Delayed-type Skin Reactions Research Articles

Efficacy of Baricitinib In Treatment of Delayed-Type Hypersensitivity Versus Irritant Skin Reactions in Healthy Adult Male Subjects

Efficacy of Baricitinib In Treatment of Delayed-Type Hypersensitivity Versus Irritant Skin Reactions in Healthy Adult Male Subjects

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Background: Persulfate salts are potent oxidizing agents in hair bleach products that accelerate the bleaching process. Ammonium and potassium persulfates may cause delayedtype and immediate skin reactions. Also allergic asthma and rhinitis have been described. Objectives: Ammonium and potassium persulfates may cause delayed-type and immediate skin reactions. Also allergic asthma and rhinitis have been described. Methods: Case 1A 36-year-old female hairdresser suffered from contact urticaria after exposure to bleaching agents for ten years. She also experienced asthma and rhinitis when she worked in the hair salon for the same period. Several minutes after accidental contact with bleaching powder she developed an urticarial reaction on the neck, facial angioedema, and dyspnoea. We performed prick-to-prick tests with serial dilutions of freshly prepared persulfates starting with 0.1%. Prick-to-prick tests with ammonium persulfate 1.0% aqua and potassium persulfate 1.0% aqua showed wheals of 8 mm (positive control 6 mm). Ten minutes after the prick-to-prick tests, she suffered from asthmatic complaints which cleared after inhalation of b2-sympathicomimetics. Patch testing with ammonium persulfate 2.5% petrolatum and potassium persulfate 2.5% aqua resulted in wheals at the test site after 20 minutes. Prick tests with ammonium and potassium persulfate 1.0% aqua were negative in four controls.Case 2A 48-year-old woman showed pruritus of the scalp and facial angioedema which started several minutes after application of a hair bleaching product. Forty-five minutes after application she fainted with increased heart rate and low blood pressure. She was treated with clemastine, dexamathasone, and saline and transferred to a hospital. Prick tests with ammonium persulfate 2.0% aqua and potassium persulfate 2.0% aqua showed wheals of 4 mm (positive control 7 mm). Intradermal testing with ammonium persulfate 0.1% aqua and potassium persulfate 0.1% aqua showed wheals of almost 20 mm. Several hours after the intradermal tests, she became increasingly dizzy which cleared after treatment with fexofenadine. Patch tests with ammonium persulfate 2.5% petrolatum and potassium persulfate 2.5% aqua were negative after 20 minutes. Intradermal tests with ammonium and potassium persulfate 0.1% aqua were negative in three controls. Results: We presented two cases of immediate type hypersensitivity to persulfates with an anaphylactic reaction in one patient. These reactions have never been adequately documented. Conclusion: It seems that the reactions are immunologic and based on release of IgE. In patients suspected of allergic reactions to persulfates, prick and patch tests should be performed. Because severe respiratory symptoms and anaphylaxis may occur, we recommend to start with prick-toprick testing.

Early peritoneal macrophage function after laparoscopic surgery compared with laparotomy in a mouse mode

The authors previously demonstrated postoperative preservation of the immune function measured by delayed-type skin reaction and tumor growth after laparoscopic surgery, as compared with laparotomy. For further elucidation of the origin of the demonstrated immune preservation, peritoneal macrophage (PMo) function was investigated 1 h after different surgical procedures. Female NMRI mice were divided into five groups: anesthesia only, abdominal skin incision, laparotomy, peritoneal carbon dioxide (CO2) insufflation, and peritoneal air insufflation. Escherichia Coli phagocytosis, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1), and interleukin-10 (IL-10) release of isolated PMo were investigated. All invasive interventions reduced the PMo phagocytosis by factors of approximately 2 to 4.7, as compared with the sham control group. Spontaneous ex vivo TNF-alpha release was significantly increased whenever the abdominal cavity was exposed to ambient air. The macrophage's ability to release TNF-alpha after E. coli exposure was diminished in the abdominal air exposure groups, as compared with the CO2 insufflation group. Reduced phagocytosis 1 h after surgical interventions suggests a contribution of PMo to the altered immune function. When exposed to CO2, PMo show a decreased basal TNF-alpha release. However, PMo also show an increased TNF-alpha release after a second immune stimulation (E. coli), suggesting a greater competency of interaction in an immune defense reaction after CO2 exposure.

