A matter of spleen

1
A matter of spleen

• Lorenzo Dagna
• San Raffaele Scientific Institute
• Università Vita-Salute San Raffaele
• Milan, Italy
• lorenzo.dagna_at_hsr.it

2
Clinical case

• Male, 66-year old, Italian
• 10-day history of loss of appetite, malaise, and
  weakness
• 7 days before admission intermittent high-grade
  fever (39C/102.2F) accompanied by profuse
  sweating, and dyspnea
• ? Levofloxacin 500 mg daily (started by his GP)
• No history of recent travels.

3
Past medical history

• congenital stenosis of pulmonary arteries
  (aneurysm)
• 1990 diagnosis of idiopathic thrombocytopenic
  purpura (corticosteroids)
• 1996 splenectomy
• 1999 vertebral crush fracture (T8)
• 2000 hyperplastic disease of the prostate
• 2003 aspecific chronic colitis with colonic
  tubulo-villous adenomatosis (mild dysplasia)
• 3 months before admission elevated LFTs

4
Physical on admission

• BP 110/70 mmHg, HR 94/min, T 38.8C (102F)
• Not in apparent acute distress, alert, oriented
• Heart tachycardia, regular rhythm, 2/6 systolic
  bruit on right parasternal
• Lungs clear to auscultation and percussion
  bilaterally
• Abdomen soft, nontender, nondistended. No
  masses. Bowel sounds within normal limits. Mild
  hepatomegaly
• Lymph nodes bilateral axillary and inguinal
  lymphadenopathy

5
Laboratory findings

• Hb 11.6 g/dL (MCV 87.0 fL), Plt 19.000WBC 3.900
  (N62 L36 M2 E0)
• creatinine 1.18 mg/dLC-reactive protein 55.51
  mg/L (normal values. 2.0-6.0)
• Na 127.7 mmol/L, K 4.49 mmol/LALT (SGPT) 81 U/L,
  AST (SGOT) 109 U/LLDH 558 U/L
• serum proteins, 76.8 g/LSPE albumin 34,
  ?-globulin 43.7(monoclonal gammopathy)
• Immunofixation IgG ? and IgG ?

6
Diagnostic workup

• Chest X-ray widening of upper cardiac shadow
  (pulmonary artery aneurysm). No
  pleuroparenchimal alterations
• Abdomen US mild hepatomegaly (16 cm right lobe
  longitudinal diam.) few small hepatic hilar
  lymph-nodes

7
Diagnostic workup

• 33 blood cultures negative (72hrs)PPD (5U)
  negative
• ANA 1640 (granular)C3, C4 normal
• Anti-HIV negAnti-HCV negAnti-HBsAg
  negWidal-Wright, anti-Brucella spp. neg

8
Diagnostic workup

• Echocardiogram (TTTE)no bacterial
  vegetationscommon pulmonary trunk aneurysm
• mild tricuspidal insufficiency

9
Diagnostic workup

• CT scan (thoraxabdomen)
• Bilateral apical pleural thickening mild
  bilateral pleural and pericardic effusion few
  small mediastinal lymph nodes (diam. lt 1 cm)
  aneurysm of the pulmonary common trunk (diam., 6
  cm)
• Bilateral iliac lymph nodes (diam., lt 2 cm)
• Two masses (diam., 4 cm) at the site of
  splenectomy (hypertrophic residual splenic
  tissue)
• Mild hepatomegaly (no focal lesions) few hilar
  lymph nodes (diam., 1.5 cm)

10
Laboratory findings (day 4)

• Hb 10.8 g/dL (MCV 86.8 fL) WBC 1.900 (N42 L56
  M2 E0)Plt 8.000
• creatinine 2.2 mg/dL
• ? ALT (SGPT) ? AST (SGOT)? LDH

11
A diagnostic procedure was performed
12
Diagnostic procedure

• A bone-marrow core biopsy was performed
• Prednisone 1 mg/kg day was started

13
Bone marrow biopsy
Leishmania spp. organisms within mononuclear
cells (Giemsa stain, 400x)
14
Leishmania testing

• Anti-Leishmania Abs pos 15,120
• Leishmania spp. PCR assay2,700,000 DNA
  equivalents/plasma mL

15
Diagnosis / Therapy

• A diagnosis of visceral Leishmaniasis was made
• Liposomal amphotericin B (3 mg/kg daily for 5
  day, then at day 14 and 21, total 21 mg/kg)

16
Visceral Leishmaniasis

• Leishmania donovani complex (L. donovani, L.
  infantum, L. chagasi)
• Transmission sandflies parenterally,
  congenitally
• Infection Macrophages reticulo-endothelial
  system

17
VL clinical laboratory features

• Often silent and subclinical(malnutrition is a
  risk factor for the development of the disease)
• Splenomegaly (soft, non-tender) more impressive
  than hepatomegaly
• Sometimes peripheral lymphadenopathy
• Anemia (BM infiltration, hypersplenism,
  autoimmune hemolysis, bleeding)
• Leukopenia (?N, ?Eo)
• Thrombocytopenia
• Hypergammaglobulinemia (polyclonal B-cell
  activation)
• Hypoalbuminemia

18
VL differential diagnosis

• Other infectious diseases that may cause fever or
  organomegaly
• typhoid fever
• miliary tuberculosis
• brucellosis
• histoplasmosis
• malaria
• Schistosomiasis
• Lymphoproliferative diseases
• leukemia
• lymphoma

19
VL diagnosis

• Demonstration of the parasites on stained
  slides(spleen, liver, bone marrow, lymph node)
• High titers of anti-Leishmania antibodies
• Leishmania skin-test reactivity
• IFN-? cellular responses to leishmanial Ags
• PCR (being field-tested)

20
VL therapy

• Pentavalent antimonial compounds (SbV) - IV/IM20
  mg SbV/kg qd for 28 days
• Lipid formulations of amphotericin B - IV2-5
  mg/kg qd (day 1-5, 14 and 21)
• Paromomycin - IV15-20 mg/kg qd for 21 days
• Pentamidine - IV, IM4 mg/kg qod or thrice weekly
  for 15-30 doses
• Miltefosine - PO2.5 mg/Kg qd for 28 days