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HYPER-IgE SYNDROME AND H2-RECEPTOR BLOCKADE
630
HYPER-IgE SYNDROME AND H2-RECEPTOR BLOCKADE
combination
SIR,-Dr Souillet and colleagues (June 17, p 1384) report clinical improvement in a patient with severe eczema and "hyper-IgE syndrome" after treatment with interferon-ot. This patient seems to have had severe atopic eczema refractory to conventional treatment and raised serum IgE levels. However, the label "hyper-IgE syndrome" is, we think, inappropriate here. Although patients with atopic eczema often have very high serum IgE levels, the term hyper-IgE syndrome was introduced by Buckley et all in 1972 to describe a group of patients with both high IgE levels and undue susceptibility to infections. The term is generally used2.3 to describe an uncommon group of patients characterised by: (a) serious recurrent bacterial infections of the skin and sinopulmonary tract, usually beginning in childhood, and usually caused by Staphylococcus aureus, although infections caused by Haemophilw; influenzae and gram-negative rods and fungal infections have been documented; (b) a serum IgE above 2000 kU/1; and (c) chronic (eczematoid) dermatitis. Coarse facies, mild eosinophilia, chronic mucocutaneous candidosis, neutrophil chemotactic dysfunction, and "cold" subcutaneous abscesses are variable features. This syndrome is very different from severe atopic dermatitis which is a common disorder. Although patients with severe atopic dermatitis may become colonised by Staph aureus, such infections are superficial and happen only during exacerbations of atopic dermatitis. Patients with hyper-IgE syndrome do not have the striking history of IgE-mediated allergy that is seen in those with atopic dermatitis. Sometimes patients have overlapping features of the two conditions, but these patients usually present at a later age.3 The distinction between the hyper-IgE syndrome (as strictly defined) and severe atopic dermatitis is worthwhile since we and others’ have observed striking clinical improvement in patients with EXPERIENCE WITH H2-RECEPTOR ANTAGONISTS IN SYNDROME
INC
=
unpaired neutrophil chemota-xis.
or ranitidine alone or in with H1-receptor antagonists. This clinical improvement is characterised by significant reduction in infective episodes. Admittedly our experience, summarised in the table, is anecdotal, but it could be the basis for a multicentre placebocontrolled study.
hyper-IgE treated with cimetidine
HYPER-IgE
Department of Immunology, East Birmingham Hospital, Birmingham B9 5ST
R. A. THOMPSON
Medical
School, University of Birmingham
D. S. KUMARARATNE
Buckley RH, Wray BB, Belmaker Z Extreme hyperimmunoglobulin E and undue susceptibility to infections. Pediatrics 1972; 49: 59. 2. Donabdin H, Gallin JI. The hyper IgE, recurrent infection (Job’s) syndrome 1.
Medicine 1983; 62: 195 3. Geha RS, Leung DYM. Hyperimmunoglobulin E syndrome. Immunol Rev 1989; 1: 155-72. 4. Mawhinney H, Killen M, Fleming WA, Roy AD. The hyperimmunoglobulin E syndrome a neutrophil chemotactic defect reversible by histamine H2 receptor blockade? Clin Immunol Immunopathol 1980; 17: 483-91.
SMALLPOX VACCINATION FOR INVESTIGATORS USING VACCINIA RECOMBINANTS
SIR,-National Institutes of Health (NIH) and Centers for Disease Control (CDC) guidelines strongly recommend smallpox vaccination for everyone working with vaccinia recombinants.1 A booster dose every three years is advised. The vaccine antigen contains about 100 million living vaccinia viruses per ml and trace amounts of polymyxin B sulphate, dihydrostreptomycin sulphate, chlortetracycline hydrochloride, and neomycin sulphate. It is distributed by the immunobiologics/drug service at CDC; 66 vials were mailed out in 1986 and 94 in 1987, each vial containing a hundred doses. According to CDC records, 599 people received vaccine in 1986 and at least 404 in 1987 (data still being compiled), although reporting is voluntary and vaccine administration is unregulated. The number of new laboratories enrolled in 1986, 1987, and 1988 were 17, 29, and 33, respectively. A rise in both supply and demand is possible since increasing numbers of investigators are working with vaccinia recombinants. The purpose of this letter is to question the NIH/CDC recommendation and to express concerns about vaccine-associated risks among laboratory workers. From authorities at NIH and CDC we learn that the rationale for the recommendation included both administrative and perceived medical concerns. The administrative reason was that there exists the forcefully worded guideline at both agencies. The perceived medical concerns cited were: 1. As opposed to the virus exposure in a laboratory accident, the vaccination would be a "controlled" vaccination. 2. Vaccination might protect against a serious eye infection subsequent to an accidental splash. 3. Theoretically, the recombinant vaccinia virus could be more virulent and thus prophylactic vaccination would be warranted. 4. Accidental inoculation could lead to antibody development to the recombinant gene product. With an HIV gene product, this could lead to a false-positive test of infection. The medical arguments seem spurious to us. An accidental "sharps" inoculation, despite its uncontrolled nature, would in all likelihood deliver a much lower antigen challenge than vaccination. Since work is carried out in a hood, a splash is unlikely; nor do we know of evidence for a protective role for smallpox vaccination in local infections, especially with a very poorly vascularised tissue such as cornea. If investigators disagree and consider a splash to be a high probability accident, we would favour use of protective eyewear such as goggles or a transparent shield rather than vaccination. The insertion of the recombinant gene at the thymidine-kinase locus2 has led to greater attenuation, not greater virulence, in laboratory strains of vaccinia.3 Although an accident could be followed by the development of antibody to various gene products, including proteins made by HIV, the resulting falsepositive screening tests for HIV infection would not be confirmed by immunoblot tests.
