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We now have the means to give a patient the drug he absolutely needs even if these have been responsible for immediate or delayed hypersensitivity reactions. We use so-called "desensitization protocols" which rely on strong experimental pathophysiological bases. We take as examples immediate hypersensitivity to aspirin/NSAID and chemotherapy and non-severe delayed hypersensitivity to antibiotic for which tolerance induction gives excellent results.

Cutaneous adverse drug reactions (CADR) are delayed hypersensivities. Their clinical presentation and severity are very diverse ranging from the frequent and benign exanthemas to the rare but severe CADR involving deep organs in the case of drug reaction with eosinophilia and systemic symptoms (DRESS) or leading to skin bulla and epidermal detachment in toxic epidermal necrolysis. The main differential diagnoses are infections, especially viral ones, which could give clinical symptoms identical to those occurring in CADR.

The prescription ot fluoroquinolones has been constantly increasing over the past decade. consequently, an increasing number of hyper-sensitivity reactions and adverse events have been reported. The aim of the review is to discuss the incidence of hypersensitivity reactions either IgE (immediate) or T cells mediated (delayed). We will make an overview ofthe diagnostic tools available to detect such hypersensitivity reactions. Finally, the specific adverse events associated with fluoroquinolones, including tendinopathy, chondrotoxicity, peripheral neuropathy or retinal detachment will be discussed.

The pathophysiology of drug allergy is complex and relies on the interaction between the drug and the immune system in combination with environmental factors, in particular viruses. Genetic predisposition plays an important role in drug allergy. Recent publications have shown the importance of HLA genes, particularly in the delayed hypersensitivity reactions. In fact, particular HLA alleles were identified as risk factors in the development of severe allergic reactions to certain drugs, identifying people at risk of hypersensitivity before initiation of specific treatment. In the future, identification of other alleles in HLA genes will improve patients care by preventing hypersensitivity reactions associated with significant morbidity and mortality.

The number of household pets increased greatly during the twentieth century, with the numbers of new pets (NP, i.e. any pet other than cats and dogs) rising especially sharply over the last decade. Contact with such animals, whose owners do not always know how to look after them properly, expose the population to new risks such as trauma, infection and allergy. While the most common allergies are respiratory, allergic skin reactions, both immediate and delayed, may also result from contact with these new allergens. The animal itself or its environment may be the cause. Herein, we review NPs and reports of allergic dermatitis associated with them.

Although most delayed drug hypersensitivity reactions are mild and show rapid improvement after drug discontinuation, there are severe systemic and/or cutaneous drug reactions which may be life-threatening. These entities are discussed here, namely DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms), acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN). Early detection of warning signs and symptoms may help to take appropriate measures precociously.

The use of heparins in the prophylaxis and treatment of thromboembolic diseases shows non-negligible risks of cutaneous lesions, which are very frequently underestimated by physicians. As this risk often originates from either delayed-type hypersensitivity reactions or life-threatening heparin-induced thrombocytopenia, a quick diagnosis and an adapted management are thus crucial. Furthermore, as most cases are emergencies, allergologic testing cannot be considered in the first place. In this context, an overview of the therapeutic as well as management recommendations is presented, taking into account the most recent treatments.

Heparin is widely used as an anticoagulant and is indicated in the prevention and treatment of thromboembolic disorders. Heparin-induced delayed-type hypersensitivity presents as eczematous lesions, either at the injection site or generally, and affects 7.5% of patients on heparin. This poses diagnostic and therapeutic issues, since an alternative anticoagulant treatment is essential and the risk of cross-reactivity may be as high as 80%, depending on the type of heparin used. If delayed-type hypersensitivity is suspected, heparin-induced thrombocytopenia must first be ruled out, and heparin should be stopped. Fondaparinux is currently the first-line alternative, with a risk of cross-reactivity estimated at only 10%. The switch from a low-molecular-weight heparin (LMWH) to another LMWH is no longer recommended. The use of unfractionated heparin, danaparoid or hirudin may be warranted in the event of recurrence with fondaparinux, and an immuno-allergological work-up is needed to specify the exact profile of cross-allergies.

