Eczematous Reaction Research Articles

A Review of Adverse Cutaneous Drug Reactions Resulting from the Use of Interferon and Ribavirin

Drug-induced cutaneous eruptions are named among the most common side effects of many medications. Thus, cutaneous drug eruptions are a common cause of morbidity and mortality, especially in hospital settings. The present article reviews different presentations of drug-induced cutaneous eruptions, with a focus on eruptions reported secondary to the use of interferon and ribavirin. Presentations include injection site reactions, psoriasis, eczematous drug reactions, alopecia, sarcoidosis, lupus, fixed drug eruptions, pigmentary changes and lichenoid eruptions. Also reviewed are findings regarding life-threatening systemic drug reactions.

Comparative Therapeutic Efficacy of Permethrin, Benzyl benzoate and Sulfur in the treatment of Scabies Patients

This study was designed to evaluate the comparative therapeutic efficacy and side effects of permethrin cream/lotion (5%), benzyl benzoate lotion (25%), and sulfur (10%), after one, three, and three days application at bed time in the treatment of patients of scabies. Sample size n=120 were randomly divided into 3 groups designated as A,B and C comprising of 40 individuals in each group patients in groups A,B and C were treated with permethrin, benzyl benzoate, and sulfur after one, three and three days treatment applications respectively. Severity of Lesions significantly decreased with permethrin after once a week treatment as compared to benzyl benzoate and sulfur, while pruritus was significantly reduced with permethrin as compared to benzyl benzoate and sulfur treatment after one, three and three treatment applications once a week respectively. Permethrin 5% proved to be very reliable but expensive and exhibited very few side effects when applied once at bed time. Benzyl benzoate lotion (25%) is cheap and effective but requires application on more than 1 day (3 days applications). The numbers of irritations and post scabious eczematous reactions were increased after benzyl benzoate treatment. Sulfur (10%) is the oldest anti scabietic in use and common in various preparations appears to be effective, is very cheap, safe but stains clothing and requires application on 3 successive days. On the basis of above mention parameters permethrin (5%, once for 8-14 hours) finds to be effective, well tolerated and safe but expensive, proved to be the drug of choice followed by benzyl benzoate and sulfur in scabietic patients.

Pollen Grains Induce a Rapid and Biphasic Eczematous Immune Response in Atopic Eczema Patients

Eyerich K, Huss-Marp J, Darsow U, et al. Int Arch Allergy Immunol. 2008;145(3):213–223 PURPOSE OF THE STUDY. To investigate the relationship between eczematous reactions in subjects with immunoglobulin E–mediated allergy to pollen grains. STUDY POPULATION. Two populations were evaluated: one population included subjects with atopic eczema who were sensitized to grass or birch pollen and who had a positive atopy patch test, and the second population included subjects without atopic eczema or atopy but who had a positive atopy patch test to nickel. In addition, as control populations, healthy volunteers and atopic subjects with eczema and sensitization to grass or birch but without a positive atopy patch test were included. METHODS. Atopy patch tests with native pollen grains were performed to delineate the effect of native pollen grains on human skin of healthy and atopic individuals. A nickel patch test served as an established model of contact dermatitis. Skin-site samples were taken for biopsy 6 to 96 hours after allergen application and investigated immunohistochemically. RESULTS. Histology of positive patch tests showed an influx of mononuclear cells (predominantly CD4+, CD25+, and CD45RO+). This influx was detected earlier in the pollen patch-test reactions compared with the immune response to nickel. A biphasic cytokine response could be detected in skin samples from the pollen patch test: interleukin 5 dominated in the early phase, and interferon γ dominated in the late phase. The nickel patch test was continuously dominated by interferon γ. CONCLUSIONS. Pollen grains induce eczematous reactions in susceptible individuals. This reaction seems clinically and immunohistochemically similar to the contact hypersensitivity reaction to nickel but follows a faster kinetic and a biphasic course: T-helper 2 and immunoglobulin E in the early (24-hour) phase and T-helper 1 predominance in the late (96-hour) phase. REVIEWER COMMENTS. This article highlights the importance of understanding that type 1 allergy-inducing antigens such as pollens can exacerbate atopic eczema in susceptible individuals. Physicians should remember to discuss this with their atopic patients before the start of pollen season.

