Inês Coutinho

HLA-B*58:01 is a risk factor for allopurinol-induced DRESS and Stevens–Johnson syndrome/toxic epidermal necrolysis in a Portuguese population

HLA‐B*58:01 is associated with allopurinol‐induced severe cutaneous adverse drug reactions (sCADR) particularly in Han Chinese, but the risk in European populations has seldom been studied.

Methylisothiazolinone: second ‘epidemic’ of isothiazolinone sensitization

Isothiazolinones are used as biocides in a wide variety of products, such as cosmetics, detergents, and industrial products. In the 1980s, a formulation with methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) was responsible for an allergic contact dermatitis ‘epidemic’. To control this phenomenon, a maximum allowed dose was set. However in 2005, MI alone was introduced in cosmetics, and this was followed by a new ‘epidemic’ of sensitization to MI and MCI/MI (1). We performed a retrospective study, consulting the medical files of patch tested patients reactive to ISs, from 2005 to 2013. MCI/MI was tested at 100 ppm in water (TROLAB® patch test allergens, Almirall Hermal

The UV filter tinosorb M, containing decyl glucoside, is a frequent cause of allergic contact dermatitis.

To the Editor: Tinosorb M (Chemotechnique Diagnostics, Vellinge, Sweden), an organic molecularly complex broad-spectrum UV filter composed of microparticles of methylene bis-benzotriazolyl tetramethylbutylphenol solubilized with decyl glucoside, propylene glycol, and xanthan gum, has rarely been described as a cause of allergic contact dermatitis (ACD). Because of its high efficacy and photostability, after 2000, it was introduced in the European and Australian markets but is still waiting approval by the Food and Drug Administration. The authors performed a retrospective study to evaluate the frequency of ACD from Tinosorb M, patients’ characteristics, and responsible allergens. In the Unit of Cutaneous Allergology of the Dermatology Department of the University Hospital of Coimbra, Tinosorb M at 10% Petrolatum (pet) was included in the photoallergens series in 2009, initially within the European Multicentre Photopatch test study, and since 2011, also in our cosmetic series for patch testing, patients with recurrent dermatitis localized mainly to the face. Between February 2009 and April 2012, among the 1033 patients studied at the department, 92 were photopatch tested using the irradiation dosis of 5 J/cm of UVA (Waldmann 7001 K), according to the guidelines published by the European Photopatch Test Task Force. An additional 87 patients were patch tested with the cosmetics series including the UV filters, namely Tinosorb M (10% pet) and bis-ethylhexyloxyphenol methoxyphenol triazine (bemotrizinol or Tinosorb S, 10% pet) and lauryl glucoside (3% pet) from Chemotechnique Diagnostics. Patch tests were applied on the upper back, for 48 hours, using Finn Chambers on Scanpor tape (Epitest Ltd, Tuusula, Finland) or, occasionally, I-Q ultra chambers (Chemotechnique Diagnostics, Vellinge, Sweden). Readings were performed at D2 and D3/D4, according to the International Contact Dermatitis Research Group recommendations (Lindberg), considering only 1+ or more intense reactions. Several personal products (facial cosmetics, sunscreens, and topical drugs) were patch tested, and rinse-off products (clearnsing agents and shampoos) were tested using the semiopen method, applying a drop of the product in a 2 2 cm area and covering it, after drying, with a semipermeable tape for 48 hours (Mefix, Molnlycke Health Care, Finland). During this period, positive patch tests to Tinosorb M were observed in 5 patients, 3 female and 2 male, between 39 and 66 years old. They had highly pruritic erythematous and scaly eczematous lesions with ill-defined borders, located mainly on the face and anterior neck (Fig. 1), with an evolution between 1 and 12 months, that recurred frequently despite topical corticosteroids (Table 1). Positive reactions (1+ or 2+) to Tinosorb M at 10% pet (Fig. 2) had an equal intensity after irradiation with 5 J/cm UVA in all patients. Patient 1, the object of a previous publication, was patch tested with purified decyl glucoside at 5% pet, kindly supplied by An Goossens (Leuven, Belgium). He had a 2+ reaction to decyl glucoside and reacted to several cosmetics containing alkyl glucoside, specially lauryl-, xylityl-, cetearyl-, myristyl-, coco-, and arachidyl glucosides, and to his own sunscreen and to several other sunscreens containing Tinosorb M (Fig. 3).

