[Paroxysmal vascular acrosyndromes: Practical approach to diagnosis and management]. / Acrosyndromes vasculaires paroxystiques : démarche pratique de diagnostic et de prise en charge.

Paroxysmal vascular acrosyndromes are related to a peripheral vasomotor disorder and presented as paroxysmal color changes of the fingers. They include primary Raynaud's phenomenon (RP), which is the most common, secondary RP and erythermalgia. They are to be distinguished from non-paroxysmal acrosyndromes such as acrocyanosis and chilblains, which are very frequent and often associated with RP, digital ischemia and necrosis, spontaneous digital hematoma and acrocholosis. The challenge of a consultation for a vascular acrosyndrome is to make positive diagnosis through history and clinical examination, and to specify its nature, to prescribe complementary exams. In any patient consulting for RP, assessment includes at least an antinuclear antibody test and capillaroscopy. For erythermalgia, a blood count and even a search for JAK2 mutation are required. A thryoid-stimulating hormon assay, a test for antinuclear antibodies, and a search for small fiber neuropathy are also performed. The treatment of RP is essentially documented for secondary RP where calcium channel blockers are indicated in first line, and iloprost in severe cases. The treatment of primitive erythermalgia is based on sodium channel blockers such as mexiletine or lidocaine infusions, and on drugs effective on neuropathic pain, such as gabapentin or amitryptiline, in case of erythermalgia associated with small fiber neuropathy. The treatment of erythermalgia associated with myeloproliferative syndromes is based on etiological treatment and aspirin.

Cutaneous drug-induced lupus erythematosus: Clinical and immunological characteristics and update on new associated drugs.

Cutaneous drug-induced lupus erythematosus (CDILE) is a lupus-like syndrome related to drug exposure which typically resolves after drug discontinuation. It can present as a systemic or a sole cutaneous form and different drugs may be associated with each form. CDILE pharmacoepidemiology is constantly changing. Indeed, older drugs primarily associated with systemic CDILE are no longer prescribed and new drugs associated with either cutaneous or systemic CDILE have emerged. The present study discusses the clinical and laboratory aspects of CDILE and the postulated pathogenesis, and it provides an update on implicated drugs. We performed a literature review to single out the new drugs associated with CDILE in the past decade (January 2010-June 2020). Among 109 drugs reported to induce CDILE in 472 patients, we identified anti-TNFα, proton-pump inhibitors, antineoplastic drugs, and, in particular, checkpoint inhibitors, as emerging drugs in CDILE. Most of the published studies are cases reports or small case series, and further larger studies as well as the development of validated classification criteria are needed to better understand and characterize their implication in CDILE.

[Raynaud phenomenon with arterial thromboses and IgG4-related disease]. / Phénomène de Raynaud avec thromboses artérielles au cours d'une maladie associée aux IgG4.

INTRODUCTION: This is a clinical case illustrating a diagnosis of an IgG4 related-disease (IgG4-RD) diagnosed in a vascular context. CASE REPORT: A 47-year-old man with no past medical history consulted for a recent and disabling Raynaud phenomenon without trophic disorder. Vascular examinations revealed multiple arterial thromboses with no abnormal finger and toe pressures. Secondly, weight loss and submandibular glands enlargement appeared, leading to the diagnosis of IgG4-RD without a link being able to be established with vascular involvement. This is the second observation of this association. A French translation of the new classification criteria for IgG4-RD published in 2019 by the American College of Rheumatology and European Ligue Against Rhumatism (ACR/EULAR) is offered with direct application to the clinical case. CONCLUSION: A Raynaud phenomenon with distal arterial thrombosis is rarely observed in the IgG4-RD.

[Two cases of unilateral chilblains associated with monoparesis]. / Engelures unilatérales associées à une monoparésie : 2 observations.

