Respiratory Medicine CME
Volume 2, Issue 3 , Pages 134-136, 2009

Acute respiratory failure and diffuse pulmonary infiltrates four weeks after rituximab therapy

  • Hadi H. Hatoum

      Affiliations

    • Indiana University-Roudebush VA medical center, 1481 west 10th street, 111P-IU, Indianapolis, IN 46202, USA
    • ,
  • George A. Sarosi

      Affiliations

    • Indiana University-Roudebush VA medical center, 1481 west 10th street, 111P-IU, Indianapolis, IN 46202, USA
    • ,
  • Kenneth S. Knox

      Affiliations

    • Southern Arizona VA Health Care System-University of Arizona, Tucson, AZ, USA
    • ,
  • Chadi A. Hage

      Affiliations

    • Indiana University-Roudebush VA medical center, 1481 west 10th street, 111P-IU, Indianapolis, IN 46202, USA
    • Corresponding Author InformationCorresponding author.

Article Outline

Summary 

We report a 51-year-old woman with known SLE on low dose prednisone, recently started on rituximab, who presents with acute respiratory failure and bilateral air space disease. After an initial treatment with broad spectrum antibiotics for healthcare-associated pneumonia and negative serologic studies, a diagnosis of pneumocystis pneumonia was established using bronchoalveolar lavage. We suggest that rituximab can be an aggravating cause of pneumocystis in patients treated with prednisone.

Keywords: Pneumocystis pneumonia, Rituximab

 

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Case report 

A 51-year-old female known to have systemic lupus erythematosus (SLE) with secondary chronic kidney disease was admitted to our hospital with a one week history of shortness of breath, fever, headache, cough and night sweats. The patient was diagnosed with SLE one year prior and was maintained on prednisone 20mg daily. She was recently started on rituximab and had a total of four weekly doses for a suspected flare up of lupus nephritis. She received the last dose four weeks prior to presentation. On hospital admission, the patient was in mild respiratory distress. Body temperature was 102.9F, respiratory rate was 20 breaths per minute, and pulse oxygen saturation was 84% while breathing room air. Blood pressure was 138/72mmHg and heart rate was 103 beats per minute. Physical examination revealed coarse bilateral inspiratory crackles.

Laboratory findings were as follows: White blood cell count was 6.6×103cells/μL with a manual differential showing 80% neutrophils and 13% lymphocytes. Hemoglobin concentration was 10.7g/dL, and platelet count was 235×103/mL. Serum chemistries showed a creatinine level of 4.3mg/dL, BUN of 49mg/dL, serum sodium of 129mmol/L, potassium of 5.8mmol/L, serum bicarbonate of 20mmol/L, chloride of 100mmol/L, LDH was 695units/L. Admission chest radiograph showed bibasilar air space disease (Fig. 1A). Chest CT revealed diffuse bilateral ground glass opacities with more confluent airspace consolidation in the lung bases (Fig. 1B).

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  • Figure 1 

    (A): Chest radiograph showing bibasilar interstitial infiltrates. (B): chest CT scan showing bilateral patchy areas of groundglass opacities with airspace consolidation in the right lung bases, and scattered, small nodular opacities.

The patient was admitted to the hospital and was treated for healthcare-associated pneumonia (HCAP) with vancomycin, cefepime and ciprofloxacin. Workup done including blood and urine cultures, urine Histoplasma and Legionella antigens, CMV titers, and HIV antibody screen were all negative. Absolute CD4 blood count was 70cells/μL.

Despite two days of broad spectrum antibiotics, the patient continued to be febrile and had worsening hypoxia and increased work of breathing. Bronchoscopy for a bronchoalveolar lavage (BAL) was performed. Cytopathologic examination of BAL smears revealed Pneumocystis jiroveci. No other pathogenic organisms were isolated. The patient was started on Trimethoprim/Sulfamethoxazole and the steroid dose was increased. Her condition subsequently improved as fever and hypoxia resolved and she recovered completely and was discharged from the hospital. CD4 count recovered spontaneously after discontinuation of rituximab. Six months later her absolute CD4 count was 539cells/μL.

