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.

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.

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.

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.

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.

Teledermatology in Times of COVID-19 Confinement: Comparing Patients' and Physicians' Satisfaction by the Standardized Brest Teledermatology Questionnaire.

The French government imposed the first COVID-19 pandemic lockdown from March 17 until May 11, 2020. Only emergency cases and teledermatology (TD) were allowed in outpatient settings. A standardized questionnaire was developed to compare the satisfaction level of patients and their treating physicians. Our main question was whether the patients would perceive TD as a valid alternative for direct physical face-to-face consultation. Eighty-two patients and their 4 treating dermatologists from one dermatology department participated in the study (43 females, 39 males) with a mean age of 46.6 years (SD ±23.9). The reason for TD was a chronic disease in the majority (87.8%), and mainly as a follow-up (96.3%). Regarding satisfaction, almost all categories rated around 9 on a 0-10 verbal analogue scale. The same level of global satisfaction could be seen between the patients and the physicians as well as for the quality of the patient-physician relation and whether all questions could be addressed during the TC. Physicians showed significantly higher scores than patients only for the category of "length" of the consultation. Gender, age, as well as distance between the clinic and home of the patient were not influencing factors for satisfaction. Regarding the technical parameters, the evaluation was mostly comparable for patients and physicians, but overall lower than the relational satisfaction parameters, especially for image quality. Patients were significantly more motivated to continue the TD after the lockdown than their treating dermatologists. We see an interest for implementing TD in specialized centers with chronic patients coming from remote places for regular follow-ups. TD cannot replace in-person patient-physician interaction, but was helpful during the lockdown. As a result, TD might become part of dermatology training to prepare for future lockdown situations.

Proposal for Cut-off Scores for Sensitive Skin on Sensitive Scale-10 in a Group of Adult Women.

Sensitive skin is commonly assessed on the basis of self-reports from patients, and sometimes questionnaires, such as the Sensitive Scale-10, are used. The severity of sensitive skin follows a continuum, from the absence of sensitive skin to very sensitive skin. The aims of this cross-sectional study were to compare subjects with and without symptomatic sensitive skin and to propose diagnostic criteria for sensitive skin. A total of 160 women, between 18 and 65 years of age, with and without sensitive skin, and without any associated skin diseases, were recruited. Mean age was 41 years old. Fifty-five percent of participants reported having "very sensitive" or "sensitive" skin. In the sensitive skin group, the participants mainly experienced skin irritability (100%), tautness (97.5%), discomfort (90%) and redness (90%). According to the receiver operating characteristic curve, a Sensitive Scale-10 (SS-10) cut-off value of 12.7 can be used to detect sensitive skin (with a sensitivity of 72.4% and specificity of 90.3%).

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 Nodular Prurigo: A European Cross-sectional Study of Patient Perspectives on Therapeutic Goals and Satisfaction.

Chronic nodular prurigo is characterized by recalcitrant itch. Patient perspectives on therapeutic goals, satisfaction with therapy and efficacy of therapeutic regimens for this condition are unknown. This questionnaire study examined these issues in 406 patients with chronic nodular prurigo from 15 European dermatological centres. Improvements in itch, skin lesions and sleep were the most important goals. Emollients, topical corticosteroids and antihistamines were the most frequently used treatments, while a minority of patients were prescribed potent medications, such as systemic immunosuppressants and gabapentinoids. Most patients were not satisfied with their previous therapy (56.8%), while 9.8% did not receive any therapy despite having active disease. A substantial number of respondents (28.7%) considered none of the therapeutic options effective. Although chronic nodular prurigo is a severe disease, most patients were not treated with potent systemic drugs, which may contribute to the high levels of dissatisfaction and disbelief in available therapies. Specific guidelines for chronic nodular prurigo and the development of novel therapies are necessary to improve care.

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.

Chronic Pruritus in the Absence of Skin Disease: A Retrospective Study of 197 French Inpatients.

