Treatment of moderate-to-severe psoriasis in adults: An expert consensus statement using a Delphi method to produce a decision-making algorithm.

BACKGROUND: New highly effective drugs for moderate-to-severe cutaneous psoriasis are regularly marketed, and the hierarchy of treatments thus requires frequent review. OBJECTIVES: A Delphi method was used to enable a structured expert consensus on the use of systemic treatments and phototherapy among adults with moderate-to-severe psoriasis. METHODS: The Delphi method consists in achieving a convergence of opinions among a panel of experts using several rounds of questionnaires with controlled feedback between rounds. A two-part Delphi questionnaire was administered online to French psoriasis experts. In the first part, 180 items related to the prescription of systemic treatments and phototherapy for adult patients with moderate-to-severe psoriasis were grouped into 21 sections covering different lines of treatment and different forms of cutaneous psoriasis. The experts voted on each proposal using an ordinal 7-point Likert scale. The second part comprised 11 open-ended questions about special indications for each therapeutic class. These were converted into 101 questions for subsequent rounds. Consensus was deemed to have been reached if more than 80% of the experts agreed with a given proposal. RESULTS: Three rounds of questionnaires were sequentially sent to 35 participants between November 2021 and March 2022. Thirty-three (94%) completed all three rounds. For plaque psoriasis, only methotrexate was recommended by the experts as first-line systemic treatment (89% of votes). Cyclosporin was advocated in pustular and erythrodermic psoriasis, and acitretin was suggested for hyperkeratotic and palmoplantar psoriasis. In the event of failure of or intolerance to non-biological systemic treatments, guselkumab, risankizumab, ixekizumab or secukinumab were recommended by more than 80% of the experts. Tumor Necrosis Factor (TNF) inhibitors remain useful for patients with cardiovascular risk factors. Special indications were provided for each therapeutic class (methotrexate/narrowband ultraviolet B phototherapy, psoralen/ultraviolet A phototherapy, cyclosporin, acitretin, apremilast, TNF inhibitors, interleukin (IL)-12/23 inhibitors, IL-17(R)A inhibitors, and IL-23 inhibitors). CONCLUSIONS: This expert consensus statement indicate that newly available IL-17 and IL-23 inhibitors may be favored over TNF and IL-12/23 inhibitors as first-line biologics. The Centre of Evidence of the French Society of Dermatology has drawn up a decision-making algorithm to guide clinicians in the therapeutic management of moderate-to-severe psoriasis.

Factors associated with tuberculosis-associated haemophagocytic syndrome: a multicentre case-control study.

SETTING: Tuberculosis (TB) is a potential trigger of haemophagocytic syndrome (HS) but little is known about the features of TB-associated HS.OBJECTIVE: To assess the risk factors associated with HS in patients with TB.DESIGN: We performed a multicentre case-control study assessing the medical records of adult patients diagnosed with proven TB with (TB/HS+) or without (TB/HS-) associated HS.RESULTS: Twenty-one patients with TB/HS+ (24% women, median age, 37 years [IQR 30-48]) were included in the study. Eleven patients (52%) were infected with human immunodeficiency virus and seven patients (33%) were immunocompromised due to other reasons. TB was disseminated in 17 patients (81%). Compared with 50 control TB patients (TB/HS-), patients with TB/HS+ were more likely to be immunocompromised (86% vs. 18%; P < 0.001) and to present with disseminated TB (80% vs. 12%; P < 0.001). The outcome was poorer in patients with TB/HS+, with a higher admission rate to intensive care (71% vs. 0%; P < 0.001) and a higher risk of death (38% vs. 7%; P = 0.005).CONCLUSION: TB/HS+ occurred more likely in immunocompromised patients and severely impaired the prognosis of TB. Further studies are needed to devise therapeutic strategies for patients with TB/HS+.

[Association between prescription of long-term systemic glucocorticoid therapy associated measures and prescriber's medical speciality]. / Prescription des mesures adjuvantes aux corticothérapies systémiques prolongées en fonction de la spécialité du prescripteur.