Interstitial Granulomatous Dermatitis: A Clinicopathological Study.

Introduction:Interstitial granulomatous dermatitis (IGD) is an uncommon granulomatous dermatitis occurring in the setting of highly reactive immune states, with a polymorphic clinical presentation. Because there is overlap with other entities [namely palisading neutrophilic granulomatous dermatitis (PNGD)], controversy exists regarding its classification. Objective:To understand if there are features allowing clear-cut distinction between IGD and PNGD. Material and Methods:Retrospective analysis of 10 cases previously diagnosed as IGD or PNGD, from 2000 to 2013, with review of the histopathologic findings and clinical correlation. Results:Six females and 4 males presented mostly with erythematous papules/nodules (n = 7) but also with erythematous annular plaques (n = 3). In 2 patients, the lesions coexisted. They were mostly distributed symmetrically on the limbs. Associated disease was observed in 6 patients. Regarding histopathology, an inflammatory infiltrate occupying the superficial and mid dermis was present in 40% of cases, with an interstitial component in all biopsies and a palisaded arrangement in 60%. Neutrophils and mononuclear cells were present in all cases in varying proportions. Necrobiosis was found in 70%, and leukocytoclasia was observed in 80% of biopsies. Conclusions:Coexistence of the interstitial and palisaded inflammatory patterns occurred in 90% of cases, with no correlation between tissue neutrophilia and the predominant pattern of the infiltrate. There was also no clear-cut correlation between the infiltrate pattern and semiologic aspect of the lesions. Therefore, the features described in our study suggest that IGD and PNGD belong to the same clinicopathological spectrum.

Benign follicular tumors

Benign follicular tumors comprise a large and heterogeneous group of neoplasms that share a common histogenesis and display morphological features resembling one or several portions of the normal hair follicle, or recapitulate part of its embryological development. Most cases present it as clinically nondescript single lesions and essentially of dermatological relevance. Occasionally, however, these lesions be multiple and represent a cutaneous marker of complex syndromes associated with an increased risk of visceral neoplasms. In this article, the authors present the microscopic structure of the normal hair follicle as a basis to understand the type and level of differentiation of the various follicular tumors. The main clinicopathological features and differential diagnosis of benign follicular tumors are then discussed, including dilated pore of Winer, pilar sheath acanthoma, trichoadenoma, trichilemmoma, infundibuloma, proliferating trichilemmal cyst/tumor, trichoblastoma and its variants, pilomatricoma, trichodiscoma/fibrofolliculoma, neurofollicular hamartoma and trichofolliculoma. In addition, the main syndromes presenting with multiple follicular tumors are also discussed, namely Cowden, Birt-Hogg-Dubé, Rombo and Bazex-Dupré-Christol syndromes, as well as multiple tumors of follicular infundibulum (infundibulomatosis) and multiple trichoepitheliomas. Although the diagnosis of follicular tumors relies on histological examination, we highlight the importance of their knowledge for the clinician, especially when in presence of patients with multiple lesions that may be the cutaneous marker of a cancer-prone syndrome. The dermatologist is therefore in a privileged position to recognize these lesions, which is extremely important to provide further propedeutic, appropriate referral and genetic counseling for these patients.

Prediction of Sentinel Node Status and Clinical Outcome in a Melanoma Centre

Background. Sentinel lymph node biopsy (SLNB) is a standard procedure for patients with localized cutaneous melanoma. The National Comprehensive Cancer Network (NCCN) Melanoma Panel has reinforced the status of the sentinel lymph node (SLN) as an important prognostic factor for melanoma survival. We sought to identify predictive factors associated with a positive SLNB and overall survival in our population. Methods. We performed a retrospective chart review of 221 patients who have done a successful SLNB for melanoma between 2004 and 2010 at our department. Univariate and multivariate analyses were done. Results. The SLNB was positive in 48 patients (21.7%). Univariate analysis showed that male gender, increasing Breslow thickness, tumor type, and absence of tumor-infiltrating lymphocytes were significantly associated with a positive SLNB. Multivariate analysis confirmed that Breslow thickness and the absence of tumor-infiltrating lymphocytes are independently predictive of SLN metastasis. The 5-year survival rates were 53.1% for SLN positive patients and 88.2% for SLN negative patients. Breslow thickness and the SLN status independently predict overall survival. Conclusions. The risk factors for a positive SLNB are consistent with those found in the previous literature. In addition, the SLN status is a major determinant of survival, which highlights its importance in melanoma management.

