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Acute interstitial nephritis (AIN) is a rare, often underdiagnosed condition and a common cause of renal failure. Drugs are the leading cause. The underlying pathophysiological condition is often a type IV hypersensitivity reaction. There are also rarer idiopathic forms, which often remain unrecognized. Additionally, the pathophysiological mechanisms are poorly understood, so that only very few promising forms of treatment are available. For some medications the overall risk is low but the side effects are relevant for the clinical routine due to the fact that they are frequently prescribed. In addition, the development of new approaches, such as immunotherapy also leads to side effects that cannot be completely predicted. For many diseases the occurrence of acute kidney injury increases the mortality and morbidity. A potentially irreversible chronic renal failure increases the incidence of further comorbidities and reduces the quality of life. Treatment is difficult and mostly empirical.

Drug hypersensitivity reactions affect over 7% of the population and are problematic both for patients and doctors. They frequently occur in the form of exanthematous drug eruptions. The clinical manifestation of delayed hypersensitivity reactions is very variable ranging from localized fixed drug eruptions to life-threatening, severe bullous mucocutaneous eruptions or systemic drug hypersensitivity syndromes. In the case of suspicion of an exanthematous drug eruption, the causality should initially be assessed according to the proposed algorithm. If both the chronology and the clinical symptoms are indicative of a delayed drug hypersensitivity reaction, the suspected drug should be avoided. Only in cases of urgent therapeutic indications and if alternative drugs are not available, the options of "treating through" and temporary tolerance induction by "desensitization" should be considered after an individual risk-benefit analysis.

The correlation between anaphylaxis after consumption of meat and the carbohydrate epitope galactose-α-1,3-galactose (α-Gal) was first described in oncologic patients treated with cetuximab. An association with tick bites and parasitosis is suspected. We report on a healthy patient who developed sudden anaphylactic reactions after the ingestion of meat. Serologic and skin tests confirmed sensitization to α-Gal. Avoiding the consumption of mammalian meat led to a complete absence of symptoms.

When there is the suspicion of an allergic reaction to betalactam-antibiotics, the allergological evaluation is an important tool to confirm the allergy and to test alternative medicaments. As all the testing methods for the allergologic evaluation (cutaneous tests and in-vitro tests) don't have a high sensitivity, a broad case report and the former documentation of the symptoms and diagnostic findings are essential, to enable a high significance of the examination and to assess the indication for the provocation test which is the gold standard in many cases. The documentation of the time flow is basic, to differentiate between immediate reactions (hours after intake) and nonimmediate reactions (several days after intake). The diagnostic evaluation not later than after six months increases the prospects for a successful allergic evaluation.Die allergologische Abklärung ist bei Verdacht auf eine Allergie auf Beta-Laktam-Antibiotika wichtig, um die Reaktion zu bestätigen und alternative Medikamente zu testen. Da jedoch alle Testmethoden der allergologischen Abklärung (Hautteste und in-vitro-Tests) eine nicht sehr hohe Sensitivität haben, ist eine vorherige umfassende Anamnese sowie die Dokumentation der Symptome und Befunde entscheidend, um eine hohe Aussagekraft der Untersuchung zu ermöglichen und die Indikation zum in vielen Fällen notwendigen Provokationstest stellen zu können. Als wesentliche Voraussetzung muss neben der Klinik der zeitliche Ablauf festgehalten werden, um zwischen einer Sofortreaktion (wenige Stunden nach Substanzeinnahme) und einer Spätreaktion (einige Tage nach Einnahme) unterscheiden zu können. Die Abklärung bis spätestens sechs Monate nach der Reaktion erhöht die Chancen einer erfolgreichen allergologischen Abklärung.En cas de suspicion d'une réaction allergique aux antibiotiques bêta-lactames, l'investigation allergique est un moyen important pour confirmer l'allergie et pour évaluer des médicaments alternatifs. Comme cependant toutes les méthodes des tests de l'évaluation allergique (tests cutanés et in-vitro-tests) n'ont pas de sensibilité élevée, une anamnèse détaillée et la documentation des symptômes sont cruciaux pour rendre hautement significative l'évaluation et pour pouvoir poser l'indication pour le test de provocation qui est souvent la méthode de référence. La documentation du déroulement de l'allergie est capitale pour différencier entre une réponse immédiate (quelques heures après la prise de l'agent) et une réponse retardée (quelques jours après la prise de l'agent). L'investigation au plus tard après six mois augmente les chances de succès d'une évaluation allergique.

