[Bilateral periostitis and arthritis: about a case of hypertrophic osteoarthropathy]. / Périostite bilatérale et polyarthrite : à propos d'un cas d'ostéoarthropathie hypertrophique pneumique.

We report the case of a 67-year-old female patient presenting swelling of the hands and feet and pain in both legs. Clinical examination and bone scintigraphy identify the triad "digital clubbing - arthritis - bilateral periostitis of the long bones", leading to a diagnosis of hypertrophic osteoarthropathy, a syndrome usually associated with pulmonary neoplasia. The thoracic CT-scan, followed by a biopsy, effectively diagnosed a right upper lobe adenocarcinoma. Surgical treatment of the neoplasia allowed the resolution of the clinical complaints and the pathological scintigraphic findings.

Nous rapportons le cas d'une patiente de 67 ans présentant des gonflements des mains et des pieds ainsi que des douleurs des deux jambes. L'examen clinique et la scintigraphie osseuse identifient la triade «hippocratisme digital - arthrites - périostite bilatérale des os longs¼, permettant de poser un diagnostic d'ostéoarthropathie hypertrophique, un syndrome habituellement associé à une néoplasie pulmonaire. Le scanner thoracique, suivi d'une biopsie, ont en effet diagnostiqué un adénocarcinome localisé au niveau du lobe supérieur droit. La prise en charge chirurgicale de la néoplasie a permis la résolution des plaintes cliniques et de l'aspect scintigraphique pathologique.

[Life-threatening flare of an underlying «paraneoplastic¼ dermatomyositis in a patient with lung adenocarcinoma treated with anti-PD-1 pembrolizuma]. / Poussée sévère d'une dermatomyosite pré-existante chez une patiente avec un adénocarcinome pulmonaire traité par pembrolizumab, un anti-PD-1.

Dermatomyositis is an autoimmune disease mainly characterized by muscle and skin involvement. Its association with cancer is known but the term «paraneoplastic¼ remains debated. We report here the case of a 71-year-old woman with a new diagnosis of dermatomyositis with, at the same time, the discovery of a lung adenocarcinoma. Lung cancer was treated with pembrolizumab, an immune checkpoint inhibitor directed against the "Programmed cell Death protein 1" (PD-1) receptor. Three weeks later, the patient presented a severe flare of dermatomyositis. Administration of intravenous corticosteroids and infliximab were ineffective. Intravenous immunoglobulins were then administered, followed by subcutaneous methotrexate, with a progressive positive evolution. Flares of pre-existing autoimmune diseases are observed under immune check point inhibitors, even when the evolution of the cancer is favourable. These immune-related adverse events are often «mild to moderate¼ and severe immune related side effects are not more frequent when the patient has a pre-existing autoimmune disease. Treatment can be maintained in the majority of cases. However, as demonstrated in this clinical case, although immune checkpoint inhibitors are not contraindicated in autoimmune diseases, the presence of myositis requires special attention given the potential severity of flares.

: La dermatomyosite est une maladie auto-immune principalement caractérisée par une atteinte musculaire et cutanée. Son association avec le cancer est connue, mais le terme «paranéoplasique¼ reste débattu. Nous rapportons ici le cas d'une patiente de 71 ans avec un nouveau diagnostic de dermatomyosite et, au même moment, la découverte d'un adénocarcinome pulmonaire. La néoplasie pulmonaire a été traitée par pembrolizumab, un inhibiteur des points de contrôle immunitaire dirigé contre le récepteur «Programmed cell Death protein 1¼ (PD-1). Trois semaines plus tard, la patiente présentera une poussée sévère de dermatomyosite, ne répondant pas à la corticothérapie intraveineuse ni à l'infliximab. Des immunoglobulines intraveineuses sont alors administrées, suivies de méthotrexate sous-cutané, avec une évolution progressivement positive. On observe des poussées de maladies auto-immunes préexistantes sous inhibiteurs de points de contrôle immunitaire, même quand l'évolution néoplasique est favorable. Ces effets secondaires immuno-induits sont souvent «légers à modérés¼ et on n'observe pas plus de manifestations indésirables «sévères¼ lorsque le patient présente une maladie auto-immune pré-existante. Le traitement peut être maintenu dans la majorité des cas. Toutefois, comme démontré dans ce cas clinique, bien que les inhibiteurs de points de contrôle immunitaire ne soient pas contre-indiqués en cas de maladie auto-immune, la présence d'une myosite nécessite une attention particulière vu la gravité potentielle des poussées.

[Remarkable medical advances in rheumatology : may be ]. / Une révolution thérapeutique en rhumatologie : oui, mais .

