AllergoOncology: ultra-low IgE, a potential novel biomarker in cancer-a Position Paper of the European Academy of Allergy and Clinical Immunology (EAACI).

Elevated serum IgE levels are associated with allergic disorders, parasitosis and specific immunologic abnormalities. In addition, epidemiological and mechanistic evidence indicates an association between IgE-mediated immune surveillance and protection from tumour growth. Intriguingly, recent studies reveal a correlation between IgE deficiency and increased malignancy risk. This is the first review discussing IgE levels and links to pathological conditions, with special focus on the potential clinical significance of ultra-low serum IgE levels and risk of malignancy. In this Position Paper we discuss: (a) the utility of measuring total IgE levels in the management of allergies, parasitosis, and immunodeficiencies, (b) factors that may influence serum IgE levels, (c) IgE as a marker of different disorders, and d) the relationship between ultra-low IgE levels and malignancy susceptibility. While elevated serum IgE is generally associated with allergic/atopic conditions, very low or absent IgE may hamper anti-tumour surveillance, indicating the importance of a balanced IgE-mediated immune function. Ultra-low IgE may prove to be an unexpected biomarker for cancer risk. Nevertheless, given the early stage of investigations conducted mostly in patients with diseases that influence IgE levels, in-depth mechanistic studies and stratification of malignancy risk based on associated demographic, immunological and clinical co-factors are warranted.

[Alpha-Gal-associated delayed red meat anaphylaxis as an occupational disease]. / Alpha-Gal-assoziierte verzögerte Anaphylaxie gegen rotes Fleisch als Berufskrankheit.

In a 30-year-old chef with recurrent delayed angioedema history as well as the experimental detection of IgE antibodies against galactose-alpha-(1,3)-galactose (alpha-Gal) pointed to alpha-Gal as the causative agent. The diagnosis, therefore, was delayed anaphylaxis due to alpha-Gal. Because of the potential relationship to his profession, we submitted a dermatologist's report BK 5101 to the liability and insurance association, whereupon his contract of employment was terminated without notice. As a consequence, we reported an occupational disease. This case demonstrates an underdiagnosed, potentially life-threatening allergy to the disaccharide alpha-Gal in red meat as an occupational disease.

[Update on meat allergy. α-Gal: a new epitope, a new entity?]. / Allergie auf Säugetierfleisch. α-Gal: Neues Epitop, neue Entität?

The association between the carbohydrate galactose-[alpha]-1,3-galactose (α-Gal) and anaphylaxis was first documented after severe hypersensitivity reactions to cetuximab, a chimeric mouse-human IgG1 monoclonal antibody approved for targeted therapy of carcinomas of colon, as well as of the head and neck region. α-Gal is a ubiquitous glycan moiety expressed on cells and tissue of non-primate mammals. Since this epitope is not expressed in humans, it is very immunogenic for them. α-Gal is located on the Fab portion of cetuximab and thus on the murine part of the chimera. The anaphylactic reactions to the antibody were mediated by IgE specific for α-Gal. Anti-α-Gal-IgE were first detected in sera of patients from the southeastern U.S. and reacted with a wide range of mammalian allergens. The geographic distribution prompted investigations of sensitization routes apart from the ingestion of red meat, such as tick bites und parasitic infections. Anti-α-Gal-IgE seems to be of clinical relevance for allergy to red meat and for the pork-cat syndrome. It is also associated with a novel form of delayed anaphylaxis, which appears more than 3 hours following the ingestion of red meat (beef, pork and lamb), a phenomenon which is still to be elucidated. For most of these patients conventional skin prick tests with commercial reagents proved insufficient for diagnosis.

Contact allergy in patients with rosacea: a clinic-based, prospective epidemiological study.

