[When rhinosinusitis reveals a systemic disease]. / Quand la rhinosinusite révèle une pathologie systémique.

This retrospective analysis is concerned with 10 patients suffering from granulomatosis with polyangitis (GPA, Wegener's disease), who were followed up in a tertiary care Ear, Nose, and Throat (ENT) department. The inaugural events took place in the ENT field (8 patients), the lung (2 patients), the vestibule (1 patient), or the oral cavity (1 patient). The ENT manifestations during the disease evolution involved the rhinologic (osetocartilaginous--6 cases; mucosal--9 cases), the otologic (3 cases), or the laryngeal area (2 cases). Facial pain was noted in 6 cases and residual hyposmia in 5. We observed 5 cases of lung involvement, 3 cases of renal involvement, and 4 cases of ocular involvement. An aseptic meningitis was seen in 1 case and the muscles were affected in 6 cases. The average delay between symptom onset and diagnosis was 26 months. Endoscopy, imaging techniques, and determination of antineutrophil antibodies (ANCA) were used to reach the diagnosis. Sinus biopsies were contributive in 6 cases. The patients were treated with immunosuppressive drugs and/or surgery. After treatment, remission was obtained in 6 patients.

[Hypercalcemia and acute renal failure: a case report of vitamin D intoxication]. / Le cas clinique du mois. Hypercalcémie et insuffisance rénale aiguë: un cas clinique d'intoxication à la vitamine D.

Vitamin D (VTD) deficiency has become a topical issue leading to screening with frequent supplementation. The latter can be dangerous and exceptionally causes overdoses. We report the case of a 20 year old patient with abdominal pain in the setting of hypercalcemia due to intoxication by VTD. This case offers the opportunity to describe the differential diagnosis of hypercalcemia and to brownse through the literature in search of clinical practice recommendations for VTD supplementation.

[Mixed connective tissue disease in childhood: report of two clinical cases]. / Les connectivites mixtes chez l'enfant: illustration par deux cas cliniques.

Sharp's syndrome, or mixed connective tissue disease, is an autoimmune chronic disease characterized by a tissue collagen abnormality. It is more common among young women, but is also described in children. The symptomatology may be different from one case to another as shown in the two presented cases. Signs and symptoms of other rheumatic diseases are commonly observed. The presence of anti-RNP antibody is requested to confirm the diagnosis. The treatment is adapted to each individual. Non-steroidal anti-inflammatory drugs, corticosteroids, and immunosuppressive drugs are the basis of treatment.

[Clinical case of the month. Adult onset Still's disease: a rare cause of acute febrile hepatitis]. / Le cas clinique du mois. La maladie de still de l'adulte: une cause rare d'hépatite aiguë fébrile.

A 63-year-old woman was hospitalized for the third time in one year for asthenia, fever and chills, jaundice, cytolysis and cholestasis. An adult onset Still's disease was diagnosed. Hepatic manifestations, diagnostic criteria and efficient therapy of AOSD will be reviewed.

[Horton's disease and extra-temporal vessel locations: role of 18FDG PET scan. Report of 3 cases and review of the literature]. / Maladie de Horton et atteintes artérielles extratemporales: utilité de la tomographie par émission de positons au 18FDG. A propos de trois observations et d'une revue de la littérature.

PURPOSE: We report three cases of Horton's disease, in which F18-Fluorine-2-Deoxy-D-Glucose (18FDG) positron emission tomography (PET) demonstrated a clinically unsuspected extra-cranial vessels hypermetabolism. METHODS: Fully corrected whole-body PET was performed in three patients (two women, one man) for exploring a marked inflammatory syndrome. Scanning was acquired 60 min after i.v. injection of 222 MBq of 18FDG in average. RESULTS: In two patients with histologically proven Horton's disease, PET alone showed increased glucose metabolism involving the carotid and sub-clavian arteries as well as the ascending aorta, aortic arch, thoracic and abdominal aorta, and the iliac and femoral arteries. In the third patient, by detecting cervical, thoracic and abdominal vessel hypermetabolism, PET non-invasively contributed to the diagnosis of giant cell arteritis. All patients had complete clinical and biological response to corticoids. PET controls performed 3- to 6-months post-treatment, confirmed the disappearance of the metabolic stigma. CONCLUSION: 18FDG PET may show an increased glucose metabolism in asymptomatic extracranial vessels locations of Horton's arterities. If these observations are confirmed on controlled trials, PET could be particularly useful for non-invasive diagnosing, staging and monitoring atypical clinical forms of Horton's disease. The metabolic imaging could also contribute to a better understanding of the pathogenesis of GCA.

