Interleukin-18 serum level before and after intralesional immunotherapy with tuberculin purified protein derivative in patients with cutaneous and genital warts.

BACKGROUND: Several studies demonstrated the efficacy of intralesional purified protein derivative (PPD) immunotherapy in warts eradication. Nevertheless, the precise induced immune mechanisms are undetermined. Injected PPD is hypothesized to induce a delayed hypersensitivity reaction associated with cytokines release. Interleukin (IL)-18 has a major role in defense against viral infection via inducing interferon-γ release from T-helper 1 and natural killer (NK) cells. Moreover, IL-18 triggers Fas ligand expression on cytotoxic T cells and NK cells enhancing their cytotoxicity against virally infected cells. AIM: The aim of this study was to assess the role of IL-18 in the response to intralesional PPD injection in patients with warts. METHODS: The study included 25 patients with warts and 25 HCs. Patients underwent PPD skin test, and only patients with positive tests were included and received intralesional PPD injections starting 72 h after the test then every 2 weeks until wart clearance or a maximum of 3 sessions. Serum IL-18 level was measured via enzyme-linked immune-sorbent assay in patients (pre-treatment and 2 weeks after the last injection) and HCs. RESULTS: After 3 sessions of injection, six (24%) patients were designated responders, nine (36%) patients showed partial response, and 10 (40%) patients were designated non-responders. Serum IL-18 level, post-treatment, was significantly higher than pre-treatment level (p = 0.025) and level in HCs (p = 0.036). Furthermore, the post-treatment level was significantly higher in responders than non-responders (p = 0.025). CONCLUSION: IL-18 is probably implicated in the immune mechanisms induced by PPD injection that cause eradication of warts.

A comparative study of topical cantharidin and intralesional PPD to treat molluscum contagiosum.

Background: The immune system plays an important part in the clearance of molluscum contagiosum (MC) and, therefore, there has lately been a trend in using immunotherapy in MC therapy. Tuberculin-purified protein derivatives (PPDs) and topical cantharidin have not earlier been compared with their effectiveness in therapyAim: The aim of this research was to determine the effectiveness and security of intralesional immunotherapy in the therapy of MC with tuberculin PPD versus topical cantharidinPatients and methods: Twenty patients with various MC lesions received topical cantharidin as control (group A) and 20 MC patients received intralesional tuberculin PPD following prior intradermal immunity tests (group B ).Results: Complete clearance of lesions was detected in 90.0% of patients in the cantharidin group; the partial response was detected in10.0% of the patients. However, in the PPD group, 85% of the patients showed a complete response and 15% showed a partial response, with no significant difference in the clinical response between the two groups. Mild side effects were detected .Conclusion: The results suggest that intralesional PPD and topical cantharidin 0.7% are effective and safe treatment modalities, but benefits of intralesional PPD is being a simple, effective and safe treatment with tolerable pain and can be an alternative treatment for multiple resistant types .

Efficacy and safety of single versus multiple intralesional immunotherapy with purified protein derivative (PPD) in the treatment of multiple verruca vulgaris.

BACKGROUND: Despite the numerous studies on the use of purified protein derivative (PPD), a protein extracted from Mycobacterium tuberculosis, in verruca vulgaris, there is no standardized regimen, and efficacy of single versus multiple injections has not been compared. METHODS: This is a randomized, open-label, superiority trial. Sixty-six patients with at least three warts in two different anatomic sites were randomized into two groups: a single injection (n = 29) and multiple injection (n = 29) groups. Patients were treated every 2 weeks until a maximum of six sessions. RESULTS: Multiple injections (79.3%) showed superior clearance rates compared to a single injection of PPD (58.6%) (P-value = 0.0236). Multiple injections also exhibited faster clearance at each time point (P = 0.048). Pain was statistically more significant in the multiple injection group (P = 0.0005). There was no statistically significant difference in incidence of adverse events (P = 0.1795). Amongst all cleared patients in both groups, there were no recurrences after 6 months. CONCLUSION: Multiple injections of warts with PPD cleared more patients with multiple common warts than the use of single injections at the end of 12 weeks and were faster in clearing patients at every time point. Single injection was better tolerated than multiple injections. Both treatments exhibited similar safety profiles and recurrence rates.

