Quality of life in neurofibromatosis 1: development and validation of a tool dedicated to cutaneous neurofibromas in adults.

BACKGROUND: Cutaneous neurofibromas (cNF), present in 95% of individuals with neurofibromatosis 1 (NF1), are considered as one of the greatest medical burden because of physical disfigurement. No specific score evaluates their impact on quality of life (QoL). OBJECTIVE: To develop a specific score assessing cNF-related QoL. METHODS: Through a multidisciplinary workshop including 10 patients, 3 expert-in-NF1 physicians, 3 health care workers (nurses and psychologist) and 1 methodologist, the French version of the Skindex-16 was modified by adding 3 items. The new cNF-Skindex was validated among patients with NF1 recruited in the ComPaRe online cohort, in France (N = 284). Construct validity was assessed by comparing it with the EQ-5D-5L, its visual analogue scale and the MYMOP2 and by assessing its association with patients' characteristics. Reliability was assessed by a test-retest. An English version of the tool was developed using a back-forward translation. RESULTS: A total of 228 individuals with NF1, with cNF answered the 19-item questionnaire. These items fitted into 3 domains: emotions, symptoms, functioning. One was dropped during analysis because >90% responders were not concerned. The cNF-Skindex significantly correlated with the EQ-5D-5L (N = 193) and MYMOP2 (N = 210) indicating good external validity: rs 0.38 (P < 0.001), and 0.58 (P < 0.001), respectively. Having >50 cNF was the only independent variable associated with the total score cNF-Skindex (ß = 15.88, 95%CI 6.96-24.81, P = 0.001), and with the 3 sub-scores: 'functioning' (ß = 2.65, 95%CI 0.71-4.59, P = 0.008), 'emotions' (ß = 17.03, 95%CI 4.11-29.96, P = 0.010) and 'symptoms' (ß = 3.90, 95%CI 1.95-5.85, P < 0.001). Test-retest reliability (N = 133) found an ICC at 0.96 demonstrating good reproducibility. CONCLUSION: The cNF-Skindex demonstrated excellent psychometric properties. The global and sub-scores were increased with higher number of cNF arguing for its use in further trials aiming to reduce their number or prevent their development. Cross-cultural validation and evaluation of its responsiveness are the next steps.

Identification of three clinical neurofibromatosis 1 subtypes: Latent class analysis of a series of 1351 patients.

BACKGROUND: Neurofibromatosis 1 (NF1) is one of the most common inherited disorders characterized by mutations in the tumour suppressor gene NF1. Its clinical manifestations are highly variable and unpredictable. A specific NF1 mutation does not predict the severity or complications of the disease. OBJECTIVE: The objective of this study was to build an empirical classification scheme without any a priori hypotheses to identify the underlying NF1 subtypes that best explain the observed heterogeneity. METHODS: We performed latent class analysis (LCA) of 1351 consecutive NF1 patients aged >17 years seen between 2002 and 2014. Data and phenotypic features were collected prospectively on a standardized form. RESULTS: The median age was 36.8 (17-81) years. A three-class model showed the best fit: 706 (52%) belonged to the LC1 'Cutaneous neurofibromas' class having preferentially cutaneous neurofibromas (99%), plexiform neurofibromas (63%) and blue-red macules (29%); 593 (44%) belonged to the LC2 'Subcutaneous neurofibromas' class characterized by the presence of at least 10 subcutaneous neurofibromas (21%) and a familial form (77%) and 52 (4%) belonged to the LC3 'Dysmorphic phenotype' class characterized by dysmorphic features (78%) and learning difficulties (87%). Patients in LC1 had a higher likelihood of developing scoliosis (RR = 1.7, 95% confidence interval (CI) [1.2-2.4]). Patients in LC2 were more likely to be men (RR = 1.4, 95% CI [1.1-1.7]). Patients in LC3 were at higher risk of having an optic pathway glioma (RR = 4.8, 95% CI [1.9-11.8]) and epilepsy (RR = 4.5, 95% CI [1.8-11.6]). CONCLUSION: Our findings invite the performance of a larger cohort study to test whether the various latent classes reflect different underlying genetic modifiers of these phenotypic traits.

