Lanolin allergy: crisis or comedy

Lanolin has been applied to human skin from at least Egyptian times. Its virtues as an emollient and vehicle for cosmetics and drugs have been extolled for centuries. 50 years ago, a fly was found in the ointment--the first case of lanolin allergy was reported (1). Since then lanolin has achieved considerable notoriety as a contact sensitizer. Dozens of articles in the dermatologic literature emphasize the high frequency of lanolin allergy. European dermatologists seem to have become especially sensitized to lanolin allergy. Medical students learn early on, that medicaments in lanolin bases are hazardous. Every novice knows that lanolin is a sensitizer! The nadir of lanolin's fall from grace has been reached in advertisements of topical drugs which emphasize the absence of lanolin in the vehicle. These denouncements by dermatologists have not slowed down the demand for lanolin. About 2 billion pounds of finished cosmetics contain lanolin or its derivatives. It is impossible to reconcile this expanding market with the apprehensions of skin doctors. It is my intention to review the history of lanolin allergy, to present experimental data on its contact sensitizing potential and to put the risk of lanolin allergy in perspective.     

The myth of lanolin allergy

Lanolin has the reputation of being an important contact sensitizer. The market place abounds with products that are labeled "lanolin free". In fact, lanolin is at most a weak contact allergen. The supposed hazards of sensitization to lanolin products are a resultant of faulty science and failure to appreciate the limitations of patch testing. Lanolin allergy is a myth created mainly by overzealous professional patch testers. No one has succeeded in sensitizing animals or humans to lanolin or wool wax alcohols. Most of the case reports are false positives, in association with the angry back syndrome.     

Hypersensitivity to hydrogenated lanolin

The number of patients with dermatitis from applied betamethasone-17-valerate ointment, which incorporated hydrogenated lanolin, rapidly increased in Japan after 1971. On patch testing, the incidence of hypersensitivity to hydrogenated lanolin is significantly higher than to anhydrous lanolin at the 1% level, that is 5.20% (26/502) with the former and 1.99% (10/502) with the latter, although sensitivity to both materials is significantly related at the 0.5% level. The possible explanations considered are that hydrogenated lanolin contains three main allergens: the first is a group of lanolin alcohols which are the common eczematogens in anhydrous lanolin; the second refers to the products of hydrogenation, composed of saturated, easily oxidized, organic substances of low molecular weight; and the third refers to traces of nickel, copper and chromium, as a result of contamination in the hydrogenation process.     

Lanolin of reduced sensitizing potential

Confirmation has been obtained that reducing the content of natural free alcohols in lanolin to below 3 % particularly in the absence of detergent residues, reduces the incidence of positive patch test reactions amongst selected lanolin-sensitive skin patients by 99.3 %. Only one reaction out of 149 subjects was recorded.     

Testing a purified lanolin preparation by a randomized procedure

Patients with a previous contact allergy to lanolin (wool alcohols and/or Amerchol L 101) were patch tested 1 to 4 years later with lanolin allergens, as well as purified anhydrous lanolin contained in a commercial cream. At this retest, only 20 out of 33 patients with a previous contact allergy to lanolin reacted to lanolin allergens, and only 1 to the purified lanolin (as is). None reacted to the commercial cream containing 6% purified lanolin, this being ascertained by patch test as well as by usage test. To avoid bias at reading, patch tests were applied in a randomized computer-based order and read blindly.     

Lanolin with reduced sensitizing potential A preliminary note

The allergens of lanolin appear to lie in the content of natural free fatty alcohols rather than in the total alcohols as hitherto supposed. The delectable incidence of allergy is increased by the simultaneous presence of detergent. Amongst selected lanolin-sensitive skin patients, removal of both free fatty alcohols and detergent from lanolin reduces the incidence of detectable hypersensitivity by 96 %. Methods are described for determining free fatty alcohols and detergent in lanolin, and for removing them.     

Lanolin and derivatives chemistry: Relationship to allergic contact dermatitis

This paper summarizes lanolin, the composition of its esters, acids and alcohols, its chemical and physical modifications, and refining. It discusses lanolin, its constituents and derivatives, and their relationship to allergic contant dermatitis.     

