Latex Sensitivity in a Macaque (<I>Macaca Mulatta</I>)

Latex Sensitivity in a Macaque (Macaca mulatta)

James D. Macy Jr., DVM,* Michael J. Huether, MD, T. A. Beattie, H. A. Findlay, and Caroline Zeiss, BVSc, PhD

Background and History: An adult Macaca mulatta was examined because of a history of multiple episodes of conjunctivitis and an acute, pruritic, dermatitic eruption that affected the axillary and inguinal regions, forearms, thorax, and neck. Methods and Results: Results of corneal staining, examination of skin scrapings and feces, fungal culture, CBC, and a thyroid profile (thyroxine/triiodothyronine concentrations) were negative or normal, with the exception of eosinophilia (1,040/mm3). Examination of a punch biopsy specimen of the skin indicated chronic, nonsuppurative eosinophilic dermatitis. Skin patch testing against 25 contact allergens was negative for a delayed-type hypersensitivity reaction. Allergen-specific IgE testing, using six monkey chow additives, also yielded negative results, but testing against latex revealed a strong positive result (0.74 KU/L) consistent with a latex allergy. A skin prick test performed by use of a latex supernatant revealed significant inflammation at the latex site at 72 h and one week. Vinyl gloves were substituted for latex gloves, and that resulted in a marked decrease in erythema, pruritus, and lichenification with no flares of dermatitis for four years. Repeat skin biopsy fourteen weeks after the original biopsy revealed normal epidermis; however, mild chronic active nonsuppurative, perifolliculitis persisted. Conclusion: Latex can induce allergic dermatitis in nonhuman primates and should be included in the differential diagnosis for atopic dermatitis.

Use of latex products has increased markedly in the healthcare ing 10 to 24 individually housed NHP that had visual, olfactory, field over the past decade. Widespread acceptance of the Center and auditory contact. The physical environment was main- for Disease Control’s universal precautions adopted in 1987 (1) tained at an ambient temperature of 21 to 23°C, relative humidi- and modifications to glove manufacturing methods to meet de- ty of 40 to 60%, with a minimum of 10 complete air changes/h, and mand has contributed to increased exposure and sensitivity of 12/12-h light/dark cycle. Diet consisted of commercial food healthcare and laboratory workers to latex (2, 3). The number of (Monkey Chow, Ralston Purina Co, St. Louis, Mo.). Water con- allergic reactions reported to the Federal Drug Administration sumption was regulated during research-related cognitive test- (FDA) sharply increased from the original reports in the 1980s ing and was provided ad libitum otherwise. Environmental to 1,100 injuries in 1992 (4). Latex allergies in human patients enrichment included daily fruits or vegetables (rotation among have varied manifestations, including irritant dermatitis, con- 18 varieties purchased by a commercial supplier), twice weekly tact urticaria, rhinitis, and conjunctivitis (4). Prior to 1984, la- food treats (rotation among 11 varieties purchased at a local tex allergies were principally manifested as contact dermatitis, grocery), and twice weekly rotation of enrichment devices (mir- a delayed type hypersensitivity reaction (4). However, in 1979, rors, chains, keys, PVC pipe, puzzle feeders, and 16 different the first case of IgE-mediated latex hypersensitivity was re- commercially available toys). The animal was seronegative for ported (5). During the 1980s, latex-induced anaphylaxis emerged Cercopithecine herpesvirus I and was negative for tuberculosis by as an increasing threat for high-risk individuals, including health- tuberculin skin testing. The animal care program is fully accred- care workers, and patients with urogenital disorders, spina bifida, ited by the Association for the Assessment and Accreditation for or a history of multiple surgical procedures (6-8). Laboratory Animal Care. Latex exposure among laboratory animal workers also has Use of the animal for research required implantation of a intensified through increased use of personal protective equip- head restraint device, eye coil, and cephalic cylinder at three years ment (PPE). For example, the CDC recommendations for labo- of age. A plastic cervical collar (Primate Products, Miami, Fla.) ratory animal workers in direct