BACKGROUND: Chilblains are inflammatory dermal lesions associated with hypersensitivity to cold, and they occur on the extremities bilaterally and symmetrically. Their onset during the course of pro-thermogenic and autoimmune diseases has been widely reported, but the association with predisposing locoregional causes is not well known. PATIENTS AND METHODS: Case 1: a 57-year-old man, who smoked 80 packets per year, presenting a deficit of the levator muscles in his right foot following lumbar sciatica with paralysis of L5, consulted for unilateral necrotic lesions of the toes recurring each winter in the paralysed limb only. Case 2: a 60-year-old man had a previous history of liposarcoma of the right side treated with radiotherapy and surgery, resulting in sequelae of monoparesis and radiation-induced arteritis. Each winter, he presented recurring unilateral purpuric macules of the toes on his right foot, with no necrotic progression. In both cases, clinical examination, disease progression over time, histology and laboratory tests confirmed the diagnosis of idiopathic chilblains. CONCLUSION: The physiopathological hypotheses posited to account for the unilateral appearance of chilblains in the event of paralysis include decreased blood flow to the paralysed limb, imbalance in neuromodulators, dysfunction of the autonomous nervous system, cutaneous atrophy with hypertrophy of underlying soft tissues, and finally, hypoesthesia aggravating the trophic disorders.

[The value of healthy skin biopsy in the diagnosis of intravascular B-cell lymphoma: A case report and systematic literature review]. / Intérêt de la biopsie cutanée en peau saine dans le diagnostic du lymphome B intravasculaire : cas clinique et revue systématique de la littérature.

BACKGROUND: Intravascular large B-cell lymphoma (ivLBCL) is a rare blood dyscrasia that is difficult to diagnose. Healthy skin biopsies may prove useful in diagnosis of the condition. Herein we report a case of ivLBCL diagnosed using this type of examination, and we provide a literature review to determine the sensitivity of such testing. PATIENTS AND METHODS: A 67-year-old woman was hospitalised for unexplained prolonged fever (UPF) and impaired general well-being. Laboratory tests revealed inflammatory syndrome, elevated LDH>2000IU/L, hepatic cytolysis and decreased prothrombin time at 47 %. Analysis for infection and medical imaging ruled out both an infectious or inflammatory origin and solid tumour. A healthy skin biopsy enabled confirmation of the diagnosis of ivLBCL. DISCUSSION: This clinical case illustrates the value of healthy skin biopsy in establishing a diagnosis of ivLBCL in patients hospitalised for UPF. Following a systematic literature review in PubMed/Medline, we included eight studies involving at least three patients designed to assess the value of healthy skin biopsy in the diagnosis of ivLBCL. The diagnostic sensitivity of this approach ranged from 67% to 100%, with a sensitivity of 100% being seen in four of the eight studies. Details of the biopsy sites were available in three studies and diagnostic sensitivity was similar overall between samples taken from the thigh, abdomen and arms. CONCLUSION: Healthy skin biopsy sampling from at least two sites constitutes a sensitive and relatively non-invasive procedure for early diagnosis of ivLBCL.

[Digital necrosis revealing cold agglutinin disease: Treatment with rituximab]. / Nécroses digitales révélant une maladie des agglutinines froides : traitement par rituximab.

BACKGROUND: Digital necrosis is rarer than lower limb necrosis and constitutes a medical or surgical emergency. Etiological evaluation is required. Cold agglutinin disease is a cause of digital necrosis but diagnosis is difficult. PATIENTS AND METHODS: Herein we report the case of a 57-year-old man presenting recent paroxysmal acrosyndrome of the left hand subsequently complicated by digital necrosis following occupational exposure to cold in his work as a forklift driver. After etiological evaluation, a diagnosis of primary cold agglutinin disease was made. Intravenous rituximab and topical treatment resulted in complete healing. DISCUSSION: Cold agglutinin disease is a rare type of auto-immune hemolytic anemia. Following exposure to cold, paroxysmal cutaneous signs are frequent. The disease may be either primary or secondary with B-cell lymphoproliferative disorder, auto-immune disease or infection. A thorough workup is required. To date, the treatment combining the best positive response rate and good safety is rituximab in weekly perfusions over a 1-month period.

[Primary cutaneous CD30+ T-cell lymphoproliferation during treatment with fingolimod: Case report and literature review]. / Lymphoprolifération cutanée primitive CD30+ sous fingolimod : un cas et revue systématique de la littérature.

