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.

Lupus erythematosus: Significance of dermatologic findings.

Herein, the different skin manifestations in patients with lupus erythematosus are reviewed, and their diagnostic, pathogenic and prognostic relevance are discussed, as well as their impact on therapeutic choices. The so-called specific lesions of LE result from an autoimmune pathomechanism and they allow diagnosis of LE by simple clinicopathological correlation since the findings are characteristic. They include the classic acute, subacute and chronic variants, characterised microscopically by interface dermatitis; the dermal variants of lupus, such as tumid lupus, displaying dermal perivascular lymphocytic infiltrate with mucin deposition under the microscope, and lupus profundus, in which lymphocytic lobular panniculitis progressing to hyaline fibrosis is found. Antimalarials are the treatment of choice for patients with specific LE lesions. The presence of some dermatological signs is the result of thrombotic vasculopathy. Their recognition allows the identification of lupus patients at increased cardiovascular risk and with a worse overall prognosis. Those signs include reticulated erythema on the tip of the toes, splinter hemorrhages, atrophie blanche, pseudo-Degos lesions, racemosa-type livedo, anetoderma, ulceration and necrosis. Those clinical manifestations, often subtle, must be recognised, and if present, patients should be treated with antiplatelet drugs. Finally, neutrophilic cutaneous lupus erythematosus includes a few entities that suggest that autoinflammatory mechanisms might play a key role in certain lupus manifestations. Among those entities, it is very important to diagnose neutrophilic urticarial dermatosis, which can mimic a classic lupus flare, because it is characterised by rash with joint pain, but immunosuppressants are not helpful. Dapsone is the treatment of choice.

Neutrophilic urticarial dermatosis: an entity bridging monogenic and polygenic autoinflammatory disorders, and beyond.

Neutrophilic urticarial dermatosis (NUD) has been described in 2009. Clinically, it is an eruption of rose or red macules or slightly elevated plaques, vanishing within 24 h. It occurs mostly on the trunk and the limbs. Extracutaneous signs such as fever or joint pain can be associated. The histopathological findings are a dense perivascular and interstitial infiltrate of neutrophils with leucocytoclasia but without vasculitis. It is often associated with other systemic diseases such as Schnitzler syndrome, adult-onset Still disease (AOSD), cryopyrin-associated periodic syndrome (CAPS) and Lupus erythematosus (LE). The pathogenesis of NUD is not well established but its association with CAPS and AOSD suggests that NUD is linked to autoinflammation. The management of NUD depends on the clinical findings and the potential associated systemic condition. Neutrophil migration inhibitors, such as dapsone or colchicine, and IL-1 antagonists, in particular, anakinra, are the main therapeutic options for the treatment of NUD. The prognostic value of NUD, especially when occurring in the setting of LE is not known and needs to be further investigated.

GLUT1 expression in human papillomavirus-positive anogenital lesions.

BACKGROUND: GLUT1, an ubiquitous glucose transporter in the mammalian cells, is upregulated in many tumours, including human papillomavirus (HPV)-induced head and neck or cervical cancer. OBJECTIVE: To study in anogenital lesions whether or not GLUT1 expression correlates with genomic high-risk HPV integration, the first step in neoplastic transformation. METHODS: Forty-three HPV-positive biopsies positive for either low-risk or high-risk HPV were selected. Paraffin sections adjacent to those tested for the presence of HPV were processed for GLUT1 immunocytochemistry. GLUT1 expression was analysed by two histologists, blinded to HPV type and status and then compared with HPV typing results. RESULTS: Two main staining patterns were observed, either staining from the basal to the granular layer or staining of superficial layers only. The first staining pattern corresponded to lesions with high number of episomal HPV-positive nuclei. Superficial staining was observed in lesions with low number of episomal HPV nuclei or when high-risk HPV was integrated in the cell genome. CONCLUSION: Our results show that GLUT1 overexpression correlates with the number of episomally infected cells in the lesion, but not with the type (low or high risk) of HPV.