Triggerung der atopischen Dermatitis durch Sporen des Austernpilzes Pleurotus pulmonarius

- Spores of the basidiomycete Pleurotus pulmonarius a species of the oyster mushrooms are widespread components in the air and established as causes of respiratory allergies. Recent reports indicate that aeroallergens such as mite allergens, pollen or animal dander may play an important role triggering atopic eczema in a subgroup of subjects with atopic dermatitis. The aim of the study was to investigate whether spores of P. pulmonarius may elicit delayed-type skin reactions in atopic subjects particularly in those with an atopic dermatitis. Sixty-five study subjects were categorized prospectively in 4 groups having atopic dermatitis or respiratory allergy with regard to the skin prick test reactivity to P. pulmonarius spore extract. Twenty nonatopic individuals served as control subjects. Atopy patch test performed with P. pulmonarius spore extract at a concentration of 1.35 mg protein per gram of petrolatum were evaluated after 48 and 72 hours. Of the subjects with atopic dermatitis, 12 of 37 (32%) showed a positive atopy patch test reaction with 7/13 (54%) also having a positive skin prick test response to the P. pulmonarius spore extract. In the study group with respiratory allergy and positive skin prick test to the Pleurotus extract 1 subject with a well-known asthma had a positive atopy patch test. No positive test reaction was observed in the nonatopic control subjects or in subjects with respiratory allergy but negative skin prick test responses to the P. pulmonarius spore extract. Our results demonstrate that spores of the oyster mushroom P. pulmonarius can induce delayed-type reactions consistent with an acute eczema in atopic individuals, particularly in those with atopic dermatitis. Furthermore, it could be shown that individuals with an air-exposed pattern of the atopic dermatitis were most reactive to the atopy patch tests with these spore extract.

Delayed-type skin reaction to the heparin-alternative danaparoid

Delayed-type skin reaction to the heparin-alternative danaparoid

Delayed-type skin reaction to the heparin-alternative danaparoid

Eczematous, infiltrated plaques at the site of subcutaneously administered heparin appear to be common. Heparinoids cannot be recommended in general as a substitute for heparin or low molecular weight heparin because delayed-type skin reactions to these molecules can also occur, as demonstrated in this case report. (J Am Acad Dermatol 2000;43:920-2.)

Autoimmune Hemolytic Anemia in a Patient With Autosomal Dominant Chronic Mucocutaneous Candidiasis

Chronic mucocutaneous candidiasis is a heterogeneous immunodeficiency syndrome characterized by recurrent candidal infections of the skin, nails, and mucous membranes. The syndrome can be associated with autoimmune conditions, especially endocrine disorders. Typically, inheritance is autosomal recessive, and abnormal T-cell-mediated immunity is thought to be the underlying deficit. We describe a 27-year-old man with chronic mucocutaneous candidiasis inherited in an autosomal dominant fashion, in whom both lymphocyte blastogenesis and delayed-type skin reactivity to Candida antigens were normal. Notable features of the case include autoimmune hemolytic anemia, probable hypoparathyroidism, and hypogonadal hypogonadism.

Discrimination between Patients with Acquired Toxoplasmosis and Congenital Toxoplasmosis on the Basis of the Immune Response to Parasite Antigens

Many persons infected with Toxoplasma gondii develop ocular lesions. Immunologic parameters in the response to T. gondii were evaluated in infected persons with and without ocular lesions and in noninfected controls. Subjects were divided into groups on the basis of presence of serum antibodies to T. gondii, presence of ocular lesions, and clinical history. Production of interleukin-2 and interferon-gamma by peripheral blood mononuclear cells from patients with probable congenital toxoplasmosis was decreased, compared with that in persons with presumed acquired infection. Cell proliferation and delayed-type skin reaction induced by soluble toxoplasma tachyzoite antigen followed the same pattern. Asymptomatic persons showed high levels of interleukin-12 and interferon-gamma, whereas persons with ocular lesions had high interleukin-1 and tumor necrosis factor-alpha responses toward soluble toxoplasma tachyzoite antigen. These data suggest that patients with ocular disease due to congenital infection show tolerance toward the parasite. Furthermore, susceptibility to ocular lesions after acquired toxoplasmosis is associated with high levels of interleukin-1 and tumor necrosis factor-alpha, whereas resistance is associated with high levels of interleukin-12 and interferon-gamma.

