Re: hypersensitivity reactions

February 18, 2010

DRUG REACTIONS

A. IgE-Mediated Reactions (Gell-Coombs Type 1)

IgE-mediated hypersensitivity reactions may occur after administration of a wide

variety of drugs, biologicals, and drug formulation agents. The most important

drug causes of immediate hypersensitivity reactions are antibiotics. Other

common drugs that cause such reactions are insulin, enzymes (streptokinase and

chymopapain), heterologous antisera (equine antitoxins and, antilymphocyte

globulin), murine monoclonal antibodies, protamine, and heparin.

58,59,60,61,62,63,64 Detailed discussions about these agents may be found in the

" Practice Parameters for the Diagnosis and Management of Anaphylaxis " J Allergy

Clin Immunol 1998;101:S505-S515). Allergic Type 1 reactions also have been

reported after exposure to excipients such as eugenol, carmine, vegetable gums,

paraben, thiomerosal, sodium metabisulfite, formaldehyde, and sulfonechloramide.

13 In the following discussion, we will consider both beta lactam and non-beta

lactam antibiotics as the major prototypes in this category.

1. Beta lactam antibiotics

Anaphylactic reactions manifested by urticaria, flushing, pruritus, laryngeal

edema, and cardiovascular collapse may occur within minutes or, less frequently,

hours after administration of beta lactam antibiotics (ie, drugs that have a

common beta lactam ring structure). Drugs in this category include penicillin,

semi-synthetic penicillins (eg, amoxicillin), cephalosporins, carbapenems (eg,

imipenem), monobactams (eg, aztreonam), and carbecephems. In addition, non-IgE

mediated immunologic reactions may also be caused by this class of drugs. These

include: cytopenias, immune complex disease such as serum sickness, vasculitis,

glomerulonephritis, fever, and non-urticarial rashes.

Penicillin. The prevalence of penicillin hypersensitivity in the general

population is not known. Up to 10% of hospitalized patients have been reported

to give a history of allergy to penicillin and, for this reason, many of these

patients receive alternative antimicrobial drugs. 65 The frequency of

anaphylaxis is estimated to be 0.01% to 0.05% with each course of penicillin. 32

The nature of the past reaction correlates somewhat with the chance of being

allergic to penicillin but history alone is not sufficiently reliable to make a

diagnosis of penicillin hypersensitivity. Thus, over 80% of patients with a past

history of penicillin hypersensitivity do not have penicillin-specific IgE

antibodies detected by skin testing. 66 Although many patients with documented

hypersensitivity to penicillin lose sensitivity with time, about 20% may

maintain their hypersensitivity status for long periods of time. Up to 46% of

patients with a history of anaphylaxis and about 15% of those with a history of

urticaria and angioedema will exhibit positive immediate hypersensitivity skin

tests to penicillin when tested at a later date. 67 The most reliable method for

evaluating IgE-mediated penicillin allergy is by skin testing to both major and

minor determinants of penicillin. Positive commercial in vitro tests (RAST or

ELISA) may suggest a diagnosis of penicillin allergy. Negative commercial tests,

however, are not reliable for excluding penicillin hypersensitivity because they

are relatively insensitive and do not test for minor determinants. 68 Although

skin testing predicts only the risk of developing an IgE-mediated reaction, this

information is of critical clinical importance because most life threatening

reactions to penicillin are the result of IgE-mediated anaphylaxis.........more.

B. Cytotoxic Reactions (Gell-Coombs Type 2)

Cytotoxic reactions are very serious and potentially life-threatening.

Immunohemolytic anemias due to drugs have clearly been identified after

treatment with quinidine, -methyldopa and penicillin. In the case of penicillin,

circulating anti-penicillin antibodies of the immunoglobulin G isotype have been

implicated. 9 The condition is rare because it apparently develops only in those

individuals capable of synthesizing an atypical variety of IgG anti-penicillin

antibody. Penicillin binding by erythrocytes is an essential preliminary step in

the sensitization process and is more likely to occur in patients receiving very

large and prolonged dose regimens of penicillin, as may be required in the

long-term treatment of subacute bacterial endocarditis. As previously discussed,

positive direct and indirect Coombs' tests in this condition also may indicate

the presence of complement on the red cell membrane or an autoantibody to an Rh

determinant. 43

Thrombocytopenia resulting from drug-induced immune mechanisms has been well

documented. The most thoroughly evaluated drugs in this category are quinine,

quinidine, acetaminophen, propylthiouracil, gold salts, and the sulfonamides.

Platelet membrane damage is mediated chiefly by circulating drug-immune serum

complexes which are absorbed onto platelet membranes.