INTRODUCTION: In order to prevent some glucocorticoid-induced adverse events, adjuvant measures are often associated with prescription of long-term (≥3 months) systemic glucocorticoid therapy. The main objective of this study was to study the association between prescription of these measures and the medical specialty of the prescriber. METHODS: A cross-sectional study was conducted through the website www.cortisone-info.fr. Patients visiting this website and receiving long-term glucocorticoid therapy were asked to fill a questionnaire asking them, among other things, the specialty of the physician who initiated glucocorticoids and the adjuvant measures they were prescribed at treatment initiation. RESULTS: In all, 1383 patients answered the questionnaire and 843 (61%) questionnaires were analyzed (women: 70.6%, median age: 59 [44-70] years, current glucocorticoid dosage: 12.5 [5-30] mg/day, maximum dose: 42 [20-60] mg/day). The main prescribers were rheumatologists (30.5%) and internists (17.3%). Most adjuvant measures were heterogeneously prescribed and depended largely on the specialty of the prescribing physician. Some probably unnecessary measures in most patients (potassium supplementation, prevention of peptic ulcer, low-sodium diet) were frequently prescribed while other consensual measures (prevention of osteoporosis, vaccinations) were prescribed to less than half of patients. In multivariable analyses, most of the studied measures were more frequently prescribed by internists than by colleagues of other specialties. Pneumologists more often vaccinated patients against influenza or pneumococcus than their colleagues. CONCLUSION: Adjuvant measures to long-term glucocorticoid therapy are heterogeneously prescribed. The prescriptions depend largely on the medical specialty of the prescribing physician.

Severe cutaneous adverse reactions due to inappropriate medication use.

BACKGROUND: The proportion of severe cutaneous adverse reactions (SCARs) that could be avoided if medication use was consistent with good medical practice is unknown. OBJECTIVES: To estimate the proportion of SCARs related to inappropriate medication use. METHODS: We carried out a retrospective study of all validated SCARs collected in a French registry between 2003 and 2016. For each case, all plausible drugs suspected of inducing SCARs (i.e. not just the drug regarded as 'the most probable') were considered with regard to (i) prescription for an inappropriate indication, (ii) unintentional rechallenge despite a previous allergy to the drug or (iii) self-medication with prescription medicines. RESULTS: In total, 602 cases were included in the analyses. Antibiotics, anticonvulsants and allopurinol were the drugs most frequently involved, accounting for more than 50% of all cases. All suspected medications were considered to have been appropriately used for 417 of the 602 individuals included in the study population [69·3%, 95% confidence interval (CI) 65·6-73·0] and inappropriately used for 144 individuals (23·9%, 95% CI 20·5-27·3). These inappropriate uses were due mainly to prescriptions for an inappropriate indication (65·8%, 95% CI 58·4-73·2) or unintentional rechallenge (20·9%, 95% CI 14·6-27·2). Allopurinol and co-trimoxazole were the drugs most frequently involved in inappropriate indications. Antibiotics were the largest group involved in unintentional rechallenge. Nonsteroidal anti-inflammatory drugs, available on prescription, were most frequently involved in inappropriate self-medication. CONCLUSIONS: Our results underline the need for respecting the appropriate indication for drugs in order to reduce the incidence of SCARs. Reducing unintentional rechallenge also seems to be a necessary preventive measure.

[What's new in internal medicine?] / Quoi de neuf en médecine interne ?

As it is practiced in France, internal medicine meets the Anglo-Saxon definition of the specialty, ie doctors "equipped to handle the broad and comprehensive spectrum of illnesses that affect adults, and are recognized as experts in diagnosis, in treatment of chronic illness, and in health promotion and disease prevention - they are not limited to one type of medical problem or organ system". This 2017 "What's new in internal medicine" will consist of 2 parts, a first part on significant publications in the field of systemic and autoimmune diseases and a second part on more diverse publications (HIV, cancer, pregnancy, well-being...) important for medicine in general and its different specialties.

