Marie-Anne Morren

ATOPIC DERMATITIS : TRIGGERING FACTORS

Atopic dermatitis is a hereditary disorder, frequently associated with allergic rhinitis and bronchial asthma. The disease may be influenced by many triggering factors such as irritants, aeroallergens, food, microbial organisms, sex hormones, stress factors, sweating, and climatologic factors. Moreover, it is important to be aware of contact allergy as a complicating factor. This review deals with recent clinical, experimental, and some therapeutic data on these triggering factors.

Protein contact dermatitis: myth or reality?

Protein contact dermatitis is a dermatosis which usually presents as a chronic eczema with episodic acute exacerbations a few minutes after contact with the offending allergen. Patch tests with the responsible allergen are usually negative, and the diagnosis can only be made by means of scratch or prick tests with the allergen. Sometimes, specific IgE antibodies can be detected in the blood. As there is considerable confusion about this entity, we have reviewed the cases reported in the literature.

Olmsted syndrome: exploration of the immunological phenotype

BackgroundOlmsted syndrome is a rare congenital skin disorder presenting with periorifical hyperkeratotic lesions and mutilating palmoplantar keratoderma, which is often associated with infections of the keratotic area. A recent study identified de novo mutations causing constitutive activation of TRPV3 as a cause of the keratotic manifestations of Olmsted syndrome.MethodsGenetic, clinical and immunological profiling was performed on a case study patient with the clinical diagnosis of Olmsted syndrome.ResultsThe patient was found to harbour a previously undescribed 1718G-C transversion in TRPV3, causing a G573A point mutation. In depth clinical and immunological analysis found multiple indicators of immune dysregulation, including frequent dermal infections, inflammatory infiltrate in the affected skin, hyper IgE production and elevated follicular T cells and eosinophils in the peripheral blood.ConclusionsThese results provide the first comprehensive assessment of the immunological features of Olmsted syndrome. The systemic phenotype of hyper IgE and persistent eosinophilia suggest a primary or secondary role of immunological processes in the pathogenesis of Olmsted syndrome, and have important clinical consequences with regard to the treatment of Olmsted syndrome patients.

Safety, Efficacy, and Dosage of 1% Pimecrolimus Cream for the Treatment of Atopic Dermatitis in Daily Practice

AbstractIntroduction: Although several controlled clinical trials have demonstrated the efficacy and good tolerability of 1% pimecrolimus cream for the treatment of atopic dermatitis, the results of these trials may not apply to real-life usage. The objective of this study was to evaluate the safety and efficacy of a pimecrolimus-based regimen in daily practice. Methods: This was a 6-month, open-label, multicenter study in 947 patients aged ≥3 months with atopic dermatitis of all severities. The investigators incorporated 1% pimecrolimus cream into patients’ standard treatment protocols on the basis of their clinical diagnosis. Use of topical corticosteroids was allowed at the discretion of the physician. Safety and tolerability were evaluated by monitoring adverse events. Efficacy was evaluated by recording changes in the Investigators’ Global Assessment scores and pruritus scores at each visit. Results: No clinically unexpected adverse events were reported. The discontinuation rate for adverse events was 2.3%. The disease improvement rate was 53.7% at week 1 and 66.9% at week 24. The pimecrolimus-based regimen was particularly effective for the treatment of lesions involving the face (improvement rate: 61.9% at week 1 and 76.7% at week 24). The greatest therapeutic response was experienced by pediatric patients with mild or moderate disease. Nonetheless, 64% and 65% of infants and children, respectively, with severe/very severe facial disease at baseline were clear/almost clear of signs of atopic dermatitis on their face at week 24. In patients aged <18 years, most of the improvement occurred within the first week of treatment, while in adults a progressive improvement was observed over the entire study period. Worsening of disease by the end of the study occurred in 9.5% of patients and was most frequent in adults (12.6%). The discontinuation rate for unsatisfactory therapeutic effect was 4.8%. The mean number of treatment days was 135.6 (SD 53.2). The mean drug consumption (non-US centers only) was 4.2g per treatment day. Drug consumption decreased over time as disease improved. In total, 47% of patients who completed the study never used topical corticosteroids over 6 months. Conclusion: In daily practice, incorporation of 1% pimecrolimus cream into patients’ standard treatment regimen is well tolerated and improves atopic dermatitis in approximately two-thirds of patients. Disease improvement is particularly evident on the face. The greatest therapeutic response is experienced by pediatric patients with mild or moderate disease. In these patients, most of the improvement is observed within 1 week from the start of treatment.

