Atypical Presentations and Altered Immunity in the Elderly
Diagnosing fever of unknown origin (FUO) in older adults presents a unique challenge, primarily because their bodies respond differently to illness. Unlike in younger individuals, whose immune systems produce a robust febrile response, the elderly often exhibit a blunted or absent fever even in the presence of a serious infection. This lack of a classic fever, combined with a weakened immune system (a process known as immunosenescence) and the presence of multiple comorbidities, often leads to non-specific symptoms such as fatigue, confusion, and generalized weakness. These altered presentations can delay both recognition and treatment of the underlying cause, underscoring the need for a tailored diagnostic strategy in this population.
Leading Causes of FUO in Older Adults
While infections frequently cause FUO in younger populations, the most common etiologies shift in geriatric patients toward inflammatory diseases. Studies confirm that multisystem diseases, which include various autoimmune and rheumatologic conditions, represent the largest category of FUO causes in the elderly. However, infections and malignancies remain significant concerns and are often present atypically.
Multisystem Inflammatory Diseases
The most frequent specific diagnosis within the multisystem category is temporal arteritis (TA), also known as giant cell arteritis. This condition causes inflammation of the large arteries, particularly those in the head, and can lead to serious complications like permanent vision loss if left untreated. Other important inflammatory conditions include polymyalgia rheumatica (PMR), which frequently co-occurs with TA, and adult Still's disease.
Infections
Despite the rise of inflammatory diseases, infections still constitute a notable portion of FUO cases in the elderly. A common finding is that common diseases present in an unusual way. Key infectious causes include:
- Tuberculosis (TB): Extrapulmonary and miliary TB are disproportionately more common in elderly patients with FUO compared to younger adults. The clinical signs can be subtle, and a chest x-ray may appear normal.
- Intra-abdominal abscesses: Abscesses can form in the abdomen or pelvis without the typical localizing symptoms found in younger patients. Early and advanced imaging techniques have made these easier to detect than in the past.
- Infective endocarditis: This infection of the heart valves is more prevalent in the elderly, particularly those with prosthetic valves or a history of hospital-acquired bacteremia. Non-specific symptoms like lethargy and fatigue often mask the condition.
Malignancies
While the relative proportion of malignancies causing FUO has decreased over recent decades due to improved diagnostic techniques, it remains an important consideration. Lymphomas are the most commonly cited type of malignancy, along with other cancers such as renal cell carcinoma, colon cancer, and multiple myeloma. A fever associated with a malignancy is known as a neoplastic fever.
Comparison of FUO Causes: Elderly vs. Younger Adults
Understanding the shift in disease prevalence is essential for clinicians evaluating FUO. While diagnostic overlap exists, the primary culprits differ significantly between age groups.
| Cause Category | Elderly Patients (≥65) | Younger Adults (<65) |
|---|---|---|
| Non-infectious Inflammatory Diseases | Most common cause. Temporal arteritis and polymyalgia rheumatica are highly prevalent. Sarcoidosis and adult Still's disease are also seen. | Less prevalent overall. Adult Still's disease, systemic lupus erythematosus (SLE), and vasculitis may occur, but are less frequent than in the elderly. |
| Infections | A significant cause, often atypical. Includes tuberculosis (especially extrapulmonary), intra-abdominal abscesses, and infective endocarditis. | Historically the most common cause. Abscesses, endocarditis, and viral infections (e.g., HIV, EBV, CMV) are common. |
| Malignancies | Less frequent than inflammatory diseases and infections. Lymphoma, renal cell carcinoma, and colon cancer are notable causes. | Can occur, but generally at a lower rate than in the elderly. Includes lymphomas and solid tumors. |
| Undiagnosed Cases | A definitive diagnosis is often reached in the majority of cases (87-95%) due to the higher likelihood of a serious underlying disorder. | A higher percentage of cases (up to 30%) may remain undiagnosed after initial workup. |
Diagnostic Approach in the Elderly Patient
The diagnostic pathway for FUO in an older adult requires a thorough and accelerated approach, given their reduced physiological reserve. A high index of suspicion for atypical presentations is paramount. The evaluation often includes:
- Comprehensive History and Physical Exam: Repeated examinations are crucial to uncover subtle clues. A detailed drug history is vital, as medication can cause drug-induced fever.
- Laboratory Studies: A high erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) level is a non-specific but important indicator of inflammation, particularly in vasculitis.
- Advanced Imaging: Computed tomography (CT) scans of the chest and abdomen are standard for identifying abscesses, lymphadenopathy, or masses. Positron Emission Tomography (PET) scanning can be valuable for locating obscure infections or malignancies.
- Invasive Procedures: A temporal artery biopsy is a crucial diagnostic step if temporal arteritis is suspected based on elevated inflammatory markers or other symptoms. Biopsies of bone marrow or lymph nodes may also be necessary.
Conclusion
While the definition of FUO remains a prolonged, unexplained fever, the most common underlying causes in the elderly are distinct from those in younger patients. Multisystem inflammatory diseases, particularly temporal arteritis, are the leading culprits. However, infectious causes like tuberculosis and malignancies like lymphoma also play a significant role and often present atypically due to the physiological changes of aging. An aggressive and systematic diagnostic evaluation is essential to identify these treatable conditions and prevent potential complications in this vulnerable population. Prompt recognition and appropriate therapeutic intervention are cornerstones of successful management.
