Showing papers on "Hypersensitivity reaction published in 1977"

Lymphocyte-stimulation tests and patch tests in carbamazepine hypersensitivity

Abstract: Seven cases of severe hypersensitivity to carbamazepine (Tegretol) were described in patients with epilepsy or trigeminal neuralgia. Clinical manifestations consisted of fever, rash, facial oedema, lymphadenopathy, impaired liver function, eosinophilia and atypical lymphocytes in the peripheral blood. Lymphocyte-stimulation tests with carbamazepine in vitro showed positive results in all cases; patch tests with carbamazepine were positive in six cases. In two cases the lymphocyte-stimulation tests with carbamazepine were found to be negative during, and shortly after, the illness. However, when the tests were repeated several months later, they turned out to be positive. Lymphocyte reactivity to PPD and PHA in vitro was also impaired during the acute phase of the disease. Thus false-negative lymphocyte-stimulation tests may be found in the first months following such a hypersensitivity reaction, probably due to impaired lymphocyte reactivity. As carbamazepine is a potent drug and is often prescribed for long periods together with other anticonvulsants, it seems important to prove that the allergic reaction is caused by carbamazepine. If the lymphocyte-stimulation test in vitro or the patch test with carbamazepine is found to be negative during or shortly after the illness, they should be repeated several months later.

Myocarditis Associated With Methyldopa Therapy

Abstract: Five patients with hypertension died as a result of myocarditis Three were treated with methyldopa and hydrochlorothiazide, two with methyldopa alone Their ages ranged from 30 to 71 years In all instances death occurred suddenly, and myocarditis was not suspected clinically The inflammatory changes in the hearts of these patients were most consistent with a hypersensitivity reaction Additionally, there was hepatitis consistent with hypersensitivity in four of the cases (JAMA237:1699-1701, 1977)

Extrinsic allergic alveolitis from bird exposure. Studies on the immediate hypersensitivity reaction.

Abstract: Summary Six patients with extrinsic allergic alveolitis had weak immediate and strong late reactions to intracutaneous injection of bird serum. Biopsy of the late reaction revealed vasculitis and immunoglobulin and complement deposition in one. The antibody responsible for the immediate hypersensitivity could be transferred in serum. It was short lasting (4 hr) and resistant to heat and 2-mercaptoethanol. No evidence of an immediate reaction in the lungs could be detected following inhalation challenge as judged by examination of spirometry, flow volume loops and single breath nitrogen washout curves.

Diphenylhydantoin-induced acute renal failure.

Abstract: A case of acute renal failure developing at two separate times after the use of diphenylhydantoin is described. On both occasions the patient also had other manifestations of a hypersensitivity reaction and recovered normal renal function after the withdrawal of the drug and institution of corticosteroid therapy.

Development of delayed-type hypersensitivity during Mycobacterium lepraemurium infection in mice.

Abstract: Various preparations of Mycobacterium lepraemurium were used to elicit delayed-type hypersensitivity in the footpad of mice infected with this organism. With a sonicated preparation of the mycobacterium, a significant increase in footpad swelling was elicited in mice infected with M. lepraemurium 5 weeks previously, but not in BCG-infected animals or uninfected controls. This footpad reaction was shown to peak at 24 h and to be associated with an infiltration of mononuclear cells. The kinetics of footpad swelling, its association with lymphoproliferation, and its dependence on T lymphocytes were each examined. The results support the hypothesis that this is a delayed-type hypersensitivity reaction. The ability to transfer this reactivity to normal mice with cells but not serum offers further confirmation that this hypersensitivity is dependent on cell-mediated immunological mechanisms rather than humoral antibody. The relevance of this to the study of the immunological response of mice to murine leprosy is discussed.

Drug-induced lung disease.

