Spectacular Improvement of Paradoxical Reaction in Tuberculosis after Tumor Necrosis Factor-Alpha Antagonist Therapy.

We report the case of a 42-year-old immunocompetent Indian patient presenting with miliary tuberculosis complicated by respiratory failure requiring intubation. Conventional quadritherapy was initiated for wild-type Mycobacterium tuberculosis. On day 29 of antibiotic treatment, persistent fever and neurological deterioration prompted the diagnosis of multiple brain and medullary tuberculomas, some surrounded by edema. Laboratory investigations ruled out meningitis and subtherapeutic drug concentrations. To enhance cerebrospinal fluid penetration, ethambutol was replaced with levofloxacin on day 30, and rifampicin doses were increased to 30 mg/kg. Dexamethasone was introduced on day 30 to address the paradoxical response to antituberculosis therapy, but neurological deterioration persisted, leading to hemiparesis and coma, with concurrent development of acute respiratory distress syndrome. As salvage therapy, an anti-tumor necrosis factor agent, infliximab (IFX), was administered on day 40. Rapid clinical improvement was observed, marked by awakening and subsequent weaning from respiratory ventilation just eight days after the first IFX infusion. The patient was discharged from the intensive care unit 10 days post-IFX initiation, with steroids discontinued one month after IFX introduction. Both antituberculosis treatment and IFX infusions (seven in total) were maintained for one year. Clinical and radiological evaluation at one year demonstrated complete clinical and radiological recovery.

Breast MALT lymphoma and AL amyloidosis complicating Sjögren's syndrome.

Marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) lymphomas of the breast with mammary amyloidosis are exceedingly rare entities. This report describes the case of women with long-standing Sjögren's syndrome presenting with breast MALT lymphoma and amyloïd light-chain (AL) amyloidosis. Breast microcalcification needle biopsy made the positive diagnosis. This unusual finding should be kept in mind. It emphasises the need for careful clinical examination of nodes and extranodal organs supposedly affected in patients with autoimmune disease.

Upper and lower gastrointestinal endoscopies in patients over 85 years of age: Risk-benefit evaluation of a longitudinal cohort.

After age 85, upper and lower gastrointestinal (GI) endoscopy may be indicated in 5% to 10% of inpatients, but the risk-benefit ratio is unknown. We studied patients older than 85 years undergoing upper and lower GI endoscopy.We analyzed a retrospective cohort of inpatients older than 85 years between 2004 and 2012, all explored by upper and complete lower GI endoscopy. Initial indications, including iron deficiency anemia (IDA), other anemias, GI bleeding, weight loss, and GI symptoms, were noted, as were endoscopy or anesthesia complications, immediate endoscopic diagnosis, and the ability to modify the patients' therapeutics. Deaths and final diagnosis for initial endoscopic indication were analyzed after at least 12 months.We included 55 patients, 78% women, with a median age, reticulocyte count, hemoglobin, and ferritin levels of 87 (85-99), 56 (24-214) g/L, 8.6 (4.8-12.9) g/dL, and 56 (3-799) µg/L, respectively. IDA was the most frequent indication for endoscopy (60%; n = 33). Immediate diagnoses were found in 64% of the patients (n = 35), including 25% with GI cancers (n = 14) and 22% with gastroduodenal ulcers or erosions (n = 12). Cancer diagnosis was associated with lower reticulocyte count (45 vs. 60 G/L; P = .02). Among the 35 diagnoses, 94% (n = 33) led to modifications of the patients' therapeutics, with 29% of the patients deciding on palliative care (n = 10). No endoscopic complications lead to death. Follow-up of >12 months was available in 82% (n = 45) of the patients; among these patients, 40% (n = 27) died after an average 24 ±â€Š18 months. Cancer diagnosis was significantly associated with less ulterior red cell transfusion (0% vs. 28%; P = .02) and fewer further investigations (6.7% vs. 40%; P = .02).Upper and complete lower GI endoscopy in patients older than 85 years appears to be safe, and enables a high rate of immediate diagnosis, with significant modifications of therapeutics. GI cancers represented more than one-third of the endoscopic diagnoses.

Adding Azathioprine to Remission-Induction Glucocorticoids for Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss), Microscopic Polyangiitis, or Polyarteritis Nodosa Without Poor Prognosis Factors: A Randomized, Controlled Trial.

