[Conversion disorder in an internal medicine department: A series of 37 cases]. / Le trouble de conversion en médecine interne: 37 observations.

OBJECTIVES: To describe the clinical characteristics of a series of patients presenting conversion disorder in a general internal medicine ward and outpatient clinic, the arguments retained by the physicians in favour of the diagnosis, the somatic and psychiatric co-morbidities, the management and the outcome of the disorder. METHODS: We report the study of 37 patients diagnosed with conversion disorder in an internal medicine department of a French university hospital over a period of 14 years. We retrospectively reviewed the charts of the patients and contacted their primary care physicians to obtain follow-up data. No structured instrument was used for the diagnosis of conversion disorder or for the assessment of psychiatric comorbidities. RESULTS: As expected, patients were mostly young females, although a great variety of age, gender, and socio-cultural background was observed. Motor symptoms predominated (62%). A relevant psychogenic factor was explicitly mentioned in only 43% of the cases. In many cases, organic disease was also present, and an organic cause for the symptom initially considered as conversion was suspected in 3 cases. Depressive and anxious disorders were present respectively in 38% and 35% of cases. A pain complaint was associated in half of the cases. Among patients for whom follow-up data is available, conversion symptoms persisted or recurred in 70% of cases and were associated with a poor quality of life. CONCLUSION: This case series confirms that the DSM-IV-TR criterion of "psychogenicity" (later abandoned in DSM-5) is highly problematic in clinical practice. It suggests a close relationship between conversion disorder and unexplained chronic pain.

Physiopathology of necrobiotic xanthogranuloma with monoclonal gammopathy.

RATIONALE: Xanthomatosis associated with monoclonal gammopathy includes hyperlipidaemic xanthoma (HX), normolipidaemic xanthoma (NX) and necrobiotic xanthogranuloma (NXG). All three pathologies are characterized by skin or visceral lesions related to cholesterol accumulation, monoclonal immunoglobulin (MIg) and hypocomplementemia. The pathophysiology underlying NXG remains unknown although the involvement of MIg is suspected. OBJECTIVE: To provide further insights into the pathophysiology of NXG, we evaluated the plasma lipid phenotype, mechanisms involved in cellular cholesterol accumulation and role of MIg in an analysis of blood and plasma markers of inflammation in 16 patients with xanthomatosis [NXG (n = 8) and NX (n = 8)] associated with monoclonal IgG relative to the relevant controls. RESULTS: The lipid profile of patients with NXG was characterized by a low HDL-C phenotype and an abnormal distribution of HDL particles. Sera from patients with NXG induced cholesterol accumulation in human macrophages. This accumulation was due in part to a significant reduction in the HDL capacity to promote cholesterol efflux from macrophages, which was not found in the case of NX. The MIg of NXG and NX patients was tested positively by ELISA to recognize a large spectrum of lipoproteins. High plasma levels of pro-inflammatory cytokines (TNFα and IL-6), soluble cytokine receptors (sIL-6R, sTNFRI and sTNFRII), adhesion molecules (VCAM-1 and ICAM-1) and chemokines (MCP-1, IL-8 and MIP-1α) were observed in both patients with NXG and NX, revealing a specific xanthoma inflammatory signature which was inversely correlated with plasma levels of anti-inflammatory HDL. However, patients with NXG were distinguished by elevated levels of IL-15 and a marked increase in the rate of intermediate CD14++CD16+ monocytes. CONCLUSION: This study revealed that NXG is characterized by impaired macrophage lipid homeostasis associated with a systemic inflammatory profile that may result from the interaction of MIg and lipoproteins.

[Health anxiety: Another epidemic to prepare for]. / L'anxiété centrée sur la santé : une autre épidémie à laquelle il faut se préparer.

