What are the symptoms and treatment options for visceral leishmaniasis in a patient with a history of immunocompromising conditions, residing in or traveling to an endemic area?

Symptoms of Visceral Leishmaniasis

Visceral leishmaniasis presents with chronic fever, weight loss, splenomegaly, and pancytopenia in patients with travel or residence history in endemic areas, with immunocompromised patients at particularly high risk for atypical presentations and disseminated disease. 1

Classic Clinical Manifestations

The hallmark symptoms of VL include:

• Chronic fever (present in 64% of patients), which may be intermittent, remittent with twice-daily spikes, or continuous 1, 2
• Progressive weight loss (21% of patients) 1, 2
• Marked splenomegaly (58% of patients), though this may be subtle or absent in HIV-coinfected individuals 1, 2
• Hepatomegaly (49% of patients) with variable severity 1, 2
• Weakness and fatigue (57% of patients) as prominent constitutional symptoms 2

Hematologic and Laboratory Abnormalities

VL characteristically causes:

• Pancytopenia affecting all cell lines, which is a defining feature 1
• Hypoalbuminemia and elevated acute inflammatory markers 1
• Elevated liver enzymes (transaminases) 1
• Hypergammaglobulinemia reflecting chronic immune stimulation 1
• Peripheral eosinopenia may be present 1

Additional Clinical Features

• Hyperpigmentation of the skin (darkening) occurs specifically in patients infected in India and Bangladesh, giving rise to the term "kala-azar" (black fever) 1
• Lymphadenopathy (36% of patients) is seen in some cases, particularly in East African VL 2
• Dry cough (13% of patients) may occur 2
• Night sweats (37% of patients) are commonly reported 2

Temporal Characteristics

• The median duration of symptoms before diagnosis is 28 days, though the onset and course are usually subacute or chronic 1, 2
• The disease can present acutely in some cases 1
• Latent infection can reactivate years to decades after initial exposure, making VL a consideration even with remote travel history 1

Special Considerations in Immunocompromised Patients

Immunocompromised individuals (HIV/AIDS, organ transplant recipients, those on TNF-α antagonists, corticosteroids, or chemotherapy) face unique challenges:

• Atypical presentations are common, with some classic features like splenomegaly being more subtle or absent 1
• Widespread parasite dissemination to atypical sites including the gastrointestinal tract, skin, and essentially any organ system 1
• Dermatologic or mucosal involvement occurs quite commonly in HIV-associated VL, which may mimic other pathologies 1
• VL may be the first opportunistic infection in persons with AIDS 1
• Haemophagocytic syndrome can develop (6% of cases), representing a severe complication 2
• Onset typically occurs within the first year post-transplant in solid organ recipients, with high-dose corticosteroid use being a major risk factor 1

Epidemiologic Context

VL should be suspected in patients with:

• History of residence or travel to endemic areas (Mediterranean basin, Indian subcontinent, East Africa, Latin America) 1, 3
• Contact with dogs (46% of patients report animal contact), as dogs are the main reservoir in zoonotic transmission areas 2
• Risk factors beyond sand fly bites including needle sharing, blood transfusion, organ transplantation, or laboratory accidents 1

Differential Diagnosis Considerations

The broad differential diagnosis includes:

• Acute presentations: malaria, typhoid fever, typhus, acute Chagas disease, acute schistosomiasis, miliary tuberculosis 1
• Subacute/chronic presentations: miliary tuberculosis, brucellosis, prolonged Salmonella infections, subacute bacterial endocarditis, disseminated fungal diseases, malaria with tropical splenomegaly syndrome, hepatosplenic schistosomiasis 1
• Non-infectious causes: lymphoma, leukemia, myeloproliferative diseases, rheumatoid arthritis with Felty syndrome, autoimmune processes, hemophagocytic lymphohistiocytic syndrome 1

Critical Clinical Pitfalls

• Do not dismiss VL based on remote travel history, as reactivation can occur decades after exposure, particularly when immunosuppression develops 1
• Absence of splenomegaly does not exclude VL in HIV-coinfected or immunocompromised patients 1
• The clinical manifestations are not specific, requiring a high index of suspicion in the appropriate epidemiologic context 1
• Untreated VL is potentially fatal, with death resulting from progressive wasting, superinfection, or hemorrhage 1, 4