S2k guidelines on diagnosis and treatment of linear IgA dermatosis initiated by the European Academy of Dermatology and Venereology.

INTRODUCTION: Linear IgA dermatosis (LAD) is a rare subepidermal autoimmune bullous disease (AIBD) defined by predominant or exclusive immune deposits of immunoglobulin A at the basement membrane zone of skin or mucous membranes. This disorder is a rare, clinically and immunologically heterogeneous disease occurring both in children and in adults. The aim of this project is to present the main clinical features of LAD, to propose a diagnostic algorithm and provide management guidelines based primarily on experts' opinion because of the lack of large methodologically sound clinical studies. METHODS: These guidelines were initiated by the European Academy of Dermatology and Venereology (EADV) Task Force Autoimmune Bullous Diseases (AIBD). To achieve a broad consensus for these S2k consensus-based guidelines, a total of 29 experts from different countries, both European and non-European, including dermatologists, paediatric dermatologists and paediatricians were invited. All members of the guidelines committee agreed to develop consensus-based (S2k) guidelines. Prior to a first virtual consensus meeting, each of the invited authors elaborated a section of the present guidelines focusing on a selected topic, based on the relevant literature. All drafts were circulated among members of the writing group, and recommendations were discussed and voted during two hybrid consensus meetings. RESULTS: The guidelines summarizes evidence-based and expert opinion-based recommendations (S2 level) on the diagnosis and treatment of LAD. CONCLUSION: These guidelines will support dermatologists to improve their knowledge on the diagnosis and management of LAD.

S2k guidelines on the management of paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome initiated by the European Academy of Dermatology and Venereology (EADV).

BACKGROUND: Paraneoplastic pemphigus (PNP), also called paraneoplastic autoimmune multiorgan syndrome (PAMS), is a rare autoimmune disease with mucocutaneous and multi-organ involvement. PNP/PAMS is typically associated with lymphoproliferative or haematological malignancies, and less frequently with solid malignancies. The mortality rate of PNP/PAMS is elevated owing to the increased risk of severe infections and disease-associated complications, such as bronchiolitis obliterans. OBJECTIVES: These guidelines summarize evidence-based and expert-based recommendations (S2k level) for the clinical characterization, diagnosis and management of PNP/PAMS. They have been initiated by the Task Force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology with the contribution of physicians from all relevant disciplines. The degree of consent among all task force members was included. RESULTS: Chronic severe mucositis and polymorphic skin lesions are clue clinical characteristics of PNP/PAMS. A complete assessment of the patient with suspected PNP/PAMS, requiring histopathological study and immunopathological investigations, including direct and indirect immunofluorescence, ELISA and, where available, immunoblotting/immunoprecipitation, is recommended to achieve a diagnosis of PNP/PAMS. Detection of anti-envoplakin antibodies and/or circulating antibodies binding to the rat bladder epithelium at indirect immunofluorescence is the most specific tool for the diagnosis of PNP/PAMS in a patient with compatible clinical and anamnestic features. Treatment of PNP/PAMS is highly challenging. Systemic steroids up to 1.5 mg/kg/day are recommended as first-line option. Rituximab is also recommended in patients with PNP/PAMS secondary to lymphoproliferative conditions but might also be considered in cases of PNP/PAMS associated with solid tumours. A multidisciplinary approach involving pneumologists, ophthalmologists and onco-haematologists is recommended for optimal management of the patients. CONCLUSIONS: These are the first European guidelines for the diagnosis and management of PNP/PAMS. Diagnostic criteria and therapeutic recommendations will require further validation by prospective studies.

Comorbidities in lichen planus by phenome-wide association study in two biobank population cohorts.

