity of the follicular epithelium, which is responsible for inflammatory processes of acne.

Acne Vulgaris↗

Clinical aspects of acne.

Acne vulgaris may present in a wide variety of clinical forms depending on the type, number and severity of the predominant lesion. Thus there may be mild, moderate or severe comedonal or inflammatory acne, the latter with many subtypes. Furthermore, the number and extent of the lesions do not necessarily predict the response to therapy, and patients may also be categorized as therapeutically responsive or therapeutically refractory. Finally, there may be alterations in the clinical manifestations and therapeutic response depending on the distribution of the lesions, age of the patient and provoking or complicating factors.

Acne Vulgaris↗

Split-face clinical and bio-instrumental comparison of 0.1% adapalene and 0.05% tretinoin in facial acne.

BACKGROUND: Adapalene and tretinoin are topical compounds active for treating acne. OBJECTIVE: To compare the efficacity and safety of adapalene 0.1% gel and tretinoin 0.05% gel in moderately severe facial acne using clinical and objective biometrological assessments. Such information is currently lacking in the literature. METHODS: The split-face method was used in 25 acne volunteers for a 6-week treatment. In addition to clinical counts of lesions, the amount of comedones was assessed using computer-assisted morphometry of cyanoacrylate follicular biopsies. The erythema index and squamometry values were used to quantitate skin irritation. RESULTS: The tretinoin formulation brought better comedolysis and clinical improvement than the adapalene formulation. Erythema was transiently more pronounced on the tretinoin-treated side. Squamometry yielded no significant difference between both products. CONCLUSION: Tretinoin 0.05% gel exhibits a greater anti-acne efficacy than adapalene 0.1% gel, although with temperate tolerability.

Acne Vulgaris↗

EEMCO guidance for the in vivo assessment of skin greasiness. The EEMCO Group.

Sebaceous gland activity has four distinct components which are sebum production (a secretion rate function), storage (a volume function), surface output (a delivery rate function) and stratum corneum permeation (an influx rate function). The oily appearance of skin results from an excess of sebum excretion and spreading over the body surface and its interaction with the skin surface. A multi-pronged approach is often useful to assess skin greasiness with precision. The clinical evaluation of skin greasiness and its shiny appearance should be further complemented by quantifying the large pores, follicular plugs and comedones. The sebum amount present at the skin surface can be measured non-invasively using one of several methods based on solvent extraction, cigarette paper pads, photometric assessment, bentonite clay and lipid-sensitive tapes. Quantitative parameters include the sebum casual level, the sebum excretion rate, the sebum replacement time, the instant sebum delivery, the follicular excretion rate, the density in sebum-enriched reservoirs and the sustainable rate of sebum excretion. A series of environmental and biological features influence the data. Hence rigorous methodological designs are mandatory to support claims. As a rule, accuracy of the methods is adversely affected by skin temperature, degree of hydration and surface roughness. An additional confounding factor is the inherent difficulty of collecting the surface lipids without a contribution from the follicular reservoir. A better understanding of factors that alter the sebum amount at the skin surface may well assist in the development of sebosuppressive agents to help the reduction of the skin greasiness and improve acne.

Humans↗

Comedolytic effect of topical retinaldehyde in the rhino mouse model.

BACKGROUND: Retinaldehyde is a key molecule in the metabolism of vitamin A by keratinocytes. In order to evaluate its range of topical activity in acne, its comedolytic effect was compared to that of retinoic acid in the same vehicle, in the rhino mouse model. METHODS: The animals were treated on the back daily for 5 consecutive days per week for 3 weeks. At the end of this period, histological slides were analyzed in order to quantify the features of comedones and epidermal thickness. RESULTS: Topical treatment with a retinaldehyde (0.05% w/w) and a retinoic acid formulation (0. 025% w/w) induced comedolysis and increased the epidermal thickness with the same intensity. CONCLUSION: These data indicate that retinaldehyde exerts a significant comedolytic activity.

Acne Vulgaris↗

Acne in infancy and acne genetics.