Lymphomatoid contact dermatitis is a delayed hypersensitivity reaction predominantly featuring T-cell infiltration. We report a case mainly involving B-cell infiltration associated with eczema and resulting from an indirect proxy contact with an allergen in a conjugal setting.A 32-year-old man had an infiltrated cutaneous lesion on the interior aspect of the left arm with eczematous lesions of the waist and the anterior aspect of the left arm which were present for 6 months. All of these lesions were unresponsive to strong local steroids. Biopsy of the infiltrated lesion showed a dense lymphoid dermal infiltration chiefly comprising B cells. Histological examination of a waist lesion revealed chronic eczema. Patch testing was performed with the ECDRG test battery. A PPD (paraphenylenediamine) patch test was the only examination yielding a positive result. Detailed questioning revealed use of a hair dye by the patient's spouse and withdrawal of the allergen resulted in complete remission of the two types of lesion.This case highlights the ability of a single allergen to induce different lymphoid phenotypes. It also underscores the value of detailed questioning in allergology.

External assessment of analytical performance is part of the quality assurance in medical laboratory. These external controls are mandatory in Switzerland since 2006 for IgE analysis. The Swiss Society for Immunology and Allergy and the Swiss external quality centers had launched a program for total IgE, IgE specific for cat epithelium, birch pollen and peanut, and multi-specific IgE. They have set up criteria for proficiency assessment. Analysis of data obtained from 2006 to 2008 in the Quality Control Center Switzerland shows that results are very good for all the methods used and that a large number of participants fulfill the requirements to obtain the certificate of QUALAB conformity.

Numerous professional or leisure activities expose individuals to plants susceptible to provoke contact allergies. The immunological mechanisms that are responsible for these ailments (delayed cellular reaction linked to allergic dermatitis or immediate IgE mediated reaction of the allergic urticaria) differ according to the plant families involved. A differential diagnosis must be made in the case of the even more frequent non-allergic reactions implying either a simple mechanical irritation, or a contact with toxic substances. The role of UV (phytophotodermatosis), as well as the contact allergy to wood is also evoked in this paper.

The immune reconstitution inflammatory syndrome is a heterogeneous collection of pathological manifestations attributed to an excessive and deregulated immune response to various infectious and non-infectious pathogens consecutive to the modification of immune status. Mycobacteria and mycoses in the context of an HIV infection are the main causes of IRIS but this syndrome is also observed with many infectious pathogens in the context of auto-immune or inflammatory diseases. An excessive specific CD4 Th1 response leading to delayed hypersensitivity with imbalanced effector and regulatory cellular immune responses is suggested. The role played by host polymorphisms remains to be investigated. The emergence of a unique syndrome gathering multiple immune-depression/reconstitution such as HIV infection and antiretroviral therapy, decrease of immune depression in transplant, recovery from neutropenia after chemotherapy for cancer, and even post-partum period, could link various specialties and help to better understand physiopathology which is crucial to elaborate preventive therapies.

Systemic contact dermatitis is a form of delayed hypersensitivity reaction seen after systemic administration of a hapten in a subject previously sensitised via the cutaneous route. There have been few reports of this condition with nickel. In this paper, we describe four cases ascribable to the presence of nickel in a peripheral venous catheter.We reviewed the dossiers of four women developing pruriginous exanthema several hours after infusion. The same type of catheter (Optiva) was used in all cases. Epicutaneous tests were performed in all four patients, as well as a challenge test comprising a serum glucose infusion given via the incriminated catheter. Testing for the presence of nickel in the catheter was performed by means of a spot-test. Quantitative nickel assays were performed in vitro using inductively coupled plasma mass spectrometry on the glucose solution infusion kits with eight sample catheters and a negative control kit.The eruptions comprised maculopapular lesions, in some cases vesicular or bullous, arranged symmetrically around the tops of the limbs, the trunk and skin folds, with involvement of the infused forearm in most cases. Two of the four patients had previously presented a number of similar episodes. All four patients exhibited frankly positive test results for nickel and the role of the Optiva) catheter was demonstrated in all four patients by means of a challenge test. The presence of nickel in the catheter was demonstrated by a positive spot-test and was confirmed by quantitative assay demonstrating variations in nickel release for the different samples of the same Optiva) catheter model.As with the few reported cases published in the literature, our four cases of systemic contact dermatitis induced by nickel in a catheter all incriminated the same type of catheter and the tests performed clearly demonstrated the causative role of the device. The cases of systemic contact dermatitis were seen chiefly in women in the immediate postoperative period; they could be confused with adverse drug reactions and subsequently lead to inappropriate withdrawal of treatment. The diagnosis, which was suggested by the appearance of the lesions (symmetry, involvement of skinfolds and buttocks, concomitant reaction at the injection site), history of prior episodes and a frankly positive epicutaneous nickel test, may be readily confirmed using a challenge test.

