Mast cell activation test in chlorhexidine allergy: a proof of concept.

BACKGROUND: Immediate drug hypersensitivity reactions are an increasing public health issue and a frequent cause of life-threatening anaphylaxis. Conventional confirmatory testing include skin tests and, for a few drugs, quantification of drug-specific immunoglobulin E (IgE) antibodies. However, none of these tests are absolutely predictive for the clinical outcome, and can yield false-negative and false-positive results. We performed a proof-of-concept study to assess whether a mast cell activation test could improve diagnosis of IgE-mediated chlorhexidine hypersensitivity, a common cause of perioperative anaphylaxis. METHODS: Human mast cells were generated from CD34+ progenitor cells and sensitised with patients' sera to become IgE+ human mast cells (dMCIgE+), and then incubated with chlorhexidine to assess degranulation. We compared the diagnostic performance of this mast cell activation test with serum from patients with and without positive skin test and basophil activation test to chlorhexidine. RESULTS: In dMC sensitised with sera from patients with a positive skin test and basophil activation test to chlorhexidine showed drug-specific and concentration-dependent degranulation upon stimulation with chlorhexidine, determined by surface upregulation of the degranulation marker CD63. In contrast, dMC sensitised with sera from patients with a negative skin test and basophil activation test to chlorhexidine were unresponsive in the mast cell activation test. CONCLUSIONS: Our study suggests that the mast cell activation test can be used to diagnose IgE/FcεRI-dependent immediate drug hypersensitivity reactions. It also shows potential to assess the clinical relevance of drug-specific IgE antibodies in their ability to elicit mast cell degranulation, and therefore discriminate between allergy and sensitisation. Extended studies are required to verify whether this technique can be used in other causes of perioperative anaphylaxis.

Prospective Single-Center Observational Study of the Allergenic Potential of Mercromina Film and Other Common Antiseptics in Patients With Contact Dermatitis. / Estudio observacional de seguridad, prospectivo y unicéntrico para determinar la capacidad alergogénica de Mercromina Film® y otros antisépticos de uso común en pacientes con dermatitis de contacto.

INTRODUCTION: Although Mercromina Film and other topical antiseptics are widely used, they are not included in the standard series recommended by the Spanish Contact Dermatitis and Skin Allergy Research Group for testing suspected allergic contact dermatitis (ACD). Furthermore, no recent studies have investigated the allergenic potential of merbromin. OBJECTIVE: To determine the allergenic potential of merbromin and compare it with that of other topical antiseptics widely used in clinical practice, including povidone-iodine, chlorhexidine, and eosin. MATERIAL AND METHODS: Prospective single-center observational safety study of 105 patients with suspected ACD seen at the dermatology department of our hospital. RESULTS: Of the 105 patients studied, 1.9% had a positive patch test to merbromin and 12.4% were sensitized to povidone-iodine. The differences in the proportion of patients with ACD to Betadine Solución Dérmica (povidone-iodine) compared with the rest of the antiseptics was statistically significant (McNemar test, P<.05). No adverse reactions were observed in any of the patients. CONCLUSIONS: Based on the patch tests conducted, Mercromina Film has very low allergenic potential. The highest allergenic potential was observed for povidone-iodine.

Chlorhexidine-related refractory anaphylactic shock: a case successfully resuscitated with extracorporeal membrane oxygenation.

IMPORTANCE: We report a patient with a life-threatening anaphylactic reaction to a chlorhexidine-coated central venous catheter, confirmed with a high serum level of chlorhexidine-specific IgE. To our knowledge, this is the first case successfully resuscitated using extracorporeal membrane oxygenation (ECMO). Great caution is required when using chlorhexidine and chlorhexidine-impregnated catheters, given that its widespread use has the potential to sensitize certain patients and may result in life-threatening anaphylaxis on subsequent exposure. OBSERVATIONS: A case report of a single patient with life-threatening anaphylactic shock to chlorhexidine, who was successfully resuscitated using ECMO. CONCLUSIONS: We have designed a flowchart for the diagnosis and management of severe anaphylaxis. This case report highlights the potential for chlorhexidine to be a source for the development of refractory anaphylactic shock. We suggest that ECMO may save the lives of patients with severe bronchospasm and refractory anaphylactic shock secondary to chlorhexidine.

Chlorhexidine Anaphylaxis Masquerading as Septic Shock.

