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IM4.1-20 | Fever and Febrile Syndromes — PBL Case

CLINICAL SETTING

Dr Kavitha is the registrar on call in the general medicine ward of a government teaching hospital in Bihar. It is September — peak monsoon season. She is accompanied by two final-year students, Arjun and Priya, who are on their medicine posting. A new patient is wheeled in: Mr Ramesh Mahto, a 48-year-old farmer from a village 80 km outside Patna. His wife, who accompanied him, reports that he has had daily high-grade fever for the past 4 weeks. He was treated at a rural health centre two weeks ago with a 3-day course of oral amoxicillin-clavulanate, which made no difference. He is weak, has lost 5 kg over the past month, and cannot work. On examination: temperature 39.4°C, BP 106/68 mmHg, pulse 96/min, pallor+++, splenomegaly 6 cm below the left costal margin, mild hepatomegaly. He has no lymphadenopathy and no skin rash. Arjun opens his notebook and writes: 'Fever 4 weeks, no diagnosis, Bihar. Think: [blank].' Dr Kavitha turns to the students: 'Before we order a single test — what is this man's most likely diagnosis, and why?'

Trigger 1: The Clinical Syndrome: Fever, Splenomegaly, and the Indian Epidemiological Context

The students deliberate. Priya immediately says: 'This is Bihar, monsoon, 4 weeks of fever, massive splenomegaly, anaemia — I'm thinking kala-azar.' Arjun counters: 'Could also be malaria, typhoid, or even lymphoma.' Dr Kavitha asks them to rank their top three differentials with reasons. She then asks for the investigation plan. A rapid rK39 antigen test is performed at the bedside: REACTIVE. She turns to the students: 'The rK39 is positive. Do we treat now, or do we need more?'

DISCUSSION POINTS

  • Rank the top three differential diagnoses for this patient's presentation in order of probability. What clinical and epidemiological features support each?
  • The rK39 antigen test is positive. What is the sensitivity and specificity of this test in Bihar, and does a positive rK39 alone constitute sufficient evidence to initiate treatment for visceral leishmaniasis without confirmatory bone marrow or splenic aspiration?
  • Why is 4 weeks of fever with splenomegaly in a Bihar farmer a different clinical problem than the same presentation in a patient from Mumbai or Chennai? How does epidemiological context change the pre-test probability?
Click to reveal Trigger 2: The Complication: Fever Persists After Treatment Initiation (discuss previous trigger first!)

Trigger 2: The Complication: Fever Persists After Treatment Initiation

The patient is admitted and started on liposomal amphotericin B (AmBisome) — the first-line NVBDCP treatment for VL in India (single dose 10 mg/kg). On day 7, he continues to have daily fever spikes of 38.8°C. A repeat CBC shows: Hb 7.1 g/dL, WBC 2,800/µL (neutrophils 68%, lymphocytes 22%), platelets 88,000/µL. Serum LDH is 1,440 IU/L, ferritin is 22,000 ng/mL, and triglycerides are 4.8 mmol/L. Dr Kavitha asks the students: 'Is this treatment failure, a superimposed new illness, or something we missed at the start?' She shows them the peripheral smear: macrophages with engulfed red blood cells, white blood cells, and platelets are visible.

DISCUSSION POINTS

  • The CBC shows pancytopenia with markedly elevated ferritin (22,000 ng/mL), elevated LDH, and hypertriglyceridaemia. The smear shows haemophagocytosis. What syndrome does this constellation suggest, and how does it relate to the underlying visceral leishmaniasis?
  • What are the five HLH-2004 diagnostic criteria? How many does this patient meet, and what is the significance of identifying HLH as a complication of VL rather than primary HLH?
  • If this patient had been started on empiric corticosteroids at a peripheral centre (without the rK39 test) for suspected autoimmune disease, what would have happened? Why is this the cardinal trap in FUO management?
Click to reveal Trigger 3: Diagnostic Crossroads: Secondary HLH and the Bone Marrow (discuss previous trigger first!)

Trigger 3: Diagnostic Crossroads: Secondary HLH and the Bone Marrow

Bone marrow aspiration is performed. The report reads: 'Hypercellular marrow with sheets of activated macrophages engulfing erythrocytes, leucocytes, and platelets. Leishman-Donovan bodies identified within macrophages. No morphological evidence of haematological malignancy.' The haematologist calls Dr Kavitha: 'This confirms secondary HLH triggered by visceral leishmaniasis. Continue AmBisome — treating the trigger is the primary intervention. You may need to add dexamethasone if he deteriorates.' Dr Kavitha explains to the students: 'This is exactly why the bone marrow was essential — not just to confirm kala-azar, but to look for what kala-azar was doing to the marrow, and to exclude lymphoma driving both.' She asks them to think about the FUO diagnostic plan they would have built for this man if the rK39 had been negative.

