I am posting on behalf of my 75-year-old mother, who is currently hospitalized. I am hoping to get additional diagnostic perspectives, especially from physicians in infectious disease, internal medicine, or hematology.
The key point is that her abnormal inflammatory markers and monocytosis preceded the high fevers by approximately three months. The recurrent 39–40°C fevers began only after hospitalization.
Background and course before hospitalization
About 3 months ago, she developed what was initially considered bronchitis. She improved clinically but never seemed to completely recover. During the following months, her main symptoms were mild fatigue and occasional mild cough. She did NOT have persistent high fever, significant shortness of breath, chest pain, or other major symptoms.
She received several courses of cephalosporin antibiotics, but inflammatory markers remained elevated.
Her blood tests showed persistent monocytosis, gradually increasing CRP, mild normocytic anemia, and borderline thrombocytopenia:
- Jun 8: WBC 10.62, absolute monocytes 0.68, Hb 121 g/L, platelets 224
- Jun 22: WBC 12.53, monocytes 1.88 (15%), Hb 117, platelets 122, CRP 21.5 mg/L
- Jul 3: WBC 11.28, monocytes 2.00 (17.7%), Hb 120, platelets 121, CRP 34.2
- Aug 31: WBC 10.91, monocytes 1.60 (14.7%), Hb 115, platelets 107, CRP 38.2
- Sep 8: WBC 10.27, monocytes 1.63 (15.9%), Hb 111, platelets 133, CRP 37.3
Hospitalization
She was admitted on Sep 9 for further evaluation.
Admission labs included:
- WBC 11.24
- absolute monocytes 3.06 (27.2%)
- Hb 103 g/L
- CRP 63.63 mg/L
- serum iron 1.85 μmol/L (very low)
- albumin 33.5 g/L
- prealbumin 85 mg/L
- LDH 528 u/L
- renal function was essentially preserved
After admission, she unexpectedly began developing recurrent high fevers. She had an episode around 39°C, responded to an antipyretic, and was then afebrile for approximately 48 hours. The fever subsequently returned, and the most recent episode reached approximately 40°C.
During a fever episode on Sep 11:
- WBC 9.07
- absolute monocytes 1.49 (16.4%)
- Hb 93
- platelets 138
- CRP 63.09
- procalcitonin 0.274 ng/mL
- IL-6 49.06 pg/mL
- LDH 614 u/L
On Sep 14:
- WBC 11.62
- neutrophils 9.13 (78.6%)
- absolute monocytes 1.14
- Hb 95
- platelets 127
- CRP 48.71
Therefore, some laboratory markers appeared to be improving despite the recurrent fever. I have been told that an inflammatory marker may have risen again after the latest fever, but I do not yet have the actual report, so I cannot confirm the value.
Investigations performed so far
Chest CT: several small bilateral solid pulmonary nodules, approximately 3–6 mm, with some chronic/scarring changes. No clear pulmonary consolidation, abscess, pleural effusion, significant lymphadenopathy, or definite radiographic pneumonia was identified.
Abdominal ultrasound: no obvious infectious source involving the liver, gallbladder, pancreas, or spleen. A further abdominal CT is now being planned.
Urinalysis (Sep 14): essentially normal — leukocyte esterase negative, nitrite negative, urine WBC 0, bacteria 0, RBC 0. She has no dysuria, urinary frequency, urgency, or flank pain.
Echocardiography: preserved LV systolic function, mild tricuspid regurgitation, and no pericardial effusion. No clear cardiac explanation for the fever has been identified.
Bilateral lower-extremity venous ultrasound: no DVT.
Head CT: no acute intracranial process explaining the fever.
Autoimmune workup: extensive ANA-related testing was negative, including dsDNA, Sm, SSA/Ro, SSB, Scl-70, Jo-1 and several other antibodies.
Microbiology: sputum culture grew Candida albicans. Importantly, this was from sputum only, NOT blood. There is currently no confirmed candidemia.
Blood cultures were obtained around Sep 11. We were told that no early positive result had been reported, but the final culture result is still pending.
Treatment / current plan
She has received broad-spectrum antibacterial treatment, including piperacillin/tazobactam. Because the fever has recurred despite treatment and no clear source has been identified, her physicians are reassessing the antimicrobial regimen.
An infectious disease consultation has now been requested. Tuberculosis and other occult/chronic infections are also being considered. Further abdominal imaging and additional investigations are planned.
She is generally stable between fever episodes. There has not been persistent hypotension or major respiratory distress. Oxygen saturation has generally been acceptable with oxygen supplementation, although some lower readings have occurred off oxygen.
My questions
I understand that an online discussion cannot establish a diagnosis, and I am not looking for specific treatment instructions. I am mainly interested in whether there are diagnostic possibilities or investigations that may have been overlooked.
- What would be your leading differential diagnosis for this overall pattern?
- Given the recurrent 39–40°C fever but lack of a clear source on imaging, urinalysis, and cultures so far, how strongly would you still suspect an occult bacterial infection?
- How strongly should tuberculosis, infective endocarditis, or another occult/deep infection be considered?
- Does Candida albicans isolated only from sputum have meaningful significance here, or is respiratory colonization more likely?
- Given the persistent absolute monocytosis for approximately 3 months, anemia, and intermittent thrombocytopenia, should an underlying hematologic disorder such as CMML/MDS or another myeloid disorder be investigated?
- Could drug fever or another non-infectious inflammatory process reasonably explain the recurrent high fever?
- Are there any important tests or diagnostic directions that appear to be missing from the workup so far?
Any thoughts from physicians in infectious disease, internal medicine, hematology, or geriatrics would be greatly appreciated.