A high prevalence of sensitization still persists in leg ulcer patients: a retrospective series of 106 patients tested between 2001 and 2002 and a meta-analysis of 1975-2003 data

BACKGROUND: Sensitization to topical treatments used in leg ulcers is common. Questioning and patch testing are used to identify causative drugs or dressings. OBJECTIVES: To study the current frequency of sensitization in our centre, to analyse previously published studies, and to compare sensitization in recent years with studies published before 1990. METHODS: A retrospective study was undertaken of all patients admitted with leg ulcers in 2001 and 2002. Of the files of 235 patients with leg ulcers reviewed, we identified 106 patients (group A) who had been patch tested in our institution between 2001 and 2002 with the European standard series and an additional series. The frequency of sensitization was compared with an earlier unpublished retrospective study in our centre of 36 leg ulcer patients tested in 1988 (group B), with a group of unselected contact dermatitis patients tested between 1 January 1997 and 31 December 2000 in our centre (group C), and with results published in the literature. We performed a computerized database search of MEDLINE and compared results obtained in recent years with those obtained before 1990 to obtain evidence of changing trends. RESULTS: Seventy-five per cent of the 106 patients had at least one positive reaction, and 57% had two or more positive reactions. Balsam of Peru was positive in 40% of cases, followed by lanolin (21%), fragrance mix (18%), trichlocarban (13%), colophony (11%), Cetavlon (cetrimide cream) (9%) and neomycin (9%). Thirty-five of the 36 group B patients had at least one positive reaction. Lanolin was the most frequent (31%), followed by balsam of Peru (22%), Cetavlon (19%), colophony (14%), terebenthene (14%), quinoline mix (11%) and benzocaine (8%). Two hundred and eighty-six of 526 patients of group C were positive in at least one test (54.4%). Three allergens gave a sensitization rate >10%: balsam of Peru (12.5%), fragrance mix (15.2%) and nickel sulphate (21.1%). Review of the literature and calculation of sensitization rates in a pool of 3043 patients extracted from 24 series, plus our own, showed persistence of high sensitization rates and a significant (8.5%) increase in sensitization between the two periods compared. There was a decrease in sensitivity to lanolin, constant sensitization to aminoglycosides, a slight increase in sensitivity to thiuram mix and glucocorticoids, and a marked increase in sensitivity to balsam of Peru in France. Newer topical treatments and dressings showed very low rates of sensitivity with the exception of hydrogels. CONCLUSIONS: Despite warnings, sensitization to topical treatments for leg ulcers is still frequent and, moreover, continues to increase, some variations reflecting local nursing practices and variations in topical treatment available. Although a decrease in sensitization rate with lanolin has been observed throughout the world, no decrease in sensitization rate has been demonstrated with aminoglycosides, and sensitization to glucocorticoids, thiuram mix and new products (hydrogels) is now increasingly being reported.     

A retrospective analysis of contact allergy to lanolin

BACKGROUND: Lanolin is often stated to be an important sensitizer but some of the available literature is based on the analysis of high-risk patients. OBJECTIVES: To analyse the frequency of contact allergy to lanolin (wool alcohols) in a central London teaching hospital patch-test population. METHODS: Review of 24,449 patients recorded on our database during 1982--96 who were tested with a standard series containing 30% wool alcohols. RESULTS: The mean annual rate of sensitivity to this allergen was 1.7%. The wool alcohols-allergic group contained a higher proportion of females (P < 0.05), and the mean age of both males and females (48.4 and 49.2 years) was higher than that of non-wool alcohols-allergic patients (41.4 and 35.9 years; P < 0.0005). There was no difference in atopic eczema status between these groups. The highest prevalence of allergy to wool alcohols was among patients with lower leg dermatitis (6.0%; 95% confidence interval, CI 4.46--7.54), followed by those with anogenital dermatitis (3.23%; 95% CI 1.81--4.65). There was an unexplained decline in the rate of positive patch tests to Amerchol L-101. However, some patients who reacted to this were negative with wool alcohols, so it may be a useful additional test reagent. The mean rates of allergy to Eucerin (0.65% per annum) and 50% hydrogenated lanolin in petrolatum (1% per annum) were low, and we no longer use these as test reagents. CONCLUSIONS: This study illustrates that lanolin sensitization has remained at a relatively low and constant rate even in a high-risk population (i.e. patients with recent or active eczema).     