Chlorhexidine is a commonly used antiseptic and disinfectant in the health-care setting. Its usage has increased in recent years with intensive campaigns and infection control guidelines to combat hospital-acquired infections. As a result, patients and health-care workers (HCW) are exposed to increasing chlorhexidine usage. In recent years, adverse reactions to chlorhexidine ranging from allergic contact dermatitis, photosensitivity, fixed drug eruptions, urticaria and anaphylactic shock have been reported. Most have been isolated case reports on adverse reactions occurring in healthy individuals or HCW. We report a case of anaphylactic shock caused by applying chlorhexidine cleansing solution and masquerading as septic shock from left-leg necrotising fasciitis.

Immediate hypersensitivity to chlorhexidine is increasingly recognised in the United Kingdom.

BACKGROUND: Chlorhexidine is widely used as an antiseptic agent. It is a potentially allergenic substance that can cause severe hypersensitivity reactions. OBJECTIVE: We describe six patients who had anaphylactic reactions attributed to chlorhexidine during surgery. These patients were exposed to chlorhexidine in gels, swabs and catheters. MATERIALS AND METHODS: Six patients from three UK centres with clinical history suggestive of anaphylaxis during surgery are reported. Detailed history, review of case notes, determination of chlorhexidine specific IgE, mast cell tryptase and skin tests were performed. RESULTS: On detailed assessment five of six patients demonstrated a previous history of reactions on re-exposure to chlorhexidine. All six patients had elevated specific IgE to chlorhexidine. Skin prick test with chlorhexidine was performed in four of the six patients and was found to be positive. CONCLUSION: Immediate hypersensitivity to chlorhexidine appears to be common but underreported in the UK. We recommend that centres investigating patients with reactions during anaesthesia and surgery should routinely include testing for chlorhexidine allergy.

IgE-mediated allergy to chlorhexidine.

BACKGROUND: Investigations at the Danish Anesthesia Allergy Centre have included testing for allergy to chlorhexidine since 1999. OBJECTIVE: To investigate whether measurement of IgE and histamine release confirm an IgE-mediated mechanism for chlorhexidine allergy. METHODS: Twenty-two patients with clinical history suggestive of chlorhexidine allergy were included. Skin tests with chlorhexidine and tryptase measurements were performed during initial investigations. Sera were analyzed retrospectively for IgE and histamine release (passive sensitization) to chlorhexidine. RESULTS: Twelve patients were skin test positive and 10 were skin test negative. Of the skin test-positive patients, 11 of 12 had IgE to chlorhexidine and 7 of 11 had a positive histamine release test. None of the skin test-negative patients had specific IgE or positive histamine release to chlorhexidine. Skin test-positive patients had higher median age (64 vs 49 y) and were mainly male (11/12 vs 6/10). In both groups, 8 patients had hypotension, but bronchospasm mainly appeared in skin test-negative patients (1/12 vs 6/10). Reactions occurred more often during urologic surgery in skin test-positive patients (5/12 vs 0/10). Baseline tryptase was higher in skin test-positive patients (median, 11.5 vs 3.7 microg/L), and 6 of 7 patients had elevated IgE to chlorhexidine in serum at the time of reaction. CONCLUSION: This study confirms that chlorhexidine allergy is IgE-mediated and that measurement of specific IgE and histamine release are good adjuncts to skin testing in patients with clinical history suggesting chlorhexidine allergy. CLINICAL IMPLICATIONS: IgE and histamine release can be used to support the diagnosis of allergy to chlorhexidine.

Symptoms of immediate chlorhexidine hypersensitivity in patients with a positive prick test.

There are numerous reports of anaphylaxis from chlorhexidine in surgical operations and other medical procedures, usually due to its application to wounds or mucous membranes. We wanted to analyse the clinical data of patients with a positive chlorhexidine prick test and perform some additional testing. We studied the case records of the patients with a positive chlorhexidine prick test and performed an open application test and tests for specific IgE. We found 33 patients with a positive prick test. 10 of them had had severe symptoms from chlorhexidine, and 11 had had only mild local symptoms. The size of the prick test reaction was mainly in line with the strength of the severest symptoms. Small 3- to 4-mm reactions were usually without obvious clinical relevance. Specific IgE could be demonstrated in 6 patients out of 14 tested by the ImmunoCAP method. Besides severe attacks, patients with a positive prick test often have milder local symptoms, such as exacerbation of dermatitis. Local symptoms from chlorhexidine-containing products may precede severe attacks. We recommend a prick test to be performed routinely when symptoms during medical interventional procedures, e.g. local and general anaesthesia, are investigated.