Should Pneumocystis jiroveci prophylaxis be recommended with Rituximab treatment in ANCA-associated vasculitis?

Reports in haematology, transplantation medicine and rheumatology indicate that Rituximab, a B cell depleting therapy, increases the risk for Pneumocystis jiroveci pneumopathy. Patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis have an increased incidence of P. jiroveci pneumopathy compared to other autoimmune diseases and Rituximab is often used to induce and maintain remission. Herein, we present a case of a patient with granulomatosis with polyangiitis treated with Rituximab for relapse that developed P. jiroveci pneumopathy 3 months after and we review the relevant literature to assess P. jiroveci pneumopathy incidence and risks factors under Rituximab. We also discuss whether P. jiroveci screening before Rituximab and P. jiroveci pneumopathy prophylaxis under Rituximab are indicated. P. jiroveci colonisation is found in 25 % of patients with autoimmune diseases. However, the association between colonisation and P. jiroveci pneumopathy development is not very strong. P. jiroveci pneumopathy incidence in ANCA-associated vasculitis patients treated with Rituximab is found to be 1.2 %. Therefore, evidence and practice do not support the use of P. jiroveci pneumopathy chemoprophylaxis in all ANCA-associated vasculitis patients receiving Rituximab. CD4 cell count cut-off does not work well in patients treated with Rituximab as it does not reflect T cell impairment following B cell depletion. To help stratify the risk of both colonisation and P. jiroveci pneumopathy development, assessment of the patient’s net state of immunodeficiency before administering Rituximab—including age, renal or lung involvement, previous infections due to T cell dysfunction, blood tests (lymphocytopenia, low CD4 cell count) and concomitant therapy—is warranted.     

Is there a role for Pneumocystis jiroveci pneumonia prophylaxis in giant cell arteritis or polymyalgia rheumatica?

BackgroundPneumocystis jiroveci pneumonia (PJP) is an opportunistic fungal infection that affects immunocompromised patients. The objective of this study was to describe the incidence of PJP among patients with giant cell arteritis (GCA) or polymyalgia rheumatica (PMR).MethodsA retrospective cohort study of incident cases of GCA and PMR was conducted using claims data from the TriNetX database to describe the incidence of PJP during the first 6 months of therapy. Additionally, a systematic review was performed to identify other publications describing PJP among patients with GCA or PMR.ResultsDuring 547 patient-years of follow-up time, no cases of PJP were identified among 1,168 cases of GCA (incident rate 0 per 1,000 person-years); during 7,446 patient-years of follow up time, one case of PJP was identified out of 15,575 cases of PMR (incident rate 0.07 cases per 1,000 patient-years). This patient was alive at last follow up. Our systematic review identified 1 case-control study, 4 cohort studies, and 18 case series / case reports of PJP among patients with GCA or PMR. The incident rate of PJP was reported from one additional study for GCA and was estimated at 0.08 cases per 1,000 person years; no additional cohort studies were identified for patients with PMR. Over the entirety of the published literature, the total number of cases identified among case series and case reports was 33, from which 4 total deaths were identified.ConclusionsPatients with newly diagnosed GCA or PMR rarely develop PJP. Existing data does not support routine prescribing of PJP prophylaxis for either group of patients.     

Pneumocystis Carinii pneumonia postrestorative proctocolectomy for ulcerative colitis: A role for perioperative prophylaxis in the cyclosporine era?

PURPOSE: Medical management of severe ulcerative colitis has used cyclosporine with increasing frequency as an adjuvant to systemic steroids and mercaptopurine. However, the effects of combined management with cyclosporine and prednisone may lead to significant immune compromise and adversely affect operative morbidity in the event urgent surgery is required. METHODS: A case is reported of a 43-year-old white male who presented with severe ulcerative colitis. The patient had been initially treated with prednisone and cyclosporine for six weeks before surgical intervention. The intractability of his ulcerative colitis caused the patient to present to surgery, where he underwent restorative proctocolectomy. RESULTS: On initial presentation, the patient manifested systemic signs of severe ulcerative colitis with hypoalbuminemia, anemia, and weight loss, despite continuous prednisone and cyclosporine management. Before surgical intervention, a chest x-ray and the patient's respiratory status were normal. A total abdominal colectomy with ileal pouch reconstruction and temporary loop ileostomy were performed without incident. On the fifth postoperative day, the patient developed respiratory failure, which was subsequently diagnosed asPneumocystis carinii pneumonia. Although ventilator support and both aggressive medical and surgical management eventually resulted in successful outcome, significant perioperative morbidity occurred. CONCLUSIONS: In the era of aggressive medical management for ulcerative colitis with both steroids and cyclosporine, the complications of immunosuppression may be significant, including opportunistic pneumonia. Prophylaxis againstP. carinii pneumonia with sulfa antibiotics should be considered, especially in patients for whom proctocolectomy is a potential end point.     

How many times can parvovirus B19‐related anemia recur in solid organ transplant recipients?