Effects of chronic exposure of hydroxychloroquine/chloroquine on the risk of cancer, metastasis, and death: a population-based cohort study on patients with connective tissue diseases.

BACKGROUND: Hydroxychloroquine and chloroquine may reduce the risk of cancer as they inhibit autophagy, in particular, in people with connective tissue diseases. METHODS: The hazard ratios of cancers, metastases, and death were assessed in adults with connective tissue diseases prescribed hydroxychloroquine/chloroquine for at least 1 year in comparison with unexposed individuals with the same underlying conditions. A competing risk survival regression analysis was performed. Data were extracted from the Health Improvement Network UK primary care database. RESULTS: Eight thousand nine hundred and ninety-nine individuals exposed to hydroxychloroquine (98.6%) or chloroquine (1.4%) and 24,118 unexposed individuals were included in the study (median age: 56 [45-66] years, women: 76.8%). When compared to the unexposed group, individuals exposed to hydroxychloroquine/chloroquine were not at lower risk of non-skin cancers (adjusted sub-distribution hazard ratio [sHR]: 1.04 [0.92-1.18], p=0.54), hematological malignancies (adjusted sHR: 1.00 [0.73-1.38], p=0.99), or skin cancers (adjusted sHR: 0.92 [0.78-1.07], p=0.26). The risk of metastasis was not significantly different between the two groups. However, it was significantly lower during the exposure period when compared with the unexposed (adjusted sHR: 0.64 [0.44-0.95] for the overall population and 0.61 [0.38-1.00] for those diagnosed with incident cancers). The risk of death was also significantly lower in those exposed to hydroxychloroquine/chloroquine (adjusted HR: 0.90 [0.81-1.00] in the overall population and 0.78 [0.64-0.96] in those diagnosed with incident cancer). CONCLUSION: Individuals on long-term exposure to hydroxychloroquine/chloroquine are not at lower risk of cancer. However, hydroxychloroquine/chloroquine may lower the risk of metastatic cancer and death.

[Amiodarone-induced immune complex cutaneous vasculitis]. / Vascularite cutanée induite par l'amiodarone.

BACKGROUND: A wide variety of drugs can cause cutaneous vasculitis. Herein we report a case of immune complex vasculitis induced by amiodarone. PATIENTS AND METHODS: A 57-year-old patient reported a recent history of pruritus associated with large erythematous, inflammatory, necrotic plaques localized on the lower limbs and back. These cutaneous lesions had appeared less than 2 months after initiation of amiodarone for supra-ventricular arrhythmia. Histological and direct immunofluorescence examinations of a skin biopsy sample revealed vasculitis with the presence of IgM and C3 immune complexes in vessels. The remaining laboratory tests were unremarkable (in particular, cryoglobulin and autoantibody tests were negative). The patient himself attributed his symptoms to the recent administration of amiodarone and spontaneously stopped the drug without medical advice. No other therapy was prescribed. Following drug withdrawal, the lesions that had been present for more than 4 months completely disappeared. No recurrence occurred after follow-up of over 6 months. The diagnosis of amiodarone-induced vasculitis was retained. DISCUSSION: Fewer than 10 cases of amiodarone-induced vasculitis have been reported in the medical literature. It is not known whether this entity is rare, under-diagnosed or under-reported.

Diversity and combinations of infectious agents in 38 adults with an infection-triggered reactive haemophagocytic syndrome: a multicenter study.