Pityriasis lichenoides: a clinical and pathological case series of 49 patients with an emphasis on follow-up.

The classification of pityriasis lichenoides (PL) into pityriasis lichenoides et varioliformis acuta (PLEVA), PL chronica (PLC) and febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is based on both clinical and chronological features. In this retrospective monocentric study, we aimed to investigate the relevance of the classification in routine practice. We enrolled 49 patients (25 female, 24 male; median age 41 years). The lesions were papular in 76% of patients, necrotic in 12% and mixed in 12%. We found three histological patterns: 'classic' (65%), 'lymphomatoid' (13%) and 'mild' (22%). The 'lymphomatoid' pattern was associated with necrotic presentation and the 'mild' pattern with papular lesions (P = 0.01). Among the 27 patients with follow-up, 18% had relapses and 44% had chronic disease. One patient had mycosis fungoides. Neither clinical nor histological findings were correlated with disease progression, and are a reflection of the intensity of epidermal injury rather than of the disease course. The term 'pityriasis lichenoides' should be preferred to the classic PLEVA/PLC/FUMHD classification.

[18F]FDG Positron emission tomography with whole body magnetic resonance imaging ([18F]FDG-PET/MRI) as a diagnosis tool in Schwannomatosis.

Schwannomatosis is a rare autosomal dominant genetic syndrome characterized by the presence of multiple schwannomas. The main symptom is neurogenic pain. The diagnosis requires the presence of several schwannomas and whole-body [18F]FDG-PET/MRI might help detect extra schwannomas in patients when the diagnosis is uncertain. Among the 25 patients treated for Schwannomatosis in our tertiary center, three men and two women had had a [18F]FDG-PET/MRI performed, and the number of schwannomas detected by [18F]FDG-PET/MRI outnumbered the number of schwannomas suspected during the clinical examination. The majority of schwannomas exhibited a radiolabeling (median of 66.7%, range 28-93%). Our findings show that [18F]FDG-PET/MRI could prove useful when suspecting schwannomatosis to accelerate diagnosis and offer optimal care to patients.

Most chilblains observed during the COVID-19 outbreak occur in patients who are negative for COVID-19 on polymerase chain reaction and serology testing.

BACKGROUND: Acral lesions, mainly chilblains, are the most frequently reported cutaneous lesions associated with COVID-19. In more than 80% of patients tested, nasopharyngeal swabs were negative on reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 when performed, and serology was generally not performed. METHODS: A national survey was launched on 30 March 2020 by the French Society of Dermatology asking physicians to report cases of skin manifestations in patients with suspected or confirmed COVID-19 by using a standardized questionnaire. We report the results for acral manifestations. RESULTS: We collected 311 cases of acral manifestations [58.5% women, median age 25.7 years (range 18-39)]. The most frequent clinical presentation (65%) was typical chilblains. In total, 93 cases (30%) showed clinical suspicion of COVID-19, 67 (22%) had only less specific infectious symptoms and 151 (49%) had no clinical signs preceding or during the course of acral lesions. Histology of skin biopsies was consistent with chilblains. Overall, 12 patients showed significant immunological abnormalities. Of the 150 (48%) patients who were tested, 10 patients were positive. Seven of 121 (6%) RT-PCR-tested patients were positive for SARS-CoV-2, and five of 75 (7%) serology-tested patients had IgG anti-SARS-CoV-2. Tested/untested patients or those with/without confirmed COVID-19 did not differ in age, sex, history or acral lesion clinical characteristics. CONCLUSIONS: The results of this survey do not rule out that SARS-CoV-2 could be directly responsible for some cases of chilblains, but we found no evidence of SARS-CoV-2 infection in the large majority of patients with acral lesions during the COVID-19 lockdown period in France. What is already known about this topic? About 1000 cases of acral lesions, mainly chilblains, were reported during the COVID-19 outbreak. Chilblains were reported to occur in young people within 2 weeks of infectious signs, which were mild when present. Most cases did not have COVID-19 confirmed by reverse transcription polymerase chain reaction (RT-PCR), and few serology results were available. What does this study add? Among 311 patients with acral lesions, mainly chilblains, during the COVID-19 lockdown period in France, the majority of patients tested had no evidence of SARS-CoV-2 infection. Overall, 70 of 75 patients were seronegative for SARS-Cov-2 serology and 114 of 121 patients were negative for SARS-CoV-2 RT-PCR.

