Specific Skin Reactions Research Articles

Subcutaneous allergen immunotherapy for asthma: A randomized, double-blind, placebo-controlled study with a standardized Blomia tropicalis vaccine

BackgroundSensitization to Blomia tropicalis (Bt) is very frequent in the tropics, and particularly in Cuba, being a significant cause of allergic asthma. Allergen immunotherapy (AIT) with Bt can be a therapeutic option, however, placebo-controlled clinical trials have not been reported. ObjectiveTo assess the therapeutic effect and safety of AIT for asthma using a standardized allergen vaccine of B. tropicalis by subcutaneous route, in allergic asthmatic patients exposed and sensitized to this mite species. MethodsA double-blind, placebo-controlled Phase II trial was conducted in 35 adults (18 with treatment and 17 with placebo), with mild to moderate asthma, predominantly sensitized to Bt. AIT was administered subcutaneously in increasing doses from 4 to 6000 Biological Units using a locally manufactured standardized extract (BIOCEN, Cuba). Patient assessment was performed using symptom-medication score (SMS), peak expiratory flow and skin reactivity relative to Histamine as measured by skin prick test (SPT). ResultsThe 12-month treatment achieved a significant (p < 0.001) decrease of SMS. Symptom score showed only 41% (CI: 26–61) of placebo values, whereas medication was 34.5% (22.4%–63.3%). Treatment was regarded clinically effective in 67% of patients (OR 32; 95%CI: 17 to 102). The effect size on symptoms and medication was higher than has been reported with equivalent allergen dosages of D. pteronyssinus and D. siboney in Cuban asthmatic patients. Skin reactivity to Bt was also significantly reduced (p = 0.0001), increasing 148-fold the allergen threshold to elicit a positive skin test. This desensitization effect was specific to Bt and did not modify the reactivity to Dermatophagoides. The change of specific skin reactivity was significantly (p < 0.05) correlated to clinical improvement. All adverse events were local with a frequency of 2.4% of injections. ConclusionsSubcutaneous AIT with Blomia tropicalis was effective and safe in asthmatic adults exposed and sensitized to this mite species in a tropical environment. Trial registrationCuban Public Registry of Clinical Trials: RPCEC00000026 (WHO International Clinical Trial Registry Platform ICTRP).

P.2.a.009 - Visuospatial planning in unmedicated major depressive and bipolar disorder: distinct and common neural correlates

This study analyzed in vivo antiviral cellular immune reactions in the Shope rabbit papilloma – carcinoma model. Antigens studied in experimentally infected domestic rabbits were cottontail rabbit papillomavirus particles produced with the athymic (nu/nu) mouse xenograft system and bacterial fusion proteins containing the major or minor capsid protein. Recall reactions to antigens were tested by classic intracutaneous tests. Positive reactions had a biphasic course. Histopathology of skin test biopsy specimens showed infiltrating polymorphonuclear cells during the early stages. Later they were replaced by predominantly perivascular infiltrates composed of mononuclear cells. Time course of swelling and infiltrates resembled a delayed-type hypersensitivity reaction. Ten of 11 regressor rabbits (p = 0.00006) and 10 of 20 progressors (p = 0.009) had positive skin tests with intact and/or denaturated virus particles and individual capsid proteins also could elicit specific skin reactions. Skin reactivity to the cottontail rabbit papillomavirus particles was also greater (p = 0.042) in regressor rabbits (8 of 11) when compared to progressors (7 of 20). Recall reactions remained detectable at post-regression times, ranging from several months up to more than 2 years. We conclude that specific skin reactions against the cottontail rabbit papillomavirus in infected domestic rabbits exist, and are strongly positive to intact particles of this papillomavirus in animals (regressors) clinically free of disease.