Intravenous immunoglobulins-induced eczematous eruption: A long-term follow-up study

Background High-dose intravenous immunoglobulins have emerged as an important therapy for various diseases. Vesicular eczematous eruption has recently been described as an intravenous immunoglobulins adverse effect. Little is known about patients' characteristics, administration regimens and long-term outcomes. Methods We retrospectively examined a series of 9 patients which had been notified to the Regional Pharmacovigilance Center for an eczematous skin reaction after intravenous immunoglobulins infusion. Results There were 8 men and 1 woman. Mean age was 56.4 years. Seven patients were treated with intravenous immunoglobulins for neurological disease. Eruption was mostly localized to palms and soles. All patients improved, either spontaneously or with systemic or topical steroid treatment. Rash recurred in 4 out of 5 patients in which immunoglobulins were readministered. Eruption did not relapse in 3 patients when immunoglobulins preparation was switched for another one. Conclusions Eczematous eruption due to infusion of immunoglobulins is rare although mostly benign side effect. Treatment withdrawal is usually not required if there is a major clinical benefit. Switching the type of IVIg is often a useful strategy.

Delayed-type hypersensitivity to low molecular weight heparins and heparinoids: cross-reactivity does not depend on molecular weight. Commentary

Summary Background Cross-reactivity is a widespread phenomenon in patients who develop cutaneous delayed-type hypersensitivity (DTH) reactions to low molecular weight heparins (LMWHs). As molecular weight is believed to be a key determinant of sensitization to heparins, the recently developed LMWH bemiparin, with the lowest molecular weight of all LMWHs, appeared to be a significant improvement. Objectives To evaluate cross-reactivity between bemiparin and several other LMWHs and heparinoids by means of subcutaneous testing. Methods Test doses of bemiparin and several other LMWHs/heparinoids were given to eight patients with a history of local eczematous reactions after subcutaneous injection of enoxaparin. Results Seven of eight patients showed cross-reactivity following subcutaneous injection of bemiparin. In addition, nearly all tested substances caused local eczematous reactions in at least some patients, with the exception of fondaparinux, which was well tolerated by all patients. Of all substances tested, bemiparin had the highest cross-reactivity with enoxaparin. Substances with a lower molecular weight did not cross-react less frequently than the others. Conclusions No significant correlation was found between the molecular weight of the tested substances and the frequency of DTH reactions. In patients with DTH to enoxaparin, the LMWH bemiparin is not a suitable alternative.

Vesicular Erythema Multiforme‐like Reaction to Para‐Phenylenediamine in a Henna Tattoo

Allergic contact dermatitis reaction to topical "black henna" tattoo is usually described secondary to the organic dye para-phenylenediamine, a derivative of analine. Allergic contact dermatitis reactions to para-phenylenediamine are well recognized and most commonly involve an eczematous reaction that may become generalized and an acute angio-edema. Only four previous instances have been reported of an erythema multiforme-like reaction to para-phenylenediamine and its derivatives, including only one mild reaction to a tattoo. A vesicular erythema multiforme-like reaction has not been reported. An erythema multiforme-like reaction to contact allergens is usually caused by potent allergens including plant quinolones in Compositae and sesquiterpene lactones in exotic woods, and it is also reported to topical drugs, epoxy resin, metals (particularly nickel), and various chemicals. A generalized vesicular erythema multiforme-like reaction is unusual, and rarely reported. We describe a 6-year-old boy who developed a localized, eczematous and severe generalized vesicular erythema multiforme-like contact allergy to para-phenylenediamine secondary to a henna tattoo. As henna tattoos are becoming increasingly popular, one should be aware of the possibility of such a reaction. This presentation also highlights the call to ban the use of para-phenylenediamine and its derivatives in dyes.