Acne is a disease that can be seen in the first year of age, early childhood, prepubertal age and puberty. Neonatal acne is due mainly to considerable sebum excretion rate, and infantile acne because of high androgens of adrenal origin in girls and of adrenal and testes in boys. These pathogenic mechanisms are characteristic in these ages. Important factors like early onset of comedones and high serum levels of dehydroepiandrosterone sulfate are predictors of severe or long-standing acne in prepubertal age. Hereditary factors play an important role in acne. Neonatal, nodulocystic acne and conglobate acne has proven genetic influences. Postadolescent acne is related with a first-degree relative with the condition in 50% of the cases. Chromosomal abnormalities, HLA phenotypes, polymorphism of human cytochrome P-450 1A1 and MUC1 gene are involved in the pathogenesis of acne. Several other genes are being studied.

Acne Vulgaris↗

Topical treatment in acne: current status and future aspects.

During the last 20 years, the number of topical and systemic drugs for the treatment of acne vulgaris has been enriched. Topical drugs on the one hand have been newly discovered or further developments of already available agents such as in the group of retinoids or galenic formulation have improved efficacy or local tolerance. Topical retinoids are a mainstay in acne treatment since 1962. All-trans retinoic acid was the first and is still in use. Its irritative potential has led to the new galenics, i.e. incorporation in microsponges and in propolyomers, which increased the tolerability significantly. The isomer of tretinoin, isotretinoin, has the same clinical efficacy, but also a lower irritancy. A real breakthrough was adapalene, a retinoid-like agent, with a different retinoid receptor-binding profile, but in addition to the same clinical efficacy on inflammatory and non-inflammatory acne lesions compared to tretinoin, a better tolerability and, therefore, compliance. Unfortunately, over the past years topical retinoids have been less used in inflammatory acne than they should be, taking the the mechanisms of action into account. Topical antimicrobials, in particular topical antibiotics, should be used less often than in the past and only for short periods to avoid the development of resistances. It seems better to combine those agents with topical retinoids, with BPO or with azelaic acid to enhance the efficacy and slow down the development of resistance. BPO is still the gold standard for papular-pustular acne of mild-to-moderate type in concentrations of 2-5%. Azelaic acid is an alternative with efficacy on the comedo and is antibacterial without development of resistances. Finally, the physical removal by electrocautery or CO(2) laser of multiple densely packed closed comedones, macrocomedones and microcysts is necessary to enhance the efficacy of topical comedolytic agents and to speed up the therapeutic results. Photodynamic therapy has not yet been proven efficacious in controlled studies. Blue and red light can probably be used in association with local agents but enhancement of the irritative potential of topical and systemic agents has to be considered.

Acne Vulgaris↗

Efficacy and safety of 0.1% retinaldehyde/ 6% glycolic acid (diacneal) for mild to moderate acne vulgaris. A multicentre, double-blind, randomized, vehicle-controlled trial.

BACKGROUND: Retinaldehyde and glycolic acid are both efficient in acne. OBJECTIVE: To evaluate the efficacy and tolerability of a 0.1% retinaldehyde/6% glycolic acid combination (Diacneal) for mild to moderate acne vulgaris. METHODS: Overall physician and patient ratings of acne symptom severity and tolerance were performed at baseline, months 1, 2 and 3. RESULTS: Mean numbers of papules, pustules and comedones were significantly reduced from month 1 onwards. A significant advantage of Diacneal over vehicle was demonstrated on the percentages of patients with ongoing healing lesions at month 2, healing ancient lesions from month 1 and patients with 'important/very important' global improvement from month 2 (50.0 vs. 26.3%) confirmed by patients at month 3 (86.1 vs. 58.8%). Products were well tolerated; only 1 patient had to stop the treatment. CONCLUSIONS: Diacneal, a combination of 0.1% retinaldehyde/6% glycolic acid, is effective and well tolerated in mild to moderate acne vulgaris.

Acne Vulgaris↗

Cetuximab-induced acne.

BACKGROUND: Cetuximab is a member of a new family of antineoplastic agents that inhibit epidermal growth factor receptor (EGFR). These molecules may induce acneiform eruptions. In this study, we aimed at evaluating (a) the characteristics of acne and (b) whether these acneiform eruptions could be improved by classical anti-acne treatments. METHODS: All patients treated with cetuximab in a single institution from October 2003 to May 2004 were prospectively evaluated. The presence of acne, its severity, need for a treatment and response to this treatment were recorded. RESULTS: 13 patients were included: 11 (85%) developed acneiform eruptions after a mean interval of 10 days. It was severe in 4/13 (31%). Comedones were never found and acne involved nonclassical sites in 3/11. Antibiotic treatment was given to 4 and local treatment to 2 patients: it was always efficient. CONCLUSION: Cetuximab-induced acne is frequent, differs from classical acne and may be treated effectively with classical modalities.