BACKGROUND: Lichen planus (LP) is a relatively frequent mucocutaneous inflammatory disease affecting the skin, skin appendages and mucosae, including oral mucosae, and less frequently the anogenital area, conjunctivae, oesophagus or larynx. OBJECTIVES: To estimate the association of LP, with emphasis on dermatological and gastrointestinal conditions, in two large independent population cohorts. MATERIALS AND METHODS: We performed a phenome-wide association study (PheWAS) and examined conditions associated with LP in two unrelated cohorts, i.e. the multicentre, community-based UK Biobank (UKB: 501 381 controls; 1130 LP subjects) and the healthcare-associated Penn Medicine BioBank (PMBB; 42 702 controls; 764 LP subjects). The data were analysed in 2021. The 'PheWAS' R package was used to perform the PheWAS analyses and Bonferroni correction was used to adjust for multiple testing. Odds ratios (ORs) were adjusted for age, sex and body mass index. RESULTS: In the UKB, PheWAS revealed 133 phenome codes (PheCodes) significantly associated with LP and most of them were confirmed in PMBB. Dermatological and digestive PheCodes were the most abundant: 29 and 34 of these disorders, respectively, were significantly overrepresented in LP individuals from both cohorts. The 29 dermatological and 12 oral disorders were often highly enriched, whereas hepatic, gastric, oesophageal and intestinal PheCodes displayed ORs in the range of 1·6-4·5. Several autoimmune disorders also exhibited OR > 5 in both cohorts. CONCLUSIONS: PheWAS in two large unrelated cohorts identified previously unknown comorbidities and may support clinical counselling of patients with LP. What is already known about this topic? Lichen planus (LP) is known to affect the skin, skin appendages and mucosae, including oral mucosae, and less frequently the anogenital area, conjunctivae, oesophagus or larynx. What does this study add? Our data provide the most comprehensive collection of associated dermatological, digestive and autoimmune disorders to date. Our findings are expected to be useful for the evaluation and management of patients with LP.

Prurigo Pigmentosa: Demographics and Characteristics in 14 Caucasian Patients.

BACKGROUND: Prurigo pigmentosa (PP) is an inflammatory dermatosis typically reported in young Asian women and characterized by recurrent papulovesicular lesions resolving with a postinflammatory reticulated hyperpigmentation. METHODS: We have included all consecutive patients with PP diagnosed in our tertiary center between 2013 and 2020. The clinical information was retrospectively collected from medical records. RESULTS: We identified 14 patients with PP. The median age at the time of diagnosis was 29.5 years (range 17-43 years), while the female-to-male ratio was 13:1. Diagnostic delay varied from 10 days to 10 years (mean of 25 months). Light microscopy studies consistently showed presence of a lymphohistiocytic infiltrate in combination in 40% of cases with neutrophils. Interface changes were found in 60% of cases. In 6 (43%) of 14 cases, there was a chronological relationship between the starting of a new diet and the development of the first flares. Treatment with doxycycline in 9 patients resulted in a complete regression of the lesions. LIMITATION: This was a retrospective study in a tertiary referral hospital. CONCLUSIONS: Our observations indicate that PP is not so rare in Europe as previously thought and is often diagnosed after a long delay. Demographics, clinical characteristics and triggering factors in Caucasian patients are similar to those described in the Asian population. Diagnosis is based on the peculiar recurrent course and distinctive clinicopathological features. Tetracyclines represent the first-line therapy in PP.

Diagnosis and management of pemphigus: Recommendations of an international panel of experts.

BACKGROUND: Several European countries recently developed international diagnostic and management guidelines for pemphigus, which have been instrumental in the standardization of pemphigus management. OBJECTIVE: We now present results from a subsequent Delphi consensus to broaden the generalizability of the recommendations. METHODS: A preliminary survey, based on the European Dermatology Forum and the European Academy of Dermatology and Venereology guidelines, was sent to a panel of international experts to determine the level of consensus. The results were discussed at the International Bullous Diseases Consensus Group in March 2016 during the annual American Academy of Dermatology conference. Following the meeting, a second survey was sent to more experts to achieve greater international consensus. RESULTS: The 39 experts participated in the first round of the Delphi survey, and 54 experts from 21 countries completed the second round. The number of statements in the survey was reduced from 175 topics in Delphi I to 24 topics in Delphi II on the basis of Delphi results and meeting discussion. LIMITATIONS: Each recommendation represents the majority opinion and therefore may not reflect all possible treatment options available. CONCLUSIONS: We present here the recommendations resulting from this Delphi process. This international consensus includes intravenous CD20 inhibitors as a first-line therapy option for moderate-to-severe pemphigus.