Extensive eczematous reaction and dyshidrotic lesions following intravenous immunoglobulin therapy

Extensive eczematous reaction and dyshidrotic lesions following intravenous immunoglobulin therapy

Amended Final Report of the Safety Assessment of Drometrizole as used in Cosmetics1

Drometrizole is used in cosmetics as an ultraviolet (UV) light absorber and stabilizer. In an earlier safety assessment, the available data were found insufficient to support the safety of this ingredient, but new data have been provided and assessed. In voluntary industry reports to the Food and Drug Administration, this ingredient is reported to be used in noncoloring hair care products, and in an industry use concentration survey, uses in nail care products at 0.07% were reported. Drometrizole has absorbance maxima at 243, 298, and 340 nm. Drometrizole is used widely as a UV absorber and stabilizer in plastics, polyesters, celluloses, acrylates, dyes, rubber, synthetic and natural fibers, waxes, detergent solutions, and orthodontic adhesives. It is similarly used in agricultural products and insecticides. Drometrizole is approved as an indirect food additive for use as an antioxidant and/or stabilizer in polymers. Short-term studies using rats reported liver weight increases, increases in the activities of enzymes aminopyrine N-demethylase, and UDP glucuronosyl transferase, but no significant effects were noted in the activities of acid hydrolases or in hepatocyte organelles. Although Drometrizole is insoluble in water and soluble in a wide range of organic solvents, a distribution and elimination study using rats indicated that some Drometrizole was absorbed, then metabolized and excreted in the urine. Drometrizole and products containing Drometrizole were nontoxic in acute oral, inhalation, and dermal studies using animals. No increase in mortality or local and/or systemic toxicity were observed in a 13-week oral toxicity study using dogs; the no observed effect level (NOEL) was 31.75 mg/kg day(- 1) for males and 34.6 mg/kg day(-1) for females. In a 2-year feeding study using rats, a NOEL of 47 to 58 mg/kg day(- 1) was reported. Developmental studies of Drometrizole in rats and mice found no teratogenic effects and a NOEL of 1000 mg/kg day(- 1) was reported. Drometrizole was not genotoxic in Ames tests, a mouse bone marrow micronucleus test, or somatic mutation assays observing interphase nuclei and chromosomal aberrations using Chinese hamsters. There was no evidence of dominant lethal effects in studies using mice or rats. Drometrizole at a 1% concentration was minimally to moderately irritating to rabbit eyes, if followed by rinsing, but mildly to severely irritating in unrinsed eyes. A nail product containing 0.03% Drometrizole, however, was nonirritating to unrinsed rabbit eyes. A nail polish containing 1.0% Drometrizole was nonirritating to rabbit skin and Drometrizole was negative for sensitization in two Magnusson-Kligman maximization tests in guinea pigs. In clinical tests, Drometrizole at 1% was nonirritating in a single-insult patch test. No irritation or eczematous reactions were observed in 300 patients (with or without dermatosis) treated with daily applications of Drometrizole for 8 weeks. In a 3-year clinical therapeutic trial conducted to evaluate the effectiveness of two UV absorbing preparations containing up to 5% Drometrizole, two hypersensitivity reactions were observed during 445 applications. Although there are case reports in which Drometrizole was considered the sensitizing agent, clinical tests of cosmetic products containing 0.03% to 1.0% Drometrizole produced no irritation, sensitization, photosensitization, or phototoxicity in a total of 436 subjects. The Cosmetic Ingredient Review (CIR) Expert Panel assumes that Drometrizole is used in both noncoloring hair care and nail care products at low concentrations. The available safety test data do not suggest any adverse effects associated with exposure to Drometrizole. This toxicologic profile, coupled with the low concentration of use and the unlikely dermal penetration of a chemical that is insoluble in water, support the conclusion that Drometrizole can be safely used in cosmetics.