Granulocytopenia also may be produced by cytotoxic antibodies synthesized in

response to such drugs as pyrazolone derivatives, phenothiazines, thiouracils,

sulfonamides, and anti-convulsives. Immunologically mediated destruction of

peripheral neutrophils occurs within minutes after readministration of the drug

and the immunologic specificity of the antibody has been verified by passive

transfer to nonsensitive volunteers (in the pre-AIDS era). 14

C. Immune Complex Reactions (Gell-Coombs Type 3)

Serum sickness was originally noted when heterologous antisera were used

extensively for passive immunization of infectious diseases. Many small

molecular weight drugs are also associated with serum-sickness-like symptoms.

These include penicillin, sulfonamides, thiouracils, and phenytoin. The chief

manifestations of fever, rash, urticaria, lymphadenopathy, and arthralgias

typically appear 1 to 3 weeks after the last dose of an offending drug and begin

to subside when the drug and/or its metabolites are completely eliminated from

the body. 34 Most of the clinical symptoms are thought to be mediated by IgG and

possibly IgM-drug complexes. The overall immune response in immune complex

reactions is heterogeneous because in some cases, IgE antibodies can also be

demonstrated and may be associated with urticarial lesions seen early in the

course of the disease.

D. Cell-Mediated Reactions (Gell-Coombs Type 4)

Allergic contact dermatitis after exposure to medications containing active

drugs, additives, or lipid vehicles in ointments is the most frequent form of

drug-mediated delayed hypersensitivity. Morphologically, it usually cannot be

distinguished from contact irritant dermatitis. Almost any drug applied locally

is a potential sensitizer but less than 40 allergens produce most cases of

contact dermatitis. Among the drugs involved, the most universally accepted

offenders are topical formulations of penicillin, local anesthetics, and

antihistamines. Potent excipient topical sensitizers include the parabens,

formaldehyde, ethylenediamine, lanolin, and thimerosal. 105 Complex topical

products may contain many potential antigens and additives and in many instances

the major component of a complex mixture may not necessarily be the sensitizer.

Photoallergic dermatitis morphologically resembles allergic contact dermatitis

and is caused by such drugs as sulfonamides, thiazides, quinidine,

chlorpromazine, and fluoroquinolones. Once induction sensitization has occurred,

elicitation of dermatitis requires minimal exposure to light. Phototoxic,

non-allergic reactions (eg, erythrosine) are histologically similar to

photoallergic inflammatory responses. As previously discussed, T-cell mediated

mechanisms (ie, CD8+ T cells) have been demonstrated in patients with late onset

cutaneous reactions such as morbilliform and bullous eruptions. 6,7

E. Miscellaneous Syndromes

Specific drugs or classes of drugs are associated with characteristic syndromes

which often do not conform with specific Gell-Coombs categories. Although

various specific immune phenomena can often be demonstrated in these syndromes,

their roles in the immunopathogenesis of the disease have not been clearly

established............

http://www.fqresearch.org/body_19.htm

-------------------------------

>

> All four Gell and Coombs classes of hypersensitivity reactions to a chemical

may co-exist.

>

> Medicare files federal lawsuit against EDS & NHIC.

>

http://www.allergy-immunology.com/Lawsuit/Medicare_Patients_File_Federal_Lawsuit\

_Against_EDS_ & _NHIC_V_3.htm

>

February 18, 2010

Immunological Mechanisms

Type I hypersensitivity is usually mediated through the IgE mechanism on the

vessel wall. Classic examples are angioedema, urticaria, and anaphylaxis due to

sensitivity to pollen, dust, mold, or food,136 or some chemicals such as toluene

diisocyanate. Ten percent of the patients with immunological involvement with

chemical sensitivity seen at the EHC-Dallas seem to fall within this category.

Type II cytotoxic damage may occur with direct injury to the cell. A clinical

example of this is seen in patients exposed to mercury.137 A group in Minamata,

Japan, developed neurological disease from eating fish exposed to toxic methyl

mercury chloride. Mercurial pesticides fall into this category. Twenty percent

of the patients with immunological involvement seen at the EHC-Dallas seem to

fall into this Type II category.

Type III shows immune complexes of completment and gamma globulin damaging the

vessel wall. A clinical example of this is lupus vasculitis. Numerous chemicals,

including procainamide and chlorothiazide, are known to trigger the autoantibody

reaction of lupus-like reactions. Many other toxic chemicals can also trigger

the autoimmune response.138 Other chemicals, such as vinyl chloride, will

produce micro aneurysm of small digital arterioles, probably due to this

mechanism.51, 139

Type IV (cell-mediated) immunity occurs with triggering of the T-lymphocyte.

