Evaluation of skin test reactions in patients with non-immediate type drug eruptions

Skin test reactions were evaluated in 242 patients who appeared to develop delayed type drug eruptions from the clinical course. The patch testing was positive in 62 (31.5%) of 197 patients tested and the intradermal testing in 105 (89.7%) of 117 patients. The positive ratios of intradermal testing were higher in maculopapular (MP), erythema multiforme (EM), and erythrodermic (ED) types than in eczematous (Ecz) type drug eruptions, while those of patch testing were comparatively high in ED, Ecz type, and anticonvulsant-induced drug eruptions. It is considered that the combination of patch testing and intradermal testing is useful for determination of causative drugs in delayed type drug eruptions.     

Value of patch tests in clindamycin-related drug eruptions

Background. Patch tests help to confirm the aetiology of the cutaneous adverse drug reactions involving delayed hypersensitivity mechanisms, but the results vary with the pattern of skin reaction and the culprit drug. Objectives. To analyse the results of patch tests in patients with cutaneous adverse drug reactions imputable to clindamycin and assess their contribution to the diagnosis. Patients and methods. Between 2005 and 2009, we studied patients with delayed cutaneous adverse drug reactions following administration of clindamycin, usually associated with other drugs. After resolution of the cutaneous adverse drug reaction, patch tests were performed with a series of antibiotics, including pure clindamycin 10% in petrolatum. Results. We studied 30 patients (23 females and 7 males) aged 33–86 years (mean 59.97 years) with generalized maculopapular exanthema where clindamycin was among the highly suspected drugs. Two patients had a previous positive involuntary rechallenge. Patch tests with clindamycin were positive in 9 of 30 patients (30%). More than 50 control patients patch tested with clindamycin were negative. Discussion. We considered the positive patch tests results with clindamycin, in the 9 patients with maculopapular exantema, to be specific, versus the negative results observed in the control group. Although the sensitivity is low (30%), they confirmed the responsibility of this antibiotic in cutaneous adverse drug reactions in which, with only chronological criteria, it was not possible to conclude on the culprit drug.     

Drug skin tests in cutaneous adverse drug reactions to pristinamycin: 29 cases with a study of cross-reactions between synergistins

The present study was made to determine the value of drug skin tests in patients with cutaneous adverse drug reactions (CADRs) due to a synergistin (pristinamycin) and to determine the frequency of cross-reactions between synergistins. 29 patients were referred during the onset of the CADR due to pristinamycin: 18 with maculopapular rash, 9 erythrodermas, 1 angioedema and 1 Stevens–Johnson syndrome. They all had patch tests with pristinamycin and, in most cases, with other synergistins [virginiamycin and dalfopristin–quinupristin (DQ)], prick tests (10 cases) and intradermal tests (IDT) (5 cases). Skin tests with synergistins were positive in 27 cases, patch tests with pristinamycin in 20/29 cases (69%), prick tests with pristinamycin in 3/9 cases on immediate (1 case) or on delayed (2 cases) readings, and IDT with DQ in 4/5 cases. Cross-reactions between synergistins occurred in 9/22 with virginiamycin and in 7/8 cases with DQ. Skin tests with synergistins are useful in investigating CADR due to pristinamycin. Synergistins are composed of 2 chains (1 depsipeptide and 1 macrocyclic lactone) with many structural analogies between all synergistins. According to the chemical structures and our results, it seems advisable to avoid all synergistins in patients with CADR due to pristinamycin.     

Relevance of skin tests with drugs in investigating cutaneous adverse drug reactions

Skin tests with drugs can be of value in investigating patients who have developed cutaneous adverse drug reactions (CADR), but their specificity and relevance remain to be determined. A false-positive result on skin testing can happen if it is not compared to results in control subjects. When performing intradermal tests (IDT), we have determined the lowest concentrations that induce false-positive results for many drugs, including betalactam antibiotics, cephalosporins, other antibiotics or non-steroidal anti-inflammatory drugs. Some drugs in their commercialized form contain sodium lauryl sulfate and can induce irritation when patch tested as such. When patch tested with colchicine at 10% in pet. or with a Cytotec pill (containing misoprostol) at 30% in pet., respectively, 80% of the 29 and 9 of the 10 negative controls developed false-positive results. Lastly, positive results of patch tests with drugs can be related to contact allergy to one of the components of the commercialized form of the drug, without any relevance to the investigation of a CADR, as observed in 2 cases with iodine or avocado oil.     

