Raffaella Rubino

Disseminated tuberculosis in a patient treated with a JAK2 selective inhibitor: a case report

BackgroundPrimary myelofibrosis is a myeloproliferative disorder characterized by bone marrow fibrosis, abnormal cytokine expression, splenomegaly and anemia. The activation of JAK2 and the increased levels of circulating proinflammatory cytokines seem to play an important role in the pathogenesis of myelofibrosis. Novel therapeutic agents targeting JAKs have been developed for the treatment of myeloproliferative disorders. Ruxolitinib (INCB018424) is the most recent among them.Case presentationTo our knowledge, there is no evidence from clinical trials of an increased risk of tuberculosis during treatment with JAK inhibitors. Here we describe the first case of tuberculosis in a patient treated with Ruxolitinib, a male with a 12-year history of chronic idiopathic myelofibrosis admitted to our Institute because of fever, night sweats, weight loss and an enlarging mass in the left inguinal area for two months.ConclusionTreatment with Ruxolitinib may have triggered the reactivation of latent tuberculosis because of an inhibition of Th1 response. Our case highlights the importance of an accurate screening for latent tuberculosis before starting an anti-JAK 2 treatment.

Cryptic Leishmania infantum infection in Italian HIV infected patients

BackgroundVisceral leishmaniasis (VL) is a protozoan diseases caused in Europe by Leishmania (L.) infantum. Asymptomatic Leishmania infection is more frequent than clinically apparent disease. Among HIV infected patients the risk of clinical VL is increased due to immunosuppression, which can reactivate a latent infection. The aims of our study were to assess the prevalence of asymptomatic L. infantum infection in HIV infected patients and to study a possible correlation between Leishmania parasitemia and HIV infection markers.MethodsOne hundred and forty-five HIV infected patients were screened for the presence of anti-Leishmania antibodies and L. infantum DNA in peripheral blood. Statistical analysis was carried out by using a univariate regression analysis.ResultsAntibodies to L. infantum were detected in 1.4% of patients. L. infantum DNA was detected in 16.5% of patients. Significant association for PCR-Leishmania levels with plasma viral load was documented (p = 0.0001).ConclusionIn our area a considerable proportion of HIV infected patients are asymptomatic carriers of L. infantum infection. A relationship between high HIV viral load and high parasitemic burden, possibly related to a higher risk of developing symptomatic disease, is suggested. PCR could be used for periodic screening of HIV patients to individuate those with higher risk of reactivation of L. infantum infection.

KIR2DL3 and the KIR ligand groups HLA-A-Bw4 and HLA-C2 predict the outcome of hepatitis B virus infection

Killer immunoglobulin‐like receptors (KIRs) regulate the activation of natural killer cells through their interaction with human leucocyte antigens (HLA). KIR and HLA loci are highly polymorphic, and certain HLA‐KIR combinations have been found to protect against viral infections. In this study, we analysed whether the KIR/HLA repertoire may influence the course of hepatitis B virus (HBV) infection. Fifty‐seven subjects with chronic hepatitis B (CHB), 44 subjects with resolved HBV infection and 60 healthy uninfected controls (HC) were genotyped for KIR and their HLA ligands. The frequency of the HLA‐A‐Bw4 ligand group was higher in CHB (58%) than subjects with resolved infection (23%) (crude OR, 4.67; P<.001) and HC (10%) (crude OR, 12.38; P<.001). Similar results were obtained for the HLA‐C2 ligand group, more frequent in CHB (84%), than subjects with resolved infection (70%) (crude OR, 2.24; P<.10) and HC (60%) (crude OR, 3.56; P<.01). Conversely, the frequency of KIR2DL3 was lower in CHB (81%) than in subjects with resolved infection (98%) (crude OR, 0.10; P<.05). These results suggest a detrimental role of HLA‐A‐Bw4 and HLA‐C2 groups, which are associated with the development of CHB, and a protective role of KIR2DL3. A stepwise variable selection procedure, based on multiple logistic regression analysis, identified these three predictive variables as the most relevant, featuring high specificity (90.9%) and positive predictive value (87.5%) for the development of CHB. Our results suggest that a combination of KIR/HLA gene/alleles is able to predict the outcome of HBV infection.

Rhabdomyolysis associated with the co-administration of daptomycin and pegylated interferon α-2b and ribavirin in a patient with hepatitis C

