Conjunctivitis in atopic dermatitis patients with and without dupilumab therapy - international eczema council survey and opinion.

BACKGROUND: Conjunctivitis is common in patients with atopic dermatitis (AD) in general and a commonly reported adverse event in AD clinical trials with dupilumab. OBJECTIVE: To survey opinions and experience about conjunctivitis occurring in AD, including those during dupilumab treatment in a group of AD experts from the International Eczema Council (IEC). METHODS: Electronic survey and in-person discussion of management strategies. RESULTS: Forty-six (53.5%) IEC members from 19 countries responded to the survey. Consensus was reached for several statements regarding diagnostic workup, referral and treatment. IEC members suggest that patients with AD should (i) routinely be asked about ocular complaints or symptoms, (ii) obtain information about the potential for conjunctivitis before starting dupilumab therapy and (iii) if indicated, be treated with dupilumab despite previous or current conjunctivitis. In cases of new-onset conjunctivitis, there was consensus that dupilumab treatment should be continued when possible, with appropriate referral to an ophthalmologist. LIMITATIONS: The study relies on expert opinion from dermatologists. Responses from few dermatologists without dupilumab access were not excluded from the survey. CONCLUSION: The IEC recommends that dermatologists address conjunctivitis in patients with AD, especially during treatment with dupilumab.

Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II.

This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus-based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This second part of the guideline covers antimicrobial therapy, systemic treatment, allergen-specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions, whereas the first part covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy. Management of AE must consider the individual clinical variability of the disease. Systemic immunosuppressive treatment with cyclosporine, methotrexate, azathioprine and mycophenolic acid is established option for severe refractory cases, and widely available. Biologicals targeting the T helper 2 pathway such as dupilumab may be a safe and effective, disease-modifying alternative when available. Oral drugs such as JAK inhibitors and histamine 4 receptor antagonists are in development. Microbial colonization and superinfection may cause disease exacerbation and can require additional antimicrobial treatment. Allergen-specific immunotherapy with aeroallergens may be considered in selected cases. Psychosomatic counselling is recommended especially in stress-induced exacerbations. Therapeutic patient education ('Eczema school') is recommended for children and adult patients. General measures, basic emollient treatment, bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy have been addressed in the first part of the guideline.

Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I.

This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus-based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This first part of the guideline covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy, whereas the second part covers antimicrobial therapy, systemic treatment, allergen-specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions. Management of AE must consider the individual clinical variability of the disease; highly standardized treatment rules are not recommended. Basic therapy is focused on treatment of disturbed barrier function by hydrating and lubricating topical treatment, besides further avoidance of specific and unspecific provocation factors. Topical anti-inflammatory treatment based on glucocorticosteroids and calcineurin inhibitors is used for flare management and for proactive therapy for long-term control. Topical corticosteroids remain the mainstay of therapy, whereas tacrolimus and pimecrolimus are preferred in sensitive skin areas and for long-term use. Topical phosphodiesterase inhibitors may be a treatment alternative when available. Adjuvant therapy includes UV irradiation, preferably with UVB 311 nm or UVA1. Pruritus is targeted with the majority of the recommended therapies, but some patients may need additional antipruritic therapy. Antimicrobial therapy, systemic anti-inflammatory treatment, immunotherapy, complementary medicine and educational intervention will be addressed in part II of the guideline.

Guidelines for the management of vitiligo: the European Dermatology Forum consensus.

The aetiopathogenic mechanisms of vitiligo are still poorly understood, and this has held back progress in diagnosis and treatment. Up until now, treatment guidelines have existed at national levels, but no common European viewpoint has emerged. This guideline for the treatment of segmental and nonsegmental vitiligo has been developed by the members of the Vitiligo European Task Force and other colleagues. It summarizes evidence-based and expert-based recommendations (S1 level).

[Metronidazole: alternative treatment for ocular and cutaneous rosacea in the pediatric population]. / Le métronidazole, alternative thérapeutique des rosacées oculaires et cutanées de l'enfant.

