Mercury-specific lymphocytes: an indication of mercury allergy in man.

In this study, 18 patients with oral lichen planus (OLP), adjacent to amalgam fillings, were tested in vitro with an optimized lymphocyte proliferation test, MELISA (memory lymphocyte immunostimulation assay) and with a patch test. Twenty subjects with amalgam fillings but without oral discomfort and 12 amalgam-free subjects served as controls. The results show that patients with OLP have significantly higher lymphocyte reactivity to inorganic mercury, a corrosion product of amalgam, compared to control groups. Removal of amalgam fillings resulted in the disappearance of oral mucosal changes, thus indicating a causal relationship. Positive responses to phenylmercury (phenyl-Hg), a bactericidal agent in root fillings and in pharmaceutical preparations, were also noted in the oral lichen group but not in the control groups. Thus, low-grade chronic exposure to mercury may induce a state of systemic sensitization as verified by Hg-specific lymphocyte reactivity in vitro.

Herpes simplex and mood: a prospective study.

The effect of mood, the common cold, amount of sleep, and sunshine on recurring herpes simplex virus (HSV) infection was investigated using daily self-reports over a 3-month period from 23 female and 15 male patients with genital herpes and 26 female and two male patients with oral herpes. Results showed recurring genital HSV infection to be preceded by reduced and decreasing overall emotional well being over a period of 10 days, with a temporary improvement in the middle of the period. This pattern was significantly represented by rated nervousness and rated alertness. Females showed more marked trends for reported mood than did the males, which could not be attributed to the menstrual cycle. Conversely, males showed a more marked, strongly significant fourth-order trend for reported amount of sleep, with nadirs on the 8th and the 3rd day before the recurrence. Neither exposure to sunshine nor the common cold showed any relation to recurrence of genital HSV infection. The common cold appeared as the major precipitating factor in oral herpes. Except for a significant fourth-order trend for rated alertness, no relationship between mood and subsequent onset was found. This negative finding was interpreted as a masking effect of the common cold. Two alternative physiological theories, the ganglion trigger theory and the skin trigger theory, were discussed in relation to present findings. It was suggested that various possible mediators between mood states and recurring herpes should be investigated using the present approach, with structured diaries as complement to the rating scales.

MELISA-an in vitro tool for the study of metal allergy.

The sensitizing properties of metals widely used in medical and dental care have been studied with the help of an optimized lymphocyte proliferative assay, MELISA. MELISA (memory lymphocyte immuno-stimulation assay) was originally developed for the screening of allergenic epitopes of drugs and other chemicals of low molecular weight, but has recently been adapted for the study of metal-induced sensitization. The patients studied suffered from various oral mucosal problems which were suspected to be caused by the release of metal ions from dental restorations. They were also troubled by chronic fatigue persisting over many years. One patient was also occupationally exposed to metals while working in a dental practice. Healthy subjects without any discomfort due to metal devices served as controls. In addition to metals used in dentistry, lymphocyte responses to organic mercurials used widely as preservatives in vaccines, eye/nose drops and contact lense fluids were studied. The results indicated that mercurials, as well as other metals such as gold or palladium, induce strong lymphocyte proliferative responses in patients with oral or systemic symptoms, but not in similarly exposed unaffected subjects. The results of MELISA performed with a pair of identical twins with chronic fatigue syndrome (CFS) indicated that metal-specific responses may be dependent on the genetics of the patient. Thus, many metals that are today accepted for use in medicine and dentistry carry a definite sensitizing risk for certain genetically predisposed individuals. Therefore, the use of these metals should be limited in the future.

Absence of specific IgE antibodies in allergic contact sensitivity to formaldehyde.