Reactive haemophagocytic syndrome (HS) is a rare condition that occurs in patients with infections, haematological malignancies or autoimmune diseases. Although various microorganisms are thought to trigger HS, most of the literature data on this topic have been gathered in single-centre case series. Here, we sought to characterize infectious triggers in a large, multicentre cohort of patients with HS. Patients were included in the present study if HS was solely due to one or more infections. Detailed microbiological data were recorded. Of the 162 patients with HS in the cohort, 40 (25%) had at least one infection and 38 of the latter (including 14 women, 36.8%) were included. The median age was 46 years. Seven patients were presumed to be immunocompetent (18.4%), whereas 19 patients (50%) were infected with human immunodeficiency virus and 12 patients (31.6%) were immunocompromised for other reasons. Twenty-seven patients (71.1%) had a single infection, whereas six (15.8%) and five (13.1%) patients had, respectively, two and three concomitant infections. We observed pyogenic bacterial infections (n = 7), tuberculosis (n = 10), non-tuberculous mycobacteriosis (n = 3), viral infections (n = 17: 11 cytomegalovirus, three Epstein-Barr virus, two human herpesvirus 8, one herpes simplex virus 2), parasitic infections (n = 8: four disseminated toxoplasmosis, one leishmaniasis, three malaria), fungal infections (n = 5: four pulmonary pneumocystosis and one candidaemia). Eighteen patients (47.4%) received corticosteroids and/or etoposide. Twelve patients died (31.6%). All multiple infections and all deaths occurred in immunocompromised patients. When compared with patients suffering from malignancy-associated HS, patients with infection-triggered HS were younger and more likely to be immunocompromised, and had a better outcome.

Primary-care physicians' patient referral patterns to private versus public hospitals for orthopaedic or trauma surgery-- French Sentinels® database, 1997-2011.

BACKGROUND: In France, primary-care physicians referring patients for admission can choose between public and private hospitals. The factors that govern their choices are unknown. METHODS: Among all patient admissions reported from 1997 to 2011 by primary-care physicians participating in the Sentinels(®) network, we identified those due to orthopaedic conditions or trauma. We then identified the factors associated with referral to a private hospital rather than to a public hospital. RESULTS: Of 45,960 admissions reported to Sentinels(®) in 1997-2011, 2794 (6.1%) were for orthopaedic/trauma care. The main reasons for admission were hip fractures (27.5%), elective orthopaedic surgery (15.5%), fractures of the humerus (5.9%), wrist fractures (5.4%), soft-tissue lesions of the forearm or hand (5.0%), and spinal injuries (4.5%). Private hospitals were chosen more often for orthopaedic/trauma patients than for patients with other conditions (40% vs. 21.6% of cases, P<0.0001). When fracture of the humerus was used as the reference, referral to private hospitals was significantly more common for elective surgery (odds ratio, 3.30 [2.02-5.40]) and hip fracture (odds ratio, 1.50 [1.03-2.18]) and significantly less common for spinal injuries (odds ratio, 0.35 [0.19-0.66]). Other factors associated with referral to private hospitals were patient age, admission decision during an office visit or in a non-emergent setting, and admission decision made by the patient's usual physician. CONCLUSION: Specific factors seem to govern decisions by primary-care physicians to refer orthopaedic/trauma patients to private vs. public hospitals. Identical pricing scales for private and public hospitals will be implemented soon in France, a change that requires further analyses. LEVEL OF EVIDENCE: Level IV.

Frequency, clinical features and prognosis of cutaneous manifestations in adult patients with reactive haemophagocytic syndrome.

BACKGROUND: Cutaneous involvement has been reported in 30-40% of children with the familial form of haemophagocytic syndrome. However, few studies have focused on cutaneous manifestations in patients with reactive haemophagocytic syndrome (RHS). OBJECTIVES: To describe the frequency, clinical features and prognosis of skin involvement in adult patients with RHS. METHODS: We conducted a retrospective study in a French university-based tertiary centre. The medical records of all adult patients with a suspected or confirmed diagnosis of RHS during a 2-year period were reviewed. Demographic, clinical, biological and histological data of patients were compared using nonparametric tests. RESULTS: The medical charts of 151 patients were reviewed, 69 of whom had a definite diagnosis of RHS (35% women; mean +/- SD age 49 +/- 17 years). The aetiology of RHS was mainly B-cell or T-cell lymphoma (n = 33) or herpesvirus infection (n = 19). Cutaneous manifestations were observed in 32 (46%) patients and were of three types: (i) specific to the underlying malignancy (Kaposi sarcoma n = 8, cutaneous lymphoma n = 4), (ii) reflecting the biological consequences of RHS (thrombopenic purpura n = 10, conjunctival jaundice n = 7), and (iii) a generalized, transient, nonpruriginous maculopapular rash (n = 18). None presented with erythroderma, or with eczematiform, ichthyosiform, psoriasiform or bullous lesions. One patient had cytophagic histiocytic panniculitis. Histological features of maculopapular rash biopsies were usually nonspecific. The rate of in-hospital death was not significantly associated with cutaneous involvement. CONCLUSIONS: A generalized, nonpruriginous, transient, maculopapular rash is frequently observed in patients with RHS. Although nonspecific, awareness of this cutaneous involvement may assist physicians in the initial diagnosis of RHS.