[Juvenile dermatomyositis: A series of 22 cases]. / Dermatomyosite de l'enfant. Série descriptive de 22 cas.

PURPOSE: To report on the characteristics of juvenile dermatomyositis (JDM). PATIENTS AND METHODS: This was a retrospective, descriptive, cross-sectional, non-interventional, multicenter study conducted in Alsace between 2000 and 2015. The patients, aged 0 to 16years, had JDM according to both the Bohan and Peter and the EULAR/ACR criteria. RESULTS: A total of 17 girls and 5 boys were included with a median age at disease onset of 7,8years (Q1-Q3: 4.4-12.9). Median duration of JDM and median patient follow-up were 2.8years and 6.2years, respectively. The most common skin symptoms were papules or Gottron's sign (86 %), nail lesions (82 %), erythema of the face (77 %) and eyelids (59 %), photosensitivity (59 %), and calcinosis (27 %). One patient presented papules with a depressed and porcelain-white center ("Degos-like" lesions). One patient had algodystrophy. Two patients were clinically amyopathic. One girl had intestinal vasculitis. Respiratory function tests were abnormal in 27 % of cases. Median treatment duration was 42 months (Q1-Q3: 19-63). Three patients had a monocyclic form, 12 had a polycyclic form, and 7 had chronic disease. CONCLUSION: The frequency of cutaneous and musculoskeletal signs is comparable to that of other large cohorts of JDM. "Degos-like" lesions and algodystrophy have not yet been described in JDM. This study highlights the type and extent of the dermatological manifestations that frequently constitute the presenting complaint in this disease.

[A case of cutaneous tuberculosis evolving for 50 years]. / Un cas de tuberculose cutanée évoluant depuis plus de 50 ans.

INTRODUCTION: Tuberculosis is an infection caused by Mycobacterium (M.) tuberculosis. It is rare in France. Clinical presentations vary, making demonstration of the cause of M. Tuberculosis difficult and rendering diagnosis and management difficult. PATIENTS AND METHODS: A 58-year-old man, born in Morocco, consulted for ulceration of the right forefoot that had been present since the age of 3 years. He had previously consulted at several dermatology departments. He had undergone numerous skin biopsies and bacteriological and mycobacteriological cultures but these did not contribute to the diagnosis. Slow extension and oozing were observed over time and resulted in functional disability. Given the evocative clinical aspect and despite further negative screening for mycobacteria, anti-TB quadrotherapy was prescribed and resulted in complete cure of the lesion. DISCUSSION: This case underscores the difficulty of diagnosing cutaneous tuberculosis. Such a diagnosis must be clinically suspected in the presence of long lasting destructive or verrucous skin lesions that fail to heal, even where cultures are negative, and anti-TB therapy should be putatively prescribed.

[Efficacy of photopheresis in the treatment of erosive lichen planus: A retrospective study]. / Efficacité de la photochimiothérapie extracorporelle dans le traitement du lichen plan érosif : étude rétrospective.

INTRODUCTION: Erosive lichen planus of the skin and mucosa is an invalidating disease that impacts the quality of life of patients and for which there is no codified treatment. Herein we report retrospective efficacy data for extracorporeal photopheresis (ECP) in the treatment of erosive lichen planus in 11 patients. PATIENTS AND METHODS: We treated 10 women and 1 man with PCE for erosive lichen planus refractory on average to two previous treatments. PCE was administered in two sessions on two successive days every two weeks at the start of treatment, followed by more widely spaced cycles. The primary evaluation criterion was partial or complete clinical efficacy. RESULTS: PCE had a positive effect on all 11 patients. We noted 6 complete remissions and 5 partial remissions. Complete remission was achieved within a mean 5.5 months, with improvement in symptoms occurring earlier. Relapse was frequent during the intervals between PCE sessions and on discontinuation of treatment but resumption of PCE once again proved effective. DISCUSSION: Our study supports the data in the literature from 28 published cases. Treatment efficacy and improvement in symptoms were rapidly apparent. PCE is generally a well-tolerated treatment, with only one patient dropping out of our study, but it imposes certain scheduling, technical and cost constraints. These constraints and the frequency of relapse underscore the question of treatment duration. The initial therapeutic schedule for PCE does not appear to modify the times required to achieve remission of erosive lichen planus.