Abstract: There are four basic mechanisms by which allergic reactions to drugs occur: (I) immediate hypersensitivity in which drug as antigen combines with IgE antibody attached to receptors on mast cells in the respiratory tract or on circulating leucocytes; (2) cytotoxic reactions in which complement causes cell membrane rupture by becoming ‘fixed’ during a reaction between antidrug antibody and drug antigen attached to the cell membrane; (3) immune-complex mediated hypersensitivity where soluble drug antigen-antibody complexes are formed when the drug antigen is present in excess; and (4) delayed hypersensitivity in which thymus-derived (T-) lymphocytes become sensitised to a drug and cause tissue-damaging cytotoxic reactions when the drug is subsequently administered. Drugs principally cause allergic untoward reactions in the lung by immediate hypersensitivity (e.g. bronchospasm) and by elicitation of soluble immune-complexes, although there is increasing evidence for the role of delayed hypersensitivity in some reactions. For a drug to be immunogenic — that is to act as an antigen — it must either be contaminated by immunogenic macromolecules, formed or introduced during production or storage of the drug, or the drug (or a reactive derivative) must be conjugated to endogenous body macromolecules (usually proteins) by covalent bonding. Drugs with related structures (e.g. the penicillins) commonly cause cross-reacting allergy. It is highly likely that host factors operate in the process of sensitisation to drugs. The most commonly seen pulmonary syndromes caused by drugs include bronchoconstriction, in which the mechanism is immediate hypersensitivity in most cases, although an effect of some drugs on the balancing mechanism between intracellular cyclic nucleotides may affect bronchial smooth muscle tone directly; pulmonary eosinophilia occasionally progressing to fibrosis, mediated by soluble immune-complexes possibly with cell-mediated mechanisms also implicated; and systemic lupus erythematosus (with pleurisy, dyspnoea and often ‘disappearing lungs’), either an activation of latent disease by a drug or a more direct effect of the drug. Investigation of a case of suspected drug-induced lung disease begins with a high index of clinical suspicion and thereafter involves demonstration of the operation of one or more of the basic mechanisms described above. Immediate hypersensitivity is indicated by tests demonstrating release of mediators from mast cells (to which drug-specific IgE is bound) on challenge with drug antigen, or demonstration of a raised serum total, or drug-specific, IgE. Evidence for the existence of immune-complex mediated hypersensitivity is provided by demonstration of circulating soluble immune-complexes (although tests for these are generally unsatisfactory at present), tissue fixed immune-complexes by immunofiuorescence of lung biopsy specimens, or detection of antinuclear antibodies. Tests for delayed hypersensitivity include lymphocyte stimulation, leucocyte or macrophage migration inhibition and cytotoxicity. The treatment of drug allergy involves the emergency treatment of anaphylaxis with adrenaline and antihistamines, and the treatment of cytotoxic, immune-complex mediated and delayed hypersensitivity-induced reactions with corticosteroids. Prevention of a second immediate hypersensitivity reaction to a drug may sometimes be achieved by hyposensitisation, but in some cases it may be possible to avoid this laborious procedure by the use of more specific monovalent hapten blockade of antibody molecules. Promising avenues for future research are the investigation of idiosyncrasy and the development of a single test which can detect allergic reactions to most drugs. Idiosyncratic reactions have a basis in the individual’s metabolism or immunology which may be susceptible to manipulation. It may be possible to define a population at risk of an allergic reaction to a certain drug or drugs thereby allowing the drug to remain in use whilst identifying the ‘at risk’ population, depriving them of the drug in question.

Evidence for a T-cell reaction in the cutaneous sarcoid granuloma

Abstract: In cutaneous sarcoidosis, mononuclear cells of granuloma have been freed and characterized by immunological tests. Of these cells, 84% of them were found to be T dependent by the E rosette test. A similar value (79%) was obtained in the stroma of delayed hypersensitivity reaction, whose immunological functions are well known. However, the physiological role of the thymus dependent pupulation within granulomas must be established.

Reagin-Mediated Hypersensitivity Reaction in the Rat Hindpaw and Its Inhibition by Antianaphylactic Drugs

Abstract: Immediate hypersensitivity reactions are usually studied locally by the passive cutaneous anaphylaxis method. In the present experiments reaginic antibody-induced hypersensitivity was produced in the rat hindpaw (passive paw anaphylaxis or PPA). Increased vascular permeability was determined by measuring the increase in paw volume. The reaction in the paw and its inhibition with antianaphylactic drugs was found to be similar to that in the skin. The PPA is fast and easy to perform and can be used to study hypersensitivity reactions in the rat.

Cyclic AMP and the mechanism of leucocyte lysosomal enzyme release during an immediate hypersensitivity reaction in vivo.