Allergic conjunctivitis is one of the most frequent reasons for a child's consultation with an ophthalmologist. Once the diagnosis of conjunctivitis is made and the clinical form is clearly established, the search for a cause is the most complicated step. Consultation with an allergist is necessary, in particular when questioning the patient points toward an allergic cause or brings up conditions suggestive of atopic disease. Ocular allergy can follow a type I hypersensitivity, i.e., mediated by IgE: most frequently this is acute and chronic allergic conjunctivitis. Demonstrating the allergen requires prick tests, which are easy to carry out and painless; their sensitivity is currently satisfactory. In vitro tests can complete the workup. In case of doubt on the allergen responsability for allergy, an allergenic provocation test can confirm or refute the allergen's involvement. Ocular allergy can also stem from a type IV mechanism, i.e., a cell-mediated mechanism such as in contact allergy involving different topical substances. In these cases, the clinical aspect and the patient's history may require consultation with a dermatologist-allergist for patch tests. To adapt practices when encountering conjunctivitis in a child, the ophthalmologist should be familiar with the allergens that may set off a conjunctivitis episode. Knowledge of the mechanisms at play also helps direct the examination toward allergy or another cause. In all these steps, collaboration between the ophthalmologist and the allergist is indispensable.

The development of in vitro blood tests that measure the delayed hypersensitivity reaction developed after contact with Mycobacterium tuberculosis will change progressively the diagnosis of M. tuberculosis infection. These blood assays (Quantiferon TB Gold, Cellestis, Australia; T-SPOT.TB, Oxford Immunotec, United Kingdom) use specific, complex M. tuberculosis antigens (ESAT-6 and CFP-10), whereas the intra-dermal Mantoux test is done with tuberculin, a complex mixture of more than 200 antigens. ESAT-6 and CFP-10 are absent from all the BCG vaccine strains used throughout the world. Significant improvement in the specificity with equivalent or increased sensitivity of the in vitro tests compared to the Mantoux test will lead eventually to replacement of the latter.

Irritable Bowel Syndrome (IBS) is a complex and heterogeneous entity that concerns about 1/4 of adults and would be responsible for 50% of gastro-enterology medical consultations. IBS etiopathogenesis and physiopathology are not yet fully known. Implications of food intolerance and allergy in this syndrome remain controversial. In this review we recall numerous mechanisms of allergy or food intolerance generating IBS, as well as clinical entities mimicking an IBS. We present a series of diagnostic tests and potential treatments. We finally propose a management strategy for these patients.