Tight skin and limited joint movements as early presentation of Hutchinson-Gilford progeria in a 7-week-old infant

We present a 7-week-old male infant with pseudoscleroderma as a primary manifestation of the Hutchinson-Gilford syndrome of premature aging. He had suffered intra-uterine growth retardation; micrognathism and a cleft palate were evident at birth. He presented with feeding difficulties and severe, diffuse scleroderma-like lesions, a faint peri-oral cyanosis and prominent scalp veins. With time, special facial features became more and more apparent: frontal bossing, prominent eyes, thin and fine nose and lips, microstomia, low-set ears and occipito-parietal alopecia. Histopathology of the skin showed an increased density and thickness of collagen in the dermis and hypodermis. Within the 1st year of life, typical skeletal characteristics were observed. The diagnosis of Hutchinson-Gilford syndrome was confirmed by analysis of the lamin A gene, revealing a heterozygous c.1824C>T (G608G) mutation. Conclusion:Hutchinson-Gilford syndrome is an extremely rare disorder of which the full clinical spectrum becomes evident with time. Sclerodermatous changes in the infant can be the first manifestation.

Diverse Cutaneous Presentations of Langerhans Cell Histiocytosis in Children: A Retrospective Cohort Study

Langerhans cell histiocytosis (LCH) is a rare disease, frequently affecting young children.

Focal facial dermal dysplasia, type IV, is caused by mutations in CYP26C1

Focal facial dermal dysplasia (FFDD) Type IV is a rare syndrome characterized by facial lesions resembling aplasia cutis in a preauricular distribution along the line of fusion of the maxillary and mandibular prominences. To identify the causative gene(s), exome sequencing was performed in a family with two affected siblings. Assuming autosomal recessive inheritance, two novel sequence variants were identified in both siblings in CYP26C1-a duplication of seven base pairs, which was maternally inherited, c.844_851dupCCATGCA, predicting p.Glu284fsX128 and a missense mutation, c.1433G>A, predicting p.Arg478His, that was paternally inherited. The duplication predicted a frameshift mutation that led to a premature stop codon and premature chain termination, whereas the missense mutation was not functional based on its in vitro expression in mammalian cells. The FFDD skin lesions arise along the sites of fusion of the maxillary and mandibular prominences early in facial development, and Cyp26c1 was expressed exactly along the fusion line for these facial prominences in the first branchial arch in mice. Sequencing of four additional, unrelated Type IV FFDD patients and eight Type II or III TWIST2-negative FFDD patients revealed that three of the Type IV patients were homozygous for the duplication, whereas none of the Type II or III patients had CYP26C1 mutations. The seven base pairs duplication was present in 0.3% of healthy controls and 0.3% of patients with other birth defects. These findings suggest that the phenotypic manifestations of FFDD Type IV can be non-penetrant or underascertained. Thus, FFDD Type IV results from the loss of function mutations in CYP26C1.

Measurement of itching: Validation of the Leuven Itch Scale

OBJECTIVE To develop the Leuven Itch Scale (LIS), which measures itching through evaluation of the dimensions of the itch experience; and to provide evidence of the validity, reliability, and responsiveness of the LIS. MATERIALS AND METHODS A clinimetric study using a longitudinal design. Patients with burns (n=46), atopic dermatitis (n=63), or chronic urticaria (n=41) were included. Evidence for validity (based on test content, relations with other variables and internal structure), reliability and responsiveness of the LIS was evaluated. RESULTS Validity evidence based on test content was demonstrated by very low percentages of invalid scores for most items. Validity evidence based on relations with other variables was found, because all hypotheses that were put forward could be accepted. With respect to validity evidence on internal structure, a significant moderate positive correlation was found between itch frequency and itch distress, and between itch frequency and severity. As hypothesized, itch severity and distress were strongly correlated. Test-retest reliability showed a moderate to almost perfect agreement for about half of the items. However, the remaining items could be subject to changes in the itch, rather than reflecting instability of the Leuven Itch Scale. In terms of responsiveness, the Leuven Itch Scale did not suffer from floor or ceiling effects and could detect changes in itch frequency in patients with burns. CONCLUSION The Leuven Itch Scale is a useful and clinimetrically sound instrument to measure pruritus in different patient populations affected by itching.