HYPER-IgE SYNDROME AND H2-RECEPTOR BLOCKADE
combination
SIR,-Dr Souillet and colleagues (June 17, p 1384) report clinical improvement in a patient with severe eczema and "hyper-IgE syndrome" after treatment with interferon-ot. This patient seems to have had severe atopic eczema refractory to conventional treatment and raised serum IgE levels. However, the label "hyper-IgE syndrome" is, we think, inappropriate here. Although patients with atopic eczema often have very high serum IgE levels, the term hyper-IgE syndrome was introduced by Buckley et all in 1972 to describe a group of patients with both high IgE levels and undue susceptibility to infections. The term is generally used2.3 to describe an uncommon group of patients characterised by: (a) serious recurrent bacterial infections of the skin and sinopulmonary tract, usually beginning in childhood, and usually caused by Staphylococcus aureus, although infections caused by Haemophilw; influenzae and gram-negative rods and fungal infections have been documented; (b) a serum IgE above 2000 kU/1; and (c) chronic (eczematoid) dermatitis. Coarse facies, mild eosinophilia, chronic mucocutaneous candidosis, neutrophil chemotactic dysfunction, and "cold" subcutaneous abscesses are variable features. This syndrome is very different from severe atopic dermatitis which is a common disorder. Although patients with severe atopic dermatitis may become colonised by Staph aureus, such infections are superficial and happen only during exacerbations of atopic dermatitis. Patients with hyper-IgE syndrome do not have the striking history of IgE-mediated allergy that is seen in those with atopic dermatitis. Sometimes patients have overlapping features of the two conditions, but these patients usually present at a later age.3 The distinction between the hyper-IgE syndrome (as strictly defined) and severe atopic dermatitis is worthwhile since we and others’ have observed striking clinical improvement in patients with EXPERIENCE WITH H2-RECEPTOR ANTAGONISTS IN SYNDROME
INC
=
unpaired neutrophil chemota-xis.
or ranitidine alone or in with H1-receptor antagonists. This clinical improvement is characterised by significant reduction in infective episodes. Admittedly our experience, summarised in the table, is anecdotal, but it could be the basis for a multicentre placebocontrolled study.
hyper-IgE treated with cimetidine
HYPER-IgE
Department of Immunology, East Birmingham Hospital, Birmingham B9 5ST
R. A. THOMPSON
Medical
School, University of Birmingham
D. S. KUMARARATNE
Buckley RH, Wray BB, Belmaker Z Extreme hyperimmunoglobulin E and undue susceptibility to infections. Pediatrics 1972; 49: 59. 2. Donabdin H, Gallin JI. The hyper IgE, recurrent infection (Job’s) syndrome 1.
Medicine 1983; 62: 195 3. Geha RS, Leung DYM. Hyperimmunoglobulin E syndrome. Immunol Rev 1989; 1: 155-72. 4. Mawhinney H, Killen M, Fleming WA, Roy AD. The hyperimmunoglobulin E syndrome a neutrophil chemotactic defect reversible by histamine H2 receptor blockade? Clin Immunol Immunopathol 1980; 17: 483-91.
SMALLPOX VACCINATION FOR INVESTIGATORS USING VACCINIA RECOMBINANTS
SIR,-National Institutes of Health (NIH) and Centers for Disease Control (CDC) guidelines strongly recommend smallpox vaccination for everyone working with vaccinia recombinants.1 A booster dose every three years is advised. The vaccine antigen contains about 100 million living vaccinia viruses per ml and trace amounts of polymyxin B sulphate, dihydrostreptomycin sulphate, chlortetracycline hydrochloride, and neomycin sulphate. It is distributed by the immunobiologics/drug service at CDC; 66 vials were mailed out in 1986 and 94 in 1987, each vial containing a hundred doses. According to CDC records, 599 people received vaccine in 1986 and at least 404 in 1987 (data still being compiled), although reporting is voluntary and vaccine administration is unregulated. The number of new laboratories enrolled in 1986, 1987, and 1988 were 17, 29, and 33, respectively. A rise in both supply and demand is possible since increasing numbers of investigators are working with vaccinia recombinants. The purpose of this letter is to question the NIH/CDC recommendation and to express concerns about vaccine-associated risks among laboratory workers. From authorities at NIH and CDC we learn that the rationale for the recommendation included both administrative and perceived medical concerns. The administrative reason was that there exists the forcefully worded guideline at both agencies. The perceived medical concerns cited were: 1. As opposed to the virus exposure in a laboratory accident, the vaccination would be a "controlled" vaccination. 2. Vaccination might protect against a serious eye infection subsequent to an accidental splash. 3. Theoretically, the recombinant vaccinia virus could be more virulent and thus prophylactic vaccination would be warranted. 4. Accidental inoculation could lead to antibody development to the recombinant gene product. With an HIV gene product, this could lead to a false-positive test of infection. The medical arguments seem spurious to us. An accidental "sharps" inoculation, despite its uncontrolled nature, would in all likelihood deliver a much lower antigen challenge than vaccination. Since work is carried out in a hood, a splash is unlikely; nor do we know of evidence for a protective role for smallpox vaccination in local infections, especially with a very poorly vascularised tissue such as cornea. If investigators disagree and consider a splash to be a high probability accident, we would favour use of protective eyewear such as goggles or a transparent shield rather than vaccination. The insertion of the recombinant gene at the thymidine-kinase locus2 has led to greater attenuation, not greater virulence, in laboratory strains of vaccinia.3 Although an accident could be followed by the development of antibody to various gene products, including proteins made by HIV, the resulting falsepositive screening tests for HIV infection would not be confirmed by immunoblot tests.