History of pre-eclampsia does not appear to be a risk factor for vascular phenotype in women with systemic sclerosis.

BACKGROUND: Vascular phenotype is associated with a poor prognosis in systemic sclerosis (SSc). The identification of its risk factors could facilitate its early detection. OBJECTIVES: To explore risk factors for a vascular phenotype of SSc, among them a history of pre-eclampsia. METHODS: This observational multicentre case-control study enrolled adult women fulfilling European Alliance of Associations for Rheumatology 2013 diagnosis criteria for SSc and having a pregnancy history≥6 months before SSc diagnosis in 14 French hospital-based recruiting centres from July 2020 to July 2022. Cases had specific vascular complications of SSc defined as history of digital ischaemic ulcers, pulmonary arterial hypertension, specific cardiac involvement or renal crisis. Women with SSc were included during their annual follow-up visit and filled in a self-administered questionnaire about pregnancy. A case report form was completed by their physician, reporting data on medical history, physical examination, clinical investigations and current medication. The main outcome was the presence/absence of a personal history of pre-eclampsia before SSc diagnosis, according to the validated pre-eclampsia questionnaire. RESULTS: 378 women were included: 129 cases with a vascular phenotype and 249 matched controls. A history of pre-eclampsia was reported in 5 (3.9%) cases and 12 (4.8%) controls and was not associated with a vascular phenotype (OR=0.96, 95% CI 0.28 to 3.34, p=0.9). Besides, Rodnan skin score and disease duration≥5 years were risk factors for vascular phenotype. CONCLUSIONS: In women with SSc and a pregnancy history≥6 months before SSc, a history of pre-eclampsia is not associated with a vascular phenotype.

Metameric pruritus as the sole manifestation of an intramedullary tumor in a toddler.

An 18-month-old child presented with persistent pruritus and excoriation involving the right T9 and T10 dermatomes. She did not exhibit any other dermatological or neurological anomalies. Based on magnetic resonance imaging investigation of the spine, T8 ganglioglioma was diagnosed and surgically removed resulting in resolution of the pruritus within a few days. This observation underlines the importance of neuroimaging in patients presenting with metameric pruritus without specific skin lesions, especially in young children.

Omalizumab in the treatment of bullous pemphigoid resistant to first-line therapy: a French national multicentre retrospective study of 100 patients.

BACKGROUND: Interest in the use of omalizumab to treat bullous pemphigoid (BP) in the event of resistance or contraindication to conventional therapies is currently based on limited evidence. OBJECTIVES: To assess the effectiveness and safety of omalizumab in BP and to identify predictive factors in response to treatment. METHODS: We conducted a French national multicentre retrospective study including patients with a confirmed diagnosis of BP treated with omalizumab after failure of one or several treatment lines. We excluded patients with clinically atypical BP, as per Vaillant's criteria. The criteria for clinical response to omalizumab were defined according to the 2012 international consensus conference. Anti-BP180-NC16A IgE enzyme-linked immunosorbent assay was performed on sera collected before initiating omalizumab, when available. RESULTS: Between 2014 and 2021, 100 patients treated in 18 expert departments were included. Median age at diagnosis was 77 years (range 20-98). Complete remission (CR) was achieved in 77% of patients, and partial remission in an additional 9%. CR was maintained 'off therapy' in 11.7%, 'on minimal therapy' in 57.1%, and 'on non-minimal therapy' in 31.2%. Median time to CR was 3 months (range 2.2-24.5). Relapse rate was 14%, with a median follow-up time of 12 months (range 6-73). Adverse events occurred in four patients. CR was more frequently observed in patients with an increased serum baseline level of anti-BP180-NC16A IgE (75% vs. 41%; P = 0.011). Conversely, urticarial lesions, blood total IgE concentration or eosinophil count were not predictive of CR. Patients with an omalizumab dosage > 300 mg every 4 weeks showed a similar final outcome to those with a dosage ≤ 300 mg every 4 weeks, but control of disease activity [median 10 days (range 5-30) vs. 15 days (range 10-60); P < 0.001] and CR [median 2.4 months (range 2.2-8.2) vs. 3.9 months (range 2.3-24.5); P < 0.001] were achieved significantly faster. CONCLUSIONS: We report the largest series to date of BP treated by omalizumab and confirm its effectiveness and safety in this indication. Serum baseline level of anti-BP180-NC16A IgE may predict response to treatment.