Health anxiety (HA) is a frequent problem (up to 20% of consultants in the context of secondary care) responsible for decreased well-being, disability, somatic and psychiatric complications, which contributes to high healthcare expenditures at the population level. It is likely, if not definitely established, that the prevalence of ACS is increasing, and this can partly be explained by the growing medicalization of society in general, the appetite of Media for health issues, and the uncontrolled use of the Internet (which can lead certain vulnerable subjects to cyberchondria). The pandemic of COVID-19 could have contributed to it, at least by the significant increase in the overall level of psychological distress in the population it has caused, although this has not formally been demonstrated to date. The diagnosis of ACS is easy, as soon as its assessment is considered as a mandatory part of any medical consultation. Certain intuitive attitudes of doctors, such as reassurance, prove to be iatrogenic for the patient with HA. The management of HA can be facilitated by an acculturation of physicians to cognitive conceptions of anxiety in general and HA in particular. HA is effectively treatable by certain psychotherapy and in the first place cognitive and behavioral therapies (CBT), but the availability of trained therapists and accessible at a lower cost is sorely lacking, particularly in France.

[Chronic fatigue: What investigations? And what for?] / Fatigue chronique : quelles investigations ? Dans quels objectifs ?

Chronic fatigue is a frequent complaint, expressed at all levels of the healthcare system. It is perceived as disabling in a high proportion of cases, and internists are frequently called upon to find "the" cause. The etiological diagnostic approach of an unexplained state of fatigue relies on the careful search for more specific clues by questioning and clinical examination. It is necessary to recognize the limited place of complementary examinations apart from the basic biological parameters. Simple rating scales can be useful in the etiological and differential diagnosis of fatigue. Chronic fatigue syndrome (CFS), in the current state of knowledge, cannot be considered as a specific pathological entity distinct from idiopathic chronic fatigue states, and does not have validated biomarkers. It is important to know that a state of chronic asthenia often results from several intricated etiological factors (biological, psychological and social), to be classified as predisposing, precipitating and perpetuating. The metabolic and cardiorespiratory exercise test has a major place in the assessment and management of fatigue, as a prerequisite for personalized retraining or adapted physical activity (APA), which are the treatments of choice for chronic fatigue.

[Rhabdomyolysis with tetraparesis secondary to hepatitis E virus infection in a patient on statins]. / Rhabdomyolyse avec tétraparésie secondaire à une hépatite virale E chez un patient sous statines.

INTRODUCTION: Neurologic and muscular damage associated with acute hepatitis due to hepatitis E virus (HEV) are rare and may be underdiagnosed. CASE REPORT: We report the case of a 56-year-old man, presenting with flaccid tetraparesis secondary to an acute rhabdomyolysis induced by acute E virus hepatitis. He fully recovered after one month under supportive treatment. DISCUSSION: Rare cases of acute rhabdomyolysis induced by HEV infection have been reported in the literature. We discuss the potential adjuvant role of statin treatment in our patient. Unexplained acute neurological conditions should prompt the search for HEV infection.

[Spontaneous periodic hypothermia syndrome: A systematic review of the literature]. / Syndrome d'hypothermie périodique spontanée : une revue systématique de la littérature.

INTRODUCTION: Periodic spontaneous hypothermia syndrome (PSHS), also known as hypersudation-hypothermia syndrome, is a rare condition characterised by the occurrence of paroxysmal attacks of spontaneous hypothermia occurring without age limit. Few studies have attempted to synthesise the available data on PSHS. The objective of this study was to summarize the literature on this condition. METHODS: A literature review was conducted using the Pubmed and ScienceDirect databases. Cases from a registry of PSHS initiated at the CHU of Saint-Étienne were added to the analysis. For each clinical case, clinical, biological and morphological data as well as therapeutic management and evolution were collected. RESULTS: Seventy-one cases of PSHS were collected. The median age at symptom onset was 21.5 years. The clinical sign most frequently associated with hypothermia was the presence of hyperhidrosis. The triad of hypothermia-hypersudation-agenesis of the corpus callosum was present in 35.7% of cases. CONCLUSION: PSHS remains a poorly known cause of hypothermia, without consensual therapeutic options. The need to better describe cases and obtain more long-term data will allow a better definition and knowledge of this syndrome.

["Long-haul COVID": An opportunity to address the complexity of post-infectious functional syndromes]. / « COVID long ¼ : une opportunité pour approcher la complexité des syndromes fonctionnels post-infectieux.

