Nonspecific Disease Presentation: The Emergency Department Perspective

Fig. 8.1
Most common causes for nonspecific complaints. (Comparison of underlying conditions for NSCs in four different studies. The study of Nickel et al. and Bhalla et al. investigate causes of ‘generalised weakness’, Rutschmann et al. set a focus on ‘home care impossible’, and Karakoumis et al. analysed NSCs in general. All studies except Nickel et al. formulated at least a top ten differential diagnosis, Nickel et al. showed only top three)

Though NSCs lack a common and universal definition, it is remarkable that distribution of underlying medical conditions is similar across the different study populations. In agreement with these observations, we showed that the NSC population also shares the same outcome with a high burden of morbidity and mortality [16]. This indicates that NSCs might seem to be diffuse complaints, but patients presenting with NSC form a distinct population. Upon identification of such a population, the question arises whether there is any advice on how to perform diagnostic workup.

8.2 Diagnostic Approach for Patients Presenting to the ED with NSCs

For specific symptoms such as chest pain, standardised pathways for diagnostic workup are available and widely used. This is possible because specific symptoms tend to be caused by a small group of diseases. In contrast, for nonspecific complaints the underlying causes are numerous and therefore the establishment of management protocols is difficult. However, a broad diagnostic workup , based on established pre-test probabilities, could be helpful for the establishment of an applicable approach (see Table 8.1). In the following we provide some advice for a general approach, and cause-specific characteristics for the three most frequent groups of underlying conditions. It might appear paradoxical to apply a cause-specific approach, when in nonspecific emergency presentation any narrowing of the wide array of differential diagnoses can be problematic. However, every step of the diagnostic procedure reduces the array of differential diagnoses. Therefore it seems feasible to focus on the three most frequent groups of underlying conditions.

Table 8.1
Special considerations for diagnostic workup for NSC patients (* see text)

Diagnostic workup

Medical history

Current complaint

History by proxy

Previously known malignancy


Physical examination

Vital signs*

Clinical indicators for dehydration*

Overall hygiene

Laboratory test

Blood count*




Creatinine, GFR

Serum osmolality, blood urea nitrogen-creatinine ratio


Metabolic panel


Further tests

12-lead electrocardiogram

Chest X-ray

Cranial imaging

Delirium/dementia screening test


8.2.1 General Diagnostic Approach History Taking

The patients’ medical history , including current complaints, is generally a vital component for the evaluation of emergency patients. Yet, history taking in older patients can be difficult: it could be shown that history taking from older patients with certain comorbidities as depression or dementia was not always reliable and additional sources for medical history should always be considered [17, 18]. History taking may contribute up to 75% of the diagnostic workup to the final diagnosis in patients with specific complaints [1922]. However in patients with NSCs, it sometimes seems to be impossible to establish working hypotheses solely based on the patients’ history. This is also reflected by the fact that some studies investigating NSCs include only patients lacking a history useful for an initial working hypothesis [3].

As it is the nature of nonspecific presentation, patients describe their symptoms vaguely. For example, patients complaining about weakness may often not be able to differentiate between ‘localised weakness’ and ‘generalised weakness’ . Yet, this differentiation can be essential, because ‘localised weakness’ is rather specific for stroke or stroke mimics, while ‘generalised weakness’ is a classic NSC with an extremely broad differential diagnosis [15]. A second example is ‘dizziness’. Older patients often struggle differentiating between ‘vertigo’ and ‘dizziness’. Besides other factors such as proprioceptive failure, visual impairment or reduced cerebral perfusion pressure, (acute or chronic) cerebrovascular disease might be an explanation. Therefore, strokes are not uncommon in patients with NSC, as neither a localisation of weakness nor the typical vertigo-complaints are helpful in these situations [3].

Besides the presenting complaint(s), the past medical history, especially the past history of cancer might help to identify the underlying conditions of NSCs. Indeed, it was shown that only 30% of cases in which malignancies caused weakness were newly diagnosed, whereas for the rest the malignancies were previously known, and the majority of these patients presented with weakness as a complication of their cancer or a deterioration of their chronic condition [15].

