ALLERGOL. ET IMMUNOPATHOL., 1998;26(1):23-26
CLINICAL CASE
Acute IgE-mediated generalized urticaria-angioedema after topical application of povidone-iodine
M. P. López Sáez, M. de Barrio, J. M. Zubeldia, A. Prieto, S. Olalde and M. L. Baeza
Sección de Alergología y Medicina y Cirugía Experimental. Hospital General Universitario
"Gregorio Marañón". Madrid. Spain.
SUMMARY
Povidone is a synthetic polymer mainly used as a dispersing or suspending agent for many pharmaceutical products. It is also used as a carrier for iodine. In many countries it is not mandatory its inclusion in drug labels so many adverse effects may be under diagnosed.
Povidone-iodine used as a topical antiseptic solution may produce allergic contact dermatitis and irritation. Povidone, when systemically administered may deposit in tissues causing local lesions and pain. Three cases of immediate hypersensitivity to this agent have been reported.
We present a patient who developed generalized urticaria and angioedema immediately after the first topical use of BetadineTM (povidone-iodine) on a right arm wound. The positive skin prick test to BetadineTM and povidone extract and the demonstration of serum specific IgE to povidone, confirmed an IgE-mediated hypersensitivity.
Key words: Immediate hypersensitivity. Povidone. Urticaria-angioedema.
Allergol et Immunopathol 1998;26:23-6.
INTRODUCTION
Povidone is a mixture of synthetic polymers of 1-vinil-2-pyrrolidone. Their molecular weights may range from 10.000 to 700.000 daltons. This product was originally introduced as a plasma expander for hemorrhagic or traumatic shocks. It is used as a suspending, dispersing, tablet binding, granulating and coating agent. It is contained in several pharmaceutical products and in hair sprays. Povidone solutions may be usde as artificial tears and for contact lens care. It is also a carrier for iodine (povidone-iodine), which is used as a disinfectant and antiseptic agent for the treatment of contaminated wounds, pre-operative preparation of the skin and mucous membranes as well as for disinfection of equipment.
Several adverse effects due to povidone or povidone-iodine have been reported. Higher molecular weight polymers may accumulate in reticuloendo-thelial cells of liver, spleen, lymph nodes and bone marrow. Panniculitis have been described in the skin, at the injection sites, and it may eventually accumulate in other skin locations (1, 2). It can induce pulmonary and arthritic symptoms and some patients have had povidone-associated fever (3).
Several cases of abnormal pulmonary lesions related to povidone inhalation of hair sprays have been reported due to alveolar macrophages deposits (4). Povidone can cause ocular lesions when used for intraocular lens (5). The application of povidone-iodine to severe burns or to large denuded skin areas may evoke the systemic adverse effects such as metabolic acidosis, hypernatraemia, and impairment of renal function due to the iodine effect (6, 7).
Rarely, povidone-iodine can cause severe allergic contact dermatitis, generalized erytema multiforme-like eruption and irritation of skin and mucous membranes (8-10). Three cases of immediate hypersensitivity to povidone or povidone-iodine have been reported in the literature, and an anaphylatic shock in a man after the intraarticular administration of povidone, but the authors in this case could not distinguish between an allergic reaction or a non specific histamine release (11).
We present a case of a patient who developed an acute generalized urticaria-angioedema to a topical povidone-iodine application. Allergic IgE-mediated mechanism is supported by in vivo and in vitro tests.
CASE REPORT
A 27 year-old-male developed itching of the soles, generalized hives and swelling of the face immediately after the first topical use of BetadineTM (povidone-iodine, 1 mg/ml) on a right arm wound. He was successfully treated with antihistamines and systemic steroids.
Skin prick test were positive to BetadineTM (Fig. 1) and to povidone extract (35 mg/ml) (Fig. 2) in our patient and negative in eight normal controls. Other iodine-containing drugs (potassium iodine, lugol''s solution, amidotrizoic acid and iopamidol) were skin tested and resulted negative.
Fig. 1--Skin prick test to BetadineTM. S: Saline serum. H: Histamine. B: BetadineTM.
Fig. 2--Skin prick test to Povidone (35 mg/ml). SS: Saline serum. H: Histamine.An anaphylaxis associated with vaginal application of povidone-iodine solution was described in 1995 by Waran et al (13). Prick test to povidone-iodine caused urticaria and generalized pruritus. It was not determined if the povidone itself or the iodine was the responsible agent.