[Chronic thoracic pain]. / Une dorsalgie malheureusement tenace.

The etiological diagnosis of chronic thoracic pain is wide, from benign mechanical disorders to tumors. Reaching the exact diagnosis in often time consuming. Despite the availability of new techniques of imagery, a meticulous clinical history and physical examination remain mandatory. They will lead the exploration. Idiopathic intercostal neuralgia does not exist.

[Still's disease in the adult]. / La maladie de Still de l'adulte.

The Adult Onset Still's Disease (AOSD) is an entity of unknown origin characterised by fever, polyarthralgias or polyarthritis, a pharyngitis, a cutaneous eruption and elevation of leucocytes. We present observations of 17 patients diagnosed during the last thirteen years. Files of hospitalized patients with suspected AOSD have been examined in a retrospective study and Yamaguchi and Kahn's criterias applied in order to confirm the diagnosis. Treatments undertaken and the evolution have been noted. The sex ratio is 1.83; the middle age of intervening from 42 to 45 years. The middle delay for the diagnosis is 3 to 8 weeks. Fever, eruption and polyarthralgias are the most frequent clinical signs. Elevation of leucocytes, hepatic cytolysis and hyperferritinemia are usual. Constantly, inflammatory tests are increased and the rheumatoid factor and the antinuclear antibodies are negative. Yamaguchi's criterias have been met by all patients. The non steroïd anti-inflammatory drugs and corticoïds constituted the main treatment. In the evolutionary shield, 6 cases of remission have been noted. The other patients evolved toward the chronicity with either a systemic or an articular shape. In the two situations, a state of corticodependance got settled with necessity of association to immunosuppressive drugs. The diagnosis of AOSD is easily done on basis of Yamaguchi's criterias. Corticoïds can permit to control the bouts. There are 3 types of evolution: remission, chronic systemic or chronic articular shape.

[Corneal ulcers associated with rheumatoid arthritis]. / Les ulcères de cornée associés à la polyarthrite rhumatoïde.

Keratoconjonctivitis sicca, scleritis and keratitis remain the major ocular manifestation, associated with rheumatoid arthritis. Corneal ulcers are a rare complication but can lead to perforation. Unstable epithelial barrier and immune disorders play a key role in the pathophysiology of such corneal melting. Moreover the association with systemic vasculitis reveals the need for an appropriate immunosuppressive treatment. New surgical approaches and early immunotherapy allow to maintain ocular integrity even if the visual prognosis is poor.

Laboratory and imaging studies used by French rheumatologists to determine the cause of recent onset polyarthritis without extra-articular manifestations.