Patterns among Patients with Chronic Pruritus: A Retrospective Analysis of 170 Patients.

Chronic pruritus profoundly affects patients' quality of life. The objective of this retrospective cross-sectional study was to characterize patients with chronic pruritus and identify patterns, in order to delineate a better diagnostic approach. Both semantic connectivity map and classical analysis were applied, linking demographic, clinical, laboratory and histopathological data with clinical and aetiological categories of 170 patients with chronic pruritus (median age 72 years, 58.2% women). The semantic map showed clinical categories separated in different hubs associated with distinct patterns concerning sex, aetiology, laboratory findings, and pharmacological treatment. Diabetes, diagnosis of cancer and psychiatric comorbidities were linked with certain clinical categories. Skin eosinophilia was a common finding of chronic pruritus, on both diseased and non-diseased skin. High frequencies of patients with chronic pruritus taking anti-arrhythmics, beta-blockers and AT-II receptor antagonists were noticed among those with underlying systemic, neurological and psychiatric diseases. This study provides a complex analysis of chronic pruritus and thus basic principles for a clinical work-up.

Successful Treatment of Iatrogenic Cutaneous Siderosis with Pigment Lasers: A Retrospective Study in 15 Consecutive Patients.

Intravenous ferric carboxymaltose is increasingly used to treat iron deficiency. However, a common side-effect is paravenous extravasation of iron preparations, resulting in cutaneous siderosis. Quality-switched (QS) lasers and, recently, picosecond (PS) lasers have been used to treat these hyperpigmentations with variable success. The optimal treatment protocol remains unclear. The aims of this study were to assess the response of cutaneous siderosis to treatment with pigment lasers and to determine the optimal wavelength, number of treatment sessions and pulse duration. Fifteen patients with cutaneous siderosis on the arms were included. The effectiveness of laser treatment was evaluated using a 5-point standard Physician Global Assessment (PGA) grading system. Differences in continuous variables between distinct groups of patients were assessed with a Mann-Whitney U test. In all 15 patients clearance of at least 50% was obtained. In 12 patients, at least 75% of pigment was removed. In conclusion, pigment lasers are an effective and safe method to treat cutaneous siderosis.

Herpes zoster of the trigeminal nerve with multi-dermatomal involvement: a case report of an unusual presentation.

BACKGROUND: Herpes zoster, also known as shingles, results from reactivation of the varicella-zoster virus. It commonly presents with burning pain and vesicular lesions with unilateral distribution and affects the thoracic and cervical sites in up to 60 and 20% of cases, respectively. The branches of the trigeminal nerves are affected in up to 20% of cases. Multidermatomal involvement of the trigeminal nerves has been only anecdotally described in immunocompetent subjects. CASE PRESENTATION: A 71-year-old previously healthy male presented with grouped vesicular and impetiginized lesions with crusts on the left half of the face of two-weeks duration. The lesions first developed on the left nasal tip and progressively worsened with unilateral appearance of vesicular lesions on the left forehead, face, ala nasi, nasal vestibulum and columella, as well as on the left side of hard and soft palate. The affected edematous erythematous areas corresponded to the distribution of the left ophthalmic (V1) and maxillary (V2) branches of the trigeminal nerve, including the infraorbital and nasopalatine nerves of the maxillary branch responsible for the oral cavity involvement. Viral DNA amplification by polymerase chain reaction confirmed the presence of Varicella zoster virus. The patient was started on oral valaciclovir with rapid recovery. CONCLUSIONS: Among immunocompetent patients, herpes zoster is considered a self-limited localized infection. Our observation provides a rare but paradigmatic example of herpes zoster with involvement of both the ophthalmic and maxillary divisions of the trigeminal nerve in an immunocompetent patient. Immunocompetence status and age-specific screening should be warranted in case of atypical involvement and according to the patient's history, while treatment with antiviral drugs should be rapidily initiated in patients at risk.

