APPROACH TO DIAGNOSIS

In approaching the case, several clinical questions came to mind. First is, what
would cause a gradual onset of generalized body weakness, low-grade fever, weight
loss, anorexia and pallor? The first thing that came to our mind was infection. Could it be
tuberculosis? Tuberculosis can present with all the features mentioned and in addition to
that, it has a really gradual onset. However, why is there no history of previous
tuberculosis if tuberculosis would present as worst as this case already? Could this be
associated with HIV? However, was the patient exposed in any way to HIV? Could it be
a malignant process? Malignancies of the white blood cells and the blood in general can
cause such symptoms, with particular emphasis on leukemia and lymphoma, however, if
it is leukemia, why is there no overt bleeding? Why is there no signs of easy bruisability?
Could her immune system be affected already by leukemia prior to current presentation?
Why is there no organomegaly? Could this be just a plain metabolic imbalance, such as
hypernatremia? Diabetes insipidus? However, why is there no history of polydipsia and
polyuria? Could there be tumor in the pituitary? Could the patient be having a late onset
apoplexy? Lastly, could this be an anemia of a chronic disease? Truly, one cannot
diagnose this patient given this history alone.
Moving on with the temporal profile of the symptoms, 2 months after the onset of
those mentioned above, multiple palpable nodules presented in the patient. Are these
just benign nodules? Were they infiltrations in the skin or subcutaneous tissue? Are they
enlarged lymph nodes? But based on the case, most likely, these are
lymphadenopathies. Also, according to Longo et al. (2014), if the enlargemen of lymph
nodes is greater than 1 cm for axillary or submandibular and 2 cm on inguinal (greater in
other literatures) for it to be considered lymphandenopathy. In the presentation of the
patient, the sizes were 5x5 cm and 3x3 cm, and these are clear-cut lymphadenopathies.
Based on literatures, presence of lymphadenopathies in at least three non-contiguous
sites further defines it as generalized. So in the case, we can say that the patient had
generalized lymphadenopathy. With this information, we then centered our analysis on
what could cause generalized lymphadenopathy in the setting of weakness, fever,
anorexia and pallor? Then we thought of infectious, immunologic or autoimmune, and
malignant etiologies. Infectious etiologies were considered primarily because according
to Henry and Longo, non-specific infections, particularly of viral or bacterial origin, are
the most frequent causes of lymphadenopathy. Based on the history alone, a chronic
type of infection is suggested, with the gradual onset of the symptoms, low grade fever,
anemia and the like. However, considering the patients course in the ward, it seems like
she was having an acute infection, particular focus of which can be suspected in the
lungs, as evidenced by her x-ray result, which revealed bilateral lung infiltrates.
However, there were also findings of nodular masses on the x-ray. Acute infections are
not known to present like this, and chronic infections such as tuberculosis, infiltrative
processes such as Sarcoidosis, or malignancy, however, can cause nodular masses in
the lungs. However, contrary to the suspicion of infection, the patients white blood cell
count was normal. Could the infection be contained such that it does not stimulate an
acute response from the patients white blood cells anymore? Under this suspicion, we
considered two etiologic causes of lymphadenopathy: tuberculosis and HIV. If what the
patient had was really infection, it can definitely explain the diagnostic findings in the
patient. The findings on the x-ray further strengthen the diagnosis of tuberculosis. This
condition can also cause a subtle to nil elevation in the white blood cell count because
one of its targets is also the immune system. Elevated lactate dehydrogenase is also a
common finding in tuberculosis. With the bacteria competing with the bodys stores of
iron, it can definitely cause anemia. In the case, the anemia is normochromic and the
level of hemoglobin and hematocrit were not quite compatible with anemia of chronic
disease or even anemia of infection. The anemia is much more fit in the setting of blood
loss? Could tuberculosis or any other infection cause blood loss in this patient? If there
were pulmonary involvement, the patient would have presented with hemoptysis by the
time she is in the ward, however, there was none. Had the tuberculosis involved the GI
tract, the patient should have presented with melena or hematochezia, but there was
none. Although, if the infection involved other organ systems, such as the pancreas, or
even the peritoneum and caused an erosion of a vessel or hemorrhage to the organ, the
bleeding may be concealed in the third spaces, such as the peritoneum, which is a
primary consideration in this case, because her abdominal examination was compatible
with a third space accumulation. Definitely, an overt coagulation disorder, such as DIC
can be ruled out in this case with the normal coagulation profile of the patient, even at
the 2nd hospital day.
Another infection considered in the case is HIV, because generalized
lymphadenopathy is a hallmark of the first stage of the disease. However, the exposure
is rather really questionable, considering the past medical, personal social and
socioeconomic profiles of the patient. And, for HIV to present this worse, it should have
been in a latter stage, and would have presented a plummeting level of WBC and would
also present with other opportunistic infections, which are quite questionable in the case.
Another clue that made us suspect that the nodes are really infected is the
presence of tenderness, which is far less common in other diagnoses. Other infectious
causes such as fungal and parasitic are not of high priority in terms of consideration
because these conditions usually present with a specific history of exposure to the
agent, and are quite rare causes of generalized lymphadenopathy.
Another consideration is an autoimmune or infiltrative disorder. Literatures would
really confuse a medical student with the vast array of immunologic conditions, which
can cause lymphadenopathy and fever and weakness. Some of those considered are
SLE, Sarcoidosis, Castlemans disease, dermatopathic lymphadenitis, Kikuchis disease,
Rosai-Dorfman disease, Histiocytosis X and other associated histiocytic conditions such
as Erdheim-Chester Disease and Malignant Histiocytosis, and inflammatory
pseudotumor. With the others being usually localized to a certain group of lymph nodes
except for Sarcoidosis, which is a common cause of generalized lymphadenopathy.
Lastly, we also considered malignancy because the presentation of the patient
really fits a malignant process, such that the patient gradually weakens, presents with
weight loss, and anorexia. Low-grade fever is another clue to a possible blood or
immune system related malignancy, such as leukemia or lymphoma. However, leukemia,
as mentioned before, usually presents with signs of low platelet count, as well as
splenomegaly, which are not present in the patient. We also considered a metastatic
malignancy; however, the lymphatic infiltrations of malignancies are usually along the
contiguous lymph nodes of the primary tumor site and would not usually with generalized
lymphadenopathy. Non-Hodgkins Lymphoma generally fit the case of the patient and is
really difficult to rule out.
Whatever may have caused the demise of the patient, two clinical findings were
for sure in the case: that the patient underwent a state of severe anemia and that the
patient was in a shock state. All of our differentials can cause anemia, but this severe?
We think that it is generally more compatible with an on-going blood loss, which may be
occult in this case. A hemolytic process is rather a hard match for the case because if
this is hemolytic, which in a sense will also cause a severe anemia as in the case, the
patient would have presented with signs of hemolysis such as jaundice and
hemoglobinuria, which are both absent in the case. The shock state of the patient was
refractory to fluid challenge and this kind of shock is usually found in sepsis. However,
for a patient to be diagnosed with septic shock, she should have signs of sepsis plus
hypotension that requires pressor therapy. Although he would fit with the latter, we are
not sure if the patient will really fit the criteria for sepsis, because although the
temperature was not revealed, the afebrile state might be below 32 degrees Celsius,
which will eventually qualify our suspicion. Could this be hypovolemic shock and that the
patient was having blood loss to the different cavities of the body, such as in the
peritoneal cavity for which we highly suspect to be rally present in this project
presentation.

Figure 1. Approach to diagnosis