A double-blind, randomized controlled trial to compare the effectiveness and safety of purified protein derivative of tuberculin antigen with Mycobacterium w vaccine in the treatment of multiple viral warts.

BACKGROUND: Present day therapeutic modalities for viral warts are mostly ablative in nature, limited by high recurrence rates and are unsuitable for numerous lesions. Immunotherapy has the potential to overcome these limitations. AIMS: This study aimed at comparing efficacy and safety of and quality of life changes with intradermal purified protein derivative (PPD) of tuberculin antigen and Mycobacterium w (Mw) vaccine in immunotherapy of warts. METHODS: Patients with multiple (≥5) warts were randomized (1:1) into two groups (PPDand, Mw vaccine groups). Fortnightly, 0.1 ml of either medicine was injected intradermally over the deltoidregion till complete resolution or a maximum of six doses. Patients were followed-up for another 3 months for recurrence. RESULTS: Sixty-four participants received either PPD or Mw vaccine. The number of warts were comparable at baseline (P = 0.089, Mann-Whitney test), and reduced significantly with treatment in both groups (P < 0.001, Friedman's ANOVA), as seen from the fourth follow-up onwards with Mw and fifth follow-up onwards with PPD (P < 0.05, Post hoc Dunn's test). Intergroup comparison showed significantly more (P < 0.05, Mann-Whitney test) reduction with Mw than PPD at the sixth and seventh follow-up. The size of warts also reduced significantly (P < 0.001) in both groups from the third follow-up onwards. Complete remission was more (P = 0.539, Fischer's exact test) in the Mw group (68.8%) than the PPD group (50%); and was significantly higher (P = 0.049, Mann-Whitney test) in patients having shorter duration of warts. Adverse events were significantly more (P < 0.001) with Mw including ulceration (50%), discharge (15.6%), pain-swelling-induration and scar at the injection site (97% each), whereas some of those receiving PPD noted erythema and scaling at the injection site (18.8%), and post-inflammatory hyperpigmentation (12.5%). No recurrence was seen till the end of the study. LIMITATION: Unicentric trial. CONCLUSION: Intradermal injection of Mw vaccine was more effective but had a higher incidence of adverse effects compared to PPD of tuberculin antigen in patients with warts.

CD14-159C/T polymorphism in the development of delayed skin hypersensitivity to tuberculin.

The skin tuberculin test (TST), an example of a delayed-type hypersensitivity (DTH) reaction, is based on measuring the extent of skin induration to mycobacterial tuberculin (PPD). Little is known about the genetic basis of TST reactivity, widely used for diagnosing TB infection. The study investigated the relationship of the single base change polymorphic variants in CD14 gene (CD14(-159C/T)) with the development of DTH to PPD in BCG-vaccinated Polish Caucasian individuals. We found persistent lack of TST reactivity in about 40% of healthy subjects despite receiving more than one dose of BCG. The TST size was negatively correlated with the number of BCG inoculations. The distribution of C/T genotype was significantly more frequent among TST-negative compared with TST-positive individuals. The concentration of serum sCD14 was positively associated with mCD14 expression, but not with the TST status or CD14(-159C/T) polymorphism. A significant increase in mCD14 expression and serum sCD14 levels was found in TB group. We hypothesize that CD14(-159C/T) polymorphic variants might be one of genetic components in the response to attenuated M. bovis BCG bacilli.

Necrotic Tuberculin Skin (Mantoux) Test Reaction: A Case Report and an Estimation of Frequency.

Tuberculin skin testing was performed on a 5-year-old girl in Phnom Penh, Cambodia. She had been immunized by Bacille de Calmette et Guérin. She was tested because of a palpable cervical node and a slightly elevated temperature. Within 48 h, a deep necrotic lesion appeared on the volar aspect of the left arm. The lesion was treated locally, and the child was not treated for suspected TB. To our knowledge, this is the first instance of necrosis in 11,392 people who received Tubersol doses since 1996 to date at our International Vaccination Center, for an estimated incidence of 0.18 per 1,000 (95% Poisson 0.04-0.70 per 1,000 doses used). At a follow-up consultation after 77 days, the lesion had scarred and the child showed no signs suggestive of active TB. Although latent TB infection remains the most likely diagnosis, other types of mycobacterial infection may be considered in the tropical setting and in the absence of signs suggestive of active TB.