Coprinus comatus (shaggy cap) is a potential source of aeroallergen that may provoke atopic dermatitis

Background: Basidiospores are universal components in the air and established as important causes of respiratory allergies. Recent reports indicate that aeroallergens may aggravate eczematous skin lesions in subjects with atopic dermatitis (AD). Objective: The aim of the study was to investigate whether spores of Coprinus comatus , a species of basidiomycetes, may elicit delayed-type skin reactions in subjects with an atopic predilection, especially dermatitis. Methods: Sixty-six study subjects were categorized in groups having AD or respiratory allergy with regard to the skin prick test (SPT) reactivity to C comatus extract. Twenty nonatopic individuals served as control subjects. Atopy patch tests (APTs) were performed with extract of C comatus spore containing tissue at a concentration of 1.35 mg of protein per gram of petrolatum (Vaseline) and C comatus cap at a concentration of approximately 5 mg of protein per gram of petroleum jelly. APT reactions were evaluated after 48 and 72 hours. Results: Of the subjects with AD completing the study, 12 (32%) of 38 showed a positive APT reaction, with 8 (57%) also having a positive SPT response to C comatus. Only 1 (9%) of 11 subjects with asthma had a positive SPT and APT response to C comatus. No positive test reaction was observed in the nonatopic control subjects or in subjects with respiratory allergy and negative SPT responses to C comatus . Conclusion: Our results demonstrate that C comatus can induce delayed-type reactions in atopic individuals, particularly in those with AD. Because spores of Coprinus species are ubiquitous, basidiomycetes have to be considered as possible aeroallergens when investigating causes of eczematous skin lesions in AD. (J Allergy Clin Immunol 1999;104:836-41.)

Intravenous challenge with heparins in patients with delayed-type skin reactions after subcutaneous administration of the drug.

Delayed‐phase reactions after subcutaneous (s.c.) injection of high‐ or low‐molecular‐weight heparins are not rare. They present as indurated s.c. swelling with overlying erythema/eczema, causing burning or itching (1). Occasionally, an exanthematous reaction supervenes. If further anticoagulation is necessary, cross‐reactivity with other anticoagulants (heparinoids), such as dermatan sulfate (OrgaranTM) or sodium pentosan polysulfate (FibrezymTM), is common (2). Even after the introduction of the new anticoagulant lepirudin (RefludanTM), heparins remain the drugs of choice, particularly for intravenous (i.v.) anticoagulation. The most important differential diagnosis from delayed‐type reactions after s.c. heparin is the initial stage of heparin‐induced skin necrosis, which may be a sign of heparin‐induced thrombocytopenia (HIT). Cutaneous necrosis is characterized by a well‐defined eschar surrounded by an inflammatory halo, and can occur either at the injection site or at distant sites.

An assessment of antigenic potential of β-lactam antibiotics, low molecular weight drugs, using guinea pig models

Allergic reactions are among the common adverse effects in humans. However, it is widely assumed that there are practically no reliable animal models for preclinical tests of low-molecular weight drugs that are available to predict such reactions. This study was designed to compare the detecting ability of test methods for antigenic potential of eight β-lactam antibiotics with which allergic outcome has been reported in humans. The tests included active systemic anaphylaxis (ASA), delayed type skin reaction (DSR), maximization test (GPMT) in guinea pigs sensitized with antibiotics emulsified with Freund's complete adjuvant, passive cutaneous anaphylaxis (PCA) and enzyme-linked immunosorbent assay (ELISA) as serological tests. PCA and ELISA though using protein-conjugates as detecting antigens, especially ELISA, showed positive reactions with relatively high incidence. On the other hand, GPMT was the most sensitive method to detect antigenic potential of antibiotics despite the use of antibiotics alone for sensitizing and challenging phases. It is suggested that GPMT can be considered the most reliable method in preclinical testing.