Acne Vulgaris↗

'Keratolytic' properties of benzoyl peroxide and retinoic acid resemble salicylic acid in man.

OBJECTIVES: Retinoic acid (RA) and benzoyl peroxide (BP) were studied, comparing their keratolytic efficacy and water barrier disruption to that of salicylic acid (SA), a well-established keratolytic, under similar conditions. PATIENTS/METHODS: Six volunteers were included in this blinded study. Eleven randomized test sites were marked on the volar forearms, containing sites for untreated skin at time zero, unoccluded, occlusion, and vehicle controls for 3 and 6 h, and each of BP, RA, and SA solutions for 3 and 6 h. At each time point, occlusion at 5 of the test sites was removed, and chromameter measurements were performed over 30 min. Each site then underwent 25 stratum corneum (SC) tape strippings. At 1, 5, and 30 min after the last stripping at each site, TEWL measurements were performed. Quantitative protein analysis of the SC from the tapes was then performed. RESULTS AND CONCLUSION: after 3 h, bp was significantly more effective in disrupting sc cohesion than sa and ra, indicating bp is a moderate keratolytic agent in addition to its antimicrobial properties. After 6 h, all three agents were similarly effective in keratolysis. Barrier disruption, as measured by TEWL, paralleled depth of SC removal. SA tended to exhibit the greatest keratolytic efficacy superficially, hence its clinical effectiveness in superficial conditions such as comedonal acne, whereas BP was more effective at deeper levels, complimenting its antimicrobial effects and enabling it to treat deeper, more inflammatory lesions. None of the agents significantly affected skin erythema. These techniques provide a robust and rapid assay for in vivo keratolytic demonstration.

Adult↗

Bacteraemia in patients with hidradenitis suppurativa undergoing carbon dioxide laser surgery: detection and quantification of bacteria by lysis-filtration.

BACKGROUND: Hidradenitis suppurativa (HS) is a cicatrising and persistent disease of apocrine gland-bearing areas in adults. The severity of this condition varies from a few suppurating lesions to widespread, disabling disease. The aetiology is obscure, but suggested contributory factors include a genetic predisposition, comedones occluding the pilosebaceous apparatus, bacterial infections, and hormonal factors. Treatment consists mainly of surgery, while medical therapies serve principally as adjunct therapy. OBJECTIVES: The aim of the study was to determine the number and type of bacteria circulating in the bloodstream in patients with HS undergoing surgical treatment with a carbon dioxide laser stripping-secondary intention technique. METHODS: Twenty-one patients (20 females and 1 male, mean age 36, range 20-55 years) were included in the study. One blood sample (8.3 ml) was taken before surgery, one during the operation and the last one 10 min after surgery. Five healthy persons (all females, mean age 36, range 23-48 years) not undergoing any operation were used as the controls. The blood was cultured by a lysis-filtration technique which had been shown to be very sensitive. Since the filter catches the microorganisms and colonies are formed during culturing, the number of bacteria in the samples is easily determined. RESULTS: In 6 patients, all samples were negative, which indicates that the method of surgery itself caused no spread of bacteria from the lesions. Bacterial growth in the first blood sample was found in 9 patients, from the second sample in 10 and from the third one in 6. In 1 patient, bacteria were detected in three samples. At least 12 bacterial species were identified. The dominating bacteria were coagulase-negative staphylococci of which most were subtyped as Staphylococcus warneri. Among the anaerobic microorganisms, Propionibacterium acnes and P.granulosum were the most frequently isolated bacteria. The bacterial findings in the blood samples accord well with the results from a previous study in which cultures were taken from the deep parts of the HS lesions. In the 5 controls, no microbial growth was detected. CONCLUSION: The carbon dioxide laser stripping technique caused no additional spread of bacteria into the bloodstream. The evaluation of cultures containing microorganisms from normal skin flora is controversial. Since the bacteria encountered in this study are in close agreement with the findings in cultures from the deeper parts of HS lesions they seem to be relevant. The growth of bacteria in the first blood sample taken before surgery may indicate that some of these patients have bacteria continuously circulating in their blood.