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.

Corticosteroids are therapeutic agents used in cases of allergy and intolerance. Due to the antiinflammatory effects of the corticosteroids, hypersensitivity reactions often are considered to be a paradox. However, delayed-type reaction to corticosteroids is a frequent phenomenon in the daily routine. Non-responding eczema, development of subacute contact eczema, systemic contact dermatitis or maculopapular exanthemas can be a clinical symptom of a delayed-type hypersensitivity reaction to corticosteroids. Immediate-type hypersensitivity reactions to corticosteroids remain uncommon. Nevertheless, they can take a severe clinical course. Patients react with anaphylaxis after systemic administration or with aggravation of an allergic reaction under therapy with corticosteroids. Allergologic testing is necessary for diagnosis and providing alternative corticosteroids in case of an emergency.

Interferon alpha (IFN-α) and interferon beta (IFN-β) are naturally occurring cytokines, which belong to the type I interferons and share the same receptor leading to very similar therapeutic effects. The immunomodulatory effect of type I interferons includes modulation of antibody production, inhibition of lymphocyte proliferation, inhibition of delayed-type hypersensitivity and enhancement of T-cell and NK-cell cytotoxicity. An increasing number of open clinical studies and case reports have demonstrated the efficacy of IFN-α for severe ocular inflammation in patients with Behçet's disease and of interferon-β, which has been used mainly for the treatment of multiple sclerosis.

Allergic reactions to drugs belong to the group of B-reactions, which are characterized not only by the pharmacologic profile of the drug but also by individual risk factors. Pharmacogenetic approaches facilitate identifying these risk factors. The most important example for Caucasian patients is NIDR (non-immediate drug reaction) to abacavir. Chinese patients possess risk factors for NIDR to allopurinol and anticonvulsants and the HLA locus on chromosome 6. Another potentially important area is assessing risk factors to prevent allergic reactions to antibiotics, especially with regard to the effective treatment of MRSA.

A 48-year-old woman developed a skin rash after taking glucocorticoids.Positive patch tests revealed type IV allergy (delayed reaction) to several glucocorticoids. In addition an eczema-like rash was produced by an oral provocation test with triamcinolone, although the patch test for this drug had been negative.We recommended avoidance of the positively-tested corticosteroids and issued a corresponding allergy pass.Type IV allergy to glucocorticoids is rare but should be considered whenever patients develop a skin rash after the use of corticosteroids.

Acute generalized exanthematous pustulosis (AGEP) is characterized by an acute disseminated eruption of multiple, non-follicular pustules. In addition, it can be associated with fever, elevated erythrocyte sedimentation rate, and leukocytosis. The pathogenesis of AGEP is still unknown; however, medications appear a likely cause in most cases. We report on 3 patients with AGEP demonstrating characteristic clinical and histologic features after taking amoxicillin, ampicillin, or diltiazem. All patients had positive patch test reactions to the suspected drugs.

During recent years demands for permanent make up and especially permanent lip liner is increasing not only in the USA but also in Germany. Adverse reactions to these products are almost unknown and not documented in literature. Declaration of contents and side effects are not required for tattoo colors, in contrast to the rules for medical treatments. Our patient developed inflammation and vesiculation within the area of tattooing three days after injection of a permanent lip liner. Treatment with steroids induced complete resolution of the lip liner-associated dermatitis. However, not only the effect of the lip liner was lost but also the natural color of her lip was partly destroyed by inflammation. Diagnostic allergy testing revealed strong delayed hypersensitivity to nickel and a mild patch test reaction to the permanent lip liner. Examination of the permanent make-up by mass spectrometry detected nickel in a concentration of 1.8 ppm. No allergic reaction could be seen when the purified red dye itself was tested. This patient with pre-existing nickel allergy developed an allergic contact dermatitis from the injection of a permanent lip liner contaminated with nickel.

