Antonella Tammaro

IL-9 Regulates Allergen-Specific Th1 Responses in Allergic Contact Dermatitis

The cytokine IL-9, derived primarily from T-helper (Th)-9 lymphocytes, promotes expansion of the Th2 subset and is implicated in the mechanisms of allergic asthma. We hypothesize that IL-9 also plays a role in human allergic contact dermatitis (ACD). To investigate this hypothesis, skin biopsy specimens of positive patch test sites from non-atopic patients were assayed using qPCR and immunohistochemistry. Along with Th2 associated cytokines, IFN-γ, IL-4, and IL-17A, expression of IL-9, and PU.1, a Th9-associated transcription factor, were elevated when compared to paired normal skin. Immunohistochemistry on ACD skin biopsies identified PU.1+CD3+, and PU.1+CD4+ cells, consistent with Th9 lymphocytes, in the inflammatory infiltrate. PBMC from nickel-allergic patients, but not non-allergic controls, show significant IL-9 production in response to nickel. Blocking studies with monoclonal antibodies to HLA-DR (but not HLA-A, B, C) or chloroquine significantly reduced this nickel-specific IL-9 production. Additionally, blockade of IL-9 or IL-4 enhanced allergen-specific IFN-γ production. A contact hypersensitivity model using IL-9−/− mice, shows enhanced Th1 lymphocyte immune responses, when compared to WT mice, consistent with our human in vitro data. This study demonstrates that IL-9, through its direct effects on Th1 and ability to promote IL-4 secretion, has a regulatory role for Th1 lymphocytes in ACD.

Allergy to nickel: first results on patients administered with an oral hyposensitization therapy.

Nickel sulphate allergy is the most common contact allergy. In fact, nickel sulphate is an ubiquitous element, contained in various objects and food; it occurs in igneous rocks, as a free metal and together with iron, but it is also a component of living organism, mainly vegetables. We carried out a clinical trial of oral hyposensitization therapy with low doses of nickel in a group of 67 patients affected by systemic allergy to this sensitizer element. We obtained good results on consequent tolerance to nickel in treated patients.

Imiquimod-Induced TLR7 Signaling Enhances Repair of DNA Damage Induced by Ultraviolet Light in Bone Marrow-Derived Cells

Imiquimod is a TLR7/8 agonist that has anticancer therapeutic efficacy in the treatment of precancerous skin lesions and certain nonmelanoma skin cancers. To test our hypothesis that imiquimod enhances DNA repair as a mechanism for its anticancer activity, the nucleotide excision repair genes were studied in bone marrow-derived cells. Imiquimod enhanced the expression of xeroderma pigmentosum (XP) A and other DNA repair genes (quantitative real-time PCR analysis) and resulted in an increased nuclear localization of the DNA repair enzyme XPA. This was dependent on MyD88, as bone marrow-derived cells from MyD88−/− mice did not increase XPA gene expression and did not enhance the survival of MyD88−/−-derived bone marrow-derived cells after UV B exposure as was observed in bone marrow-derived cells from MyD88+/+ mice. Imiquimod also enhanced DNA repair of UV light (UVL)-irradiated gene expression constructs and accelerated the resolution of cyclobutane pyrimidine dimers after UVL exposures in P388 and XS52. Lastly, topical treatment of mouse skin with 5% imiquimod cream prior to UVL irradiation resulted in a decrease in the number of cyclobutane pyridimine dimer-positive APC that were found in local lymph nodes 24 h after UVL irradiation in both wild-type and IL-12 gene-targeted mice. In total, these data support the idea that TLR7 agonists such as imiquimod enhance DNA repair in bone marrow-derived cells. This property is likely to be an important mechanism for its anticancer effects because it protects cutaneous APC from the deleterious effects of UVL.

Contact Allergy to Disperse Blue Dye in Goggles for Swimming-Bath

We report two unusual cases of contact allergy to blue disperse dyes in two patients who made daily use of blue-dyed goggles for swimming-bath, documented with patch tests. We obtained good results by avoiding the use of these dyed goggles.

Topical and systemic therapies for nickel allergy.

&NA; Nickel allergy can result in both cutaneous and systemic manifestations, and can range from mild to severe symptoms. A severe form of this allergy is the Systemic nickel allergy syndrome, clinically characterized by cutaneous manifestions (contact dermatitis, pompholyx, hand dermatitis dyshydrosis, urticaria) with chronic course and systemic symptoms (headache, asthenia, itching, and gastrointestinal disorders related to histopathological alterations of gastrointestinal mucosa, borderline with celiac disease). This review aims to briefly update the reader on past and current therapies for nickel contact allergy.

