Non-scarring alopecia of lupus erythematosus: A comprehensive review.

BACKGROUND: Although non-scarring alopecia (NSA) is a frequent clinical finding in patients with systemic lupus erythematosus (SLE), it has been poorly described in the literature. It is considered a nonspecific sign in the current classification of skin lesions of LE. The aim of this study was to give an updated overview of the spectrum of NSA in LE patients, with emphasis on the clinical significance thereof. METHOD: We conducted a review of the English literature using the PubMed-Medline database using the keywords "Alopecia" + "Lupus erythematosus". Publications describing LE patients with NSA were included. RESULTS: Data for 237 patients from 27 publications were analyzed. Ninety-one patients had diffuse NSA, 43 had patchy NSA, 83 had lupus hair, 3 had alopecia of dermal cutaneous LE, and 17 had alopecia of linear and annular lupus panniculitis of the scalp. Patients with diffuse/patchy NSA and lupus hair shared the following features: strong association with systemic activity of LE, subtle clinical/trichoscopic signs of inflammation, histological aspect consistent with lesions specific to cutaneous LE, high likelihood of response to SLE therapy, and absence of progression to scarring alopecia. Association with SLE was rare in patients with dermal cutaneous LE or linear and annular lupus panniculitis of the scalp, and skin-directed therapies were most often effective. One patient of each subtype progressed to scarring alopecia. DISCUSSION: Diffuse/patchy NSA and lupus hair may represent a topographic variation of a single entity specific for LE. Prospective studies are warranted to further document the clinical significance of this manifestation.

Genetics of adnexal tumors: An update.

Cutaneous adnexal tumors form a vast heterogeneous group that include frequent entities that are mostly benign, as well as rare tumors that are occasionally malignant. In contrast to cutaneous tumors arising from the interfollicular epidermis that develop as a result of accumulation of UV-induced DNA damage (basal cell carcinoma, squamous cell carcinoma), the oncogenesis of adnexal tumors is related to a broad spectrum of genetic mechanisms (e.g., point mutation, fusion genes, viral integration, etc.). In this setting, specific and recurrent genetic alterations have been progressively reported, and these allow better classification of these entities. For certain of them, immunohistochemical tools are now available, enabling precise integrated histological and molecular diagnosis since certain entities are linked to well-defined alterations. In this context, we aim in this review to summarize the main molecular tools currently available for the classification of adnexal tumors.

Post-traumatic ulcerated and chronic necrobiosis lipoidica of the elbow: A new entity?

BACKGROUND: Necrobiosis lipoidica (NL) is a chronic granulomatous dermatosis usually affecting the lower limbs, although less common sites have been described. Herein we report a series of cases of NL located on the elbow, with an unusual presentation and occurring after trauma or surgery. OBSERVATIONS: Our series includes three men and one woman, with a mean age of 64 years. Three had undergone surgery for elbow bursitis and one had had trauma after a fall from a horse, with exposure of subcutaneous tissue prior to healing. Within 5 years, they had all developed an atrophic erythematous annular plaque with papular and telangiectatic edges, with recurrent episodes of ulceration and scarring. Repeated tests for infectious agents were negative. Histological examinations showed granulomas and necrobiosis with palisading or early-stage palisading. Partial healing was achieved in two patients after 6 months of doxycycline. Treatment with adalimumab resulted in disappearance of the ulcers at 6 months in one patient. DISCUSSION: Unusual sites of NL impose consideration of other types of palisading granuloma or mycobacterial infections, which we were able to rule out. Two other cases of NL of the elbow similar to ours are reported in the literature. These cases, involving multiple ulcerations over a very long period of time, probably constitute a distinct entity because of the very distinct character of these 6 cases. Tetracyclines are partially active and tumour necrosis factor alpha (TNF)-alpha inhibitors may offer an option.

Dermatopathology in Strasbourg during the German Occupation (1940-1945).