Efficacy and satisfaction of surgical treatment for hidradenitis suppurativa.

BACKGROUND: Surgery is a radical treatment for hidradenitis suppurativa (HS) and may be considered as the only one potentially curative. OBJECTIVES: To characterize HS recurrence in patients after surgery and assess the risk factors of recurrence. METHODS: We conducted a monocentric retrospective cohort study. All consecutive patients who had surgery (January 1, 2012 to March 31, 2017) were included. We estimated the rate of recurrence of HS lesions after surgery (<1 cm from the scar), and recurrence-associated factors were analysed by univariate then multivariate logistic regression, estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 75 patients [median age 31.4 years (range 16-71); 36 females], corresponding to 115 interventions were included. The Hurley score at surgery was III for 70 (60%) patients. In total, 61/115 (53%) interventions involved wide excision and 50 (43%) limited local excision. The localizations were axillary folds (n = 46; 40%), buttocks (n = 15, 13%), genital area (n = 13; 11%), perineal area (n = 12; 10%) and inguinal folds (n = 18; 16%). We observed 11 (10%) complications and 40 (35%) recurrences. On multivariate analysis, probability of recurrence was associated with only one-stage surgical closure [OR 3.2 (95% CI 1.4-7.3), P = 0.005]. Overall, 44 (52%) patients were completely satisfied and 22 (26%) partially satisfied, and most (81%) considered the surgery the best treatment. CONCLUSIONS: Hidradenitis suppurativa recurrence in our study was 35% and associated with one-stage surgical closures, but two-thirds of patients were satisfied with surgical treatment and would recommend surgery.

High-concentration topical capsaicin in the management of refractory neuropathic pain in patients with neurofibromatosis type 1: a case series.

AIM: The aim of this case series was to report the use of 8% topical capsaicin patch (marketed under the trade name Qutenza®) a in the management of refractory neuropathic pain (NP) in adult patients with type 1 neurofibromatosis (NF1). METHODS: Capsaicin has been suggested for NF1 patients suffering from refractory peripheral NP despite several years of analgesic treatments. The patch was applied for 60 minutes on the painful area, with tolerability control (blood pressure, intensity of pain and dermal reaction). The evaluation was done at the beginning of treatment and during the 2 months following the first treatment (phone calls at weeks 1, 2, 4 and 8). The primary efficacy criterion was the response rate: a patient was considered to be responding if he or she reported an average relief ≥30% at the time of the follow-up calls. The secondary criteria were: interference scores (QCD), Patient Global Impression of Change (PGIC) and overall treatment satisfaction, self-reported by the patient. RESULTS: Eight patients (5 females/3 males, 41.8 ± 8.2 years of age) received a first treatment with capsaicin. Patients had pre-existing pain for 6.6 years (±6.0) and were currently receiving an average of 6.1 (±3.9) different analgesics. The response rate was 37.5%. The three responders felt globally improved and satisfied, with the improvement in overall condition as interference scores decreased. Apart from the expected local reactions, the treatment was not accompanied by systemic side effects. CONCLUSIONS: As suggested in this case series, capsaicin provided pain relief in certain NF1 patients with resistant NP. The response rate is that expected in multi-line refractory NP. A significant benefit on the overall condition of some patients was observed. In addition, this topical treatment is administered every 3 months without systemic effects. This study is limited by the small number of patients, but was intended to describe a new and well tolerated alternative treatment.