OBJECTIVE: To assess the effectiveness and tolerance of systemic metronidazole in the treatment of childhood ocular and cutaneous rosacea. METHOD: Single-center multidisciplinary retrospective study. PATIENTS: Children aged between 1 and 15, with ocular and/or cutaneous rosacea, treated in the pediatric ophthalmology and dermatology department of Bordeaux, France, from January 1996 to September 2009. RESULTS: Eleven patients out of 20 had ocular and cutaneous rosacea, three had ocular symptoms only, and six had cutaneous symptoms only. In 11 patients (55%), the ocular symptoms preceded the skin disease. Meibomian cyst and phlyctenular conjunctivitis were the main symptoms. Keratitis was seen in four patients and lower corneal ulcer in two cases. The papulopustular form was the most frequent dermatologic form. All patients with ocular involvement received first-line treatment of eyelid hygiene. No topical ophthalmic treatment such as corticosteroid or cyclosporine 0.5% or 2% was used. Thirteen patients who showed no improvement despite eyelid treatment, the association of ocular and cutaneous rosacea, severe ocular involvement with keratitis, and severe recurrent cutaneous rosacea were treated orally. Two patients, aged between 12 and 14 years, received treatment with an anti-inflammatory dose of doxycycline for 2 to 3 months and achieved complete remission. One 22-month-old patient received oral treatment with erythromycin at a dose of 250 mg three times daily for 4 months. Ten patients, aged 12 to 64 months, were treated with systemic Metronidazole. Treatment lasting at least 3 months at a dose between 20 and 30 mg/kg per day was necessary to obtain complete and lasting remission. An early cessation of treatment, before 3 months, seems associated with partial remission of the disease and early recurrence. In cases complicated by ocular keratitis and corneal ulcer, prolonged treatment lasting 6 months led to clinical remission. The short courses (3-6 months) were preferred to long-term administration to prevent neurological toxicity. Maintenance therapy was based on eyelid hygiene. No recurrences and no toxic effects were observed at a median of 48 ± 6 months. CONCLUSION: Childhood ocular rosacea is not rare, but is often misdiagnosed. It often precedes skin symptoms but it can remain isolated. Metronidazole could be alternative treatment for ocular and cutaneous rosacea in the pediatric population.

ETFAD/EADV eczema task force 2009 position paper on diagnosis and treatment of atopic dermatitis.

BACKGROUND: The diagnosis of atopic dermatitis (AD) is made using evaluated clinical criteria. Management of AD must consider the symptomatic variability of the disease. METHODS: EADV eczema task force developed its guideline for atopic dermatitis diagnosis and treatment based on literature review and repeated consenting group discussions. RESULTS AND DISCUSSION: Basic therapy relies on hydrating topical treatment and avoidance of specific and unspecific provocation factors. Anti-inflammatory treatment based on topical glucocorticosteroids and topical calcineurin antagonists is used for exacerbation management and more recently for proactive therapy in selected cases. Topical corticosteroids remain the mainstay of therapy, but the topical calcineurin inhibitors, tacrolimus and pimecrolimus are preferred in certain locations. Systemic anti-inflammatory treatment is an option for severe refractory cases. Microbial colonization and superinfection may induce disease exacerbation and can justify additional antimicrobial/antiseptic treatment. Systemic antihistamines (H1) can relieve pruritus, but do not have sufficient effect on eczema. Adjuvant therapy includes UV irradiation preferably of UVA1 wavelength or UVB 311 nm. Dietary recommendations should be specific and given only in diagnosed individual food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Stress-induced exacerbations may make psychosomatic counselling recommendable. 'Eczema school' educational programmes have been proven to be helpful.

Epicutaneous aeroallergen sensitization in atopic dermatitis infants - determining the role of epidermal barrier impairment.