or close contact with non-human was placed to facilitate transfer into an acrylic restraint chair, primates (NHP) include gloves as part of PPE (9). Under such con- which was used for transport to and restraint in an adjacent labo- ditions, latex exposure risks encompass the glove wearer as well ratory where the animal performed ocular and manual motor as the animals that are being handled. We report latex sensitiv- delay response tasks. Electrophysiologic recordings during ity in an adult rhesus macaque (Macaca mulatta). To our knowl- these tasks were used to investigate areal topography of the edge, it is the first report of latex sensitivity in a NHP. prefrontal and occipital cortex. Testing sessions were performed three to five times weekly, lasted approximately four hours, and Case Report included performance-based fruit juice rewards. Experimental An eight year-old, nursery-reared male Macaca mulatta was use of the animal was approved by the Institutional Animal housed individually in an 48 × 25 × 35-in cage in a room contain- Care and Use Committee. Clinical history included once or twice yearly surgical debri- Received: 6/18/01. Revision requested: 7/26/01. Accepted: 9/07/01. Yale University School of Medicine, PO Box 208016, New Haven, Connecticut dement to remove excess granulation tissue underlying the 06520-8016. cephalic cylinder and repair of the eye coil, and multiple im- *Corresponding author. 467 Vol 51, No 5 Comparative Medicine October 2001 plant-associated infections. The implant infections, characterized by a malodorous discharge, developed during the ages of 4, 7, 8, 9, 10, and 11 years. During the tenth year, meningitis was suspected because anorexia, lethargy, and postural alterations were coincident with infection. Otherwise, all other infections (apart from the discharge) were subclinical. Over an eight-year interval, 22 bacterial culture and susceptibility testings were performed on samples from the cephalic cylinder and implant margin. At least two of the following organisms were recovered from each sample: Escherichia coli, Staphylococcus, Streptococ- cus, Corynebacterium, Bacteriodies, and Fusobacterium spp. Im- plant-associated bacterial infections were treated on the basis of results of culture and antibiotic sensitivity testing, using systemic (Baytril [enrofloxacin Bayer Pharmaceuticals, Shawnee Mission, Kans. {2.5 mg/kg, i.m. twice daily}]; Cefadroxil [Fort Dodge Pharmaceuticals, Fort Dodge, Kans. {25 mg/kg, p.o. twice daily}]; Cefazolin [Bristol Myers-Squibb, Princeton N.J. {25 mg/kg, i.m. twice daily}], sulfamethoxazole trimethoprim [Shein, Florham Park, N.J. {6 mg/kg once daily}] and Gentamycin [American Pharamceutical Partners, Hauppauge, N.Y.{2 mg/kg loading dose, followed by 1 mg/kg once daily}]) and local antibiotic therapy. The latter was achieved by lavaging the cylinder with antibiotic solutions: enrofloxacin (7 mg/ml), cephalexin (TEVA Pharma- ceuticals, Sellerville, Pa. [1 mg/ml]). Gentamycin solution [4 mg/ ml], neomycin-polymixin-bacitracin (Pharmaderm, Mellville, N.Y.) Figure 1. Erythematous dermatitic eruption affecting inner arm and or Gentocin ophthalmic ointment (Gentamycin, Schering Plough, axilla of the affected macaque. Kenilworth, N.J.) was applied to the wound margins and interior of the cylinder. Cephalic implant hygiene was performed tus affected the ventral aspects of the neck, abdomen, arms, and one to three times per week, and included lavage of the cylinder periorbital areas (Fig. 2); bilateral conjunctivitis also was present. interior and cleaning of the implant margins with 10% Excoriations were noted on his chest and ventral abdomen but no Nolvasan (chlorhexadine, Fort Dodge, Iowa) 10% betadine solu- pustules were noted. The differential diagnosis included allergic tion (Purdue Fredrick Co, Norwalk, Conn.), or 1% sodium hy- skin disease (atopy, food allergy, contact dermatitis, drug-induced pochlorite (Clorox Corporation, Oakland, Calif.). Others have eruptions), pyoderma, dermatophytosis, and ectoparasitism. reported similar experiences with cephalic implant infections in The diagnostic assessment, performed on the animal under non-human primates and recommend a similar approach to im- ketamine anesthesia (10 mg/kg, i.m., Ketamine HCl, Fort Dodge, plant hygiene (10). Routine healthcare included tuberculin skin Fort Dodge, Iowa) included