BACKGROUND: Fingolimod is an oral immunomodulator approved for relapsing-remitting multiple sclerosis. We report a case of a primary cutaneous CD30+ T-cell lymphoproliferation occurring 6 months after initiation of fingolimod. Based on a systematic literature review, the characteristics of these fingolimod-induced lymphoproliferative disorders are described. PATIENTS AND METHODS: A 56-year-old woman developed cutaneous indurated and ulcerated nodular lesions 6 months after starting fingolimod for active relapsing-remitting multiple sclerosis. Histological examination of a punch biopsy sample demonstrated a polymorphous dermal infiltrate containing large atypical CD30+ cells, leading to diagnosis of primary cutaneous CD30+ anaplastic large-cell lymphoma. Chest-abdomen-pelvis CT scans were performed to rule out secondary cutaneous anaplastic large-cell lymphoma. Spontaneous clinical regression was observed and after assessing the benefit/risk ratio, it was decided to continue fingolimod under strict surveillance, with no relapse occurring by month 18. DISCUSSION: A systematic review of PUBMED/Medline and Embase identified seven other cases of lymphoproliferative disorders occurring during fingolimod treatment, including two other cases of primitive cutaneous CD30+ lymphoproliferative disorders. CONCLUSION: Even if cutaneous CD30+ lymphoproliferative disorders occur only rarely during fingolimod treatment, dermatologists should nevertheless be aware of this association for which strict dermatological surveillance is required. We would also stress that these CD30+ lymphoproliferative disorders can disappear spontaneously, as in our case, even if treatment by fingolimod is continued.

[Cancers associated with systemic sclerosis involving anti-RNA polymerase III antibodies]. / Néoplasies associées à une sclérodermie systémique avec anticorps anti-ARN polymérase III.

BACKGROUND: The incidence of cancer is increased in patients with systemic sclerosis (SSc). Further, recent studies have also shown that the presence of anti-RNA polymerase III antibodies is associated with a higher incidence of cancer in this population. PATIENTS AND METHODS: Herein we present the cases of two men aged 56 and 23 years presenting SSc without anti-Scl70 or anti-centromere antibodies but with anti-RNA polymerase III antibodies. Clinical symptoms led us to prescribe more laboratory exams and both patients were diagnosed with cancer of the nasopharyngeal area. DISCUSSION: Anti-RNA polymerase III antibodies are useful for SSc diagnosis in patients without anti-centromere or anti-Scl70 antibodies. Their presence must lead physicians to screen for associated cancer, even in the absence of clinical signs.

[Unusual course of CD8+ epidermotropic cutaneous T-cell lymphoma]. / Lymphome cutané épidermotrope agressif CD8+ d'évolution inhabituelle.

BACKGROUND: Aggressive epidermotropic cutaneous T-cell lymphoma (AECL) is a rare and aggressive form of lymphoma that exhibits systemic spread within a few months that is not preceded by any indolent form. Herein, we report a case of AECL occurring on foot lesions present for six years, and initially diagnosed as Woringer-Kolopp disease, or pagetoid cutaneous T-cell lymphoma. PATIENTS AND METHODS: A male patient presented an ulcerated lesion of the ankle that had been present for six years. Biopsy revealed pagetoid migration of CD8+, CD2-, CD5-, CD7+, CD30- and CD56- lymphocytes with expression of cytotoxic markers and of Ki67 in over 60% of cells. The resulting diagnosis was one of pagetoid cutaneous T-cell lymphoma, also known as Woringer-Kolopp disease. Despite treatment with methotrexate and carmustine, the ulcer worsened rapidly within two months. Subsequent biopsy revealed epidermal and dermal infiltration with large cells of identical phenotype to that seen in the previous biopsy, with angiocentrism and expression of Ki67 in over 90% of cells, pointing to a diagnosis of AECL. Progression to disseminated ulceronecrotic lesions occurred rapidly, and the patient died of sepsis within a few months. DISCUSSION: AECL is characterised by ulcerative-haemorrhagic lesions that develop aggressively without any preceding mild cutaneous lesions. Median survival is 12 months. Histological analysis shows pagetoid epidermotropism comprising large monomorphic CD8+, CD2- and CD5- cells with markers for cytotoxicity and high expression of Ki67. The initial indolent phase in the case we report herein accounts for the diagnostic confusion at the outset with Woringer-Kolopp disease. Negative status of CD2 and CD5 labels may allow prompt diagnosis of AECL.