Severe cutaneous adverse reactions due to inappropriate medication use.

BACKGROUND: The proportion of severe cutaneous adverse reactions (SCARs) that could be avoided if medication use was consistent with good medical practice is unknown. OBJECTIVES: To estimate the proportion of SCARs related to inappropriate medication use. METHODS: We carried out a retrospective study of all validated SCARs collected in a French registry between 2003 and 2016. For each case, all plausible drugs suspected of inducing SCARs (i.e. not just the drug regarded as 'the most probable') were considered with regard to (i) prescription for an inappropriate indication, (ii) unintentional rechallenge despite a previous allergy to the drug or (iii) self-medication with prescription medicines. RESULTS: In total, 602 cases were included in the analyses. Antibiotics, anticonvulsants and allopurinol were the drugs most frequently involved, accounting for more than 50% of all cases. All suspected medications were considered to have been appropriately used for 417 of the 602 individuals included in the study population [69·3%, 95% confidence interval (CI) 65·6-73·0] and inappropriately used for 144 individuals (23·9%, 95% CI 20·5-27·3). These inappropriate uses were due mainly to prescriptions for an inappropriate indication (65·8%, 95% CI 58·4-73·2) or unintentional rechallenge (20·9%, 95% CI 14·6-27·2). Allopurinol and co-trimoxazole were the drugs most frequently involved in inappropriate indications. Antibiotics were the largest group involved in unintentional rechallenge. Nonsteroidal anti-inflammatory drugs, available on prescription, were most frequently involved in inappropriate self-medication. CONCLUSIONS: Our results underline the need for respecting the appropriate indication for drugs in order to reduce the incidence of SCARs. Reducing unintentional rechallenge also seems to be a necessary preventive measure.

Treatment of prurigo with methotrexate: a multicentre retrospective study of 39 cases.

BACKGROUND: Prurigo is a common primary pruritic condition. Treatment is challenging. Methotrexate (MTX) is effective for the treatment of pruriginous dermatoses, but its use in prurigo has been little studied. OBJECTIVES: To investigate the efficacy and safety of MTX in the treatment of difficult-to-treat prurigo. METHODS: Patients from six university dermatology departments treated with MTX between 2006 and 2016 for difficult-to-treat prurigo (i.e. with failure to conventional therapies) were included in this retrospective multicentre study. Patients with other pruritic dermatoses were excluded. Clinical efficacy was recorded after 3, 6 and 12 months of treatment: (i) subjective efficacy, that is, evaluation of the pruritus by the patient and (ii) objective efficacy, that is, assessment of cutaneous lesions by the physician: complete or almost complete remission (CR) (healing of lesions), partial remission (PR) (incomplete improvement of lesions) or failure (no improvement or worsening). The overall response rate (ORR) included CR and PR. RESULTS: Thirty-nine patients with previous failure of topical steroids, H1-antihistamine drugs or phototherapy were included. The median weekly dose of MTX was 15 mg (range 5-25 mg). The median follow-up was 16 months (2-108). The mean time between onset of MTX and objective efficacy was 2.4 ± 1.2 months and the mean duration of response was 19 ± 15 months. The ORR was 91% at 3 months [n = 36, CI 95% (81.2-100.8%), CR 44%], 94% at 6 months [n = 32, CI 95% (85.7-102.2%), CR 56%] and 89% at 12 months [n = 28, CI 95% (77.4-100.6%), CR 57%]. Seven patients stopped MTX because of failure, and five because of the discovery of hepatocarcinoma (n = 1), elevated transaminases (n = 1), infectious pneumonitis (n = 1) or gastrointestinal symptoms (n = 2). CONCLUSION: Methotrexate is a therapeutic option in difficult-to-treat prurigo.