Parvovirus B19 (PB19) infection is known to cause acute erythroblastopenia‐mediated anemia in solid organ transplant (SOT) recipients. Intravenous immunoglobulins (IVIg) and the decrease of immunosuppression level are supposed to induce a long‐term remission, although no consensus exists about the dose and the schedule of IVIg administrations. However, a few reports have shown that PB19‐related anemia can recur despite this treatment, with a maximum of 3 recurrences reported. In this report, we describe in detail the cases of 2 kidney recipients with PB19 infection. They experienced, respectively, 9 and 7 PB19‐related anemia recurrences. Immunosuppression level was decreased and IVIg were administered at each recurrence followed by a transitory normalization of hemoglobin level and a decrease of serum PB19 viral load. Episodes were separated by several months. These patients raise an original therapeutic management question about a frequent viral infection in SOT recipients. One patient is currently receiving IVIg every 3 months as a secondary prophylaxis without recurrence to date. These 2 case reports are followed by a review of the literature.     

How aggressively should blood pressure be treated in renal transplant recipients?

Renal transplantation is the treatment of choice for many patients with endstage renal disease. Patient survival is improved compared with dialysis for all patient ages and racial groups. Renal allograft survival is closely connected with recipient blood pressure. Blood pressure treatment goals that improve patient outcome have been defined for patients with nontransplant renal disease but not for patients with renal transplants. Extrapolating from data from nonrenal transplant patients suggests that aggressive treatment of hypertension in renal transplant patients may improve allograft and patient survival.     

Should we be performing more combined hematopoietic stem cell plus solid organ transplants?

Both bone marrow and solid organ transplants (SOTs) can be life saving for a wide variety of diseases. We reviewed the literature and summarized the experiences of dual transplants. In total, 37 patients received a SOT for organ failure after a previous hematopoietic stem cell transplant. In all, 12 subjects received SOTs followed by a bone marrow transplant, while three patients received simultaneous SOTs and bone marrow transplants. Of these 52 patients, 37 were alive at the time of the original report at follow-up times ranging from 3 months to 8 years. A special registry for data collection may prove helpful for obtaining long-term follow-up data and providing outcome information that may improve future patient survival.     

Should intravesical Bacillus Calmette‐Guérin be employed in transplant recipients with bladder carcinoma?

H.‐Y. Sun, N. Singh. Should intravesical Bacillus Calmette‐Guérin be employed in transplant recipients with bladder carcinoma?
Transpl Infect Dis 2010: 12: 358–362. All rights reserved Abstract: Bacillus Calmette‐Guérin (BCG) exerts its antitumor activity through induction of pro‐inflammatory cytokines, while immunosuppressive agents prevent organ rejection by suppressing pro‐inflammatory and promoting anti‐inflammatory responses. Thus, in the setting of transplant populations, the use of intravesical BCG for bladder cancer has the possibility of either promoting allograft rejection or being rendered ineffective by the action of immunosuppressive agents that block pro‐inflammatory responses. We discuss the potential immunologic interactions between BCG and immunosuppression, and review relevant outcomes in renal transplant recipients with bladder cancer receiving intravesical BCG.     

Infections and solid organ transplant rejection: a cause-and-effect relationship?

Although evidence is far from being conclusive, several studies have suggested that infections could trigger rejection in different transplant settings. In this review we examine the evidence linking cytomegalovirus (CMV), adenovirus, enterovirus, parvovirus, and herpes simplex virus infections to the vasculopathy leading to cardiac allograft rejection, the association between CMV and chronic kidney, lung, and liver graft rejection, and the association of human herpesvirus 6 reactivation with CMV-related disease in kidney and liver transplant recipients. We also review the numerous antiviral prophylactic or pre-emptive treatments in use to control CMV infection, and suggest that they do not limit immune reactions leading to graft rejection or lower the risk of developing post-transplantation atherosclerosis in allograft recipients. Finally, we emphasise the need for prospective, international studies to clarify the role of infections in transplant rejection, to look at virus-to-virus interactions, and to establish specific therapeutic strategies. Such strategies must not rely exclusively on expensive antiviral agents but also on vaccination or other, innovative approaches, such as the use of agents able to inhibit the activity of natural killer cells, which might have an important role in acute allograft rejection.     

A dose-escalation regimen of trimethoprim–sulfamethoxazole is tolerable for prophylaxis against Pneumocystis jiroveci pneumonia in rheumatic diseases

Abstract

Objective To investigate the safety and efficacy of a dose-escalation regimen of trimethoprim–sulfamethoxazole (TMP/SMX) for prophylaxis against Pneumocystis jiroveci pneumonia (PCP) in rheumatic diseases.

Methods Data from 41 patients, who received glucocorticoids with or without immunosuppressive agents and prophylactic use of TMP/SMX, were retrospectively analyzed. Thirteen patients were started on a daily dose of 10 % of single-strength (SS) TMP/SMX, which was increased gradually (dose-escalation group), while 28 patients were started on 1 SS tablet daily (routine group).

Results In the dose-escalation group, the retention rate was 100 % at 6 months. In the routine group, 5 patients discontinued TMP/SMX; the retention rate was 82.1 %. Moreover, the retention rate when taking a daily dose of 50 % or more of SS TMP/SMX, or 1 SS tablet thrice-weekly, was significantly higher in the dose-escalation group (100 versus 71.4 %, P = 0.032). No PCP was observed in the dose-escalation group; however, 1 patient in the routine group, who had discontinued TMP/SMX, developed PCP. The rate of adverse effects was less, although nonsignificant, in the dose-escalation group (30.8 versus 46.4 %, P = 0.344).

Conclusions In rheumatic diseases, a dose-escalation regimen of TMP/SMX resulted in a higher retention rate and was safer than the routine regimen.