[Münchausen syndrome with forgery on biologic results. A case report]. / Pseudoleucémie par falsification d'examens biologiques: genèse d'un syndrome de Münchausen.

Münchausen syndrome is a disorder defined by the following: acute factitious symptoms leading to inappropriate investigation and therapy, a restless journey from hospital to hospital and autobiographical falsification. We report here a 20-year-old woman who presented at our hospital consultation of internal medicine with laboratory-test results suggesting the diagnosis of leukemia. A new complete blood cells count and a medullogram by sternal puncture did not show any abnormality. Comparative examination of laboratory-test sheets lead to the diagnosis of Münchausen syndrome as some results had been falsified. With unlimited access to information through internet and word or image processing softwares, laboratory results have become easy to falsify nowadays, particularly for patients with Münchausen syndrome, who may then be quite difficult to diagnose accurately in the context of medical consultation.

[In-hospital mortality and stay duration of internal medicine patients: prognosis value of biochemical markers commonly performed on admission]. / Mortalité hospitalière et durée de séjour des patients non programmés en médecine interne: valeur pronostique de paramètres biochimiques usuels à l'admission.

PURPOSE: Little is known about prognosis values of biochemical markers in internal medicine patients. We have examined retrospectively the relationship between inhospital mortality or stay duration and several biochemical markers commonly performed on admission in internal medicine patients. METHODS: Among all stays unplanned in our department during the year 2004, we collected data about 8 blood biochemical markers (sodium, potassium, chloride, bicarbonate, anion gap, urea nitrogen, creatinin, proteins), performed between the day before and the day after admission. Mixed Cox regression models computed hazard ratios for mortality associated with biochemical markers concentration. The relationship between biochemical markers concentration and duration stay was investigated in mixed linear regression models. RESULTS: In 2004 our department totalized 1199 unplanned stays by 1054 distinct patients (age: 69.9+/-19.2 y, women: 59.2%), among which 59 deceased during stay. Biochemical markers were available for 977 (81.5%) stays (stay duration: 17.5+/-16.0 days). Inhospital mortality was significantly associated with plasma concentration on admission of potassium, proteins, anion gap and with urea nitrogen/creatinin ratio. Among survivors, duration stay was significantly associated with plasma concentration on admission of sodium, chlore, and anion gap. CONCLUSION: Biochemical markers performed on admission need particular attention as they provide immediate information about short term prognosis of internal medicine patients.

Idiopathic systemic capillary leak syndrome: cutaneous involvement can be misleading.

BACKGROUND: Systemic capillary leak syndrome (SCLS) is a severe disorder characterized by unexplained rapid transfer of considerable volumes of plasma from the intravascular to the extravascular compartment. For some cases of SCLS, no aetiology is evident and these cases are reported as idiopathic (ISCLS). OBJECTIVES: To describe the cutaneous findings in 3 patients with ISCLS. RESULTS: Cutaneous involvement consisted in sclerosis, livedo, purpura and photodistributed maculopapular erythematous rash. Dermal mucinosis was proven by biopsy in 1 patient. No underlying disease was diagnosed during follow-up. CONCLUSION: The above-mentioned cutaneous findings can be present during acute attacks of ISCLS. They seem specifically related to the ISCLS and not indicative of an underlying disease.