BACKGROUND: The cause of recent onset polyarthritis can be difficult to identify. OBJECTIVE: To determine which laboratory and imaging studies French rheumatologists recommend, not taking cost into account, for the diagnosis of recent onset polyarthritis without extra-articular manifestations. METHODS: From the list of the French Society for Rheumatology, a random sample of 210 rheumatologists was selected, who were asked to complete a questionnaire on the laboratory and imaging studies they would recommend in two fictional cases of recent onset polyarthritis (possible rheumatoid arthritis (RA)-case 1 and probable RA-case 2). RESULTS: In case 1, the following were recommended by over 75% of respondents: hand radiographs, rheumatoid factors (RFs), and antinuclear antibodies (ANA) (92%, 98%, and 98%, respectively). 50-74% of respondents recommended radiographs of the feet, knees, and chest (50%, 57%, and 66%, respectively); blood cell counts, erythrocyte sedimentation rate (ESR), serum assays of C reactive protein (CRP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (65%, 74%, 67%, and 62%, respectively). 25-49% recommended determination of creatinine and proteinuria, HLA-B27, antikeratin antibody, radiographs of the pelvis, and synovial fluid analysis. Several investigations were recommended less often in case 2 than in case 1. Nevertheless, some laboratory and imaging studies (radiographs of hand, feet, knees, chest x rays, blood cell counts, ANA, RF, antikeratin antibody, CRP, ESR, creatinine, AST and ALT, proteinuria, and joint aspiration) were recommended by more than 25% of respondents in both cases. CONCLUSION: Wide variations were found among rheumatologists, indicating a need for standardisation. Some laboratory and imaging studies are recommended by at least 25% of respondents in recent onset polyarthritis with or without clues suggesting RA. In contrast, many tests were considered useful by fewer than 25% of the respondents in both cases.

Increased synovial fluid levels of interleukin-12, sCD25 and sTNF-RII/sTNF-RI ratio delineate a cytokine pattern characteristic of immune arthropathies.

The assessment of cytokines and their soluble receptors in the synovial fluid (SF) of inflammatory arthropathies may be useful in studying pathogenetic and immunoregulatory mechanisms underlying different diseases. The aim of this work was to study the cytokine network occurring in inflammatory arthropathies and to identify a cytokine profile which is characteristic of an immune-mediated synovitis. Levels of IL-12, as well as IL-4, IL-8, IL-10, IFN-gamma, sCD25, TNF-alpha and its soluble receptors were measured in the SF of various arthropathies, i.e. non-inflammatory arthropathies: "control" meniscus pathology (n = 21), osteoarthritis (n = 22) and chronic crystal arthritis (n = 9); a non-immune inflammatory arthropathy: acute crystal arthritis (n = 11); 2 immune inflammatory arthropathies: reactive arthritis (ReA) (n = 23) and rheumatoid arthritis (RA) (n = 44). SF levels of IL-10, TNF-alpha and sTNF-RII were found to be increased in the three inflammatory arthropathies compared to the "control" meniscus group. Within the inflammatory group, acute crystal arthritis was characterized by a significantly higher sTNF-RI/TNF-alpha ratio and ReA by a significantly lower sTNF-RII/TNF-alpha ratio compared to the two other diseases. The two immune arthropathies, RA and ReA, were characterized by increased SF levels of IL-12, sCD25 and of the sTNF-RII/sTNF-RI ratio. ReA differed however from RA by showing lower IL-8 and IL-4 levels, higher IFN-gamma levels and a higher IL-12/IL-10 ratio, suggesting a more prevalent Th1 profile in ReA SF. Our data indicate that the measurement of SF cytokines and soluble receptors may discriminate between each inflammatory arthropathy and might be useful in clinical practice.

Effective treatment of Jo-1-associated polymyositis with T-cell-depleted autologous peripheral blood stem cell transplantation.

A patient with Jo-1 antibody-associated polymyositis (Jo-1 PM) had a Karnofsky score of 40% and severe muscle, liver and lung damage that was refractory to standard therapy. The female patient received an autologous T-cell-depleted haematopoietic stem cell transplant (HSCT) after myeloablative conditioning. The transplant procedure was complicated by severe adult respiratory distress syndrome (ARDS) and adenovirus-associated haemorrhagic cystitis as well as cytomegalovirus (CMV) reactivation. The patient's creatinine phosphokinase (CPK) and alanine transaminase (ALT) values were normal on day 21. The patient's strength has improved remarkably and her dyspnoea is subjectively improved. At 15 months after the transplant, the patient was well with a Karnofsky score of 80% and had been off any therapy, including steroids, for 14 months.

Matrix metalloproteinase-3 serum levels are correlated with disease activity and predict clinical response in rheumatoid arthritis.