In this work, we address the issue of prolonged symptoms following an infection by SARS-CoV-2, labeled "long COVID". This clinically unspecific syndrome must be put in perspective with the post-infectious syndromes known for a long time but ultimately poorly understood and little studied, qualified, for lack of convincing arguments for a unambiguous pathophysiology and better terms, as functional somatic syndromes. The clinical implications for clinical care ("holistic" work-up and care of patients), for research (need for truly "bio-psycho-social" investigations), and the social implications of "long COVID" (social construction of the syndrome through the experiences of patients exposed on social networks, inequalities in the face of the disease and its socioeconomic consequences) are considered. "Long COVID" must be view, because of its expected prevalence, as an opportunity to address the complexity of post-infectious (functional) syndromes, their risk factors, and the biological, psychological and social mechanisms underlying them.

[Myelofibrosis: A review]. / Les myélofibroses.

Myelofibrosis is a BCR-ABL1-negative chronic myeloproliferative neoplasm that includes primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. It is characterized by stem cell-derived clonal proliferation that is often, but not always, accompanied by somatic mutations, which are classified into driver mutations (JAK2, CALR, or MPL), subclonal mutations and fibrosis on bone marrow biopsy. Myelofibrosis commonly demonstrates splenomegaly, constitutional symptoms, anemia, thrombocytosis, or thrombocytopenia. Patients may also be asymptomatic. Complications as thromboembolic or hemorrhagic events can reveal the disease. Primary myelofibrosis is the least common myeloproliferative neoplasm but is associated with poor survival and acute leukemic transformation. In contrast to the significant progress made in understanding the disease's pathogenesis, treatment for myelofibrosis remains largely palliative. The JAK2 inhibitor, ruxolitinib is not sufficient in eliminating the underlying myeloid progenitor clone, as disease inevitably returns with therapy discontinuation. Allogeneic hematopoietic stem cell transplantation is the only therapeutic option that offers potential cure. The development of novel treatment strategies aimed at slowing or even reversing disease progression, prolonging patient survival and preventing evolution to blast-phase are still lacking.

[Rituximab immunomonitoring in autoimmune diseases: a support tool in clinical practice?] / Immunomonitoring du rituximab appliqué aux maladies auto-immunes : une aide pour la pratique clinique ?

INTRODUCTION: Immune monitoring of monoclonal antibodies is a helpful tool in optimizing the management of patients treated with TNF blockers, especially in gastroenterology. In contrast, studies evaluating the interest of such monitoring are lacking for other monoclonal antibodies used in autoimmune diseases, including rituximab despite its widespread use in the field for almost 15 years. Hence, we conducted a study whose goal was to describe the clinical and biological characteristics of all patients who had a rituximab immune monitoring. METHODS: All the clinical, biological and therapeutic data attached to the demands (from 2015 onwards) we received for immune monitoring of rituximab (measurements of rituximab serum levels and anti-rituximab antibodies using the drug-sensitive assay LISA-TRACKER Duo Rituximab®), were retrospectively reviewed. Suspected cases of hypersensitivity and secondary non-response were included. RESULTS: Several medical specialities (nephrology, haematology, neurology, rheumatology, internal medicine) were represented among the 18 records included in the study (out of 23 demands), 10 being suspected cases of hypersensitivity and 8 secondary non-responders. All 6 patients whose symptoms were consistent with the classical presentation of serum sickness, as well as half of the secondary non-responders, were positive for antirituximab antibodies. CONCLUSION: This detailed real world case study illustrates the potential benefits of rituximab immune monitoring (especially anti-rituximab antibodies) in autoimmune diseases, suggesting it could be helpful in suspected cases of serum sickness, as well as secondary non-response (B-cell non-depletion being an early red flag). Larger and disease-specific studies are warranted to support these findings.

[Characteristics of patients admitted from emergency units in 18 internal medicine departments and organisation of these departments: A cross sectional study from SNFMI (SiFMI study group) in 2015]. / Caractéristiques des patients admis en médecine interne dans 18 hôpitaux français en aval des urgences et organisation de ces services : enquête transversale de la SNFMI (groupe d'étude SiFMI) en 2015.

