Severe cutaneous eruptions following the topical use of preparations containing bufexamac: Is it time to reconsider its registration in Australia?

Despite being a well-recognised cause of allergic contact dermatitis with an embargo in many countries around the world, bufexamac is available over the counter in topical preparations in Australia. We present a series of patients who developed severe cutaneous eruptions after the topical application of bufexamac containing preparations to highlight the potential risks of this medication, as well as advocate for the reconsideration of its registration by the Therapeutic Goods Administration in Australia.

Contact sensitization in patients with suspected cosmetic intolerance: results of the IVDK 2006-2011.

BACKGROUND: Ingredients of leave-on cosmetics and body care products may sensitize. However, not every case of cosmetic intolerance is due to contact sensitization. OBJECTIVE: To describe the frequency of contact sensitization due to cosmetics in a large clinic population, and a possible particular allergen pattern. METHODS: Retrospective analysis of data from the Information Network of Departments of Dermatology, 2006-2011. RESULTS: Of 69 487 patients tested, 'cosmetics, creams, sunscreens' was the only suspected allergen source category in 10 124 patients (14.6%). A final diagnosis 'allergic contact dermatitis' was stated in 2658 of these patients (26.3%).Compared to a control group, there were significantly more reactions to fragrance mixes I and II, balsam of Peru, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) and lanolin alcohols. No special pattern of fragrance sensitization could be identified. Among the preservatives, MI was by far the leading allergen, while sensitization to other widely used compounds like parabens or phenoxyethanol was rare. CONCLUSIONS: True allergic reactions to cosmetic ingredients are rarer than generally assumed. Limitation of exposure to MI in leave-on cosmetics and body care products is urgently needed.

Allergic contact dermatitis to topical preparations of bufexamac.

In Australia bufexamac is mainly used for pharmacist-initiated local treatment of various dermatoses. The European Medicines Agency's Committee for Medicinal Products for Human Use recently recommended that marketing authorisation for bufexamac-containing preparations be revoked throughout the European Union because of the risk of severe allergic contact dermatitis. We retrospectively reviewed the patch test database at the Skin and Cancer Foundation Inc. and identified 19 cases of positive reactions to bufexamac (5% petrolatum) from 451 people patch tested. The bufexamac reaction was deemed relevant to the presenting dermatitis in 13 of 19 (68%) patients. Bufexamac allergic contact dermatitis is under-reported in the English literature. We wish to emphasise the severity and the unusually polymorphic eruptions observed in some of the cases. Clinicians should consider the possibility of allergic contact dermatitis to bufexamac-containing preparations in all patients where there is a history of exposure, even if used for only a short time.

[Bufexamac-induced pigmented purpuric eruption]. / Kontaktallergie durch Bufexamac unter dem Bild einer chronischen Pigmentpurpura.

We report on a case of a bufexamac-induced allergic contact dermatitis with hematogenous dissemination presenting with the clinical and histological picture of a pigmented purpuric eruption. To our knowledge this is the first report on a bufexamac-induced pigmented purpuric dermatosis. It represents a further example of the clinical variety of cutaneous side-effects caused by bufexamac.

Chronic urticaria due to Blastocystis hominis.

A 24-year-old woman had a 9-week history of second to third daily urticaria that began after an episode of contact urticaria to topical bufexamac. She was found to have an underlying gastrointestinal infection with Blastocystis hominis. This was thought to be clinically relevant as she had a history of mild chronic diarrhoea. After treatment of the Blastocystis hominis, her urticaria ceased. This could indicate the importance of performing stool microscopy and culture on all patients with chronic urticaria of unknown aetiology. The relationship of urticaria to intestinal parasites and the possibility that non-steroidal anti-inflammatory medications could act as cofactors that help precipitate an urticarial reaction is discussed.