Effects of adjuvants on bovine humoral and cellular responses to hypodermin A

Hypodermin A, a serine protease of the first-instar larva of the common cattle grub, Hypoderma lineatum (Villers), when formulated with complete Freund's adjuvant and administered to naive calves, will elicit protective immunity defined by an increase in in vivo larval mortality. This study evaluated two veterinary acceptable adjuvants, alhydrogel and amphigen (alone and in combination), for suitability as an adjuvant for hypodermin A. Complete Freund's adjuvant (CFA) is not an acceptable adjuvant for use because of adverse reactions at the injection site. The veterinary acceptable adjuvants were not as effective as CFA in inducing an antibody response as detected in the peripheral circulation. Of the adjuvants evaluated, the mixture of alhydrogel and amphigen induced the highest serum antibody response to hypodermin A. All adjuvants evaluated induced comparable immediate-type skin test responses, and the mixture of alhydrogel and amphigen was most comparable with CFA in terms of delayed-type skin reaction and resultant cellular infiltration at the reaction site. Although the mixture of alhydrogel and amphigen, when compared with CFA, did not elicit comparable levels of responsiveness in all parameters tested, the overall performance of the mixture suggests it to be worthy of further efficacy investigation in a vaccine formulation with hypodermin A.

Patch Test Reactions to the Acetone-Soluble Fraction of Human Dander in Atopic Dermatitis

An acetone-soluble fraction of human dander provoked positive patch test reactions in 45 (38%) of 120 patients with atopic dermatitis. The positive patch tests were rare in normal controls and clinical controls. The positive patch test reactions histologically showed spongiosis and mononuclear cell migration in the epidermis, edema and mononuclear cell infiltrate in the upper dermis. Scratch tests with the acetone-soluble human dander fraction were positive in only 2 (2%) of the 120 patients examined. It was suggested that in a considerable number of patients with atopic dermatitis, an acetone-soluble fraction of human dander provokes a delayed-type skin reaction without inducing an immediate-type skin reaction.

Antigenicity study of trandolapril (RU44570)

Antigenicity of trandolapril (RU44570) was evaluated using the following six standpoints: 1. active systemic anaphylaxis (ASA) in guinea pigs; 2. passive cutaneous anaphylaxis (PCA) in guinea pigs with serum of sensitized guinea pigs; 3. histamine release from lung tissue of sensitized guinea pigs; 4. Schultz-Dale reaction with isolated ileum of sensitized guinea pigs; 5. passive cutaneous anaphylaxis (PCA) in rats with serum of sensitized mice; and 6. delayed type skin reaction by Maximization test in guinea pigs. In the test of immediate type reactions, guinea pigs were sensitized by RU44570 (p.o.), an FCA emulsion of RU44570 (s.c.) or an FCA emulsion of incubate solution of RU44570 and normal guinea pig's serum, and mice were sensitized by a mixture of RU44570 and alum (i.p.). In the test of delayed type reaction, guinea pigs were sensitized by intradermal injection and patch application. 1. ASA in guinea pigs: No anaphylaxis symptoms were observed in any of the sensitized guinea pigs. 2. PCA in guinea pigs: PCA titer of sera from all the sensitized animals was less than 1. 3. Histamine release from lung tissue: No histamine release was observed in any of the isolated lung tissue. 4. Schultz-Dale reaction: No contraction was observed in any of the isolated ileums. 5. PCA in rats: PCA titer of sera from sensitized BALB/c and C3H/He mice was less than 5. 6. Delayed type skin reaction test: No skin reactions were observed in any of the sensitized guinea pigs. From these results, it is concluded that RU44570 has no antigenicity under the conditions of the present study.