INTRODUCTION: The activity of the Strasbourg Dermatology Clinic was interrupted in September 1939 by the outbreak of the Second World War and the evacuation of the hospital. After annexing Alsace to the Reich, the German authorities demanded that physicians return to work, which resumed at the Dermatology Clinic, and was now entirely Germanized, in particular the laboratory of dermatopathology. Our aim was to study activity in the histopathology laboratory between 1939 and 1945. MATERIAL AND METHODS: We studied all the histopathology reports contained in three registers written in German. We collected patient data, clinical elements and diagnoses by microscopy. There were a total of 1202 cases between September 1940 and March 1945. The records were in a good state of preservation, enabling exhaustive analysis. RESULTS: The number of cases peaked in 1941 and diminished thereafter. The average age of patients was 49 years, and the sex ratio was 0.77. Patients were referred from Alsace or other Reich territories; referrals from other regions of France or other countries had ceased. There were 655 cases in dermatopathology, with a predominance of tumor lesions, followed by infections and inflammatory dermatoses. We noted 547 cases of non-cutaneous diseases, mainly in gynecology, urology, and in ear, nose, throat and digestive surgery; their numbers peaked in 1940-41, then tapered off progressively. DISCUSSION: Thedisruptions associated with thewar were manifested by the use of German language and the cessation of scientific publications. The lack of general pathologists in the hospital resulted in numerous cases in general pathology. Skin biopsies were mainly diagnostic and focused on skin cancers, whereas inflammatory and infectious diseases predominated before the war. No traces of data related to unethical human experimentation were identified in these archives, in contrast to other institutes in Strasbourg that were truly Nazified. CONCLUSION: These data from the Strasbourg Dermatology Clinic contain valuable information for the history of medicine and provide an insight into the functioning of a laboratory under the Occupation.

Burden of visible [face and hands] skin diseases: Results from a large international survey.

BACKGROUND: While numerous surveys over the last decade have evaluated the burden of skin diseases, none have focused on the specific impact of disease-location on the hands and face. AIM: The purpose of our study was to evaluate the burden of 8 skin diseases on the multidimensional aspects of subjects' daily lives in respect to their location on visible body areas (face or hands) versus non-visible areas. METHODS: This was a population-based study in a representative sample of the Canadian, Chinese, Italian, Spanish, German and French populations, aged over 18 years using the proportional quota sampling method. All participants were asked (i) to complete a specific questionnaire including socio-demographic characteristics, (ii) to declare if they had a skin disease. All respondents with a skin disease were asked (iii) to specify the respective disease locations (hands, face, body) and (iv) to complete the DLQI questionnaire. Respondents with 8 selected skin diseases were asked (v) to complete a questionnaire evaluating the impact of the skin disease on their daily life, including their professional activity, social relations, emotional and intimate life, leisure, sports activities and perceived stigma. RESULTS: A total of 13,138 adult participants responded to the questionnaire, of whom 26.2 % (n = 3,450) had skin diseases, and 23.4 % (n = 3,072) reported having one of the 8 selected skin diseases. Fifty-three percent were women and the mean age was 39.6 ±â€¯15.5 years. The QoL was mostly impaired when the visible localization was solely on the hands as compared with the face (38 % had a DLQI > 10 versus 22 % respectively). More subjects with a visible localization on the hands reported felt-stigma, having difficulty falling asleep and felt that their sex life had been affected. CONCLUSION: Special attention should be given to patients with skin disease on the hands and face as they are at higher risk of social exclusion and lower quality of life.

Bullous haemorrhagic dermatitis induced by heparins and other anticoagulants: 94 cases from French pharmacovigilance centres and a literature review.