BACKGROUND: Sensitization to atopens is an early phenomenon that overlaps with the onset of atopic dermatitis (AD) in infancy. Early epidermal barrier impairment may facilitate the epicutaneous penetration of atopens. OBJECTIVE: To correlate transepidermal water loss (TEWL) and aeroallergen sensitization in infants with AD. METHODS: In this cross-sectional study we enrolled 59 AD children and 30 controls aged 3-12 months. Transepidermal water loss in uninvolved skin, specific immunoglobulin E, atopy patch test (APT) and skin prick tests were performed with respect to seven aeroallergens, i.e., Dermatophagoides pteronyssinus, D. farinae, cat, dog, birch pollen, ambrosia, and cockroach. Environmental conditions were assessed by a questionnaire, and the house dust mite (HDM) concentration was determined in dust samples. RESULTS: Eighty-nine percent of AD infants had a positive APT vs one out of eleven controls. AD infants had a significantly higher mean TEWL than controls (27.4 vs 11.1 g/m(2)/h, P < 0001). Children with two or more positive APT had higher TEWL than the others (31.1 vs 19.0 g/m(2)/h, P < 0.025). No correlation was found between indoor APT results and exposure to HDM, cats, and dogs at home. CONCLUSIONS: This study confirms the high prevalence of delayed sensitization to indoor and outdoor aeroallergens in AD infants, and shows that the higher the TEWL, the higher the prevalence of sensitization to aeroallergens. These data are in favor of a major role of a constitutive epidermal barrier impairment in determining early atopen sensitization in infants with AD.

A prospective study of the incidence of complications associated with dermatological surgery.

BACKGROUND: Dermatological surgery is a relatively new and expanding subspecialty within dermatology. Little information is available about complications in this kind of surgery in the European setting. OBJECTIVES: The aim of this study was to assess the incidence of anaesthetic, haemorrhagic and infectious complications in dermatological surgery and to highlight the factors associated with these complications. METHODS: Data were collected prospectively over a 3-month period for all surgical procedures performed by a network of dermatologists (n = 84 dermatologists) in France, including the excision of all benign or malignant tumours but excluding sebaceous cysts and pyodermas. Information was collected regarding dermatologists, patients, procedures and complications. RESULTS: A total of 3788 surgical procedures were available for review; 236 complications, mostly minor, occurred in a total of 213 surgical procedures (6%), bleeding being the most common (3%). Vaso-vagal syncope was the main anaesthetic complication (51 of 54). Infectious complications occurred in 79 patients (2%). Superficial suppuration accounted for 92% of surgical site infections. Only one patient had a systemic infection. Complications requiring additional antibiotic treatment or repeat surgery accounted for only 22 cases of 3788 (1%). No statistically significant correlation was found with the characteristics of the dermatologists, especially with respect to their training or amount of surgical experience. Similarly, no link could be established between complications and surgical conditions. Multivariate analysis showed that anaesthetic or haemorrhagic complications were independent factors for infectious complications. Sex, administration of an anticoagulant or immunosuppressant, type of procedure performed and duration exceeding 24 min were independent factors for haemorrhagic complications. CONCLUSIONS: This study shows a low rate of complications associated with dermatological surgery performed by dermatologists under local anaesthesia on an outpatient basis.

[New treatments of atopic dermatitis]. / Nouveaux traitements de la dermatite atopique.