BACKGROUND: Rosacea is a relatively common inflammatory skin disease of unknown prevalence. The proportion of contact allergy complicating rosacea and its therapy, respectively, is largely unknown. OBJECTIVE: To estimate the prevalence of specific contact allergy in rosacea patients and to compare this with the prevalence observed in the general population and in general patch test patients. PATIENTS/METHODS: In this prospective monocentre study, 78 patients with rosacea were investigated for contact sensitizations via patch testing the standard series, constituents of topical formulations, preservatives, fragrances, topically applied drugs and, if available, patient's own products. RESULTS: Positive reactions occurred to nickel (II) sulphate (12 of 78, 15.4%), fragrance mix I (4 of 77, 5.2%), balsam of Peru (8 of 77, 10.4%; significantly elevated prevalence compared to that observed in the population-based KORA study), potassium dichromate (4 of 78, 5.1%) and Lyral (3 of 78, 3.8%). Regarding topical antibiotics, only 1 of 78 (1.3%) patients was positive to neomycin sulphate, and none to metronidazole; however, 6 of 75 (8%) patients were positive to gentamicin sulphate, and 4 of 76 (5.3%) patients were positive to framycetin sulphate. No allergic but irritant patch test reactions, instead, were provoked by various patients' own products as well as by the irritant sodium lauryl sulphate (SLS) even in low concentrations. CONCLUSION: Despite the limited power of the study, a strikingly high prevalence of contact allergy to gentamicin sulphate was observed, which is probably due to antibiotic treatment of rosacea-associated eye symptoms. The reactions to the irritant SLS probably mirror the extreme skin sensitivity in rosacea.

[First manifestation of psoriasis vulgaris in tumor necrosis factor receptor-associated periodic syndrome during treatment with etanercept]. / Erstmanifestation einer Psoriasis vulgaris bei Tumornekrosefaktor-Rezeptor-1-assoziiertem periodischem Syndrom unter Therapie mit Etanercept.

Drugs antagonizing tumor necrosis factor (TNF) alpha have been increasingly and successfully used in the treatment of psoriasis vulgaris and psoriatic arthritis. We report a patient with TNF receptor 1-associated periodic syndrome (TRAPS) who received TNF-alpha antagonist etanercept. A month later, the patient developed for the first time generalized psoriasis vulgaris. This paradoxical phenomenon has been reported sporadically in patients receiving TNF-alpha antagonists for other inflammatory diseases. The cause of psoriasis induced by TNF-alpha antagonists is still obscure.

[Disseminated granulomatous type IV reaction after a tattoo]. / Disseminierte granulomatöse Typ-IV-Reaktion nach Tätowierung.

Localized type-IV allergies to tattoo dyes are quite common. p-Phenylenediamine, which is used as a black pigment in temporary henna tattoos, is a particularly potent allergen. Generalized type IV reactions are very rare, however. Disseminated granulomatous reactions on tattoo dyes have so far not been reported in the literature. We describe the case of a 54-year-old female patient who had such a reaction pattern after a tattoo owing to a previously unknown sensitization to potassium dichromate.

Pyoderma gangraenosum, a rare, but potentially fatal complication in paediatric oncology patients.

Pyoderma gangraenosum (PG) is a serious chronic, ulcerative skin disorder afflicting both adults and children. As PG is often associated with systemic diseases (>50%) such as inflammatory bowel disease, rheumatoid arthritis or haematological disorders, it requires a multidisciplinary approach. This disorder is not commonly reported in paediatrics; therefore children with PG represent a particularly difficult diagnostic challenge. Clinical diagnosis is often delayed and PG is only considered after eliminating other causes of cutaneous ulcers. We report a 4-year-old boy with secondary myelodysplastic syndrome following treatment for acute lymphoblastic leukaemia who presented with a massive inflammatory, ulcerative proliferation of the lower lip which was diagnosed as PG. We have reviewed the literature with reference to diagnostic criteria and treatment options of this disorder that is particularly rare in childhood.

Rosacea and contact allergy to cosmetics and topical medicaments--retrospective analysis of multicentre surveillance data 1995-2002.