Acne prevalence and associations with lifestyle: a cross-sectional online survey of adolescents/young adults in 7 European countries.

BACKGROUND: Although acne vulgaris is a common skin disorder, limited epidemiological data exist specifically for European populations. OBJECTIVE: To determine the prevalence of self-reported acne among young people in Europe and evaluate the effect of lifestyle on acne. METHODS: We conducted a cross-sectional population-based online survey in representative samples of individuals aged 15-24 years in Belgium, Czech and Slovak Republics, France, Italy, Poland and Spain (n = 10 521), identified by a quota sampling method based on age, geographic location and socio-professional category. RESULTS: The overall adjusted prevalence of self-reported acne was 57.8% (95% confidence interval 56.9% to 58.7%). The rates per country ranged from 42.2% in Poland to 73.5% in the Czech and Slovak Republics. The prevalence of acne was highest at age 15-17 years and decreased with age. On multivariate analysis, a history of maternal or paternal acne was associated with an increased probability of having acne (odds ratio 3.077, 95% CI 2.743 to 3.451, and 2.700, 95% CI 2.391 to 3.049, respectively; both P < 0.0001), as was the consumption of chocolate (OR 1.276, 95% CI 1.094 to 1.488, for quartile 4 vs. quartile 1). Increasing age (OR 0.728, 95% CI 0.639 to 0.830 for age 21-24 years vs. 15-17 years) and smoking tobacco (OR 0.705, 95% CI 0.616 to 0.807) were associated with a reduced probability of acne. CONCLUSION: The overall prevalence of self-reported acne was high in adolescents/young adults in the European countries investigated. Heredity was the main risk factor for developing acne.

Idiopathic linear IgA bullous dermatosis: prognostic factors based on a case series of 72 adults.

BACKGROUND: Linear IgA bullous dermatosis (LABD) is a clinically and immunologically heterogeneous, subepidermal, autoimmune bullous disease (AIBD), for which the long-term evolution is poorly described. OBJECTIVES: To investigate the clinical and immunological characteristics, follow-up and prognostic factors of adult idiopathic LABD. METHODS: This retrospective study, conducted in our AIBD referral centre, included adults, diagnosed between 1995 and 2012, with idiopathic LABD, defined as pure or predominant IgA deposits by direct immunofluorescence. Clinical, histological and immunological findings were collected from charts. Standard histology was systematically reviewed, and indirect immunofluorescence (IIF) on salt-split skin (SSS) and immunoblots (IBs) on amniotic membrane extracts using anti-IgA secondary antibodies were performed, when biopsies and sera obtained at diagnosis were available. Prognostic factors for complete remission (CR) were identified using univariate and multivariate analyses. RESULTS: Of the 72 patients included (median age 54 years), 60% had mucous membrane (MM) involvement. IgA IIF on SSS was positive for 21 of 35 patients tested; 15 had epidermal and dermal labellings. Immunoelectron microscopy performed on the biopsies of 31 patients labelled lamina lucida (LL) (26%), lamina densa (23%), anchoring-fibril zone (AFz) (19%) and LL+AFz (23%). Of the 34 IgA IBs, 22 were positive, mostly for LAD-1/LABD97 (44%) and full-length BP180 (33%). The median follow-up was 39 months. Overall, 24 patients (36%) achieved sustained CR, 19 (29%) relapsed and 35% had chronic disease. CR was significantly associated with age > 70 years or no MM involvement. No prognostic immunological factor was identified. CONCLUSIONS: Patients with LABD who are < 70 years old and have MM involvement are at risk for chronic evolution.

Cold-associated perniosis of the thighs histopathologically mimicking lupus. Six observations.