The development of new drugs is a significant activity in a university hospital that favors access to therapeutic novelties to patients. Rheumatology, whose drug armamentarium was poor in the 1980s, has benefited from the huge progresses of immunology in the 1980-1990s, allowing a therapeutic revolution in whom the academic hospital of Liège (CHU Liège) has been strongly implicated. First protocols with anti-TNF-? monoclonal antibodies have been applied in 1997. Sixty-one protocols have been initiated in rheumatoid arthritis, 12 in ankylosing spondylitis, 10 in psoriatic arthritis, 9 in systemic erythematosus lupus, 3 in giant cell arteritis, 1 in polymyalgia rheumatica, 5 in osteoarthritis and 4 in osteoporosis. Potential and pitfalls will be discussed disease by disease and also by drug categories. The balance remains globally positive, but remission is far from be reached.

La recherche clinique médicamenteuse est une activité importante dans un hôpital universitaire. Elle valide des nouveautés thérapeutiques et fait bénéficier les patients de traitements novateurs bien avant leur mise sur le marché. La rhumatologie est une discipline dont l'arsenal thérapeutique était pauvre dans les années 1980, et les immenses progrès de l'immunologie, réalisés entre 1980 et 1995, lui ont permis de vivre une véritable révolution thérapeutique à laquelle notre service a amplement participé. C'est en 1997 que les premiers traitements par anticorps monoclonaux anti-TNF-? (les traitements dits biologiques) ont été utilisés au CHU de Liège. Soixante et une études seront initiées dans la polyarthrite rhumatoïde, 12 dans la spondylarthrite ankylosante, 10 dans la polyarthrite psoriasique, 9 dans le lupus érythémateux disséminé, 3 dans l'artérite temporale de Horton, une dans la pseudopolyarthrite rhizomélique, une dans la sclérodermie, 5 dans l'arthrose, 4 dans l'ostéoporose. Les espoirs et les déceptions observées dans les différentes indications, et avec les différentes molécules, sont analysées. Le bilan est globalement positif, mais les résultats encore insuffisants que pour arriver au concept de rémission.

[Congenital heart block revealing a maternal systemic disease : pathophysiology and therapeutic approaches]. / Bloc auriculoventriculaire congénital révélateur d'une pathologie maternelle systémique : physiopathologie et approches thérapeutiques.

Immunologic congenital atrioventricular block is due to the presence of anti-SSA and anti-SSB antibodies in maternal blood. This pathology is often diagnosed when the status is irreversible and is consequently associated with a high morbi-mortality. Close monitoring for high risk pregnancies can help to diagnose first and second degrees heart block and treatments can be offered when the block is still reversible. Fluorocorticoids, betamimetics and hydroxychloroquine use is not consensual. Studies are still in progress to prove their utility. We report the antenatal managing of a patient in which Goujerot-Sjögren disease was diagnosed after the revealing of an atrioventricular block in her fetus. After a brief physiopathological description, we present the current knowledge in preventive and curative treatments.

Le bloc auriculoventriculaire congénital d'origine immunologique est lié à la présence dans le sang maternel d'anticorps anti-SSA et anti-SSB. Le diagnostic est le plus souvent posé à un stade irréversible et est alors associé à une morbi-mortalité importante. La surveillance rapprochée des grossesses à risque permet de diagnostiquer des blocs de premier et deuxième degré et de proposer des traitements à un stade réversible de la maladie. L'utilisation de corticoïdes fluorés, de bêtamimétiques et de l'hydroxychloroquine n'est pas consensuelle. Des études sont toujours en cours pour valider leur utilité. Nous rapportons la prise en charge anténatale d'une patiente chez qui le diagnostic de syndrome de Goujerot-Sjögren a été posé suite à la découverte d'un bloc auriculoventriculaire chez son fœtus. Après un bref rappel physiopathologique, nous exposons l'état actuel des connaissances en ce qui concerne les traitements préventifs et curatifs.

Restriction of spontaneous and prednisolone-induced leptin production to dedifferentiated state in human hip OA chondrocytes: role of Smad1 and ß-catenin activation.

OBJECTIVE: The aetiology of OA is not fully understood although several adipokines such as leptin are known mediators of disease progression. Since leptin levels were increased in synovial fluid compared to serum in OA patients, it was suggested that joint cells themselves could produce leptin. However, exact mechanisms underlying leptin production by chondrocytes are poorly understood. Nevertheless, prednisolone, although displaying powerful anti-inflammatory properties has been recently reported to be potent stimulator of leptin and its receptor in OA synovial fibroblasts. Therefore, we investigated, in vitro, spontaneous and prednisolone-induced leptin production in OA chondrocytes, focusing on transforming growth factor-ß (TGFß) and Wnt/ß-catenin pathways. DESIGN: We used an in vitro dedifferentiation model, comparing human freshly isolated hip OA chondrocytes cultivated in monolayer during 1 day (type II, COL2A1 +; type X, COL10A1 + and type I collagen, COL1A1 -) or 14 days (COL2A1 -; COL10A1 - and COL1A1+). RESULTS: Leptin expression was not detected in day1 OA chondrocytes whereas day14 OA chondrocytes produced leptin, significantly increased with prednisolone. Activin receptor-like kinase 1 (ALK1)/ALK5 ratio was shifted during dedifferentiation, from high ALK5 and phospho (p)-Smad2 expression at day1 to high ALK1, endoglin and p-Smad1/5 expression at day14. Moreover, inactive glycogen synthase kinase 3 (GSK3) and active ß-catenin were only found in dedifferentiated OA chondrocytes. Smad1 and ß-catenin but not endoglin stable lentiviral silencing led to a significant decrease in leptin production by dedifferentiated OA chondrocytes. CONCLUSIONS: Only dedifferentiated OA chondrocytes produced leptin. Prednisolone markedly enhanced leptin production, which involved Smad1 and ß-catenin activation.

