successful antiviral treatment of chronic hepatitis c in patients with rare comorbidities two case reports

Abstract Antiviral therapy in patients suffering from chronic hepatitis C virus (HCV) infection and rare comorbidities cannot be easily started, as it can reduce the likelihood of a good therapeutic response with an increased frequency of side effects. We report two patients presenting unusual comorbidities associated with chronic C hepatitis: one with the Ehlers-Danlos Syndrome (EDS), a rare genetic disease caused by a defect in collagen synthesis, the other one with the Charcot Marie Tooth (CMT) disease, an uncommon but severe form of demyelinating peripheral neuropathy. Both patients were successfully treated with pegylated Interfe-ron (Peg-IFN) and ribavirin (RBV) combined therapy, with the achievement of a sustained viral response (SVR) and a low occurrence of adverse effects. Up to now there are no reports of patients suffering from chronic C hepatitis associated with these uncommon but severe comorbidities treated with antiviral therapy. In conclusion, in such clinical situations, anti-HCV therapy may be started and tailored, especially if the patient is highly motivated and if optimal predictors of response (i.e. young age, favourable genotype and low baseline viraemia) do exist

La sarcopenia nell’anziano con HIV

La sarcopenia è una sindrome caratterizzata dalla perdita progressiva e generalizzata di massa scheletrica e forza muscolare associata ad un aumentato rischio di disabilità fisica, bassa qualità di vita, comorbosità e morte. Nella popolazione generale, la perdita di massa muscolare è strettamente dipendente dall’età e dalla quantità di tessuto muscolare raggiunto con l’accrescimento. In condizioni fisiologiche la massa muscolare diminuisce di circa l’1-2% all’anno dopo i 50 anni. Le donne subiscono una perdita accelerata di tessuto muscolare in età più precoce rispetto agli uomini, e questo fenomeno si accelera a partire dalla menopausa; tuttavia, gli uomini perdono più massa muscolare nel corso della loro vita rispetto alle donne

Successful antiviral treatment of chronic hepatitis C in patients with rare comorbidities. Two case-reports

Antiviral therapy in patients suffering from chronic hepatitis C virus (HCV) infection and rare comorbidities cannot be easily started, as it can reduce the likelihood of a good therapeutic response with an increased frequency of side effects. We report two patients presenting unusual comorbidities associated with chronic C hepatitis: one with the Ehlers-Danlos Syndrome (EDS), a rare genetic disease caused by a defect in collagen synthesis, the other one with the Charcot Marie Tooth (CMT) disease, an uncommon but severe form of demyelinating peripheral neuropathy. Both patients were successfully treated with pegylated Interfe-ron (Peg-IFN) and ribavirin (RBV) combined therapy, with the achievement of a sustained viral response (SVR) and a low occurrence of adverse effects. Up to now there are no reports of patients suffering from chronic C hepatitis associated with these uncommon but severe comorbidities treated with antiviral therapy. In conclusion, in such clinical situations, anti-HCV therapy may be started and tailored, especially if the patient is highly motivated and if optimal predictors of response (i.e. young age, favourable genotype and low baseline viraemia) do exist

Successful antiviral treatment of chronic hepatitis C in patients with rare comorbidities. Two case-reports

Antiviral therapy in patients suffering from chronic hepatitis C virus (HCV) infection and rare comorbidities cannot be easily started, as it can reduce the likelihood of a good therapeutic response with an increased frequency of side effects. We report two patients presenting unusual comorbidities associated with chronic C hepatitis: one with the Ehlers-Danlos Syndrome (EDS), a rare genetic disease caused by a defect in collagen synthesis, the other one with the Charcot Marie Tooth (CMT) disease, an uncommon but severe form of demyelinating peripheral neuropathy. Both patients were successfully treated with pegylated Interferon (Peg-IFN) and ribavirin (RBV) combined therapy, with the achievement of a sustained viral response (SVR) and a low occurrence of adverse effects. Up to now there are no reports of patients suffering from chronic C hepatitis associated with these uncommon but severe comorbidities treated with antiviral therapy. In conclusion, in such clinical situations, anti-HCV therapy may be started and tailored, especially if the patient is highly motivated and if optimal predictors of response (i.e. young age, favourable genotype and low baseline viraemia) do exist

Disease Progression in HIV Late Presenters: the Role of HIV Clinical Indicator Diseases Prior to HIV Diagnosis

Late diagnosis represents a major challenge in the control of HIV epidemics. The rate of disease progression is higher among late presenters. In Europe, HIV Clinical Indicator Diseases (CIDs) have been proposed to improve early diagnosis

