Sima Halevy

Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms : does a DRESS syndrome really exist?

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Acute generalized exanthematous pustulosis (AGEP) – A clinical reaction pattern

Background: A wide range of diseases or reactions can cause pustular eruptions of the skin. In this spectrum there seems to be a subgroup with characteristic clinical features and a typical course which is mostly caused by drugs for which the term acute generalized exanthematous pustulosis (AGEP) has been established.

A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs.

Background Stevens–Johnson syndrome (SJS) and its severe form, toxic epidermal necrolysis (TEN), are rare but life-threatening cutaneous adverse reactions to drugs, especially to allopurinol, carbamazepine, lamotrigine, phenobarbital, phenytoine, sulfamethoxazole, oxicam and nevirapine. Recently, a strong association between carbamazepine and allopurinol induced SJS or TEN has been described with respectively, HLA-B*1502 and HLA-B*5801 in a Han Chinese population from Taiwan and other Asian countries. Objective The objective is to further investigate the relationship between SJS/TEN and HLA-B in a large number of patients in a European population. Methods HLA-B genotyping was performed on 150 patients included in a European study (RegiSCAR) of SJS and TEN. We focused on patients related to ‘high-risk’ drugs including: 31 cases related to allopurinol, 28 to sulfamethoxazole, 19 to lamotrigine and 14 to oxicam. Results Sixty-one percent of 31 allopurinol-induced SJS/TEN patients carried the HLA-B*5801 allele and the figure was 55% for 27 patients of European ancestry [odds ratio=80 (34–187)], (P<10−6) as previously observed in Han Chinese. For other drugs, two rare alleles showed a weaker association with SJS/TEN in a limited number of patients: B*38 for sulfamethoxazole or lamotrigine-related patients, and B*73 for oxicam. Conclusion At variance with prior results in Asia, this study shows that even when HLA-B alleles behave as strong risk factors, as for allopurinol, they are neither sufficient nor necessary to explain the disease. Further investigations are necessary to delineate the exact role of the HLA region in SJS/TEN, and to look for other associations in other regions of the genome.

Risk factors for acute generalized exanthematous pustulosis (AGEP)—results of a multinational case–control study (EuroSCAR)

Background  Acute generalized exanthematous pustulosis (AGEP) is a disease characterized by the rapid occurrence of many sterile, nonfollicular pustules usually arising on an oedematous erythema often accompanied by leucocytosis and fever. It is usually attributed to drugs.

780 nm low power diode laser irradiation stimulates proliferation of keratinocyte cultures: Involvement of reactive oxygen species

The purpose of this study was to determine irradiation parameters of a 780 nm low power CW diode laser (6.5 mW) leading to enhanced proliferation of cultured normal human keratinocytes (NHK). The possible role of reactive oxygen species (ROS) in this response was evaluated.

Lichenoid drug eruptions

Lichen planus-like or lichenoid eruptions from certain drugs and compounds can closely mimic idiopathic lichen planus. The patients history and physical examination histopathologic criteria, and certain tests can assist in the differentiation between a lichenoid drug eruption and idiopathic lichen planus and in the identification of the offending drug.

Comprehensive Survival Analysis of a Cohort of Patients with Stevens Johnson Syndrome and Toxic Epidermal Necrolysis

Stevens-Johnson syndrome and toxic epidermal necrolysis are severe cutaneous adverse reactions that are of major concern because of high mortality rates. On the basis of data collected in the RegiSCAR study, the aim was to assess risk factors (including modalities of patient management) for mortality, regardless of the cause, up to 1 year after the reaction. Within this cohort, the mortality rate was 23% (95% confidence interval (CI) 19-27%) at 6 weeks and 34% (95% CI 30-39%) at 1 year. Severity of reaction was a risk factor for mortality only in the first 90 days after onset, whereas serious comorbidities and age influenced mortality beyond 90 days and up to 1 year after onset of reaction. The risk of death for patients with identified drug cause was borderline lower than for patients with a reaction of unknown cause (hazard ratio 0.66, 95% CI 0.45-0.96). The study could not provide conclusive evidence regarding patient management. This large-scale population-based follow-up study of such patients confirmed high in-hospital mortality and revealed a remarkable number of deaths after discharge, which could mainly be attributed to severe comorbidities and older age, whereas the impact of severity of reaction on the risk of death was limited to the first few weeks.