Atopic patch testing

Atopic dermatitis is a major problem among the urban population and it can be aggravated or triggered by various allergens. Atopic patch test can be used as a diagnostic tool in characterizing patients with allergen triggered atopic dermatitis. 1. Patch testing to reproduce an eczematous reaction by applying prick test allergens under occlusion on intact skin. 2. To find the allergen associated with atopic dermatitis. 3. To find the specific allergen which causes or exacerbates atopic dermatitis in a given subject. Seventy five subjects with atopic dermatitis were included in our study and patch tests using prick test allergens were applied to the back. Reading was done after 48 and 72 hours Out of the 75 subjects tested, 47% showed positive reactions, parthenium accounted for 42% of all positive reactions. Epicutaneous application of prick test antigen on intact skin can produce a reaction. Parthenium is commonest allergen in Bangalore. Counselling based on patch test reports may help to reduce morbidity and improve quality of life.

"Extra-edge Effect": A Further Problem in Patch Test Diagnosis?

Sir, In vivo diagnostic tests may cause side-effects. The well-known, typical side-effects of patch testing are active sensitization, irritant reactions, scars, alteration of pigmentation, pustular or microbial infection, reaction to plaster or test devices, and “angry back syndrome” (1). Systemic symptoms are not unusual among patients undergoing patch tests; 5% of tested patients complain of rashes, high temperature and flare-up reactions (2). A particular patch test side-effect, the “edge-effect”, is reported for irritant substances. A similar reaction is also described sporadically for different allergens using Finn Chambers on Scanpor; test substances, not evenly dispersed under the Finn Chamber accumulate around the perimeter of the chamber, causing a stronger allergic reaction at the rim (3, 4). Another peculiar “edge-effect” has been observed testing potent corticosteroids: at the 48-h control the eczematous reaction is evident only on the outer edge of the patch test site, while at the later readings, the entire patch test site becomes eczematous. This phenomenon may be explained by the anti-inflammatory effect of the corticosteroid reinforced by the patch test occlusion during the first 48 h (5). In the case presented here, a strange patch test sideeffect was observed, characterized by an allergic skin reaction localized on the external edge of some patch test cells.

Allergic Drug Eruption Secondary to Intravenous Acyclovir

A 62-year-old woman presented at our department 10 days after returning from a trip to Alaska. Over the previous 7 days she had developed headache, elevated temperature and disseminated erythematous vesicles. The only medication she was taking at this time was L-thyroxine 75 mg once daily for treatment of hypothyroidism. Her skin showed widespread vesicles on an erythematous base without palmar and plantar affection. There was no mucous membrane involvement. The patient was otherwise healthy. A diagnosis of disseminated herpes zoster infection was made subsequently, indicating the need for systemic antiviral treatment. A polymerase chain reaction (PCR) was performed and confirmed varicella zoster infection. According to the patient, she had formerly developed eczema to external acyclovir and external betamethasone. Otherwise, her personal and family history was negative for skin diseases. Due to this medical history of a potential acyclovir sensitization a prick-test was performed, whose results were negative. Given the negative prick results, a test dose of 70 mg acyclovir (1 mg/kg bodyweight), equivalent to 10% of the regular dose, was given intravenously. After 8 h, the patient developed a plain macular erythema with slight infiltration of the popliteal fossae and the trunk (Fig. 1). There was no other medication given at that point. The rash was topically treated with corticosteroids (betamethasone), leading to a complete remission of the exanthema within 2 days. The zoster infection also regressed with out any further treatment or any complications. There was no evidence for neurological involvement at any point. For further diagnostic work-up, we presented the patient to our allergy department, where prick-testing and epicutaneous testing for acyclovir (tablets), valacyclovir (tablets) and a topical preparation (acyclovir, propylene glycol, natrium lauryl) were performed. Patch tests showed a pronounced eczematous reaction (++) at 48, 72 and 96 h for each of the 3 substances. Prick-testing remained negative, as did epicutaneous and prick-testing of corticosteroid series (Fig. 2).

