Fever in immunocompromised patients results in a different differential diagnosis than fever in the immunocompetent. One must first consider the causes of fever that are most common in these patients. In patients with HIV, bacterial infections are most common as the etiology, but these patients can have fevers from almost any infectious process and several neoplastic processes related to infections. Patients with cancer are most often febrile due to infection (67% of cases) which is most often bacterial (90%) followed by fungal (6%) and viral (4%). Noninfectious causes comprise 23% of cases and include DVT and PE, medications including chemotherapy (bleomycin, chloramphenicol, cisplatin, daunorubicin, hydroxyurea, vincristine, 6-mercaptopurine), and certain cancers themselves that predispose to fever (lymphoma, leukemia, myxoma, and renal cell carcinoma).
When considering a general approach to fever, one can use the excellent approach highlighted in Lauren’s post about FUO or the following ones (more simple but less comprehensive):
F – Fat thermogenesis – etiologies that increase shivering and heat production by fat, (ex. malignant hyperthermia)
E – Exposure (ex. heat stroke)
V – VTE
E – Endocrine (ex. hyperthyroidism, pheochromocytoma)
R – Release – any etiology that impairs release of heat through sweating or vasodilation
I – Inflammation – encompasses any condition that causes release of inflammatory cytokines that trigger the hypothalamus to reset the body’s thermostat (ex. sepsis, autoimmune conditions, cancer)
S – Substances – drugs or medications that cause fever through these mechanisms or others (such as NMS, Serotonin Syndrome)
H – Hypothalamus
The second consideration in work up of fever is what etiologies are likely in our specific patient. This comes down to key host factors such as specific immunodeficiencies (CD4 count in HIV positive patients, neutropenia or other immune defects in patients with cancer depending on type of cancer, type of therapy, and how recently they have received chemotherapy), where the host lives (higher prevalences of certain infections in specific regions), and where the host receives care (recent hospitalizations, hospital-based profile of infection). Also, keep in mind that these patients are vulnerable to having multiple sources of fever (could be infection as well as the medication to treat the infection, cancer and the chemotherapy, etc).
A helpful mnemonic specific to HIV positive patients with fever is:
- O – Oncologic – Lymphoma, KS
- P – Pneumonia – PJP, Histo, Cocciodio, bacterial pneumonias
- P – PML
- O – Oral candida
- R – Retinitis (CMV)
- T – Tuberculosis
- U – Usual Causes (typical causes of fever in immunocompetent patients can also occur in HIV-positive patients)
- N – Nontuberculous Mycobacteria (MAC)
- I – Immune Causes (IRIS, HLH)
- S – Skin (Shingles, HSV)
- T – Toxoplasmosis
- I – Intestinal (CMV, Cryptosporidium)
- C – Cryptococcal Meningitis
Remember that if infected, these patients may be unable to localize the site of their infection because they are unable to mount an inflammatory response. This may lead to a very nonspecific history. For HIV=positive patients, always check for thrush (oral candida) – this is a clue to a CD4 count <200. In these patients and patients with cancer, be careful to assess for sites of infection on exam and to check relevant labs (first tier including blood cultures, UA, and CXR). If patients have indwelling catheters, cultures should be drawn from these, as gram positive infections are increasingly prevalent in immunocompromised patients.
Given the high prevalence of infection and potentially life-threatening consequences if not treated, immunocompromised patients should receive empiric antibiotics while ruling out infection. If a specific source is identified, antibiotics can be narrowed. Stay tuned for an approach to antibiotics at future sessions of afternoon delight!
References:
Walter EJ et al. The pathophysiological basis and consequences of fever. Crit Care. 2016; 20: 200.
Pizzo PA. Fever in Immunocompromised Patients. The New England Journal of Medicine. 341(12): 893-899.
Patel DM, Riedel DJ. Fever in Immunocompromised Hosts. Emerg Med Clin N Am. 2013; 1059-1071.
Heller HM et al. Case 31-2013: A 29-Year-Old Man with Abdominal Pain, Fever, and Weight Loss. N Engl J Med. 2013; 369: 1453-61.
Anglaret X et al. Causes and empirical treatment of fever in HIV-infected adult outpatients, Abidjan, Cote d’Ivoire. AIDS. 2002; 16(6): 909-918.
Toussaint E et al. Causes of fever in cancer patients (prospective study over 477 episodes). Support Care Cancer. 2006; 14: 763-769.
Pasikhova Y. Fever in Patients With Cancer. Cancer Control. 2017; 24(2): 193-197.
Kang DH et al. Significant Impairment in Immune Recovery Following Cancer Treatment. Nurs Res. 2009; 58(2): 105-114.