Caroline Gaudy-Marqueste

A severe case of ipilimumab-induced guillain-barré syndrome revealed by an occlusive enteric neuropathy: a differential diagnosis for ipilimumab-induced colitis.

Ipilimumab is a fully human monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4 recently approved for the treatment of metastatic melanoma and currently under investigation in the adjuvant setting of high-risk stage III melanoma. The blockade of CTLA-4 induces activation of T cells, with an expected increase in the immunological reaction directed to cancer. We report a case of ipilimumab-induced Guillain-Barré syndrome revealed by an occlusive enteric neuropathy. Two weeks after the second dose of ipilimumab, our patient started to complain of abdominal meteorism and nausea. Within a few days, an occlusive syndrome developed. Wall biopsies during colonoscopy revealed a slight edema of the mucosa and a high number of lymphocytic follicles, leading to the diagnosis of ipilimumab-induced immune colitis. A respiratory failure occurred and a neurological deficiency developed rapidly. The diagnosis of polyradiculoneuritis was retained. Despite IV steroids, tacrolimus than plasmatic exchanges, the patient died within a few days because of multivisceral failure. Polyradiculoneuritis is a rare but very severe immune-mediated complication of ipilimumab. Occlusive enteric neuropathy may mimic the digestive symptoms of colitis, which is so frequent under ipilimumab.

Urticaria and quality of life

The common perspective of physicians on chronic urticaria (CU) refers to a benign disorder with no pain and no threat to function or life. Heath-related quality-of-life (HRQOL) tools have demonstrated the extent to which physicians underestimate the impact of this disorder. From the patient perspective, CU affects as many dimensions of the HRQOL as some life-threatening diseases or well-recognized disabling chronic skin disorders, such as psoriasis or atopic dermatitis. Pruritus as well as swelling and wheals triggered by unavoidable events, such as pressure or sweating, greatly contribute to HRQOL impairment. Recent trials have suggested that dermatology-specific HRQOL instruments could be more relevant than more objective severity scores when studying and comparing the benefit of various therapeutic strategies in chronic idiopathic urticaria.

Quality of Life in Alopecia Areata: A Study of 60 Cases

TO THE EDITOR Alopecia areata (AA) is a chronically relapsing skin disorder characterized by a sudden loss of hair. Because the perception of patients may differ significantly from those of their health-care providers, quality of life (Qol) appears to be a more relevant criterion to assess the severity of this disease than clinical evaluation such as AA extension. To our knowledge, only one Turkish study investigated the impact of AA on Qol using short form 36 (SF36), indicating lower Qol levels compared with sex-matched individuals (Gulec et al., 2004). In this study, Qol was assessed using a generic instrument. Because only three dimensions were affected and results may be linked to the specific culture, a confirmation was needed. We used an approach combining generic and specific measures to assess the impact of AA on French patients’ Qol, to compare Qol levels with those observed in the general population and in other dermatological conditions, and finally to determine the impact of clinical characteristics and sociodemographic factors on Qol. Subjects were aged over 16 years, presenting with a minimum of 8 weeks AA history, having given informed consent to participate, and having the French language as their native language. Sociodemographic data and characteristics of the disease (duration and course, treatments in the recent period, affected surfaces on the scalp and other areas involved) were recorded. The severity of each AA was reported using visual analogical scales (0–10) by reference to (i) all the AA cases seen in daily practice; (ii) all cases of all skin disorders. Three selfadministered questionnaires were used to assess Qol: the generic and worldwide-used SF36 (Leplege et al., 1998, 2001; Coste, 2001), and two ‘‘chronic skin disorders’’-specific Qol instruments with French validated available versions, the VQ-Dermato (Grob et al., 1999, 2009) and the Skindex (Chren et al., 1996, 1997; Leplege et al., 2003). To better figure out the level of QoL in AA, we compared AA scores with those available in literature related to the French population: (1) rare dermatological diseases including hidradenitis suppurativa (Wolkenstein et al., 2007) and neurofibromatosis type 1 (Wolkenstein et al., 2001); (2) chronic/frequent dermatological diseases including psoriasis, chronic idiopathic urticaria, and atopic dermatitis (Grob et al., 2005); (3) general population: French ageand sex-matched controls (Leplege et al., 2001). This study was conducted in adherence to the Helsinki guidelines. Institutional approval was not required for experiments. After having given their inform consent, 60 patients were included (39 women and 21 men); their mean age was 40.1 years (SD 15.2) and median AA duration was 6 years (2 months to 60 years). Course of the disease was stable in 25 subjects and unstable in 35. The median of the scalp surface involved was 77%. The median of severity score was 6.5 (range 4.0–9.0) by reference to the AA patients and 3.5 (range 2.0–6.0) by reference to the patients presenting any skin disorder. Mental health and vitality were the most altered SF36 dimensions, whereas physical functioning, role physical and body pain were the least ones. Regarding VQ-Dermato, daily life, leisure activity, and physical discomfort were the least altered dimensions. For Skindex, emotions dimension was the most affected and symptoms the least one. Compared with the general population and with patients suffering from other dermatological conditions (Table 1), AA patients presented significantly altered Qol for almost all the SF36 dimensions. For VQ-Dermato, AA patients reported (i) significantly better (mood state, leisure activity, daily life, and physical discomfort) or worse scores (self-perception) than psoriasis, chronic idiopathic urticaria, and atopic dermatitis patients; (ii) being less bothered to treatment-induced restrictions than psoriasis, but more than chronic idioAbbreviations: AA, alopecia areata; Qol, quality of life; SF36, short form 36