An enzyme linked immunosorbent assay (ELISA) was developed to detect specific IgE: Briefly, 100 µl of povidone in PBS (10 mg/ml), potassium iodine, lugol''s solution, amidotrizoid acid and iopamidol were applied to a 96 well microtiter plate for 24 hours at 4° C. The plate was washed three times with Casein Thimerosal Buffer and blocked with 0.5% BSA in PBS for one hour. After washing, 100 * of patient''s and five control''s sera were incubated in triplicate for 2 hours at 37° C. The plate was thoroughly washed 4 more times and 100 * of peroxidase-labeled anti human IgE (1:500) was applied for 1 hour at 37° C. After washing, peroxidase substrate solution was added and the reaction stopped with 2 N Sulphuric Acid.
ELISA resulted slightly positive to povidone and negative to the rest of the iodine products (table I). None of the control sera reacted to any of these preparations.
| Table I | |||||
Serum specific IgE (ELISA) to povidone | |||||
| O.D.490 | Povidone | Lugol''s solution | Potassium iodide | Amidotrizoic | Iopamidol |
| Patient | 0.158 | 0.020 | 0.062 | 0.015 | 0.016 |
| Control | 0.007 | 0.011 | 0.017 | 0.020 | 0.062 |
DISCUSSION
Three cases of allergic reactions to povidone have been reported. In 1989, Moneret-Vautrin and coauthors (12) described a patient who suffered a bronchospastic reaction two hours after a hysterosalpingography with contrast media containing povidone. The intradermal tests were positive to povidone-iodine 0.1 mg/ml and povidone alone (0.1 mg/ml), and negative to other iodine compound (TélébrixTM: meglumine ioxithalamate). In vitro histamine release and basophil degranulation resulted positive.
Recently, Azofra and Carbajo (14) reported a case of anaphylactic shock after shoulder infiltration with a corticosteroid that contained povidone as excipient (Cortidene depotTM). The corticosteroid (paramethasone), as well as two other excipients included in the formulation (bezalkonium and sorbitol) was ruled out by negative provocation tests. The patient suffered an urticaria after the intramuscular administration of povidone (the third excipient). An intradermal test with this agent (0.5 µg/ml) was positive.
In vitro specific IgE to povidone was not determined in any of three cases, although the first one demonstrated a positive histamine release.
We report a patient who developed an acute generalized urticaria-angioedema after the first topical application of BetadineTM. Allergic IgE-mediated pathogenesis is supported by skin prick test and in vitro assay. The IgE ELISA demonstrated the presence of specific IgE in patient''s serum. A weak positive result was obtained may be because a low absorption of the molecule to the microtiter plate. Non specific binding was ruled out because the negative results obtained to other molecules and with five control sera to povidone.
It is probable that our patient had been previously sensitized by the administration of other pharmaceutical preparations containing povidone as excipient. This product is contained in several preparations including antihistamines, diuretics, analgesics, etc, and anaphylactic reactions to this compound are increasingly being reported. In many countries it is not mandatory the inclusion of povidone in drug labels, generating an important problem when allergists study adverse reaction to these drugs. We alert Health Authorities of the relevance of a full description in all pharmacological labels.
RESUMEN
La povidona es un polímero sintético principalmente usado como dispersor y coadyuvante de la solubilidad en múltiples preparados farmacológicos. También es empleada como vehículo del yodo. Su identificación en las etiquetas de los fármacos no es obligatoria en muchos países, lo que dificulta el diagnóstico de sus reacciones adversas.
La povidona iodada, usada como solución antiséptica, puede producir dermatitis de contacto e irritación. La povidona, cuando es administrada sistemáticamente, puede depositarse en diversos tejidos causando lesiones locales. Tres casos de hipersensibilidad inmediata a este compuesto se han descrito en la literatura.
Presentamos el caso de un paciente que sufrió urticaria y angioedema generalizados tras la primera aplicación tópica de Betadine® (povidona iodada, 1 mg/ml) en una herida del brazo derecho. Las pruebas cutáneas en prick con Betadine® y con extracto de povidona y la detección de IgE sérica específica a povidona, confirman un mecanismo de hipersensibilidad mediada por IgE.
Palabras clave: Hipersensibilidad inmediata. Povidona. Urticaria-angioedema.
REFERENCES
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12. Moneret-Vautrin DA, Mata E, Gerard H, Tréchot M. Allergie probable à la polyvidone, responsable d''un accident à un produit iodé de contraste: à propos d''un cas d''asthme après hystérosalpingographie. Allergie et Immunologie 1989;21:196-9.
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14. Azofra J, Carbajo MP. Hipersensibilidad frente a un excipiente: polivinilpirrolidona. Rev Esp Alergol Inmunol Clin 1996;11:243-5.
| Correspondence: M. Luisa Baeza Sección de Alergia. HGU Gregorio Marañón C/ Dr. Esquerdo, 46 28007 Madrid. SPAIN |