Immunologic reactions are customarily divided into two broad categories, cell-mediated and antibody-mediated. An interplay between these two pathogenetic principles is indicated by reactions such as cutaneous basophil hypersensitivity, late-phase reaction, and cutaneous lesions indistinguishable from regular allergic contact dermatitis lesions after sensitization with IgE antibodies against certain haptens. In the present study, 23 patients with a history of a positive epicutaneous test to formaldehyde participated. On retest, 15 showed a positive reaction. Eight patients were Phadiatop positive, indicating an atopic diathesis, and eight had a history of or ongoing atopic dermatitis. On RAST test, only two, nonatopic patients had specific IgE antibodies to formaldehyde. In the cellular infiltrates of biopsies from epicutaneous test sites, cells reactive with monoclonal antibodies against IgE were found in positive and negative formalin tests, both in atopics and nonatopics, as well as in control biopsies from nonlesional skin. Double immunofluorescence staining experiments showed that IgE occurred on Langerhans' cells. The proportion of IgE-positive cells correlated to the level of serum IgE, but not to atopy. These cells were also found both in the epidermis and in the dermis in nonatopic patients. ICAM-1 occurred on keratinocytes in all patient groups. This study does not support the hypothesis that specific IgE antibodies are active in the pathogenesis of contact sensitivity to formaldehyde either in atopic or in nonatopic patients.

One year acyclovir suppression of frequently recurring genital herpes: a study of efficacy, safety, virus sensitivity and antibody response.

The efficacy of oral acyclovir 400 mg twice daily in suppressing frequently relapsing genital herpes simplex was evaluated in an open multicenter study. Seventy-one patients were treated for 12 months. During treatment, 73% of the patients were completely free of symptoms when taking the tablets continuously, and another 14% had mild symptoms such as erythema and/or itching at single occasions. An accidental treatment interruption for 2-4 days led to mild but definite herpes episodes within a few days in 5 otherwise symptom free patients. Definite herpes episodes despite acyclovir medication occurred in 3 cases (4%). No noteworthy side effects were recorded during the acyclovir treatment. After withdrawal of acyclovir, herpes relapsed within 1-4 weeks in 69% of the patients. The frequency of relapses during the following months was reported to be equal to that before the treatment period in most of the patients. Acyclovir susceptibility of the isolated herpes simplex virus (HSV) strains did not change during treatment. The mean titres of antibodies against HSV type-common glycoprotein antigen, HSV-2 type-specific antigen and varicella zoster virus antigens decreased significantly during treatment with acyclovir.

Lymphocyte transformation test for diagnosis of isothiazolinone allergy in man.

The lymphocyte transformation test (LTT) has been used for evaluation of in vitro lymphocyte responses in 18 patients with dermatitis and positive patch tests to 200 ppm of a combination of 5-chloro-2-methylisothiazolinone and 28methylisothiazolinone (MCI) in nine patients with dermatitis unrelated to MCI and in seven subjects without skin diseases. Two workers sensitized by occupational exposure to a formulation containing 1,2-benzisothiazolin-3-one (BIT) were also studied. Lymphocytes from nine patch-test-positive patients proliferated vigorously to MCI in vitro. Lymphocytes from the remaining nine patients were not stimulated. Lymphocytes from two BIT-sensitized workers responded to BIT in vitro. The lymphocyte proliferation to isothiazolinones indicates the presence of memory cells in the patients' blood and confirms immunologic reaction to the inducing agent. To establish clinical relevance of LTT results, 12 MCI patch-test-positive patients underwent "use test" with lotion containing 15 ppm MCI. Four of five LTT-positive patients were use-test-positive, whereas seven of seven LTT-negative patients were use-test-negative. LTT-positive and lotion-positive patients responded to 100 ppm or lower concentrations of MCI on patch testing, whereas seven of eight LTT-negative and lotion-negative patients responded to 200 ppm only. In the case of MCI, proliferation was due to the chlorinated component, indicating that this part contains an allergenic epitope. Finally, MCI-specific lymphocyte proliferation was observed only in patients with MCI-positive skin test, but not in nine patients with dermatitis induced by other agents, or in seven subjects without skin diseases. Thus, the lymphocyte transformation test is able to distinguish between irritant and allergic skin responses. It may also be valuable in establishing the clinically relevant patch-test concentration of allergens with irritative properties.

Comparative multi-center study with TRUE Test and Finn Chamber Patch Test methods in eight Swedish hospitals.