INTRODUCTION: Patients admitted from emergency units represent a large portion of the population in internal medicine departments. The aim of this study is to identify characteristics of patients and organization of these departments. METHODS: Between June 29th and July 26th 2015, voluntary internal medicine departments from the SiFMI group prospectively filled anonymized internet forms to collect data of each patients admitted in their ward from emergency units, during seven consecutive days. RESULTS: Three hundred and sixty-five patients from emergency departments were admitted in 18 internal medicine inpatients departments, totalling 1100 beds and 33,530 annual stays, 56% of them for emergency units inpatients. Mean age was 68 years, 54% were women, mean Charlson score was 2.6 and 44% of the patients took at least three drugs. Main causes of hospitalization were infectious (29%) and neurological (17%) diseases. Mean length of stay was 9.2 days. The medical team was composed by a median value of 4,5 [2,75-6,25] senior full-time equivalents, 86% were internists. Each department except one received residents, two third of them were from general medicine. CONCLUSION: This study highlights a high organizational variability among internal medicine departments and patients, and sets internal medicine as a specialty with a great capacity to achieve an integrative/comprehensive management of patients and to offer a comprehensive basis for physicians in training.

Fatal aspergillosis complicating severe SARS-CoV-2 infection: A case report.

As aspergillosis is a well-known complication of severe influenza, we suggest that SARS-CoV-2 might be a risk factor for invasive aspergillosis (IA). We report the case of an 87 year-old woman, with no history of immune deficit, admitted in our emergency room for severe respiratory distress. Coronavirus disease 2019 (COVID-19) diagnosis was confirmed by a SARS-CoV-2 reverse transcriptase polymerase chain reaction (PCR) on nasal swab. On day 14, pulmonary examination deteriorated with haemoptysis and a major increase of inflammatory response. A computed tomography (CT) scan revealed nodules highly suggestive of IA. Aspergillus antigen was found highly positive in sputum and blood, as was Aspergillusspp PCR on serum. Sputum cultures remained negative for Aspergillus. This patient died rapidly from severe respiratory failure, despite the addition of voriconazole. Considering SARS-CoV-2 acute respiratory distress syndrome (ARDS) as an acquired immunodeficiency, we report here a new case of "probable" IA based on clinical and biological arguments, in accordance with the last consensus definition of invasive fungal disease. On a routine basis, we have detected 30% of aspergillosis carriage (positive culture and antigen in tracheal secretions) in critically ill patients with COVID-19 in our centre. Further studies will have to determine whether sputum or tracheal secretions should be systematically screened for fungal investigations in intensive care unit (ICU) COVID-19 patients to early diagnose and treat aspergillosis.

[Chronic-granulomatous disease]. / La granulomatose septique chronique.

Chronic-granulomatous disease (CGD) is a rare inherited primary immunodeficiency syndrome caused by a defective oxidative metabolism of phagocytic cells. Dysfunction of the membranous NADPH oxidase complex leads to a greatly increased susceptibility to severe fungal and bacterial infections, early in childhood. The most severe and frequent type of GCD is the X-linked transmitted form caused by mutations in the CYBB gene encoding the redox element of the oxidase complex, gp91phox or Nox2. However, very rare autosomal recessive CGD affecting other oxidase components than Nox2 are characterized by mild-clinical manifestations that could appear later at the adult age. Long-term antibiotic prophylaxis is essential to prevent infections associated with CGD, but approaches based on hematopoietic stem-cell transplantation and gene therapy offer valuable hope in a near future.

[Olanzapine induced rhabdomyolysis and serum creatine kinase increase]. / Rhabdomyolyse et élévation des enzymes musculaires sous olanzapine.

INTRODUCTION: "Atypical" antipsychotics tend to replace traditional antipsychotics as first line therapy for psychotic disorders, due to their better side-effect profile with fewer extrapyramidal manifestations, allowing a better observance. Nevertheless, second-generation antipsychotics may also lead to adverse events such as metabolic disorders, agranulocytosis or muscle damage. Cases of rhabdomyolysis (aside neuroleptic malignant syndrome) have been reported in patients receiving olanzapine (Zyprexa). METHODS: We reviewed the cases of olanzapine induced rhabdomyolysis reported to the French national database of drug adverse events and retrieved additional cases published in the medical literature. RESULTS: We collected 13 cases from the French pharmacovigilance database and eight additional cases from the literature. Seventeen patients needed hospitalization. Creatine kinase (CK) rate ranged between 413 and 34,500 UI/L. Outcome was favorable in 85% of the cases (17 out of 20 cases) after discontinuation of olanzapine. CONCLUSION: Although rhabdomyolysis is a rare side effect (< 1%) of olanzapine, this adverse event should be evoked when a patient with olanzapine presents with muscle pain, unexplained fatigue or weakness. Prompt dosage of CK should be performed. However, it remains uncertain whether a mild and asymptomatic muscle enzyme increase without any metabolic disorder requires the discontinuation of olanzapine therapy.