Topical steroids are still used suboptimally, but remain the mainstay of atopic dermatitis treatment. Topical steroid phobia is rampant in many countries, a real advantage for the entry on the market of topical immunomodulators (TIMs), which inhibit both antigen specific and non-specific T cell activation in the skin, by blockade of gene transcription of proinflammatory cytokines such as IL2 and TNF alpha. Topical tacrolimus and pimecrolimus have the most advanced clinical development. Tacrolimus, already used orally in transplantation medicine, is already available in France since 2003 as a 0.03% ointment for children (Protopic, Fujisawa). Its introduction on the market has substantially changed prescription habits in atopic dermatitis. Recalcitrant adolescent and adult head and neck lesions are the major target, but the drug is is also widely used in children, with a good safety profile. The risk of herpes virus superinfections did not increase significantly in clinical trials but needs further monitoring. Long-term prescription will need a closer look at a still much debated increased skin cancer risk. The marked efficacy on thin skin sites and absence of atrophogenic properties of the drug balance its side effects at the first applications on inflamed skin (pruritus, burning sensation). Clinical studies using pimecrolimus (Elidel, Novartis), marketed as a 1% cream, show a satisfactorily efficacy profile in adults and children including infants. The drug is better tolerated and is already widely introduced on the international market since 2002 with a pediatric positioning, but is nor available yet in 2004 in France. Besides phototherapy, systemic immunosuppressants remain useful drugs in severe disease especially in older children and adolescents, cyclosporin remaining the leading drug. Preventive immunomodulation modifying the intestinal microflora is very promising approach which deserves a large-scale assessment.

Saline spa water or combined water and UV-B for psoriasis vs conventional UV-B: lessons from the Salies de Béarn randomized study.

OBJECTIVE: To study the effects of UV-B therapy and saline spa water given alone or in combination for the treatment of psoriasis. DESIGN: Randomized, controlled, comparative study with blinded observers. SETTING: Salies de Béarn, saline spa water center located in the southwest of France. PARTICIPANTS: Seventy-one adult patients with psoriasis with a Psoriasis Area and Severity Index (PASI) score greater than 10. INTERVENTION: Patients were randomly assigned to 1 of 3 treatments: spa water alone (group A); UV-B 311-nm phototherapy alone (group B); and a combination of the 2 therapies (group C). The 3 groups were treated on a daily basis 5 days a week for a total of 21 days. MAIN OUTCOME MEASURES: Change in PASI score from baseline as determined by an investigator blinded to randomization; variation in quality of life, adverse effects, and long-term effects (1 year after treatment). RESULTS: Four patients dropped out because of secondary effects. Efficacy was similar in groups B and C, with changes in PASI of -64% and -55%, respectively at 3 weeks. For group A, change in PASI was -29%, thus showing a minor therapeutic effect of saline spa water alone and poor efficacy compared with groups B and C (P<.001). More adverse effects were reported in groups A and C but did not reach significance. Combined saline spa water and UV-B therapy had no sparing effect on UV-B dosages. One year after treatment, no long-term benefit could be attributed specifically to a given regimen, but the patients had overall significantly better PASI scores than at baseline. CONCLUSIONS: Saline spa water alone had a minor therapeutic effect in psoriasis, and the beneficial effect of bathing to enhance phototherapy was not demonstrated.

Widespread cutaneous carcinomas associated with human papillomaviruses 5, 14 and 20 after introduction of methotrexate in two long-term PUVA-treated patients.

BACKGROUND: PUVA treatment for patients with severe psoriasis has been demonstrated to be highly effective. However, an increased risk of nonmelanoma and melanoma skin cancers has been reported. It is generally accepted that the risk of squamous-cell carcinoma (SCC) is significantly increased in patients with long-term PUVA therapy. The role of methotrexate (MTX) and infection with oncogenic human papillomaviruses which may act as cocarcinogens is poorly documented. CASE REPORTS: Two cases of multiple SCCs associated with numerous PUVA keratoses and PUVA freckles after long-term PUVA therapy and subsequent treatment with MTX are presented. In 1 case, the tumor progressed to metastatic SCC. Tumors and scrapings of psoriatic skin lesions were analyzed for the presence of oncogenic human papillomavirus (HPV) genotypes. The genotype of HPV-5, -14 and -20 was detected in scrapings and skin tumors using PCR amplification. CONCLUSION: These observations support the concept that long-term PUVA treatment is carcinogenic and rise questions concerning an additional influence of MTX in the development and progression of skin cancer. The risk of metastatic SCC seems to be underestimated in high-dose PUVA-treated patients due to longer latency for developing metastases and the small number of studies with long-term follow-up. Treatment with MTX should be considered cautiously in patients previously exposed to high doses of PUVA. The presence of oncogenic HPVs in carcinomas and psoriatic skin lesions detected only with the highly sensitive nested PCR method is not necessarily a proof of their implication in skin carcinogenesis.

