Veronica Bellini

Successful treatment of severe pyoderma gangrenosum with pimecrolimus cream 1

© 2007 The Authors 113 JEADV 2008, 22, 101–136 Journal compilation

The Epidermal Growth Factor Receptor Inhibitor-Related Skin Toxicity Index (EGFRISTI): a new tool for grading and managing skin adverse reactions to epidermal growth factor receptor inhibitors.

Background: Skin toxicity is frequent and debilitating in oncologic patients treated with epidermal growth factor receptor inhibitors (EGFRIs). Grading and management of skin adverse events (AEs) are poorly standardized. Materials and Methods: We developed a new score (EGFRISTI: Epidermal Growth Factor Receptor Inhibitor-Related Skin Toxicity Index) which is able to quantify and monitor all EGFRI-related dermatologic AEs over time. The utility of this tool was validated in 130 patients treated with 5 different EGFRIs including both monoclonal antibodies and tyrosine kinase inhibitors. Results: The mean baseline EGFRISTI score was 26.9 (range: 6.0-64.5). Mild toxicity was found in 55 patients (42.3%), moderate toxicity in 43 (33.1%), and severe toxicity in 32 patients (24.6%). After the first-line toxicity treatment, an EGFRISTI score reduction of >75% was obtained in 31 patients (34.1%) and one of 50% in 40 patients (43.9%), while an improvement of <50% was observed in the remaining 20 subjects (22.0%). Conclusions: The EGFRISTI is a simple and reliable tool to quantify and express the severity of all clinical signs and symptoms of EGFRI skin toxicity with a single numerical value, to choose the most suitable therapy, and to measure its efficacy.

Deflazacort hypersensitivity: a difficult-to-manage case of systemic allergic dermatitis and literature review

Management of corticosteroid (CS) hypersensitivity is not easy, and the choice of an alternative CS is difficult, owing to the high frequency of cross-reactions. Deflazacort has been reported to be a safe alternative in subjects with CS hypersensitivity (1), and reports of deflazacort hypersensitivity are rare (2–7). Here, we report a difficult-to-manage case of systemic allergic dermatitis caused by deflazacort.

Drug- and virus- or bacteria-induced exanthems: the role of immunohistochemical staining for cytokines in differential diagnosis.

Background The differential clinical diagnosis between drug-induced exanthema (DIE) and virus- or bacteria-induced exanthema (VBIE) is frequently not easy because the serologic analysis for virus and bacteria and skin tests are not always exhaustive. In these cases, only the oral challenge test is nullifying. Objectives This study wants to identify 1 or more structural changes and/or cytokine markers that might be helpful in discriminating the etiology and the possible correlation with the clinical features, type of the involved drug, blood and skin eosinophilia, and time of skin biopsy. Methods Involved non–sun-exposed skin biopsy specimens were obtained from 36 patients with DIE and 30 patients with VBIE. Blood investigations, skin tests, and oral rechallenge tests were carried out in all subjects. The histopathologic features and the immunohistochemical expression of a cytokine panel [fatty acid synthase–ligand, granzyme B, interleukin (IL) 2, IL-4, IL-5, IL-10, IL-13, interferon &ggr;, perforin, tumor necrosis factor &agr;] were analyzed. Conclusions Finally, DIE and VBIE have distinct skin cytokine profile (IL-5 alone or in combination with granzyme B and perforin in DIEs was statistically more frequent than in VBIEs, mainly when skin biopsy was carried out within 2 days from clinical onset), which might be helpful in discriminating the etiology.

Bullous nonpigmenting multifocal fixed drug eruption due to pseudoephedrine in a combination drug: clinical and diagnostic observations.

