[Atypical purpuric oedema of the nose during granulomatosis with polyangiitis]. / Un œdème purpurique du nez atypique au cours d'une granulomatose avec polyangéite.

INTRODUCTION: Granulomatosis with polyangeitis or Wegener's disease is a necrotizing vasculitis of small and medium vessels associated with antineutrophil cytoplasmic autoantibodies (ANCA). The most frequent sites are lung, ear, nose and throat and kidney. PATIENTS AND METHODS: We report the case of a 47-year-old woman presenting purpuric oedematous plaque with bullous detachment of the nose and hospitalised for the assessment of two suspicious neoplastic lung lesions discovered as a result of a recent stroke and repeated seromucosal otitis. Granulomatosis with polyangeitis was suspected because of multiple systemic lesions. The histopathology of skin lesions and laboratory investigation results were consistent with this diagnosis. A favourable outcome was achieved with corticosteroids and rituximab. DISCUSSION: The diagnosis of GPA is based on criteria established by the American College of Rheumatology. The cutaneous clinical aspect described in our case confirms the polymorphism of the cutaneous lesions possibly associated with this disease. They are rarely isolated but, in some cases, allow early diagnosis with improved prognosis, which remains severe in the absence of treatment.

[Sarcoid-like granulomatosis associated with eosinophilic fasciitis]. / Fasciite de Shulman associée à un infiltrat granulomateux sarcoïdosique.

BACKGROUND: Eosinophilic fasciitis (EF) is a rare condition characterized by swelling of the extremities, sclerodermatous evolution and frequent hypereosinophilia. Hematological disorders, including aplastic anemia, solid tumors and autoimmune diseases, may be associated with EF. EF is usually not associated with granulomatous diseases. CASE REPORT: Herein we describe the case of an 80-year-old man with symmetrical swelling and sclerosis of the legs, typical of EF, associated with skin and lymph node granulomas. Oral prednisone treatment resulted in complete clinical remission. DISCUSSION: Association of EF and granulomatous disease is uncommon. Our case highlights the possible association of EF with sarcoidosis-like reactions.

[Reversible posterior leukoencephalopathy syndrome in a patient presenting granulomatosis with polyangiitis]. / Syndrome d'encéphalopathie postérieure réversible au cours d'une granulomatose avec polyangéite.

BACKGROUND: Reversible posterior leukoencephalopathy syndrome (RPLS) is characterised by clinical neurological features of sudden onset and brain MRI findings such as T2/Flair white matter hyperintensities. RPLS can occur in autoimmune diseases, and rarely in systemic vasculitis. We report a case of RPLS in a woman presenting granulomatosis with polyangiitis (Wegener's granulomatosis). PATIENTS AND METHODS: A 22-year-old female patient was treated with methylprednisolone pulses for granulomatosis with polyangiitis and neurological impairment. A few hours after the second pulse, the patient had seizures, blindness and confusion associated with high blood pressure and acute renal failure. MRI revealed a high-intensity area on T2-Flair weighted images of the occipital-temporal lobes. The patient was treated with antiepileptic and antihypertensive medications, oral steroids and cyclophosphamide; the clinical and radiological findings proved reversible over the ensuing days. DISCUSSION: The occurrence of RPLS in systemic vasculitis is rare. Six cases of RPLS associated with granulomatosis and polyangiitis have been reported. It appears important to screen for high blood pressure in patients recently treated with corticosteroids for vasculitis as this condition may represent a precipitating factor for RPLS.

[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.

[A rapidly progressive orbital tumor in a seven-year-old girl revealing a primitive systemic vasculitis]. / Une tumeur orbitaire rapidement évolutive chez une fillette de 7 ans révélant une vascularite systémique primitive.

Orbital tumor lesions in pediatric population encompass a wide range of pathological processes, which are very different in etiology and prognosis. They usually require an emergency in histological diagnosis because of their quick growth. Beside malignant and benign tumors, the inflammatory pseudo-tumors group included dysimmune orbital involvement secondary to systemic vasculitis such as granulomatosis with polyangiitis (ex-Wegener's granulomatosis). We report the case of a seven-year-old girl suffering from a severe primitive ANCA vasculitis, revealed by an orbital mass.

