The immunosuppressed patient

Published on 14/03/2015 by admin

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Last modified 14/03/2015

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Chapter 42 The immunosuppressed patient

Patients with immunosuppression present with emergencies related to their increased susceptibility to infection and to their underlying condition.

The most frequently encountered causes of immunocompromise vary according to the location and specialisation of the institution, with cancer, AIDS and solid organ transplant being the commonest conditions. Other causes of immunocompromise are immunosuppressive and/or cytotoxic therapy for non-malignant disease, post-splenectomy, congenital immune defects and marrow failure due to drugs or infection.

The signs and symptoms of infection are often diminished and patients may present with subtle and non-specific findings and deteriorate rapidly. Fever may be the sole presenting symptom, but even that may be masked by the presence of drugs such as corticosteroids. Therefore, infection must be considered in the differential diagnosis of the immunocompromised patient presenting with non-specific symptoms.

The immune system consists of innate and adaptive components. Innate immunity stems from intact epithelial barriers, phagocytic cells (neutrophils and macrophages), natural killer cells and the complement system. Innate immunity does not require prior exposure to the infective agent for rapid activation.

Adaptive immunity is conferred by lymphocytes and their products. T cells act against intracellular microbes and provide cell-mediated immunity. Humoral immunity is conferred by B cells and the antibodies they produce, which are active against extracellular microbes.

Failure of a component of the immune system leads to vulnerability to different infective agents.

T cell defects occur in acquired immune deficiency syndrome (AIDS), immunosuppressive therapy and congenital severe combined immune deficiency (SCID) and leave patients susceptible to bacterial sepsis, infections with intracellular bacteria (tuberculosis (TB), Listeria), viral infections (cytomegalovirus (CMV), Epstein-Barr (EBV), varicella), fungal infections (Candida, Cryptococcus, Pneumocystis) and protozoal infection (Toxoplasma).

B cell defects occur in haematological malignancies, myeloma, AIDS and congenital disorders such as common variable immune deficiency. Patients are predisposed to infection by encapsulated bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria), staphylococci, giardia and enterovirus.

Granulocyte defects including neutropenia result from chemotherapy, marrow aplasia or infiltration, drug reactions, myelodysplasia and rarely from congenital defects. Patients are vulnerable to infection by gram negative bacilli including Pseudomonas, gram positive cocci such as staphylococci and viridans streptococci, and fungi such as Candida and Aspergillus.

Complement defects lead to susceptibility to infection with Neisseria and pyogenic bacteria, as well as predisposing to autoimmunity.

Asplenia predisposes to severe infections due to encapsulated bacteria including Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis.

In addition to infections, fever in the immunocompromised patient may be due to malignancy, drugs and allograft rejection.

Improvements in the management of the conditions associated with immunodeficiency have led to improved long-term survival and better quality of life for these patients. Nonetheless, there remains the potential for severe infections with rapid deterioration and death. Early aggressive care is essential, which includes early, rapid investigation, early institution of broad spectrum antibiotics, application of treatment protocols for sepsis and the use of ventilatory support where indicated. Non-infective causes such as rejection must be considered, especially in transplant patients. Early ICU referral and a team approach involving treating haematologists, oncologists, human immunodeficiency virus (HIV) specialists or transplant physicians is essential in the deteriorating patient. The patient’s wishes should be ascertained early, particularly in those with severe advanced disease or chronic progressive conditions that have been unresponsive to intervention.

CANCER PATIENTS

Cancer patients are at risk of severe infection due to immunosuppression induced by their disease and its treatment. Most at risk are patients undergoing therapy for haematological malignancies or stem cell transplant, who have severe and prolonged neutropenia. The risk of infection rises as the neutrophil count falls.

Febrile neutropenia

Febrile neutropenia is defined as fever above 38.0°C in a patient with a neutrophil count < 0.5 × 109/L or < 1 × 109/L with predicted decline.

Associated signs of infection may be present such as tachypnoea, tachycardia, altered mental state, dehydration and acidosis. Localising signs may be absent; however, a thorough examination of the lungs, oropharynx, skin, catheters, perineum and perianal area, sinuses and urinary tract is essential and may reveal the site of infection. Non-specific symptoms in the absence of fever may still indicate infection, especially if the patient is on high-dose corticosteroids.

Management

NONINFECTIOUS COMPLICATIONS OF CANCER AND ITS TREATMENT

HIV INFECTION

Patients with HIV infection most commonly present with complications of immunosuppression and its treatment. With the improved prognosis of HIV in the era of highly active antiretroviral treatment (HAART), patients increasingly present with medical or surgical conditions unrelated to HIV and, while their treatment may be complicated by their HIV, their outcome and survival may be excellent.

Primary HIV infection

Within 1 to 6 weeks of infection (sometimes up to 12 weeks), 50–70% of patients develop a symptomatic illness. In most cases this is mild to moderate in severity and does not usually present to the emergency department. The seroconversion illness can resemble infectious mononucleosis. Patients develop fever, fatigue, anorexia, headache, nausea and vomiting. Myalgias and arthralgias, a non-exudative pharyngitis, rashes and diarrhoea are common. Severe cases may develop meningism or encephalitis.

Pulmonary infections

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