Chronic pruritus (CP) can occur in the absence of skin diseases, and may be secondary to various causes. The aim of this study was to retrospectively analyse the causes of CP without skin disease in a cohort of patients from the dermatology department, including all patients hospitalized for management of their CP between 2008 and 2018. A total of 197 patients with CP without skin disease were included, mean age 66.7 years, 50.8% men. The main causes identified were psychogenic pruritus (41.1% of patients), neuropathic (36.5%), endocrine (12.2%), haematological (9.6%) and iatrogenic (7.1%) causes. The cause was unknown in 20.8% of patients. Total percent is more than 100 because some patients had several etiologies. Only one aetiology of CP was identified in most patients (69.5%), and 2 aetiologies (in 18.3%) or more (in 12.2%). Concerning symptomatic treatments, emollients were prescribed for 40.6% of patients and topical steroids for 20.3%. Among systemic treatments, gabapentinoids (33%), antidepressants (27.4%) and antihistamines (25.3%) were prescribed. The efficacy of these treatments was rarely complete.

Characteristics of Pruritus in Bullous Pemphigoid and Impact on Quality of Life: A Prospective Cohort Study.

Pruritus is a common symptom of bullous pemphigoid (BP), but has been poorly studied. The aim of this study was to analyse the characteristics of pruritus in patients with BP and its impact on their quality of life. A multicentre prospective observational study (in 15 French hospitals) was performed. A total of 60 patients were included, with a mean age of 77.4 years. Pruritus occurred daily in 85% of patients, with a mean pruritus intensity of 5.2/10. Tingling sensations were present in 72.4% of patients and burning sensations in 68.9%. Pruritus was exacerbated by stress, fatigue and xerosis. The mean ItchyQol score was 56.2/110 and the mean 5-D Itch Scale score was 16.5/25. The severity of pruritus was not related to age, sex, BP activity score, eosinophilia, or anti-BP230 and anti-BP180 autoantibodies. This study revealed that pruritus in BP is poorly tolerated and is an important cause of impaired quality of life.

Central mechanisms of itch: A systematic literature review and meta-analysis.

In recent years, studying the central mechanism of itch has gained momentum. However, a proper meta-analysis has not been conducted in this domain. In this study, we tried to respond to this need. A systematic search and a meta-analysis were carried out to estimate the central mechanism of itch. The itch matrix comprises the thalamus and the parietal, secondary somatosensory, insular and cingulate cortices. We have shown that the basal ganglia (BG) play an important role in itch reduction. Finally, we explored itch processing in AD patients and observed that the itch matrix in these patients was different. In conclusion, this is the first meta-analysis on the central mechanisms of itch perception and processing. Our study demonstrated that different modalities of itch induction can produce a common pattern of activity in the brain and provided further insights into understanding the underlying nature of itch central perception.

Usefulness of Psychiatric Intervention in a Joint Consultation for the Treatment of Burning Mouth Syndrome: A Monocentric Retrospective Study.

Primary burning mouth syndrome is a term used for chronic oral mucosal pain with no identifiable organic cause. The aim of the study was to evaluate the usefulness of a psychiatric intervention for treating burning mouth syndrome based on a joint consultation with a psychiatrist and a dermatologist. The study was proposed to all patients who visited this consultation group between 2001 and 2017 for the treatment of primary burning mouth syndrome. The patients answered a questionnaire that was administered via mail. Of the 57 patients diagnosed with primary burning mouth syndrome, 38 were included. Seven patients (18.4%) no longer had pain; 8 (21.1%) estimated that the pain had decreased by greater than 50%; 11 (28.9%) estimated the decrease at between 30 and 50%, and 12 (31.6%) estimated a less than 30% decrease. Only 14 patients (36.8%) remained under treatment with antidepressants, as compared to 63.2% before the psychiatric intervention. This psychiatric intervention could be considered a valuable tool in the global burning mouth syndrome treatment strategy.

Characteristics of Pruritus in Relation to Self-assessed Severity of Atopic Dermatitis.