Nickel contact sensitivity in the guinea pig. An efficient open application test method.

Nickel contact sensitivity was successfully induced in guinea pigs using an open epicutaneous application method. Immediately after pretreatment with 1% aqueous sodium lauryl sulfate, upper back skin was treated daily for 4 weeks with 0.3%-3% nickel sulfate in either a 1% lanolin cream (Vaseline, pH 5 SAD crème) or hydroxypropyl cellulose. Weekly intradermal injections with aluminium potassium sulfate were used as adjuvant. The animals were challenged twice with a one week interval, with nickel sulfate 2% in water and 1% in petrolatum, respectively. The response rates in the test groups treated with nickel sulfate 1% or 3% in the lanolin cream or 1% in hydroxypropyl cellulose were significantly different from the response rate in the control group. Considering both readings at both challenges, the frequency of sensitization was 57-93% (8 of 14 to 13 of 14 animals) in the group treated with 1% in the lanolin cream, 60-100% (9/15 to 15/15 animals) in the group treated with 3% in the lanolin cream, and 67-75% (8/12 to 9/12 animals) in the group treated with 1% in hydroxypropyl cellulose. Rechallenge of initially sensitized animals 10 weeks later confirmed that a lasting contact allergy had been obtained.     

Softisan – a new vehicle for patch testing

Petrolatum is a good vehicle for many patch test allergens, because it is stable, unreactive, and allergy to it is rare (1, 2). Some difficulties exist, however, when water-soluble allergens are tested, because emulsifiers are often needed; these can change the properties of both the test material and the vehicle itself (3, 4). In the present study, we compared petrolatum with a new lanolin substitute based on vegetable fatty acids as a patch test vehicle for nickel sulphate.     

An investigation of the irritant and allergenic properties of daffodils (Narcissus pseudonarcissus L., Amaryllidaceae)

Irritancy of daffodil flowers and bulbs was assessed using various fresh plant preparations, solvent extracts and some of the known Amaryllidaceae alkaloids on guinea pigs. Sensitization was also carried out on guinea pigs using these plant preparations, solvent extracts and 7 fractions obtained after preparative chromatography of the bulb ether extract. Only 1 fraction, containing 2 alkaloids, was capable of inducing delayed hypersensitivity in the animals; the sensitivity achieved, however, was weak. The substances were identified as masonin and homolycorin, which acted as elicitors, but masonin may also be a sensitizer. While homolycorin is a known daffodil constituent, masonin has not been found previously in Narcissus pseudonarcissus. 3 other alkaloids as well as chelidonic acid and isorhamnetin were non-elicitors in the sensitized guinea pigs.     

The functional state of the pituitary-thyroid gland system in patients with eczema

The function of the hypophyseo-thyroid system has been examined by radioimmunoassays in 185 patients suffering from eczema. In 62% of patients thyroid function has been found increased. The findings evidence a relationship between the severity of thyroid dysfunction and the clinical pattern of the disease. Experiments with guinea pigs in whom hyperthyrosis has been induced have demonstrated that thyroxine can induce allergic DNCB-dermatitis in guinea pigs.     

Effect of vehicle on elicitation of DNCB contact allergy in the guinea pig

22 DNCB sensitized guinea pigs were challenged with varying amounts dissolved in alcohol, acetone and olive oil. DNCB applied in alcohol resulted in almost 100% positive reactions; the test scores correlated to dose. When similar amounts were applied in alcohol and acetone, the former produced a significantly higher degree of positivity. The importance of defining allergen concentration, volume or weight of test substance applied and test are size, when comparing test results in guinea pigs and humans, is emphasized.     

Attempts to induce sensitization in guinea pigs with nickel complexes.