¿Trataremos la tuberculosis con vacunas en el siglo XXI ? / Will We Be Treating Tuberculosis With Vaccines in the XXI Century?

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Successful treatment of acute systemic anaphylaxis in a western lowland gorilla (Gorilla gorilla gorilla).

This brief communication describes the successful treatment of acute systemic anaphylaxis in a wild-born but captive infant western lowland gorilla (Gorilla gorilla gorilla) in the Republic of Congo. The infant demonstrated signs of acute respiratory distress, lingual swelling, and reaction to intradermal tuberculin, given 55 hr earlier. Details of the treatment with steroids, anesthetic induction, and i.v. epinephrine are all reported, and potential antigens that may have initiated the anaphylactic shock are discussed.

Measurement of CD4+ and CD8+ T-lymphocyte cytokine secretion and gene expression changes in p-phenylenediamine allergic patients and tolerant individuals.

Factors predisposing to individual susceptibility to contact allergic dermatitis are ill defined. This study was designed to characterize the response of allergic and tolerant individuals' T-lymphocytes after exposure to p-phenylenediamine (PPD). Peripheral blood mononuclear cells (PBMCs) from allergic patients proliferated when treated with PPD and Bandrowski's base (BB) and secreted IL-1alpha, -1beta, -4, -5, -6, -8, -10, and -13; IFN-gamma; tumor necrosis factor-alpha; MIP-1alpha/beta; MCP-1 (monocyte chemotactic protein-1); and RANTES. PBMCs from tolerant individuals were stimulated to proliferate only with BB, and they secreted significantly lower levels of Th2 cytokines. Principal component analysis showed that genes are differentially expressed between the patient groups. A network-based analysis of microarray data showed upregulation of T helper type 2 (Th2) gene pathways, including IL-9, in allergic patients, but a regulatory gene profile in tolerant individuals. Real-time PCR confirmed the observed increase in Th2 cytokine gene transcription in allergic patients. Purified CD4+ and CD8+ T cells from allergic patients were stimulated to proliferate and secrete Th2 cytokines following antigen exposure. Only CD4+ T cells from tolerant individuals were stimulated by BB, and levels of Th2 cytokines were 80% lower. The nature of the antigenic determinant stimulating PBMCs and levels of Th2 cytokines, including IL-9, was confirmed in a validation cohort. These studies show increased activity of Th2 cytokines in CD4+ and CD8+ T cells from individuals with allergic contact dermatitis.

Preventable mix-ups of tuberculin and vaccines: reports to the US Vaccine and Drug Safety Reporting Systems.

BACKGROUND: Errors involving the mix-up of tuberculin purified protein derivative (PPD) and vaccines leading to adverse reactions and unnecessary medical management have been reported previously. OBJECTIVES: To determine the frequency of PPD-vaccine mix-ups reported to the US Vaccine Adverse Event Reporting System (VAERS) and the Adverse Event Reporting System (AERS), characterize adverse events and clusters involving mix-ups and describe reported contributory factors. METHODS: We reviewed AERS reports from 1969 to 2005 and VAERS reports from 1990 to 2005. We defined a mix-up error event as an incident in which a single patient or a cluster of patients inadvertently received vaccine instead of a PPD product or received a PPD product instead of vaccine. We defined a cluster as inadvertent administration of PPD or vaccine products to more than one patient in the same facility within 1 month. RESULTS: Of 115 mix-up events identified, 101 involved inadvertent administration of vaccines instead of PPD. Product confusion involved PPD and multiple vaccines. The annual number of reported mix-ups increased from an average of one event per year in the early 1990s to an average of ten events per year in the early part of this decade. More than 240 adults and children were affected and the majority reported local injection site reactions. Four individuals were hospitalized (all recovered) after receiving the wrong products. Several patients were inappropriately started on tuberculosis prophylaxis as a result of a vaccine local reaction being interpreted as a positive tuberculin skin test. Reported potential contributory factors involved both system factors (e.g. similar packaging) and human errors (e.g. failure to read label before product administration). CONCLUSIONS: To prevent PPD-vaccine mix-ups, proper storage, handling and administration of vaccine and PPD products is necessary.