The objective of this study was to explore characteristics of pruritus in atopic dermatitis (AD) in relation to the severity of AD. A web-questionnaire was used, which included the Patient-Oriented SCORing Atopic Dermatitis index, the 5-D itch scale and the Brest questionnaire. A total of 170 participants were included (86.5% women, mean age 30.9 years). Severity of AD was mild for 8.2% of patients, moderate for 38.2% and severe for 53.5%. Mean 5-D itch scale was 13.2. The mean intensity of pruritus was 5.8, and mean sleep loss was 4.7 (from 0 to 10). The participants frequently described burning (61.8%) and stinging (58.8%); these symptoms suggest a neuropathic component. Pruritus was worse in severe AD compared with moderate AD, exhibiting a higher impact on sleep and more associated symptoms. The majority of participants reported sleep disturbance as a result of pruritus. The characteristics of pruritus varied depending on the severity of AD.

Clinical Characteristics of Pruritus in Systemic Sclerosis Vary According to the Autoimmune Subtype.

Pruritus is a frequent symptom in systemic sclerosis (SSc), with a prevalence of 40-65%, but its pathophysiology is poorly understood. This study investigated the immunological component of pruritus. Fifty-six patients with SSc responded to a standardized questionnaire regarding both SSc disease and pruritus characteristics. Among patients with SSc, those with pruritus did not display a particular immunological profile (inflammatory, humoral, and/or cellular factors), but pruritus was, in most cases, concomitant with the development of SSc. Thus, pruritus characteristics were evaluated further, according to the detection of anti-centromere autoantibodies (ACA), into ACA+ (n = 17) and ACA- (n = 19). The ACA+ subgroup was characterized by a longer evolution of SSc and pruritus, pruritus present outside the sclerotic area, and a shorter daily duration of pruritus. In conclusion, the concomitant appearance of the 2 processes and the differences observed between ACA+ and ACA- subgroups support the presence of an immunological component in pruritus.

Definition of Sensitive Skin: An Expert Position Paper from the Special Interest Group on Sensitive Skin of the International Forum for the Study of Itch.

Sensitive skin is a frequent complaint in the general population, in patients, and among subjects suffering from itch. The International Forum for the Study of Itch (IFSI) decided to initiate a special interest group (SIG) on sensitive skin. Using the Delphi method, sensitive skin was defined as "A syndrome defined by the occurrence of unpleasant sensations (stinging, burning, pain, pruritus, and tingling sensations) in response to stimuli that normally should not provoke such sensations. These unpleasant sensations cannot be explained by lesions attributable to any skin disease. The skin can appear normal or be accompanied by erythema. Sensitive skin can affect all body locations, especially the face". This paper summarizes the background, unresolved aspects of sensitive skin and the process of developing this definition.

Pruritus: an underrecognized symptom of small-fiber neuropathies.

BACKGROUND: Small-fiber neuropathies (SFN) are diseases of small nerve fibers that are characterized by autonomic and sensory symptoms. OBJECTIVE: We sought to evaluate sensory symptoms, especially pruritus, in patients with SFN. METHODS: A questionnaire was given to patients with SFN. RESULTS: In all, 41 patients responded to the questionnaire (71.9% response rate). The most frequent sensory symptoms were burning (77.5%), pain (72.5%), heat sensations (70.2%), and numbness (67.5%). Pruritus was present in 68.3% of patients. It appeared most often in the evening, and was localized to the limbs in a distal-to-proximal gradient, although the back was the most frequent location (64%). Exacerbating factors were fatigue, xerosis, sweating, hot temperature, and stress. Cold water was an alleviating factor. LIMITATIONS: Recall bias associated with filling out the questionnaire, relatively small sample size, and the uncontrolled, retrospective nature of the study were limitations. CONCLUSION: Pruritus occurs frequently in patients with SFN and could be recognized as a possible presenting symptom, especially if there are other sensory or autonomic symptoms.