[Inappropriate low glycated hemoglobin and hemolysis]. / L'hémolyse : une cause d'erreur dans l'interprétation de l'hémoglobine glycosylée.

Hemoglobin A1c (HbA1c), measured regularly in the patients with diabetes, is the major form of stable glycated hemoglobin and has to be maintained below 6.5% to prevent or decrease the risk of chronic complications. HbA1c reflects mean blood glucose levels of the previous 3 months. We report the case of a particularly low HbA1c in a diabetic patient despite high plasma glucose levels, that was induced by auto-immune hemolysis related to an Evans syndrome. All hemolytic disorders can be responsible for falsely reassuring HbA1c values. Clinicians must be aware that hematologic status has to be considered for the correct interpretation of HbA1c results.

[One or more functional somatic syndromes? Comparison of the health status of fibromyalgia and electro-hypersensitive people]. / Un ou plusieurs syndromes somatiques fonctionnels ? Comparaison de l'état de santé de personnes fibromyalgiques et électro-hypersensibles.

INTRODUCTION: Functional somatic syndromes, grouping somatic symptoms without an organic explanation, are defined either by their predominant symptoms or by an attribution to an, often hypothetical, cause. Due to many similarities, some authors consider that there is only one FSS due to a general phenomenon of "somatization". The objective of this work was to compare two functional somatic syndromes, one defined by its symptoms, fibromyalgia, and the other by a specific contested attribution, electro-hypersensitivity. METHOD: Fibromyalgia or electro-hypersensitive participants (EHS) were recruited from September 2016 to April 2017 through associations of patients in Auvergne-Rhône-Alpes. Home interviews included the collection of medical, psychopathological, and symptom histories. The assessment of psychological distress, quality of life and the search for other functional somatic syndromes was performed through structured questionnaires, self-administrated scales, and clinical examination. RESULTS: Sixteen fibromyalgia subjects and sixteen EHS subjects were included. There are differences in symptomatology, although many symptoms are common to both conditions. Lifetime history of psychiatric disorders and current psychological distress and psychopathology are frequent in both groups but more prevalent in fibromyalgia subjects. The experience of the symptoms, their interpretation, the diagnostic itineraries and the therapeutic behaviours differ radically according to the group, even if for all socio-professional impact is high and quality of life are altered. CONCLUSION: The health status of fibromyalgia persons is overall worse than the health status of electro-hypersensitive individuals in this small sample. Despite the overlap in symptoms and a similar impact on daily functioning, this exploratory study suggests that heterogeneous mechanisms of "somatization" may be at stake in functional somatic syndromes.

[First-episode psychosis as primary manifestation of medical disease: An update]. / Premier épisode psychotique révélant une affection médicale générale : mise au point pour l'interniste.

A huge variety of medical diseases may potentially present with isolated psychotic symptoms, and disease-specific treatment or management is available for a significant part of them. The initial medical work-up of a first-episode psychosis (FEP) is of crucial importance. This literature review aimed to identify medical conditions potentially revealed by FEP, to list the warning signs of secondary psychosis, and to discuss a screening strategy. Underlying organic conditions may be drugs and medications, neurologic diseases, infections, inflammatory and/or autoimmune pathologies, and metabolic disorders whether of hereditary origin. Each patient presenting with a first-episode psychosis should be evaluated with a precise anamnesis, a careful clinical examination, and routine laboratory tests. Brain imaging and tests (depending on the context) should be performed in the presence of atypical clinical features or "red flags", leading to suspect an organic disease.

Lyme borreliosis and other tick-borne diseases. Guidelines from the French scientific societies (II). Biological diagnosis, treatment, persistent symptoms after documented or suspected Lyme borreliosis.