Rhabdomyolysis is a rare adverse effect reported with daptomy-cin use. Here we report the first case of creatinine phosphokinase (CPK) elevation with rhabdomyolysis developing during the co-administration of daptomycin and pegylated interferon a-2b and ribavirin. We describe the case of a patient with a history of intravenous drug abuse and hepatitis C admitted to our division because of fever and pain in the right gluteal region. The patients general condition was poor, but his physical examination was unremarkable, except for the presence of a right gluteal abscess. The patient had been taking pegylated interferon a-2b and ribavirin for 5 months without reporting side effects. On admission, liver function tests were within normal limits, serum CPK level was slightly elevated (518 U/L; normal values 39 –308 U/L), lactate dehydrogenase (LDH) was 580 U/L (normal values 240–480 U/L), serum creatinine was 1.6 mg/dL and estimated CL CR was 124.8 mL/min. The white blood cell (WBC) count showed neutrophil leucocytosis (WBC 11 580 cells/mm 3 , 87.1% neutrophils) and a low platelet count (72 000 cells/mm 3). All other laboratory findings were within normal limits. Hepatitis C virus (HCV) RNA viral load was undetectable. Blood cultures were performed. The patient was started on empirical antibiotic therapy with levofloxacin (750 mg once daily intravenously) and piperacillin/ tazobactam (4.5 g every 6 h intravenously). Due to lack of improvement of symptoms and fever after 48 h, levofloxacin was switched to daptomycin (500 mg daily intravenously). The second dose was administered, by mistake, 4 h before it should have been. Five days after admission, after only two doses of daptomycin, the patient suddenly complained of weakness and diffuse aches in the proximal thighs and arms. Serum CPK levels were very high (12 933 U/L) and further elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT), 371 and 67 IU/L, respectively, were also noted. A urine drug screen was performed to rule out damage related to illicit substance use, and the results were negative. Blood cultures were positive for methicillin-resistant Staphylococcus aureus (MRSA). Suspecting daptomycin-induced rhabdomyolysis, treatment was switched to linezolid (600 mg twice daily intravenously) and meropenem (1 g every 8 h intravenously). The patient was hydrated (2 L/day) to preserve renal function, and this was strictly monitored throughout the course; urinalysis was positive for myoglobin. Although daptomycin had been interrupted, CPK levels and AST/ALT levels continued to increase for 5 days after and on the …

A case of Brucella endocarditis in association with subclavian artery thrombosis

Brucellosis is a common zoonosis, endemic in Mediterranean countries, and caused by bacteria of Brucella genus. Brucellosis is a systemic infection and the clinical presentation varies widely from asymptomatic and mild to severe disease. Cardiovascular complications are extremely rare. We present a case of arterial thrombosis in a previously healthy young patient with Brucella endocarditis. Careful attention must be paid to any sign or symptom of thrombosis in patients affected by brucellosis, regardless of the presence of endocarditis and cardiovascular risk factors.

Severe Mediterranean spotted fever complicated by acute renal failure and herpetic oesophagitis.

Mediterranean spotted fever (MSF) is a tick-borne disease caused by Rickettsia conorii. Recently, complicated cases have been more frequently reported, even in previously healthy patients. We describe a case of severe MSF complicated by acute renal failure and associated with herpetic oesophagitis. Acyclovir therapy resulted in remission of oesophageal symptoms within 48 h.

Probable disseminated Mycobacterium abscessus subspecies bolletii infection in a patient with idiopathic CD4+ T lymphocytopenia: a case report

IntroductionRapidly growing mycobacteria are opportunistic pathogens in patients with underlying risk factors. Mycobacterium abscessus subsp. bolletii is a newly recognized member of rapidly growing mycobacteria, isolated from respiratory tract and cutaneous infections.Case presentationWe describe a case of chronic disseminated infection caused by M. abscessus subsp. bolletii in a 38-year-old Sri Lankan man with idiopathic CD4+ T lymphocytopenia. Idiopathic CD4+ T lymphocytopenia is a rare cause of immunodysfunction that, similar to human immunodeficiency virus infection, causes a depletion of CD4+ T lymphocytes. M. abscessus subsp. bolletii infection was diagnosed by culture isolation from two sputum samples.ConclusionsTo the best of our knowledge this is the first report of M. abscessus subsp. bolletii disseminated infection in a patient affected by idiopathic CD4+ T lymphocytopenia. In contrast to previous reports, the isolate of M. abscessus subsp. bolletii presented intermediate resistance to clarithromycin and was susceptible to cefoxitin and imipenem.

The Downside of an Effective cART: The Immune Restoration Disease

The prognosis of patients infected with human immunodeficiency virus (HIV) type 1 has dramatically improved since the advent of the highly active antiretroviral therapy (HAART), which have enabled sustained suppression of HIV replication and recovery of CD4+ T cells count [1-3]. However, many patients in resource-poor settings still start HAART at a late stage of HIV infection when they already have advanced immunodeficien‐ cy [4,5]. Immune reconstitution in HIV infected patients is characterized by replenishment of immune cells depleted directly or indirectly by HIV infection, by regeneration of primary and secondary lymphoid organs, by restoration of pathogen-specific T, B and NK cells and by a regulation of the reconstituted immune system [2]. It is unclear whether complete im‐ mune reconstitution ever occurs but individuals with human immunodeficiency virus infec‐ tion starting antiretroviral therapy when they are very immunodeficient are susceptible to immune reconstitution disorders. This phenomenon is known as a multitude of names in‐ cluding “immune reconstitution inflammatory syndrome (IRIS)”, “immune reconstitution or restoration disease” (IRD) or immune reconstitution syndrome” and includes various forms of a clinical deterioration as a consequence of a rapid and dysregulated restoration of anti‐ gen specific immune responses causing an exuberant inflammatory reaction and a cytokines storm [1-3]. This was first noted following the introduction of zidovudine monotherapy in the early 1990s, when localized forms of Mycobacterium avium intracellulare (MAI) infection where observed in association with the recovery rather than failure of cellular immune re‐ sponse [6]. Later, in 1992, French MA et al showed that the disease associated with Mycobac‐ terium avium complex (MAC) infection occurred after nucleoside analogue therapy and correlated with restoration of delayed hypersensitivity (DTH) responses to mycobacterial antigens [7].