A cross sectional study aimed to evaluate the effect of antigenic preparation (Leishmania infantum versus Leishmania major) and dose of leishmania antigens (5 x 10(6) versus 2.5 x 10(6) parasites in the same volume) on the reproducibility of delayed type hypersensitivity leishmania skin test. Results showed that among 34 individuals involved from visceral leishmaniasis endemic area. 26 (76.5%) had a positif Leishmania infantum leishmania (L-L. infantum) test and 27 (79.4%) to Leishmania major leishmania (L-L. major). Mean size of cutaneous reaction was 5.94 +/- 2.86 mm for L-L. infantum and 5.41 +/- 3.23 mm for L-L. major, with a significant positive linear association (p10-3). Intra-class correlation coefficient was 0.80 (CI95% = [0.64-0.93]) and concordance Kappa (kappa) was 0.57 (CI95% = [0.40-0.74]). Among 153 individuals from zoonotic cutaneous leishmaniasis. 92.9% revealed a positive test for both types of leishmanin (L-L. major full dose versus L-L. major half dose). Mean size of cutaneous reaction was 12.61 +/- 4.65 mm for the reference test and 11.30 +/- 3.95 mm for diluted one, with a positive linear association (p10-3). Intra-class correlation coefficient was 0.78 (IC95% = [0.71-0.84]) and concordance Kappa (kappa) was 0.82 (IC95% = [0.73-0.91]). These results demonstrate a limited effect of leishmania antigenic variation and antigen dose on the reproducibility of delayed type hypersensitivity induced by the leishmanin test.

The atopy patch-test has been shown to be useful in diagnosis of delayed reactions in infants with atopic dermatitis or digestive symptoms. The combination of skin prick testing and patch testing can significantly enhance the accuracy in diagnosis of specific food allergy in infants with atopic dermatitis or digestive symptoms.

Iodinated contrast media are responsible for immediate or delayed adverse reactions. Because of the wide use of these products, one must consider them as drugs. The delay and nature of the undesirable events must be carefully recorded because in some selected cases, a true allergic mechanism can be proved. Cutaneous skin tests identify the culprit drug and find safe alternative for the patient.

Chronic fatigue syndrome or benign myalgic encephalomyelitis has been extensively described and investigated. Although numerous immunological abnormalities have been linked with the syndrome, none have been found to be specific. This article describes the detection of delayed-type hypersensitive responses to certain common environmental antigens in almost fifty per cent of patients with this syndrome. Such hypersensitivity can be detected by the intradermal administration of antigens derived from commensal organisms like the yeast Candida albicans, and then monitoring for a systemic reaction over the following six to forty eight hours. This approach can be consolidated by performing lymphocyte activation tests in parallel and measuring in vitro T-cell activation by Candida albicans antigens by three-colour flow cytometry based on CD3, CD4 and either CD69 or CD25. Another useful parameter is the kinetics of neopterin excretion in the urine over the course of the skin test. The results showed that the intensity of the DTH response correlated with the number of T-cells activated in vitro. Various factors have been implicated in the fatigue of many patients, notably lack of sleep. However, it remains difficult to establish causality in either one direction or the other. This work is in the spirit of a multifactorial approach to the group of conditions referred to as "chronic fatigue syndrome".

Delayed hypersensitivity to heparins and heparinoïd is a problem for prophylaxis of thrombo embolic diseases. The hirudins did not seem to have any cross-reactivity with the two others groups of anticoagulants. We present two clinical cases of delayed type reactions to heparins and heparinoïd and we reviewed the literature about adverse reactions to low molecular weight heparins and the alternative possibilities.

Buccal mucosal allergies are rare because the conditions for sensitization are less favourable in the buccal environment. Clinical presentation is dominated by subjective manifestations (hardening, hypersialorrhea, "burning mouth" syndrome). Extradental etiologies are linked with cosmetic and medicinal topics, as well as dental etiologies caused by metals, alloys of mercury and resins.

Eczema is a skin inflammatory reaction mediated by antigen-specific T cells. Two main disorders belong to this group: contact dermatitis and atopic dermatitis. The pathophysiological mecanisms involved in both disorders are similar and include, at the cellular level, three elements: the antigen (hapten or environmental antigen), antigen-presenting cells belonging to the group of dendritic cells and antigen-specific T cells. The Langerhans cell responsible for antigen handling and presentation to specific T cells appears to play a central role for the generation of the inflammatory reaction.