INFEZIONE CUTANEA DISSEMINATA DA MYCOBACTERIUM KANSASII IN PAZIENTE CON LEUCEMIA LINFATICA CRONICA

Premesse: Mycobacterium kansasi è un micobatterio atipico responsabile di quadri polmonari anche gravi, soprattutto in pazienti compromessi (BPCO) o immunocompromessi (HIV, neoplasie, chemioterapie). Obiettivo: riportiamo il caso di un paziente affetto da leucemia linfatica cronica (LLC), con infezione disseminata cutanea da M. kansasii associata ad interessamento polmonare. Risultati: il paziente giungeva alla nostra osservazione per la comparsa da alcuni mesi di una lesione ulcerata, secernente e dolente a livello della coscia sinistra, associata a tosse poco produttiva. Dall'anamnesi emergeva puntura di insetto nella sede della lesione e storia di leucemia linfatica cronica plurirefrattaria, in trattamento con steroide a basse dosi. Gli esami ematici mostravano linfocitosi assoluta, PCR <0.4 mg/dl. Il paziente era apiretico e in discrete condizioni generali; negative sierologie per HIV, toxoplasma, lue, CMV. Test QuantiFERON positivo. L'esame istologico della lesione mostrava tessuto fibroso e macrofagi a citoplasma zaffato da bacilli PAS positivi e Ziehl-Neelsen positivi mentre le colture dalla lesione e dall'escreato risultavano positive per M. kansasii, resistente a isoniazide. RX torace e TC torace erano negativi. Si iniziava pertanto terapia con Rifampicina (600 mg die), Claritromicina (500 mg x 2 die) ed Etambutolo (400 mg x 3 die), con guarigione completa dell'ulcera e scomparsa della tosse. Durante il ricovero si è assistito anche a riacutizzazione della LLC, per cui si riprendeva terapia immunosoppressiva con Ibrutinib. Attualmente il paziente ha completato 6 mesi di terapia (durata prevista del trattamento, 12-18 mesi), con ottima tollerabilità. Conclusioni: le micobatteriosi non tubercolari rappresentano patologie ubiquitarie, sostenute da microrganismi il cui serbatoio è prevalentemente ambientale. Nel paziente immunocompromesso non è raro riscontrare forme disseminate da M. kansasii, contraddistinte soprattutto da un coinvolgimento polmonare. Nel nostro caso tuttavia, la localizzazione cutanea è stata predominante, mentre il quadro polmonare, del tutto secondario. Rari sono i casi di coinvolgimento cutaneo da M. kansasii riportati in letteratura: Ad oggi, le descrizioni di localizzazione extrapolmonare da M. kansasii, riguardano in prevalenza forme settiche ed osteo-articolari in pazienti con patologie reumatiche (borsiti, tenosinoviti), mentre solo 4 (dal 2003), pazienti HIV positivi o con co-morbidità ematologica. Nel nostro caso resta da chiarire se l'interessamento cutaneo sia stato conseguente alla puntura di insetto contaminatasi con le secrezioni respiratorie infette, o se esso stesso sia stato fonte di successiva disseminazione ematogena al polmone. L'infezione da M. kansasii dovrebbe sempre sospettata in paziente ematologici, anche in caso di quadri clinici non usuali, come quello cutaneo

PLASMABLASTIC LYMPHOMA OF ORAL CAVITY WITH GASTRIC AND BONE-MARROW INVOLVEMENT IN A YOUNG PATIENT WITH MOTHER-TO-CHILD TRANSMITTED HIV