Érythème pigmenté fixe secondaire à la prise d’éthambutol

Fixed drug eruption (FDE) is a specific skin reaction and the only exclusively medicinal dermatosis. Among the drugs usually responsible are the antituberculous antibiotics including rifampicin and, less often, isoniazid and pyrazinamide. FDE after taking ethambutol is rarely described. A 32-year old HIV negative patient presented a FDE localized to the internal surface of the lips and the interdigital folds during the 4th month of antituberculous treatment comprising rifampicin, isoniazid and ethambutol. The diagnosis was supported by the characteristic appearances of the lesions of FDE and their early reappearance in the same areas after accidental reintroduction of antituberculous triple therapy including ethambutol. Double-agent therapy with rifamicin and isoniazid was tolerated well. Discovery of FDE requires a rigorous search for the responsible medicine. During antituberculous treatment, the practitioner has to bear in mind the potential role of ethambutol, which is possibly potentiated by rifampicin.

Antiulcer drugs promote oral sensitization and hypersensitivity to hazelnut allergens in BALB/c mice and humans

Hazelnut allergy can be a consequence of sensitization to cross-reactive pollen, especially from the Fagales family. However, severe allergic reactions after ingestion of hazelnuts without associated pollen allergy have been reported. In these cases, oral sensitization by hazelnut ingestion is plausible. We have reported that antiulcer drugs promote oral sensitization to digestion-labile food allergens. Because hazelnut proteins were sensitive to gastric digestion in our in vitro assay, we aimed to analyze the effect of antiulcer treatment on oral sensitization to hazelnut proteins. BALB/c mice were fed hazelnut extract with or without antiulcer drugs. In parallel, gastroenterologic patients (n = 153) were screened during antiulcer treatment for specific immunoglobulin (Ig) E to hazelnut and inhalative allergens in vitro and in vivo. Mice fed hazelnut extract in combination with antiulcer drugs formed anaphylactogenic IgG1 toward hazelnut and developed type I skin reactivity to hazelnut extract. In the human study population, 5 of 153 (3.3%) patients developed hazelnut-specific IgE, 4 of 5 developed specific skin reactivity, 3 of 5 had a positive result to oral provocation, and 2 of 5 manifested a food allergy to hazelnut after a 3-mo course of antiulcer treatment. Immunoblot testing with recombinant allergens showed that hazelnut, but not Fagales pollen, was the genuine elicitor in mice and humans. Our experimental and epidemiologic data suggest that the intake of antiulcer drugs may lead to the induction of immediate-type food hypersensitivity toward hazelnut.

Skin Reactions in Patients with Influenza Treated with Oseltamivir: A Retrospective Cohort Study

Oseltamivir phosphate is an FDA-approved treatment for influenza that has been available for prescription use in the USA since 1999. The present report describes findings from a post-marketing safety study of skin reactions associated with oseltamivir use. All patients in the claims-derived Ingenix Research Database with a physician diagnosis of influenza and/or a dispensing of oseltamivir between 1 December 1999 and 31 March 2002 were identified. Cohort eligibility criteria included minimum baseline enrolment duration of 3 months, age of at least 1 year and no influenza vaccination on the date of influenza diagnosis or oseltamivir dispensing. Patients were classified into two primary cohorts, influenza diagnosis and oseltamivir dispensing on the same day, and influenza diagnosis but no oseltamivir at any time, and a cohort included for secondary analyses comprising patients who received an oseltamivir dispensing without an influenza diagnosis on the same day. Outcomes included general skin reactions and several specific skin reactions. Events occurring during the 30 days following the date of influenza diagnosis or oseltamivir dispensing were examined using Cox proportional hazards models. Model covariates included age, use of another influenza drug, month and year of index date, and use of antitussives. Adjusted rate ratios for the general class of skin reactions among the primary cohort of oseltamivir users versus non-users were 1.05 (95% CI: 0.88-1.24) for incident cases and 0.98 (95% CI: 0.77-1.24) among patients with a history of a skin reaction. Similar results were seen for the other skin reaction categories, and secondary analyses investigating the oseltamivir users without influenza revealed no elevation in risk. It is concluded that oseltamivir use does not appear to be associated with an increased risk of skin reactions.

