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The absent and vanishing spleen: Congenital asplenia and hyposplenism—two case reports

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    The absent and vanishing spleen: Congenital aspleniaand hyposplenismtwo case reports


    1Department of Paediatric Intensive Care, UniversityMedical Centre St. Radboud,Nijmegen, TheNetherlands, 2Department of

    Paediatric Immunology, University Medical Centre St. Radboud, Nijmegen, The Netherlands, and 3Department of Internal

    Medicine, University Medical Centre St. Radboud, Nijmegen, The Netherlands

    AbstractTwo unrelated patients are reported: one with isolated familial asplenia diagnosed postmortem, the other with isolatedhyposplenism diagnosed after recurring invasive bacterial infections. Because both children died of fulminant septic shock, theimportance of early diagnosis of splenic dysfunction is evident. Clues for an early diagnosis of congenital asplenia are recurrentinvasive bacterial infections, Howell-Jolly bodies in the blood smear or a relative with congenital isolated asplenia. Althoughthe guidelines for infection prevention in asplenismpatient education, antibiotic prophylaxis and vaccinationare welldefined, controversy remains as to how to differentiate hyposplenism from functional asplenism.

    Conclusion: Based on the present observations, we define a patient as functionally asplenicand therefore at risk for life-threatening infectionswhen Howell-Jolly bodies are present in the blood smear, a very small spleen is found by ultrasound,or splenic blood flow is compromised.

    Key Words: Familial congenital isolated asplenia, hyposplenism, Howell-Jolly bodies, Streptococcus pneumoniae sepsis

    Asplenia as a risk factor for life-threatening infections

    was first described in the middle of the last century.

    Since then, the absence of splenic function has been

    recognized as a major risk factor for severe over-

    whelming infections, with a lifetime risk of 0.25% and

    a mortality over 50% [15]. Often, the absence of a

    normal functioning spleen is known from the patients

    history, and preventive measures can be taken. How-

    ever, congenital isolated asplenia and hyposplenism

    are rare diseases that usually remain undiagnosed

    until life-threatening bacterial infections have oc-

    curred. Recurrent severe infections, especially with

    pneumococci, the presence of Howell-Jolly bodies in

    the blood smear, or a relative with congenital isolated

    asplenia should alert the physician to assess splenic

    function. Still, as shown by the two following cases,

    early recognition of congenital asplenia remains


    Case reports

    Case A

    A 2.5-y-old girl with a history of Streptococcus pneumo-

    nia meningitis at the age of 6 mo was admitted to our

    paediatric intensive care unit with severe septic shock,

    preceded by 1 d of fever and signs of an upper res-

    piratory tract infection. On admission she had a heart

    rate of 210 bpm, a blood pressure of 55/40 mmHg, a

    capillary refill of over 5 s, and extensive petechiae and

    ecchymoses; TcSaO2 was 50%. She was intubated and

    ventilated, i.v. fluids and dopamine were started, and

    ceftriaxon and amoxicillin were given. Laboratory

    investigation showed a severe metabolic and respira-

    tory acidosis, renal failure and elevated liver enzymes,

    electrolyte disorders, diffuse intravascular coagulation,

    anaemia and severe thrombocytopenia. Blood cultures

    and skin biopsies did not reveal micro-organisms;

    Correspondence: F. Halbertsma, Department of Paediatric Intensive Care, University Medical Centre St. Radboud, PO Box 9101, 6500 HB Nijmegen,

    The Netherlands. Fax: (0)24 35 41 612. E-mail: [email protected]

    (Received November 24, 2003; revised May 3, 2004; accepted May 7, 2004)

    Acta Pdiatrica, 2005; 94: 369383

    ISSN 0803-5253 print/ISSN 1651-2227 online # 2005 Taylor & Francis Group Ltd

    DOI: 10.1080/08035250410022350

  • however, with the history of Streptococcus pneumonia

    meningitis, a pneumococcal sepsis was suspected, and

    splenic dysfunction was considered. Ultrasound of

    the abdomen did not reveal a spleen without other

    intra-abdominal abnormalities. The heart showed a

    decreased (sepsis-related) contractility but was other-

    wise normally structured. Despite massive fluid

    replacement, extensive inotropic support, mechanical

    ventilation and correction of electrolyte, and haemato-

    logical disorders, the patient died within 24 h. Autopsy

    was not permitted. Familial screening revealed a nor-

    mal spleen in a younger sister; however, in a younger

    brother no spleen was detected and, in his blood smear,

    Howell-Jolly bodies were present.