Introduction: Incidence of non-Hodgkin lymphoma (NHL) is 200 times higher in HIV-positive patients than otherwise healthy persons. Plasmablastic lymphoma (PBL) accounts for less than 3% of all NHL in HIV patients and it’s associated with very poor prognosis. Immunodeficiency and HIV viremia are major risk factors for developing cancers, and high adherence to highly active antiretroviral therapy (HAART) has a protective role. Case: We report here a case of 21-year-old HIV positive boy, presented to our Emergency Room for persisting dysphagia, vomit and weight-loss. He had a history of mother-to-child HIV transmission and multiple virological failures due to his poor HAART-adherence. On oral examination a mass in mandibular gingiva and one in hard palate were detected in association with oral candidiasis. Blood test revealed T-CD4+ cells 16/µl and HIV viral load 161.000 copies/µl. An esophagogastroduodenoscopy showed a 70 mm diameter mass on gastric small curvature. Total body CT scan documented also bilateral expansive lesions of maxillary sinus. Biopsies of gingival, palatine and gastric lesions were performed and all showed CD138+, CD20-, Epstein-Barr-virus (EBV)-associated PBL. Osteomedullary biopsy was positive for bone marrow involvement. The patient (classified as IV/B Ann-arbor stage) re-started HAART and initially underwent 2 CHOP regimens without benefits, thus DHAP chemotherapy was started, but also this proved ineffective. The patient received radiotherapy combined to corticosteroids and gemcitabine until his death, that occurred during a hospitalization for febrile neutropenia 6 months after PBL diagnosis. Conclusions NHL is the most common HIV related cancer after Kaposi’s sarcoma. AIDS-related NHLs are predominantly aggressive high-grade B-cell lymphomas, such as PBL. This, like in our case, is characterized by weak/absent expression of conventional B-cell markers (CD20,CD45), by strong expression of plasma cell marker(CD138) and by EBV-relationship. Recognition of this entity by pathologists and clinicians is not easy but mandatory in order to start correct and early treatment. This lymphoma shows a tropism to the oral cavity, but involvement of areas other than head and neck (such as gastrointestinal tract) is rarely described. In literature, the apparent rarity of extra-oral sites and of such an advanced stage, as our patient, may be due to a closer follow up of HIV patients (among whom this lymphoma is more common) in addition to a lack of recognition. To the best of our knowledge, this is the first report of this entity in a vertically transmitted HIV-positive young man. This case highlights the increased risk of NHL in young people with vertical HIV infection, because of persistent immunodeficiency and viremia. Indeed low adherence to HAART, typical in this group of patients, might represent an emerging problem and NHL screening should be offered, in association with intervention to improve adherence, such as HAART simplification, if possible

SUCCESFULL TREATMENT OF PULMONARY NOCARDIOSIS WITH LINEZOLID

Nocardiosis is an opportunistic infection, with high mortality especially in immunocompromised patients. Up to one-third of patients with nocardiosis, however, are immunocompetent and the occurrence of the disease in these patients especially with chronic obstructive pulmonary disease (COPD) as the present case, can delay diagnosis and lead to rapidly respiratory failure. A 82-years-old men, affected by COPD and chronic HBV-related hepatitis, was admitted in November 2012 to a regional hospital because of fever and cough (July 2012), with temporary benefit from a previously prescribed antibiotic treatment. He underwent chest High-Resolution-TC (HRTC) which showed lower left lobe pneumonia and was treated with ceftriaxone, with subsequent apyrexia. After discharging fever and cough relapsed and he was again admitted in hospital. HRTC showed widespread focal areas of pneumonia and a bronchoscopy was performed. Bronchial washing culture showed Nocardia spp colonies, but microbial identification was not done. A therapy with trimethoprim-sulphamethoxazole (TMP-SMX, TMP 240 mg-SMX 1200 mg TID) intravenously (i.v) was started, with initial slow improvement of clinical conditions, followed by relapse of fever and increasing values of white blood cells and reactive-C-protein (RCP, 15.2 mg/dl). The patient was thus admitted at our Institution in January 2013 and antibiotic therapy was intensified (TMP 240 mg-SMX 1200 mg QID plus amikacin 1 g QD i.v). Clinical conditions improved and WBC and RCP values decreased. A lung TC showed no differences with the previous one. After 2 weeks he developed respiratory failure; a chest x-rays showed a significant widespread pneumonia and RCP values increased; amikacin was ended and meropenem 4g daily i.v was started. One week after, no clinical, laboratory or radiologic improvement was observed; TMP-STX was discontinued and Linezolid 1200 mg daily i.v was started. Respiratory failure rapidly disappeared. After two weeks of treatment, clinical conditions markedly improved, RCP values decreased and radiological findings were less extended. Therapy is still ongoing. This will be switched orally and continued for 4-6 months, according to clinical and radiological findings. Optimal antimicrobial treatment regimens for nocardiosis have not been firmly established. Moreover, as described for N. farcinica in Northern Italy, resistance to first-line regimens can occur, but most laboratories are not able to identify species and perform antibiogram, thus therapy can be quite empiric. TMP-SMX resistance, as this case remarks, can develop in vivo after initial effective treatment. Linezolid administration has been successfully reported for brain abscess and pneumonia caused by different Nocardia spp, because of its efficacy and good penetration in lung and CNS. Oral formulation is useful for long-lasting treatment as required, although bone-marrow and neurologic toxicity must be carefully evaluated

SIGNIFICANCE OF PROGNOSTIC VALUE OF ANEMIA IN PREDICTING OPPORTUNISTIC INFECTIONS IN HIV-INFECTED LATE PRESENTER PATIENTS STARTING ANTIRETROVIRAL THERAPY