The serodiagnosis of Lyme borreliosis is based on a two-tier strategy: a screening test using an immunoenzymatic technique (ELISA), followed if positive by a confirmatory test with a western blot technique for its better specificity. Lyme serology has poor sensitivity (30-40%) for erythema migrans and should not be performed. The seroconversion occurs after approximately 6 weeks, with IgG detection (sensitivity and specificity both>90%). Serological follow-up is not recommended as therapeutic success is defined by clinical criteria only. For neuroborreliosis, it is recommended to simultaneously perform ELISA tests in samples of blood and cerebrospinal fluid to test for intrathecal synthesis of Lyme antibodies. Given the continuum between early localized and disseminated borreliosis, and the efficacy of doxycycline for the treatment of neuroborreliosis, doxycycline is preferred as the first-line regimen of erythema migrans (duration, 14 days; alternative: amoxicillin) and neuroborreliosis (duration, 14 days if early, 21 days if late; alternative: ceftriaxone). Treatment of articular manifestations of Lyme borreliosis is based on doxycycline, ceftriaxone, or amoxicillin for 28 days. Patients with persistent symptoms after appropriate treatment of Lyme borreliosis should not be prescribed repeated or prolonged antibacterial treatment. Some patients present with persistent and pleomorphic symptoms after documented or suspected Lyme borreliosis. Another condition is eventually diagnosed in 80% of them.

Lyme borreliosis and other tick-borne diseases. Guidelines from the French Scientific Societies (I): prevention, epidemiology, diagnosis.

Lyme borreliosis is transmitted en France by the tick Ixodes ricinus, endemic in metropolitan France. In the absence of vaccine licensed for use in humans, primary prevention mostly relies on mechanical protection (clothes covering most parts of the body) that may be completed by chemical protection (repulsives). Secondary prevention relies on early detection of ticks after exposure, and mechanical extraction. There is currently no situation in France when prophylactic antibiotics would be recommended. The incidence of Lyme borreliosis in France, estimated through a network of general practitioners (réseau Sentinelles), and nationwide coding system for hospital stays, has not significantly changed between 2009 and 2017, with a mean incidence estimated at 53 cases/100,000 inhabitants/year, leading to 1.3 hospital admission/100,000 inhabitants/year. Other tick-borne diseases are much more seldom in France: tick-borne encephalitis (around 20 cases/year), spotted-fever rickettsiosis (primarily mediterranean spotted fever, around 10 cases/year), tularemia (50-100 cases/year, of which 20% are transmitted by ticks), human granulocytic anaplasmosis (<10 cases/year), and babesiosis (<5 cases/year). The main circumstances of diagnosis for Lyme borreliosis are cutaneous manifestations (primarily erythema migrans, much more rarely borrelial lymphocytoma and atrophic chronic acrodermatitis), neurological (<15% of cases, mostly meningoradiculitis and cranial nerve palsy, especially facial nerve) and rheumatologic (mostly knee monoarthritis, with recurrences). Cardiac and ophtalmologic manifestations are very rarely encountered.

[Systemic sclerosis in men]. / Sclérodermie systémique chez l'homme.

PURPOSE: To study the initial clinical features and describe the outcome of systemic sclerosis in a cohort of French men. METHODS: Patients with systemic sclerosis based on Leroy's criteria were included. In this retrospective study we compared a cohort of men to a cohort of women, diagnosed between 1997 and 2005 in departments of internal medicine and rheumatology. RESULTS: One hundred and twenty-one patients were included amongst which thirty-six men. The mean follow-up duration was 6.5 years. The time to diagnosis was significantly shorter in men than in women. Diffuse cutaneous systemic sclerosis, cutaneous ulcers and interstitial syndrome on chest radiograph were more frequent at diagnosis in men than in women. An environmental factor (silica) was observed in only nine men. During the follow-up, incidence of restrictive lung disease was significantly higher in men than in women (37% versus 14% p=0.01) with higher rates of oxygen dependency (22% versus 5% p<0.01). Cumulated survival rates in men were 92% at 5 years, 72% at ten years and 43% at 15 years, respectively. The mean survival was 13 years in men (IC 95%: 10-16) versus 23 years in women (IC 95%: 10-36) with no statistical difference (p=0.27). CONCLUSION: If interstitial and restrictive lung disease, oxygen dependency and diffuse systemic sclerosis were more frequent in men than in women, this data did not provide any evidence of survival difference between men and women with systemic sclerosis.