OBJECTIVE: To demonstrate that serum matrix metalloproteinase-3 (MMP-3) is a variable associated with disease activity and with the response to treatment in rheumatoid arthritis (RA). METHODS: Serum MMP-3 levels were measured and compared to biological and clinical disease activity variables in 20 patients with active RA assessed serially during a one year prospective open label trial with methotrexate or tenidap. RESULTS: MMP-3 levels were significantly correlated with C-reactive protein (CRP) and interleukin 6 serum levels as well as with the disease activity score (DAS), not only at start in untreated patients but also during the 12 month followup period in both treated groups. Early changes (after 0.5, 1, 2, or 3 months) in MMP-3 levels were significantly associated with change in DAS observed 4 to 6 months later. CONCLUSION: In addition to CRP, a systemic marker of inflammation, serum MMP-3 may serve as a consistent synovial derived marker of RA disease activity, early changes of which predict disease outcome.

Increased synovial fluid levels of soluble CD23 are associated with an erosive status in rheumatoid arthritis (RA).

Synovial fluid (SF) levels of soluble CD23 (sCD23) were determined in 96 patients presenting with an inflammatory knee effusion (73 with RA and 23 with reactive arthritis (ReA) serving as a control inflammatory non-erosive group) and were correlated with the degree of joint destruction, with local immune parameters (IL-1beta, IL-3, IL-4, IL-6, IL-8, IL-10, IL-12 and sCD25) and with serum markers of inflammation, C-reactive protein and erythrocyte sedimentation rate. RA patients, classified as erosive or not according to Larsen's grade, were separated as follows: (i) 13 patients with non-erosive RA; (ii) 16 RA patients with erosions in hands but not in knees, matched for disease duration with the first group; (iii) 44 RA patients with hand and knee erosions, matched with the second group for rheumatoid factor positivity but of longer disease duration. SF sCD23 levels were significantly increased in both erosive RA groups compared with non-erosive diseases, whether RA or ReA (P < 0.05), whose SF levels were not different. SF IL-10 showed a similar profile to that of SF sCD23 and was the only other parameter characteristic of erosive RA, but no direct correlation was found between the two. SF sCD23 was significantly correlated with IL-12 (r = 0.65, P = 0.0001) and sCD25 (r = 0.39, P = 0.0019) exclusively in the two erosive RA populations. In conclusion, these data showing that increased levels of sCD23 are not only found in the SF of erosive joints but also in knee SF of patients with erosive RA but without knee x-ray-diagnosed erosions suggest that this parameter might be of predictive value for joint destruction. Longitudinal studies are however needed to confirm its potential clinical interest.

Synovial fluid matrix metalloproteinase-3 levels are increased in inflammatory arthritides whether erosive or not.

OBJECTIVE: To study the levels of matrix metalloproteinase-3 (MMP-3) in the knee synovial fluid (SF) of inflammatory arthropathies (rheumatoid arthritis whether erosive or not, reactive arthritis, acute crystal arthritis) and degenerative arthropathies [chronic crystal disease, osteoarthritis and (control) meniscus pathology] and to correlate them with the degree of joint destruction, local inflammatory and immune parameters and systemic markers of inflammation. METHODS: SF levels of MMP-3 (precursor, active and tissue inhibitor of MMP-bound forms), tumour necrosis factor (TNF) alpha, soluble TNF receptors I and II, interleukin (IL)-6 and soluble IL-6 receptor were measured by ELISA in 107 inflammatory and 53 degenerative arthropathies. RESULTS: MMP-3 levels in SF were (i) significantly higher in inflammatory than in degenerative arthropathies; (ii) not related to the degree of joint destruction; (iii) significantly correlated with the levels of all SF markers tested and with erythrocyte sedimentation rate and serum levels of C-reactive protein and fibrinogen. CONCLUSION: Increased MMP-3 levels in SF are found in inflammatory arthropathies and are not specific for erosive joint diseases. MMP-3 in SF is therefore a potential candidate for the assessment of the inflammatory process in joints. However, the exclusive determination of the active form could indicate the degree of joint destruction.