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS syndrome) or the drug hypersensitivity syndrome is a delayed and serious skin disease. It is manifest by a severe skin reaction associated with a severe visceral attack (adenopathy, hepatitis, nephritis, interstitial pneumopathy...) and haematological anomalies (raised hypereosinophilia...). The severe visceral attack is the main cause of death, which is estimated at around 10%. The principal drugs responsible are the aromatic anti-convulsants, sulphamides and minocycline. A large number of cases have been described with phenytoin, more rarely with carbamazepine and phenobarbitone.

Delayed type hypersensitivity (DTH) to Candida albicans is commonly observed in human. Abnormal DTH has already been described but its diagnosis is difficult to ascertain. We present now a clinical and biological study in 60 patients with a clear distinction between these two kind of Candida albicans DTH. Clinical abnormal Candida albicans DTH was characterized by a syndromic reaction 24 to 48 hours after intradermal injection. This reaction was characterized by an exacerbation of clinical symptoms. In vitro, activation of whole blood with Candida albicans antigen was detected by using flow cytometry after staining for activating markers. CD 25 positive T cells were detected in a 7 days culture in all patients. Percentage of CD 25 positive T cells was correlated to the intensity of the local cutaneous DTH reaction. CD 69 positive T cells were detected after a one day culture only in patient who presented a syndromic reaction to intradermal injection.

Cockroach and house dust mites (Dermatophagoides pteronyssinus, Dp and farinae, Df) are the most often implicated aeroallergens in severe asthma, hay fever and conjunctivitis. Cockroach allergy is still unknown in atopic dermatitis.146 children with atopic dermatitis-aged 6 months to 15 years- have been patch tested with the European standard series and some aeroallergens. We have studied the sensitisation to cockroach allergens and compared to Dp and Df.113 children reacted positively at least to one of the 3 aeroallergens (77 p. 100), 61 children had a positive reaction to cockroach (42 p. 100) and 29 simultaneously to the 3 allergens.Delayed hypersensitivity to house dust mites in young children with atopic dermatitis suggests early epicutaneous sensitization due to an altered epidermal barrier. For us, cockroach could also be implicated in some flare-ups of atopic dermatitis. Eviction of cockroach and house dust mite should be proposed for children with a positive patch test to cockroach.

Melaleuca alternifolia is a coniferous tree found in tropical regions, the needles contain an essential oil that is used in medical and cosmetic products. The essential oil contains turpentines (limonene, alpha-pinene, phellandrene) that are potentially allergenic.In 1997, 1216 patients were patch tested in our dermatoligic unit. Fourteen of them tested because of eczema used products containing tea tree oil. The patients used creams, hair products and essential oils containing Melaleuca alternifolia for cosmetic reasons and to treat skin affections. They were patch tested for a standard panel of allergens, topical emulgators, perfumes, plants, topical medications, metal, gloves, topical disinfectants and preservatives, dental products and rubber derivatives. Products containing Melaleuca alternifolia were tested concentrated or diluted.We report on 7 cases of patients with an allergic contact dermatitis due to tea tree oil. Two of them also exhibited from a delayed type IV hypersensitivity towards fragrance-mix or colophony suggesting the possibility of cross reaction or an allergic group reaction caused by contamination of the colophony with the volatile fraction of turpentines.The allergic potential of low concentrations of Melaleuca alternifolia is presumed to be low on healthy skin. Photoaged Melaleuca alternifolia must be considered to be a stronger sensitizer.