Psychogenic and neurogenic components in patients with psychogenic or neuropathic pruritus: PRURINEURO: A non-interventional single-centre prospective assay.

Background: The causes of pruritus are multiple and commonly classified into six different categories: dermatological, systemic, neuropathic, psychogenic, mixed and idiopathic. In clinical practice, psychogenic and neurogenic mechanisms tend to be separated in the etiological diagnosis of neuropathic or psychogenic disorders; nevertheless, studies investigating the respective psychogenic and neurogenic components are lacking. Objective: The main objective of this work was to highlight the differences and potential common characteristics between psychogenic pruritus and neuropathic pruritus. Methods: This study was a noninterventional single-centre prospective assay. Patients with neuropathic (NP) or psychogenic (PP) pruritus were proposed to participate. The psychogenic and neurogenic components of pruritus in these patients were evaluated using six validated questionnaires or criteria, namely, the diagnosis criteria of psychogenic pruritus, the NP5 questionnaire, the Brest Pruritus Qualitative Assessment Questionnaire, Hospital Anxiety and Depression Scale, Toronto Alexithymia Scale, and DN4i. Results: Twenty-five patients with NP and 15 with PP were included. A difference between the two groups was observed for NP5, with mean scores of 2.8 ± 0.9 and 1.4 ± 1 for the NP and PP groups, respectively (p < 0.0001). For depression, the average score was 3.5 ± 3.9 for the NP group and 7.5 ± 5.1 for the PP group (p < 0.02). Conclusion: While neuropathic and psychogenic disorders are different diagnoses, neuropathic and psychogenic components may exist simultaneously in patients with NP or PP.

Pruritus and brain tumours: A prospective and descriptive study.

Background: Pruritus, especially localised to the nostrils, has been reported as a specific sign of brain tumours. Objectives: The main goal of this study was to estimate the prevalence of pruritus in a group of patients with brain tumours. The second outcome was to better characterise this pruritus with a specific questionnaire and a skin examination. Methods: From June 2020 to September 2021, all patients with a diagnosis of brain tumour were included in this prospective, monocentric study. If the patient suffered from pruritus, a dermatological examination was performed. Results: Two hundred patients with brain tumours were included. Thirty-five of them suffered from pruritus (17.5%). Among them, 15 patients did not present with any skin disease, and 8 could have neuropathic pruritus according to the NP5 questionnaire. No patients presented with pruritus of the nostrils. Discussion: This study did not show clear evidence of specifically localised pruritus induced by brain tumours. Conclusion: Pruritus observed in patients with brain tumours seems not to be caused by the brain malignancies in most cases. The specific localization to the nostrils cannot be considered a specific marker.

Sensitive Skin Syndrome: A Low-Noise Small-Fiber Neuropathy Related to Environmental Factors?

Background and Objectives: Patients frequently complain of mild, transient, unpleasant skin sensations that cannot be diagnosed as common neuropathies. Dermatologists have termed these symptoms "sensitive skin syndrome." This narrative review was performed for a better knowledge by other specialists. Databases and Data Treatment: Publications on pain in sensitive skin syndrome were obtained from PubMed. Results: There is a growing body of data supporting the concept that sensitive skin is a type of small-fiber neuropathy. The arguments are based on clinical data, a decrease in intra-epidermal nerve fiber density, quantitative sensory testing abnormalities and an association with irritable bowel syndrome and sensitive eyes. Sensitive skin is triggered by environmental factors. Sensitive skin is a frequent condition, with a lifetime prevalence of ~50% according to self-reports. Conclusions: Mild levels of skin pain or itch are frequently experienced by patients, who rarely report them. There is a need for a better knowledge of sensitive skin because it can be the first level of small-fiber neuropathies.

Efficacy of Treatments for Cholestatic Pruritus: A Systemic Review and Meta-analysis.

