S. Abad

Tenofovir-Related Fanconi Syndrome with Nephrogenic Diabetes Insipidus in a Patient with Acquired Immunodeficiency Syndrome: The Role of Lopinavir-Ritonavir-Didanosine

Tenofovir-related tubular damage, like all other recently reported cases, occurred in patients receiving the protease inhibitor (PI) ritonavir, often with lopinavir. Increased plasma concentrations of didanosine were also observed after the addition of tenofovir. It was suspected that tenofovir with PIs interacted with renal organic anion transporters, leading to nephrotoxic tubular concentrations of tenofovir and systemic accumulation of didanosine. Until there is a better understanding of these interactions, close monitoring is recommended for patients receiving tenofovir, PIs, and didanosine.

Biotherapies in inflammatory ocular disorders: Interferons, immunoglobulins, monoclonal antibodies

Biotherapies used in clinical practice for the treatment of ophthalmologic manifestations of systemic diseases include interferons (IFN), intravenous immunoglobulins (IVIG) and monoclonal antibodies (anti-TNF, anakinra, tocilizumab and rituximab). Several open prospective studies have shown the effectiveness of IFN-α (78 to 98% complete remission) for the treatment of severe uveitis in Behcets disease. IFN is capable of inducing prolonged remission and continued after his arrest, in 20-40% of patients. Side effects (flu-like, psychological effects) limit its use in practice. Anti-TNFα (infliximab and adalimumab) represents an attractive alternative therapeutic in severe uveitis refractory to immunosuppressants, especially in Behcets disease. They are almost always (>90% of cases) and rapidly effective but their action is often suspensive. Anti-TNFα requires an extended prescription or takes over from another immunosuppressant once ocular inflammation has been controlled. IVIG are used for the treatment of Kawasaki disease and Birdshot disease. Several open or retrospective studies showed their effectiveness for the treatment of severe and refractory cicatricial pemphigoid. Tolerance of IVIG is good but their efficacy is transient. Rituximab showed an efficacy in few observations of various inflammatory eye diseases (uveitis, scleritis and idiopathic inflammatory pseudo-tumors or associated with granulomatosis with polyangiitis) and cicatricial pemphigoid. The risk of infection associated with this biotherapy limits its use in refractory diseases to conventional therapy. Anakinra (a soluble antagonist of IL-1R) showed interesting results in terms of efficiency in one small open study in Behcets disease. Its safety profile is good and with a quick action that could be interesting for the treatment of severe uveitis.

Efficacy of Biological-Targeted Treatments in Takayasu Arteritis Multicenter, Retrospective Study of 49 Patients

Background— The goal of this work was to assess the safety and efficacy of biologics (ie, tumor necrosis factor-&agr; antagonists and tocilizumab) in patients with Takayasu arteritis. Methods and Results— This was a retrospective, multicenter study of the characteristics and outcomes of 49 patients with Takayasu arteritis (80% female; median age, 42 years [20–55 years] treated by tumor necrosis factor-&agr; antagonists [80%] or tocilizumab [20%]) and fulfilling American College of Rheumatology or Ishikawa criteria. Factors associated with complete response were assessed. Eighty-eight percent of patients with Takayasu arteritis were inadequately controlled with or were intolerant to conventional immunosuppressive therapy (median number, 3 [1–5]). Overall response (ie, complete and partial) to biological-targeted treatments at 6 and 12 months was 75% and 83%, respectively. There were significantly lower C-reactive protein levels at the initiation of biological-targeted treatments (22 mg/L [10–46 mg/L] versus 58 mg/L [26–76 mg/L]; P=0.006) and a trend toward fewer immunosuppressants drugs used before biologics (P=0.054) in responders (ie, complete or partial responders) relative to nonresponders to biological-targeted treatments. C-reactive protein levels and daily prednisone dose significantly decreased after 12 months of biological-targeted treatments (30 versus 6 mg/L [P<0.05] and 15 versus 7.5 mg [P<0.05] at baseline and 12 months, respectively). The 3-year relapse-free survival was 90.9% (83.5%–99%) over the biological treatment period compared with 58.7% (43.3%–79.7%; P=0.0025) with disease-modifying antirheumatic drugs. No difference in efficacy was found between tumor necrosis factor-&agr; antagonists and tocilizumab. After a median follow-up of 24 months (2–95 months), 21% of patients experienced adverse effects, with biological-targeted treatments discontinued in 6.6% of cases. Conclusion— This nationwide study shows a high efficacy of biological-targeted treatments in refractory patients with Takayasu arteritis with an acceptable safety profile.Background— The goal of this work was to assess the safety and efficacy of biologics (ie, tumor necrosis factor-α antagonists and tocilizumab) in patients with Takayasu arteritis. Methods and Results— This was a retrospective, multicenter study of the characteristics and outcomes of 49 patients with Takayasu arteritis (80% female; median age, 42 years [20–55 years] treated by tumor necrosis factor-α antagonists [80%] or tocilizumab [20%]) and fulfilling American College of Rheumatology or Ishikawa criteria. Factors associated with complete response were assessed. Eighty-eight percent of patients with Takayasu arteritis were inadequately controlled with or were intolerant to conventional immunosuppressive therapy (median number, 3 [1–5]). Overall response (ie, complete and partial) to biological-targeted treatments at 6 and 12 months was 75% and 83%, respectively. There were significantly lower C-reactive protein levels at the initiation of biological-targeted treatments (22 mg/L [10–46 mg/L] versus 58 mg/L [26–76 mg/L]; P =0.006) and a trend toward fewer immunosuppressants drugs used before biologics ( P =0.054) in responders (ie, complete or partial responders) relative to nonresponders to biological-targeted treatments. C-reactive protein levels and daily prednisone dose significantly decreased after 12 months of biological-targeted treatments (30 versus 6 mg/L [ P <0.05] and 15 versus 7.5 mg [ P <0.05] at baseline and 12 months, respectively). The 3-year relapse-free survival was 90.9% (83.5%–99%) over the biological treatment period compared with 58.7% (43.3%–79.7%; P =0.0025) with disease-modifying antirheumatic drugs. No difference in efficacy was found between tumor necrosis factor-α antagonists and tocilizumab. After a median follow-up of 24 months (2–95 months), 21% of patients experienced adverse effects, with biological-targeted treatments discontinued in 6.6% of cases. Conclusion— This nationwide study shows a high efficacy of biological-targeted treatments in refractory patients with Takayasu arteritis with an acceptable safety profile. # CLINICAL PERSPECTIVE {#article-title-34}

