Case Reports, like we're on a episode of house
23M in Kenya, presenting with months of LOW, persistent fevers, and abdo fullness, found to have massive splenomegaly.
examination: massive splenomegaly (10 cm below costophrenic margin, and will definitely cross midline) and hepatomegaly
pancytopaenic on bloods, plt's down to 40s
diagnosis confirmed on BMAT (parasite seen)
normal HIV, liver and kidney function
Bodies seen on the BMAT below are part of the lifecycle of the parasite that is intracellular, hence you can see the macrophages/neutrophils loaded with them, even bursting
think of it when you get a patient with pancytopaenia and hepatosplenomegaly, who either traveled to or is in/from a tropical/subtropic region (where sand flies are)
cause - protozoa parasite Leishmania, transmitted by infected sandflies
Epidemio (when to consider it)
tropics, subtropics (South America, Asia, AFrica), Southern Europe
Microbiology/Transmission
parasite, replicates intracellularly (Leishmania donovani)
transmitted in sand flies (can be unnoticeable and usually bite in dawn or dusk - evenings or night), can also be transmitted via needles/blood
more common in rural areas
I've simplified this, but is more extensively covered in StatPearls and Wiki (there's different species of Leish and sandflies that transmit it)
once bitten, the protozoa are phagocystosed by skin macrophages, which then becomes full of the "bodies" (part of the lifecycle). Eventually these burst to release more of the bodies that infect more macrophages
they eventually are spread via blood to liver/spleen/BM and LNs
ancient, records of disease date back to Egyptian mummies from 3000 BC --> positive DNA amplication for Leishmania and on papyrus from 1500 BC
multiple physicians from different times have described the disease, but it's named for 2 who described the parasite's intracellular ovoid body stage in smears from infected patients in India: Lt General William Boog Leishman and Captain Charles Donovan (Ronald Ross named the bodies after the 2 --> "Leishman Donovan bodies"
significant disease in Allied troops in Sicily in WWII, called "jericho buttons" (image on wiki from a WWI trooper serving in the middle east)
Leishman: Scottish pathologist and British Army medical officer, later it's director general in the 20s, did extensive research into the parasite named for him by Sir Ronald Ross. He mistook the parasite he observed for trypanosomes (cause of Chagas in South America and African sleeping sickness in Africa)
Donovan: Irish parasitologist, medical officer in India, observed an epidemic across India just after the rebellion of 1857, discovered the "bodies" in spleen tissue as the causative agent for what the locals called "kala azar" (severe visceral leishmaniasis - see below)
Donovan also discovered the "bodies" of Klebsiella granulomatis, hence these too are named after him (cause of ulcerative granulomas)
It became scandalous as both wanted credit for the "discovery" of this newly identified organism. So Sir Ronald Ross named it for both of them.
Sir Ron, by the way, won a Nobel in Medicine for discovering that malaria is transmitted via mossies (this was also a source of scandal, he was meant to share it with another physician who he accused of fraud - and they never received the award)
finally, it was actually a Russian physician who identified it first, but well, he published in a little known Russian journal which was promptly forgotten.
cutaneous type vs visceral organ type (spleen, liver, bones)
cutnaeous: can be there for years and resemble leprosy, causes an open chronic wound (most common), incubation 2-4 weeks on average (nodules at site of inoculation that eventually form ulcers), can heal spontaneously in 2-5 yrs
in diffuse cutaneous cases, can affect face, ears, extensor surfaces
can be muscosal = eg nasal symptoms/epistaxis, severe: perforated septum, this occurs in 1/3 after resolution of cutaenous symptoms (can be severe/lifte threatning, as it can affect vocal cords and cartilage, but oddly not bone)
visceral (incubation periods of up to years until immuncompromise): fever, weight loss, hepatosplenomegaly (spleen more than liver), pancytoaepnia, high total protein and low albumin with hypergammaglobulinaemia
this has seasonal peaks related to sandfly habits and humidity
interestingly it is an infective cause of massive splenomegaly, such that it crosses the midline
Extreme - but noticeable hepatosplenomgealy/abdo fullness, from medscape
can be atypical in HIV co infected patients, LAD in seom regions like Africa
Kala azar = black fever in some severe cases (fatal due to secondary mycobacterial infection or bleeding), refers to damage fto spleen, liver and anaemia
serology not great (minimal humoral response to the parasite), so often requires histopath (tissue sample) for which BMAT is safest in visceral organ involvement
visualisation of amastigotes (or Leishman-Donovan bodies), as intracellular --> can be seen in macrophages (small round bodies) post Giemsa staining
PCR of DNA also possible (as done in the Egyptian mummies)
liposomal amphotericin B (holy shit strong stuff) in visceral, PO: miltefosine (caution in pregnancy), all have significant ADRs, or paromycin. however, mortality of 10% if visceral left untreated
mixed results with azoles
in HIV co infection - start the HAARTs! can improve survival, mortality is 30% in HIV patients
cutaneous: stibolgluconate (have never heard of these drugs) and megluaine antimoniate, but limited disease often spotnaeously gets cleared by the innate system
use DEET insect repellant at dawn and dusk
loose fitting clothing that covers all skin
no vaccine (were attempts at vaccinating dogs, which decreased rates)
sandflies are smaller than mossies, so requires small netting
Differentials for hepatosplenomegaly
Wiki - Haven't covered pathophysio, but wiki does extensively
DermNet - great resource for all things derm, that my derm colleagues pointed out to me