Cholestatic itch is a disabling symptom that may be secondary to liver or biliary diseases. Management of cholestatic pruritus is complex. A systematic review and meta-analysis on the efficacy of treatments for cholestatic pruritus were performed. PubMed and Cochrane Library were searched using the algorithm "(hepatitis OR cholestatic OR liver) AND (pruritus OR itch) AND (management OR treatment OR treatments)" for 1975-2019. Of the 2,264 articles identified, 93 were included in a systematic review and 15 in a meta-analysis (studies evaluating pruritus with a visual analogue scale). Some treatments act by reducing levels of pruritogens in the enterohepatic cycle, others modify the metabolism or secretion of these pruritogens, or act on pruritus pathways. A further possible treatment is albumin dialysis. However, due to many heterogeneities in the reviewed studies it is difficult to identify and recommend an optimum treatment. Only 15 studies were included in the meta-analysis, due to the small number of randomized studies using a visual analogue scale.

Efficacy of topical and systemic treatments for atopic dermatitis on pruritus: A systematic literature review and meta-analysis.

Introduction: Pruritus is a major and burdensome symptom in atopic dermatitis (AD). The number of systemic treatments available for AD has increased recently, enabling improved patient relief. Objective: To evaluate the effect of AD treatments on pruritus. Methods: A systematic literature review and a meta-analysis were conducted to evaluate and compare the effects of treatment used in AD on pruritus. PubMed and Embase databases were searched to find articles published between January 1990 and December 2021. Topical and systemic treatments were studied in patients aged ≥10 years. Results: Among the 448 articles identified, 56 studies were retained in the systematic review. A total of 15 studies evaluated topical treatments: topical corticosteroids (TCS; 2), calcineurin inhibitors (6), PDE4 inhibitors (3), and Jak inhibitors (4). A total of five studies were included in the meta- analysis. All treatments had a positive effect on pruritus, with a mean overall reduction of 3.32/10, 95% IC [2.32-4.33]. The greatest reduction was observed with halometasone (mean: 4.75), followed by tofacitinib 2% (mean: 4.38). A total of 41 studies evaluated systemic therapies: cyclosporine (6), phototherapy (5), azathioprine (2), dupilumab (9), anti-IL 13 (5), nemolizumab (3), Jak inhibitors (9), mepolizumab (1), and apremilast (1). A total of 17 studies were included in 2 meta-analyses according to the concomitant use or not of TCS. In the meta-analysis without TCS, the overall decrease was 3.07/10, 95% IC [2.58-3.56]. The molecules with the highest efficacy on pruritus were upadacitinib 30 mg (mean: 4.90) and nemolizumab (mean: 4.81). Discussion: The therapeutic arsenal for AD has increased rapidly, and many molecules are under development. The primary endpoint of clinical trials is most often a score that assesses the severity of AD; however, the assessment of pruritus is also essential. The majority of molecules have a positive effect on pruritus, but the improvement varies between them. Efficacy on pruritus is not always correlated with efficacy on AD lesions; therefore, these two criteria are crucial to evaluate. The limitations of this study were the heterogeneity in the assessment of pruritus, the moment of the assessment, and the concomitant application of TCS or not for studies evaluating systemics. In the future, it would be useful to use standardized criteria for assessing pruritus.

Observational case-control study of small-fiber neuropathies, with regards on smoking and vitamin D deficiency and other possible causes.

Introduction: Small fiber neuropathies (SFNs) are disorders of skin nerve endings inducing pruritus, burning pain, numbness, and paresthesia. The aims of this study were to search for putative etiologies of SFN and their occurrence in a cohort of patients and to compare patients with SFN to a group of patients without SFN to highlight potential factors associated with SFN. Methods: This study was observational, retrospective, and monocentric. All patients with symptoms of SFN who underwent skin biopsies with intraepidermal nerve density counts were included. Patients with a count lower than 5 percentiles were considered to be in the SFN group. Other patients were considered to be the control group. Results: A total of 162 patients with SFN and 161 controls were included. No cause was identified for 108 patients (61.7%). The established causes were autoimmune diseases (9.1%), diabetes or glucose intolerance (8%), medication (4%), liver disease (3.4%), and monoclonal gammopathy of undetermined significance (2.9%). Current or former smokers were more numerous in the SFN group (26.5%) than in the control group (16.1%), while vitamin D amounts were significantly lower in the SFN group than in the control group. Discussion: Hence, tobacco smoking and vitamin D deficiency might be new putative causes of SFN.