A Case of Cellulitis Associated with Coral Injury

Corals are the marine organism that belongs to the phylum Cnidaria, and are one of the common causes of superficial injury in the marine environment. In addition to acute reactions such as burning or stinging pain and erythema, coral injuries may present with complications such as foreign body reactions, bacterial infections, and/or localized eczematous reactions. A 23-year-old male presented with an erythematous edematous tender patch with centrally grouped vesicles on the left ankle; the injury had occurred during skin-scuba diving 2 days before. A biopsy of the lesion treated with hematoxylin-eosin stain showed epidermal necrosis with subepidermal blisters and neutrophilic panniculitis. Herein we report a case of cellulitis caused by the nematocyst stings of corals.

Pollen Grains Induce a Rapid and Biphasic Eczematous Immune Response in Atopic Eczema Patients

Introduction: Eczematous reactions to type I allergy-inducing antigens are documented in a subgroup of patients with atopic eczema. Yet, the underlying immunological mechanisms are not well understood. Material and Methods: To delineate the effect of native pollen grains on human skin of healthy and atopic individuals we performed patch tests (atopy patch test with native pollen grains, PPT). Nickel patch tests (NPT) served as an established model of contact dermatitis. Skin site biopsies were taken 6–96 h after allergen application and investigated immunohistochemically. Results: Histology of positive patch tests showed an influx of mononuclear cells (predominantly CD4+, CD25+, CD45RO+). This influx was detected earlier in the PPT reaction than in the immune response to nickel. A biphasic cytokine response could be detected in the PPT: IL-5 dominated in the early, IFN-γ in the late phase. The NPT was continuously dominated by IFN-γ. Dendritic cell subpopulations imitated the earlier kinetics of the mononuclear infiltrate. Discussion: Thus, pollen grains induce eczematous reactions in susceptible individuals. This reaction appears clinically and immunohistochemically similar to the contact hypersensitivity reaction to nickel but follows a faster kinetic and a biphasic course: Th2 and IgE in the early (24 h) and Th1 predominance in the late (96 h) phase.

The prevalence of allergic contact sensitization in a general population in Tromso, Norway

Objectives. This study investigated the prevalence of contact sensitization in a general adult population and the relationship between the history of metal dermatitis and sensitization to metal allergens.Study Design. A cross-sectional population study using patch tests and a questionnaire was conducted among adults in Tromso, Northern Norway.Methods. A random sample of 830 participants aged 18–75 years were invited to participate in the patch testing and completed a 1-page self-administered questionnaire. Of the adults, 531 (64%) were actually TRUE tested (using a standardized, ready-to-apply patch test system) and completed the self-administered questionnaire about ear piercing, metal reactions, skin reactions to different allergens, atopic dermatitis, eczema, cooking equipment and diet.Results. The study showed that nickel (19.2%; women 31.1% and men 5.0%), fragrance mix (3.4%) and cobalt (1.7%) were the most prevalent allergens causing contact sensitization. For all other allergens, less than 1.1% tested positive. Eighty-four (45.2%) subjects with a positive history of metal dermatitis had negative patch tests.Conclusions. Contact sensitization was found frequently in this general adult population, especially to nickel and perfumes with a predominance among females. An eczematous reaction caused by cheap earrings seemed to be the best indicator for metal sensitivity.