ヒドロキシアパタイトおよびβ‐リン酸三カルシウムの抗原性に関する実験的検討

The antigenicity of two products of hydroxyapatite (HAP), supplied by two Japanese manufacturers, and three products of tricalcium phosphate (β-TCP), supplied by two Japanese and one American manufacturers, was studied by means of delayed type skin reactions in guinea pigs.Skin reactions were elicited by injection of the ceramic into the dorsal skin 13 or 14 days after being immunized by intradermal injection of HAP or β-TCP into the dorsal flanks or footpads of guinea pigs.After 24 hours. skin reactions were assessed by measuring the diameter of erythema and the degree of hemorrhage and induration.The results were as follows:1. Antigenicity was not detected for the HAP obtained from Asahi Optical Co., Ltd. and LION Co., Ltd.(self setting α-TCP) by means of skin reactions.2. Antigenicity was not detected for the β-TCP obtained from Asahi Optical Co., Ltd. and Kyocera Co., Ltd.3. In contrast, β-TCP from MITER, INC, USA (Synthograft®) induced delayed type hypersensitivity (DTH) 24 hours after antigen elicitation. The reaction appeared to be based on tuberculin and Jones-Mote types of reactions.4. In the present study, Arthus reaction was not seen in any group of animals, indicating that HAP and β-TCP did not induce antibody formation.

Relationship between autoimmune diseases and pneumoconiosis

In recent years, with the aging of patients with pneumoconiosis, autoimmune diseases as a complication have been observed. One of the reasons for this may be that autoimmune diseases are prone to develop among the elderly. On the other hand, it has been reported that dust itself, such as silica for example, has adjuvant effect. A review of the recent literature published in Japan and abroad was made to clarify the relationship between pneumoconiosis and autoimmune diseases and the following results were obtained. 1) Disorders which accompany pneumoconiosis: Scleroderma, rheumatoid arthritis, systemic lupus erythematosus (SLE), and disorders of the kidney and liver have been reported. In Japan, about 30 cases of pneumoconiosis accompanied with autoimmune diseases have been reported. In many of the reports, patients with pneumoconiosis and scleroderma have a past history of exposure to silica. In both case studies and case control studies, patients with rheumatoid arthritis and history of silica exposure are prone to develop pneumoconiosis. 2) Immunological studies of patients with pneumoconiosis: As for humoral immunity, elevation of polyclonal gamma-globulin, especially IgG, has been often reported together with high positive rate of autoantibodies such as antinuclear antibodies. In cellular immunity, decreased delayed type skin reaction and decreased CD4/8 ratio have been reported. In human leukocyte antigen (HLA) typing the elevated frequency of DR4 has been reported. In the study of BAL increased production of superoxide anion O2- by alveolar macrophages has been observed. 3) EXPERIMENTAL STUDIES: Silica is well known for its toxicity to cells and also for its adjuvant effect. In the German Democratic Republic, patients with scleroderma and history of long term silica exposure are recognized as patients with occupational disease even though pneumoconiosis is not clearly demonstrated on X-ray film. It is difficult from this review to nrake a definite conclusion regarding the relation between silicosis and autoimmune diseases. There is a need to repeat this review of the literature on autoimmune diseases and pneumoconiosis in the near future.

Rhipicephalus appendiculatus: Immunochemical isolation, identification and characterization of tick gut antigens recognized by IgGs derived from rabbits repeatedly infested with ticks

Immune resistance to infestation by the brown ear tick, Rhipicephalus appendiculatus Neumann, was induced in rabbits by repeated tick feeding. Antibodies from the rabbits resistant to ticks were purified and used to isolate tick midgut antigens. Purified immunoglobulin G (IgGs) from rabbits immune to tick infestations demonstrated, by immunoblotting, nine protein subunits with molecular weights ranging from 12,000 to 92,000 daltons. Immuno-adsorption studies revealed an aggregated native protein with a molecular weight greater than 500,000 daltons as resolved by polyacrylamide gel electrophoresis (PAGE). Sodium dodecyl sulphate (SDS)-PAGE of this protein molecule revealed the presence of 14 protein subunits similar to some of those detected by the immunoblots. Their molecular weights ranged from 14,000 to 165,000 daltons. Sera from rabbits immunized with the 500,000 dalton molecule formed a weak precipitating arc in the immunodiffusion test, confirming its immunogenicity. The reproductive potential of ticks fed on rabbits immunized with the purified protein molecule was slightly affected compared to controls. The protein molecule also had the capacity to induce immediate and delayed type skin reactions when injected into rabbits resistant to adult R. appendiculatus , as opposed to control tick-naive rabbits.