Numerous chemicals such as phenol, pesticides, organohalides, and some metals

will also alter immune responses, triggering lymphokines, and producing the Type

IV reactions.138 Clinical examples are polyarteritis nodosa, hypersensitivity

angitis, Henoch-Schonlein pupura, and Wegener's granulomatosis.1, 139 A recent

study done at the Environmental Health Center-Dallas on 104 proven

chemically-sensitive individuals (70 vascular, 27 asthmatic, and 7 rheumatoid),

comparing them with 60 nomral controls, showed that those manifesting a chemical

sensitivity through their vascular tree had suppression of the suppressor

T-cells (greater than 4 S.D.).47 Clearly the larger portion of our patients with

immunological involvement fall into the Type III and IV categories.

http://www.aehf.com/articles/env_aspects_of_cs.html

>

> DRUG REACTIONS

>

> A. IgE-Mediated Reactions (Gell-Coombs Type 1)

> IgE-mediated hypersensitivity reactions may occur after administration of a

wide variety of drugs, biologicals, and drug formulation agents. The most

important drug causes of immediate hypersensitivity reactions are antibiotics.

Other common drugs that cause such reactions are insulin, enzymes (streptokinase

and chymopapain), heterologous antisera (equine antitoxins and, ant

February 21, 2010

Just wanted to add this article on Chemical Exposure that you and others might

be interested in.

Myriam

Chemical Exposure

New Report: Reductions in Toxic Chemical Exposure Would Make Americans

Healthier, Wealthier

2010-01-21

According to a new analysis released today, " The Health Case for Reforming the

Toxic Substances Control Act, " the U.S. has the opportunity to prevent chronic

disease and reduce health care costs by overhauling federal chemical policy.

Evidence is strong and growing that chemical exposure is contributing to the

rise in many chronic diseases, according to this new report.

As the U.S. debates the costs of health care and its reform, " The Health Case "

documents the enormous health care costs of treating chronic diseases and

conditions linked to chemical exposure, according to recent studies.

Conservative estimates show that reducing the incidence of these diseases by 0.1

percent could save $5 billion per year in health care costs. The coalition has

estimated health care cost savings on a state-by-state basis.

The federal chemical safety law, the Toxic Substances Control Act (TSCA), has

not been updated since 1976. The EPA has identified comprehensive reform of the

toxics law as a key priority. Of the 80,000 chemicals used in the U.S., EPA has

required safety testing on only 200. And 60,000 chemicals -- including bisphenol

A -- were grandfathered in for use without testing for health safety. New

legislation to update the toxics law will be introduced by Sen. Lautenberg

(D-NJ) and Rep. Bobby Rush (D-IL) in early 2010.

" Scientific evidence is strong and growing, that chemicals are contributing to

the alarming increases in serious health problems, " says Charlotte Brody, RN, of

the Safer Chemicals, Healthy Families coalition and lead author of the report.

" But meanwhile the federal law that is supposed to protect us has stayed frozen

in time. "

" The use of chemicals is pervasive in our modern society and, when properly

tested and used, they improve the quality of life for families here and

throughout the world, " said U. S. Rep. Bobby L. Rush, chairman of the Energy and

Commerce Subcommittee on Commerce, Trade and Consumer Protection. " But just

because chemicals have value, does not mean they are always beneficial to our

health, particularly the health and maturation of young children and those whose

health has already been compromised. As we work to reform TSCA, I will continue

to vigorously prod industry to seek out and invest in the development of safer,

more viable alternatives to hazardous chemicals and substances. I applaud the

Campaign's release of today's report, which goes a long way toward shedding

light on a constructive way to move forward. "

During the last 30 years, tens of thousands of peer reviewed studies have built

a large body of evidence demonstrating that chemical exposure can cause and

contribute to some of our nation's most serious health problems -- from

childhood cancer to infertility. The report details the rates at which some of

these health problems have been increasing.

The full report and state-based economic information is available at

www.saferchemicals.org Follow us on Twitter, @saferchemicals

Source: Press Release

Author: Safer Chemicals, Healthy Families Coalition

February 22, 2010

Thank you for this! I have put it on my facebook page-hope it changes at least

one person's mind!

--- In , " moldusegirl7898 " <moldusegirl7898@...>

wrote:

>

> Just wanted to add this article on Chemical Exposure that you and others might

be interested in.

>

> Myriam

>

> Chemical Exposure

>

> New Report: Reductions in Toxic Chemical Exposure Would Make Americans

Healthier, Wealthier

> 2010-01-21

>

> According to a new analysis released today, " The Health Case for Reforming the

Toxic Substances Control Act, " the U.S. has the opportunity to prevent chronic

disease and reduce health care costs by overhauling federal chemical policy.

Evidence is strong and growing that chemical exposure is contributing to the

rise in many chronic diseases, according to this new report.

>

> As the U.S. debates the costs of health care and its reform, " The Health Case "

documents the enormous health care costs of treating chronic diseases and

conditions linked to chemical exposure, according to recent studies.

>

> Conservative estimates show that reducing the incidence of these diseases by

0.1 percent could save $5 billion per year in health care costs. The coalition

has estimated health care cost savings on a state-by-state basis.

>

> The federal chemical safety law, the Toxic Substances Control Act (TSCA), has