Switching biologics in children with psoriasis: Results from the BiPe cohort.

BACKGROUND: There is currently little information on switching biologics in pediatric psoriasis. OBJECTIVE: To evaluate the real-world clinical practice and safety of switching biologics in the "Biological Treatments for Pediatric Psoriasis" (BiPe) cohort. METHODS: Data for all 134 patients included in the BiPe cohort were analyzed. A further evaluation of the subpopulation of patients who switched from a first-line biologic to a second-line biologic was then conducted. Drug survival rates were also compared between biologics given as first-line or second-line agents. RESULTS: Overall, 29 patients (female: 55%; mean age: 16.6 ± 3.0 years) switched between two biologics. Etanercept (ETN) was the first-line biologic used in 23 patients: 16 (69.6%) switched to adalimumab (ADA) and seven (30.4%) to ustekinumab (UST). Six patients received first-line ADA and switched to UST. Loss of efficacy (62.1%), primary inefficacy (20.7%), and parental choice (6.9%) were the main reasons for switching biologics. One (3.4%) of the switches was performed because of adverse events or intolerance. For UST and ADA, the 18-month drug survival rate did not differ according to whether the agent was given as a first-line or second-line biologic (UST: P = .24; ADA: P = .68). No significant differences in drug survival rates were observed between the three different switches (ADA to UST, ETN to ADA, and ETN to UST). CONCLUSION: Our study provided key insights into the real-life clinical practice of switching biologics in pediatric psoriasis patients. However, more information and guidance on switching biologics in pediatric psoriasis are needed to improve real-life practice and outcomes.

Pruritus, Pain, and Depression Associated with the Most Common Skin Diseases: Data from the French Study "Objectifs Peau".

BACKGROUND: The prevalence and impact of pruritus, pain, and other sensory symptoms in skin diseases are poorly known. OBJECTIVE: To assess the frequency of these symptoms with dermatoses and their association with depression using data from the "Objectifs Peau" survey. METHODS: A representative sample of 20,012 French individuals was created using the usual quota method. RESULTS: When patients suffered from both pruritus and skin pain, they had a higher relative risk of psychological suffering (2.9) than those who suffered only from pruritus (1.4) or skin pain (1.2). Pruritus was reported in 48.55% of patients with acne, 43.24% with mycoses, 44.35% with warts, and 36.51% with rosacea. For skin pain, the results were 11.22%, 27.59%, and 16.13% for atopic dermatitis, acne, and warts, respectively. Other unpleasant sensations, such as tingling or burning, were also frequently reported. CONCLUSION: Pruritus, pain, or other sensory symptoms were found to be common not only in classic pruritic skin diseases but also in acne, rosacea, or warts. The association of pruritus and pain dramatically increased psychological suffering. These symptoms must be systematically searched for in patients, especially since new therapeutic possibilities are emerging for the symptomatic treatment of pruritus.

Chilblains during lockdown are associated with household exposure to SARS-CoV-2: a multicentre case-control study.

OBJECTIVES: During the COVID-19 pandemic, numerous cases of chilblains have been reported. However, in most cases, RT-PCR or serology did not confirm SARS-CoV-2 infection. Hypotheses have been raised about an interferon-mediated immunological response to SARS-CoV-2, leading to effective clearance of the SARS-CoV-2 without the involvement of humoral immunity. Our objective was to explore the association between chilblains and exposure to SARS-CoV-2. METHODS: In this multicentre case-control study, cases were the 102 individuals referred to five referral hospitals for chilblains occurring during the first lockdown (March to May 2020). Controls were recruited from healthy volunteers' files held by the same hospitals. All members of their households were included, resulting in 77 case households (262 individuals) and 74 control households (230 individuals). Household exposure to SARS-CoV-2 during the first lockdown was categorized as high, intermediate or low, using a pre-established algorithm based on individual data on symptoms, high-risk contacts, activities outside the home and RT-PCR testing. Participants were offered a SARS-CoV-2 serological test. RESULTS: After adjustment for age, the association between chilblains and viral exposure was estimated at OR 3.3, 95% CI (1.4-7.3) for an intermediate household exposure, and 6.9 (2.5-19.5) for a high household exposure to SARS-CoV-2. Out of 57 case households tested, six (11%) had positive serology for SARS-CoV-2, whereas all control households tested (n = 50) were seronegative (p = 0.03). The effect of potential misclassification on exposure has been assessed in a bias analysis. DISCUSSION: This case-control study demonstrates the association between chilblains occurring during the lockdown and household exposure to SARS-CoV-2.