skin scrapings of three erythematous, testing for tuberculosis every four months. pruritic sites, fungal culture of hair and dander, fecal parasitologic At eight years of age, an acute pruritic, erythematous, dermatitic examination, fluoroscein staining of the cornea (Fluorets, Chauvin eruption was observed in the cervical region (adjacent to his plas- Pharmaceuticals, Essex, England), CBC, and blood biochemical tic collar), forearms, axillae, thorax, inguinal (bilateral) region analysis (CBC, Antech diagnostics, Farmingdale, N.Y.), and full- (Fig. 1), and thorax. Treatment consisted of a bath with a mois- thickness skin biopsy of an affected site on the abdomen. Infec- turizing shampoo (Hydra Pearls, Evsco Pharmaceticals, Buena, tious organisms were not detected by culture and/or parasitologic N.J. ), topical application of antibiotic/corticosteroid ointment examination. Corneal defects were not detected by fluoroscein (Panolog Fort Dodge Pharmaceuticals, Fort Dodge, Kans.), and staining. Results of the CBC were within normal limits, except systemic administration of antihistamine (Benedryl, diphenhy- for eosinophilia (1,040/ mm3, 10% of total white count). Using dramine, Parke-Davis, Morris Plains, N.J. [1 mg/kg of body weight, aseptic technique, a biopsy specimen consisting of a full-thick- i.m.]). Over the next three days, intensity of the pruritus and ery- ness 0.50-cm round piece of skin was excised from the ventral thema decreased, except adjacent to the collar. On day five of aspect of the abdomen and was preserved in neutral-buffered the episode, the collar was removed, the animal was bathed 10% formalin. Histologic examination of hematoxylin and eosin- again, Panalog was applied topically to the pruritic areas, and stained skin sections revealed moderate superficial perivascu- diphenhydramine (2.5 mg/kg) was given intramuscularly for lar dermatitis consistent with allergic reaction. The epidermis five subsequent days. After completion of therapy, pruritus and was markedly hyperplastic (acanthotic) (Fig. 3A). Numerous erythema gradually resolved over the subsequent five days. small vessels surrounded by moderate numbers of mononuclear However, the previously affected cervical, thoracic, and abdomi- cells and eosinophils occupied the superficial dermis (Fig. 3C). nal skin became lichenified. Mild pruritus developed occasion- Therapy consisted of a bath with Tar Gel shampoo (Person & ally over the next four months and was treated with a single Covy, Glendale, Calif.), administration of diphyenhydramine application of Topical Panalog and A&D ointment (Schering (2.5 mg/kg, i.m.) and childrens’ aspirin (PDK Laboratories, Plough, Memphis, Tenn.). Hauppauge, N.Y.; 81 mg, PO) and all treats were discontinued). Four months later, an acute rash, similar to the initial episode, Three days later, severe pruritus recurred and diphyenhydramine developed on the abdomen and legs. Erythema and intense pruri- (2.5mg/kg, i.m.) was re-administered. 468 Latex Sensitivity in a Macaque

Pasteur pipette and were allowed to penetrate the scarified skin for one to two minutes. The same procedure was performed on the right side, using sterile, pharmaceutical grade saline. The left and right inoculation sites were compared visually at 24, 48, and 72 h, and one week. At 24 and 48 h, both sites were inflamed and there was little difference between the two sites. How- ever, after 48 h, the latex site remained inflamed whereas the saline site inflamation was decreasing. One week later, the latex site was devoid of erythema, but was lichenified and flaky, compared with the saline site (Fig. 4). These results are consistent with a negative immediate-type hypersensitivity (type I) reaction and a positive delayed-type hypersensitivity (type IV) reaction. Vinyl gloves were substituted for latex gloves for direct animal contact and contact with caging, food, or enrichment devices. In addition to latex avoidance, we also restricted certain foods, such as bananas, avocados, chestnuts, and kiwis, because they are known to aggravate latex allergies because of cross-re- active allergenic epitopes (12). Six weeks after discontinuing latex contact, a marked decrease in erythema, pruritis, and lichenification was noted. Systemic or topical medications were not administered during this period. A second skin biopsy specimen was taken