Elevation of IL-9 in Extreme Patch Test Reactions Suggests It Is an Inflammatory Mediator in Allergic Contact Dermatitis.

To the Editor: Interleukin 9 is a cytokine classically considered to be associated with the Th2 lymphocyte subset; however, an IL-9 producing T-cell subset, Th9, has recently been recognized and implicated in the pathogenesis of allergic inflammation. Despite the known role of this cytokine in various forms of allergic inflammation, the role of IL-9 specifically in allergic contact dermatitis (ACD) has not been fully established. A recent collaborative study conducted by the Departments of Dermatology at the University of Maryland School of Medicine and the University of Rome has contributed to our evolving understanding of the role of IL-9 in ACD by demonstrating that IL-9 serves a regulatory role by modulating allergen-specific IFN-F production by Th1 cells. In the study, a 5-fold increase in gene expression of IL-9 as well as a 2to 3-fold increase in the Th9 transcription factor PU.1 was present in skin biopsies from 7 patients with positive patch test results to nickel. Furthermore, approximately 4% of the infiltrating CD3/CD4 T cells in positive patch test biopsies from 5 patients with ACD to different allergens were found to be Th9 cells. A robust, dose-dependent production of IL-9 in vitro by peripheral blood mononuclear cells derived from 7 nickel-allergic patients was observed in response to increasing doses of nickel. It was also demonstrated that IL-9 acts to regulate allergen-specific Th1 lymphocyte responses indirectly by enhancing IL-4 production by Th2 lymphocytes. These in vitro data were confirmed in a contact hypersensitivity model using IL-9/ mice, which demonstrated enhanced Th1 lymphocyte immune responses when compared with wildtype mice. Surprisingly, irritant contact dermatitis was impaired in IL-9 mice compared with wild-type mice, suggesting a role for IL-9 in promoting an inflammatory response during contact dermatitis. This prompted us to study IL-9 production in extreme cases of ACD at the protein level (ex vivo). We studied 5 extreme bullous patch test reactions (3+) elicited by patch testing with paraphenylenediamine in highly allergic patients. Blister fluid was aspirated at the 48or 72-hour readings and studied for IL-9 content using an IL-9Yspecific enzyme linked immunosorbent assay. High levels of IL-9 were identified in all 5 ACD specimens (1589 T 459 pg/mL; n = 5). In addition, we measured IL-9 levels in 3 normal human serum controls and blister fluid from 3 different control blistering skin diseases: an ischemic blister, an edema blister, and bullous pyoderma gangrenosum (PG). Interleukin 9 levels were undetectable in all of these samples with the exception of PG, in which IL-9 was mildly elevated (199 pg/mL) (Fig. 1). Significantly elevated levels of IL-9 in extreme patch test reactions suggest that IL-9 may serve as an inflammatory mediator in ACD. The cellular source of IL-9 in the blister fluid is currently unknown, possibly T cells, mast cells, or another cell type. Although further studies are necessary to clarify the role of IL-9 as an inflammatory mediator in ACD, our study contributes to the growing body of evidence that Th9 has an important role in allergic skin reactions and suggests that Th9 and its associated cytokine, IL-9, represent a potential target for immunotherapy in the treatment of nonatopic allergic skin diseases.

Manganese oxidation state as a cause of irritant patch test reactions.

BackgroundManganese chloride (MnCl2) 2.5% is included in the extended metals patch test series to evaluate patients for contact hypersensitivity to this metal salt. ObjectivesThe objective of this study was to prospectively determine the rate of allergic and irritant patch test reactions to MnCl2 (Mn(II)), Mn2O3 (Mn(III)), and KMnO4 (Mn(VII)) in a cohort of patients undergoing patch testing. MethodsFifty-eight patients were patch tested with MnCl2, Mn2O3, and KMnO4, each at 2.5% in petrolatum. Patch readings were taken at 48, and 72 or 96 hours, and scored using standard methods. Cultured monolayers of keratinocytes (KCs) were exposed to MnCl2, Mn2O3, and KMnO4 in aqueous culture medium, and cell survival and cytokine release were studied. ConclusionsMnCl2 caused irritant patch test reactions in 41% of the cohort, whereas Mn2O3 and KMnO4 caused a significantly lower rate of irritant reactions (both 3%). No allergic morphologies were observed. Similarly, in cultured KC monolayers, only MnCl2 was cytotoxic to KC and induced tumor necrosis factor &agr; release.The oxidation state of manganese used for patch testing affects the irritancy of this metal salt, as Mn(II) caused an unacceptably high rate of irritant reactions in a cohort of patients. In vitro studies confirmed these clinical data, as only Mn(II) was cytotoxic to cultured monolayers of KC.