Risk Factors in Elderly People for Lentigo Maligna Compared With Other Melanomas: A Double Case-Control Study

OBJECTIVE To assess lentigo maligna (LM) as an epidemiological entity separate from other melanomas (OMs) in elderly people. DESIGN Double age- and sex-matched case-control study to compare the risk factors for LMs and OMs. SETTING General community. Patients A total of 76 patients with LM were paired by age and sex with 76 patients with OMs and 152 controls. MAIN OUTCOME MEASURES The association of melanoma risk with the following potential risk factors: sun exposure history by 10-year periods, frequency of sunburns, phenotypic traits, density of freckles and sun sensitivity at age 20 years, counts of nevi larger than 2 mm in diameter on the face and forearm, skin aging features (as assessed using a photographic scale), and history of basal and/or squamous cell carcinomas. RESULTS Risk of LMs and OMs were similarly associated with history of sunburns, light skin type, and freckling. Cumulative chronic outdoor and occupational sun exposures were not risk factors in any of the 2 groups of melanomas. Lentigo maligna differed from OMs by the absence of a detectable association with the number of nevi and a greater association with nonmelanoma skin cancers. CONCLUSIONS Although chronically sun-exposed skin is a prerequisite for LM, risk of LM does not increase with the cumulative dose of sun exposure, but LM is associated with sunburn history, like all other types of melanomas. The main epidemiological characteristic of LM is the absence of an apparent relation with the genetic propensity to develop nevi. This epidemiological profile is in accordance with recent molecular findings and may also account for the histoclinical and evolutive characteristics of LM.

LBR mutation and nuclear envelope defects in a patient affected with Reynolds syndrome