292 individuals were patch tested with twelve allergens, using a new patch test technique, TRUE Test (TT). As controls, the same allergens in standard concentrations in petrolatum were applied using the Finn Chamber technique (FC). The allergen doses used in TT were chosen according to results from a previous serial dilution patch test study. There were reactors to all twelve allergens. The concordance of positive reactions between TT and FC was 78%. 10% were indicated only with TT and 12% FC only. Irritant reactions occurred in the same order of magnitude for the two tests. Weak positive, uncertain, and irritant reactions observed with the different test methods used, indicate minor errors of allergen dosage in both. The investigation indicates that the TRUE Test method is simple to handle, is well standardized and gives good accuracy with the 12 allergens investigated.

Side-chain-specific lymphocyte responses in workers with occupational allergy induced by penicillins.

Eight workers with clinically diagnosed or suspected occupational allergy caused by penicillins were studied by the lymphocyte transformation test (LTT) and by skin test. The majority of the workers handled bacampicillin, some of them had been in contact with benzylpenicillin and one worked with azidocillin only. Six workers had eczema and 2 workers suffered from rhinitis only. Lymphocytes from workers with bacampicillin-induced symptoms responded to this drug in vitro by an increased 3H-thymidine incorporation and by lymphoblastogenesis. Bacampicillin-specific allergy had been confirmed by positive patch test in 5 workers. Lymphocytes from bacampicillin-allergic workers did not respond to other penicillins such as benzylpenicillin or azidocillin in vitro. However, such penicillins were antigenic in vitro since lymphocytes from an azidocillin patch test positive worker proliferated on exposure to azidocillin in vitro. The findings at the cellular level were further supported by the specificity of the skin test. Thus, bacampicillin patch test positive workers had a negative skin reaction to benzylpenicillin. In conclusion, these data suggest the role of penicillin side chains in the sensitization process underlying occupational allergy to penicillins. LTT can be used as a tool for studying antigenic specificities involved in a sensitization process leading to penicillin allergy.

The lymphocyte transformation test for diagnosis of drug-induced occupational allergy.

Twenty-five workers with clinically diagnosed or suspected occupational hypersensitivity caused by contact with bacampicillin, alprenolol, and/or quinidine were studied by the lymphocyte transformation test and by skin tests. Ten healthy exposed workers, 16 job applicants, and seven healthy nonexposed laboratory workers served as control subjects. Lymphocyte transformation was measured by 3H-thymidine uptake into DNA and by counting of lymphoblasts on cell smears. Lymphocytes from workers with contact eczema or with eczema in combination with conjunctivitis and rhinitis responded to offending drugs in vitro as demonstrated by an increased 3H-thymidine incorporation and by the presence of lymphoblasts in the cultures. In vitro proliferative responses were reproduced during a 4-year period. Drug-specific allergy was confirmed by positive patch test in most workers with eczema. In addition, bacampicillin-specific lymphocyte proliferation was also observed in workers with suspected bacampicillin hypersensitivity but with negative skin tests. They suffered mostly from eczema in combination with conjunctivitis and rhinitis or from conjunctivitis/rhinitis only. Lymphocytes from most control subjects did not respond in vitro to bacampicillin, alprenolol, or quinidine. Weak proliferative responses to bacampicillin were observed in two of the 16 job applicants. The exquisite specificity of drug-induced lymphocyte responses is demonstrated. Thus, lymphocytes from a quinidine-sensitive worker did not respond in vitro to the quinidine stereoisomer, quinine. Furthermore, lymphocytes from a bacampicillin-sensitive worker responded to some penicillins, such as pivampicillin and ampicillin, but not to others, such as benzylpenicillin or pivmecillinam. These data suggest the role of N-acylamido side chain in the sensitization of lymphocytes from this particular donor. In conclusion, lymphocyte transformation test can be used for the detection of offending agents in occupationally sensitized workers. Furthermore, lymphocytes from such individuals may serve as a model for study of specificity of cellular reactions underlying drug-induced hypersensitivity.

Treatment of recurrent genital herpes simplex infections with oral acyclovir.

