Differentials
Hyperreactive malarial splenomegaly (HMS)
SIGNS / SYMPTOMS
Differential for visceral leishmaniasis (VL).
Formerly called tropical splenomegaly syndrome.
The clinical presentation can mimic VL but fever is a less consistent feature.[101]
A clinical response to antimalarials also helps distinguish the diagnoses.
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Major criteria for HMS diagnosis are splenomegaly >10 cm on CT scan, high titers of antimalarial antibodies, and IgM titers >2 standard deviations above the mean of the local population.
Plasmodium species in the peripheral blood smear are typically not found.
In practice, VL must be ruled out by specific serologic or parasitologic tests.[101]
Malaria infection
SIGNS / SYMPTOMS
Differential for visceral leishmaniasis (VL).
As malaria is more acute than VL, patients present with fever of shorter duration and mild or absent splenomegaly.
Recurrent malaria can be more difficult to distinguish from VL, as fever can be longer lasting and intermittent, and the spleen markedly enlarged.
Patients unresponsive to effective antimalarials should be investigated for VL, as dual infection is common in endemic areas.
INVESTIGATIONS
Malaria can be diagnosed by microscopic exam of a stained, thin, and thick smear of peripheral blood or by a rapid diagnostic test detecting circulating antigens specific to P falciparum or other species.[102]
Schistosomiasis
SIGNS / SYMPTOMS
Differential for visceral leishmaniasis.
Splenomegaly, secondary to portal hypertension, can be massive.
Chronic schistosomiasis does not cause fever but the patient may present with concomitant infection such as malaria, typhoid fever, or tuberculosis.[103]
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Chronic Schistosoma mansoni infection is diagnosed by the presence of characteristic eggs in the stools or by antibody-based assays.
Abdominal ultrasound, CT scan, or MRI show the typical features of hepatic schistosomiasis and signs of portal hypertension.[103]
Leprosy
SIGNS / SYMPTOMS
Differential for disseminated cutaneous leishmaniasis.
Residence in/travel to an endemic area.
Absence of ulcerative lesions.
Presence of neuropathy.
INVESTIGATIONS
Histopathology: positive for acid-fast bacilli.
Paracoccidioidomycosis
SIGNS / SYMPTOMS
Differential for mucosal leishmaniasis.
Residence in/travel to an endemic area.
Skin lesions often involve the face: for example, the nasal and oral mucocutaneous borders.
INVESTIGATIONS
Histopathology: large yeasts that form multiple buds (sometimes called a pilot wheel or Mickey Mouse ears).
Blastomycosis
SIGNS / SYMPTOMS
Differential for cutaneous leishmaniasis.
Residence in/travel to an endemic area.
Fungal skin lesions can appear nodular, ulcerated, or verrucous, and typically have a raised, irregular border.
INVESTIGATIONS
Histopathology: acute inflammation with or without necrosis, granuloma formation, and multinucleated giant cells. Large yeasts that characteristically form a single broad-based bud (may be described as having a ‘footprint’ morphology).
Disseminated histoplasmosis
SIGNS / SYMPTOMS
Differential for visceral leishmaniasis.
Residence in/travel to an endemic area.
Skin lesions are uncommon but may occur in disseminated histoplasmosis.
Fever, splenomegaly, and pancytopenia may be found.
INVESTIGATIONS
Histopathology: visualization of Histoplasma capsulatum; this looks very similar to an amastigote but without a rod-shaped kinetoplast.
Sarcoidosis
SIGNS / SYMPTOMS
Differential for cutaneous leishmaniasis.
Tender erythematous nodules on lower extremities.
The granulomatous lesion of leishmaniasis recidivans can mimic sarcoidosis.
INVESTIGATIONS
Skin biopsy: noncaseating granulomas.
Cutaneous tuberculosis
SIGNS / SYMPTOMS
Differential for cutaneous leishmaniasis.
Cutaneous tuberculosis may present with similar skin lesions; however, they are uncommon in tuberculosis.
INVESTIGATIONS
Biopsy, histopathology, culture, and/or polymerase chain reaction of lesions distinguish tuberculosis.
Squamous cell carcinoma of the skin
SIGNS / SYMPTOMS
Differential for cutaneous leishmaniasis.
History of skin cancer or sun damage to skin.
Appears as erythematous papules or plaques that often have a scale or hemorrhagic crust, or as a nodule. May bleed easily, ulcerate, or exhibit rapid growth.
INVESTIGATIONS
Biopsy: keratinocyte atypia.
Basal cell carcinoma
SIGNS / SYMPTOMS
Differential for cutaneous leishmaniasis.
History of skin cancer or sun damage to skin.
Presents as pearly papules or plaques with rolled borders, telangiectasia, and ulceration when tumors become larger.
INVESTIGATIONS
Biopsy: tumor nests with basaloid differentiation, with large nuclei and scant cytoplasm.
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