Therapeutic Strategies and Outcomes in Neuropsychiatric Systemic Lupus Erythematosus: An International Multicenter Retrospective Study.

OBJECTIVES: The management of neuropsychiatric systemic lupus erythematosus (NPSLE) poses considerable challenges due to limited clinical trials. Therapeutic decisions are customized based on suspected pathogenic mechanisms and symptom severity. This study aimed to investigate therapeutic strategies and disease outcome for patients with NPSLE experiencing their first neuropsychiatric (NP) manifestation. METHODS: This retrospective cohort study defined NP events according to the American College of Rheumatology case definition, categorizing them into three clusters: central/diffuse, central/focal and peripheral. Clinical judgment and a validated attribution algorithm were used for NP event attribution. Data included demographic variables, SLE disease activity index, cumulative organ damage, and NP manifestation treatments. The clinical outcome of all NP events was determined by a physician seven-point Likert scale. Predictors of clinical improvement/resolution were investigated in a multivariable logistic regression analysis. RESULTS: The analysis included 350 events. Immunosuppressants and corticosteroids were more frequently initiated/escalated for SLE-attributed central diffuse or focal NP manifestations. At 12 months of follow-up, 64% of patients showed a clinical improvement in NP manifestations. Focal central events and SLE-attributed manifestations correlated with higher rates of clinical improvement. Patients with NP manifestations attributed to SLE according to clinical judgment and treated with immunosuppressants had a significantly higher probability of achieving clinical response (OR 2.55, 95%CI 1.06-6.41, p= 0.04). Age at diagnosis and focal central events emerged as additional response predictors. CONCLUSION: NP manifestations attributed to SLE by clinical judgment and treated with immunosuppressants demonstrated improved 12-month outcomes. This underscores the importance of accurate attribution and timely diagnosis of NPSLE.

Q-uestioning the Diagnosis: An Educational Case Report.

Rationale: Q fever is a zoonotic infection that may lead to acute or long-term renal injury. Given its rare incidence, Q fever is not often considered on the initial differential diagnosis for glomerular disease which can lead to delays in treatment. This case highlights the importance of avoiding early diagnostic closure and revisiting the differential diagnosis in the setting of an atypical clinical presentation or response to treatment. Presenting Concerns: A 52-year-old female was referred for assessment of possible glomerulonephritis. She described a 3-month history of bilateral lower extremity rash, intermittent knee pain with swelling, and a 2-year history of subjective fevers. Urinalysis showed persistent microscopic hematuria, and her creatinine was elevated at 94 umol/L (baseline 59 umol/L). Her initial investigations included an elevated C-reactive protein (CRP) and rheumatoid factor with a weakly positive anti nuclear antibody (ANA). Diagnoses: Kidney biopsy was consistent with an immune complex mesangial proliferative glomerulonephritis. Light microscopy showed diffuse global mesangial hypercellularity. Immunofluorescence was positive for trace mesangial IgG and kappa, 1+ IgM, lambda and C1q, and 2+ C3. Electron microscopy showed mesangial electron dense deposits. These findings were felt to be most in keeping with mesangial proliferative lupus nephritis; however, it was acknowledged that clinical and laboratory findings supporting this diagnosis were lacking. Interventions: Following treatment with oral prednisone her symptoms resolved, and renal function improved. However, she was unable to taper off prednisone completely without her symptoms returning. Additional immunosuppressive therapies were trialed, but she remained steroid dependent with disease flares related to prednisone tapers. Her atypical response to treatment led to consideration of alternative diagnoses, and further investigation revealed positive Q fever serology (phase-I IgG 1:1892, phase II IgG 1:8192, phase-I and -II IgM < 1:16). She was diagnosed with long-term Q fever and was treated with doxycycline and hydroxychloroquine. Outcomes: She remained on treatment for 2 years. During this time, her symptoms resolved, hematuria disappeared, and her creatinine returned to baseline. Following cessation of therapy, her Q fever IgM titres rose, and she was restarted on doxycycline and hydroxychloroquine indefinitely. Teaching Points: (1) Keeping a broad differential diagnosis in the setting of atypical clinical features or unexpected response to therapy is important for ensuring accurate diagnosis and appropriate treatment. (2) Clinical improvement in relation to immunosuppressive therapy does not preclude an infectious cause of glomerular disease.

