Integrated, multidisciplinary care for hand eczema: design of a randomized controlled trial and cost-effectiveness study

Background: The individual and societal burden of hand eczema is high. Literature indicates that moderate to severe hand eczema is a disease with a poor prognosis. Many patients are hampered in their daily activities, including work. High costs are related to high medical consumption, productivity loss and sick leave. Usual care is suboptimal, due to a lack of optimal instruction and coordination of care, and communication with the general practitioner/occupational physician and people involved at the workplace. Therefore, an integrated, multidisciplinary intervention involving a dermatologist, a care manager, a specialized nurse and a clinical occupational physician was developed. This paper describes the design of a study to investigate the effectiveness and cost-effectiveness of integrated care for hand eczema by a multidisciplinary team, coordinated by a care manager, consisting of instruction on avoiding relevant contact factors, both in the occupational and in the private environment, optimal skin care and treatment, compared to usual, dermatologist-led care. Methods: The study is a multicentre, randomized, controlled trial with an economic evaluation alongside. The study population consists of patients with chronic, moderate to severe hand eczema, who visit an outpatient clinic of one of the participating 5 (three university and two general) hospitals. Integrated, multidisciplinary care, coordinated by a care manager, including allergo-dermatological evaluation by a dermatologist, occupational intervention by a clinical occupational physician, and counselling by a specialized nurse on optimizing topical treatment and skin care will be compared with usual care by a dermatologist. The primary outcome measure is the cumulative difference in reduction of the clinical severity score HECSI between the groups. Secondary outcome measures are the patient's global assessment, specific quality of life with regard to the hands, generic quality of life, sick leave and patient satisfaction. An economic evaluation will be conducted alongside the RCT. Direct and indirect costs will be measured. Outcome measures will be assessed at baseline and after 4, 12, 26 and 52 weeks. All statistical analyses will be performed on the intention-to-treat principle. In addition, per protocol analyses will be carried out. Discussion: To improve societal participation of patients with moderate to severe hand eczema, an integrated care intervention was developed involving both person-related and environmental factors. Such integrated care is expected to improve the patients' clinical signs, quality of life and to reduce sick leave and medical costs. Results will become available in 2011

Patch Testing in Adverse Drug Reactions

Patch testing primarily indicated for the study of T-cell-mediated allergic contact dermatitis also has an important place in the diagnosis of T-cell-mediated (non-immediate) drug eruptions, which include maculopapular exanthema, DRESS, SJS/TEN, AGEP, SDRIFE, fixed drug eruption, and drug photoallergy. When facing a possible drug eruption, it is of outmost importance to characterize the clinical pattern and obtain a complete history of drug exposure and its chronologic relation with the onset or aggravation of cutaneous lesions. After resolution of the eruption, patch testing can be used as a safe form of cutaneous provocation to confirm the culprit drug and crossreactive chemicals. A positive test performed according to the recommendations is highly specific and reproducible, even after long intervals. Patch testing can be performed as a first step before an oral challenge, which has more risks and is contraindicated in severe drug eruptions. It is advised to patch test all possible culprits and related drugs, as patch testing can also be used to study concomitant sensitizations and cross-reactions, which can vary with the drug, way of exposure and pattern of the drug reaction. A positive cross-reactive reaction can advise future drug avoidance, whereas a negative reaction can be an indication for using the drug in an oral challenge to ascertain its safety. Methodology and interpretation of patch testing in drug eruptions is similar to allergic contact dermatitis. As there are few commercialized patch test substances, in most cases drugs have to be prepared in-house, whenever possible in a final dilution of the active principle at 10% pet. Application on the back and occlusion for 48 h is recommended except in fixed drug eruptions where duplicate tests are needed, one of them applied for 24 h on a residual lesion. Patch test reactivity with drugs depends mainly on the culprit drugs and on the clinical pattern of the eruption. Patch testing is positive mostly in maculopapular exanthemas, DRESS, and fixed drug eruptions and less often in SJS/TEN. For drugs like abacavir, carbamazepine, pristinamycin, and tetrazepam, patch tests are almost always positive, and reactivity to aminopenicillins and other antibiotics, diltiazem, and radiocontrast media and some NSAIDs is usually above 20% or higher in selected cases with high clinical imputability. Allopurinol and sulfasalazine cannot be identified by patch testing, and sensitivity of patch tests for several drugs is not known. Therefore, a negative patch test cannot exclude a possible culprit, but a positive patch test is almost always relevant, can confirm drug imputability, evaluate cross-reactions, and study the mechanisms involved in the reaction

Diagnosing lanolin contact allergy with lanolin alcohol and Amerchol L101

Background: The prevalence of lanolin contact allergy in dermatitis patients varies from 1.2% to 6.9%. Different lanolin derivatives are used in patch testing. Objectives: To determine which combination of lanolin derivatives is most effective in patch testing for the diagnosis of lanolin contact allergy. Methods: A retrospective analysis of patients patch tested between 2016 and 2017 was performed. Patients were eligible if they had been tested with lanolin alcohol 30% pet., Amerchol L101 50% pet., and a supplementary series containing other lanolin derivatives. Lanolin alcohol and Amerchol L101 were tested in duplicate. Results: Of 594 patients, 28.6% (95% confidence interval [CI]: 25.1%-32.3%) had a positive patch test reaction to at least one lanolin derivative. Reactions to lanolin alcohol (14.7%, 95%CI: 11.3%-18.2%) and Amerchol L101 (15.0%, 95%CI: 11.5%-18.5%) were common in the routinely tested series. Reactions to other test preparations were significantly less frequent (P < 0.05). The addition of Amerchol L101 to lanolin alcohol significantly increased the number of positive cases (odds ratio 1.79, P < 0.001). Conclusions: The combination of lanolin alcohol and Amerchol L101 is effective in patch testing for the diagnosis of lanolin contact allergy. Routinely testing with other lanolin derivatives may not be worthwhile, as it detects only a few additional patients

Allergic contact dermatitis to nickel: Modified in vitro test protocols for better detection of allergen-specific response

To date, no in vitro test is suitable for routine diagnosis of contact allergy. The aim of our study was to establish improved in vitro test protocol for the detection of antigen-specific responses of lymphocytes from patients with allergic contact dermatitis to nickel (Ni-ACD). Blood leucocytes from 14 Ni-ACD patients and 14 controls were cultured in the presence of 'cytokine cocktails' skewing lymphocytes towards 'type 1' [interferon-γ (IFN-γ)-secreting] or 'type 2' [interleukin (IL)-5 and IL-13-secreting] phenotypes. The cocktails consisted of IL-7 and, respectively, either IL-12 or IL-4. Cell responses to nickel were measured with enzyme-linked immunospot assay (ELISpot), enzyme-linked immunosorbent assay (ELISA), and lymphocyte proliferation test (LPT). Significant differences between patients with Ni-ACD and controls were found for the 'type 2' cytokines IL-13 and IL-5, with further increase of allergen-specific responses occurring when cultures were supplemented with IL-7 and IL-4. No significant differences were found for IFN-γ. The best correlate to clinical diagnosis was LPT with 'type 2' skewing (r = 0.739, P < 0.001), followed by IL-13 ELISpot with 'type 2' skewing (r = 0.654, P < 0.001). The non-radioactive method that correlated best with LPT was IL-2 ELISpot (r = 0.809, P < 0.001). Overall, we conclude that combining ELISpot assay with proposed modifications of culture conditions improves detection of specific lymphocyte responses in contact allergy to nickel