[Oral manifestations in Crohn's disease - Two patient cases from the clinic]. / Orale Manifestationen bei Morbus Crohn

Crohn's disease (CD) is an inflammatory disease of the gastrointestinal system. It is suspected to be caused by a combination of genetic and environmental factors and changes in the patient's intestinal microbiome. As opposed to colitis ulcerosa, which usually only affects the large intestine, CD may affect various parts of the gastrointestinal tract. Many patients show oral lesions related to CD, which sometimes can precede the first gastrointestinal symptoms. Specific oral lesions include granulomatous cheilitis, cobblestone-like mucosal tags and linear ulcerations. Non-specific lesions occur in the form of angular cheilitis and opportunistic candidiasis, aphthous ulcerations, reduced salivation, dental caries and many more. We present two cases of patients suffering from Crohn's disease with different oral manifestations and discuss the dentist's role in early detection of specific oral lesions and the importance of the follow-up care of affected patients.

[Pulmonary complications of Chronic Granulomatous Disease]. / Complications pulmonaires de la granulomatose septique chronique.

Chronic Granulomatosis Disease (CGD) is an inherited immune deficiency due to a mutation in the genes coding for the subunits of the NADPH oxidase enzyme that affects the oxidative capacity of phagocytic cells. It is characterized by increased susceptibility to bacterial and fungal infections, particularly Aspergillus, as well as complications associated with hyperinflammation and granulomatous tissue infiltration. There exist two types of frequently encountered pulmonary manifestations: (1) due to their being initially pauci-symptomatic, possibly life-threatening infectious complications are often discovered at a late stage. Though their incidence has decreased through systematic anti-bacterial and anti-fungal prophylaxis, they remain a major cause of morbidity and mortality; (2) inflammatory complications consist in persistent granulomatous mass or interstitial pneumoniae, eventually requiring immunosuppressive treatment. Pulmonary complications recurring since infancy generate parenchymal and bronchial sequelae that impact functional prognosis. Hematopoietic stem cell allograft is a curative treatment; it is arguably life-sustaining and may limit the morbidity of the disease. As a result of improved pediatric management, life expectancy has increased dramatically. That said, new challenges have appeared with regard to adults: difficulties of compliance, increased inflammatory manifestations, acquired resistance to anti-infectious therapies. These different developments underscore the importance of the transition period and the need for multidisciplinary management.

[Paradoxical tuberculosis reaction]. / Réaction paradoxale tuberculeuse.

Paradoxical tuberculosis reaction is defined as the aggravation of lesions present at diagnosis or the development of new lesions under anti-tuberculosis treatment, after exclusion of other alternate causes. It affects 5 to 30% of tuberculosis patients, with a variable prevalence depending on the site of infection and the clinical background. The diagnosis of paradoxical reaction is one of elimination, and requires having ruled out therapeutic failure, notably linked to poor compliance and/or to the presence of mycobacterial antibiotic resistance. The severity of paradoxical tuberculosis reaction lies in its neurological impairment. Despite its clinical importance, the mechanisms involved remain poorly understood and its management is not consensual. Corticosteroids are the cornerstone in the medical management. The role of anti-TNF agents, currently proposed in cases of corticodependence or corticoresistance, remains to be properly defined.

Cardiac valvular involvement in granulomatosis with polyangiitis in long-term observation.