Long-term Outcome of Chilblains Associated with SARS-CoV-2.

Numerous cases of chilblains have been observed in the course if the COVID-19 pandemic. The aims of this study were to provide comprehensive follow-up data for patients reporting chilblains, and to determine the risk factors for incomplete recovery. Patients referred to 5 hospitals in France between March and May 2020 for chilblains were surveyed on December 2020. A teleconsultation was offered. Among 82 patients reporting chilblains, 27 (33%) reported complete recovery, 33 (40%) had recurrences of chilblains after their hands and feet had returned to normal, and 22 (27%) developed persistent acral manifestations, mostly acrocyanosis, with or without further recurrences of chilblains. Most recurrences of chilblains occurred during the following autumn and winter. A past history of chilblains was not associated with recurrences or persistent acral manifestations. Women had a significantly higher risk of developing recurrences or persistent acral manifestations (odds ratio 1.30; 95% confidence interval 1.06-1.59). In conclusion, two-thirds of patients reporting chilblains at the start of the COVID-19 pandemic experienced persistent or recurrent acral manifestations after a 10-month follow-up.

Chronic itch: emerging treatments following new research concepts.

Until recently, itch pathophysiology was poorly understood and treatments were poorly effective in relieving itch. Current progress in our knowledge of the itch processing, the numerous mediators and receptors involved has led to a large variety of possible therapeutic pathways. Currently, inhibitors of IL-31, IL-4/13, NK1 receptors, opioids and cannabinoids, JAK, PDE4 or TRP are the main compounds involved in clinical trials. However, many new targets, such as Mas-related GPCRs and unexpected new pathways need to be also explored.

Use of Cosmetic Products in Real Life by Women with Facial Sensitive Skin: Results from an Exposure Study and Comparison with Controls.

Triggering factors of sensitive skin are supposed to be physical, chemical (cosmetics, water, and pollutants), and occasionally psychological (stress). A recent meta-analysis showed that the most important triggering factor declared by subjects is the use of cosmetics. This study was designed to compare the consumption of cosmetic products in women with sensitive skin and controls. After a dermatological examination, women between the ages of 18 and 65 years with or without sensitive skin were recruited. They completed different questionnaires about the presence of sensitive skin and use of 28 cosmetics that could be applied on the face. The amount per application was recorded for all products used at least once a week on the face. In total, 160 women were included, with a mean age of 41 ± 13 years. Two groups of 40 women were created based on the sensitive scale (SS-10 score), with the lowest SS-10 scores (nonsensitive skin group) and the highest SS-10 score (sensitive skin group). The number of products used daily was similar in the 2 groups. Women with sensitive skin were significantly more frequent users of liquid soap/soap-free gel cleansers than those without sensitive skin (70 vs. 43%). There was no difference concerning the frequency of use of products in the 2 groups. Concerning the amount of product used by application, women with sensitive skin used twice as much cream per application compared with the women without sensitive skin: 511 ± 438 µg versus 290 ± 203 µg (p = 0.039). Concerning the composition of the cosmetic products used, the only difference concerned phenoxyethanol, which was more often present in the moisturizer of women without sensitive skin (66.7%) than in those with sensitive skin (32.4%) (p = 0.007). Women with sensitive skin were more likely to buy products recommended for sensitive skin by manufacturers. The relationship of causality between the use of cosmetics and sensitive skin cannot be established. Women with sensitive skin used different cosmetic products than women without sensitive skin. Women with sensitive skin used a higher amount of moisturizer, used products recommended for sensitive skin, and bought more cosmetic products at pharmacies than supermarkets. We hypothesized that subjects with sensitive skin are looking for products that improve the sensation of skin sensitivity.