BACKGROUND: Bullous haemorrhagic dermatitis (BHD) is an uncommon and highly particular side effect of various forms of heparins. METHODS: To better characterise the disease, we collected all cases from French Pharmacovigilance centres recorded over a 20-year period (37 cases) and performed a Medline literature search up to June 2020 (57 cases). RESULTS: In all, 94 patients were identified (male/female ratio: 2.2) of mean age 73.5±12.1 years (31-94). Patients were treated with enoxaparin (n=66), unfractionated heparin (n=11), fondaparinux (n=10), tinzaparin (n=4), bemiparin (n=1), reviparin (n=1), dalteparin (n=1), and 4 with other anticoagulants: warfarin (n=3) and rivaroxaban (n=1). All cases presented with 1 to more than 100 haemorrhagic vesicles and bullae, distant from the injection sites, located mainly on the lower (75%) or upper limbs (69%). The lesions were asymptomatic, except in 5 patients who had pruritic or painful lesions. The interval between treatment initiation and BHD ranged from 6 hours to 30 days (mean: 8.4±7 days). Biopsy (n=53) showed intraepidermal or subcorneal cavity with red cells (n=39) or junctional blisters (n=10), with eosinophilic infiltrate only rarely. Direct immuno-fluorescence was negative in 19/20 cases and indirect immunofluorescence was negative in 8/8. The outcome was favourable in all cases, including in 12 patients for whom heparin was maintained. A 93-year-old patient died of compressive haematomas unrelated to BHD. We found 5 cases similar to BHD due to other anticoagulants. DISCUSSION: This is the largest comprehensive series of this adverse effect due to heparins or, more rarely, to other anticoagulants. Dermatologists must be aware of BHD, since this benign side effect does not necessarily require interruption of treatment. It is rare, considering the large-scale prescription of heparins, and occurs mainly in male patients aged over 70. Although the presentation is highly typical, the physiopathology is difficult to understand, as coagulation parameters are usually normal. Aging, skin fragility or mechanical factors might play a role.

Rosacea: Treatment targets based on new physiopathology data.

Over the past 15 years, numerous clinical, epidemiological and physiopathological articles have been published on rosacea. There is now increasing evidence that rosacea is an inflammatory disease characterised by abnormal innate immune response, major vascular changes, and increased colonisation by Demodex mites, along with a genetic predisposition and multiple external aggravating factors. It is thus possible to define treatment targets and possible treatments: 1) permanent vascular changes (medical and instrumental treatments); 2) flushing (betablockers, botulinum toxin); 3) innate immunity (antibiotics, nonspecific antioxidants and anti-inflammatory molecules); 4) a neurovascular component (analgesics, antidepressants); 5) Demodex (antiparasitic drugs); 6) microbiome; 7) skin barrier impairment (cosmetics and certain systemic drugs); 8) sebaceous glands (isotretinoin, surgery); 9) environmental factors (alcohol, coffee, UV exposure). Treatment recommendations are now available in many countries and benefit from the new phenotypic approach to rosacea, in which every sign or symptom is considered separately rather than having to deal with overlapping subtypes. Since the 2000s, many good quality clinical trials have been published in the field of rosacea and many others are still ongoing. Rosacea is a complex disease involving many different mechanisms and with numerous possible treatments, but there are still some important unmet needs with regard to optimal care.

Position paper on a simplified histopathological classification of basal cell carcinoma: results of the European Consensus Project.

BACKGROUND: Histopathological classification of basal cell carcinoma (BCC) has important prognostic and therapeutic implications, but reproducibility of BCC subtyping among dermatopathologists is poor. OBJECTIVES: To obtain a consensus paper on BCC classification and subtype definitions. METHODS: A panel of 12 recognized dermatopathologists (G12) from nine European countries used a modified Delphi method and evaluated 100 BCC cases uploaded to a website. The strategy involved five steps: (I) agreement on definitions for WHO 2018 BCC subtypes; (II) classification of 100 BCCs using the agreed definitions; (III) discussion on the weak points of the WHO classification and proposal of a new classification with clinical insights; (IV) re-evaluation of the 100 BCCs using the new classification; and (V) external independent evaluation by 10 experienced dermatopathologists (G10). RESULTS: A simplified classification unifying infiltrating, sclerosing, and micronodular BCCs into a single "infiltrative BCC" subtype improved reproducibility and was practical from a clinical standpoint. Fleiss' κ values increased for all subtypes, and the level of agreement improved from fair to moderate for the nodular and the unified infiltrative BCC groups, respectively. The agreement for basosquamous cell carcinoma remained fair, but κ values increased from 0.276 to 0.342. The results were similar for the G10 group. Delphi consensus was not achieved for the concept of trichoblastic carcinoma. In histopathological reports of BCC displaying multiple subtypes, only the most aggressive subtype should be mentioned, except superficial BCC involving margins. CONCLUSIONS: The three BCC subtypes with infiltrative growth pattern, characteristically associated with higher risk of deep involvement (infiltrating, sclerosing, and micronodular), should be unified in a single group. The concise and encompassing term "infiltrative BCCs" can be used for these tumors. A binary classification of BCC into low-risk and high-risk subtypes on histopathological grounds alone is questionable; correlation with clinical factors is necessary to determine BCC risk and therapeutic approach.