Human herpesvirus 8-associated hemophagocytic lymphohistiocytosis in human immunodeficiency virus-infected patients.

We retrospectively reviewed 5 cases of hemophagocytic lymphohistiocytosis (HL) associated with human herpesvirus 8 (HHV-8) reactivation in human immunodeficiency virus (HIV)-infected patients. All patients had clinical and biological features characteristic of HL. Pulmonary symptoms were present in all patients and were frequently life threatening. The mean number of HL episodes was 6. Four patients had HL-associated Kaposi sarcoma, and 3 had multicentric Castleman disease. The mean CD4 cell count was 200 cells/mm(3). HIV loads were stable in all patients. All patients had high levels of HHV-8 in peripheral blood mononuclear cells during attacks, and a significant increase in this parameter before the attacks was seen in 3 patients. Although 2 patients died of HL, 3 are still alive and receiving etoposide therapy (mean follow-up, 3 years). HHV-8-related HL is associated with life-threatening symptoms and biological HHV-8 reactivation, and it may be controlled in the long term by etoposide therapy combined with highly active antiretroviral therapy.

Primary glenohumeral degenerative joint disease: factors predisposing to arthroplasty.

OBJECTIVE: To evaluate the natural history of shoulder osteoarthritis (OA), in particular the requirement for arthroplasty over time, and to determine the potential predisposing factors for such arthroplasty. METHODS: In- and out-patients with the diagnosis of OA of the shoulder seen between January 1990 and December 1994 were contacted by mail or telephone in 2000. Evaluation at the time of diagnosis: demographics, clinical and radiological data were evaluated at the time of diagnosis. The follow-up evaluation consisted of a questionnaire sent to each patient inquiring whether they had had recourse to shoulder arthroplasty and, if not, evaluated their willingness regarding this surgical approach. For the statistical analysis the requirement for arthroplasty over time was evaluated using the Kaplan-Meier technique. Potential factors predisposing to arthroplasty were determined using a Cox-model analysis. RESULTS: The questionnaire was answered by 72 of the 86 contacted patients. No difference was observed in clinical and radiological variables at the time of diagnosis between responders and non-responders. The requirement for arthroplasty was low (respectively 5% and 13%, 5 and 10 years following the onset of the symptoms). Nearly half of the patients who had not undergone surgery thought that arthroplasty would have been the treatment of choice to improve their quality of life since more than one year at the time of completing the questionnaire. Two variables were picked up in the Cox analysis, with a probability of shoulder replacement higher in patients with concomitant osteonecrosis of the humeral head (p = 0.02) and a non-eccentric glenohumeral OA (p = 0.011). CONCLUSION: The low percentage of patients with arthroplasty over time, together with patient perception, suggest underuse of this surgical approach in shoulder OA.

[Perception of organ grafts by internists]. / Perception de l'activité de greffe d'organe par les médecins internistes.

INTRODUCTION: At the time when organ transplantation occupies a preponderant place in the treatment of many pathologies, the role of the internist in the care of grafted patients remains confidential and poorly defined. PATIENTS AND METHODS: A questionnaire was sent to 730 internist practitioners. The aims of this questionnaire were to evaluate 1) their level of knowledge and practice of transplantation; 2) their declared interest on the subject; and finally 3) their perception of the theoretical place of the internists in the transplantation. RESULTS: Two hundred twenty-five answered. Although nearly 80% of the practitioners who answered this investigation declared themselves interested in the subject of transplantation, more than 60% considered their theoretical and practical knowledge on the subject to be insufficient. Nearly 70% said they felt ill at ease when faced with a grafted patient in consultation. Nearly two experts out of three considered that the role of the internist in the follow-up of grafted patients should be reinforced but less than 50% of them wished to be more involved, directly and personally. DISCUSSION: Whereas grafted patients frequently suffer from polypathologies that could be treated in internal medicine, a majority of internists do not wish to be directly implicated and/or do not feel qualified to treat these patients. The inherent risk in this is to see this specialty gradually excluded from the care networks available to grafted patients.