Abstract: The pleural cavity of rats was used to study the effect of altering leucocyte cyclic AMP content on the release of B-glucuronidase activity during an immediate hypersensitivity reaction. The effect on intravenous colchicine was also studied. Despite an increase of 135 to 235% in leucocyte cyclic AMP content no decrease in B-glucuronidase release was observed. Similarly, colchicine had no effect on enzyme release. It was concluded that the cyclic nucleotides and leucocyte microtubules may have no significant role to play in the release of lysosomal enzymes during acute inflammation in vivo.

Adjuvant arthritis: immune responses and effects of Tilorone or interferon in partially suppressing the disease

Abstract: The injection of complete Freund’s adjuvant into rats induces a chronic arthritis which resembles human rheumatoid arthritis or Reiter’s syndrome in many respects1,2. The pathogenesis of adjuvant-induced arthritis has not yet been clearly established. It is generally believed to be the result of a delayed hypersensitivity response to bacilli on their components3, such as peptidoglycans4 which resist degradation by mammalian lysosomal enzymes5 and may remain in macrophages to serve as a persistent source of immunogen6. Alternatively, the disease has been speculated to result from the development of autoantibodies and/or specifically sensitized lymphocytes acting against the animals’ own tissue (i.e. in autoimmune phenomenon)7,8. There is a third possibility, namely, that adjuvant arthritis may involve the activation of latent virus by a yet undefined hypersensitivity reaction of the host9. Similar suggestions have also come from the work of Kupusta and his associates10,11 , who observed that the interferon-inducers (anti-viral) such as statolon and Pyran copolymer provide a degree of suppression of the otherwise induced state.

Cellular evaluation of hypersensitivity to 2,4-dinitrochlorobenzene.

Abstract: A suitable modification of the "skin window" method makes it possible to evaluate hypersensitivity reaction to 2,4-dinitrochlorobenzene at cellular level. Probands are sensitized by epicutaneous application of 0.2 ml of 1% solution of the tested substance, and after 14 days 1 drop of this solution is applied in the same manner on a freshly scraped area of the "skin window". An imprint preparation is taken 48 hours later and examined microscopically. Presence of lymphoid elements, eosinophils and basophils points to a normally developed hypersensitivity reaction. Presence at the same time of rather great amounts of large monocytogenic macrophages and neutrophilic granulocytes is an expression of an unspecific inflammatory reaction taking a normal course. Suitability of the described procedure for routine application is discussed.

Treatment of epilepsy.

Abstract: To the Editor. — In the article "Reversible Renal Failure and Myositis Caused by Phenytoin Hypersensitivity" (236:2773-2775, 1976), Michael and Mitch reported the case of a patient taking phenobarbital and phenytoin simultaneously; a skin rash developed followed by a serious constellation of symptoms that they concluded were "presumably caused by phenytoin hypersensitivity." Subsequently, Wilensky (237:2600-2601, 1977) challenged the etiologic role of phenytoin in this case since both phenobarbital and phenytoin have independently provoked similar hypersensitivity syndromes in the past. We agree that it is usually impossible to identify unequivocally the offending agent when a patient has a hypersensitivity reaction while receiving multiple drug therapy; however, based on our experience in the treatment of thousands of patients with phenobarbital and phenytoin, singly and in combination, we believe that the cutaneous eruption and the other hypersensitivity manifestations described by Michael and Mitch were more likely due to phenytoin. The primary purpose of

Massive hepatic necrosis in a patient receiving allopurinol concomitant medication.

Abstract: To the Editor.— In response to an inquiry, we welcome the opportunity to provide some important information not included in our article. "Massive Hepatic Necrosis in a Patient Receiving Allopurinol" (237:473, 1977). Concomitant medications included hydralazine hydrochloride, propranolol hydrochloride, and hydrochlorthiazide. The patient had been receiving these drugs intermittently for four years and continuously for the previous two years, with normal liver functions. This, and the strong temporal relationship between the initiation of allopurinol and the onset of the hypersensitivity reaction, convinced us that allopurinol was responsible for her death. Previous reports of severe allopurinol hypersensitivity have emphasized the association with thiazides. 1 Since thiazides cause hyperuricemia, the concomitant use of allopurinol is probably common. The association in cases of severe hypersensitivity may be coincidental.