Contact allergic dermatitis to gold in a tattoo: a case report.

The art of tattooing has increasing in recent decades. Allergic sensitivity to one of the pigments is the most frequent cause of dermatological reactions at the site of the tatoo. Gold is a new pigment used in tatooing, because of its bright yellow color and luster. Allergy to this metal is uncommon. To our knowledge, this is the first reported case of allergic contact dermatitis to gold in a tattoo.

Unusual case of linear anetoderma in children.

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Fingertip Dermatitis: Occupational Acrylate Cross Reaction

Allergic contact dermatitis due to acrylates present in the workplace is a disease frequently reported among dentists, printers, and fiberglass workers.1 Recently, the number of cases of contact allergic dermatitis among beauticians specialized in sculpting artificial nails has increased. The use of sculptured nails (also called acrylic or porcelain nails) is becoming increasingly popular in beauty treatment centers, and they are also available in kits for do-it-yourself applications at home. In recent years we have witnessed an increase in the incidence of allergic contact dermatitis (ACD) caused by the acrylic products used in artificial nails. ACD mostly affects the professional beauticians who handle the product, but can also be observed in end users.2 A 35-year-old woman, economist and manicurist for hobby for 4 years, presented with severe fingertip dermatitis and nail plate dystrophy ( Fig. 1 A, B ) . Eighteen months previously, she had had hair extensions and developed a transient pruritic rash on her arms that cleared after removing the hair extensions. Acrylate adhesive is used to attach hair extensions and may have been applied in this case. A year previously, she began to work with sculptured acrylic nails and shortly thereafter developed severe vesicular dermatitis on her hands and fingers. About two years, the patient also relates to practice decoupage and use acrylic glue. She stopped working with artificial nails because contact with nail-sculpturing materials was suspected as the cause of her dermatitis. A few months later, she applied artificial nails on herself and a day later developed severe fingertip dermatitis, which was present on clinical examination, together with nail plate dystrophy. Patch testing was performed with a European baseline series (TRUE test panels 1 and 2) supplemented with pet.-based selected allergens from a series of adhesive and acrylate chemicals F.I.R.M.A. (Benzoyl peroxide 1%, Methyl methacrylate 2%, Hydroxyethyl methacrylate 2-HEMA 2%, Tripropylene glycol diacrylate 0.1% , Trimethylolpropane triacrylate 0.1% , Urethane diacrylate 0.1%, Urethane diacrylate 0.05%, Ethyl cyanoacrylate [ECA] 10%, Hydroquinone 1%) applied in Finn Chambers on Scanpor tape and read according to the International Contact Dermatitis Research Group scoring scale at D3 and D7. A TRUE patch test was positive to nickel sulphate (D3+++, D7+) and cobalt (D3+, D7 ++). Special series for acrylate chemicals F. I. R. M. A. was positive for ethylcyanoacrylate (ECA) 10% (D3+, D7++). Allergic reactions to sculptured nails can appear within months or years after use by both professional users and end users, because contact with these substances is in both cases protract in time. Symptoms of sensitization to acrylates in professional beauticians―generally women― consist of subacute or chronic eczema located on the pads of the fingers that come into direct contact with the acrylic resin.3 Typically the fingertip of the first, second, and third finger of both hands are affected―the nondominant hand from holding the client’s nail, and the dominant hand from holding the brush. Lesions also frequently occur on the sides of the hands where these rest on work surfaces is likely to carry monomer residues. Typical symptoms are pruritus, fingertip dermatitis and pain once fissures develop. Eczematous lesions frequently occur away from the site of contact as the result of transportation of residues of either the glue monomer or the powder polymer ( which can also contain the monomer) from the hands to more distant areas of skin. Symptoms in end users differ from those in professional users. The first sign is itchiness at the nail base, with paronychia, painful nails, and, occasionally, paresthesia subsequently developing. The nail base often becomes dry and thickened, and Allergology International. 2014;63:609-610