INTRODUCTION AND OBJECTIVES: Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic autoantibody (ANCA)-associated systemic vasculitis and is characterized by inflammation of blood vessels. The aim of the present study was to assess cardiac valvular changes in patients with GPA in a cohort of 105 patients followed for a mean of six years. METHODS: We followed 105 patients (mean age 50.4 years, 67 female) for a mean of 6.2±1.3 years. Echocardiography and laboratory tests were performed in all patients. RESULTS: At baseline, 43% of patients were diagnosed with aortic regurgitation (AR), which was the most common valvular lesion. Moreover, it was the only valvular involvement that significantly increased during observation (p=0.01). In a multivariate model, only D-dimer level was a predictor of AR in this group of patients (OR 8.0 (95% CI: 1.7-38.2, p=0.01). CONCLUSIONS: Involvement of the heart valves is a common finding in patients with GPA, but significant valvular disease is a rare complication. The most common valvular disease in this group of patients is AR. Aortic valves are also the most prone to degeneration in the course of the vasculitis.

[Peripheral neuropathies during systemic diseases: Part I (connective tissue diseases and granulomatosis)]. / Neuropathies périphériques au cours des maladies de système : partie I (connectivites et granulomatoses).

Systemic diseases (connective disease, granulomatosis) may be associated with peripheral neuropathies. The diagnosis can be complex when the neuropathy is the presenting manifestation of the disease, requiring close collaboration between neurologists and internists. Conversely, when the systemic disease is already known, the main question remaining is its imputability in the neuropathy. Regardless of the situation, the positive diagnosis of neuropathy is based on a systematic and rigorous electro-clinical investigation, specifying the topography, the evolution and the mechanism of the nerve damage. Certain imaging examinations, such as nerve and/or plexus MRI, or other more invasive examinations (skin biopsy, neuromuscular biopsy) enable to specify the topography and the mechanism of the injury. The imputability of the neuropathy in the course of a known systemic disease is based mainly on its electro-clinical pattern, on which the alternatives diagnoses depend. In the case of an inaugural neuropathy, a set of arguments orients the diagnosis, including the underlying terrain (young subject), possible associated systemic manifestations (inflammatory arthralgias, polyadenopathy), results of first-line laboratory tests (lymphopenia, hyper-gammaglobulinemia, hypocomplementemia), autoantibodies (antinuclear, anti-native DNA, anti-SSA/B) and sometimes invasive examinations (neuromuscular biopsy).

[Anti-IL-5 in severe asthma associated with eosinophilic granulomatosis with polyangiitis. Real-life study]. / Anti-IL-5 dans l'asthme sévère associé à une granulomatose éosinophilique avec polyangéite. Étude en vie réelle.

INTRODUCTION: Eosinophilic granulomatosis with polyangiitis (EGPA) is a form of necrotizing vasculitis affecting small vessels and typically characterized by severe glucocorticoid (GC)-dependent eosinophilic asthma. While mepolizumab, which is indicated at a dose of 100mg/4weeks in severe eosinophilic asthma, has been shown to be an effective treatment for EGPA-related asthma at a dose of 300mg/4weeks, it was only recently approved at this dose. METHODS: This retrospective, single-center, observational study was conducted to investigate over a 5-year period (2014-2019) the effect of mepolizumab 100mg/4weeks at 12months in patients with EGPA and glucocorticoid-dependant severe asthma. Response to treatment was defined as reduction in daily dose of oral corticosteroids to at most 5mg/day or reduction in annual exacerbation by at least 50%. RESULTS: Thirty patients were included, of whom twenty-three were treated (two were not fully evaluable). Among the 21 evaluable treated patients, 13 (62%) had responded at 12months. At baseline, non-responders had lower FEV1 levels and lower blood eosinophil levels than responders. CONCLUSIONS: Mepolizumab at a "severe asthma" dose (100mg/4weeks) is effective in treatment of GC-dependent severe asthma in most patients with EGPA.

[Characteristics of cardiac involvement in eosinophilic granulomatosis with polyangiitis]. / Caractéristiques de l'atteinte cardiaque au cours de la granulomatose éosinophilique avec polyangéite.