Background Lamins are proteins of the nuclear envelope involved in ‘laminopathies’, an heterogeneous group of diseases sharing clinical similarities with systemic sclerosis (SSc). Methods In this context, a search was undertaken for mutations in LMNA, encoding Lamins A/C, and ZMPSTE24, LBR, LMNB1, LMNB2, MAN1, SYNE1a and LAP2, encoding Lamins A/C molecular partners, in a Caucasian woman affected with Reynolds syndrome, a particular nosologic entity specifically associating limited cutaneous SSc and primary biliary cirrhosis. Results Coding regions and intron-exon boundaries of these genes were PCR amplified and sequenced, revealing a single heterozygous missense mutation in LBR exon 9 (c.1114C/T; p.R372C). This variant was absent in 400 control chromosomes. The mutation was predicted to induce a change in Lamin B receptor (LBR) tertiary structure and molecular interactions by bioinformatic tools. Further functional explorations were performed on the patients fibroblasts and lymphoblastoid cell lines. On the latter, the expression levels of LBR, Lamins A/C, Lamin B1, Lamin B2, and HP1a were conserved. Conversely, in the patients skin fibroblasts, LBR and the aforementioned molecular partners showed dramatically reduced or abolished expression levels. The immunofluorescence analyses performed on both cell lines corroborated these findings. Conclusion The fibroblast specific abnormalities observed suggest that this particular LBR mutation might have dominant negative deleterious effects in a tissue specific fashion, possibly through the perturbation of the interactions or stability of the nuclear envelope protein network. LBR mutations might thus be associated with Reynolds syndrome.

Ugly Duckling Sign as a Major Factor of Efficiency in Melanoma Detection

Importance Understanding the contribution of the ugly duckling sign (a nevus that is obviously different from the others in a given individual) in intrapatient comparative analysis (IPCA) of nevi may help improve the detection of melanoma. Objectives To assess the agreement of dermatologists on identification of the ugly duckling sign and estimate the contribution of IPCA to the diagnosis of melanoma. Design, Setting, and Participants The same 2089 digital images of the nevi of a sample of 80 patients (mean age, 42 years [range, 19-80 years]; 33 men and 47 women), as well as 766 dermoscopic images from a subset of 30 patients (mean age, 40 years [range, 21-75 years]; 12 men and 18 women), were randomly presented to the same 9 dermatologists for blinded assessment from September 22, 2011, to April 1, 2013. The first experiment was designed to mimic an IPCA situation, with images of all nevi of each patient shown to the dermatologists, who were asked to identify ugly duckling nevi (UDN). The second experiment was designed to mimic a lesion-focused analysis to identify morphologically suspicious nevi. Data analysis was conducted from November 1, 2012, to June 1, 2013. Main Outcomes and Measures Number of nevi labeled UDN and morphologically suspicious nevi, specificity of lesion-focused analysis and IPCA, and number of nevi identified for biopsy. Results Of the 2089 clinical images of nevi from 80 patients (median number of nevi per patient, 26 [range, 8-81]) and 766 dermoscopic images (median number of nevi per patient, 19 [range, 8-81]), all melanomas were labeled UDN and as morphologically suspicious nevi by the 9 dermatologists. The median number of UDN detected per patient was 0.8 among the clinical images of nevi (mean, 1.0; range, 0.48-2.03) and 1.26 among the dermoscopic images (mean, 1.4; range, 1.00-2.06). The propensity to consider more or fewer nevi as having ugly duckling signs was independent of the presentation (clinical or dermoscopic). The agreement among the dermatologists regarding UDN was lower with dermoscopic images (mean pairwise agreement, 0.53 for clinical images and 0.50 for dermoscopic images). The specificity of IPCA was 0.96 for clinical images and 0.95 for dermoscopic images vs 0.88 and 0.85, respectively, for lesion-focused analysis. When both IPCA and lesion-focused analyses were used, the number of nevi considered for biopsy was reduced by a factor of 6.9 compared with lesion-focused analysis alone. Conclusions and Relevance Intrapatient comparative analysis is of major importance to the effectiveness of the diagnosis of melanoma. Introducing IPCA using the ugly duckling sign in computer-assisted diagnosis systems would be expected to improve performance.