[Ungual lesions in lupus erythematosus: A retrospective study of 14 patients]. / Lupus érythémateux et atteinte unguéale : étude rétrospective sur 14 patients.

INTRODUCTION: There are few studies focusing on ungual lesions in patients with lupus erythematosus (LE). The aim of this study is to describe our experience with ungual lesions in LE patients. MATERIALS AND METHODS: A multicentric retrospective descriptive study was performed at the dermatology departments of the university hospitals in Strasbourg and at the Tenon hospital in Paris and involved reviewing the medical records and photographs of patients with ungual lesions. RESULTS: Fourteen patients were included: 12 (86 %) were women with a median age of 38 years (28-78 years). All patients had cutaneous LE presenting as follows: 3 isolated forms (21 %), and associated with systemic LE (LES) for remaining 11 patients (79 %). The most frequent ungual or peri-ungual lesions were longitudinal ridging (12 patients, 86 %), onycholysis and cuticular alterations (8 patients each, 57 %), pterygium (7 patients, 50 %), melanonychia, onychoschizia and subungual hyperkeratosis (5 patients with each, 36 %). Among patients with pterygium and onychoschizia, respectively 6 (86 %) and 5 (100 %) presented the discoid LE subtype, while respectively 6 (86 %) and 4 (80 %) had multisystemic involvement. DISCUSSION: Ungual lesions do not appear specific and do not in themselves allow diagnosis of LE. They can in fact occur in other diseases such as connective tissue disorders. However, their diagnosis is important because certain of them, such as pterygium, can lead to severe ungual dystrophia, with functional consequences. In our study, pterygium and onychoschizia appeared to be associated with cutaneous discoid lupus erythematosus and multisystemic involvement. The coexistence of peri-ungual lesions related to cutaneous lupus erythematosus and/or multisystemic involvement does not out differentiation of lupus ungual lesions and post-inflammatory lesions.

[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.

[Ulceration of lymphomatous skin lesions in a patient with Sezary syndrome treated with brentuximab-vedotin]. / Ulcérations de lésions cutanées lymphomateuses sous brentuximab-védotin chez un patient atteint de syndrome de Sézary.

BACKGROUND: Brentuximab-vedotin (BV), an anti-CD30 agent combined with an anti-neoplastic agent, has recently yielded promising results in the treatment of cutaneous T-lymphomas such as Sezary syndrome. Surprisingly, these results are observed regardless of levels of CD30 expression by tumour cells. PATIENTS AND METHODS: Herein, we report the case of a 52-year-old man with Sézary syndrome (SS) with skin and lymph node involvement, and whose tumour cells were not expressing CD30 at the time of disease progression. His disease was refractory to several lines of treatment, and a partial response was obtained using BV therapy, with secondary ulceration of SS-specific skin lesions. DISCUSSION: Ulceration of our patient's skin lesions was concomitant with clinical improvement and the semiology was identical to cases of skin ulceration under methotrexate in patients with psoriasis or mycosis fungoides. The mechanism of action appears to be related to sudden interruption of the cell cycle in a context of rapid cell renewal, although the way in which the antibody acts on keratinocytes has not yet been fully elucidated.

[Acute generalized pustular bacterid followed by Sweet's syndrome and erythema nodosum]. / Pustulose aiguë généralisée post-streptococcique suivie d'un syndrome de Sweet et d'un érythème noueux.