IgE-binding proliferative responses and skin test reactivity to Cop c 1, the first recombinant allergen from the basidiomycete Coprinus comatus

Background: Basidiomycetes spores are ubiquitously distributed, found throughout the year in outdoor and indoor air, and represent relevant sources of aeroallergens associated with allergy and asthma. Objective: Cloning and characterization of Coprinus comatus (shaggy cap mushroom) allergens is essential to elucidate their molecular characteristics and to improve the diagnosis of allergy. Methods: A complementary DNA (cDNA) library of C comatus displayed on phage surface was screened with sera of basidiomycete-sensitized individuals. Subcloning and high-level expression of one of the enriched cDNAs allowed the isolation of a [His] 6-tagged recombinant protein formally termed rCop c 1. The allergenic properties of rCop c 1 were investigated in vitro by ELISA, inhibition experiments, immunoblots, and proliferation assays and in vivo by skin tests. Results: The rCop c 1–encoding cDNA spans 435 bp and contains an open reading frame of 246 bp, predicting a protein of 8.96 kd without significant sequence homology to known proteins. Immunoblots with [His] 6–rCop c 1 fusion protein show a background free IgE-binding band of the expected size that can be completely inhibited by crude C comatus extracts in ELISA. rCop c 1 induced specific proliferative responses in PBMCs of C comatus–sensitized individuals. The incidence of sensitization to rCop c 1 among 92 sera of basidiomycete-sensitized individuals tested in ELISA was 25%, indicating that Cop c 1 is an intermediate allergen. However, prick tests showed that less than 2 pmol of the rCop c 1 protein was able to induce strong specific skin reactions in sensitized individuals. Conclusions: rCop c 1, the first cloned allergen from the genus Coprinus, fulfills all the criteria required to be classified as a clinically relevant allergen. The data demonstrate at the molecular level the presence of sensitizing molecules among Basidiomycetes, the most important source contributing to the total spore load in the outdoor air. (J Allergy Clin Immunol 1999;104:630-6.)

Unilateral laterothoracic exanthem: A clinicopathologic study of forty-eight patients

Background: Four years ago, we began seeing young children with an unusual, predominantly unilateral, morbilliform and eczematous, self-limited cutaneous eruption. It appeared to correspond to unilateral laterothoracic exanthem (ULE) reported from France and to an eruption described as “a new papular erythema of childhood” in the United States. Objective: We conducted a prospective study of ULE to define its clinical evolution, pathology, and therapy. In addition, we performed epidemiologic and microbiologic investigations in an attempt to determine the cause of ULE. Method: We studied 48 children with ULE. In some patients, blood, urine, stool, as well as skin biopsy specimens were analyzed. Results: ULE is a morbilliform, eczematous eruption that often begins close to the axilla and spreads to become bilateral, although it usually retains a unilateral predominance. Patients' mean age at onset is 24.3 months, with a female predominance (2:1) and mean duration of 5 weeks, followed by spontaneous resolution that may or may not be improved with topical corticosteroids. It is characterized by a unique eccrine lymphocytic infiltration. Although signs of infection were reported by most patients, no one infectious agent was identified. No significant epidemiologic factor was found. Conclusion: ULE, in young children, is a self-limited morbilliform and scarlatiniform eruption that may represent a specific skin reaction to one or more infectious agents.

Skin Test to Assess Immunity Against Cottontail Rabbit Papillomavirus Antigens in Rabbits with Progressing Papillomas or After Papilloma Regression

This study analyzed in vivo antiviral cellular immune reactions in the Shope rabbit papilloma-carcinoma model. Antigens studied in experimentally infected domestic rabbits were cottontail rabbit papillomavirus particles produced with the athymic (nu/nu) mouse xenograft system and bacterial fusion proteins containing the major or minor capsid protein. Recall reactions to antigens were tested by classic intracutaneous tests. Positive reactions had a biphasic course. Histopathology of skin test biopsy specimens showed infiltrating polymorphonuclear cells during the early stages. Later they were replaced by predominantly perivascular infiltrates composed of mononuclear cells. Time course of swelling and infiltrates resembled a delayed-type hypersensitivity reaction. Ten of 11 regressor rabbits (p = 0.00006) and 10 of 20 progressors (p = 0.009) had positive skin tests with intact and/or denaturated virus particles and individual capsid proteins also could elicit specific skin reactions. Skin reactivity to the cottontail rabbit papillomavirus particles was also greater (p = 0.042) in regressor rabbits (8 of 11) when compared to progressors (7 of 20). Recall reactions remained detectable at post-regression times, ranging from several months up to more than 2 years. We conclude that specific skin reactions against the cottontail rabbit papillomavirus in infected domestic rabbits exist, and are strongly positive to intact particles of this papillomavirus in animals (regressors) clinically free of disease.

