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ESSENTIALS OF DIAGNOSIS

  • Fever and other symptoms may be blunted because of immunosuppression.

  • A contaminating organism in an immunocompetent individual may be a pathogen in an immunocompromised one.

  • The interval since transplantation and the degree of immunosuppression can narrow the differential diagnosis.

  • Empiric broad-spectrum antibiotics may be appropriate in high-risk patients whether or not symptoms are localized.

GENERAL CONSIDERATIONS

Immunocompromised patients have defects in their natural defense mechanisms resulting in an increased risk for infection. In addition, infection is often severe, rapidly progressive, and life threatening. Organisms that are not usually problematic in the immunocompetent person may be important pathogens in the compromised patient (eg, Staphylococcus epidermidis, Corynebacterium jeikeium, Propionibacterium acnes, Bacillus species). Therefore, culture results must be interpreted with caution, and isolates should not be disregarded as solely contaminants. Although the type of immunodeficiency is associated with specific infectious disease syndromes, any pathogen can cause infection in any immunosuppressed patient at any time. Thus, a systematic evaluation is required to identify a specific organism.

A. Impaired Humoral Immunity

Defects in humoral immunity are often congenital, although hypogammaglobulinemia can occur in multiple myeloma, chronic lymphocytic leukemia, small lymphocyte lymphoma, and in patients who have undergone splenectomy. Patients with ineffective humoral immunity lack opsonizing antibodies and are at particular risk for infection with encapsulated organisms, such as Haemophilus influenzae, Neisseria meningitides, and Streptococcus pneumoniae. Although rituximab is normally thought of as being linked to impaired cellular immunity, it has been associated with the development of Pneumocystis jirovecii infection and progressive multifocal leukoencephalopathy (PML) as well as with hepatitis B reactivation.

B. Granulocytopenia (Neutropenia)

Granulocytopenia is common following hematopoietic cell transplantation (“stem cell transplantation”) and among patients with solid tumors—as a result of myelosuppressive chemotherapy—and in acute leukemias. The risk of infection begins to increase when the absolute granulocyte count falls below 1000/mcL, with a dramatic increase in frequency and severity when the granulocyte count falls below 100/mcL. The infection risk is also increased with a rapid rate of decline of neutrophils and with a prolonged period of neutropenia. The granulocytopenic patient is particularly susceptible to infections with gram-negative enteric organisms, Pseudomonas, gram-positive cocci (particularly Staphylococcus aureus, S epidermidis, and viridans streptococci), Candida, Aspergillus, and other fungi that have recently emerged as pathogens such as Trichosporon, Scedosporium, Fusarium, and the mucormycoses.

C. Impaired Cellular Immunity

Patients with cellular immune deficiency encompass a large and heterogeneous group, including patients with HIV infection (see Chapter 31-01); patients with lymphoreticular malignancies, such as Hodgkin disease; and patients receiving immunosuppressive medications, such as corticosteroids, cyclosporine, tacrolimus, and other cytotoxic medications. This latter group—those who are immunosuppressed as a result of medications—includes patients who have undergone solid organ transplantation, many patients receiving therapy for solid tumors, and patients receiving prolonged high-dose corticosteroid treatment (eg, ...

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