from a site adjacent to the original biopsy site (14 weeks after the original biopsy). There was marked reduction in epidermal thickness, and almost complete resolution of superficial dermal neovascularization and perivascular inflammation Figure 2. Periorbital dermatitis and conjunctivitis of the affected macaque in this report. (Fig. 3B). Small numbers of eosinophils and mononuclear cells persisted around vessels (Fig. 3D). The eosinophilia and biopsy findings were suggestive of al- Eliminating direct contact with latex prevented further rashes lergy and prompted allergen-specific testing. A thin-layer, rapid- and virtually eliminated pruritus. On occasion, accidental expo- use epicutaneous allergen patch test (Pharmacia Research Center, sure to latex occurred. These exposures (total of five) were prophy- Copenhagen, Denmark) was performed to determine whether lactically treated with diphenhydramine (2.5 mg/kg/d for 1 to 2 the skin lesions were caused by contact hypersensitivity. The days) and did not result in erythema or pruritus. The clinical im- test contained 25 commercially available contact allergens provement was substantiated microscopically by an overall de- (Table 1) that were selected on the basis of the animal’s expo- crease in inflammatory infiltrates and edema in the second biopsy sure (direct and indirect) to them or were used in the environment. specimen. Results of latex-specific IgE testing performed by the The two patches (containing 12 and 13 allergens each) were ban- same laboratory were negative at three months, and one, two, and daged to depilated skin on the animal’s back, with the boundaries three years after eliminating latex exposure. Thus, this NHP has of the patches delineated by a non-toxic marker; the patches were an underlying atopic dermatitis that is exacerbated by latex. removed after 48 h. There was no evidence of inflammation corresponding to areas of contact to allergens at 48 and 72 h. Discussion The possibility of food and/or latex allergy was investigated by Latex is a sap derived from the rubber tree Heva brasiliensis, submitting serum to a commercial laboratory for allergen-specific which contains the natural hydrocarbon cis, 1,4-polyisoprene. IgE testing (IBT Reference Laboratory, Lexena, Kans.) by use of The sap is processed by heating, followed by addition of sulfur, an FDA-approved chemiluminescent liquid phase immunoassay ammonia, and other chemicals, including preservatives, accel- (DPC). There was no IgE specific reactivity to peanuts, wheat, glu- erators, antioxidants. ten, white potato, sweet potato, or brewers yeast. However, latex The resulting product contains 93 to 95% polyisoprene and elicited a strong positive response (0.74 kU/L); values < 0.25 kU/L various amounts of allergenic proteins. Cornstarch powder, are considered negative results). An aged-matched control animal which is used to treat the surface of gloves, acts as a carrier for also had negative values for all antigens tested. latex proteins but is rarely a primary allergen (13, 14). Although An additional latex-specific allergy test, referred to as a “skin synthetic rubber also contains polysioprene, it does not contain the prick” or “scratch” test was performed. Briefly, 20 one square proteins found in latex (2, 4, 15, 16). centimeter pieces of latex glove (Evolution One, Micorflex Cor- In the human population, the range of allergic reactions to poration, Reno, Nev.) were placed in 5 ml of sterile saline and natural rubber includes: irritant dermatitis characterized by shaken periodically for two hours (11). The animal was anesthe- dryness, pruritus, and fissuring; flare of atopic dermatitis; con- tized (ketamine, 10 mg/kg, i.m.), a saphenous vein catheter was tact dermatitis characterized by erythema, swelling, pruritus, placed (as a precaution for treating anaphylaxis), the skin over and blisters; contact urticaria, which can include generalized the dorsum was shaved, and two 1-cm2 areas (left and right sides) urticaria, allergic rhinitis, and conjunctivitis; and asthma (4). were scarified five times (cross hatch pattern), using a 20-gauge Latex allergy can be manifested as immediate-type IgE-medi- needle. Two drops of the latex solution were delivered to the scari- ated (type 1) reaction to proteins contained in natural rubber or fied areas of the left lateral aspect of the dorsum by use of a as T cell-driven delayed-type (type IV) contact hypersensitivity, 469 Vol 51, No 5 Comparative Medicine October 2001