BACKGROUND: Equestrian cold panniculitis has been described since 1980 in horse riders or in stable employees. Histological aspect is underdescribed. PATIENTS AND METHODS: We describe clinical and histological features of six horse riding or stable employees patients presenting with upper lateral thigh lesions during the winter months between 2014 and 2016 in our dermatological department. RESULTS: Six horse riding or stable employees ladies without any known disease presented with similar symptoms. They had urticarial or violaceous, slightly pruritic, sometimes necrotic lesions of the upper lateral thighs. Clinically, equestrian cold panniculitis, insect bite or a caustic dermatitis was suspected. Four of these patients had a cutaneous biopsy. They all showed a similar histological appearance resembling lupus erythematosus, combining dermo-epidermal lesions, with foci of interface dermatitis, an abundant dermal lymphocytic infiltrate and a dermal mucinosis. Hypodermal infiltration was present on samples including subcutis. Laboratory workup for systemic disease was unremarkable for two patients and not performed for the four others, having no other clinical sign of lupus. All patients improved rapidly with very high potent topical steroids. CONCLUSION: Cold-associated perniosis of the thighs should be considered whenever a histopathological appearance of lupus is associated with lesions of the upper lateral thighs in patients practicing horse riding. This disease belongs to the spectrum of miscellaneous cold-induced dermatoses in which histopathological lesions identical to lupus can be encountered.

[Aseptic cutaneous breast abscesses associated with ulcerative colitis]. / Abcès cutanés aseptiques récidivants des seins associés à une rectocolite hémorragique.

BACKGROUND: Inflammatory bowel diseases are associated with a broad range of cutaneous lesions. Herein we report the first case of aseptic skin abscesses associated with ulcerative colitis. CASE REPORT: Since March 2008, a 40-year-old woman presented with bilateral mammary abscesses, relapsing despite repeated antibiotic treatment. She was followed for ulcerative colitis diagnosed in 2011 by means of a rectal biopsy. Despite four surgical procedures, there was no improvement in her mammary abscesses and bilateral mastectomy was then proposed because of the persistent symptoms. Her general state of health remained stable. Clinically, there were bilateral inflammatory nodes with fistulae and pus. These lesions were extremely painful. Mild inflammatory syndrome was noted, but the immunological tests revealed nothing of note. Bacteriological, parasitological and mycological tests on biopsy specimens were negative. Histological examination of a surgical biopsy revealed lymphoplasmacytic infiltration of the dermis and subcutis with altered polymorphonuclear cells and epithelioid granuloma. The CT-scan showed no other remote lesions. The final diagnosis was cutaneous aseptic abscess syndrome associated with ulcerative colitis. Colchicine 1mg/day was initiated and resulted in regression of the skin lesions, with complete remission at one year of follow-up. DISCUSSION: Aseptic abscess syndrome must be considered in the event of recurrent aseptic cutaneous abscesses which may be associated with inflammatory bowel disease. Surgery should be avoided and treatment should be based on suitable drug therapy.

Dermatomyositis: factors predicting relapse.

BACKGROUND: The course of dermatomyositis (DM) can be chronic with relapses, which are associated with major morbidity. OBJECTIVE: The aim of this study was to identify presentation features that predict DM relapses. METHODS: We retrospectively reviewed data of patients with DM recorded from 1990 to 2011, including muscle biopsy results. Characteristics of patients with and without relapses were compared. Hazard ratios (HRs) were estimated using a Cox model. RESULTS: We identified 34 patients, with a mean age of 46 ± 17 years (range, 18-77) and 24 (71%) women. The muscle and skin abnormalities relapsed in 21 (61%) patients. By univariate analysis, two presentation features were significantly associated with a subsequently relapsing course, namely, dysphonia [HR = 3.2 (1.2-8.5)] and greater skin lesion severity defined as a Cutaneous Disease Area Severity Index [CDASI] > 20 [HR = 3.5 (1.2-7.9)]. CONCLUSION: Dysphonia and skin lesion severity at disease onset must be recorded, as they significantly predict a relapsing disease course.