Tuberculosis Due to Mycobacterium bovis after Alemtuzumab Administration

We describe a patient with relapsing B chronic lymphocytic leukemia who developed systemic bacille Calmette-Guérin infection (BCGitis) after administration of alemtuzumab (Campath-1H).

Aortitis in giant cell arteritis: diagnosis with FDG PET/CT and agreement with CT angiography

OBJECTIVES To assess the detection rate of aortitis in giant cell arteritis (GCA) with fluorodeoxyglucose positron emission tomography/computed tomography (PET) and to compare the findings with CT angiography (CTA). METHODS Fifty-two GCA patients and 27 controls were included. GCA patients had a PET scan at diagnosis (35/52) or during relapse (17/52). Concomitant CTA was performed in 35/52 patients. Aortitis was defined as FDG uptake higher than the liver for PET and wall thickness≥3mm for CTA. Agreement between PET and CTA was evaluated by the kappa coefficient and Spearman correlation coefficient. RESULTS Aortitis was diagnosed using PET in 40% (14/35) of patients at diagnosis and in 0% of controls (0/27). Agreement was perfect between PET and CT at a patient-based level, and very good at a vascular segment-based level (kappa: 0.72 to 1). PET was positive in 35% (6/17) of patients scanned during GCA relapse, showing aortitis (n=4) and/or articular uptake (n=4). Discrepancies between PET and CT were observed only in relapsing GCA (n=3). Correlation between the maximum standardized uptake value and wall thickness was moderate at diagnosis (r: 0.57 to 0.7) and not statistically significant during relapse. CONCLUSIONS The detection rate of aortitis in GCA patients using PET is 40%, approximately in the range of CTA rates, suggesting that the two techniques have similar sensitivity. PET seems valuable in relapsing GCA, allowing the detection of vascular and articular activities.

Maladie de Whipple diagnostiquée primitivement sarcoïdose

Resume Introduction La maladie de Whipple est une affection multisystemique liee au bacille non cultivable Tropheryma whipplei. Nous rapportons un cas trompeur de “sarcoidose” devenant “maladie de Whipple” avec endocardite. Observation Le diagnostic de sarcoidose a ete porte chez un patient de 61 ans sur des donnees cliniques, radiographiques, endoscopiques et histologiques. La reponse initiale a la corticotherapie a ete bonne mais le patient restait dependant de 35 mg/j de prednisone. L’apparition d’un syndrome inflammatoire clinique et biologique majeur a fait douter du diagnostic. Le diagnostic d’une endocardite a hemocultures negatives, sans possibilite de “decapitation” par antibiotherapie prealable a ete pose, avec mise en evidence echographique d’une masse arrondie de 1 cm de diametre appendue a la grande valve mitrale avec insuffisance mitrale grade 2. Les autres causes d’endocardites a hemocultures negatives ont ete ecartees. La maladie de Whipple a ete envisagee et le diagnostic retenu sur la positivite d’une biopsie duodenale en PCR pour Tropheryma whipplei, l’histologie restant negative. Un traitement par gentamycine et amoxicilline en intra-veineux a ete poursuivi 3 semaines, remplace par cotrimoxazole oral. L’echographie transoesophagienne de controle ne montrait plus la masse mitrale. Le patient, sous cotrimoxazole, sevre depuis 13 mois de prednisone, reste asymptomatique. Conclusion Ce cas illustre les difficultes de diagnostic differentiel entre sarcoidose et maladie de Whipple, mais aussi l’importance de cette distinction.