Adult↗

Quantification of epidermal histological changes induced by topical retinoids and CD271 in the rhino mouse model using a standardized image analysis technique.

The rhino mouse has been used as an experimental model to screen topically active comedolytic agents. Adult rhino mice were treated on the back once daily for 5 consecutive days per week during 3 weeks. Skin histological preparations were analyzed by image analysis techniques to quantify the number of epidermal comedones, comedo profile and epidermal thickness. Using both a negative (treated with acetone) and a positive (treated with Aberel gel 0.025%) control group of animals in all experiments conducted over a period of about 3 years, we defined the upper and lower limit of acceptability of the results. Topical treatment with an acetone solution of all-trans retinoic acid (0.01, 0.03, 0.1%) and 13-cis-retinoic acid (0.1%) induced comedolysis and a marked increase in epidermal thickness. Commercial preparations of all-trans retinoic acid (Aberel lotion, gel and cream, Retin A cream, Retacnyl cream) presented a similar comedolytic activity. However, the epidermal thickening was higher with Retin A and weaker with Retacnyl. CD271, a new modulator of cell differentiation, applied either in acetone solution (0.01, 0.1%) or in lotion, gel or cream formulations (0.1%) also demonstrated a marked activity (i.e. comedolysis and epidermal thickening). These data confirm that the rhino mouse model can be used to assay drugs applied either in solvent or in topical formulations. Activity in this model compares favorably with published clinical observations in the treatment of acne.

Acne Vulgaris↗

Rate and topography of follicular sebum excretion.

We have designed a combined method using a lipid-absorbent tape and skin surface stripping to evaluate the relationship between the follicular sebum excretion rate and the microanatomy of the follicular duct openings. Many sebaceous follicles appear quiescent in normals and with acne patients. Most of the large spots on the lipid-absorbent tape are due to the confluence of smaller ones. 'Open' comedones in acne are functionally closed.

Acne Vulgaris↗

Isotretinoin--an explanation for its long-term benefit.

Isotretinoin is of undisputed benefit in the treatment of acne. In doses of 1 mg/kg/day for 4 months the drug produces a highly significant reduction in sebum excretion rate (90 +/- 3%) in comedone formation as measured by assessing follicular casts (70 +/- 5%), and in surface Propionibacterium acnes. However, the mechanisms of long-term clinical remission are not well understood. There are however, risk factors which predetermine the outcome to treatment with isotretinoin. Younger subjects (14-19 years) and those who have had acne for less than 6 years, respond less well than older subjects. Subjects with more truncal acne also fare less well than those with predominantly facial acne. A return of the reduced sebum excretion rate to within 10% of the pre-treatment level also is a poor prognostic factor. This and future studies could lead to development of more logical dose regimes depending, for example, on the age of the patient; duration of acne and its site. However, until proven otherwise, this study confirms our earlier data, and that of the German multi-centres and Strauss et al (1), that the optimum dose schedule for treating acne patients is 1 mg/kg/day regime.

Acne Vulgaris↗

Water-based versus alcohol-based benzoyl peroxide preparations in the treatment of acne vulgaris.

Forty-eight patients with acne vulgaris in the face were treated with a water-based (Basiron) and an alcohol-based (Panoxyl) 5% benzoyl peroxide preparation. A randomized double-blind, contralateral study was used. No difference in clinical effect was found. Treatment for 8 weeks resulted in at least 50% reduction in the number of closed comedones, papules and pustules in over 80% of the patients. In more than 70% of the patients, the reduction exceeded 75%. The water-based Basiron caused significantly less skin irritation than the alcohol-based preparation of Panoxyl.

Acne Vulgaris↗

Comedo formation following cobalt irradiation.

After cobalt-60 therapy 3 patients developed open and closed comedones in the face corresponding to the treatment fields. Biopsies showed extensive dermal elastotic material. It is suggested that the elastotic fibres may contribute to a change in the supporting function of the dermis and a secondary sebum retention and comedo formation.

Acne Vulgaris↗