[A common and insidious side-effect: allergic contact dermatitis caused by bufexamac used in the treatment of dermatitis. Results from the Information Network of Departments of Dermatology (IDVK)]. / Eine heimtückische und häufige Nebenwirkung: Kontaktallergien durch das Ekzemtherapeutikum Bufexamac. Ergebnisse des IVDK.

BACKGROUND AND OBJECTIVE: Bufexamac is a non-steroidal, anti-inflammatory drug used in the topical treatment of atopic dermatitis, stasis dermatitis and perianal eczema. The substance is known to cause severe allergic contact dermatitis (ACD) as an adverse effect (AE), which may be indistinguishable from the eczema which is to be treated. Hence the diagnosis of this AE is often considerably delayed. In order to estimate the quantitative importance of ACD to bufexamac, data of the Information Network of (German) Departments of Dermatology (IVDK) from July 1999 to December 2004 were analysed. PATIENTS AND METHODS: During the study period, 39,392 unselected patients from 40 German departments of the IVDK were patch tested with bufexamac (5 % pet). The results of the reading after 72 hours were analysed. The dichotomized patch test result was further assessed for possible risk factors from the patients' history and clinical diagnosis by Poisson regression analysis. RESULTS: In 560 of 39,392 patients contact allergy to bufexamac was diagnosed, i. e. 1.4 % (95 % confidence interval: 1.3 - 1.5), standardized for sex and age. The Poisson regression analysis revealed a significantly increased risk associated with the following factors: multiple sensitization, perianal eczema, underlying atopic dermatitis, leg dermatitis, female gender and residence in areas of Germany other than Eastern Germany. The latter observation can be explained by low prescription rates in Eastern Germany. CONCLUSION: Bufexamac is an important allergen. Extrapolating the frequency of 1.4 % in our data to the whole German population by the CE-DUR approach yields an estimate of about 6000 cases per year. In view of the high frequency of sensitization, the pitfalls in diagnosis, the severity of the course of disease and the lack of efficacy of this drug, the risk to benefit ratio is obviously critical.

[Severe allergic contact dermatitis with generalized spread due to bufexamac presenting as the "baboon" syndrome]. / Schwere allergische Kontaktdermatitis mit generalisierter Streuung auf Bufexamac unter dem Bild eines "Baboon"-Syndroms.

HISTORY AND CLINICAL FINDINGS: A 48-year-old woman presented with acute, pruritic, sharply demarcated, erythematous, maculopapulous exanthem in the anogenital area with disseminated maculae over the back. Several days before, the patient had applied as topical treatment a bufexamac-containing ointment to the anal region. INVESTIGATIONS: The patch test showed an allergic test reaction to bufexamac. DIAGNOSIS: The case presents a serious allergic contact dermatitis with generalization, imitating a baboon syndrome, unequivocally linked to the previous topical treatment. CONCLUSION: During the last 10 years allergic reactions to bufexamac have increasingly been reported, sometimes with erythema multiforme-like reactions. Because of the high rate of sensitization, the serious clinical course of bufexamac allergy and the insidious symptoms of this side effect, sometimes mimicking the disease to be treated, the substance should be used neither for proctological nor for dermatological diseases, even more as these patients are considered to be at high risk of developing allergic contact dermatitis because of the abnormal skin barrier. Considering the data presented, the use of bufexamac should be critically reassessed.

[A severe epicutaneous test reaction to the bufexamac in a hemorrhoidal therapeutic preparation]. / Schwere Epikutantestreaktion auf Bufexamac in einem Hämorrhoidal-Therapeutikum.