AIM OF THE STUDY: Our study aimed to identify the characteristics of cardiac involvement in eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: We conducted a retrospective analytic study including EGPA cases diagnosed between 2000 and 2019 in an internal medicine department. Diagnosis was made according to the 1990 American College of Rheumatology criteria and the 2012 Chapel Hill Concensus. RESULTS: Eleven EGPA cases were included, 64% of patients were female. Median age at diagnosis was 52 years [42-58]. Heart damage revealed EGPA in 55% of cases with a significant predominance of women (p=0.015). The main cardiac manifestations were myocarditis, ischemic cardiomyopathy due to small vessel vasculitis, cardiac tamponade and intracardiac thrombus. Cardiac magnetic resonance imaging (MRI) mainly showed subendocardial hyposignal in early infusion and late enhancement in the same areas, nodular by locations, associated with impaired left ventricle function and micro-infarctions by distal vasculitis. Cardiac damage was associated to ANCA negativity in 83.3% of cases. The median Birmingham Vasculitis Activity Score version3 (BVAS v3) was 16 [10-17]. Under conventional treatment, no relapses had occurred. The median vasculitis damage index (VDI) was 2 [1-2.3] and the mortality rate was zero after a mean follow-up of 43 months. CONCLUSION: Cardiomyopathy is a frequent revealing mode of EGPA. A late onset asthma and hypereosinophilia should guide the diagnosis. As ANCA research often turns out to be negative, histological evidence is recommended in this context. The contribution of cardiac MRI in the diagnosis of EGPA remains to be defined.

[A Rare Cause of Hypercalcemia]. / Eine seltene Ursache der Hyperkalzämie.

A Rare Cause of Hypercalcemia Abstract. Sarcoidosis is a rare cause of hypercalcemia, which is in most cases caused by primary hyperparathyroidism or a malignant tumor. Other rare causes include vitamin D intoxication, other granulomatous diseases (such as tuberculosis, or fungal infection) or mutiple myeloma. Because of the broad differential diagnosis, a systematic diagnostic approach is crucial to establish the correct diagnosis. Therapeutic measures include volume replacement and subsequent administration of bisphosphonates. If hypercalcemia is caused by sarcoidosis, therapy with systemic corticosteroids is indicated.

[Silica causes difficulties]. / La silice cause des difficultés.

Silicosis and sarcoidosis are two very distinct entities in the literature. All the additional non-invasive examinations, including the chest CT scan, often do not differentiate them. The history, including occupational exposure to identified silica particles, is a discriminating factor. However, due to the pathogenic power of silica, it would be possible to have the simultaneous development of these two pathologies in the same patient. To illustrate this situation, here is the case of a 62-year-old patient, who presented initially with a picture of dyspnea and productive cough. The chest CT showed micronodular peribronchovascular infiltrates and mediastinal lymphadenopathy. The other additional examinations did not find anything specific. In the diagnostic process, the patient had multiple endoscopic samples which did not make it possible to be conclusive on one or the other of these pathologies. He therefore underwent a surgical lung biopsy which revealed histological lesions compatible with the two pathologies. Recent studies suggest that inhaled particles, especially silica, could be responsible for the pattern of sarcoidosis. However, it is difficult to say whether, in this case, silica was responsible for the development of sarcoidosis.

[Bone involvement in cat scratch disease]. / Atteinte osseuse dans la maladie des griffes du chat.

INTRODUCTION: Cat scratch disease caused by Bartonella henselae with bone involvement is a rare presentation. CASE REPORT: We report a case of disseminated bartonellosis with multifocal osteomyelitis and multiple visceral involvement in an immunocompetent adult. Diagnostic confirmation was obtained by PCR on lymphadenopathy. In addition to our observation, 31 cases of bartonellosis with bone involvement were reported in the literature. Diagnosis is based on a combination of history, serology and PCR performed on tissue. The antibiotic treatment allows recovery in all cases. CONCLUSION: Cat scratch disease in its systemic form with bone involvement is a rare and difficult diagnosis for the clinician and an invasive approach is often required to obtain the diagnosis.

[Common variable immunodeficiency disorders: Part 2. Updated clinical manifestations and therapeutic management]. / Les déficits immunitaires communs variables (DICV) : partie 2. Mise à jour clinique et thérapeutique.

