Pneumocystis Jirovecii (Carinii) (PCP)

Epidemiology

Risk Factors

  • Agammaglobulinemia
  • Anti-CD20 Therapy (see Anti-CD20 Therapy): possible risk factor
  • Anti-Tumor Necrosis Factor-α (Anti-TNF) Therapy (see Anti-Tumor Necrosis Factor-α Therapy): infliximab, etanercept, adalimumab
    • Little is known about the role of TNFα in the host defense against PCP, but infliximab decreases peripheral and gut mucosal CD4 counts in patients with Crohn’s Disease [MEDLINE] [MEDLINE]
    • Relative Risk: infliximab > etanercept/adalimumab
    • Dosing: patients had received an average of 2 drug infusions
    • Mean Latency Between Drug Infusion and Onset of Symptoms: 21 days
    • Mortality Rate: 27% [MEDLINE]
  • Bendamustine (see Bendamustine): case report
  • Chlorambucil (see Chlorambucil)
  • Chronic Lymphocytic Leukemia (CLL) (see Chronic Lymphocytic Leukemia): few reported cases of PCP with CLL alone, however, risk appears to be the greatest in CLL patients that have received steroids and/or fludarabine
  • Common Variable Immunodeficiency (CVID) (see Common Variable Immunodeficiency)
  • Corticosteroids (see Corticosteroids): equivalent to >16 mg prednisone/day for at least 8 wks [MEDLINE]
  • Cyclophosphamide (Cytoxan) (see Cyclophosphamide)
  • Cyclosporine A (see Cyclosporine A)
  • Good’s Syndrome: a B-cell immunodeficiency syndrome
  • Human Immunodeficiency Virus (HIV) (see Human Immunodeficiency Virus)
    • CD4<250 (most cases occur with CD4 <100 though)
    • Only 5% of cases occur in HIV patients with CD4 >400
  • Methotrexate (see Methotrexate)
  • Tofacitinib (Xeljanz) (see Tofacitinib)

Microbiology

  • Pneumocystis Jirovecii: although formerly thought to be a protozoan, rRNA subunit analysis links it phylogenetically to fungi
    • Transmission: could be either reactivation of latent infection or airborne acquisition of new infection

Clinical Presentations

General Comments

  • Non-AIDS Cases: typically have a more severe clinical presentation and are often associated with the tapering of an immunosuppressive agent (such as prednisone or cyclophosphamide)
  • Immune Reconstitution Inflammatory Syndrome (IRIS) (see Immune Reconstitution Inflammatory Syndrome)

Normal Chest X-Ray Presentation

  • Epidemiology: occurs in 10% of cases
    • However, in such cases, chest CT is abnormal

Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome)

  • Epidemiology: xxx

Alveolar Pneumonia (see Pneumonia)

  • Diagnosis
    • LDH: elevation is highly sensitive, but not very specific (as can also be elevated in other pulmonary processes, such as bacterial pneumonia or tuberculosis)
    • Chest X-Ray (see Chest X-Ray)
      • Alveolar infiltrates
    • Chest CT (see Chest Computed Tomography)
      • Mosaic Pattern or Ground-Glass Infiltrates: most common pattern is that with central densities
      • Lymphadenopathy: uncommon
      • Pneumatoceles/Pneumocysts: may occur (see Cystic-Cavitary Lung Lesions)
    • Bronchoscopy with Bronchoalveolar Lavage (BAL) (see Bronchoscopy): typically higher BAL neutrophil counts and lower organism counts are seen in non-AIDS cases
  • Clinical: pneumonia-like presentation

Cryptogenic Organizing Pneumonia (COP) (see Cryptogenic Organizing Pneumonia)

  • Epidemiology: xxx
  • Clinical: may have pneumonia-like presentation

Interstitial Pneumonia (see Interstitial Lung Disease)

  • Diagnosis
    • LDH: elevation is highly sensitive, but not very specific (as can also be elevated in other pulmonary processes, such as bacterial pneumonia or tuberculosis)
    • Chest X-Ray (see Chest X-Ray): interstitial infiltrates
    • Chest CT (see Chest Computed Tomography): mosaic pattern or ground-glass infiltrates
      • Lymphadenopathy: uncommon
    • Bronchoscopy with Bronchoalveolar Lavage (BAL) (see Bronchoscopy): typically higher BAL neutrophil counts and lower organism counts are seen in non-AIDS cases
  • Clinical
  • Example: 40 y/o white female on prednisone 40 mg PO qday, tapered to 30 mg qday 1 wk prior to admission (not on PCP prophylaxis), who presented with faint interstitial infiltrates on CXR 5 days prior to admission, then, worsening interstitial infiltrates on day of admission -> PCP was diagnosed by bronchoalveolar lavage