EGF receptor expression and growth of psoriatic and normal human keratinocytes are modulated by 1.25 (OH)2-vitamin D3 ex vivo.

Calcitriol or 1.25 (OH)2-vitamin D3 is used in the treatment of psoriasis as an inhibitor of cell proliferation. We studied the action of calcitriol ex vivo on the growth of psoriatic and normal human keratinocytes, and on the expression of the EGF receptor. Third passaged normal and psoriatic keratinocytes were seeded (10(4)/cm2) in 24-well dishes in serum-free medium (MCDB supplemented with amino acids, with either 0.1 or 1.1 mM of calcium) and 10(-9) M calcitriol. When subconfluence was reached, cell counts and 125I-EGF binding studies were performed. Cell counts showed at least a 50% decrease in growth under all conditions studied (normal or psoriatic keratinocytes; 0.1 or 1.1 mM calcium) when calcitriol was added. 125I-EGF binding studies showed a decrease in total receptor numbers in the presence of calcitriol with acceleration of binding at low concentrations of 125I-EGF. Scatchard plot analysis showed only one type of high affinity receptor. Receptor sites were decreased (30% to 40% of controls) in the presence of calcitriol together with a decrease in the dissociation constant. In conclusion, at almost physiological concentrations ex vivo, calcitriol strongly decreased normal and psoriatic keratinocyte growth. This potent antiproliferative effect could in part be explained by the capacity of calcitriol to downregulate EGF receptor expression.

Contact allergy to aeroallergens in children with atopic dermatitis: comparison with allergic contact dermatitis.

Immediate and delayed cutaneous hypersensitivity are believed to be implicated in the physiopathology atopic dermatitis (AD). The purpose of this study was to evaluate Type I and Type IV allergy to aeroallergens in children with AD. 59 children (mean age 5.2 years), presenting with AD according to Hanifin and Rajka's criteria, were skin tested (patch and corresponding prick tests) with common environmental aeroallergens and a restricted panel of the European standard series over a 1-year period. History and clinical data were carefully recorded using a standardized evaluation sheet; total and specific IgE serum levels were evaluated. 17 of 59 patients (28.8%) had at least 1 positive patch test, 32 of 59 patients (54.2%) had at least 1 positive prick test. Corresponding patch and prick tests were observed in 8 out of 17 patients. 5 children with positive patch tests had negative prick tests. Irritant pustular reactions (2/59, i.e. 3%), "angry back" reactions (6/59, i.e. 10%) and doubtful reactions (3/59, i.e. 5%) were excluded from the positive group. Positive patch tests observed included, in decreasing order: D. pteronyssinus and D. farinae (26.8%), garden trees (12.2%), plantain (9.8%), timothy grass, mugwort and damp area trees (4.9% each), and orchard grass (2.44%). 6 children with positive aeroallergen patch tests and 11 children with negative aeroallergen patch tests had at least 1 positive patch test to standard allergens. All children with an irritant reaction to aeroallergens had no reaction to standard patch tests. The relevance of aeroallergens in upgrading the severity of AD lesions has still to be explored by challenge studies and by long-term follow-up.

Treatment of port-wine stains with the 585-nm flashlamp-pulsed tunable dye laser: a study of 74 patients.