Uveitis Induced by Various Cross-Reactive Antigens in Guinea Pigs

In order to investigate possible immunopathogenic mechanisms in the recurrence of uveitis, cross-reactive proteins were tested for their capacity to induce experimental uveitis. Guinea pigs were immunized with porcine serum albumin (PSA) in complete Freund's adjuvant (CFA) by subcutaneous injection. Fourteen or 28 days after the immunization, PSA, bovine (BSA), sheep (SSA), equine (ESA), rabbit (RSA) serum albumin, bovine gamma globulin (BCG) or ovalbumin (OA) was injected into the vitreous. Uveitis occurred in the eyes injected with PSA, BSA, SSA, ESA or RSA, but not BGG or OA. Serum antibodies and erythematous delayed-type skin reactions against PSA, BSA, SSA, ESA and RSA were positive in animals immunized with PSA in CFA. In an adoptive transfer study, humoral and cellular immunity recognized cross-reactive antigens and uveitis developed. Once a guinea pig is sensitized, uveitis may occur or recur from subsequent intravitreal challenge by antigens that are not completely the same but have a cross-reactivity with the immunizing antigen.

Macrophage-activating T-cell factor(s) produced in an early phase of Legionella pneumophila infection in guinea pigs.

Protective immunity of guinea pigs against Legionella pneumophila was studied by infecting the animals with a sublethal dose (about 2 x 10(4) CFU) of the organism. The bacteria multiplied in the liver, spleen, and lungs up to day 4 after the intraperitoneal infection. The live bacteria in these organs decreased quickly thereafter and were eliminated by day 7. A delayed-type skin reaction and lymphoproliferation of spleen cells to Formalin-killed L. pneumophila were detected from days 5 and 6, respectively, after infection. Peritoneal macrophages obtained from guinea pigs infected 6 days previously inhibited the intracellular growth of L. pneumophila. Antigen-stimulated spleen cell factor prepared from infected guinea pigs inhibited the intracellular growth of the organism in macrophages obtained from uninfected animals. Antigen-stimulated spleen cell factor prepared from spleen cells treated with anti-guinea pig T-cell monoclonal antibody did not inhibit growth. The activity of antigen-stimulated spleen cell factor was labile to pH 2 treatment, and the factor could not be absorbed by L. pneumophila antigen, suggesting that it contains gamma interferon. Our data show that T-cell-mediated immunity begins to work from an early period of infection with L. pneumophila in guinea pigs.

Natural killer cells in inflammatory lesions and transplanted tumors in mouse skin.

The mode of natural killer (NK) cell migration to the sites of inflammation and transplanted tumors was investigated by using dry ice for physical irritation and 1-fluoro-2,4 dinitrobenzene (DNFB) for chemical irritation in mouse ear. In experiments with transplanted tumors, NK cell sensitive tumor cells (RL male 1) and insensitive tumor cells (p815) were transplanted into the ears of C3H and BALB/c mice, respectively. Employing a polyclonal rabbit antiserum against asialoGM1 (GA1), and a monoclonal rat antiserum against Thy-1 in an immunohistochemical double-staining technique, we enumerated the number of Thy-1-positive and asialoGM1-positive (Thy-1+ GA1+) cells and Thy-1-negative and asialoGM1-positive (Thy-1-GA1+) cells at various times of irritation. Following physical irritation, Thy-1-GA1+ cells (108.8 +/- 4.5/mm2 at 24 h and 71.2 +/- 3.8/mm2 at 48 h) were found in the epidermis, whereas Thy-1+GA1+ cells were not found. In delayed-type skin reaction by DNFB, Thy-1-GA1+ cells (87.1 +/- 5.8/mm2 at 24 h and 60.7 +/- 2.9/mm2 at 48 h) and Thy-1+GA1+ cells (26.4 +/- 3.6/mm2 at 24 h and 15.3 +/- 4.3/mm2 at 48 h) were found in the dermis. Since it was reported by previous investigators that Thy-1+GA1+ cells are NK cells, we assumed that NK cells infiltrated nonspecifically in the dermis in delayed-type skin reaction by DNFB. In the tumor transplant experiments, the GA1+ cells were found near both types of tumors, but they were in contact with RL male 1 and not with p815. Because it was reported that GA1+ monocytes do not have cytotoxicity against tumor cells, our findings suggest that GA1+ cells migrate nonspecifically to the sites of inflammation, and that the NK cells among them may make direct contact with the tumor cells when they encounter NK cell sensitive tumors.