[Depression as a common complication of systemic lupus erythematosus]. / La vignette diagnostique de l'etudiant. La dépression est une complication fréquente du lupus érythémateux disséminé: considérations épidémiologiques, pathogéniques et thérapeutiques.

Systemic lupus erythematosus (SLE) is an inflammatory disease with multiple and disabling consequences, including the psychological status. The prevalence of major depressive episodes among patients suffering from SLE is significantly higher than in healthy people, or people suffering from other inflammatory diseases. While it is obvious that its chronic disease status with a frequently pejorative ending, as well as the number of treatments it requires, are contributing factors, it is likely that due to its pathogenic mechanisms, SLE causes direct injury to the brain, leading to a depressive symptomatology. Numerous hypotheses are under consideration. We shall review them all, recall a few epidemiologic features, add histology and medical imaging contributions and discuss the importance of setting up a fitting therapy for such patients.

[The management of systemic lupus erythematosus with biological therapies]. / Traitement du lupus érythémateux dissémine par les médicaments biologiques.

The efficacy and safety of targeted biological therapies have been analyzed in patients suffering from systemic lupus erythematosus. In renal lupus, infliximab has shown prolonged improvement of the renal function after the induction period (small open studies), whereas abatacept had no significant efficacy (randomised controlled study). In renal and non renal lupus, rituximab did not confirm its efficacy in two randomised controlled studies. In non renal lupus, epratuzumab has shown efficacy in a phase IIb. Belimumab at the high posology of 10 mg/kg has also shown significant efficacy in two large randomised controlled studies.

[Genetic and environmental interactions on the development of rheumatoid arthritis]. / Interactions de la génétique et de l'environnement sur le développement de la polyarthrite rhumatoïde.

Rheumatoid arthritis (RA) more and more becomes a syndrome, rather than a disease, with genetic, hormonal and environmental influences, among which smoking and the microbiota generate focused interest. The shared epitope and PTPN22 loci are associated with RA, and, particularly, with the "classical" form with anti-citrullinated peptide antibodies (ACPA) and IgM-rheumatoid factor (IgM-RF) positivity. Pregnancy is associated with a--temporary--remission of RA. Epidemiological studies have shown that oral contraception, parity and hormonal replacement therapy influence the severity of RA, and, this is still discussed, its incidence. Smoking is the first environmental factor strongly associated with RA, specifically with the shared epitope and with ACPA. The study of the microbiota is a novel emerging field that will help us to better understand patterns and evolution of RA.

[Rhupus: when rheumatoid arthritis meets lupus]. / Le rhupus: à la frontière entre polyarthrite rhumatoïde et lupus érythémateux disséminé.

There exists diseases in rheumatology fulfilling classification criteria for either rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). They are called "rhupus". We retrospectively analyzed the data base "GLIMS" of the CHU de Liège from the starting date of november 2005 until april 2011 to identified those patients that were positive for the anti-sDNA antibody marker of SLE and for the anti-CCP antibody, marker of RA. Fourteen patients were identified and two other patients were added, one suffering from SLE, and the other from RA, and likely to be rhupus. Of the 16 patients analyzed, 9 were real RA with anti-dsDNA antibodies induced by anti-TNF-alpha therapies. Seven were candidates to be rhupus and 6 were retained. They were all women, with a median age of 51 years and in addition were all anti-SS-A antibody positive.

[Retroperitoneal mass in children : clinical cases of Wilms tumor and neuroblastoma]. / Le cas clinique du mois. Les masses rétropéritonéales chez l'enfant : a propos d'une tumeur de Wilms et d'un neuroblastome.

Detection of a retroperitoneal mass in children needs a fast and accurate exploration. We present the case-reports of 2 children under the age of 5 years admitted to the University Hospital of Liège, one with a Wilms tumor and one with a neuroblastoma.

[Exploring . . . a retroperitoneal mass in children]. / Comment j'explore ... une masse retroperitoneale chez l'enfant.