Figure 3. A and C. Skin biopsy specimens taken on initial examination of the affected macaque. Notice marked epidermal hyperplasia (indicated by white parenthesis in A). Numerous superficial dermal vessels (black arrowheads in A) are present. These are surrounded by moderate numbers of mononuclear inflammatory cells (star, C), perivascular edema (white arrowhead, C), and eosinophils (black arrow, C). B and D. Biopsy specimen taken 14 weeks later. Notice decreased epidermal hyperplasia (indicated by white parenthesis in B), superficial inflammation, and much reduced vascularity (B and D). Small numbers of mononuclear cells and a few eosinophils are present around dermal vessels (arrow, D). H&E stain; magnification, 100× (A and B) and 400× and D). presumably to the chemical additives (2, 4, 17). There is clinical sistent with a delayed-type hypersensitivity response. These evidence suggesting that type-IV sensitivities to rubber addi- findings are consistent with concurrent type-I sensitivity to tives may progress to type-I allergies to latex proteins (2). It is natural rubber proteins and type-IV hypersensitivity to chemi- well recognized that atopic dermatitis in humans is a substan- cal additives used in latex manufacturing. tial risk factor for developing type-I latex hypersensitivity (17). The diagnosis of latex allergies in people requires a history of Although atopic dermatitis has been reported in a rhesus latex contact and a positive latex-specific IgE test result. Histori- macaque, latex hypersensitivity has not been reported (18). cally, IgE-specific tests were specific but relatively insensitive (11, In this instance, the acute onset of intense erythema, pruri- 19). This may be, in part, because the latex allergen is incompletely tus, conjunctivitis, and urticaria and increased latex-specific characterized (15) and a standardized latex antigen was not avail- IgE titer are consistent with type-I immediate-type hypersen- able at the time of testing. Therefore, a scratch test is often used to sitivity reaction. However, the intervening atopic dermatitis, char- document type-I latex hypersensitivity in suspected allergy among acterized by low-grade, chronic pruritis, dryness, and lichenifi- people negative for latex-specific IgE. The scratch test is reported cation, and the delayed response (48 h) to the prick test are con- to be sensitive but carries the risk of provoking an anaphylactic re- 470 Latex Sensitivity in a Macaque

Table 1. Contact allergens used in skin testing of the affected macaque The risk of latex sensitivity is positively correlated with dura- Nickel sulfate Phenol formaldehyde tion, frequency, and type of latex exposure (2, 4). In addition to Wool alcohols Paraben mix healthcare workers, individuals with repeated mucous membrane Neomycin sulfate Carba mix Potassium dichromate Black rubber mix contact or intraoperative parenteral exposure are at substantial Canine mix Isothiazolinone risk (2, 4, 17). The animal described in this report had repeated Fragrance mix Quaternium Colophony Expoxy resin exposure to latex through nursery rearing, implant and debride- Quinoline mix Balsam of Peru ment surgeries, task training, and frequent testing sessions. Phenylenediamine Thiruam mix Once latex avoidance procedures were adopted, pharmacologic Ethylenediamine Formaldehyde Cobalt dichloride Mercapto mix intervention was not required. A decrease in intense pruritus was Thimerosal Methyl methacrylate noted in the immediate two weeks following use of vinyl gloves and Mercaptobenzothiazole the dermatitis improved (subjectively) over the following month. Since the avoidance of direct latex contact (4 years), there has not been a recrudescence of acute, urticaria, erythematous dermatitis, conjunctivitis, or intense pruritus in the macaque. However, a few episodes of inadvertent latex exposure (contact with a latex-gloved hand) occurred, after which antihistamines were administered transiently for prophylaxis to prevent urticaria and pruritus. A low-grade atopic dermatitis characterized by isolated, transient episodes of mild pruritus ensued. This case indicates that latex hypersensitivity should be considered in NHP with acute or chronic allergic dermatitis.