INTRODUCTION: Streptococcal infections can cause various skin manifestations related to the direct action of the offending organism itself or to a reactional mechanism. Reactional manifestations are less well known and understood, and they include generalized acute pustulosis belonging to the spectrum of neutrophilic dermatoses. We report a case of generalized acute pustulosis followed by Sweet syndrome and erythema nodosum occurring after a streptococcal infection. PATIENTS AND METHODS: A 60-year-old woman was consulting for a diffuse pustular rash after a throat infection, with high levels of anti-streptolysin (337 U/L) and anti-streptodornase (2560 U/L). The biopsy showed folliculitis and a neutrophilic infiltrator of the dermis, and bacteriological and mycological cultures were sterile. The patient then developed papules evoking Sweet syndrome followed by nodules typical of erythema nodosum after 20 days. A favourable outcome was achieved under colchicine. DISCUSSION: Generalized acute pustulosis is a form of neutrophilic dermatosis whose mechanisms, area predilection and treatment are poorly known. The clinical presentation of this patient was initially typical and the secondary progression to lesions like those in Sweet syndrome is consistent with the pathophysiological continuity and overlap of these entities.

[Ungual lesions in lupus erythematosus: A literature review]. / Lupus érythémateux et atteinte unguéale : revue de la littérature.

INTRODUCTION: There are few studies focusing on ungual lesions in patients with lupus erythematosus (LE). The aim of this study is to describe the type and the prevalence of ungual lesions among LE patients. PATIENTS AND METHODS: A systematic literature review with analysis of individual data was performed by searching the MEDLINE database for scientific articles using the keywords "lupus erythematosus" and "nail". RESULTS: Two-hundred and eighty-seven cases were collated including 55.1% women, with an average age of 32.2±11 years. The most common ungual or peri-ungual lesions were longitudinal ridging (83 patients, 28.9%), peri-ungual erythema (62 patients, 21.6%), onycholysis (60 patients, 20.9%), melanonychia (34 patients, 11.8%) and dyschromia (33 patients, 11.5%). An association between the presence of onycholysis and peri-ungual erythema and disease activity was noted [respectively 33 (38.8%) and 26 (30.6%) patients out of 85 with active disease versus 3 (5.8%) and 4 (7.7%) patients out of 52 with non-active disease, P<0.001 and P=0.018]. Screening for fungal infection was performed in one third of the cases, with proven onychomycosis in 34.7% of cases. DISCUSSION: Ungual lesions are not specific and do not permit diagnosis of LE. They can in fact occur in other diseases such as connective tissue disorders. However, their diagnosis is important because they may be the presenting sign in LE, and certain of them may be associated with more active disease. Onychomycosis is frequently a confounding factor in such immunocompromised patients.

[Generalized granuloma annulare: A clinicopathological study]. / Granulome annulaire généralisé : étude anatomoclinique.

BACKGROUND: Granuloma annulare (GA) is a benign granulomatous skin disorder that is generalized (GGA) in 15 % of cases. Although many case reports describe a relationship between GGA and systemic diseases, few large series have been published, and their association is debated. We present herein a series of GGA in order to describe their clinical and histological features. PATIENTS AND METHODS: We included all biopsy-proven cases of GA presenting at the dermatopathology laboratory of Strasbourg where generalized (i.e. over 10 lesions). Clinical features were obtained from patients' medical files. RESULTS: We included 35 GGA, with a sex ratio of 0.5. The mean age was 54 years. Lesions were annular or non-annular in equal measure and were symptomatic in 25 % of cases. Most patients (77 %) had an associated disease, already known in 60 % of cases, including dyslipidemia (27 %), diabetes mellitus (20 %), immunosuppressive drugs (17 %), atopy (17 %), auto-immune disease (17 %), hematological disease (14 %), and cancer (9 %). Histological analysis revealed the predominant pattern to be interstitial (54 %) rather than palisading (20 %), having no correlation with clinical type. Eosinophils were frequent (46 %) in GA but were not correlated with systemic disease or drug taking. Among the 40 % of patients treated, 50 % had a successful outcome on topical corticosteroids, doxycycline, antimalarial drugs or phototherapy. DISCUSSION: GGA differs from localized GA, which is mostly associated with an already known systemic disease, whether metabolic, infectious or neoplastic, uncorrelated with clinical or histological features, and screening is necessary.