The aim of the current study was to elucidate the incidence of allergic reactions to metal/metal articulations in revised total hip arthroplasties.Between 1 January 1997 and 31 January 2002 a consecutive series of tissue samples from 13 revised total hip arthroplasties with metal/metal articulations were histopathologically examined for signs of delayed type hypersensitivity (DTH). Mean age at the time of revision of the eight women and five men was 58.7 years. The prostheses were revised after a mean follow-up of 45 months. Indications for revision were progressive osteolysis of the proximal femur in 12 cases and instability in one case. All patients were clinically and radiologically evaluated after a mean follow-up of 52 months (min. 22, max. 74) after revision.No signs of infection were found in either histopathological or microbiological examinations. In ten cases, perivascular lymphocytic infiltrates could be found as a sign of DTH. After revision and changing of the articulation all osteolyses healed.In 10/13 cases (76.9%) signs of DTH could be detected. The fact that all osteolyses healed after changing the articulation may give a strong hint that there is an immunological contribution to this radiological changes. Metal/metal articulations cannot be recommended as the optimum implant for young patients, as the number of patients with allergic reactions to nickel, chrome or cobalt is increasing continuously.

Failure to tolerate prosthetic material can lead to a variety of clinical findings. A 55-year-old woman had a total replacement of the right knee. Two weeks later she developed pruritic skin lesions over the joint, as well as pain and impaired function. Allergic testing showed clinically relevant Type IV sensitization to methylmethacrylate, as well as to various formulations of the bone cement, including one with an added antibiotic. The symptom complex of pruritic skin lesions in the area of the prosthesis, pain and disability, as well as relevant Type IV sensitization justified replacing the prosthesis.

Allergy is a very uncommon cause of diarrhoea. Other mechanisms, medical diseases and infections, psychological and pseudoallergic reactions, intolerance reactions, and enzyme defects/deficiency, and many other conditions are much more common. If food allergy is strongly suspected diagnosis may be difficult, even for allergologists, as it requires a mosaic of history, skin and in vitro tests, diagnostic diet, and even provocation tests. It is important to recognise diarrhoea "accompanying" allergic urticaria and anaphylactic reactions as part of the symptomatology of the primary dermatological or allergic disease and to refer the patient to the appropriate specialist.

Specific immunotherapy (SIT) represents the only specific treatment that can be offered to allergic patients apart from allergen avoidance. SIT has been widely used in pollen allergic rhinitis. Clinical efficacy has been demonstrated in several controlled clinical trials and depends on the specific allergen the individual patient is sensitive to, the quality and total amount of allergen applied, and the SIT schedule. In classic SIT, gradually increasing dosages of the allergen extract are injected subcutaneously. Several dosage schedules for subcutaneous SIT can be applied. In Cluster-SIT, 2 - 3 injections per day of treatment are given once a week during induction treatment.In this study, we investigated 64 patients (33 female, 31 male) from 18 to 54 years (26.9 +/- 5.1 years) in terms of side-effects of Cluster-SIT during induction treatment.The total amount of enlarged local reactions (grade 1) was n = 77 or 15.2 % of all injections. Of these, 68 (88 %) were classified as immediate reactions, 8 (11 %) were late phase reactions and 1 (1 %) was immediate as well as late phase reaction. Of all enlarged local reactions, 48 (62 %) were grade 1 reactions, 13 (17 %) were grade 2 reactions, 13 (17 %) were grade 3 reactions and 1 (1 %) was a grade 4 reaction. The total amount of systemic reactions was n = 22 or 4.3 % of all injections. Of these, 19 (86 %) were classified as immediate reactions, 3 (14 %) were delayed reactions. Of all systemic reactions, 18 (82 %) were grade 1 reactions and 4 (18 %) grade 2 reactions. Grade 3 or grade 4 reactions did not occur. There were no differences in gender or age regarding the occurrence of side effects (all p0.05).Frequency and severity of adverse side effects in Cluster-SIT correspond to those in other dosage schedules. On behalf of security aspects, Cluster-SIT could become an interesting alternative dosage schedule for dose increase during SIT. Furthermore, in Cluster-SIT with allergoids, induction treatment can be carried out in two treatment days of approximately 2.5 hours each.