Emergency Consultations in Dermatology in a Secondary Referral Hospital in Southern Switzerland: A Prospective Cross-Sectional Analysis.

BACKGROUND/AIMS: The spectrum of dermatological emergencies is broad. Only a few studies have assessed the profile of dermatological conditions resulting in an emergency visit in a referral hospital. We sought to assess the conditions prompting an urgent dermatological visit and to compare the diagnoses with those made during the regular scheduled encounters. METHODS: We performed a cross-sectional study of all patients with a cutaneous problem attending our emergency consultation during a 7-month period. The study variables were gender, age, duration of symptoms, diagnosis, need for hospitalization and/or follow-up. We further evaluated patients attending scheduled visits to compare the demographic characteristics and diagnoses between the two groups. RESULTS: Six hundred fifty-two consecutive patients with an urgent dermatological consultation were included. Three hundred sixty (55.2%) were women and 292 (44.8%) were men. Infectious diseases (32.8%) as well as various forms of eczema (24.8%) constituted the most frequent causes for an emergency visit. Approximately 40% of emergency visits took place more than 1 week after the development of the cutaneous manifestations. The most frequent disorders seen in the 1,738 control patients included benign melanocytic and nonmelanocytic tumors (27.2%) and malignant skin lesions (11.5%). CONCLUSIONS: Our study indicates that the dermatological diagnoses in the emergency visits significantly differ from those of the routinely scheduled appointments. In a significant portion of patients, the use of an emergency consultation was not justified. This study provides support to the idea that a specific training is required to manage dermatological emergencies and that efforts should be made to reduce unjustified emergency visit use.

Dipeptidyl peptidase IV inhibitors, a risk factor for bullous pemphigoid: Retrospective multicenter case-control study from France and Switzerland.

BACKGROUND: Case reports have suggested an association between dipeptidyl peptidase-4 inhibitors (DPP4is) and development of bullous pemphigoid (BP). OBJECTIVE: To evaluate the association between DPP4i treatment and development of BP. METHODS: We conducted a retrospective 1:2 case-control study, comparing case patients with diabetes and BP with age- and sex-matched control patients with diabetes issued from Swiss (Bern) and French (Marseille) dermatologic departments from January 1, 2014, to July 31, 2016. RESULTS: We collected 61 case patients with diabetes and BP and 122 controls. DPP4is were associated with an increased risk for development of BP (adjusted odds ratio, 2.64; 95% confidence interval, 1.19-5.85; P = .02), with vildagliptin showing the highest adjusted odds ratio (3.57 [95% confidence interval, 1.07-11.84; P = .04]). Stratified analysis showed a stronger association in males and patients age 80 years or older. DPP4i withdrawal and the initiation of first-line treatments led to clinical remission in 95% of cases. LIMITATIONS: This was a retrospective study in tertiary referral hospitals. We focused the analysis on DPP4i intake, without analyzing the potential isolated effect of metformin. CONCLUSIONS: DPP4is, especially vildagliptin, are associated with an increased risk for development of BP. Their use needs to be carefully evaluated, particularly in high-risk patients, such as males and those age 80 years or older.

Chronic hand eczema: A prospective analysis of the Swiss CARPE registry focusing on factors associated with clinical and quality of life improvement.