[Cellular therapy and leg ulcers: Future approaches]. / Thérapie cellulaire et ulcères de jambe : l'avenir ?

The prevalence of leg ulcers, which are most commonly caused by venous insufficiency, is high in Europe. Current treatments are fairly unsatisfactory, with long healing times in many cases, as well as a high risk of relapse. Over the last 15 years, improved understanding of the cellular and molecular mechanisms at work in delayed wound healing has contributed to the development of cellular therapy in this field. The use of keratinocytes or cultured fibroblasts, whether autogenic or allogenic, has been of little value in terms of either healing times or rates of complete healing. For the moment, there are very few allogenic skin substitutes available; they are expensive and have been insufficiently studied in the indication of leg ulcers. Pluripotent mesenchymal adult stem cells have proved capable of accelerating wound healing in animal models and their study in chronic wounds in humans is currently awaited.

[Diagnosis of vascular acrosyndromes]. / Diagnostic des acrosyndromes vasculaires.

Vascular acrosyndromes are associated with vasomotor disorders. They may be paroxysmal, like Raynaud's phenomenon, whitening of the fingers on exposure to cold, or erythromelalgia, a painful form of erythema induced by exposure to heat. Others are permanent or semi-permanent, such as acrocyanosis, chilblains, spontaneous haematoma of the fingers, acrocholose and digital ischaemia or necrosis. Diagnosis of the type of acrosyndrome at issue is based primarily on clinical examination and history-taking. Capillaroscopy and antinuclear antibody assay are key examinations essential for distinguishing between primary and secondary Raynaud's phenomenon and connective tissue disorders. Complete blood counts, screening for thyroid dysthyroidism, and antinuclear antibody assay can help distinguish between primary erythromelalgia and erythromelalgia secondary to a systemic disease, principally myeloproliferative syndrome. In the case of acrocyanosis, spontaneous digital haematomas and typical bilateral chilblains, examinations are of no value. For the other permanent and semi-permanent acrosyndromes such as digital ischaemia and purpuric or livedoid lesions, screening for arterial or thrombotic disease is necessary.

[Bullous rash around a peritoneal dialysis catheter exit site]. / Éruption bulleuse péri-ombilicale autour d'un cathéter de dialyse péritonéale.

BACKGROUND: Cutaneous eruption around a peritoneal dialysis (PD) catheter exit site is a rare complication. Herein we report a case of bullous eruption; we discuss the diagnostic approach and the related therapeutic implications. PATIENTS AND METHODS: A 63-year-old man presented a bullous periumbilical eruption two months after initiation of PD. Cultures of laboratory samples ruled out an infectious origin and systemic corticosteroids initiated at 0.5mg/kg for suspected eosinophilic peritonitis produced significant improvement of the cutaneous eruption. Recurrence of the bullous eruption was observed upon dose-reduction of the corticosteroid. Skin histology showed a clinical picture of eczema and direct immunofluorescence was negative. Patch testing was carried out using the European Standard Battery comprising antiseptic, cosmetic and plastic series; a semi-open test was performed with the dressing used for PD, and ROAT was carried out on the povidone iodine (Betadine™) 10% used for topical care during PD. The patch testing and ROAT were positive (++), confirming contact dermatitis due to Betadine™. The eruption totally disappeared on substitution of Betadine™ by chlorhexidine for topical antisepsis of the PD catheter, thus enabling PD to be continued rather than instituting hemodialysis. DISCUSSION: Allergic contact dermatitis around a PD catheter is a rare and little-known complication. In the present case, ROAT testing showed sensitization to Betadine™ and enabled an alternative antisepsis solution to be found, allowing PD to be continued.

[Clinical and capillaroscopic regression of CD30 anaplastic lymphoma associated with limited cutaneous systemic sclerosis following autologous bone marrow transplantation]. / Régression clinique et capillaroscopique après autogreffe de moelle d'une sclérodermie systémique cutanée limitée associée à un lymphome anaplasique CD30.