References 1. Centers for Disease Control. 1987. Recommendations for prevention of HIV transmission in health care settings. MMWR. 36S:2-18. 2. Hamann, C. P. 1993. Natural rubber latex protein sensitivity in re- view. Am. J. Contact Dermat. 4(1):4-21. 3. Hunt, L. W., A. F. Fransway, C. E. Reed, L. K. Miller, R. T. Jones, M. C. Swanson, and J. W. Yungiger. 1995. An epidemic of occupational allergy to latex involving health care workers. Journal of Oc- cupational and Environmental Medicine. 37(10):1204-1209. 4. Wooding, L. G., S. S. Teuber, and M. E. Gershwin. 1996. Latex allergy. Compr. Ther. 22 (6):384-392. 5. Nutter, A. F. 1979. Contact urticaria to rubber. Br. J. Dermatol. 101:597-598. 6. Turjanmaa, K., T. Reunala, R. Tuimala, and T. Karkkainenet. 1984. Severe IgE-mediated allergy to surgical gloves. Allergy 39S:35. Abstract. 7. Slater, J. E. 1989. Rubber anaphylaxis. N. Engl. J. Med. 320:1126-1130. Figure 4. Scratch testing: saline (arrowhead) and latex (arrow) sites 8. Ownby, D. R., M. Tomlanovich, N. Sammons, and J. McCol- after 7 days following scratch testing. lough. 1991. Anaphylaxis associated with latex allergy during bar- ium enema examinations. Am. J. Roentgenol. 156:903-908. 9. Centers for Disease Control. 1987. Guidelines for prevention of Herpesvirus simiae (B-virus) infection in monkey handlers. action. In the case reported here a positive latex-specific IgE titer MMWR. 36(41):680-683, 687-689. and negative scratch test results are not internally consistent, but 10. Lee, G., P. Danneman, P., R. Rufo, R. Kalesnykas, and V. Eng. comparable results have been reported in people (20). One possible 1998. Use of chlorine dioxide for antimicrobial prophylactic main- tenance of cephalic recording devices in rhesus macaques. explanation is lack of a standardized latex antigen solution for Contemp. Topics Lab. Anim. Med. 37(2):59-63. testing. Thus, the scratch test latex solution is made de novo and 11. Reitschel, R. L., and J. F. Foweler, Jr. 1995. Allergy to rubber, p. may vary widely because yields of latex proteins differ 50- to 3000- 727-729. Fisher’s contact dermatitis, 4th ed. Williams and Wilkins, fold from surgical gloves batches (2, 4, 21-23). For example, one Baltimore, Md. study indicated that skin prick positivity of 19 brands of latex 12. Lavaud, F., A. Prevost, C. Cossart, L Guerin, J Bernard, and S. Kockhman. 1995. Allergy to latex, avocado pear, and banana: gloves varied from 8 to 87% (24). These findings exemplify the po- evidence for a 30 kD antigen in immunoblotting. J. Allergy Clin. tential variability associated with scratch testing. Immunol. 95:557-564. Skin testing results can be confounded by chronic disease 13. Seggev, J. S., T. P. Mawhinney, J. W. Yunginger, and S. R. (25). However, results of a study suggested that mast cell “re- Braun. 1990. Anaphylaxis due to cornstarch surgical glove powder. Ann. Allergy 65:152-155. leasibility” was not significantly impacted in people with chronic 14. Fisher, A. A. 1987. Contact urticaria and anaphylactoid reaction urticaria (26). It is important to note that tuberculin skin testing due to corn starch surgical glove powder. Cont. Dermat. 