Justification: La fièvre Q est une infection zoonotique qui peut entraîner l'insuffisance rénale aiguë ou chronique. D'incidence rare, la fièvre Q n'est généralement pas considérée dans le diagnostic différentiel initial de la glomérulonéphrite, ce qui peut retarder le traitement. Ce cas souligne l'importance d'éviter de poser un diagnostic précoce et d'envisager un diagnostic différentiel lors d'une présentation clinique atypique ou d'une réponse inattendue au traitement. Présentation du cas: Une femme de 52 ans envoyée pour l'évaluation d'une possible glomérulonéphrite. La patiente disait avoir une éruption cutanée bilatérale des membres inférieurs et une douleur intermittente au genou avec enflure depuis trois mois, ainsi que des épisodes de fièvre subjective au cours des deux dernières années. L'analyze d'urine a révélé une hématurie microscopique persistante et un taux de créatinine élevé à 94 umol/L (59 umol/L initialement). Ses premiers examens ont montré une élévation de la CRP et du facteur rhumatoïde, ainsi qu'un titer d'ANA faiblement positif. Diagnostic: La biopsie rénale était compatible avec une glomérulonéphrite mésangiale proliférative à complexe immun. La microscopie optique a démontré une hypercellularité mésangiale diffuse globale. L'immunofluorescence des cellules mésangiales a révélé des traces d'IgG, de kappa, d'IgM, de chaînes lambda et de fragments C1q 1+ et de C3 2+. La microscopie électronique a montré des dépôts denses aux électrons en localization mésangiale. Ces résultats ont été jugés comme plus conformes à la néphrite lupique mésangiale proliférative; on a toutefois reconnu que des résultats cliniques et de laboratoire appuyant ce diagnostic faisaient défaut. Intervention: Après un traitement par prednisone orale, les symptômes de la patiente se sont résorbés et sa fonction rénale s'est améliorée. Il ne lui a toutefois pas été possible de cesser complètement la prednisone sans une réapparition de ses symptômes. D'autres traitements immunosuppresseurs ont été mis à l'essai, mais la patiente est restée dépendante des stéroïdes en raison de poussées de la maladie liées aux réductions de la dose de prednisone. Cette réponse atypique au traitement a mené l'équipe soignante à envisager d'autres diagnostics. Des examens supplémentaires ont révélé une sérologie positive pour la fièvre Q (IgG phase I 1:1892; IgG phase II 1:8192; IgM phase I et II <1:16). La patiente a reçu un diagnostic de fièvre Q chronique et a été traitée avec de la doxycycline et de l'hydroxychloroquine. Résultats: La patiente a reçu le traitement pendant deux ans au cours desquels ses symptômes se sont résorbés, son taux de créatinine est revenu à la valeur initiale et l'hématurie est disparue. Après l'arrêt du traitement, ses titres d'IgM de fièvre Q ont augmenté et la patiente a dû reprendre indéfiniment le traitement par doxycycline et hydroxychloroquine. Enseignements tirés: (1) Pour garantir un diagnostic précis et le traitement approprié, il est important d'envisager un diagnostic différentiel étendu en présence de caractéristiques cliniques atypiques ou d'une réponse inattendue au traitement. (2) L'amélioration clinique liée au traitement immunosuppresseur n'exclut pas une étiologie infectieuse de la glomérulonéphrite.

Validity of the Italian algorithm for the attribution of neuropsychiatric events in systemic lupus erythematosus: a retrospective multicentre international diagnostic cohort study.