Common variable immunodeficiency disorders (CVID) are the most common symptomatic primary antibody deficiency in adults with an estimated prevalence of 1/25,000. The most frequent clinical manifestations are upper respiratory tract infections (including pneumonia, bronchitis, and sinusitis) predominantly with Streptococcus pneumoniae or H. influenzae. However, CVID are complicated in 20 to 30 % of cases of non-infectious manifestations which have been well characterized in recent years. Several complications can be observed including autoimmune, lymphoproliferative, granulomatous or cancerous manifestations involving one or more organs. These complications, mostly antibody-mediated cytopenias, are correlated with a decrease in the number of circulating switched memory B cells. Replacement therapy with polyvalent gammaglobulins has greatly improved the prognosis of these patients but it remains poor in the presence of digestive complications (especially in the case of chronic enteropathy and/or porto-sinusoidal vascular disease), pulmonary complications (bronchiectasis and/or granulomatous lymphocytic interstitial lung disease) and when progression to lymphoma. Much progress is still to be made, in particular on the therapeutic management of non-infectious complications which should benefit in the future from targeted treatments based on knowledge of genetics and immunology.

[Rare Forms of Mastitis]. / Entzündliche Brusterkrankungen: Klinik und Diagnostik der seltenen Mastitis-Formen.

Rare Forms of Mastitis Abstract. Inflammatory breast diseases caused by bacterial infections represent the main cause for mastitis in breastfeeding and non-breastfeeding women. The clinical appearance and a standardized evaluation can indicate rare inflammatory breast diseases. An underlying comorbidity or the evidence of rare pathogens could be suggestive. However, core needle biopsy is the main step in diagnostics. Malignancy, e.g. an inflammatory breast cancer must consistently be excluded. This mini review outlines a few rare inflammatory breast diseases, their initial presentation, and how to diagnose them accurately.

[A perimyocarditis revealing eosinophilic granulomatosis with polyangiitis]. / Une périmyocardite révélatrice d'une granulomatose éosinophilique avec polyangéite : une nouvelle observation.

Churg-Strauss syndrome (CSS) or eosinophilic granulomatosis with polyangiitis is a systemic vasculitis characterized by necrotizing arteritis, eosinophilic infiltration and extravascular granuloma; that may involve several organs. Cardiac involvement is the first cause of death in this vasculitis. These include myocarditis, pericarditis, coronary heart disease, dysrhythmias, and rarely valvular involvement. We report the observation of CSS revealed by acute perimyocarditis.

[Diagnostic difficulties of chronic pulmonary berylliosis in France]. / Difficultés diagnostiques de la bérylliose pulmonaire chronique en France.

INTRODUCTION: The epidemiology of chronic beryllium disease (CBD) in France is poorly understood. The aim of this study was to determine the number of prevalent cases of CBD in France between 2010 and 2014. METHODS: We conducted a national survey using a specific questionnaire distributed by the professional pathology services. RESULTS: In total, 33 CBD cases were reported in France, with a diagnosis established between 1982 and 2014. 85% (28/33) of CBD cases resulted from professional exposure and mostly concerned foundry workers (39%). A definite diagnosis defined by the association of an abnormal beryllium lymphocyte proliferation test and of a granulomatous inflammatory response in the lung, was obtained in 29/33 cases (88%). The other cases were probable CBD, defined by a granulomatous lung disease with a beryllium exposure, but without evidence of beryllium sensitisation. The diagnosis of granulomatous disease was confirmed a mean of 4 years after the end of exposure. The median delay between diagnosis of a granulomatous disease and diagnosis of CBD was 2 years (range 0-38 years). A genetic predisposition was found in 14 of 17 tested patients (82%). CONCLUSION: In this study, we report 33 cases of CBD followed in France between 2010 and 2014. The poor understanding of CBD and the exposure leading to it, the late development after the end of exposure, the complexity of the diagnosis and the similarities with sarcoidosis may explain the small number of cases reported.