In an 80‑year‑old patient with new‑onset weakness and labs showing neutrophilic leukocytosis, lymphopenia, monocytosis, markedly elevated C‑reactive protein, mild renal insufficiency (eGFR 55 mL/min/1.73 m², BUN/creatinine ratio 26) and low albumin, what is the most likely diagnosis and initial management?

Likely Diagnosis: Occult Infection or Malignancy with Systemic Inflammatory Response

This 80-year-old patient with weakness, marked neutrophilic leukocytosis (WBC 14.6, neutrophils 11.7), lymphopenia (1.1), monocytosis (1.6), and strikingly elevated CRP (119 mg/L) most likely has an occult infection, underlying malignancy, or inflammatory condition requiring urgent investigation.

Key Laboratory Abnormalities and Their Significance

Inflammatory Markers

• CRP of 119 mg/L (normal 0-10) indicates severe systemic inflammation and is far too elevated to attribute to chronic kidney disease alone 1
• The combination of elevated CRP with low albumin (3.7 g/dL) reflects acute inflammation rather than nutritional deficiency, as inflammation causes hypoalbuminemia independent of nutritional status 1
• ESR of 13 mm/hr is relatively low compared to the markedly elevated CRP, which may suggest acute rather than chronic inflammation 1

Hematologic Abnormalities

• Neutrophilic leukocytosis (81% neutrophils, absolute count 11.7) with lymphopenia (8%, absolute 1.1) is the classic pattern of bacterial infection or systemic inflammatory disease 1
• Monocytosis (1.6, normal 0.1-0.9) suggests chronic inflammation, intracellular infection (such as tuberculosis), or malignancy 1
• The absence of immature granulocytes argues against leukemoid reaction but does not exclude serious pathology 1

Renal Dysfunction

• eGFR 55 mL/min/1.73 m² with BUN/creatinine ratio of 26 (elevated) suggests prerenal azotemia or dehydration superimposed on chronic kidney disease 1, 2
• The creatinine of 1.32 mg/dL may underestimate renal dysfunction in an elderly patient with reduced muscle mass 2, 3

Iron Studies

• Low iron (34 ug/dL), low TIBC (206 ug/dL), and borderline iron saturation (17%) indicate anemia of chronic disease/inflammation, NOT iron deficiency 1
• In iron deficiency, TIBC would be elevated; the low TIBC here confirms inflammatory anemia 1

Most Likely Differential Diagnoses

1. Occult Infection (Highest Priority)

• Bacterial infection (pneumonia, urinary tract infection, intra-abdominal abscess, endocarditis) is the most common cause of this laboratory pattern in elderly patients 1
• The elevated BUN/creatinine ratio suggests possible dehydration from infection 1
• Tuberculosis or atypical mycobacterial infection should be considered given monocytosis and chronic presentation 1

2. Occult Malignancy

• Solid tumors or hematologic malignancy can present with constitutional symptoms, leukocytosis, and markedly elevated inflammatory markers 1
• The combination of weakness, weight loss (if present), and these labs warrants malignancy workup 4

3. Adult-Onset Still's Disease (AOSD)

• AOSD classically presents with fever, leukocytosis (often >15,000 with >80% neutrophils), and markedly elevated ferritin 1
• However, ferritin level is not provided in these labs, which is critical for diagnosis 1
• CRP >100 mg/L is common in AOSD 1
• The absence of reported fever, rash, or arthritis makes this less likely but not excluded 1

4. Vasculitis (Less Likely)

• ANCA-associated vasculitis can present with constitutional symptoms and renal dysfunction, but typically shows more pronounced renal abnormalities 1
• The relatively preserved renal function and absence of active urinary sediment make this less likely 1

Critical Immediate Investigations Required

Infection Workup (First Priority)

• Blood cultures (at least 2 sets from different sites) before any antibiotics 1
• Chest X-ray to evaluate for pneumonia or other pulmonary pathology 1
• Urinalysis with microscopy and urine culture to exclude urinary tract infection 1, 5
• Complete metabolic panel repeated to assess renal function trajectory 1

Inflammatory/Rheumatologic Workup

• Serum ferritin level is essential: values >1,000 ng/mL with >80% sensitivity for AOSD; glycosylated ferritin <20% has 93% specificity when combined with 5-fold ferritin elevation 1
• Procalcitonin to differentiate bacterial infection from non-infectious inflammation 1
• Lactate dehydrogenase (LDH) for tissue breakdown or hemolysis 1

Malignancy Screening

• CT chest/abdomen/pelvis to evaluate for occult malignancy, lymphadenopathy, or intra-abdominal pathology 1, 4
• Peripheral blood smear to evaluate for hematologic malignancy 1, 4
• Age-appropriate cancer screening including colonoscopy if not up to date, given monocytosis 4

Additional Studies if Initial Workup Negative

• Echocardiogram if endocarditis suspected (especially with any cardiac murmur) 1
• Temporal artery biopsy if giant cell arteritis suspected (though ESR is relatively low) 1
• Bone marrow biopsy if hematologic malignancy suspected 4

Immediate Management Priorities

Supportive Care

• Assess volume status and provide IV hydration if prerenal azotemia confirmed to improve renal function 1
• Monitor vital signs closely, especially temperature, blood pressure, and oxygen saturation 1
• Daily monitoring of complete blood count, renal function, and inflammatory markers 1

Empiric Antibiotic Therapy Decision

• Do NOT start empiric antibiotics until blood cultures obtained unless patient is hemodynamically unstable or has sepsis 1
• If sepsis is present (hypotension, altered mental status, organ dysfunction), initiate broad-spectrum antibiotics immediately after cultures drawn 1
• Choice of antibiotics should be guided by suspected source and local resistance patterns 1

Avoid Common Pitfalls

• Do not attribute the low albumin to malnutrition alone—the elevated CRP indicates inflammation is the primary driver 1
• Do not assume the anemia is simple iron deficiency—the low TIBC confirms anemia of chronic disease/inflammation 1
• Do not delay imaging studies in an elderly patient with unexplained systemic inflammation and constitutional symptoms 1
• Do not overlook tuberculosis in patients with monocytosis and chronic symptoms, even without classic risk factors 1

Specific Considerations for Renal Dysfunction

• Adjust medication dosing for eGFR 55 mL/min/1.73 m², particularly antibiotics and contrast agents 1
• Avoid nephrotoxic agents (NSAIDs, aminoglycosides, IV contrast if possible) given baseline CKD 1
• Monitor for acute-on-chronic kidney injury with daily creatinine measurements 1

Clinical Reasoning Summary

The constellation of marked neutrophilic leukocytosis, lymphopenia, monocytosis, CRP >100 mg/L, and constitutional weakness in an 80-year-old demands urgent evaluation for life-threatening conditions. The pattern strongly suggests either occult infection (most common) or systemic inflammatory disease. The elevated BUN/creatinine ratio indicates prerenal component, possibly from dehydration related to underlying illness. The key is to obtain blood cultures and imaging immediately before initiating empiric therapy, unless the patient is septic. If initial infection workup is negative and ferritin is markedly elevated (>1,000 ng/mL), AOSD becomes more likely and would require rheumatologic consultation 1. Malignancy screening is essential given age and laboratory abnormalities 4.