Psoriasis pustulosa generalizada inducida por prueba de la tuberculina / Generalized pustular psoriasis induced by tuberculin testing

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Urticaria and angioneurotic edema due to the temporary henna tattoo.

Temporary henna tattoo, which has become popular among young people, is obtained from the mixture of the plants Lawsonia alba or Lawsonia inermis and paraphenylenediamine (PPD). In forming reactions frequent development of anti-PPD substance is noticed. A 13-year old boy who started itching, erythema, enduration on the application area, increasingly urticarial rash, conjunctivitis and swelling of the lips 48 h after being applied the temporary henna tattoo was hospitalized. He had a local reaction to henna tattoo when he was 5-year old. He was treated with parenteral corticosteroids and oral antihistaminic drugs. Skin reactions persisted for 18 days. The patient showed no early reaction to henna 10% and PPD 1% concentration in saline solution but did late reaction (after 48 h) to PPD in diameter of 12x13 mm in prick test in 3 weeks after the reaction. A case who developed angioneurotic edema and urticaria to temporary henna tattoo noticed that the henna tattoo is not an innocent application and young people need to be informed on this subject.

Sex-related differences in tuberculin reaction, free and total testosterone concentrations in patients with autoimmune disorders and controls.

Earlier studies reported the associations among testosterone hormone, autoimmunity, and left-handedness. In the present study, sex differences in tuberculin reaction, a measure of cell-mediated hypersensitivity, serum free and total testosterone levels in controls and patients with autoimmune diseases were studied. There was a sex difference in right and left tuberculin reactions in controls, but not in patients. Both right and left tuberculin reactions were smaller in male and female patients than male and female controls. Free and total testosterone levels were higher in male controls than in male patients. Total testosterone levels were higher in female controls than in female patients. These results suggest that autoimmune diseases may be associated with a decrease in the blood testosterone concentrations.

Vaccination technique, PPD reaction and BCG scarring in a cohort of children born in Guinea-Bissau 2000-2002.

The rates of positive tuberculin skin test (TST) reactions and BCG scarring after BCG vaccination vary between studies and populations. Tuberculin reactivity and BCG scarring may be related to better child survival in low-income countries. We therefore studied determinants for TST reaction and scarring in Guinea-Bissau. In a cohort of children born in suburban Bissau from March 2000 to July 2002, we assessed a Mantoux test with Purified protein derivative (PPD) (SSI, 2 T.U.) at 2 (2689 children), 6 (N=2148) and 12 months (N=1638) of age, and BCG scar was assessed at 2 (N=2698) and 6 months (N=2225) of age. In a subgroup of the children the vaccination technique was monitored by direct observation of post-vaccination wheal and route of administration. Three different types of BCG vaccine supplied by the local Extended Programme on Immunization were used. At 6 months of age the rate of PPD reactors (>1mm) after BCG vaccination was 25% and the rate of scarring was 89%. One BCG strain was associated with fewer PPD reactors (OR=0.54 (0.31-0.91)) and BCG scars (OR=0.13 (0.05-0.37)) and larger post-vaccination wheals produced more PPD reactions (OR 1.21 (95% CI 1.02-1.43)) and BCG scars (OR 1.66 (1.24-2.21)). In the multivariable analyses of BCG-vaccinated children assessed at 6 months of age, monitoring of vaccination technique and type of BCG vaccine were important. This was not changed by control for other determinants, including sex, season, vaccination place, birthplace, ethnic group, low birth weight, place of residence, education and civil status of mother. We reason that vaccination technique and BCG strain are important for PPD reaction and scarring in response to BCG vaccination. Considering that these responses are associated with better infant survival, the importance of monitoring vaccination technique and of different BCG strains should be evaluated with respect to infant mortality.

[Infection of children with tuberculosis and the nature of tuberculin sensitivity in the infected]. / Infitsirovannost' tuberkulezom detei i kharakter tuberkulinovoi chuvstvitel'nosti u infitsirovannykh.

In the Kharkov Region, the rate of tuberculosis infection in children was 28.8%; among them children with a curve of tuberculin reactions was 3.8%; most of them had a moderate sensitivity to tuberculin. The remaining 71.2% of the examinees were not infected with tuberculosis; more than 50% of them (41.1%) had postvaccinal allergy.