In 2.5 % of cases excessive reaction with formation of blisters and local necrosis is seen after tuberculin skin testing with Mendel-Mantoux technique. The objective of this prospective study was to determine whether this rate can be reduced by pretesting. 426 contacts of cases with contagious pulmonary tuberculosis were examined in a public health office. A tuberculin skin test in Mendel-Mantoux technique with 1 unit purified tuberculin Behring (GT 1, bioequivalent to 0.5 units PPD-S) was applied and the results read after 3 to 7 days. Negative results were retested with 10 units (GT 10, bioequivalent to 5 units PPD-S). 422 patients completed the examination course as planned. In two cases forming of blisters was noticed. The difference between this observed rate of 0.5 % and the published rate of 2.5 % is highly significant. The alternative hypothesis that pretesting reduces the rate of excessive reactions can be assumed.

We report the case of a a 60 year-old worker in the pharmaceutical industry who suffered from recurring contact dermatitis. Initially the contact dermatitis was limited to the hands; later on it became generalized. The patient had been working on a drug filling line in a pharmaceutical plant for more than 20 years. Eight years after starting this job he had developed allergic hand dermatitis to 2,6-diaminopyridine (patch test positive); this healed upon cessation of exposure. Ten years later he again developed hand dermatitis which progressed to generalized dermatitis and conjunctivitis. Under systemic and local therapy with corticosteroids and cessation of work, it healed nearly completely. Four months after returning to work, the patient experienced a first episode of severe asthma and generalized dermatitis with conjunctivitis following exposure to hydroxychloroquine the day before. The asthma and dermatitis improved after systemic corticosteroid therapy and stopping work. His condition continued to fluctuate, when though the patient was transferred at work and now wore rubber gloves. Eight months later he again developed a generalized dermatitis. Patch testing revealed delayed-type sensitizations to hydroxychloroquine (tested in concentrations of 0. 1%, 0.5%, 1% and 2%). Equivalent tests in five healthy volunteers were negative. The patch test reactions were pustular, while a biopsy was interpreted as a multiform contact dermatitis reaction. Bronchial exposure with hydroxychloroquine dust produced a delayed bronchial obstruction over the next 20 hours, which progressed to fever and generalized erythema (hematogenous contact dermatitis). After removing exposure to 2,6-diaminopyridine and hydroxychloroquine, the patient went on to develop a contact dermatitis to latex (patch test positive). However, skin prick tests with latex and patch tests with rubber additiva were negative. Hydroxychloroquine is well known to cause drug reactions. To our knowledge, contact dermatitis to this substance has not yet been reported. It is noteworthy that the patch test reactions were pustular and of multiform morphology and that bronchial exposure to the allergen resulted in asthma and a generalized drug reaction. Pathogenetically the asthmatic reaction seems to be on a delayed-type mechanism as is also seen with ampicillin, cobalt and nickel induced asthma.

Inflammatory demyelinating diseases of the nervous system, such as multiple sclerosis or the Guillain-Barré syndrome represent severely disabling disorders, often seen by the neurologist, with still only limited means for therapeutical intervention. The underlying pathomechanisms remain in large part elusive, however mounting evidence suggests that enzymes of the family of matrix metalloproteinases are of relevance in the pathogenesis of these disorders. Experimental in vivo data as well as results from other medical fields emphasize that the selective inhibition of these proteases could be a promising therapeutical approach. The following review summarizes the role of matrix metalloproteinases in inflammatory demyelinating diseases of the central as well as peripheral nervous system and discusses the therapeutical application of synthetic inhibitors in these disorders.

Allergies caused by metallic implants are often thought to be a reason for postoperative complications like bone necrosis or loosening of the prosthesis.In a prospective study, we investigated allergic sensitivity against components of stainless steel implants, including titanium, in 112 patients shortly before surgical operation. The same tests were then repeated in 100 of these patients exactly one year after operation. There were three different kinds of procedures: 1. titanium implants, mainly total hip replacements, 2. regular steel implants, 3. surgery without any implants (control group). Any differences from the process of regular healing were regarded as postoperative complications.A sensitivity against nickel (Ni) was diagnosed in three of these 100 patients (3%) before surgery. These patients, of whom two received a nickel-containing implant and one a titanium arthroplasty, did not show any postsurgical complications. Furthermore, three patients (3%) acquired a new sensitivity against metals during the study-interval of one year. Two of these three patients were women, who developed a postsurgical sensitivity against nickel or chrome but got titanium arthroplasties, which did not contain any nickel. These two women wore metal-containing jewelry, which might be the reason for the newly acquired metal-sensitivities, and both showed postsurgical complications. The third patient, who has developed a postsurgical sensitivity against components of his steel arthroplasty, did not reveal any complications.We conclude that the rate of allergic sensitization against metal-components of arthroplasties is low in our patients. Additionally, skin-sensitivity against components of alloys and platings was not associated with a higher rate of postsurgical complications in our patients. We did not see any sensitivity against titanium. In conclusion, metallic implants are not a cause of allergies to a relevant extent, nowadays.