BACKGROUND: Hand eczema (HE) is common and may follow a chronic disease course. So far, prospective studies investigating the risk factors for disease progression as a prerequisite for targeted prevention are scarce. OBJECTIVE: To evaluate the overall association of HE-associated factors with clinical and quality of life (QoL) improvement during a follow-up of 2 years. METHODS: Data of the prospective patient cohort (N = 199) followed by the Swiss chronic HE (CHE) registry on long-term patient management (CARPE-CH) were analysed by means of both classic regression and semantic map analyses. RESULTS: Both severity of HE and QoL significantly improved over the period of 2 years (P < .001). However, 20% of patients had moderate to severe HE after 2 years of follow-up. As factors associated with an unfavourable CHE clinical course and QoL, environmental exposures, male sex, occupational skin disease, job loss or change at baseline, allergic contact dermatitis, a chronic disease course, palmar localization and widespread eczema were identified. CONCLUSIONS: Analysis of prospective data from CARPE-CH shows a complex pattern of associations among variables as shown by semantic map and classic statistical analyses. Factors related to occupational exposure had the highest impact on CHE.

Drug therapy of advanced cutaneous squamous cell carcinoma: is there any evidence?

PURPOSE OF REVIEW: There are few randomized controlled studies to guide the treatment of advanced cutaneous squamous cell carcinoma. The existing treatments are mostly based on case reports and small case series. Here we review recently available insights concerning the treatment of locally advanced and metastatic squamous cell carcinoma, with a special emphasis on novel targeted therapy and immunotherapy. RECENT FINDINGS: Surgery and combination of chemotherapy and radiation therapy have been long considered the gold standard options for advanced squamous cell carcinoma. The detection of clinically relevant driver mutations has opened the door to the use of novel targeted therapies. Recent studies have shown that aggressive cutaneous squamous cell carcinoma is characterized by a very high mutational background. Furthermore, the importance of the defective immunosurveillance in the growth of cutaneous squamous cell carcinoma and the critical role of programed cell death protein 1 and programmed death-ligand 1 interaction in skin tumor development provides a rationale for the use of immune checkpoint inhibitors. SUMMARY: Epidermal growth factor receptor inhibitors have shown to have satisfactory antitumor activity with acceptable side-effect profile. However, their place in management of advanced cutaneous squamous cell carcinoma alone or in combination with either radiation therapy and/or chemotherapy needs to be better characterized. The available preliminary findings suggest that immune checkpoint inhibitors represent a potentially valuable alternative in cutaneous aggressive squamous cell carcinoma, promising a further expansion of their indication spectrum. Randomized controlled studies will allow us to better characterize their practical value.

Eosinophils as putative therapeutic targets in bullous pemphigoid.

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering skin disease and is characterized by the presence of autoantibodies directed against the hemidesmosomal proteins BP180 and BP230 that can be detected in the skin and serum of BP patients. Histologically, the dermal infiltration of eosinophils is obvious. The objective of this review was to present evidence that eosinophils play a key role in the pathogenesis of BP. Eosinophils, together with cytokines and chemokines regulating their production, recruitment and activation, are abundantly present in lesional skin, in blisters and in peripheral blood of patients with BP. Recently, using a cryosection model, eosinophils were demonstrated to induce dermal-epidermal separation in the presence of BP antibodies. Thus, eosinophils and their products, as well as mediators regulating their function, present promising targets for the treatment of BP.

One gene but different proteins and diseases: the complexity of dystonin and bullous pemphigoid antigen 1.

Since the immunochemical identification of the bullous pemphigoid antigen 230 (BP230) as one of the major target autoantigens of bullous pemphigoid (BP) in 1981, our understanding of this protein has significantly increased. Cloning of its gene, development and characterization of animal models with engineered gene mutations or spontaneous mouse mutations have revealed an unexpected complexity of the gene encoding BP230. The latter, now called dystonin (DST), is composed of at least 100 exons and gives rise to three major isoforms, an epithelial, a neuronal and a muscular isoform, named BPAG1e (corresponding to the original BP230), BPAG1a and BPAG1b, respectively. The various BPAG1 isoforms play a key role in fundamental processes, such as cell adhesion, cytoskeleton organization, and cell migration. Genetic defects of BPAG1 isoforms are the culprits of epidermolysis bullosa and complex, devastating neurological diseases. In this review, we summarize recent advances of our knowledge about several BPAG1 isoforms, their role in various biological processes and in human diseases.