Changes in skin reactivity, specific IgE and IgG levels after one year of immunotherapy in olive pollinosis

Changes in specific skin reactivity, specific IgE and specific IgG after immunotherapy (IT) were investigated in olive pollinosis. Thirty patients, receiving IT with commercial extracts, were studied in comparison with a control group of seven patients, receiving only drug therapy. Skin reactivity, IgE and IgG were assessed before starting IT and 1 year later. Definite changes in the three considered parameters occurred in patients given IT with Olea europaea extracts; no variation was observed in the control group. The specific skin reactivity, evaluated by means of quantitative skin prick tests, significantly decreased (Skin Index geometrical mean from 2.73 to 0.88, P less than 0.001); the specific IgE, measured by RAST, were surprisingly decreased (from 7.76 to 4.74 PRU/ml, P less than 0.001); the specific IgG, measured by ELISA, in basic conditions were detectable only in nine patients of 30, while, after IT, they were found in almost all patients with a remarkable increase (from 5.48 to 266.89 AU/ml, P less than 0.001). No correlation was found among the changes in the considered parameters, suggesting that, at least in olive pollinosis, specific skin reactivity, specific IgE and specific IgG are three variables depending on IT but reciprocally independent.

Changes in skin reactivity, specific IgE and IgG levels after one year of immunotherapy in olive pollinosis

Changes in specific skin reactivity, specific IgE and specific IgG after immunotherapy (IT) were investigated in olive pollinosis. Thirty patients, receiving IT with commercial extracts, were studied in comparison with a control group of seven patients, receiving only drug therapy. Skin reactivity, IgE and IgG were assessed before starting IT and 1 year later. Definite changes in the three considered parameters occurred in patients given IT with Olea europaea extracts; no variation was observed in the control group. The specific skin reactivity, evaluated by means of quantitative skin prick tests, significantly decreased (Skin Index geometrical mean from 2.73 to 0.88, P &lt; 0.001); the specific IgE, measured by RAST, were surprisingly decreased (from 7.76 to 4.74 PRU/ml, P &lt; 0.001); the specific IgG, measured by ELISA, in basic conditions were detectable only in nine patients of 30, while, after IT, they were found in almost all patients with a remarkable increase (from 5.48 to 266.89 AU/ml, P &lt; 0.001). No correlation was found among the changes in the considered parameters, suggesting that, at least in olive pollinosis, specific skin reactivity, specific IgE and specific IgG are three variables depending on IT but reciprocally independent.

Lung function, atopy, specific hypersensitivity, and smoking of workers in the enzyme detergent industry over 11 years.

A study of 2800 workers employed in three factories of the two major manufacturers of enzymatic products in the United Kingdom covering 11 years of operation from 1969 to 1980 showed that 2344 workers had sufficient lung function data to meet the operational criteria and these were analysed in three separate groups by factory locations. Spirometry and prick tests for specific skin reactions to standardised enzyme were performed at six monthly intervals for the first six years of the study and then annually. Factory enzyme dust and total dust measurements were made to determine the degree of dust exposure of the subjects. The lung function of the factory groups was analysed for the effects of working in the detergent industry, the degree of exposure to enzymes, skin prick test positivity to enzymes, atopicity, and smoking. The 4.5% of workers who had experienced respiratory effects from enzymes were analysed separately. Exposure to the enzyme allergen has had no significant long term effect on the lung function of the detergent workers. A higher proportion of atopics than non-atopics became skin test positive to the allergen and more smokers than non-smokers were sensitised. The overall lung function of detergent workers showed 39 ml/year loss in FEV1 on the 11 year longitudinal study and 51 ml/year loss on the lateral (cross sectional) analysis with better lung function in the south east than the north west of England. In the development of the methodology for the study several potential problems were discovered that could remain unrecognised in a cross sectional analysis performed in isolation.