Allergic reactions in tattoos are comparatively rare. In most cases the reactions are caused by different red pigments. While in the past these reactions have been ascribed to mercury salts (cinnebar) and cadmium sulphide, now synthetic inorganic azo dyes have also been found to be responsible for such reactions. A 42-year-old man presented with an allergic reaction in the red parts of his tattoos. Histologically a chronic granulomatous, partly fibrous inflammation with transfollicular elimination of pigment granules was found. Spontaneous regression in a part of the inflammatory reaction was observed, simultaneously with depigmentation and scarring of the overlying skin. The pigment used for tattooing was found to be an aromatic azo derivative. In addition to a positive cutaneous reaction to the dye, the patient also showed a positive patch test to Napthol AS, used for the coupling of different dyes in the textile industry.

Administration of X-ray contrast media is essential in many radiologic procedures such as angiography, computed, tomography, and many other diagnostic methods. These substances have become made more tolerable since the introduction of the first water-soluble X-ray media. Adverse drug reactions decreased by the factor 4 with the development of nonionic contrast media compared to the elder ionic substances. At the same time, a shift to more frequent delayed reactions occurred. Currently the dimeric contrast media for intravascular use are suspected of causing frequent delayed side effects, especially with rashes and other cutaneous symptoms. In this paper, the reasons for adverse reactions independent of drug administration, are discussed. Causes related to patients and geographic differences are reviewed. Summing up, it may be said that the new dimeric contrast media are well tolerated drugs. A higher incidence of adverse drug reactions is not evident from scientific studies. A shift to more delayed side effects, especially, reactions is possible. The mechanism is still unclear. Additionally a classification of the time of incidence of side effects is proposed.

A 63-year-old man developed a mild hemorrhagic diathesis which led to the diagnosis of chronic lymphatic leukemia. Treatment with prednisone and chlorambucil was initiated. During the first 10 day-cycle (10 mg chlorambucil and 100 mg prednisone) no side effects were noted. On the 8th day of second cycle (10 mg chlorambucil and 25 mg prednisone) the patient noticed fever, tiredness, myalgia, pruritus and erythema on the skin. The third cycle (10 mg chlorambucil alone) hat to be stopped on the second day due to the development of myalgia, generalized erythroderma with exfoliation and edema of the face and arms. In the patch-test with chlorambucil, a strongly positive (histologically verified) allergic reaction was noted. A lymphocyte stimulation test (detecting in vitro lymphocytes sensitized to chlorambucil) was also positive. These findings, together with the marked clinical reaction to chlorambucil alone, led to the diagnosis of a delayed hypersensitivity reaction to chlorambucil. Such well documented allergic reactions to chlorambucil are very rarely described in the literature. Up to now only 1 case of immune hemolytic anemia, 1 case of Lyell-syndrome, 2 cases of delayed hypersensitivity reactions and a few cases of less well documented type I reactions have been described. In all these cases no crossreactivity with other alkylating agents occurred, and hence all patients could be successfully treated with cyclophosphamide.

Interleukin 2 (IL2) production is known to bypass T-helper-cell function in the generation of an antitumour response. The present analysis was designed to assess the effects of application of renal cancer vaccine with and without IL2 on delayed-type hypersensitivity (DTH) skin responses to the vaccine itself and tumour cell challenge. The renal cancer vaccine consisted of Newcastle disease virus (NDV)-infected autologous irradiated tumour cells and topical application of low-dose rIL2 (75,000 Cetus units). As a result, the coadministration of a supplement of rIL2 proved to be important for augmentation of DTH responsiveness to tumour cell challenge. Patients with aneuploid tumours vaccinated without rIL2 developed an anergy to the vaccine throughout vaccination. This effect could be reversed by the topical coapplication of this cytokine. While the treatment of renal cancer patients with IL2-based immunotherapy regimens appears to be effective in advanced renal cell carcinoma the IL2-supplemented vaccines should be tested to assess their benefit in the situation of "minimal disease" after surgery especially in high-risk patients with aneuploid tumours.