HISTORY AND FINDINGS: A 49-year-old woman presented with acute perianal vesicular/bullous contact dermatitis. Other areas were over the trunk, face, neck and wrists. She reported occasional application of an ointment (Mastu S) to treat her hemorrhoids. INVESTIGATION: Patch tests (basic series, anal block, own ointment, local anesthetic, cosmetics) provoked strong vesicular and bullous reactions of persisting crescendo type, spreading far beyond the site of application, to Bufexamac, to a derivative of hydroxxamine acid, and to local applied ointment with mild or moderate antiinflammatory action. TREATMENT AND COURSE: A week after the patch tests there was a flare-up of the previous foci of dermatitis. These reactions subsided two days later after intravenous injection of prednisolone. The skin lesions healed after rapid reduction of the systemic treatment and local application of corticosteroids, bathing with tanning substances and basic preparations. CONCLUSION: While Bufexamac is not absorbed when applied rectally, perianal contamination may not be avoidable on intra-anal application and can produce sensitization.

Delayed contact hypersensitivity to non-steroidal anti-inflammatory drugs.

Several non-steroidal anti-inflammatory drugs (NSAIDs) are available for topical treatment of acute soft tissue trauma or degenerative musculoskeletal disorders; the NSAID bufexamac is mainly used for therapy of chronic inflammatory skin diseases. In order to assess the occurrence of contact allergy to NSAIDs in 371 consecutive patients presenting for diagnosis of presumed contact allergy, patch tests were performed with a standard series and additionally with a series of NSAIDs, comprising acetylsalicylic acid, bufexamac, diclofenac, etofenamate, felbinac, flufenamic acid, ibuprofen, indomethacin, and piroxicam. 17 individuals (4.6%) exhibited delayed hypersensitivity to one of the NSAID preparations: 12 patients (3.2%) had patch test reactions to bufexamac, 2 (0.5%) to etofenamate, 2 (0.5%) to indomethacin, and 1 patient (0.3%) to flufenamic acid. These patch test results corresponded well to the individual history in 11 individuals (including 10 patients with reactions to bufexamac), and in 2 patients the clinical relevance of the reactions was probable. In view of the high frequency of allergic contact reactions to bufexamac, we propose to test this drug particularly in patients with atopic eczema or other chronic eczematous diseases.

Photo Koebner phenomenon in erythema-multiforme-like eruption induced by contact dermatitis due to bufexamac.

A photo Koebner phenomenon following contact dermatitis due to bufexamac is described. A 52-year-old man presented with dermatitis on his buttocks and an erythema-multiforme (EM)-like eruption near the original lesion and on sun-exposed areas. He had been using bufexamac ointment (Anderm(R)) around and inside the anus for a few weeks before he noticed exacerbation. On patch testing, he exhibited severe contact sensitivity to bufexamac. Phototesting performed on his first visit showed that he had an abnormal reaction to UVB. An EM-like eruption similar to the original lesions developed around the irradiated sites. In this case, photosensitivity does not seem to be a drug-induced photoallergy due to systemic or topical use, but rather a photo Koebner phenomenon.

Epidemiological significance of bufexamac as a frequent and relevant contact sensitizer.

Bufexamac-containing ointments and creams are widely used by many patients with eczematous disorders as an alternative to topical corticosteroids. Recent studies provide evidence of a notable prevalence of contact sensitization in patch test populations. The aim of this study was to assess the frequency of use of this topically-applied drug by eczema patients in general, and to evaluate its potential to cause allergic contact reactions. 500 routinely patch tested patients (f:m = 377:123) were tested with bufexamac 5% and Parfenac ointment (the only commercial product available in Austria) in addition to the standard and other series of the German Contact Dermatitis Group. The packaging of the commercial product was shown to the entire study population, to decide whether or not they had ever used this product. In addition, their general practitioner was contacted to verify the anamnestic data. A total of 30 patients agreed that they had definitely used bufexamac, 5 others having probably applied it. The indication for and the duration of treatment were noted. Positive and relevant patch test reactions to bufexamac, as well as the bufexamac-containing ointment, were seen in 20 out of these 35 patients (57%), and sensitization occurred even after short-term application. Our study demonstrates that bufexamac has to be assumed to be a topical drug with a very high sensitization rate in an unselected patch test population (4% of 500 patients), and should therefore be added to the standard series.