Page 2567 - Hematology_ Basic Principles and Practice ( PDFDrive )

2290 Part XIII Consultative Hematology

lining of the stomach and enter the proboscis of the sandfly, allowing fever similar to classic malaria, with malnutrition, bleeding, hepatitis,
them to be inoculated in the human host while the sandfly takes a and/or acute renal failure.
blood meal. Promastigotes are taken up by macrophages, where they
become amastigotes by simple fission.
The large, elongated, fusiform promastigote measures 15 to Immunocompromised Hosts
20 µm in length and 0.5 to 3.5 µm in width. Cultured promastigotes
may also demonstrate rounded forms 4 to 5 µm in diameter. In Coinfection with HIV and VL is now a well-recognized clinical
Giemsa or other Romanowsky stains, a large nucleus and smaller, entity in the Mediterranean region and undoubtedly occurs more
149
148
distinct rodlike kinetoplast are obvious. The organisms must be widely 145–147 (for review, see Lindoso et al and Alvar et al ). VL
distinguished from Histoplasma capsulatum. occurs in the setting of late-stage acquired immunodeficiency syn-
+
drome (AIDS) with CD4 lymphocyte counts of less than 200 ×
6
10 /L. Patients present with fever, splenomegaly, and pancytopenia
Pathology with frequent and sometimes atypical involvement of the gastro-
intestinal and respiratory systems and skin. The typical hematologic
Parasites spread within macrophages to local lymph nodes and then features of VL are sometimes absent, and serologic tests are often
to the liver, spleen, and bone marrow. They are also present more negative, although antibodies to 14- and 16-kDa Leishmania antigens
150
widely, in particular in the gastrointestinal tract and epidermis. In the may be detected by Western blot analysis. However, organisms are
subclinical cases, a cellularly mediated immune response causes a plentiful in bone marrow and even in buffy coat preparations. Some
granulomatous lesion and resolution of the infection. However, in patients may have few symptoms, and the diagnosis of VL in
clinical VL little if any inflammatory response to the rapidly extensive immunocompromised patients requires a high index of suspicion.
and expanding parasite-laden macrophages is seen. Where it shows, Treatment is difficult, with poor responses to pentavalent antimony.
a granuloma develops at the site of the initial inoculation but may Liposomal amphotericin is the drug of choice. However, relapses are
not be apparent at the time of presentation. usual, and maintenance treatment is required. 148
VL may also occur after transplant and after immunosuppressive
treatments, including chemotherapy, rituximab, or other immunode-
Clinical Features of Visceral Leishmaniasis ficiency states. 151,152 Although patients present with a typical combi-
nation of fever, pancytopenia, and splenomegaly, the diagnosis may
The spectrum of clinical disease is wide, ranging from asymptomatic be missed if not considered.
infection to acute or chronic illness. Perhaps only 1% to 3% of all
infections are symptomatic, with an incubation period of 10 days to
10 years but typically between 3 and 6 months. Hematologic Features
The high number of seropositive individuals in relation to clinical
153
cases suggests that spontaneous cure without symptoms or with mild VL causes a moderate normocytic, normochromic anemia. The
systemic symptoms and hepatosplenomegaly occurs in the majority pathogenesis of anemia is multifactorial and includes hemodilution,
154
of individuals. In a large series of children with VL in Brazil, the shortened RBC survival, and reduced erythropoiesis. The plasma
overall case fatality rate was 10%, and mucosal bleeding, jaundice, is low, with plentiful stored iron typical of the anemia of chronic
155
dyspnea, bacterial infections, and low neutrophil count of less than disease. One report has suggested that Epo levels are reduced
3
156
3
500/mm or low platelet count of less than 50,000/mm were associ- compared with what would be expected for the degree of anemia.
ated with a poor outcome. 142 Occasionally, folate deficiency secondary to malabsorption and/or
In endemic areas, a significant number of seropositive children, increased cell turnover or coexistent iron deficiency are associated
who do not develop classic VL, have a subclinical form of disease with macrocytic or microcytic anemia, respectively. 157
with malaise, fever, poor weight gain, intermittent cough, diarrhea, The direct Coombs test results are usually positive for C3 com-
hepatomegaly, and variable splenomegaly. In these cases, leishmania ponents, and IgG and anti-I agglutinins may be present, but the
143
were neither cultured nor seen in bone marrow aspirates. There are presence and strength of the test is not correlated with the severity
also reports of VL presenting as mild, nonspecific illness with fever, of the anemia. The positive direct Coombs test results appear to be
158
fatigue, cough, and abdominal pain in army personnel returning from caused by absorbed immune complexes onto erythrocytes. The
the Middle East. In these cases, L. tropica was isolated from bone neutrophil survival is reduced, and the differential white blood cell
marrow or lymph nodes. 144 count shows neutropenia, relative lymphocytosis, and low eosinophil
Patients with typical chronic VL often present with malaise and levels, with a white blood cell count typically in the range 2 to 4 ×
9
considerable fatigue and the slow onset of low-grade fever, anorexia, 10 L.
159
and weight loss. They usually have anemia, progressive and occasion- Neutrophil function may be impaired. Pancytopenia is more
ally massive splenomegaly, hepatomegaly, lymphadenopathy, and severe in those with concurrent HIV infection. A leukemoid reaction
hypergammaglobulinemia, with increasing skin pigmentation (hence to infection has been reported.
9
the name kala-azar from the Hindi for “black sickness”). Patients may Typically the platelet count is reduced to 50 to 200 × 10 /L as
have jaundice, petechia, or purpura; heart murmurs; and edema. The platelet survival is reduced. Mucosal bleeding may occur, but exten-
size of the spleen is related to the length of infection and severity of sive purpura is uncommon.
the pancytopenia. In Africa, patients may have diffuse polymorphic The prothrombin time is usually mildly prolonged to 2 to 4
papular lesions at presentation. Oral, nasal, nasopharyngeal, and seconds longer than in control subjects, secondary to impaired liver
laryngeal ulcers may occur during active disease or after treatment. function. Fibrinolytic activity is increased, and in advanced cases,
The large spleen, often extending to the right iliac fossa, may be fibrinogen levels may be reduced. Disseminated intravascular coagu-
painful. Other features of acute disease include cough, epistaxis, and lation or vasculitis may occur. 153,159 Full coagulation screening is
in some severe cases concurrent infection of the respiratory or gastro- advisable if a splenic aspirate or bone marrow biopsy is planned.
intestinal tracts and/or tuberculosis. The bone marrow is usually hypercellular, with increased ery-
The typical features of VL may be preceded by bacteremia, bacte- throid, myeloid, and platelet precursors. Lymphocytes may be
rial infection, acute hepatitis, or Guillain-Barré syndrome. VL may increased, and macrophages contain Leishman-Donovan bodies (Fig.
160
be associated with hepatic necrosis, cholecystitis, or neuropathy. 158.8). If weight loss and malabsorption are extensive, the marrow
Occasionally, lymphadenopathy may occur without systemic features may undergo gelatinous transformation.
of the disease. Here histology shows noncaseating granulomas and The mechanisms of leukopenia and thrombocytopenia are multi-
amastigotes within macrophages. A more acute presentation in recent factorial. There is evidence for reduced bone marrow production of
immigrants and visitors to endemic areas may include a high periodic granulocytes and platelets and also for their autoimmune destruction