A 3-step synthesis, starting from substituted isatoic anhydride was used to prepare substituted 3-(2-mercaptoethyl)quinazoline-2,4(1H,3H)-diones 4. Reaction of 1 with cystamine afforded bis[2-(2-amino-benzoyl-amino)ethyl]disulfanes 2. Reaction of 2 with ethyl chloroformate and subsequent reduction of the heterocyclic disulfanes 3 gave mercaptoethylquinazoline-2,4-diones 4a-f.N-1 methyl and benzyl substituted derivatives 4b and 4c, respectively, show immuno-stimulating activity in various tests.

A series of 3-mercaptoalkylthieno[2,3-d]pyrimidine-2,4(1H,3H)-diones 3 was prepared and their immuno-stimulating activity was examined. The title compounds were obtained conveniently by hydrolytic ring cleavage of fused thiazolo- or 1,3-thiazino-thienopyrimidines 1 under alkaline or acidic reaction conditions. The ms fragmentation of the thieno[2,3-d]pyrimidine-2,4-diones 3 is discussed. In the delayed type hypersensitivity (DTH) test some compounds 3 showed immuno-stimulating activities in the range of isoprinosine.

We report the case of a 51-year-old patient with a Paget von Schrötter-Syndrome of the right arm who underwent a successful lysis therapy with 9 x 10(6) IU streptokinase (Streptase) i.v. over 3 days. 36 h after ending the lysis therapy he developed a generalized eczema, which was interpreted as a drug-induced allergic reaction of the arthus type (Coombs III). He received methylprednisolone p.o. with an initial dose of 40 mg, tapered to 0 over 5 days. One day after the efflorent rash the patient developed fever for 12 h (with 38.8 degrees C maximum) and a gonarthritis of the left knee, and 24 h later of both knees. An echocardiogram showed a small pericardial effusion without hemodynamic influence. On the following 2 days a minimal proteinuria of 0.28 and 0.22 g/l was found. Subsequently and after a follow-up of 2 years, the patient was totally free of pathologic clinical and laboratory findings. We interpret this unusual case as a delayed hypersensitivity reaction to streptokinase with a paradoxical occurrence of clinical symptoms formally fulfilling the diagnostic criteria of "rheumatic fever".

In the last few years the allergenic potential of rubber has been receiving more and more attention. Its widespread application in medical devices and everyday objects has increased exposure to this allergen. The central role of rubber in the prevention of HIV infection has certainly played a part in this development. Latex allergy manifests itself as immediate type allergy (type I), delayed type allergy (type IV) or as a combination of both types of hypersensitivity. In this review the different types of latex allergy are illustrated by means of selected case reports. Immediate type allergy to latex leads to contact urticaria, but it may also cause generalized urticaria, bronchial asthma or even anaphylactic reactions (contact urticaria syndrome). Hence, not only dermatologists and allergologists are confronted with latex allergy. Immediate type hypersensitivity can be proven by skin prick test and RAST (radio allergosorbent test). Contact dermatitis in patients using rubber gloves is generally due to delayed type hypersensitivity to rubber additives. However, a recently observed case suggests the possibility of isolated delayed type hypersensitivity to natural latex.

Following epicutaneous application of a potential contact sensitizing agent (hapten) allergic contact dermatitis results if sensitizing rather than tolerizing signals become dominant. Whereas downregulatory signals are poorly defined it has become clear that epidermal Langerhans cells play an important role in the induction of contact allergy. The current hypothesis is that in vivo, subsequent to deposition of antigen, resident Langerhans cells mature into potent immunostimulatory, antigen-carrying dendritic cells which migrate via the afferent lymphatics and after their arrival in the draining lymph node select and sensitize clones of antigen-specific T-cells from the circulating pool. These T-cells produce Interleukin-2 and Interferon-gamma, and, thus, constitute so-called type 1 helper T-cells (Th 1). Recent progress has shed light on some major unknowns in this sequence of events such as regulatory influences, nature of the T-cell receptor ligand, and extravasation of T-cells at the site of hapten deposition. For example, epidermal cell-derived cytokines seem important for initiation (Interleukin-1) and sustenance (GM-CSF) of the induction phase. Hapten-specific T-cells seem to see hapten molecules bound to peptides in the groove of the MHC molecules, and specific endothelial adhesion molecules (ELAM-1) mediate extravasation of skin-homing T-cells that carry a specific ligand (CLA). The recent development of techniques to grow murine as well as human Langerhans cells and dendritic cells in large numbers will allow researchers to further elucidate the pathogenesis of contact hypersensitivity and will ultimately lead to the design of novel strategies for immodulation and tolerance induction.