Variations in cell-mediated immunity to Trypanosoma cruzi during experimental Chagas' disease.

Mice infected with bloodstream forms of Trypanosoma cruzi were found unable to respond significantly to subcutaneous stimulation with parasite antigens with a delayed-type hypersensitivity skin reaction during the acute phase of the disease. Consistent with this observation, peritoneal cells collected from infected mice during the acute period were unresponsive in in vitro assays for production of macrophage migration inhibitory factor. By contrast, both specific skin reactivity and significant inhibition of macrophage migration were noted during the chronic stage, i.e. when parasitaemias were on the decline or undetectable and mortality no longer occurred. Given the similarity between the kinetic changes in cell-mediated immunity monitored by in vivo tests and their in vitro correlate, the latter was used to explore the possible role of suppressor T cells in the causation of immunodeficiency recorded during the acute phase. Peritoneal cells from acutely infected animals failed to alter production of macr...

Salmonella typhimurium infection in calves: delayed specific skin reactions directed against the O-antigenic polysaccharide chain.

Specific delayed skin reactions developed after intradermal injection of Salmonella typhimurium lipopolysaccharide in 12-week-old calves which had been orally infected with S. typhimurium 5 weeks earlier. Uninfected calves showed no delayed skin reactions. Skin biopsies from skin swellings showed a massive infiltration of mononuclear cells in the skin of infected calves but not in those of uninfected calves. Persistence of infection in infected calves was confirmed by isolation of S. typhimurium from fecal specimens. The delayed skin reactions could be shown to be specific and directed against the O-polysaccharide chain of the lipopolysaccharide since none of the lipopolysaccharide chain of the lipopolysaccharide since none of the lipopolysaccharide preparations from a rough mutant of S. typhimurium, two strains with different O-polysaccharide chains, or lipid A elicited skin reactivity. To cause a reaction, the O-polysaccharide had to be in a macromolecular complex, since skin swellings were seen only after injections of either O-polysaccharide chains cross-linked by 1,2,3,4-diepoxybutane or octasaccharides from the O chain covalently linked to a straight 12-carbon aliphatic chain forming an artificial glycolipid. Injection of the pure octasaccharides of O-polysaccharide chains failed to elicit delayed skin reactions.

Skin test as herd diagnosis for Aujeszky's disease (Pseudorabies) in swine

Summary The value of a skin test for the diagnosis of Aujeszky's disease (pseudorabies) in swine was examined. Semipurified and concentrated antigens, obtained by ether/tween 80 inactivation of Aujeszky's disease virus, were inoculated intradermally into seronegative, experimentally infected and vaccinated swine and into pigs with maternal antibodies. A specific skin reaction, characterized by a visible indurated swelling, was observed within 24 hours in animals with active immunity, No reaction was seen in pigs with maternal immunity or in seronegative uninfected and unvaccinated animals. In the infected and vaccinated groups, 89% and 58% respectively of the animals with seroneutralizing antibodies were positive by the skin test response. Positive reactions were observed as early as 8 days after the infection. All but one seronegative animals remained free of antibodies after 2 consecutive skin tests and the course of decline of maternal antibodies was not changed. An earlier skin test did not lead to sensitization for a later application. The present results, together with field experience on 8 farms, revealed that the skin test could be considered a reliable method for diagnosis of Aujeszky's disease in swine on a herd basis.

IMMUNOCHEMOTHERAPY OF LUNG CANCER*

After surgical resection of their primary lung cancer, 33 patients were randomized into one of three groups. The first received high-dose methotrexate once per month with citrovorum rescue, for 3 months. The second group were immunized monthly with a homogenate of Freund's complete adjuvant and carefully characterized soluble antigen derived from allogeneic lung cancer cells of appropriate histology, for 3 months. The third group received a combination of methotrexate and immunization monthly, for 3 months. Each patient was monitored immunologically before, during, and after the treatment period, by use of delayed hypersensitivity reactions to recall and cancer antigens, in vitro lymphocyte response to mitogens, and mixed lymphocyte blocking factor activity. The group that received methotrexate showed little change in skin reactivity, a reduction of blocking factor activity, and significant rebound overshoot in in vitro lymphocyte performance. The immunized group showed a tendency to production of blocking factor activity, striking conversion and enhancement of skin reactivity, and little change in in vitro lymphocyte performance. The immunochemotherapy group showed dramatic increases in specific skin reactivity to cancer antigens, up to 2 years after treatment, in vitro lymphocyte rebound overshoot, and reduction of blocking factor activity production. Classic life table analysis of the probability of freedom from metastases in patients with stage-I cancer indicate that the disease-free interval in patients who received methotrexate is longer than in historic and concomitant controls but not as long as in those who received immunization. The best group appear to be those who received combination immunochemotherapy. We emphasize that the small numbers in this pilot study do not yet allow firm conclusions to be made.