BACKGROUND: In rare cases, tumors are associated with secondary Raynaud's phenomenon in systemic sclerosis (SSc). We report the case of a patient presenting cutaneous limited SSc associated with CD30 anaplastic lymphoma with cutaneous and lymph node involvement in whom the capillaroscopic scleroderma pattern regressed completely after autologous bone marrow transplantation, with complete remission of the lymphoma. CASE REPORT: A 37-year-old man presented bilateral Raynaud's phenomenon associated with digital ulcers contracted one year earlier but subsequently neglected. Right axillary lymph nodes and regional cutaneous tumors were present, leading to the diagnosis of CD30+ anaplastic lymphoma with cutaneous and lymph node involvement. Chemotherapy containing cyclophosphamide achieved only partial remission of the lymphoma. Clinical examination showed bilateral Raynaud's phenomenon, sclerodactyly, a right axillary subcutaneous nodule and a pathological Allen's test for the right hand. Antinuclear antibodies were positive without any other immunological abnormalities, and capillaroscopy showed an SSc pattern with numerous megacapillaries. Digital blood pressure was reduced in the right index and the left middle fingers, in which ulcers of the pulp were observed. Bone marrow transplantation was performed, resulting in complete remission of the lymphoma and disappearance of the sclerodactyly, with no recurrence of the pulp ulcers and complete normalization of capillaroscopic appearance and digital pressure. DISCUSSION: This case raises the question of authentic SSc and neoplasia and highlights the importance of capillaroscopy in the follow-up of SSc. The complete regression of SSc and of capillaroscopic abnormalities could be explained by the paraneoplastic nature of SSc or by the direct action of the chemotherapy and bone marrow transplantation.

Prognostic factors associated with healing of venous leg ulcers: a multicentre, prospective, cohort study.

BACKGROUND: Some prognostic markers of venous leg ulcer (VLU) healing have been evaluated, mostly in retrospective studies. OBJECTIVES: To identify which clinical characteristics, among those known as possible prognostic factors of VLU healing, and which VLU-associated sociodemographic and psychological factors, are associated with complete healing at week 24 (W24). METHODS: A prospective, multicentre, cohort study was conducted in 22 French dermatology departments between September 2003 and December 2007. The end point was comparison between healed and nonhealed VLUs at W24, for patient clinical and biological characteristics; psychological, cognitive and social assessments; affected leg inclusion characteristics; venous insufficiency treatment and percentage of initial wound area reduction during follow-up. RESULTS: In total, 104 VLUs in 104 patients were included; 94 were analysed. The mean VLU area and duration were 36.8 ± 55.5 cm2 and 24.8 ± 45.7 months, respectively. At W24, 41/94 VLUs were healed. Univariate analysis significantly associated complete healing with superficial venous surgery (P = 0.001), adherence to compression therapy at W4 (P = 0.03) and W24 (P = 0.01), ankle-joint ankylosis (P = 0.01) and mean percentage of VLU area reduction at W4 (P = 0.04). Multivariate analysis retained superficial venous surgery during follow-up [odds ratio (OR) 8.4, 95% confidence interval (CI) 1.9-48.2] and percentage reduction of the VLU area at W4 (OR 1.6, 95% CI 1.0-2.14) as being independently associated with healing. CONCLUSIONS: These results indicate that complete healing of long-standing, large VLUs is independently associated with ablation of the incompetent superficial vein and percentage of wound area reduction after the first 4 weeks of treatment.

[Hypertensive leg ulcers: epidemiological characteristics and prognostic factors for healing in a prospective cohort]. / Angiodermites nécrotiques : caractéristiques épidémiologiques et facteurs pronostiques de cicatrisation dans une cohorte prospective.