Another important component of history taking is medication history. It can often be obtained by proxies or family physicians, and about 11% of all underlying conditions can be attributed to medication [11]. Therefore, gathering all information on medication may be decisive in patients with NSC. Physical Examination

Another diagnostic step is the objective measurement of patient’s status via monitoring of vital signs. Thereby, the disease severity in acute settings can be classified by measurement of the four vital signs—pulse, temperature, blood pressure, and respiratory rate. These are standardised methods and have well-established normative ranges. However, reference ranges in older patients can be altered. Moreover, vital signs in older patients are less sensitive due to physiological and pathological changes occurring with age [23]. For example, older patients may have higher systolic pressures due to arterial stiffness occurring with age [23]. Unfortunately, individual baseline parameters are often unknown. If known, relative changes from individual baseline parameters are very helpful for risk stratification. It could be shown that relying on vital signs in older patients can cause undertriage of critically ill patients [24]. However, in some studies investigating NSCs, patients with severely deviating vital parameters were excluded, as hypotension, fever, and tachycardia often trigger specific workups that are standardised in many EDs [9]. Even though physical examination can be important for upgrading pre-test probabilities using, e.g. heart auscultation [25], it could be shown that in patients with NSC, only one of almost 600 cases was diagnosed by physical examination alone [26].

History taking and physical examinations generally are the main part in the diagnostic workup. Yet, this essential part of diagnostic workup in patients with SC often can be less effective in patients with NSCs. One possible approach is, to lower laboratory testing threshold and thereby complementing missing information to establish a working hypothesis (see Table 8.1).

8.2.2 Causes-Specific Approach

In the following, we describe the characteristics of the three most common groups of conditions. For the diagnostic workup in patients lacking a working hypothesis, this will allow to focus on a single group and reduce the wide diagnostic array. Infections

The classical clinical manifestation of infections is fever. The definition of fever in older patients is still under discussion and a temperature increase by 1.1°C from baseline is hardly feasible in emergency settings [27]. Yet, data indicate that the normative temperature range in older patients may be different from younger patients [27]. However, fever is no mandatory sign for infections and can be absent or blunted in 20–30% of the cases [27]. These alterations should be carefully taken into account when screening for infections.

To confirm the working hypothesis ‘infection’ , laboratory examinations are a pivotal part of the diagnostic workup. The exams for infections generally include complete blood count (especially white blood count) and C-reactive protein (CRP). However, these two markers lack sensitivity and specificity [28]: leucocytosis may be absent, and CRP can increase late. Therefore measurement of Procalcitonin (Pro-CT) can be helpful [26, 29]. However, even Procalcitonin has not been shown to be as sensitive and specific as emergency physicians have hoped for [28].

Further workup should aim at the identification of the infection focus. There are multiple infections causing NSCs, but two most common infections causing NSCs are urinary tract infections (UTI) and pulmonary infections [3, 5, 7, 15]. Urinalysis is a useful tool to detect urinary tract infections only in addition to clinical symptoms reference to UTI chapter (see Chap. 16). Results of urine cultures may arrive too late to diagnose patients. Infectious Diseases Society of America (IDSA) guidelines presume clinical symptoms besides detection of the pathogen in the urine for the diagnosis and treatment of UTI [30]. Therefore there is no advice for antibiotic treatment of bacteriuria in older patients as long as infection is asymptomatic [31]. However, it remains challenging to define ‘asymptomatic’ in the case of a nonspecific presentation (such as weakness) or a patient with delirium. The second common infection is pulmonary infection : More than half of all older patients with pneumonia can have non-respiratory symptoms [32]. Another prospective multicentre study showed that patients aged 65 and older frequently have no cough (20%), no dyspnoea (35%), no fever (50%) [33]. Therefore indication for chest X-ray should be handled liberally in older patients presenting with NSC.

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May 1, 2018 | Posted by in Uncategorized | Comments Off on Nonspecific Disease Presentation: The Emergency Department Perspective
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