A total of 113 patients with recurrent genital herpes were enrolled in a multicentre cross-over study. Two consecutive recurrences were treated with either oral acyclovir 200 mg or matching placebo five times daily for five days. Acyclovir significantly reduced the time to crusting and healing and the duration of new lesions and symptoms. Acyclovir was not found to have any clinically significant effect on the haematological or biochemical parameters measured, or to have caused adverse events and was well tolerated. Early self-initiated treatment may abort a recurrent attack of genital herpes without progression to the ulcerative or crusting stage.

Genital herpes: oral treatment with acyclovir.

Orally administered acyclovir has been shown to have an effect on genital herpes simplex virus infections. In primary infections, all published trials report a significantly reduced duration of viral shedding and an accelerated healing time, but the effect of the drug on the severity of clinical symptoms was less apparent. Acyclovir does not seem to prevent virus latency nor to influence subsequent genital recurrences. The treatment of recurrent infections was not reported to show as good as by primary infections. However, the drug did shorten the time of viral shedding as well as prompt the reduction of lesions. The clinical response was improved if the therapy was self-initiated by the patients and acyclovir was also reported to cause recurrent attacks to abort. No serious adverse events caused by the drug have been published. As the risk for development of viral resistance associated with prolonged or repeated administration of acyclovir is not known, it should be used with caution and primarily patients with initial herpes genitalis and in patients with painful and frequent recurrences.

Buckwheat allergy: health food, an inhalation health risk.

Thirteen out of 28 persons (14 men and 14 women) employed in a company which imports, prepares and distributes plant products used in spices and as ingredients in so-called health food, had developed work-related symptoms in the form of rhinitis, conjunctivitis, asthma, itch or urticaria. The symptoms occurred in connection with specific work operations, especially in the grinding and packaging of buckwheat. Seven out of 25 examined persons (28%) had at least one positive allergy test (prick test or RAST) against buckwheat. Furthermore, one person had positive RAST against extract from castor-oil bean. The correlation between positive allergy tests and work-related symptoms is significant. Fourteen persons were also patch tested. All were negative except one person who had a positive patch test against nickel. The nickel allergy was diagnosed before this study was done and had no relation to the work. The levels of airborne dust in the breathing zones of the workers when they performed dust-forming work were around and below 5 mg/m3. When buckwheat flour was packaged, the airborne dust levels were about 1-2 mg/m3. Thus, exposure to comparatively low levels of buckwheat dust may induce a definite risk of rapidly ensuing allergy. It is also obvious that persons without atopic stigmata, such as an earlier history of allergy or the occurrence of allergic diseases in relatives, risk becoming allergic. A conclusion is that health food could be a danger, when it is inhaled.

Atopic hand dermatitis: a comparison with atopic dermatitis without hand involvement, especially with respect to influence of work and development of contact sensitization.

A group of 77 patients with atopic hand eczema were compared with 136 atopic dermatitis patients without hand manifestations. Age distribution was identical in the two groups, peaking at 25-39 years of age. Both groups were dominated by female patients. No differences existed between them with respect to atopic heredity, occurrence of other atopic manifestations, or distribution of serum IgE values. The fingers represented the predilection sites for hand involvement. Patients with hand lesions changed jobs more frequently (p less than 0.001) than those with unaffected hands, and change from a wet or unclean occupation was more common (p less than 0.001) than from a dry one. Change of work entailed improvement in the skin status of both groups. Prevalence of positive patch test reactions was high and statistically identical in both groups. Occurrence of positive responses did not explain the development of hand affliction; in only 3 patients did the test result correspond to exacerbation of the hand eczema. The number of positive reactions was high in patients with low serum IgE levels, while high levels were associated with fewer positive patch test reactions.

Comparison between 24- and 48-hour exposure time in patch testing.

A pilot study was performed to compare the results obtained by leaving the test substances recommended by ICDRG on the backs of the patients for 24 and 48 h, respectively. The Pirilä chamber test method was used. We got different results between the two methods of application time as reported, and intend to continue the study.