Due to cross-reactions between unfractionated heparins, low-molecular-weight heparins and sometimes heparinoids, cutaneous delayed hypersensitivity reactions might be a problem for the choice of therapeutic alternative. We report on two cases of sensitization to heparins and heparinoids.One woman developed localized skin reaction to a low-molecular-weight heparin, then a generalized maculopapular rash when an intravenous injection of unfractionated heparins was performed. The second patient had a localized then extended reaction to a low-molecular-weight heparin and was referred for the choice of a well tolerated method to obtain anticoagulation during a pulmonary surgery.Patch tests, prick tests, intradermal and subcutaneous tests were performed with several unfractionated heparins, low-molecular-weight heparins, danaparoid and lepirudin in both cases.In the first case, tests performed with both heparins and heparinoid were positive and the use of lepirudin was proposed if anticoagulation was necessary. In the second case the subcutaneous danaparoid injection induced a localized reaction on the injection site. Danaparoid injections were continued associated with localized applications of dermocorticoids without any side effect.Cutaneous delayed hypersensitivity reactions occur on the injection site but can also be generalised. Cross reactions might be unexpected therefore skin-tests are necessary to guide the choice of a therapeutic alternative. In case of intolerance to both heparins and heparinoids various solutions may be proposed such as the application of topical corticosteroids on the injection site or the administration of hirudins. There is no cross sensitization between heparins and hirudins, but the use of hirudins is restricted and requires specific monitoring.

Mantoux test expresses a delayed hypersensitivity induced after either BCG vaccination or a BK contact. In France, a purified protein fraction is used. The quality of technique and lecture are essential. The lowest positivity limit is5 mm. Sensitivity and specificity are imperfect. For the interpretation of positivity, the most important factors are the age of vaccination (the younger the child is, the lower the reaction is) and the infection prevalence rate in the group considered (the lowest it is, the highest a criteria may be used for induration15 mm). The background is most important for interpretation. The main situations are a postvaccinal test, a diagnosis of infection (or illness) or the environment of a contagious adult. A lot of situations are less clear and require the knowing of a risk factor (risk people, contagion...). In spite of these limits, Mantoux test is the only valid technique, useful when considered with other points: collective (prevalence of the illness in some groups) or individual (contagion, clinical or radiological signs...).

Ethyl alcohol sensitization is rare and can induce immediate contact urticaria or delayed eczema. Patch tests performed with ethanol can provoke an irritative reaction and are not well codified.We report on 4 cases of contact dermatitis due to alcohol in 4 women. Eczema was due to alcohol contained in the reservoir of a transdermal transfer system with estrogens in 2 cases and related to the application of alcoholized antiseptic lotions in the other 2 cases. In 2/4 cases we observed a co-sensitization with corticosteroids.Patch tests were performed with alcohol at 95 degrees diluted at 70 p. 100 and at 10 p. 100 in water and read after 20 minutes then on day 2 and day 4.Positive results were obtained in 4/4 cases when alcohol was tested diluted at 70 p. 100 in water and in 3/4 cases when diluted at 10 p. 100 in water. No irritant reaction was observed in 140 negative controls.Immediate after 20 minutes and delayed readings of patch tests performed with ethyl alcohol diluted at 70 p. 100 seem to be convenient in diagnosing cutaneous delayed hypersensitivity to alcohol. Co-sensitization between corticosteroids and alcohol could be due to an aldehyde deshydrogenase deficiency.

Prescriptions of tamoxifen can be expected to increase over the next few years, particularly for primary prevention of breast cancer. We report a case of a delayed tamoxifen-induced skin reaction.A 50-year-old woman was hospitalized for a diffuse maculopapulous eruption which developed four months after beginning a tamoxifen regimen instituted to prevent recurrence of breast cancer after surgery, chemotherapy and radiotherapy. The eruption resolved rapidly after withdrawal of tamoxifen. The same skin reaction occurred 9 hours after rechallenge with tamoxifen. Patch tests performed later with Nolvadex tablets crushed in vaseline were negative.Tamoxifen-induced skin reactions are uncommon. The likelihood that tamoxifen was the cause in this case was very high (C3S3 = I4, B2). The late onset (4 months) in this case is remarkable and misled us to look for another cause which could not be found. Challenge with tamoxifen confirmed its causal role. Once again, negative patch tests were found in this type of skin reaction.

Chronic urticaria has multiple etiologies, amongst them food allergy, which is not the most frequent. We report a clinical case of chronic urticaria due to cow milk, where paradoxically the responsibility of the food was shown by an epidermo test when the prick test was negative. Development confirmed the responsibility of cow milk. We discuss the mechanisms that relate chronic urticaria to delayed hypersensitivity.