Human Polyomavirus-6 Infecting Lymph Nodes of a Patient With an Angiolymphoid Hyperplasia With Eosinophilia or Kimura Disease

Human polyomavirus 6 (HPyV6) is most often detected at the skin surface of healthy individuals. Here, we demonstrate for the first time that HPyV6 also infects internal tissues. We provide direct evidence of HPyV6 infecting a lymph node of a patient with an angiolymphoid hyperplasia with eosinophilia or Kimura disease.

Texture descriptors based on adaptive neighborhoods for classification of pigmented skin lesions

Abstract. Different texture descriptors are proposed for the automatic classification of skin lesions from dermoscopic images. They are based on color texture analysis obtained from (1) color mathematical morphology (MM) and Kohonen self-organizing maps (SOMs) or (2) local binary patterns (LBPs), computed with the use of local adaptive neighborhoods of the image. Neither of these two approaches needs a previous segmentation process. In the first proposed descriptor, the adaptive neighborhoods are used as structuring elements to carry out adaptive MM operations which are further combined by using Kohonen SOM; this has been compared with a nonadaptive version. In the second one, the adaptive neighborhoods enable geometrical feature maps to be defined, from which LBP histograms are computed. This has also been compared with a classical LBP approach. A receiver operating characteristics analysis of the experimental results shows that the adaptive neighborhood-based LBP approach yields the best results. It outperforms the nonadaptive versions of the proposed descriptors and the dermatologists’ visual predictions.

Congenital and Disseminated Pyogenic Granuloma-like Vascular Lesions

We report an exceptional case of multiple cutaneous and visceral neonatal pyogenic granuloma (PG) initially suggestive of a diffuse neonatal haemangiomatosis. CASE REPORT A full-term female newborn, with no significant past medical history, was referred to our department for treatment of an acute respiratory distress syndrome of neurological origin at day 8 of life. At birth, she presented with 3 small angiomatous papules and 4 subcutaneous nodules suggestive of neonatal hae-mangiomatosis (NH) (Fig. 1). A brain MRI revealed a highly vascularised brain stem tumour suggestive of glioma (Fig. 2), associated with 2 abnormal hepatic lesions consistent with infantile haemangiomas (IH) on ultrasound and CT scan. Methylprednisolone was started for the suspected glioma-associated oedema, and vincristine and propranolol were introduced for NH. After initial improvement, an acute intracranial hypertension related to cystic evolution of the disease necessitated surgical resection at the age of 2 months. Pathological examinations of the brain, cutaneous and subcutaneous lesions were similar, showing a vascular lobular proliferation of capillaries highly suggestive of PG. The misdiagnosis of glioma was eliminated. The GLUT-1 antigen marker was negative, ruling out the diagnosis of NH-like infantile haemangioma (Fig. 3). Lymphatic marker (D2-40) was also negative and eliminated a multifocal lymphangioendotheliomato-sis with thrombocytopaenia (MLT). Cutaneous and hepatic lesions gradually regressed. She is currently in complete remission after completing a treatment over 18 months with propranolol but a spontaneous improvement can not be excluded. DISCUSSION

LMNA, ZMPSTE24, and LBR Are Not Mutated in Scleroderma

Scleroderma is a rare multisystemic disease of unknown etiology presumed to develop in genetically predisposed patients. Since patients affected with scleroderma develop clinical features similar to those observed in some laminopathies, we decided to screen at the genomic level a cohort of 27 patients affected with either localized or systemic scleroderma for mutations in three lamin-related genes: LMNA, encoding A-type lamins; ZMPSTE24, encoding a protease involved in lamin A processing; and LBR, encoding the lamin B receptor. No mutation was retrieved, whereas 25 polymorphic sequence variations were identified, 7 of which were unreported. Functional analyses performed for three of these allowed exclusion of an impact on splicing. Multiplex ligation-dependent probe amplification analysis showed no LMNA deletion or duplication. Altogether our results suggest that LMNA, ZMPSTE24, and LBR sequence variations are not major genetic determinants involved in scleroderma pathogenesis.