Cutaneous Collagenous Vasculopathy: A Rare Form of Microangiopathy Successfully Treated with a Combination of Multiplex Laser and Optimized Pulsed Light with a Review of the Literature.

Cutaneous collagenous vasculopathy (CCV) is a rare idiopathic microangiopathy of the cutaneous vasculature characterized histologically by the presence of dilated small blood vessels with flat endothelial cells and thickened walls containing hyaline material in the upper dermis. We report an elderly patient presenting with an extensive form of CCV involving the trunk, upper and lower limbs. She was treated with Multiplex PDL 595-nm/Nd:YAG 1,064-nm laser and optimized pulsed light. This approach, which has never been reported for CCV so far, resulted in a striking and almost complete clearance of the widespread lesions. We here review our knowledge about CCV and therapeutic options available with a survey of the literature.

Swiss S1 Guidelines on the Systemic Treatment of Psoriasis Vulgaris.

Psoriasis vulgaris is a common, chronic inflammatory skin disease with a prevalence of 1.5-2% in Western industrialized countries. A relevant percentage of patients suffer from moderate-to-severe psoriasis and experience a significant reduction in quality of life. The choice of an adequate therapy could help to prevent disease and exacerbation of comorbidity, which could increase quality of life, avoid hospitalization and avoid reduction of working days. The present guidelines are focused on the initiation and management of systemic therapies in cases of moderate-to-severe plaque-type psoriasis in adults to optimize treatment response, adherence and quality of life. This first version of the Swiss S1 guidelines presents therapeutic recommendations which are based on a systematic literature search as well as an informal expert consensus of dermatologists in Switzerland.

Efficacy and Survival of Systemic Psoriasis Treatments: An Analysis of the Swiss Registry SDNTT.

BACKGROUND: The Swiss psoriasis registry SDNTT (Swiss Dermatology Network for Targeted Therapies) records the long-term safety and effectiveness of systemic treatment regimens for psoriasis. PATIENTS AND METHODS: Patients with moderate to severe psoriasis are included in the SDNTT when treatment with a conventional systemic agent or biologic is initiated that was not previously used by the respective patient. Patients are followed over a 5-year period. Clinical data are obtained every 3-6 months using standardized case report forms. Here, baseline data and follow-up data for 1 year of patients included from October 2011 until December 2014 were analyzed. RESULTS: Within 39 months, 323 patients from 7 tertiary dermatology centers in Switzerland were recruited in the SDNTT; 165 patients received biologics and 158 conventional systemic therapies. Patients treated with biologics had a significantly higher severity (PASI 11.3 vs. 9.2, BSA 15.6 vs.11.9, psoriatic arthritis 36.4 vs. 10.8%; p ≤ 0.005, p ≤ 0.013, p ≤ 0.001) and a longer duration of illness (19.2 vs. 14.4 years, p ≤ 0.003) compared to patients starting a conventional systemic treatment. PASI reduction was satisfying in both treatment groups, with 60.6% of patients treated with biologics achieving PASI75 after 1 year compared to 54.2% of patients receiving conventional systemic drugs (nonsignificant). On average, the drug survival in patients receiving a biologic therapy was significantly longer than those receiving conventional systemic treatments (30.5 vs. 19.2 months, p ≤ 0.001). CONCLUSIONS: In the real-world setting of a prospective national therapy registry, the application of current therapeutic guidelines for patients with moderate to severe psoriasis resulted in a PASI reduction of approximately 70% within the first year of treatment, but current therapeutic targets of PASI75 and PASI90 were reached in only 58 and 36% of patients, respectively, at 1 year, highlighting a gap in efficacy between selective clinical trials and the real-world setting.