DISCUSSION POINTS

  • Why is bone marrow aspiration the most important investigation when a patient with suspected VL has pancytopenia and markedly elevated ferritin? What does it add beyond the rK39 antigen test?
  • In secondary HLH triggered by VL, what is the priority: treat the trigger (AmBisome) or suppress the cytokine storm (dexamethasone + etoposide per HLH-2004)? On what principle is this prioritisation based?
  • If the rK39 had been negative, construct the prioritised step-wise diagnostic plan you would have used for this patient — a 48-year-old Bihar farmer with 4-week fever, splenomegaly, pancytopenia, and weight loss. Which diagnoses must be excluded and in what sequence?
Click to reveal Trigger 4: Recovery, Communication, and Prevention (discuss previous trigger first!)

Trigger 4: Recovery, Communication, and Prevention

Mr Ramesh Mahto responds well to AmBisome, with defervescence by day 10 and steady haematological recovery. He is discharged on day 18. Before discharge, Dr Kavitha asks Arjun and Priya to observe while she counsels the patient and his wife. She explains the diagnosis (kala-azar), the treatment given, the need for follow-up (clinical + parasitological cure at 1 month), and tells them that all household contacts should be screened. She also explains that the disease is transmitted by the sand fly (Phlebotomus argentipes) and that indoor residual spraying and bed net use (where recommended) are preventive measures. She asks the students: 'After 18 days, this man's fever is gone. How do you define cure in kala-azar, and what is the risk of relapse?' She also turns to them: 'His wife has been anxious and asking questions in every family meeting. What communication errors did you see me make, and what would you have done differently?'

DISCUSSION POINTS

  • How is cure defined in visceral leishmaniasis (kala-azar) according to NVBDCP criteria? What is the difference between initial parasitological response, clinical cure, and definitive cure at 6 months?
  • The physician mentioned household contact screening. Why is household contact screening important in kala-azar, and what is the recommended screening approach under the National Kala-azar Elimination Programme?
  • Reflect on the communication skills demonstrated in this case. Using the five-step framework for communicating in prolonged fever (diagnosis/uncertainty, investigation purpose, treatment plan, expected timeline, red flags), evaluate what was done well and what could be improved. What specific red flag symptoms should this patient's family have been taught before the first admission?

Group Task Assignments

  • Using this case as a model, construct a one-page algorithm for the approach to a patient presenting with fever plus splenomegaly in a high-VL-burden Indian state (Bihar, Jharkhand, Uttar Pradesh, West Bengal). The algorithm should specify: (1) the first bedside test, (2) when to proceed to bone marrow aspiration, (3) when to initiate treatment without histological confirmation, and (4) what conditions must be simultaneously considered.
  • Debate the following proposition: 'rK39 antigen positivity alone, without bone marrow confirmation, is sufficient to initiate anti-leishmanial therapy in a patient from a VL-endemic area with clinical features consistent with kala-azar.' Divide the group into proponents and opponents; each side should cite the NVBDCP guidelines and relevant studies.
  • Design the ideal communication package for a VL patient being discharged from a government hospital in rural Bihar: (1) a verbal script for explaining the illness in simple Hindi/Bhojpuri terms, (2) a written red-flag card, and (3) a community-level message for the ASHAworker accompanying him back to the village.
  • Identify all the points in this patient's journey where the FUO management framework could have changed the outcome: from the initial presentation at the rural health centre (amoxicillin for 3 days), to the risk of empiric corticosteroids, to the importance of epidemiological pre-test probability. For each decision point, state what should have been done and what principle would have guided it.

Learning Issues

Research these questions and bring your findings to the discussion.

  1. [IM4.9] What is the Petersdorf-Beeson definition of FUO, what are its four subtypes, and in the Indian epidemiological context, what are the three diagnoses that must always be excluded in classic FUO regardless of presentation?
  2. [IM4.12] How do the four categories of FUO aetiology (infectious, inflammatory/autoimmune, malignant, miscellaneous) differ in proportional frequency in Indian hospital series compared to Western case series, and what does this mean for investigation sequencing?
  3. [IM4.13] What is the role of bone marrow aspiration and biopsy in the investigation of FUO? What conditions does it diagnose (TB, kala-azar, haematological malignancy, HLH), what is its sensitivity for each, and when is it indicated?
  4. [IM4.18] What is secondary HLH (haemophagocytic lymphohistiocytosis), what are the HLH-2004 diagnostic criteria, and what are the common infectious triggers in India (VL, EBV, TB)? How does treatment of the trigger differ from primary HLH treatment?
  5. [IM4.19] What is the NVBDCP first-line treatment for visceral leishmaniasis in India, what is the recommended regimen (drug, dose, route), and what are the criteria for treatment failure? How does co-infection with HLH change the management priority?
  6. [IM4.20] What are the key components of communicating a diagnosis of prolonged fever (FUO or identified cause) to a patient and family, particularly when the disease carries stigma (as kala-azar does in some communities) or when the treatment course is long and requires follow-up?