Alopecia universalis associated with impaired interleukin-4 production and low serum IgE level

A 17-year-old female presented with alopecia universalis, which appeared following widespread eczematous dermatitis. An immunohistochemical study demonstrated that CD8(+) T cells infiltrated into hair follicles with satellite cell necrosis of keratinocytes. The precedence of the autosensitization dermatitis suggested that T cells concerned with the eczematous reaction also attacked hair follicles, or alternatively, that those T cells sequentially activated another population of cytotoxic T cells. We found that she had a continuously low level of serum IgE (<1 units/ml), and this abnormality urged us to investigate interleukin (IL)-4 production of T cells. Although the patient had a normal number of CD4(+) T cells, the production of IL-4, but not IL-10, was profoundly impaired as assessed by a reverse transcriptase polymerase chain reaction analysis, suggesting the possible relationship between the baldness and IL-4 reduction. The autoimmune hair loss might occur via activation of cytotoxic T cells and Th(1) cells as a result of a relief from IL-4 control.

Lactase‐induced occupational protein contact dermatitis and allergic rhinoconjunctivitis

Enzymes are high-molecular-weight proteins and highly sensitizing occupational allergens used widely in industrial processes. Lactase has been described to cause work-related respiratory and conjunctival immunoglobulin (Ig)-E-mediated sensitizations in workers in the pharmaceutical industry. In these previous reports, allergic rhinoconjunctivitis or asthma was confirmed with prick tests but not by challenge tests. Lactase previously has not been described as a cause of immediate or delayed contact skin reaction. Furthermore, there are no previous reports of lactase-specific IgE. We report a case of protein contact dermatitis and allergic rhinoconjunctivitis from occupational exposure to lactase in a pharmaceutical worker. The patient exhibited strong positive responses to lactase in prick tests. In an open application test, lactase elicited whealing, and in patch testing, lactase elicited an eczematous reaction. Serum lactase-specific IgE antibodies were demonstrated in immunospot and radioallergosorbent test assays, and lactase-IgE-binding fractions and their specificities were examined in immunoblot and immunoblot inhibition assays. The chamber challenge test was performed to detect the association between lactase sensitization and rhinoconjunctival symptoms. Our results have confirmed the previous observations that lactase can induce occupational IgE-mediated respiratory and conjunctival sensitizations, but they show that contact skin reactions caused by lactase may also occur.

Patch test reactivity to a cobalt–chromium–molybdenum alloy and stainless steel in metal‐allergic patients in correlation to the metal ion release

Nickel, chromium, and cobalt released from stainless steel and CoCrMo alloys have been postulated to trigger hypersensitivity reactions. The objective of this study was to assess the ion release from a CoCrMo alloy and stainless steel in vitro and the cutaneous reactivity to it by patch test. 52 metal-allergic patients and 48 non-allergic controls were patch tested to stainless steel and CoCrMo discs. In addition, using atomic absorption spectrometry, the release of nickel, cobalt, and chromium from both materials was assessed upon 2-day exposure to distilled water, artificial sweat (AS), and cell culture medium. There was low nickel ion release from stainless steel (0.3-0.46 microg/cm(2)/2 days) and CoCrMo discs (up to 0.33 microg/cm(2)/2 days) into the different elution media. Chromium release from the 2 materials was also very low (0.06-0.38 microg/cm(2)/2 days from stainless steel and 0.52-1.36 microg/cm(2)/2 days from CoCrMo alloy). In contrast, AS led to abundant cobalt release (maximally 18.94 microg/cm(2)/2 days) from the CoCrMo discs, with concomitant eczematous reaction upon patch testing: 0 of the 52 metal-allergic patients reacted to stainless steel discs and 5 of the 52 patients to CoCrMo discs (all 5 patients were cobalt allergic and 3 also nickel and chromium allergic). None of the controls reacted to the discs. Apart from nickel being a focus of allergological research, our results point to the possibly underestimated association of cobalt release and potential hyperreactivity to CoCrMo alloy.