Nonpigmenting fixed drug eruption (NPFDE) is a clinically recognizable entity first reported in 1987 as a variant of FDE characterized by large and well-circumscribed erythematous plaques, rarely bullous, appearing repeatedly in the same area and shortly after drug readministration without residual pigmentation. In NPFDE, the site of lesions does not remain heavily pigmented after resolution because of the absence of hydropic degeneration of the basal cell layer and of pigmentary incontinence. Among the reported causes of NPFDE, pseudoephedrine hydrochloride (Ph) is the drug most commonly associated and the bullous form was described only in 1 of the 3 patients reported by Shelley and Shelley. As in patients with classic FDE, a challenge test with the suspected drug is the gold standard in establishing the diagnosis. In fact, a patch test with the offending drug, especially when applied on the previous lesions, may help diagnosis of NPFDE, but its sensitivity and its diagnostic value are unknown. However, this diagnostic algorithm is not easy to perform when the culprit drug is in a combination tablet and when it is not available individually on the market, as in the case reported below. A 38-year-old woman affected by allergic rhinoconjunctivitis was referred to us in April 2015 for many round, large, and itchy scarlet-colored edematous multifocal plaques symmetrically localized on the upper and lower limbs, lower back, and buttocks (Figure 1, A), and on the right-hand palm (Figure 1, B), and the nape. In the latter, the plaque was centered by a serous blister (Figure 1, C ). All lesions developed 6 hours after the single administration of a combination tablet containing Ph (60 mg), triprolidine hydrochloride (Th) (2.5 mg), and paracetamol (P) (300 mg). Lesions spontaneously disappeared within 2 weeks with no residual pigmentation. The patient reported that the same drug was administered several times during the last 5 years and that 1 year before similar lesions had appeared 10 hours after the administration of the same drug (second tablet on day 2). Two months later, we carried out patch tests both on uninvolved skin (upper back) and on previously involved skin (buttock) with the combination tablet as is. This was diluted 25% and 50% w/v in petrolatum (pet) and in dimethyl sulfoxide (DMSO) (Table I). No positive reactions were observed. Although we warned the patient not to take Ph-, Th-, and P-based drugs, in July 2015, she self-administered a combination tablet containing Ph (60 mg) and Th (2.5 mg). Five hours after, all the plaques relapsed in all previous sites and with the same clinical features. The lesions spontaneously resolved in 10 days with no residual pigmentation. In view of this positive self-rechallenge and according to the patient, we subsequently performed an oral challenge test with P (day 1: 0.3 mg, and 3.0 mg 12 hours later; day 2: 30.0 mg, and 300.0 mg 12 hours later) to definitely exclude this antiinflammatory drug, with negative result. Only in September 2015 we were able to obtain separately Ph and Th to clarify the etiological role of these 2 compounds and to specify the culprit drug. The 2 chemicals were patch tested as reported in Table I. Strong positive reaction to Ph 10% in DMSO on previous buttock plaque was observed. Diagnosis of multifocal bullous NPFDE due to Ph was made. The reported case presents some atypical clinical features. To our knowledge, among the cases of NPFDE due to pseudoephedrine reported in the literature, ours is the second bullous form described. Moreover, compared with multifocal classic FDE, our patient was younger (third decade vs sixth decade of life), the latency time was shorter (5-10 hours vs 24 hours to some days), and clinical course was shorter (10-14 days vs 1-6 weeks). Our patient raises the problem of the methodology and diagnostic value of allergological tests in NPFDE caused by Ph in a combination tablet. Ph is marketed in Italy only in combination with 2 or more active ingredients. For this reason, we first patch tested the combination tablet with false negative result, likely due to Ph low concentration in a tablet that is not able to elicit a positive patch test response. Positive self-rechallenge with PhþTh in a combination tablet allowed us to confirm the clinical but not the precise etiological diagnosis of NPFDE; the latter was possible only when Ph was singularly patch tested. In conclusion, our findings support the diagnostic utility of the patch test in NPFDE when performed (i) with the culprit drug, (ii) on the previously affected area, and (iii) employing DMSO as a vehicle with the function of a penetration enhancer. Moreover, this diagnostic procedure performed by us is relevant because it is well known that serious generalized, bullous, mucosal, and cutaneous reactions may be elicited by the challenge test in cases of FDE.

Histopathologic features of erythematous papulopustular eruption to epidermal growth factor receptor inhibitors in cancer patients

Erythematous papulopustular eruption (EPPE) is the most frequent skin adverse event to epidermal growth factor receptor (EGFR) inhibitors but its histopathologic features have been poorly studied. As EPPE is a strong predictor of patients treatment response, the EPPE histopathologic features and their correlations with skin eruption severity and involved drug were investigated.

Contact allergy to isoconazole nitrate with unusual spreading over extensive regions

Correspondence: Luca Stingeni, Department of Medicine, Section of Clinical, Allergological and Venereological Dermatology, University of Perugia, 06156 Perugia, Italy; Polo Ospedaliero, Universitario Santa Maria della Misericordia, Sant’Andrea delle Fratte, 06156 Perugia, Italia. Tel: +39 0755783452; Fax: +39 0755783498. E-mail: luca.stingeni@unipg.it Conflicts of interest: The authors declare no conflict of interests. allergens in the 1990s (1); however, the last published report of contact allergy to isoconazole nitrate dates back to 1997 (2).