PCP1

PCP2

Lung Nodules (see Lung Nodule or Mass)

Pleural Effusion (see Pleural Effusion-Exudate)

  • Epidemiology: rarely causes pleural effusion
  • Diagnosis: usually exudative

Pneumothorax (see Pneumothorax)

  • Epidemiology: predisposed by presence of pneumocysts

Upper Lobe Cavitary Disease (see Cystic-Cavitary Lung Lesions)

  • Epidemiology: may be seen in patients who have been receiving inhaled pentamidine prophylaxis
  • Diagnosis
    • Bronchoscopy with Bronchoalveolar Lavage (BAL) (see Bronchoscopy): typically higher BAL neutrophil counts and lower organism counts are seen in non-AIDS cases
  • Clinical: mimics tuberculosis

Treatment

Antimicrobials

  • Sulfamethoxazole-Trimethoprim (Bactrim) (see Sulfamethoxazole-Trimethoprim)
    • First-Line Therapy
    • Regimen: 3 week course
    • Resistance: cases of sulfamethoxazole-trimethoprim resistant PCP have been reported
  • Alternative Agents
  • Antimicrobial Response Rates: believed to be better in AIDS-related cases than in non-AIDS cases

Corticosteroids (see Corticosteroids)

  • Indications: room air pO2 <70
  • Regimens

Prophylaxis

Indications

Transplant

  • Bone Marrow Transplant (BMT)/Stem Cell Transplant (SCT) (see Bone Marrow Transplant)
    • Allogeneic: prophylaxis is typically administered for 6 mo after engraftment (as long as immunosuppressives are administered)
      • Prophylaxis may be required for longer in patients receiving immunosuppression for graft vs host disease
    • Autologous: prophylaxis should be administered in patients with an underlying hematologic malignancy (lymphoma, multiple myeloma, leukemia), especially when intensive treatment regimens have included a purine analog (cladribine, fludarabine) or high-dose corticosteroids
  • Solid Organ Transplant: prophylaxis is indicated for 6 mo-1 yr after transplant and during periods of high-dose immunosuppression (such as during the treatment of acute rejection)

Immunosuppressive Administration

  • Alemtuzumab (Campath, MabCampath, Campath-1H, Lemtrada) Administration (see Alemtuzumab): prophylaxis is indicated for a minimum of 2 mo after completing therapy or until the CD4 count is >200 cells/ul
  • Anti-Tumor Necrosis Factor-α (Anti-TNF) Therapy (see Anti-Tumor Necrosis Factor-α Therapy): prophylaxis should be considered, although this has not been adopted as a standard of care
  • Concomitant Purine Analog (Cladribine, Fludarabine) + Cyclophosphamide Administration (see Fludarabine and Cyclophosphamide)
  • Concomitant Temozolomide (Temodar, Temodal) + Radiation Therapy (see Temozolomide): prophylaxis is indicated until recovery of lymphopenia
  • Concomitant Temsirolimus + Corticosteroids or Other Immunosuppressives (see Temsirolimus, [[Temsirolimus]]): prophylaxis should be considered in these patients
  • Corticosteroid Administration (see Corticosteroids, [[Corticosteroids]]): prophylaxis is indicated for those receiving the equivalent of prednisone >20 mg qday for at least 1 mo

Primary Immunodeficiency States

Other

Agents

References

  • Pneumocystis carinii pneumonia in patients with connective tissue disease. Chest 1992; 101:375-378
  • Pneumocystis carinii pneumonia in patients without AIDS. Clin Infect Dis 1993; 17:S416-S422
  • Pneumocystis carinii pneumonia during immunosuppressive therapy for antineutrophil cytoplasmic autoantibody-positive vasculitis. Arch Intern Med. 1995 Apr 24;155(8):872-4 [MEDLINE]
  • Treatment and prophylaxis of Pneumocystis carinii pneumonia. Semin Respir Infect 1998; 13:296-303
  • Tumor necrosis factor alpha antibody (infliximab) therapy profoundly downregulates the inflammation in Crohn’s ileocolitis. Gastroenterology 1999; 116:22-28 [MEDLINE]
  • Pneumocystis carinii pneumonia with oral candidiasis after infliximab therapy for Crohn’s disease. Dig Dis Sci 2004; 1458- 1460 [MEDLINE]
  • Pneumocystis jiroveci (carinii) pneumonia after infliximab therapy: a review of 84 cases. Dig Dis Sci 2007; 52:1481-1484 [MEDLINE]
  • Pneumocystis carinii pneumonia in a patient on etanercept for psoriatic arthritis. Ir J Med Sci 2007; 176:309-311
  • Pneumocystis carinii pneumonia in a rheumatoid arthritis patient treated with adalimumab. Scand J Infect Dis 2007; 39:475-478