Allescheria boydii and Aspergillus fumigatus skin test antigens.

May, Lewis K. (Woman's Medical College of Pennsylvania, Philadelphia), Ralph A. Knight, and H. William Harris. Allescheria boydii and Aspergillus fumigatus skin test antigens. J. Bacteriol. 91:2155-2157. 1966.-Protein and polysaccharide fractions were extracted from culture filtrates of Allescheria boydii and Aspergillus fumigatus by the methods of Seibert and of Heidelberger, and injected intradermally into guinea pigs previously infected with these fungi. The diameter of erythema and induration was determined at 8, 24, and 48 hr. The protein and polysaccharide antigens yielded specific skin reactions in homologously infected guinea pigs. Erythema appeared at 8 hr with both the protein and polysaccharide antigens. At this time, the polysaccharide skin tests showed erythema and a central blanched wheal. A similar wheal was not observed with the protein. The erythema of the polysaccharide reaction began fading at 24 hr, whereas the protein reaction remained unchanged through 48 hr with both antigens. In guinea pigs, the area of erythema was more constant and thus easier to measure than was induration.

Delayed hypersensitivity. III. Specific desensitization of guinea pigs sensitized to protein antigens.

Guinea pigs rendered hypersensitive (delayed-type) to protein antigen can be completely and specifically desensitized by a single injection containing a sufficient amount of the corresponding antigen. Although 1 to 2 mg. of specific antigen are required for complete desensitization, as little as 20 microg. suffices to decrease the size of specific skin reactions in sensitized animals. The duration of non-reactivity lengthens as the amount of antigen in the desensitizing injection is increased, but skin reactivity eventually returns and is accompanied by the appearance of excess circulating antibody. Desensitization can be accomplished with the antigen-antibody complex as well as by "free" antigen. The appearance of delayed skin reactions can be prevented in fully sensitized animals by intravenous desensitization 2 or more hours after intradermal challenge or by simply skin testing with a desensitizing dose of specific antigen. Injection of a desensitizing dose of antigen into specifically sensitized animals also results in a transient anergic state, the implications of which are discussed.

A skin test for the diagnosis of pregnancy

T HE use of skin re’actions as an aid in clinical diagnosis of many conditions has long been recognized as a valuable proceldure. The Van Pirquet, Schick, Dick reactions and the use of various proteins intradermally for the purpose of detecting allergic sensitivity have all proved their clinical usefulness, There are so many biologic differences between pregnant and nonpregnant individuals that the possibility of being able to differentiate between these groups by means of a skin reaction to some antigen seemed not too remote. Falls and Bartlett,l in 1914, attempted to extract a protein from the placenta which might be used for this purpose. The results were unsatisfactory, due to the fact that the methods employed were not sufficiently refined to yield a pure protein as was hoped, but a mixture of proteins was obtained which led to nonspecific reactions. By using better methods of extraction and preparation of the placental proteins, Cohen and Freda attempted to produce precipitin reactions and specific skin reactions that might be useful diagnostically. When the precipitin reaction was tried, serum of known pregnant women reacted positively in about 7.5 per cent of the cases. The serum of males a,ud normal females did not react. Certain nonpregnant women with gynecologic pathology gave a rather high percentage of false positive reactions which nullified the usefulness of this method for practical diagnostic purposes. The use of placental tissue extracts in producing skin reactions was to some extent successful, since about 75 per cent of the patients tested by intradermal injections gave positive reactions if pregnancy existed and negative if no pregnancy were present. This result was in accord with the results reported by Esch,” Englehorn and Wintz,4 Gruskin5 and Schwartz6 who made similar tests have reported a higher percentage of correct diagnosis. The high percentage of false reactions (25 per cent) rendered the use of these procedures for diagnostic purposes useless, and so it was decided to try to find an antigen that would give more specific reactions. The possibility of using proteins extracted from breast tissue was suggested, since it was thought that during pregnancy the cells of the breast might secrete a protein of somewhat different compositiou than other body proteins. On further consideration this idea was rejected in favor of using colostrum which must contain the proteins produced by the breast in early pregnancy. By using this material the contamination of