Sarcoidosis: recognition and treatment guidelines.

Sarcoidosis is a systemic disorder of unknown aetiology characterised by noncaseating granulomas leading principally to bilateral hilar lymphadenopathies, pulmonary infiltration and skin and eye lesions. Sarcoidosis may involve other organs, including peripheral lymph nodes, liver, spleen, nervous and musculoskeletal systems, heart, ear, nose and kidney. Although the clinical involvement of liver and heart is relatively uncommon, hepatic and cardiac granulomas are present at autopsy in about 70 to 80% and 25 to 50%, respectively, of patients with this disease. The diagnosis of sarcoidosis includes compatible clinical and/or radiological presentations and histological evidence of noninfectious and noncaseating epitheloid cell granulomas in the absence of other identifiable agents responsible for such histological lesions. Disease course is variable and usually characterised by frequent remissions, but it may become progressive and chronic in a small percentage of patients. The optimal treatment of sarcoidosis remains poorly defined. In patients with progressive pulmonary dysfunction as well as in those with severe extrapulmonary localisations, systemic corticosteroids usually represent the first approach, limited by long term toxicity and frequent relapses after treatment interruption. In the presence of refractory or corticosteroid-dependent forms of the disease, antimalarial drugs or low dosage methotrexate may be used with prolonged benefit. The indications for immunosuppressive agents such as azathioprine, chlorambucil, cyclophosphamide and cyclosporin are uncommon and limited because of potentially serious adverse effects and lack of information on their long term efficacy. In the case of ocular and limited cutaneous manifestations, local corticosteroid therapy may be useful.

The frequency of cutaneous vasculitis is not increased in patients with rheumatoid arthritis treated with methotrexate.

OBJECTIVE: To analyse the frequency, type, and immunohistological features of clinical cutaneous vasculitis developing in patients with rheumatoid arthritis (RA) treated or not with methotrexate as well as their demographic, clinical and biological characteristics. METHODS: Ninety-one patients with RA receiving 9.5 mg/wk of methotrexate (MTX) were compared for an average observation time of 18 months to 130 matched patients with RA treated with various drugs excluding MTX. RESULTS: Whether receiving MTX or not, 5.4% of patients with RA developed a clinical cutaneous vasculitis. There were significant differences between both groups for 2 variables only: a higher percentage of polyneuropathies and a higher level of immune complex-plasma levels in non-MTX patients. The immunohistological analysis did not differentiate both groups. CONCLUSION: The percentage of cutaneous vasculitis that developed under MTX therapy was not different from that occurring as a natural complication of longstanding severe RA.

[Acute tubulo-interstitial nephropathy with uveitis: apropos of case]. / Néphropathie tubulo-interstitielle aiguë avec uvéite: à propos d'un cas.

We report another case of acute interstitial nephritis with uveitis (TINU syndrome) in a 35-year-old woman. About thirty cases were described since the first ones 20 years ago. We discuss the assessment needed to reach the diagnosis. The evolution is unusually favourable with steroid therapy.

Low-dose methotrexate: an effective corticosteroid-sparing agent in the musculoskeletal manifestations of sarcoidosis.

Extrapulmonary sarcoidosis, and particularly the presence of musculoskeletal complications of the disease, may require chronic corticosteroid therapy. In five patients with biopsy-proven sarcoidosis and presenting recalcitrant forms of the disease, we introduced low-dose oral methotrexate (MTX) [10 mg/week (7.5-15)] for 30 months (16-34) to control the clinical and biological symptoms as well as to try to reduce the intolerated steroid posology. Beneficial effects were observed within 8-12 weeks in all patients, which allowed a reduction of 59% (35-75) of the corticosteroid posology, and maintained with a follow-up of 3 yr in 4/5 patients. No significant toxicity was observed. MTX appears to be an efficient, safe and corticosteroid-sparing therapeutic agent for the treatment of recalcitrant musculoskeletal manifestations of sarcoidosis.