Topical treatment of Old World cutaneous leishmaniasis caused by Leishmania major: A double-blind control study

BACKGROUND A controlled study of the efficacy of topical paromomycin sulfate (PR) and methylbenzethonium chloride (MBCl) in cutaneous leishmaniasis (CL) has not yet been performed. OBJECTIVE The therapeutic effect of an ointment containing 15% PR and either 12% or 5% MBCl (15/12 or 15/5 P-ointment) on patients suffering from Old World CL was examined in a randomized, double-blind, cross-over study. METHODS Thirty-nine patients with Old World CL caused by Leishmania major were treated topically, twice daily, for 10 to 20 days with 15/12 or 15/5 P-ointment and 10 to 20 days with a placebo ointment to achieve a total of 30 days of treatment in all groups. RESULTS In the P-ointment-treated groups, 74.2% (29 of 39 patients) of the patients were cured versus 26.6% (4 of 15 patients) in the placebo-treated group. Little difference was found between the 15/12 and 15/5 P-ointment groups. CONCLUSION In most of the patients treated with the active ingredients, total elimination of the parasites was achieved within the first 10 days of treatment.

Gamma/delta T-cell lymphoma involving the subcutaneous tissue and associated with a hemophagocytic syndrome.

A case of gamma/delta-positive T-cell lymphoma localized primarily in the subcutaneous adipose tissue and associated with an extensive hemophagocytic syndrome and a rapid, fatal outcome is presented. Previous reports of gamma/delta cutaneous and subcutaneous T-cell lymphomas are reviewed. To define the characteristics of a T-cell subset of neoplastic cells bearing the gamma/delta receptor in a subcutaneous lymphoma, we undertook clinical and laboratory examinations, morphological evaluation of biopsies, electron microscopy, and extensive immunohistochemical studies. Immunohistochemical studies showed that the neoplastic cells expressed the gamma/delta T-cell receptor (CD3+, C gamma M1+) and were CD2+, CD43+, CD45+, CD45RO+, PCNA+, but were beta F1-, CD1-, CD4-, CD8-, CD15-, CD20-, CD25-, CD30-, CD45R-, CD57-, CD68-, Mac 387-, and HLA Dr-. To the best of our knowledge, this is the first report of a subcutaneous T-cell lymphoma of gamma/delta type involving the subcutaneous tissue and associated with a hemophagocytic syndrome.

Cutaneous bronchogenic cyst : Delineation of a poorly recognized lesion

Abstract: Bronchogenic cyst is a benign congenital developmental abnormality of the embryonic foregut. The most common extrapulmonary location of these lesions is the mediastinum. Over 50 cases of cutaneous bronchogenic cyst were reported in the English literature. Nevertheless, it is poorly recognized by clinicians and is sometimes confused with branchial cyst. In almost all cases the diagnosis is established by histopathologic examination. We report an unusual clinical presentation of bronchogenic cyst in a 4‐year‐old girl and review the literature. This lesion is four times more common in males than in females. The most common location is the suprasternal notch, followed by the presternal area, neck, and scapula. The characteristic histologic findings are a ciliated pseudostratified epithelial lining with the presence of smooth muscle cells, goblet cells and, less frequently, cartilage. Our review of the clinical and histologic features of all reported cases further delineates this entity and may facilitate its clinical diagnosis. Bronchogenic cyst should be included in the differential diagnosis of congenital cystic and nodular skin lesions on the upper chest, upper back, and neck.