Overlap between maculopapular exanthema and drug reaction with eosinophilia and systemic symptoms among cutaneous adverse drug reactions in a dermatology ward.

Inpatients with cutaneous adverse drug reactions (CADR) with overlapping features between maculopapular exanthema (MPE) and drug reaction with eosinophilia and systemic symptoms (DRESS) were examined.

Histopathology of the Exanthema in DRESS Is Not Specific but May Indicate Severity of Systemic Involvement.

Objective:Exanthema in drug reaction with eosinophilia and systemic symptoms (DRESS) has no specific clinical diagnostic hallmark and there are few histopathologic studies. The aim of this study was to describe dermal–epidermal histopathologic features in DRESS and correlate them with the culprit drug, viral reactivation, or systemic organ involvement. Methods:Skin biopsies were independently evaluated by 2 dermatopathologists who characterized the main histological patterns and scored dermal and epidermal changes, which were further correlated with clinical and laboratorial data. Results:In 15 DRESS patients (9 male/6 female patients, mean age 53.3 years), the main observation was lymphocyte exocytosis (1.87 ± 1.25), spongiosis (0.93 ± 0.94), scattered keratinocyte necrosis (1.70 ± 1.44), basal cell vacuolization (2.13 ± 1.42), lymphocyte infiltration around dermal vessels (2.93 ± 0.92) or at the dermal–epidermal junction (2.07 ± 1.12), often with eosinophils and extravasated erythrocytes, swollen endothelial cells, and intravascular neutrophils but no vasculitis. Histopathologic patterns were classified mainly as spongiotic (5), erythema multiforme-like (3), or lichenoid (2). There was a significant positive correlation between the intensity of lymphocyte infiltration and the severity of hepatic cytolysis (r = 0.51; P < 0.05) and eosinophilia (r = 0.51; P < 0.05). No correlation was observed between the intensity and type of dermal inflammation and the degree of epidermal damage or the culprit drug. Human herpes virus type 6–positive patients had a pseudolymphomatous reaction or a perifollicular localization of the infiltrate. Conclusions:Histopathology in DRESS is variable with no specific diagnostic aspect, but there is a possible correlation between the intensity of the lymphocyte infiltrate and DRESS severity, namely, liver cytolysis.

Immediate ex-vivo dermoscopy of a nail bed biopsy specimen – a useful procedure for melanonychia

bulocystic squamous cell carcinoma as a differential diagnosis. Infundibulocystic squamous cell carcinoma which is known to have the distinctive histopathological features of numerous microor dilated infundibular cysts with minimal cytological atypia that infiltrate and penetrate deep into the underlying tissue. In our case, the tumour cells without evident nuclear atypia did not penetrate in the deep dermis and clinical manifestation of which present symmetrical, exophytic and central erosion. Furthermore, long-standing history indicated the benign lesion, so we excluded infundibulocystic squamous cell carcinoma. The dermoscopic features of millia-like cysts often resemble those of seborrhoeic keratosis; however, in our case, typical dermoscopic features of seborrhoeic keratosis, such as comedolike openings, fingerprint-like structures and brain-like appearances, were not observed. We regarded the lack of brownish background as a unique characteristic. We think these features, especially the multiple millia-like cysts on a background of reddish plaques, might be helpful in the clinical diagnosis of keratoacanthoma en plaque. In conclusion, this is the first report to describe the dermoscopic features of keratoacanthoma en plaque with infundibulocystic hyperplasia. When we encounter reddish plaques with ‘millia-like cysts on an erythematous background’ in dermoscopy, we must consider keratoacanthoma en plaque with infundibulocystic hyperplasia as a differential diagnosis.

Do you know this syndrome? Dyspigmentation along the Blaschko lines caused by trisomy 7 mosaicism

Dyspigmentation along the Blaschko lines is strongly suggestive of a mosaic skin disorder. We report a 9-year-old male patient who presented with swirls and streaks of both hypo and hyperpigmentation involving the entire body. Additionally, he had hypertrichosis, musculoskeletal and minor neurodevelopment abnormalities but no intellectual disability. Cultured fibroblast displayed trisomy 7 mosaicism, which can explain this pigmentary phenotype. Widespread dyspigmentation associated with involvement of other organs should prompt systemic examination to detect additional anomalies and genetic evaluation should be considered, even with normal fetal karyotype.