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Discussion 

P. jiroveci pneumonia (PCP) is the most common opportunistic infection in AIDS patients. Less frequently, PCP is seen in non-HIV immunosupressed patients with hematologic malignancies, organ transplantation, inflammatory disorders, and solid tumors.1

Our patient has SLE. She had a negative HIV antibody screen. Both humoral and cellular arms of her immune system are suppressed, since she was on prednisone and rituximab. Rituximab is a monoclonal antibody that selectively targets and depletes CD20+B lymphocytes. B-cell depletion affects antibody production, antigen presentation and T cell activation. SLE treatment with rituximab has been shown to affect both the cellular and humoral immune response.2

The temporal relationship between rituximab infusion and the development of PCP suggest that rituximab predisposed our patient to pneumocytis infection. Rituximab has been proposed as a risk factor for PCP infection. The mechanism leading to infection is not clear. In one case series, one of three patients with refractory pemphigus vulgaris who were treated with rituximab developed fatal pneumocystis pneumonia 4 months after finishing therapy.3 In a recent study, the incidence of PCP was 13 % in a population of 46 lymphoma patients who received rituximab-CHOEP-14 chemotherapy.4, 5 Rituximab can also cause profound CD4 depletion. Patients with HIV-associated NHL had a moderate reduction in their CD4 cell count after 6 cycles of treatment with chemotherapy and rituximab.6 In addition, chronic use of corticosteroids is a known risk factor for PCP in non-AIDS patients. Other opportunistic infections such as CMV retinitis, pulmonary tuberculosis, salmonellosis and cryptosporidiosis have been reported in patients receiving rituximab.

In conclusion, we suggest that the combination of rituximab and systemic corticosteroids steroid predisposed our patient to pneumocystis infection. Further studies are needed to better define this association and determine whether PCP prophylaxis is indicated in those who receive rituximab.

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Conflict of interest statement 

The authors have no competing interests to declare. The manuscript has been reviewed and approved by all authors.

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References 

  1. Yale SH, Limper AH. Pneumocystis carinii pneumonia in patients without acquired immunodeficiency syndrome: associated illness and prior corticosteroid therapy. Mayo Clin Proc. 1996 Jan;71(1):5–13
  2. Vallerskog T, Gunnarsson I, Widhe M, Risselada A, Klareskog L, van Vollenhoven R, et al. Treatment with rituximab affects both the cellular and the humoral arm of the immune system in patients with SLE. Clin Immunol. 2007 Jan;122(1):62–74
  3. Morrison LH. Therapy of refractory pemphigus vulgaris with monoclonal anti-CD20 antibody (rituximab). J Am Acad Dermatol. 2004 Nov;51(5):817–819
  4. Kolstad A, Holte H, Fossa A, Lauritzsen GF, Gaustad P, Torfoss D. Pneumocystis jirovecii pneumonia in B-cell lymphoma patients treated with the rituximab-CHOEP-14 regimen. Haematologica. 2007 Jan;92(1):139–140
  5. Spina M, Jaeger U, Sparano JA, Talamini R, Simonelli C, Michieli M, et al. Rituximab plus infusional cyclophosphamide, doxorubicin, and etoposide in HIV-associated non-Hodgkin lymphoma: pooled results from 3 phase 2 trials. Blood. 2005 Mar 1;105(5):1891–1897
  6. De Paoli P, Vaccher E, Tedeschi R, Caffau C, Zanussi S, Bortolin MT, et al. Lymphocyte subsets and viral load in patients with HIV-associated non-Hodgkin's lymphoma treated with anti-CD20 monoclonal antibody and chemotherapy. Cancer Immunol Immunother. 2001 May;50(3):157–162

PII: S1755-0017(08)00105-X

doi:10.1016/j.rmedc.2008.12.004

Respiratory Medicine CME
Volume 2, Issue 3 , Pages 134-136, 2009

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