Eczematous reactions to food in atopic eczema: position paper of the EAACI and GA2LEN

Food allergy and atopic eczema (AE) may occur in the same patient. Besides typical immediate types of allergic reactions (i.e. noneczematous reactions) which are observed in patients suffering from AE, it is clear that foods, such as cow's milk and hen's eggs, can directly provoke flares of AE, particularly in sensitized infants. In general, inhaled allergens and pollen-related foods are of greater importance in older children, adolescents and adults. Clinical studies have revealed that more than 50% of affected children with AE that can be exacerbated by certain foods will react with a worsening of skin eczema either alone or in addition to immediate symptoms. Adolescents and adults may also react to foods, but reactions to 'classical' food allergens, such as hen's eggs and cow's milk, are not as common as in childhood. Some patients with AE do react to pollen-associated foods. Food-induced eczema should not be neglected by the allergologist: On the one hand, food can be a relevant trigger factor of persistent moderate-to-severe AE; on the other hand, unnecessary diets which are not based on a proper diagnosis may lead to malnutrition and additional psychological stress on patients suffering from AE. Eczematous reactions to food can only be diagnosed by a thorough diagnostic procedure, taking into account the patient's history, the degree of sensitization and the clinical relevance of the sensitization. The latter has often to be proven by oral food challenges. Upon oral food challenge it is most important to evaluate the status of the skin with an established score (e.g. SCORAD, EASI) after 24 h and later because otherwise worsening of eczema will be missed.

Delayed-type hypersensitivity to low molecular weight heparins and heparinoids: cross-reactivity does not depend on molecular weight

Cross-reactivity is a widespread phenomenon in patients who develop cutaneous delayed-type hypersensitivity (DTH) reactions to low molecular weight heparins (LMWHs). As molecular weight is believed to be a key determinant of sensitization to heparins, the recently developed LMWH bemiparin, with the lowest molecular weight of all LMWHs, appeared to be a significant improvement. To evaluate cross-reactivity between bemiparin and several other LMWHs and heparinoids by means of subcutaneous testing. Methods Test doses of bemiparin and several other LMWHs/heparinoids were given to eight patients with a history of local eczematous reactions after subcutaneous injection of enoxaparin. Seven of eight patients showed cross-reactivity following subcutaneous injection of bemiparin. In addition, nearly all tested substances caused local eczematous reactions in at least some patients, with the exception of fondaparinux, which was well tolerated by all patients. Of all substances tested, bemiparin had the highest cross-reactivity with enoxaparin. Substances with a lower molecular weight did not cross-react less frequently than the others. No significant correlation was found between the molecular weight of the tested substances and the frequency of DTH reactions. In patients with DTH to enoxaparin, the LMWH bemiparin is not a suitable alternative.

Depletion of CD4+CD25+ human regulatory T cells in vivo: Kinetics of Treg depletion and alterations in immune functions in vivo and in vitro

The aim of this study was to investigate whether depletion of CD4(+)CD25(+) regulatory T cells (Treg) from melanoma patients affects immune responses against tumors. By application of recombinant IL-2-diphteria toxin fusion protein, also known as ONTAK, we were able to significantly reduce the frequency of Treg in peripheral blood, whereas other cell populations remained unaffected. The reduction of Treg started immediately after the first bolus of ONTAK with a dose of 5 microg ONTAK per kg bodyweight and lasted for 13 days with subsequent recovery thereafter. Successive ONTAK treatments further reduced the number of circulating Treg. Using the contact sensitizer DCP we show that all patients developed vast eczema after Treg depletion, whereas no or only mild eczematous reactions were detectable before ONTAK treatment. Corresponding induction of DCP-specific CD4(+) and CD8(+) T cells were detectable. Moreover, after immunization of ONTAK treated patients with tumor antigen peptides, MelanA/MART-1 and gp100, significant induction of peptide specific CD8(+) T cells could be observed in 90% of the patients treated. These cells displayed effector functions, as they were able to lyse peptide-pulsed target cells and secreted IFNgamma upon restimulation. In aggregate, our data indicate that ONTAK depletes Treg in vivo significantly, resulting in enhanced immune functions and substantial development of antigen-specific CD8(+) T cells in vaccinated individuals.