OBJECTIVE: In most patients with nonsevere systemic necrotizing vasculitides (SNVs), remission is achieved with glucocorticoids alone, but one-third experience a relapse within 2 years. This study was undertaken to determine whether the addition of azathioprine (AZA) to glucocorticoids could achieve a higher sustained remission rate of newly diagnosed nonsevere eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA), microscopic polyangiitis (MPA), or polyarteritis nodosa (PAN). METHODS: All patients included in this double-blind trial received glucocorticoids, gradually tapered over 12 months, and were randomized to receive AZA or placebo for 12 months, with stratification according to SNV (EGPA or MPA/PAN). The primary end point was the combined rate of remission induction failures and minor or major relapses at month 24. RESULTS: Ninety-five patients (51 with EGPA, 25 with MPA, and 19 with PAN) met the inclusion criteria, were randomized, and received at least 1 dose of AZA (n = 46) or placebo (n = 49). At month 24, 47.8% of the patients receiving AZA versus 49% of the patients receiving placebo had remission induction failures or relapses (P = 0.86). Secondary end points were comparable between the AZA and placebo arms. These included initial remission rate (95.7% versus 87.8%), total relapse rate (44.2% versus 40.5%), and glucocorticoid use. Two patients in the placebo arm died; 22 patients in the AZA arm (47.8%) and 23 patients in the placebo arm (46.9%) experienced ≥1 severe adverse event. For EGPA patients, the primary end point (48% in the AZA arm versus 46.2% in the placebo arm) and the percent of patients who experienced asthma/rhinosinusitis exacerbations (24% in the AZA arm versus 19.2% in the placebo arm) were comparable between treatment arms. CONCLUSION: Addition of AZA to glucocorticoids for the induction of remission of nonsevere SNVs does not improve remission rates, lower relapse risk, spare steroids, or diminish the EGPA asthma/rhinosinusitis exacerbation rate.

Outcome of endoscopy-negative iron deficiency anemia in patients above 65: A longitudinal multicenter cohort.

After the age of 65 years, iron deficiency anemia (IDA) requires the elimination of digestive neoplasia and is explored with upper and lower gastrointestinal (GI) endoscopy. However, such explorations are negative in 14% to 37% of patients. To further evaluate this issue, we evaluated the outcomes of patients aged over 65 years with endoscopy-negative IDA.We retrospectively analyzed the outcomes of in-patients over the age of 65 years with IDA (hemoglobin <12 g/dL and ferritin <70 µg/L) who had negative complete upper and lower GI endoscopies in 7 tertiary medical hospitals. Death, the persistence of anemia, further investigations, and the final diagnosis for IDA were analyzed after at least 12 months by calling the patients' general practitioners and using hospital records.Between 2004 and 2011, 69 patients (74% women) with a median age of 78 (interquartile range (IQR) 75-82) years and hemoglobin and ferritin levels of 8.4 (IQR 6.8-9.9) g/dL and 14 (IQR 8-27) µg/L, respectively, had endoscopy-negative IDA, and 73% of these patients received daily antithrombotics. After a follow-up of 41 ±â€Š22 months, 23 (33%) of the patients were dead; 5 deaths were linked with the IDA, and 45 (65%) patients had persistent anemia, which was significantly associated with death (P = 0.007). Further investigations were performed in 45 patients; 64% of the second-look GI endoscopies led to significant changes in treatment compared with 25% for the capsule endoscopies. Conventional diagnoses of IDA were ultimately established for 19 (27%) patients and included 3 cancer patients. Among the 50 other patients, 40 (58%) had antithrombotics.In endoscopy-negative IDA over the age of 65 years, further investigations should be reserved for patients with persistent anemia, and second-look GI endoscopy should be favored. If the results of these investigations are negative, the role of antithrombotics should be considered.

Paradoxical anti-TNF-associated TB worsening: Frequency and factors associated with IRIS.

OBJECTIVES: Paradoxical tuberculosis (TB) worsening, an example of the immune reconstitution inflammatory syndrome (IRIS), is an increasing phenomenon now described in several settings, including anti-tumor necrosis factor (TNF) discontinuation during biotherapy-induced TB. To better recognize it, we analyzed the frequency and factors associated with anti-TNF-induced TB-IRIS. METHODS: Case-control study on anti-TNF-associated TB patients. IRIS cases, defined with the following consensus criteria, were matched to two controls (anti-TNF-associated TB without IRIS). IRIS frequency was based on the French RATIO registry. Conditional logistic-regression identified IRIS risk factors. RESULTS: Fourteen patients developed anti-TNF-associated TB-IRIS within medians of 45 [IQR 22-131] days after starting anti-TB therapy and 110 [IQR 63-164] days after the last anti-TNF infusion. Each case was matched to two controls by year of TB diagnosis. IRIS-associated factors were (odds ratio [95% CI]): disseminated TB (11.4 [1.4-92.2], P=0.03), history of Mycobacterium tuberculosis exposure (12.7 [1.6-103.0], P=0.02) and steroid use at the time of TB diagnosis (4.6 [1.2-17.2], P=0.02). The RATIO registry IRIS frequency was 7%. CONCLUSION: After stopping biotherapy, paradoxical anti-TNF-associated TB worsening occurred most often in patients with disseminated TB. Although diagnosis remains difficult, physicians must be aware of IRIS because prolonged anti-TB treatment is not needed but, paradoxically, immunosuppressant reintroduction may be.

Latent Tuberculosis Infection Screening and 2-Year Outcome in Antiretroviral-Naive HIV-Infected Patients in a Low-Prevalence Country.