Over 20 months, we have treated 74 patients (59 children less than 12 years of age) with port-wine stains (PWS) using a 585-nm flashlamp-pulsed dye laser (SPTL-1, Candela Corp., Wayland, Mass., USA) after topical anesthesia with Emla cream. A 5-point reference color scale was used to evaluate the results. 45 patients had at least one treatment on the entire surface of the lesion. A mean of 88 impacts per session was delivered. There was a significant decrease in color in around two thirds of the cases after one complete treatment with a gradual tendency to improvement after subsequent treatments. Younger age at the beginning of treatment was not found to be predictive of a better outcome after the first treatment. In around one third of the cases, positive test site treatment was not correlated with significant improvement after one treatment. Lesions situated on the limbs were less responsive than those on the head and neck. Except for problems due to absence of general anesthesia in young children enduring repeated stressful and sometimes painful procedures, the overall impression is that early treatment of PWS is possible with very limited risks of scarring using this technique.

Production of epidermal sheets in a serum free culture system: a further appraisal of the role of extracellular calcium.

Rhenwald and Green's technique is currently the standard method for growing stratifying epidermal cell cultures. The serum free system developed in Ham's laboratory (MCDB 153) was designed to grow keratinocyte monolayers in clonogenic conditions. Our aim was to optimize conditions in serum-free MCDB 153 for culturing epidermal sheets from adult normal skin, and to assess the effect of extracellular calcium and temperature on proliferation and differentiation of cultured keratinocytes. Sixteen strains derived from plastic surgery specimens (mean age of donors 37 years; range 5-89) were used. Primary cultures were seeded at an optimal density of 8 x 10(4) cells/cm2 in primary cultures and 10(4) cells/cm2 in secondary cultures in complete medium including EGF, insulin, hydrocortisone and bovine pituitary extract, supplemented with isoleucine, tyrosine, methionine, phenylalanine, tryptophane and histidine. Amino acid (AA) supplementation allows a 5.8-fold increase in cell counts at confluency and monolayers with densely packed cells are obtained. In AA supplemented cultures, confluency is obtained in 16 +/- 3 days in primary cultures and in 13 +/- 0.5 days at first passages. Switches to 1.1 mM calcium at first or second passages resulted in a significant increase in cell counts (P less than 0.001), when compared with AA supplemented low calcium cultures. Low temperature/low calcium cultures resulted in a 50% decrease in cell counts. Low temperature/high calcium cultures gave similar cell counts as the 37 degrees C controls. AA and calcium supplemented cultures were evaluated for differentiation markers: involucrin expression was increased, keratins 5, 6, 14, 17 were expressed, and the sheets were 6-10 layers thick by electron microscopy, with keratohyalin granules and cornified envelopes appearing at layers 3-6 (from basal layer). Dispase treatment allowed an easy detachment of these sheets. These results show that the culture medium MCDB 153 can be adapted without serum supplementation to batch culture of human adult keratinocytes to produce epidermal sheets suitable for grafting. They also indicate that extracellular calcium in physiological range of concentration is not a sufficient signal for growth arrest when other growth conditions are optimized.

[Lichenoid pityriasis (parapsoriasis guttata) in children. Report of 17 cases]. / Pityriasis lichénoïde (parapsoriasis en gouttes) de l'enfant. A propos de dix-sept cas.

Seventeen cases of pityriasis lichenoides diagnosed over a nine-year period in children under 15 years of age are reported. Patients with this benign disease develop papular skin lesions covered with thick, coherent scales which detach in a single piece (reminiscent of sealing wax). Pruritus is not marked. Lesions may be necrotic (Mucha Habermann's small pox-like form, n = 6) or mild (leukodermic form, n = 2). Half of the patients studied developed several episodes and total duration of the disease exceeded two years in one third of cases. Recovery occurred after one or two episodes in half the children. Scars developed in some patients with severely necrotic lesions. None of the patients developed lymphoma. All patients with lymphomatoid papulosis progressing to lymphoma reported in the literature were adults. Pathogenesis of pityriasis lichenoides remains unknown but may involve lymphocytic vasculitis. No truly effective therapy is available. However, oral macrolides can be used especially in patients with early manifestations suggesting an infectious disease. Emollients, heliotherapy and ultraviolet therapy may also be recommended.