Lymphogranuloma of the Colon

THE voluminous literature recently accumulated on the subject of venereal lymphogranuloma contains no specific reference to involvement of the supra-anal portions of the colon by this condition. It is the purpose of this paper to describe three such cases complicating known rectal involvement: two in the transverse colon and one extensively in the descending and sigmoid. History.—Copeland, as early as 1811, suspected the venereal origin of stricture of the rectum. The condition was established as a definite pathological entity by the publication, in 1913, of a monograph by the Frenchmen, Nicolas, Durand, and Favre. It remained for Frei, in 1925, to introduce a diagnostic skin test based on a specific skin reaction which immediately placed the differential diagnosis on a sound basis. In 1930, the disease was transmitted to animals (monkeys) by intracerebral inoculations by the Swedish scientists, Hellerström and Wassen. Levaditi later substituted the mouse as a more suitable animal for experimentation. In 1932, Wolf, Sulzberger, and Wise introduced the cutaneous test in this country. Etiology.—The disease is due to an unknown filtrable virus and its frequency varies directly with the degreee of sex hygiene rather than racial susceptibility. Venereal lymphogranuloma is not related to granuloma inguinale, another venereal disease consisting of chronic, luxuriant ulcers produced by Donovan's bodies. The disease produces definite systemic reactions such as fever, headaches, secondary anemia, hyperglobulinemia, high sedimentation rate, and anti-complementary Wassermann reactions, in addition to the long described local acute and chronic tissue responses. Pathology.—Involvement of the colon grossly occurs by the formation of a granuloma and microscopically by the usual picture seen in a chronic non-specific granulomatous reaction, there being no pathognomonic pathological picture in this disease. Pathogenesis.—The anatomical basis for the sequelæ of venereal lymphogranuloma of the rectum is mostly stasis due to the occlusion of the lymphatics by destruction of the lymph glands, resulting in ulceration, elephantiasis, and fistulæ formation which is responsible for the spread to the buttocks and other extensions upward, such as parametritis and peritonitis. Roentgen Diagnosis.—The disease is manifested roentgenographically in the rectum by the demonstration of either extensive exudative inflammation, stricture, or fistulæ formation, depending on the stage of the disease. The changes higher in the colon are similar, and when found associated with known rectal involvement, must be considered as due to the same etiology. It is not the province of this paper to enumerate the clinical diagnostic criteria for the rectal diagnosis (history, controlled Frei tests, biopsy, etc.) but, whenever a case so labelled clinically shows an associated colon lesion and further shows reactions to the Frei therapeutic antigen, the etiology is self-evident.

The direct skin test in allergy

1. 1. The skin of younger children and infants gives a greater response to trauma than does that of older individuals. This may be due to liberation of a toxic substance in the skin cells. 2. 2. Clinically this finding may interfere with the interpretation of specific allergy tests, particularly when the intracutaneous method is used. 3. 3. Specific skin reactions dependent on an antibody presence (reagin of Coca) are rare in infants under four months, regardless of sensitivity or contact with allergen. With increasing age, the antibody likewise increases, apparently following a general immunologic law. 4. 4. Skin tests may become negative following these conditions: 4.1. (a) Severe allergic reactions. 4.2. (b) Graded therapy. 4.3. (c) Freedom from contact. 4.4. (d) Epinephrin administration. Skin reaction may also fail because of faulty preparations of the test substances (allergens) or because of inability of the individual to form the skin test antibody, even though he is clinically sensitive.