Clinicopathologic analysis of trichoblastoma and comparison with nodular basal cell carcinoma.

BACKGROUND: Trichoblastoma (TB) is an uncommon benign follicular tumour for which clinical data is limited since most reports originate from pathology studies. OBJECTIVE: To describe the clinical aspects of TB. METHODS: This is an ancillary study of a prospective multicentre cohort of 2710 clinically suspected basal cell carcinoma (BCC), including 935 nodular BCCs. Sixty-two cases were TB: they were analysed and compared to 935 nodular BCCs. RESULTS: TB mostly occurred in females (61% vs. 43% for BCC, P<0.01) of mean age 63 years. They were located on the head and neck, mainly on the nose and forehead, in 87% of cases. The mean size was 8.1mm, 77% were<10mm (55% of BCCs, P<0.001), 8% were ulcerated (vs. 21% of BCCs, P<0.02), and 47% persisted for more than 1 year (34% of BCCs, P<0.05). Most cases had a clinical presentation similar to nodular BCC, except for 5 small, flat, white papules and 1 anfractuous plaque. LIMITATIONS: Cases originated from a series of tumours clinically suspected as BCCs. DISCUSSION: Some 2.6% of tumours clinically diagnosed as BCC are in fact TB. TB occurs on the head, are more frequent in women, and are smaller and of longer duration than BCC. In most cases, clinical diagnosis on clinical grounds is difficult.

Androgen receptor expression in epidermal and adnexal tumours.

INTRODUCTION: Androgen receptor (AR) immunohistochemistry is used in general pathology and in dermatopathology, particularly for sebaceous tumours. The goal of this study was to quantify AR expression in benign and malignant epidermal tumours and adnexal tumours. METHODS: We studied AR expression in 301 skin lesions using standard immunohistochemistry and compared 10 trichoblastomas, 10 sebaceomas and 10 hidradenomas using 5 markers (cytokeratin 7 and 8, PHLDA1, BerEp4 and AR). RESULTS: The rates of AR expression were: 22% in basal cell carcinomas, 3% in squamous cell carcinomas, 92% in sebaceous tumours, 10% in follicular tumours and 22% in sweat gland tumours. Benign sebaceous tumours were AR+ in 97% of cases. Only 12% of sebaceous carcinomas showed no AR staining. The immunohistochemical profiles of the comparative study were as follows: sebaceoma: AR+, CK7-, CK8-, PHLDA1-, BerEp4-; hidradenoma: AR-, CK7+, CK8+, PHLDA1+, BerEp4+; trichoblastoma: AR-, CK7-, CK8-, PHLDA1+, BerEp4+. DISCUSSION: AR staining was positive in 92% of sebaceous tumours, including sebaceomas, in some cases indicative of Muir-Torre syndrome. AR staining is therefore highly sensitive for the diagnosis of sebaceous tumours, but it is non-specific and is best used in combination with other antibodies, notably anti-CK8 and PHLDA1, particularly to distinguish sebaceoma from hidradenoma or trichoblastoma.

Clinical factors predictive for histological aggressiveness of basal cell carcinoma: A prospective study of 2274 cases.

INTRODUCTION: Since surgery is the first-line treatment for basal cell carcinomas (BCC), the histological aggressiveness of the disease must be clinically predicted in order to apply optimal safety margins that ensure a high rate of complete resection while minimising the risk of recurrence. OBJECTIVES: To evaluate clinical predictive factors of histological aggressiveness of BCC, we conducted a national prospective multi-centre study. METHODS: All consecutive patients presenting for BCC surgery were included, and standardised clinical data collected, and slides were submitted for review. Trabecular, micronodular and morpheaform BCCs were classified as aggressive. RESULTS: Of the 2710 cases included, 2274 were histologically confirmed. Clinical subtyping was correct in 49.9% of superficial BCCs, 86.2% of nodular BCCs and only 22% of aggressive BCCs. By multivariate analysis, aggressive BCCs were more frequently ulcerated (45%), indurated (70%), showed adherence (8.6%), and were associated with high-risk anatomical zones (50.3%, P<0.0001). These predictive clinical features may be helpful for decision making.