Abnormal lipid storage related to adipocyte shrinkage in acquired partial lipodystrophy (Barraquer-Simons syndrome).

BACKGROUND: Acquired partial lipodystrophy (APL) is characterized by the gradual symmetrical loss of subcutaneous fat starting from the face, spreading towards the upper part of the body and sparing the lower extremities. OBJECTIVE: We report a 33-year-old woman with facial lipodystrophy, loss of buccal fat pads and breast fat tissue. The subcutaneous fat was preserved in other anatomic regions, and we noted some excess of fat accumulation in the lower abdomen and thighs. She had a low serum level of C3 that was positive for a polyclonal immunoglobulin C3NeF in the serum. She was diagnosed with APL. METHODS: We examined fat from lipoatrophic and healthy areas and compared it to subcutaneous fat samples from a healthy control. RESULTS: Using scanning electron microscopy, we saw shrunken adipocytes with numerous small lipid droplets detaching from the surface of the adipocytes as compared to the classic aspect of adipose tissue in the control subject where the cytoplasm is occupied by one big lipid droplet. A loss of contact between adipocytes was observed in the APL patient when compared to the normal network of adipocytes in the control subject. The healthy fat seemed not affected by lipoatrophy; we observed normal-sized adipocytes, though their surface was not as regular as in the control samples. CONCLUSION: The significance and mechanism of the electron microscopic findings are unknown, but they suggest adipocyte shrinkage related to a defect in the retaining triglycerides, which could contribute to the pathogenesis of this disorder.

[Hyperpigmentation]. / Hyperpigmentations.

The key diagnostic tool for hyperpigmentation is histopathology, which may be accompanied by certain laboratory tests. Hyperpigmentation may result from excess melanin (hypermelanosis), cutaneous iron deposits (hemosiderosis), cutaneous carotene deposits (carotenoderma), or cutaneous deposits of a substance not normally found in the skin (dyschromia). The different types of hypermelanosis may be classified as either localised or generalised. The former generally correspond to skin tumours and may form a cutaneous expression of complex syndromes, which most notably include cardiac abnormalities, or to pigmented forms of inflammatory and/or infectious dermatoses. Diffuse hypermelanosis is frequently a sign of systemic disease, generally metabolic or endocrine disease, or else it may result from pharmaceutical therapy. Herein we review the various causes of hyperpigmentation and the corresponding therapy.

[Histopathological study of basaloid follicular hamartoma]. / Hamartome folliculaire basaloïde : étude anatomoclinique.

INTRODUCTION: Basaloid follicular hamartoma (BFH) is a rare tumor first described in 1985. It bears clinical and histologic similarities with basal cell carcinoma (BCC), in particular the so-called infundibulocystic form. We performed a single-center clinicopathological study of a series of typical cases of this entity that is occasionally difficult to diagnose. MATERIALS AND METHODS: All cases of BFH seen at the Dermatopathology Laboratory of Strasbourg University Hospital were included and analyzed by means of HE staining and Ber-EP4 and PHLDA1 immunolabelling. Diagnosis was made in the event of basaloid proliferation with anastomosing cords developed from a hair follicle. Clinical data were collected from clinical files. RESULTS: We identified 15 cases in 13 patients of mean age 44.8 years (range: 4 to 90) and the sex-ratio was 5/8. Lesions consisted of flesh-colored papules measuring 0.3 to 1.2cm in diameter, without any preferential site. Three patients had multiple lesions consisting of several coalescent papules on a breast for one, sparse papules on the back for another, and hundreds of linear unilateral BFHs, associated with osseous abnormalities, characteristic of Happle-Tinschert syndrome, for the third. All tumors were limited to the superficial and mid dermis, with a vertical orientation and connection to the epidermis in 14 of the 15 patients. In some cases, the outermost cells were basophilic while the central cells were eosinophilic. Peripheral palisading and clefting were frequently observed. Keratin cysts or sebaceous ducts were consistently present, indicating follicular differentiation. Ber-EP4+ cells were restricted to the periphery of the cords and PHLDA1 was weakly expressed. DISCUSSION: BFH is a rare entity that must be differentiated from BCC. It presents as solitary or multiple lesions, either grouped in plaques or with a generalized or linear unilateral distribution. Generalized BFH may be associated with autoimmune diseases and linear unilateral BFH with osseous, dental and cerebral abnormalities in Happle-Tinschert syndrome. It is important to distinguish BFH from BCC to avoid inappropriate aggressive treatment.