Introduction Anemia represents a well-known complication of HIV infection, especially in end-stage disease. Several factors could have an impact on Hemoglobin (HB) level in this disease, such as opportunistic infections, neoplasia and drugs. Many studies have demonstrated how developing of anemia is related with an higher incidence of AIDS, non-AIDS defining events or deaths, even if most of them concern to pre-HAART era; to our knowledge, few data examine the relationship between HB level at baseline and the risk of new AIDS events and new admissions to hospital among late presenters (LP) in the HAART-era. Methods We analyzed retrospectively patients’ data with new diagnosis of HIV and less than 350 T-CD4 cells/µL in period 2008-2013 in 2 HIV centers of North Italy; Santa Maria della Misericordia of Rovigo and Sant’Anna - University of Ferrara hospitals. Patients were sorted by HB level at baseline and divided in two groups: Group A and Group B, with and without anemia, respectively. Anemia was defined according the World Health Organization definition (Hb <13.0 g/dL in males, <12.0 g/dL in females). Chi-square Fisher’s exact test was emplojed to analyze differences among the two groups for new AIDS-events, new hospital admissions and virological failure. T-student test was used to evaluate differences among cell-T CD4+ in two groups. Results Of the 233 new diagnoses reported in 2008-2013 by the two centers, 47.6% were LP patients. Of these, 56 (71.8%) were males (22 Group A; 34 Group B) and 22 (28.2%) were females (12 Group A; 10 Group B). The median age of LP was 43 years (IQR 35-52) in Group A and 43 (IQR 36-52) in Group B. Risk factors related with HIV transmission were HET in 45 patients (20 Group A, 25 Group B), MSM in 12 (6 Group A, 6 Group B), IDU in 3 (2 Group A, 1 Group B), Other/Unknown 18 (6 Group A, 12 Group B). Of the 233 new diagnoses, 111 (47.6%) were LP; of these, (7.2%) died. Due to lack of data, 25 patients were excluded. 34 LP patients (43.6%) had anemia at diagnosis, compared to 44 (56.4%) patients without anemia. Total median values of T-CD4+-cells observed at the moment of diagnosis of HIV was 116/µL (IQR 59-217); in Group A, 74/µL (IQR 50-147) compared to 180/µL (IQR 76-245) (p0,05). Virological failure occurred in 11 patients (32.3%) in Group A, 9 (20.5%) in Group B (p>0,05). After beginning of HAART, 9 patients developed at least one new AIDS event (total number of new AIDS-events was 13) in Group A, 1 (1 new AIDS events) in Group B (p 0,05) Conclusion Despite beginning of HAART, patients who present late at diagnosis continue to have high risk of developing new AIDS-events or to be re-admitted at hospital. Both patient groups at moment of diagnosis had a median of T-CD4 cells count <200/µL, thus being at risk of developing AIDS. HB value before starting HAART seems to have an important prognostic role to pinpoint, among LP, who has an higher risk of new AIDS events. For this reason LP with anemia should be monitored with a closer follow-up to identify as soon as possible worsening of health-condition

Brain Abscess Sustained by Actinomyces meyeri in an Immunocompetent Patient

Actinomycosis is a rare granulomatous disease, caused by filamentous Gram positive anaerobic bacteria, which may become pathogenic following disruption of anatomical barriers with invasion of host’s deep tissues and dissemination of infection to any site of the organism. A. israelii is found in most clinical presentations. We describe a case of a 41 years-old immunocompetent woman affected by thalamic abscess due to Actinomyces meyeri, presenting with fever, headache, vomit, confusion. A brain Computed Tomography (CT) and a Magnetic Resonance Imaging (MRI) revealed an expansive thalamic lesion with wide central necrosis and perilesionaledema. The patient was immediately addressed to a first evacuation of the mass, followed by a second drainage because of recurrence of the abscess. Microbiological and histological findings from intraoperatory specimens, resulted positive for A. meyeri. Ampicillin 20 g plus rifampicin 1200 mg/day was started, followed by ceftriaxon 4 g/day for 2 weeks and by amoxicillin 3 g/day. The treatment was discontinued after 9 months; brain MRIs performed at the end of therapy and after 3 and 6 months from the interruption of therapy revealed a gradual but complete resolution of cerebral abscess. Actinomycosis is an infrequent but severe disease that can mimic tuberculosis, nocardiosis and malignancies. Cases of cerebral actinomycosis reported in literature are limited, but those from A. meyeri are extremely rare. Moreover this pathogen is often related to disseminated disease, especially in immunocompromised patients. There is no consensus about treatment of cerebral actinomycosis: different types of regimens are proposed; we firstly administered ampicillin (12-16 g/day for at least six months), plus rifampicin, to enhance their penetration in CNS. Actinomycosis requires a prompt diagnosis and antibiotic treatment (often in combination with surgery) in order to avoid dissemination and prevent complications