The usefulness of skin tests to prove drug hypersensitivity

BACKGROUND: Suspected drug hypersensitivity is common. Only a minority of cutaneous adverse drug reactions (CADRs) are allergic in origin and will reappear after the next exposure. Methods to confirm suspected CADRs are needed and skin testing could serve as one possibility. OBJECTIVES: To analyse the usefulness of skin tests in revealing drug allergy. The relevance of skin test results was evaluated with drug provocation studies. METHODS: During 1989-2001, 947 patients with a history of suspected CADR were examined with skin tests including patch tests (PTs) (826 patients), skin prick tests (SPTs) (935 patients) and photopatch tests (12 patients). The occurrence of positive and negative test reactions to different drugs was correlated with clinical history. Drug provocation was carried out in 246 patients. RESULTS: Antimicrobial drugs were suspected and tested most often. A positive PT reaction to one or more drug was seen in 89 of 826 (10.8%), most often to beta-lactams, clindamycin and trimethoprim. A positive SPT reaction was seen in 10 of 935 (1.1%) patients. Challenge was carried out in 17 patients with positive skin test results. Thirteen of 16 (81.2%) PT positives developed exanthema, three remained negative and one SPT-positive patient developed urticaria. Among skin test negatives, 207 of 229 (90.4%) challenges were negative and 22 of 229 (9.6%) were positive, 12 with exanthema, three with fixed drug eruptions and seven with urticaria. CONCLUSIONS: Skin testing, especially the PT, was a useful screening method to find a cause of CADR if the reaction was exanthema and if antimicrobial, cardiovascular or antiepileptic drugs were suspected. The SPT detected occasional positives with antimicrobials. In cases of fixed drug eruption, PTs performed at the earlier reaction site were useful. When skin tests are negative or dubious, oral challenge should be carried out to confirm the association.     

Patch tests versus use tests in skin irritation risk assessment

In the risk assessment of the ability of a substance or preparation to cause skin irritation, a patch test involving human volunteers is often seen as providing definitive information. However, the skin exposure conditions found in an occluded patch may be far removed from those in a particular use situation, not least for such reasons as the high dose per unit area, the duration of exposure and the maceration of the skin. Whilst these factors may enhance sensitivity in the identification of intrinsic hazard, they may do little to ensure accurate safety evaluation for real use. In this paper, we report data from a series of studies with an unmarketed facial skin cosmetic product. Whilst the product was unexpectedly highly irritating in a standard patch test in 30 volunteers, subsequent use tests, including a 6× daily open application to the elbow for 3 weeks and 2× daily application in a half-face test lasting 3 to 4 weeks and involving 52 volunteers failed to show any evidence of skin irritation. It is concluded that the most meaningful results for skin irritation risk assessment are likely to come from studies which involve relevant patterns of exposure.     

Non-pigmenting fixed drug eruption caused by allylisopropylacetylurea

An unusual case of a non-pigmenting fixed drug eruption caused by allylisopropylacetylurea is reported. Several hours after taking an analgesic (New Kaiteki A^®), a 30-year-old Japanese woman, who had experienced similar eruptions several times after taking other analgesics, developed numerous variously sized, itchy, round-to-oval erythematous eruptions on the trunk and extremities. After she discontinued taking this drug, all such eruptions resolved within 2 weeks, without leaving postinflammatory pigmentation. Patch testing with New Kaiteki A^® itself and one of its active ingredients, allylisopropylacetylurea, on lesional skin, but not on uninvolved skin, showed positive erythematous reactions after 2 days.