[Anatomoclinical and immunohistochemical study of 8 cases of dermatomyofibroma]. / Étude anatomoclinique et immunohistochimique de 8 cas de dermatomyofibromes.

INTRODUCTION: Dermatomyofibroma (DMF) is a rare, benign tumour that is little-known among clinicians. However, it has typical clinical, histological and immunohistochemical features that distinguish it from other fibrous tumours. METHOD: We report herein on the clinical, histological and immunohistochemical aspects of eight cases of DMF identified between 2008 and 2019 at the dermatopathology laboratory of Strasbourg. RESULTS: Five men and three women of average age at diagnosis of 21 years and 9 months (range: 9 to 54 years) were included. Lesions ranged in size from 1 to 11cm. Most cases involved the upper body (6 cases), with one case on the abdomen and one on the side. The lesions presented as a solitary asymptomatic red or reddish brown nodule or plaque that gradually developed. The plaques were hard and caused functional discomfort on movement of the neck. Well-circumscribed spindle cell proliferation was noted in the reticular dermis parallel to the epidermis, without mitotic figures or cytological atypia. The subcutis was infiltrated in 5 cases. Expression of calponin was positive in all cases but one, while that of caldesmon, PS100 and desmin was negative. Expression of smooth muscle actin was positive in 2 cases, and both cases were also positive for stromylesin-3. CD34 was positive in 2 cases. DISCUSSION: DMF is an extensive tumour capable of attaining large diameters and must be completely excised. The main differential diagnoses of DMF are dermatofibrosarcoma protuberans, dermatofibroma, fibrous hamartoma, myofibromatosis and cheloid. It can be identified based on various factors, whether clinical (young age, extensive lesion), histological (horizontal proliferation in the reticular dermis) or immunohistochemical (positive expression of calponin).

[Clinical heterogeneity of poikilodermatous mycosis fungoides: A retrospective study of 12 cases]. / Hétérogénéité clinique du mycosis fongoïde poïkilodermique : étude rétrospective de 12 cas.

INTRODUCTION: Poikilodermatous mycosis fungoides is a rare and indolent clinical variant of mycosis fungoides (MF). It can be difficult to distinguish from poikilodermatous parapsoriasis, a group of chronical dermatoses that may sometimes progress to MF. We aimed to specify the clinical, histopathological and developmental features of these entities by means of a retrospective study of 12 cases followed in our center. PATIENTS AND METHODS: We identified cases of poikiloderma for which a diagnosis of MF or parapsoriasis was made by the physician. Photographs and histological slides were reviewed, and a final diagnosis of MF was made if the International Society for Cutaneous Lymphoma criteria for the diagnosis of early MF were fulfilled. RESULTS: Twelve patients were included, 10 of whom met of the MF criteria. 5 patients had large poikilodermatous patches or thin, well-defined plaques ; 3 patients had the same lesions associated with classical MF lesions ; finally, 4 patients had widespread ill-defined erythematous lesions in a net-like pattern, described as parakeratosis variegata, including 3 MF. 2 patients with well-defined lesions (one associated with classical MF lesions) progressed to the tumoral stage whereas none of the patients with parakeratosis variegata presented such progression. A total of 5 patients had a high skin phototype (IV and V). Two patients had squamous cell carcinoma on poikilodermatous lesions. DISCUSSION: Our study suggests that poikilodermatous MF covers a heterogeneous clinical spectrum comprising on one hand a presentation of delimited lesions sharing classical MF risk of progression, and on the other, an entity similar to parakeratosis variegata, an entity overlooked in the French nomenclature, which was particularly benign in our small series, raising the question of its affiliation to the MF group. This question merits further investigation in a larger-scale study.