BACKGROUND: Diagnosis and treatment of latent tuberculous infection decrease the incidence of tuberculosis (TB) in HIV-infected patients. OBJECTIVES: To evaluate the diagnostic yield of two IFN-γ release assays and tuberculin skin testing for the screening of latent infection in HIV-infected patients. METHODS: We performed a prospective study in 29 referral centers for HIV care in France. Asymptomatic, antiretroviral-naive patients infected with HIV-1 who consented to participate underwent two commercial tests (T-SPOT.TB and QuantiFERON-TB Gold In-Tube ELISA test [QFT]) and skin test at enrollment and were followed up for clinical events during 24 months. RESULTS: Between March 2009 and 2011, 506 patients were included, of whom 415 performed the three tests. Median age was 38 years (interquartile range, 31-45 yr), with median CD4 cell count of 466/µL (337-615 µL), and HIV viral load of 4.5 log10 copies/ml (3.6-4.9 log10 copies/ml). At least one IFN-γ release assay was positive for 55 (13.5%) patients: QFT (n = 43), T-SPOT.TB (n = 34), both (n = 22). Skin test was positive (>5 mm) in 66 (15.9%) patients, with intertest agreement at 81 to 86%. On multivariate analysis, positive IFN-γ release assay was only correlated with country of birth (8.4% for France vs. 17.9% for high-prevalence countries, P = 0.004). Of the 55 patients with positive IFN-γ release assay, 8 (14.5%) developed active TB, all within 120 days. No other case of active TB was diagnosed. Once active TB was excluded, IFN-γ release assay-based latent infection prevalence was 11.8%. CONCLUSIONS: Systematic screening for latent TB infection by IFN-γ release assay identifies a population at high risk of active TB over the next months. An extensive diagnostic work-up for active TB must follow positive IFN-γ release assay, before considering treatment of latent infection. Clinical trial registered with www.clinicaltrials.gov (NCT00805272).

Paradoxical exacerbation of tuberculosis after TNFα antagonist discontinuation: beware of immune reconstitution inflammatory syndrome.

Paradoxical worsening of tuberculosis associated with immune reconstitution during antiretroviral therapy in patients with HIV infection is known as the immune reconstitution inflammatory syndrome (IRIS). Here, we report a case of paradoxical worsening of IFN-alpha induced tuberculosis in a patient experiencing reconstitution of pathogen-specific immune responses after discontinuing TNFα antagonist therapy. This case serves to alert clinicians that complications such as tuberculosis may worsen after TNFα antagonist discontinuation. This situation may paradoxically require readministration of the immunosuppressive drug in some patients.

Deaths occurring during the first year after treatment onset for polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: a retrospective analysis of causes and factors predictive of mortality based on 595 patients.

Although combining corticosteroids and cyclophosphamide has greatly improved the prognoses of severe necrotizing vasculitides, some patients continue to have fulminating disease and die within the first year of diagnosis. To evaluate the characteristics of these patients, we retrospectively studied the files of 60 patients who died within the first year (20 patients with hepatitis B virus-associated polyarteritis nodosa [HBV-PAN], 18 with non-HBV PAN, 13 with microscopic polyangiitis [MPA], and 9 with Churg-Strauss syndrome [CSS]) and 535 first-year survivors (89 patients with HBV-PAN, 182 with non-HBV PAN, 140 with MPA, and 124 with CSS), 85 of whom died during a mean follow-up of 6.4 years. The 2 groups were compared for prognostic factors defined by the five-factor score (FFS) and Birmingham Vasculitis Activity Score at baseline, clinical signs, treatment, outcome, and causes of death. For first-year nonsurvivors, the clinical signs predictive of death were as follows: renal involvement (hazard ratio [HR], 1.6; 95% confidence intervals [CI], 1.09-2.3) or central nervous system involvement (HR, 2.3; 95% CI, 1.5-3.7), and a trend toward cardiomyopathy (HR, 1.4; 95% CI, 1.000-2.115). Older patients died earlier (HR, 1.04; 95% CI, 1.023-1.051). Gastrointestinal symptoms were most frequently associated with early death from HBV-PAN, while 83% of CSS patients died of cardiac involvement. Treatment had no significant impact on early death, except for patients with FFS > or = 2, for whom steroids alone were associated (p < 0.05). The major cause of early death was uncontrolled vasculitis (58%), followed by infection (26%). Cyclophosphamide-induced cytopenia and infection were responsible for 2 deaths. Despite these iatrogenic complications, early deaths were more frequently the consequence of insufficient or inappropriate therapy.

Tenofovir-related nephrotoxicity in human immunodeficiency virus-infected patients: three cases of renal failure, Fanconi syndrome, and nephrogenic diabetes insipidus.

We report 3 cases of renal toxicity associated with use of the antiviral agent tenofovir. Renal failure, proximal tubular dysfunction, and nephrogenic diabetes insipidus were observed, and, in 2 cases, renal biopsy revealed severe tubular necrosis with characteristic nuclear changes. Patients receiving tenofovir must be monitored closely for early signs of tubulopathy (glycosuria, acidosis, mild increase in the plasma creatinine level, and proteinuria).