The role of contact allergy in rosacea has rarely been investigated. In this retrospective study, 361 out of 76,697 patients tested and documented by the Information Network of Departments of Dermatology between 1995 and 2002 had rosacea. Patch tests included standard series and constituents of cosmetics and topical medicaments. 118/361 had additionally been patch tested with their own cosmetics/medicaments. Positive reactions occurred to nickel (II) sulfate in 9.3%, fragrance mix in 8.8%, thimerosal in 6.9%, Myroxylon pereirae resin in 5.9%, potassium dichromate in 4.6% and propolis in 2.8%. Whereas rosacea patients had a significantly higher risk of contact allergy to propolis compared to the remaining patients, in an age- and sex-adjusted analysis, contact allergy to nickel was significantly less frequent in this group. For Lyral, the risk was elevated, albeit not significantly. Only 2/329 patients were positive to neomycin sulfate and 1/100 to gentamicin sulfate, among the panel of (topical) antibiotics tested. Among 118 patients tested with their own products, 3 were tested to metronidazole, 1 reacting positively. Irritant or doubtful patch test reactions were provoked by various substances (vehicles, oxidants and preservatives of various creams), which might also be clinically important, considering the heightened sensitivity of rosaceous skin.

[Sunlight-induced granulomatous reaction to permanent lip liner]. / Sonnenlichtgetriggerte granulomatöse Reaktion auf Permanent Lip-Liner.

The demand for permanent make up and especially permanent lip liner has increased in recent years in Germany. Information about complications is not available in the medical literature, because tattooing is a trade whose results and problems are not monitored and documented, as is the case for medical procedures. A female patient with permanent lip liner experienced no complications for one year. Then, after intensive sun exposure she developed solid, linear papules along the outer margin of her lips. Histology revealed a granulomatous tissue reaction with a marked lymphohistiocytic infiltrate including epithelioid histiocytes. Treatment with topical steroids over three weeks led to a complete healing without relapse. To the best of our knowledge this is the first report on UV-light-induced granulomatous reaction to permanent lip liner.

Actinic superficial folliculitis.

Actinic superficial folliculitis was first described in 1985, and since then only three reports have been published. Clinically and histopathologically this disease is very particular and has been suggested to be considered as an entity. We report on a 30-year-old man who presented with an extensive superficial follicular pustulosis on his back, shoulders and upper chest after exposure to intense heat and subsequent sweating on a sunny day. The pustules arose within 24-36 h afterwards. Histology and immunohistochemistry revealed subcorneal pustules, suppurative folliculitis and an infiltrate consisting of T cells, macrophages and neutrophils around the hair follicle, sebaceous glands and small vessels. To the best of our knowledge this is the fourth report on actinic superficial folliculitis and the first on which a characterization of the inflammatory infiltrate has been performed. Because of the impressive, unique symptoms and the characteristic histology we agree with those who have suggested that actinic superficial folliculitis is a new entity.

Safety and efficacy of imiquimod 5% cream in the treatment of penile genital warts in uncircumcised men when applied three times weekly or once per day.

This dose-escalation study was performed to evaluate safety and efficacy of imiquimod 5% cream in the treatment of uncircumcised men with penile warts associated with the foreskin. The cream was applied 3 times/week (n=34) or once per day (n=30) over 8+/-2 h. Imiquimod 5% cream was safe in both treatment groups. However, the 3 times/week regimen was better tolerated with a lower incidence of local skin reactions. In both groups, the 2 most frequently reported local skin reactions were erythema and erosion; they were more severe with the once-daily dosing. The most frequently reported application site reactions were burning, pruritus and irritation or pain (once-daily patients only). Total clearance was achieved in 62% of the patients in the 3 times/week group and by 57% in the once-daily group. Thus, imiquimod 5% cream administered 3 times/week was the optimal dosing regimen in the treatment of penile warts in uncircumcised men.

Epidermolysis bullosa acquisita with ultraviolet radiationsensitivity.