The task of the immune system consists of destroying foreign structures in order to prevent the invasion of living organisms by pathogens. This destruction often provokes adverse effects defined as hypersensitivity reactions. The classification of hypersensitivity reactions proposed by Gell and Coombs is based on effector mechanisms. Although this framework remains largely used, recent work demonstrated the occurrence of profound similarities between different classes of hypersensitivity reactions. Indeed, all these reactions involve the activation of adhesion mechanisms intended to allow the local recruitment of blood leukocytes and cytokine production. The concept of a separation between two different modes of immune response induced by two different T lymphocyte subpopulations (TH1 and TH2) proved useful in understanding hypersensitivity reactions, although it represents only an approximation. Recent results were an incentive to develop new diagnostic and therapeutic strategies whose usefulness will be evaluated in the near future.

Though most often asymptomatic, tuberculous infection induces a delayed hypersensitivity reaction in the host by activating cellular immunity thus rendering the host refractory, "a priori", to a new infection; at least provided that the infecting dose is not massive or that the immune system of the host is not compromised. Less that ten per cent of immuno-competent individuals infected by Mycobacterium tuberculosis will develop tuberculous disease during their life. The intradermal reaction (IDR to tuberculin) in revealing delayed hypersensitivity to Mycobacterial antigens is in the absence of obvious signs, the only means of diagnosing a tuberculous infection in an individual. It is performed in France by an intradermal injection of 0.1 mls (10 U) of Merieux tuberculin. The response is read at 72 hours. In those who have not had BCG vaccination, an area of induration with a diameter of greater than or equal to 10 mm gives a positive result and is evidence of a tuberculous infection. The test is negative if the diameter is less than 5 mm and indeterminate between 5 and 9 mm. These indeterminate reactions may be the consequence of previous BCG vaccination or of a contact with atypical Mycobacteria in the environment. An IDR of greater than or equal to 10 mm less than ten years after BCG vaccination would not permit any discrimination between a reaction to the vaccine or an authentic tuberculous infection. On the other hand, an IDR of greater than 10 mm ten years after BCG vaccination is evidence of renewed contact with wild tubercle bacilli in 88 per cent of cases. In individuals whose immune defence is altered in particular in patients infected with HIV the threshold of positivity for IDR is lowered to 5 mm.

By measuring the activation of different cell models (lymphocytes and lymphocytic subsets) in the presence of Candida albicans with flow cytometry reading, it is possible to show that successive dilutions of Candida albicans can lead to lymphocyte activation in abnormally-sensitized subjects. In a first trial, 10 subjects were tested in duplicate. The decrease of activity of the dilutions does not appear to be regular in relation to the progression of the dilutions. The activity of the dilutions wanes relatively rapidly with the first dilutions, then recurs later very distinctly, at the 6th dilution, then ebbs, then reappears in similar manner at the 9th, the 14th, and finally, the 19th dilution. Cell reactivity appears to differ depending on the subject. It can be represented through the calculated slope of the regression line, for each series of data. It therefore appears feasible to determine a threshold of reactivity and a scale of sensitivity, to make it possible to specify the degree of abnormal reactivity existing at a given time for a given subject. The constancy of the activity of the different dilutions tested, on 10 cultures of a single cell suspension, is especially well demonstrated in the second trial, showing unusually small standard deviations. Thus, the question arises as to the exact nature of the observed phenomenon and of its analysis from a physical-chemical point of view, with regard to the pharmacological effect of successive dilutions of Candida albicans.

Abnormal delayed-type hypersensitivy to Candida albicans, since it results in an excessive reaction of the immune system, is very difficult to diagnose. This study shows that the syndromic reaction observed after intradermal injection of an extract of Candida albicans, in patients suspected of abnormal delayed-type hypersensitivy to this antigen, is associated with the presence of specific circulating T cells, detectable through cell culture in the presence of Candida albicans. There is a very significant correlation between the clinical symptoms, the cutaneous tests, and the lymphocyte activation tests. This abnormal reactivity essentially involves the CD8 cells.