16:224-225. in nonhuman primates has been inconsistent and false-nega- 15. Bubak, M. E., C. E. Reed, A. F. Fransway, J. W. Yunginger, R. T. tive results have been reported. Thus, anergy and the potential Jones, C. A. Carlson, and L. W. Hunt. 1992. Allergic reactions to for species-specific variability when using human-based test an- latex among health-care workers. Mayo Clin. Proc. 67:1075-1079. 16. Tarlo, S. M., L. Wong, J. Roos, and N. Booth. 1990. Occupational tigens should be considered when interpreting skin test results asthma caused by latex in a surgical glove manufacturing plant. J. in nonhuman primates (27, 28). Allergy Clin. Immunol. 85:626-631. 471 Vol 51, No 5 Comparative Medicine October 2001

17. Cormio, L., K. Turjanmaa, M. Talja, L. C. Andeersson, and M. 23. Tomazic, V. J., T. J. Withrow, and R. G. Hamilton. 1995. Charac- Ruuto. 1993. Toxicity and immediate allergenicity of latex gloves. terization of the allergen(s) in latex protein extracts. J. Allergy Clin. Clin. Exp. Allergy. 23:618-623. Immunol. 95(5):635-642. 18. Patterson, R., and K. Harris. 1981. Chronic pruritic dermatitis in 24. Turjanmaa, K., K. Laurila, S. Mäkinen-Kijunen, and T. Reunala. asthmatic monkeys: a subhuman primate analogue of atopic derma- 1998. Rubber contact urticaria: allergenic properties of 19 brands of titis? Int. Arch. Allergy Appl. 64:332-337. latex gloves. Cont. Dermat. 19:362-367. 19. Moneret-Vautrin, D. A., E. Beaudouin, S. Widmer, C. Mou- 25. Barry, M. A., A. M. Regan, L. M. Kunches, M. E. Harris, S. A. ton, G. Kanny, F. Prestat, C. Kohler, and L. Feldmann. 1993. Bunce, and D. E. Craven. 1987. Two stage tuberculin testing with Prospective study of risk factors in natural rubber latex hyper- control antigens in patients residing in two chronic disease hospi- sensitivity. J. Allergy Clin. Immunol. 92:668-677. tals. J. Am. Geriatr. Soc. 35:147-153. 20. Hadjiliadis, D., D. E. Banks, and S. M. Tarlo. 1996. The relation- 26. Pelta-Fernandez R., R. F. Gonzalo, S. M. Rubio, and N. A. ship between latex skin prick test responses and clinical allergic Ortega. 1988. Skin reactions to histamine and compound 40/80 responses. J. Allergy Clin. Immunol. 97(6):1202-1206. in chronic urticaria: a diagnostic tool. Allergol. Immunopathol. 16:23-25. 21. Yunginger, J., R. Jones, A. Fransway, J. Kelso, M Warner, 27. Smith, A. W., and H. Wolochow. 1973. Comparison of old tubercu- and L. Hunt. 1994. Extractable latex allergens and protein in lin and purified protein derivative in Macaca mulatta. Lab. Anim. disposable medical gloves and other rubber products. J. Allergy Sci. 23:373-376. Clin. Immunol. 93:836-842. 28. Davis, J. A., M. Hayre, and J. Linn. 1988. Delayed cutaneous hy- 22. Jones, R. T., M. E. Bubak, V. A. Gosselin, and J. W. Yunginger. persensitivity response in tetanus toxoid sensitized rhesus monkeys; 1992. Relative latex allergen contents of several commercial la- predictor of anergy and value in tuberculin skin testing. Lab. Anim. tex gloves (Abstract). J. Allergy Clin. Immunol. 89:225. Sci. 38:413-416.

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Latex Sensitivity in a Macaque (&lt;I&gt;Macaca Mulatta&lt;/I&gt;)

Latex Sensitivity in a Macaque (<I>Macaca Mulatta</I>)