Detection of a retroperitoneal mass in children needs a fast and accurate exploration. Wilms tumor and neuroblastoma, the most frequent, will be presented more in detail including their clinical and biological characteristics, their diagnostic tests and their primary therapeutic treatments.

[Non-hormonal treatments of postmenopausal osteoporosis]. / Traitements non hormonaux de l'ostéoporose postménopausique.

In the last decade, several medications have been registered and marketed in osteoporosis. They have demonstrated their antifracture efficacy. Subsequently, the clinical management of osteoporosis becomes more sophisticated and complex. Bisphosphonates (alendronate, risedronate, ibandronate, ibandronate and zoledronate) have demonstrated their efficacy on the axial and appendicular skeleton. On scientific grounds, it seems difficult to distinguish between them, in terms of efficacy and/or safety. A special interest should be focused on the optimisation of patients' adherence, which remains poor with the daily and weekly formulations. Raloxifene, a selective estrogen receptor modulator, has shown antifracture efficacy at the level of the lumbar spine and, also, exerts collateral benefits on the breast. The peptides from the parathyroid hormone family are simulators of bone formation. They showed antifracture efficacy at the axial and appendicular skeleton. Due to their prohibitive costs, their use should be restricted to patients with severe osteoporosis. Strontium ranelate, with its unique mode of action combining inhibition of bone resorption and stimulation of bone formation, is characterized by a wide scatter of activity, both in terms of skeletal sites positively affected and of patients experiencing benefits of its administration. Currently, it is the only drug which has shown an extensive anti-fracture efficacy in elderly subjects over 80 years old.

Unusual presentation of osteopoikilosis.

We present a case of osteopoikilosis in a 74-year-old woman with hip pain, presenting multiple osteoblastic lesions of the axial skeleton including an osteoblastic large lesion of her left femur. The imaging findings on X-rays and computed tomography are provided along with the discussion of the differential diagnosis on the basis of the recent literature.

Strontium ranelate in the prevention of osteoporotic fractures.

Osteoporosis results from a decrease in bone strength yielding increased susceptibility to fractures. Hip and spine fractures are a major cause of morbidity and mortality in the elderly population. With an increasingly ageing world population, early prevention of bone loss is essential for adequate control of this condition. Strontium ranelate (PROTELOS((R))), an oral drug for postmenopausal osteoporosis, has been reported to decrease bone resorption and to stimulate bone formation. The efficacy in reducing vertebral fractures, non-vertebral including hip fractures, and the safety of strontium ranelate has been initially demonstrated over 3 years in the SOTI (Spinal Osteoporosis Therapeutic Intervention) and TROPOS (TReatment Of Peripheral OSteoporosis) studies and confirmed recently over up to 5 years. A preplanned analysis of a sub-group of patients aged 80 years and over showed that, currently, strontium ranelate is the only antiosteoporotic agent to reduce vertebral and non-vertebral fractures in this age group.

Prevalence of vitamin D inadequacy in European postmenopausal women.

OBJECTIVE: Inadequate vitamin D level is associated with secondary hyperparathyroidism and increased bone turnover and bone loss, which in turn increases fracture risk. The objective of this study is to assess the prevalence of inadequate serum vitamin D levels in postmenopausal European women. There are no clear international agreements on what constitutes a level of vitamin D inadequacy, but recent publications suggest that the circulating level of vitamin D should be over 80 nmol/L or at least between 50 and 80 nmol/L. MATERIAL AND METHODS: Assessment of 25-hydroxyvitamin D [25(OH)D] was performed in 8532 European postmenopausal women with osteoporosis or osteopenia. European countries included France, Belgium, Denmark, Italy, Poland, Hungary, United Kingdom, Spain and Germany. Two cut-offs of 25(OH)D inadequacy were fixed : < 80 nmol/L and < 50 nmol/L. RESULTS: Mean (SD) age of the patients was 74.2 (7.1) years, body mass index was 25.7 (4.1) kg/m(2). Level of 25(OH)D was 61.0 (27.2) nmol/L. There was a highly significant difference of 25(OH)D level across European countries (p < 0.0001). The lowest level of 25(OH)D was found in France [51.5 (26.1) nmol/L] and the highest in Spain [85.2 (33.3) nmol/L]. In the whole study population, the prevalence of 25(OH)D inadequacy was 79.6% and 32.1% when considering cut-offs of 80 and 50 nmol/L, respectively and when considering patients aged less than 65 years, the prevalence reached 86% (cut-off of 80 nmol/L) and 45% (cut-off of 50 nmol/L). CONCLUSION: This study indicates a high prevalence of vitamin D [25(OH)D] inadequacy in European postmenopausal women. The prevalence could be even higher in some particular countries. A greater awareness of the importance of vitamin D inadequacy is needed to address this public health problem.