A 37-year-old male patient developed a bullous eruption and erythematous plaques mainly in exposed areas following prolonged sun exposure. In addition, blisters were noted on oral and nasal mucous membranes. Histopathological examination of a lesional skin biopsy revealed a subepidermal blister. Linear deposition of IgG and C3 at the epidermal basement membrane zone was revealed by direct immunofluorescence microscopy of a perilesional skin biopsy. Indirect immunofluorescence on 1 mol/L salt-split skin showed binding of autoantibodies to the dermal side of the split. Immunoblot analysis of dermal extracts demonstrated that the patient's serum contained IgG antibodies against type VII collagen, whereas no reaction was seen with epidermal extracts or by enzyme-linked immunosorbent assay using a recombinant form of bullous pemphigoid 180. Standardized ultraviolet (UV) radiation provocation induced blistering with both UVA (13.5 J/cm2) and UVB (0. 04 J/cm2) within 24 h clinically and histologically. External and systemic UV-protective medication and nine cycles of high dosage immunoglobulins given intravenously (1.2 g/kg body weight over 2-3 days every 4 weeks) resulted in the cessation of blister formation. To the best of our knowledge, this is the first report of a case of epidermolysis bullosa acquisita with sensitivity to UV.

Superantigens and their association with dermatological inflammatory diseases: facts and hypotheses.

Superantigens have been suggested to play an important role in the pathogenesis of several inflammatory skin diseases as well as systemic diseases such as atopic dermatitis, psoriasis, vasculitis, T-cell lymphoma and autoimmune diseases. Infections often precede the onset and relapse of these diseases, and antibiotic treatment with or without additional glucocorticosteroids and immunoglobulins is occasionally successful. Superantigens are microbial proteins that are able to stimulate up to 20% of the naive T-cell population in a non-specific way. They are produced by gram-positive and -negative bacteria as well as by viruses, parasites and yeasts. The importance of the pathogenic role of superantigens is determined by the potency to induce inflammation by extensive cytokine release after T-cell stimulation and/or T-cell-mediated cytotoxicity and, thereby, tissue damage. Furthermore, superantigens may be able to induce autoimmune processes by stimulation of autoreactive T-cells as well as autoantibody production by stimulation of B-cells. Among the diseases associated with superantigens, atopic dermatitis, guttate and chronic plaque psoriasis, as well as Kawasaki disease, are by far the best-characterized. Nevertheless, conflicting results have been obtained and formal proof of a pathogenic role of superantigens in these diseases is still lacking. The aim of this review is to summarize the data on superantigens in terms of their distribution in microorganisms, their interactions with the adaptive immune system and their contribution to skin pathology.

[Allopurinol as an inducer of acute graft-versus-host-like drug reaction. Case report with review of the literature]. / Allopurinol als Auslöser einer akuten Graft-versus-Host-ähnlichen Arzneimittelreaktion. Fallbericht mit Literaturübersicht.

Although drug eruptions resembling graft-versus-host disease are rare, GvH-like reactions to the sulfhydryl group of drugs (penicillamine, captopril, gold sodium), phenobarbital and hepatitis vaccine have been described. Clinical reports concerning acute GvH-like drug rash are very uncommon and restricted to acetylsalicylic acid and spironolactone. We report on a patient who developed an acute GvH-like drug reaction caused by allopurinol. To our knowledge this variant of cytotoxic drug eruption has not yet been reported in literature.

[Induction of multiple melanocytic nevus cell nevi in 2 children with malignant hematologic systemic diseases and chemotherapy-induced immunosuppression]. / Induktion multipler melanozytärer Nävuszellnävi bei zwei Kindern mit malignen hämatologischen Systemerkrankungen und Chemotherapie-bedingter Immunsuppression.

Two children developed multiple melanocytic naevi after polychemotherapy administered for acute lymphoblastic leukaemia in one and for non-Hodgkin lymphoma in the other. Induction of naevi does not seem to be related to specific agents used in chemotherapy, but rather to the immunosuppression resulting from multiple-agent chemotherapy. There are reports in the literature of both intrinsically and iatrogenically immunosuppressed patients who have developed multiple melanocytic naevi.