OBJECTIVE: To validate the Italian algorithm of attribution of neuropsychiatric (NP) events to systemic lupus erythematosus (SLE) in an external international cohort of patients with SLE. METHODS: A retrospective cohort diagnostic accuracy design was followed. SLE patients attending three tertiary care lupus clinics, with one or more NP events, were included. The attribution algorithm, applied to the NP manifestations, considers four weighted items for each NP event: (1) time of onset of the event; (2) type of NP event (major vs minor), (3) concurrent non-SLE factors; (4) favouring factors. To maintain blinding, two independent teams of assessors from each centre evaluated all NP events: the first provided an attribution diagnosis on the basis of their own clinical judgement, assumed as the 'gold standard'; the second applied the algorithm, which provides a probability score ranging from 0 to 10. The performance of the algorithm was evaluated by calculating the area under curve (AUC) of thereceiver operating characteristic curve. RESULTS: The study included 243 patients with SLE with at least one NP manifestation, for a total of 336 events. 285 (84.8%) NP events involved the central nervous system and 51 (15.2%) the peripheral nervous system. The attribution score for the first NP event showed good accuracy with an AUC of 0.893 (95% CI 0.849 to 0.937) using dichotomous outcomes for NPSLE (related vs uncertain/unrelated). The best single cut-off point to optimise classification of a first NPSLE-related event was≥7 (sensitivity 87.9%, specificity 82.6%). Satisfactory accuracy was observed also for subsequent NP events. CONCLUSIONS: Validation exercise on an independent international cohort showed that the Italian attribution algorithm is a valid and reliable tool for the identification of NP events attributed to SLE.

Positron Emission Tomography/Computerized Tomography in Newly Diagnosed Patients with Giant Cell Arteritis Who Are Taking Glucocorticoids.

OBJECTIVE: Large vessel uptake on positron emission tomography/computerized tomography (PET/CT) supports the diagnosis of giant cell arteritis (GCA). Its value, however, in patients without arteritis on temporal artery biopsy and in those receiving glucocorticoids remains unknown. We compared PET/CT results in GCA patients with positive (TAB+) and negative temporal artery biopsies (TAB-), and controls. METHODS: Patients with new clinically diagnosed GCA starting treatment with glucocorticoids underwent temporal artery biopsy and PET/CT. Using a visual semiquantitative approach, 18F-fluorodeoxyglucose (FDG) uptake was scored in 8 vascular territories and summed overall to give a total score in patients and matched controls. RESULTS: Twenty-eight patients with GCA and 28 controls were enrolled. Eighteen patients with GCA were TAB+. Mean PET/CT scores after an average of 11.9 days of prednisone were higher in patients with GCA compared to controls, for both total uptake (10.34 ± 2.72 vs 7.73 ± 2.56; p = 0.001), and in 6 of 8 specific vascular territories. PET/CT scores were similar between TAB+ and TAB- patients with GCA. The optimal cutoff for distinguishing GCA cases from controls was a total PET/CT score of ≥ 9, with an area under the receiver-operating characteristic curve of 0.75, sensitivity 71.4%, and specificity 64.3%. Among patients with GCA, these measures correlated with greater total PET/CT scores: systemic symptoms (p = 0.015), lower hemoglobin (p = 0.009), and higher platelet count (p = 0.008). CONCLUSION: Vascular FDG uptake scores were increased in most patients with GCA despite exposure to prednisone; however, the sensitivity and specificity of PET/CT in this setting were lower than those previously reported.

Application of the International Germ Cell Consensus Classification to the Nova Scotia population of patients with germ cell tumours.

BACKGROUND: The International Germ Cell Consensus Classification (IGCCC) is the internationally accepted, clinically based prognostic classification used to assist in the management and research of metastatic germ cell tumours (GCTs). The goal of this study was to determine whether the IGCCC is applicable to a population-based cohort. METHODS: We completed a retrospective chart review of patients who received diagnoses of GCT in Nova Scotia between 1984 and 2004 and who received treatment with platin-based chemotherapy for metastatic disease. We assigned the IGCCC to each patient based on the site of the primary lesion, the presence or absence of nonpulmonary visceral metastases and prechemotherapy tumour marker values. We calculated Kaplan-Meier estimates of 5-year progression-free survival (PFS) and overall survival for each IGCCC group. RESULTS: The study cohort comprised 129 patients. The distribution and outcomes in each group of patients in Nova Scotia was similar to that published in the IGCCC. Among patients with nonseminoma GCTs (NSGCT) 61% had good, 22% had intermediate and 17% had poor prognoses. Among those with seminomas, 85% had good and 15% had intermediate prognoses. Among patients with NSGCTs, the 5-year PFS was 90%, 69% and 55%, and the 5-year overall survival was 94%, 84%, 61% in the good, intermediate, and poor prognostic categories respectively. Among patients with seminomas, the 5-year PFS was 95% and 50% and the 5-year overall survival was 94% and 50% in the good and intermediate prognostic categories, respectively. CONCLUSION: The IGCCC seems applicable to a population-based cohort, with similar distribution of categories and clear prognostic ability.