Investigations with different spleen extracts of varied composition and purity have shown immunomodulatory effects. In the present study the in vivo effect of a bovine spleen hydrolysate (Prosplen) on a radiation-induced immunodeficiency model is demonstrated. Intraperitoneal application of 1 mg/g bw hydrolysate 3/times a week caused a highly significant acceleration of the restitution of the humoral and cell-mediated immunoreactivity towards sheep erythrocytes in sublethally (600 cGy) radiated mice: plaque-forming cells in the spleen, hemagglutination, hemolysistiter of the serum, delayed type of hypersensitivity = DTH reaction. The immunoreactivity of the treated groups reached normal levels within 6-8 weeks, whereas in the groups receiving placebo this was observed after 10 weeks at the earliest. Cytofluorometric investigations revealed an accelerated restitution of the B-lymphocyte fraction in the spleen. Mice that was not irradiated showed no effect after treatment with the hydrolysate. Similar results were obtained using an ultrafiltrate of the hydrolysate.

A 63-year-old female, with type II diabetes mellitus, diagnosed in 1967, was started on combination therapy with sulphonylureas and human depot insulin in May 1989, because of inadequate blood sugar control with sulphonylureas alone. Within 3 months she began to develop nodular skin reactions at the site of injection, 12-24 hours after insulin injections. Intradermal testing demonstrated delayed (Gell and Coombs type IV) hypersensitivity to protamine. No specific IgE or IgG antibodies were demonstrable. She was changed to protamine-free human delayed action insulin. After an initial reaction-free period, red urticarial lesions, attributable to immediate (Gell and Coombs type I) hypersensitivity to human insulin, appeared at the injection sites. There were no other complications with continued insulin therapy, and after about 6 weeks no further local reactions were detectable. When an allergic reaction to an insulin preparation is suspected, careful immunological investigation should be performed, to ensure adequate treatment without risk to the patient.

Infection is a frequent cause of morbidity and mortality after multiple trauma. Although impaired immune function has been assumed to be associated with the development of infection and sepsis in trauma victims, its predictive role is still controversial. In a prospective study, the predictive value of the immunological in vivo response to intradermally applied recall antigens was compared with serial determinations of routine parameters. PATIENTS AND METHODS. Using the commercially available Multitest device, the cutaneous delayed-type hypersensitivity (DTH) response to seven standardized recall antigens was sequentially tested at defined time intervals in 35 mechanically ventilated multiple-trauma patients (4 females, 31 males). Routine clinical and laboratory parameters (FiO2, lactate, creatinine, platelet count, absolute and differential white blood cell (WBC) count) were determined every day. Injury severity scores (ISS), infections, and intensive care unit (ICU) mortality were prospectively documented by the same investigator. RESULTS AND DISCUSSION. The overall ICU mortality was 23%. In survivors, the mean ISS was 29.5, in nonsurvivors 38.9 (P less than 0.05). Mortality significantly increased in association with sepsis. Interestingly, the DTH response and severity of the trauma did not show any interdependence. Immediately after ICU admission, DTH testing failed to correlate with either infection or mortality: most of the multiply traumatized patients were anergic on initial skin testing. In the early posttraumatic stage, the serum levels of creatinine or lactate, lymphocyte and promyelocyte counts, and FiO2 proved to be more reliable predictors. In the later course, however, a good correlation was found between sequential skin test results and the development of infection. Beginning on the 4th day after trauma, DTH scores below 5 mm defined a population with a high incidence of developing a clinically important septic episode. In conclusion, lactate, FiO2, and WBC counts are early indicators of an impending poor outcome, whereas the skin test response is not. In the later course, however, the sequentially determined DTH response may substantially contribute to the identification of multiple-trauma patients at increased risk of infection.