BACKGROUND: The data concerning changes in the characteristics of hypertensive leg ulcers (HLU) were taken from open studies in a small patient cohort. The aim of this study was to describe the epidemiological characteristics and to identify prognostic factors for healing in a prospective cohort of 59 patients presenting HLU. PATIENTS AND METHODS: The cohort comprised patients included in a randomized, double-blind, controlled study published elsewhere; the patients were receiving becaplermin gel (Regranex(®)) or Duoderm Hydrogel™ once daily for eight weeks for the most recent wound. Total follow-up was 12 weeks. RESULTS: The epidemiological analysis was performed for 59 consecutive patients randomized in 17 dermatology departments. Mean patient age was 74.5 ± 9 years and 61% were female. Mean wound duration was 11.1 ± 9 weeks and median wound area was 16 cm(2) (q1; q3: 8; 25.5). Among, 94.9% of patients had hypertension and 39.7% were diabetic. A homolateral peripheral pulse was present in 91.5% of patients. At the end of follow-up, complete wound healing was obtained in 30.5% of the patients. In univariate analysis, neither the foregoing criteria nor the treatment group were significantly associated with healing during the study. CONCLUSION: This study confirms female predominance, old age, prevalence of diabetes and delay in the diagnosis of HLU. The prognosis for healing does not appear to be dependent on wound duration, wound area or the presence of moderate peripheral arterial disease, doubtless because this condition progresses by episodes of flare-up and under specific conditions.

Scurvy in hospitalized elderly patients.

OBJECTIVES: The aim of this study was to systematically screen hospitalized elderly patients for clinical symptoms of scurvy and to confirm the diagnosis with biological measures. SETTINGS: Geriatric acute care ward. MEASUREMENTS: Scurvy symptoms (one or more among perifollicular hyperkeratosis, petechiae or bruises, haemorrhagic features caused by venous puncture, severe gingivitis). We compared associated diseases, nutritional status, need for assistance for feeding, serum albumin, transthyretin, B9 and B12 vitamins, iron status and Serum Ascorbic Acid Level (SAAL) and outcome (in-hospital mortality) between scurvy and scurvy free patients. RESULTS: 18 patients with clinical symptoms of scurvy (scurvy group) were identified out of 145 consecutive patients (12%). They were compared to 23 consecutive control patients with no clinical symptoms of scurvy (scurvy-free group). SAAL was significantly lower (1.09 +/- 1.06 vs 4.87 +/- 4.2 mg x L-1, p < .001) and vitamin C deficiency more frequent (94 vs 30 %, p < .001) in the scurvy group. Moreover, in scurvy group, coronary heart disease (39 vs 9 %, p=.028), need for assistance for feeding (56 vs 13 %, p=.006) and in-hospital deaths (44 vs 9 %, p=.012) were more frequent. CONCLUSION: Ninety-four percent of patients with clinical symptoms of scurvy had vitamin C deficiency. Our results suggest that in hospitalized elderly patients, clinical symptoms allow scurvy diagnosis. Scurvy could be a frequent disease in elderly patients admitted to acute geriatric ward.

[Incidence of undiagnosed skin cancers in a geriatric hospital]. / Fréquence des cancers cutanés non diagnostiqués en hôpital gériatrique.

BACKGROUND: The incidence of non melanoma skin cancers is closely correlated with age. The aim of this prospective study was to evaluate the prevalence of undiagnosed skin cancers among patients hospitalized in rehabilitation and long-term care units in a geriatric hospital. PATIENTS AND METHODS: All the patients, resident in four rehabilitation and long-term care units and for whom no dermatological advice had been given, were systematically examined by a dermatologist. Clinical data included patient age at the time of the study, gender, relevant historical information, skin phototype and description of the cutaneous lesions. Biopsies were performed for all lesions of suspicious appearance. RESULTS: Three hundred and six patients (79.4% women and 20.6% men aged from 55 to 103 years) were included in the study. Among all the patients, 69.3% were hospitalized for more than one year. Skin phototype was clear for 93.5% of the patients. Thirty-two out of 306 patients (10.5%) presented 42 suspicious lesions and these were diagnosed by histological examination as 16 basal-cell carcinomas, seven squamous cell-carcinomas and two in situ melanomas. Skin cancers were localised on the head and neck in 80% of cases. The prevalence of patients with skin cancers was 5.6% in this population. CONCLUSION: The prevalence of skin cancers among patients hospitalized in geriatric hospitals justifies improved training of geriatricians regarding early recognition and dermatological assessment of cutaneous tumours.