Sensitizing oat extracts in cosmetic creams: is there an alternative?

A 33-year-old woman suffered from atopic eczema and allergic rhinoconjunctivitis, and was known to have type-I reactions to house dust mite, cats, dogs, malassezia, nut mixture, walnuts, shrimp, lobsters, and asparagus, all of which she strictly tried to avoid. However, treatment with topical corticosteroids, tacrolimus, oral antibiotics or antifungal therapy did not always yield the expected improvement in her dermatitis. The patient was referred to our contact allergy unit because she developed an itchy and erythematous eruption with papules and patchy lesions on the face immediately after the application of a moisturizer ‘Exomega emollient cream with omega 6 and vitamin B3 for atopic and very dry skin’ of A-Derma® (Pierre-Fabre, CastanetTolosan, France). She had been using this cream for approximately 1 year, but the symptoms had been present for about 6 months. The skin lesions were localized at the application site and faded a few hours after the application. She had no extracutaneous symptoms. However, later on, she noticed that immediately after she had eaten certain biscuits or bread containing oatmeal, she experienced itching and swelling of her lips, as well as pruritic, erythematous papules and patchy lesions on the trunk, never having experienced this previously. The patient was patch tested with the European baseline series and her own cosmetic products, using van der Bend® chambers (van der Bend, Brielle, The Netherlands) mounted on Micropore® (3 M; St Paul, MN, USA) and fixed on the intact skin of the back with Mefix (Mölnlycke, Göteborg, Sweden) acrylic tape. The readings were performed at D2 and D4, but all tests, including that with her emollient cream, gave negative results. Because of the appearance of the symptoms immediately after application of the emollient, prick tests with the cream as is, histamine as a positive control and physiological saline as a negative control were performed. A wheal and flare reaction to histamine and the emollient cream were observed (Fig. 1). A blood sample showed an elevated total IgE level (1328 kU/l; reference value, ≤126 kU/l) and slightly elevated specific IgE antibodies to oat (1.23 UA/ml), as compared with wheat (0.12 UA/ml), rye (<0.10 UA/ml), barley (0.11 UA/ml), corn (0.31 UA/ml), and gluten (<0.10 UA/ml). Further prick tests with the different components of the cream, provided by the company, showed a 2+ wheal and flare reaction (Fig. 2) only to the Avena sativa alcoholic extract, (with a 1+ wheal and flare reaction to histamine, the positive control). We subsequently sent the patient’s serum to Pierre Fabre laboratories in France, who further analysed the immunoreactivity to the A. sativa extract present in the cream, as well as to a newly prepared oat extract, from which the company had eliminated the proteins. With the application of enzyme-linked immunosorbent assay (ELISA) tests, immunoreactivity of our patient’s serum to the causal oat extract was detected (although not confirmed by western immunoblot), but not to the protein-free extract. Pierre Fabre laboratories tested the sera of 3 other cereal-sensitized patients with five different extracts of oat (four proteinic extracts and one extract without proteins): two of them reacted with different intensities to all of the extracts, except for the new proteinfree extract; the third one did not react to any of the extracts tested. The new extract has now replaced the former one in the commercialized products.

Contact allergy in children

Contact allergy in children is more frequent than previously suspected. Certain contactants are characteristic of children and may be responsible for unusual clinical presentations. Metals (jewelry, mobile phones), ingredients of pharmaceutical and cosmetic products, para-phenylenediamine in tattoos, rubber additives (in shoes, toys, diapers, sports equipment, and so on), plastics, resins (including those used in glues, orthopedic devices, electronic devices), and plants are allergens in children. In adolescents, sometimes occupational allergens are also possible. If there is a suspicion by history and clinical picture, or there is an unexplained eczema at particular body sites, patch testing should be performed at all ages. Patch testing in children is safe, but false-positive reactions are possible. Indeed, positive reactions must be interpreted carefully, particularly in atopics since their skin is readily irritated; this is especially the case for metals. An abbreviated baseline series, supplemented with allergens suggested by the history, should be used.