Mechanics hands in patients with antisynthetase syndrome: 25 cases.

BACKGROUND: Antisynthetase antibodies (ASA) are directed against aminoacyl-tRNA-synthetases, ubiquitous enzymes of which eight types have hitherto been described. They are seen primarily in antisynthetase syndrome (ASS), in which diffuse interstitial lung disease is associated with inflammatory myopathy, joint involvement and cutaneous signs, in particular mechanic's hands. The aim of this study was to determine the prevalence and semiological characteristics of cutaneous involvement in patients presenting ASA. PATIENTS AND METHODS: We carried out a retrospective study of the medical files of patients with ASA diagnosed at the Strasbourg University Hospital between 1994 and 2009. RESULTS: We identified 22 women and 3 men presenting ASS (n=21), dermatomyositis (n=3) or sclerodermatomyositis (n=1). Mean age at the time of diagnosis was 56 years (12-79). The most commonly seen antibodies were anti-Jo1 (n=19), with the other cases of ASA involving anti-PL12 (n=3), anti-PL7 (n=2) and anti-EJ (n=1) antibodies. Five patients died from pulmonary complications. Mechanic's hands (characteristic plaques and papules along the edge of the first fingers on both hands) were found in 10 patients with ASS (7 cases) or dermatomyositis (3 cases), at the time of diagnosis in 7 cases and during a systemic episode in 3 cases. Muscular involvement was seen in all patients: 9 had diffuse interstitial lung disease and 8 had joint involvement. Cutaneous signs regressed totally or partially in all patients under treatment; in 6 patients, worsening was seen during systemic episodes of the disease. One of the 10 patients died through pulmonary complications. DISCUSSION: Mechanic's hands are a key indicator in cases of ASA and its outcome is intimately linked with underlying systemic involvement, particularly pulmonary. The characteristic semiology enables this disorder to be recognised and allows differentiation from psoriasis or irritant contact dermatitis of the hands, and it does not vary according to antibody. Whether or not the disease is life-threatening is unaffected by the presence of this sign.

Bedside reasoning on causes and mechanisms of diseases in the era of precision medicine: a timeless story?

This is a short reflection about bedside reasoning in clinical medicine, emphasizing the importance of distinguishing between causes and mechanisms of diseases. All complex/sporadic diseases result from interactions between a genetic predisposition and environmental factors. The main disease mechanisms resulting in clinical signs involve inflammation, insult of vessels or nerves, pharmacological or hormonal dysfunction, altered metabolism and overload, tumoral proliferations, intrinsic dysfunction, malformation and traumatism. Different mechanisms can occur during the same disease process. The practical consequences of identifying causes and mechanisms of diseases are illustrated. As a unifying concept, a very simple diagnostic flow chart that puts the patient, and not the disease, into centre of reflection and that bridges the gap between basic knowledge and patient care is provided. This diagnostic flow chart helps both the experienced physician and the medical student to perform a complete diagnostic process, addressing the specificities of the clinical findings, the pathogenesis and the causative factors, an aim that has become possible in the era of precision medicine. Two examples of patients with a dermatologic presentation highlight this diagnostic process, which paves the way to rational therapy and to translational research.