A technique for the induction of sensitization in pigs with a nickel-alanine conjugate has been reported by other investigators. Similar results were observed in our experiments in mini-pigs. However, using the identical technique, we were unable to induce sensitization in guinea pigs with NiSO4, with nickel-alanine or other nickel-amino acid complexes, or with a complex of nickel with soluble guinea pig skin extract. These results indicate that nickel-amino acid complexes and nickel-guinea pig skin complex were not antigenic in guinea pigs with this technique. Hypotheses for the apparent failure to induce sensitization are proposed.     

The usefulness of detailed information to patients with contact allergy

To find out if patients with contact allergy are helped by computerized information lists, a retrospective study was carried out on 58 patients with contact allergy to lanolin, traced through our local database DALUK. All were sent a questionnaire about their usage of the information list, clearance of their eczema, their education and other details. Clearance of the patient's eczema was found to correlate with use of the information list. It was also found that the effectiveness of the information depended on factors such as education, family circumstances, ethnic background and, most of all, how and where the information list was used.     

Role of keratinases in dermatophytosis. IV. Reactivities of sera from guinea pigs with heat-inactivated keratinase II.

Complement-fixing antibodies to the heat-inactivated keratinase II of Trichophyton mentagrophytes var. granulosum were detectable in sera from approximately 40% of the Hartley strain guinea pigs previously infected with this dermatophyte. However, no precipitating antibodies to the heat-inactivated keratinase II were detectable in these sera. Guinea pigs immunized with the heat-inactivated keratinase II had both complement-fixing and precipitating antibodies to the keratinase II. Circulating antibodies in sera from both the infected and the immunized guinea pigs also reacted with the active keratinase II but did not inhibit its proteolytic activity.     

Harnessing the skin–thyroid connection for wound healing: a prospective controlled trial in guinea pigs

Background. Different elements of the hypothalamic–pituitary–thyroid axis have been found to be implicated in the normal physiology of the human skin. Their effects on wound healing and hair growth in rats have been described previously. There is close homology between the thyroid hormone receptors in humans and guinea pigs. Aim. To assess the effect of different doses of topical 3,3′,5‐triiodo‐L‐thyronine (T3) and recombinant human thyroid‐stimulating hormone (TSH) on wound healing in guinea pigs. Methods. Wounds were dressed every other day for 7 days, during which clinical measurements of the wounded areas were performed. Histological examination was performed at the end of the study. Results. Application of high and low concentrations of topical T3 but not TSH demonstrated a significant dose‐dependent reduction in the wound surface area through a process of contraction. The main significant histological result was an increase in the hair‐follicle count. Conclusion. Topical T3 enhances wound healing in guinea pigs, primarily by wound contraction. As this is a critical stage in healing of chronic ulcers, topical T3 could be a useful treatment for wounds.     

Deposition of Complement in the Lesions of Experimental Cutaneous Candidiasis in Guinea Pigs

Deposits of C3 have been demonstrated at the dermo-epidermal junction in the lesions of experimental cutaneous candidiasis in guinea pigs. The deposits were granular in character and similar to those previously found in the lesions of chronic mucocutaneous candidiasis in humans. Immunoglobulin, C4 and candida antigen were not detected in the lesions. C3 was also found in a similar pattern at the dermo-epidermal junction of candida-infected skin from homozygous C4-deficient guinea pigs. From these observations, it is postulated that complement deposition occurs in these lesions as a result of alternative pathway activation, perhaps by cell wall components from the infecting organisms.     

Prevention of nickel-induced allergic contact reactions with pentoxifylline

In this study, we investigated the effect of pentoxifylline, an inhibitor of TNF-α, on the contact sensitivity response induced by nickel. For induction, open epicutaneous sensitization by NiSO₄. 6H₂O (25% aq.) solution was applied on the backs of 38 albino guinea pigs 5 days a week for 4 weeks. NaCl (0.9%) solution was applied epicutaneously to 10 albino guinea pigs as a control group. 19 were sensitized by nickel and developed positive patch test reactions. Patch tests were repeated after 10 of the sensitized pigs were given pentoxifylline 20 mg/kg/day orally. At the end of this study, only 2 positive patch test reactions were observed in the pentoxifylline-treated group, while 7/9 of the untreated guinea pigs developed positive reactions. These results suggest that pentoxifylline inhibits the contact sensitivity response induced by nickel only during drug administration.