IgG4-related diffuse perineural disease

A 55-year-old woman had right exophthalmia. Eleven years previously, she had orbital irradiation for refractory nonspecific orbital inflammation. PET/CT revealed FDG uptake in the right orbit and paravertebral masses (figure 1, A and C). MRI showed an enlargement of the right optic nerve and orbital muscles, and a diffuse infiltration involving lumbodorsal and sacral nerve roots (figure 1, B and D). The orbital biopsy demonstrated immunoglobulin G4 (IgG4)+ plasma cell infiltrate and a storiform fibrosis (figure 2), identical to the histopathologic features of the nerve root biopsy, and suggestive of IgG4-related diffuse perineural disease.1,2 No treatment was started in the absence of neurologic symptoms. One year later, the patient had no further symptoms.

Efficacy of tocilizumab highlighted by FDG-PET/CT in a patient with relapsing polychondritis-associated aortitis

Relapsing polychondritis (RP) is a rare systemic inflammatory disease primarily affecting the ears, nose and tracheobronchial tree cartilage, but also the cardiovascular system. Cardiovascular complications are the second cause of mortality in RP. We report the case of a woman with a corticosteroid-resistant RP-associated aortitis, who was successfully treated with tocilizumab (TCZ). The FDG-PET/CT was a useful tool for diagnosing aortitis and assessing the effect of biotherapy. We conducted a systematic literature review confirming this is the first case of rapid and sustained remission in a patient with corticosteroid-resistant RP-associated aortitis after TCZ treatment administered as a first-line immunotherapy. However, further studies are needed to confirm the beneficial effect of TCZ used in this life-threatening condition.

Avis d’experts pour le traitement des uvéites non infectieuses

Conventional immunosuppressive drugs, anti-TNF alpha and other biotherapies used in clinical practice are capable of controlling non-infectious anterior uveitis, posterior uveitis and panuveitis. The present work has been led by a multidisciplinary panel of experts, internists, rheumatologists and ophthalmologists and is based on a review of the literature. In case of corticodependency or sight-threatening disease, conventional immunosuppressive drugs (methotrexate, azathioprine and mycophenolate mofetil) and/or anti-TNF alpha (adalimumab, infliximab) are used to achieve and maintain remission. Interferon is an efficient immunomodulatory treatment, as a second-line therapy, for some therapeutic indications (refractory macular edema, Behçets vascularitis). Other biologics, especially tocilizumab, are showing promising results. Local treatments (corticosteroids, sirolimus etc.) are adjuvant therapies in case of unilateral inflammatory relapse. Therapeutic response must be evaluated precisely by clinical examination and repeated complementary investigations (laser flare photometry, multimodal imaging, perimetry, electroretinography measures).

Macroanévrysmes multiples, une complication rare d’une vascularite de type périartérite noueuse

u cours d’une maladie de Wegener [1]. Cette complication rare a évolué favoralement sous corticoïdes et immunosuppresseurs et n’a pas nécessité de drainage algré les signes initiaux d’hypertension intracrânienne. Certaines observations omparables sont rapportées dans d’autres vascularites, notamment dans le cadre ’un neuro-Behcet [2], ou d’un syndrome de Kawasaki [3]. La présentation cliique, souvent dominée par des céphalées et de la fièvre, amène au diagnostic ’épanchements sous duraux uniou bilatéraux, avec une excellent réponse linique au traitement de la maladie de fond. La physiopathologie de ces épanhements n’est pas clairement établie. Les hypothèses d’une hyperhémie causée ar l’inflammation méningée, de troubles de résorption liés à la pachyméningite u de la participation d’une vascularite des vaisseaux sous duraux peuvent être oulevées. onclusion.– L’épanchement sous dural bilatéral spontané est une complication xceptionnelle de la pachyméningite de la maladie de Wegener. Le traitement mmunosuppresseur peut permettre de traiter cette complication sans avoir ecours à la chirurgie. éférences 1] Shiotani A, et al. Intern Med 1997;36:514–8. 2] Suzuki N, et al. Ann Rheum Dis 2003;62:374–5. 3] Bailie NM, et al. Eur J Paediatr Neurol 2001;5:79–81.