A review is given on allergens in topical ophthalmological drugs, which are of importance as to allergic type IV-skin reactions. The diagnostic proceedings are demonstrated and the special importance of patch testing and chamber scarification test is outlined by a case report.

The allergic reaction of the human nasal mucosa (Type I Coombs and Gell) can be divided in an immediate- and a late-phase reaction. The degranulation of IgE-bearing mast cells is crucial for the initiation of the immediate phase (app. 30 min). Mediators of these cells - especially histamine - cause the typical allergic symptoms. Some of the patients develop a late-phase reaction after a symptom-free interval. Eosinophils migrate into the epithelial lining and release mediators. Furthermore, mast cells increase in number in the epithelium. Other cells like macrophages and T lymphocytes may be involved as well. While the released mediators cause an unspecific mucosal hyperreactivity, the increased number of IgE-bearing mast cells leads to a specific immunological augmentation of the nasal reaction ("priming effect"). The allergic pathomechanism can be reduced by drugs at different points.

The various disorders occurring after sclerotherapy for hemorrhoids comprise excessive local reactions, necrosis followed by hemorrhage and allergic reactions. Symptoms, prevention and therapy of these adverse effects are detailed.

In 31 children with different cytostatic treated malignancies delayed cutaneous hypersensitivity (DCH) and their relationship to different peripheral white blood-cell counts was investigated. DCH was assessed by a multi-antigen-test device, which allows the simultaneous intracutaneous application of 7 standardized recall-antigen solutions. The grade of DCH reaction was measured by a "score", which reflects the sum of the diameters of all single positive reactions. The follow-up time was 3 years for each patient. At start of therapy 17 out of 31 children had pathologically decreased score values. In 16 out of these 17 children score values increased to normal during the cytostatic treatment. Patients with score values increasing from low to normal had a significant better outcome of their disease than patients with other score courses. A good correlation was found between an increase of score values and tumor-mass reduction. No positive correlation between the score and the peripheral white blood-cell counts could be evaluated, but a significant reciprocal correlation was found between the score and the peripheral absolute lymphocyte counts. Cytostatic drugs had no influence on the score. The results suggest, that the DCH can reveal immunological alterations, which are caused by the extent of tumor burden and by specific influences on the immune system and which are almost not influenced by the administration of cytostatic drugs.

The question: in which parts of the lungs do obstructions occur after inhalative provocation with immediate and delayed reactions, and after bronchospasmolysis, has been investigated. The following parameters were measured in more than 30 children with delayed and more than 70 children with immediate responses: FEV1, MF25-75%, PF, RawOS (oscillometrically), Raw (shutter) employing the shutter method, Rawtot, TGV, RV, RV/TLC and AEX (area under the expiratory flow-volume curve. The above parameters were determined prior to, during the positive immediate and delayed reaction, and after bronchospasmolysis. The examinations were carried out with the body plethysmograph manufactured by Ganshorn-Electronic, and the FD-5 (Siregnost) made by Siemens. The allergens: hous dust mites (D. pteronyssinus and D. farinae), grasses and fungi (Alternaria, Cladosporium, Aspergillus and Penicillium) obtained from the firm of Bencard, were nebulized in increasing concentrations, using the ultrasound nebulizer manufactured by Heyer. The forced spirogram, in the first instance FEV1, permits the best assessment of the changes occurring in the lungs during these challenges. A breakdown in terms of MIF25-75% permits assignment to the deeper and higher airways. In the case of the immediate reactions, the inhalation of beta-sympathomimetics leads to complete bronchospasmolysis, while in the case of the delayed reaction, bronchospasm is no longer fully reversible owing to oedema and inflammation. This can be documented with the aid of the parameter FEV1, MF25-75%, PF, AEX and RV. The examinations using the oscillometric RawOS method are the least suitable for establishing the late reactions or residual obstruction following bronchospasmolysis.

After a short historical review about the detection of reagins by Coca and Prausnitz-Küstner 1921-1923 and about their physico-chemical characterisation as IgE-antibodies by Ishizaka and Johansson 1967-1968 the definition and the clinical relevance of atopy is discussed. The IgE-regulation by interleukins and the pathomechanism of IgE-mediated allergies is reviewed. Of special importance is the IgE-mediated inflammatory late-reaction and the--therefore caused--unspecific hyperreactivity of the stricken tissue, both characteristic features of asthma bronchiale as well as atopic dermatitis.