    Case B

    Patient B is a girl with a history of Streptococcus pneu-

    monia arthritis at the age of 18 mo, and a Haemophilus

    influenza arthritis of the knee and elbow at the age of

    21 mo. The immunological analysis revealed a normal

    white blood cell count and differentiation, normal

    immunoglobulin classes and subsets, and complement

    functionality assays. No spleen could be detected on

    ultrasound; however, by scintigraphy, a well-perfused,

    though small spleen was demonstrated. As no Howell-

    Jolly bodies were seen in the blood smear, further

    prophylaxis was refuted.

    At the age of 10 y, she presented with overwhelming

    septic shock, for which prompt inotropic support, i.v.

    fluids and plasma products, mechanical ventilation,

    antibiotics (amoxicillin and ceftazidim) and cortico-

    steroids were started. Blood cultures revealed large

    quantities of Streptococcus pneumonia, and were detect-

    able even in the ordinary blood smear. Despite inten-

    sive treatment, the patient died within 24 h. Autopsy

    revealed a nearly completely involuted spleen (51.5 g;normal 4150 g). Familial screening showed normalspleens in two younger, healthy brothers.


    Isolated congenital asplenia and hyposplenism are rare

    causes of asplenia, of which less than 65 cases have

    been reported (Table I) [6,7]. As the two reported

    cases illustrate, these highly dangerous conditions are

    usually diagnosed after infections have occurred.

    The aetiology of asplenia in isolated congenital

    asplenia is unknown. In familial congenital asplenia

    both autosomal-dominant as well as recessive inheri-

    tance patterns have been observed [6]. Mutations in

    the HOX-11 gene are a candidate gene for these

    defects, as HOX-11 knockout mice are asplenic [8].

    Specific mutations or deletions in humans have not

    yet been detected. The spleen has an important

    immunological function in host defence against

    bacteria that have a polysaccharide capsule such as

    S. pneumoniae, Neisseria meningitides or Haemophilus

    influenzae, and bacteria such as Capnocytophaga cani-

    morsus, Salmonella spp. or E. coli, or protozoa such as

    Plasmodium falciparum and Babesia microti. As Gram-

    positive bacteria such as S. pneumoniae are not sus-

    ceptible to complement mediated lysis and are poorly

    opsonized by classic opsonins, an adequate splenic

    function is essential for the elimination of these

    bacteria from the bloodstream. Clearance of these

    bacteria requires intimate contact with effector cells

    in the venous sinuses of the splenic red pulp. This is

    even more important in children under 2 y of age,

    as B cells are unable to mount an adequate antibody

    response to the T-cell-independent polysaccharide

    capsule. When adequate levels of antibodies are pres-

    ent, as a result of earlier contact with the micro-

    organisms or vaccination, the risk for overwhelming

    infections is diminished. Impaired filtration by the

    spleen is reflected by the presence of Howell-Jolly

    bodies in erythrocytes. In newborns with a normal

    spleen, they may be seen during the first 2 wk of

    life as well [9]. Splenic absence can usually be con-

    firmed with ultrasound, CT or scintigraphy. Recurrent

    severe infections in a patient with otherwise normal

    immunological findings, or the presence of Howell-

    Jolly bodies in the blood smear should alert the physi-

    cian to the presence of an impaired splenic function.

    Since 50% of cases of congenital isolated asplenia

    are familial, early screening in relatives is strongly


    Table I. Classification of asplenia.

    Congenital& Isolated

    familial non-familial

    & Syndromatic

    Ivemark Storkmorken Kartagener Meckel Pallister-Hall Cystic liver, kidney, pancreas MLRD (microgastria-limb reduction defects


    Smith Fineman Meyers Schmidt

    Acquired& Splenectomy

    Trauma Haemolytic anaemia ITP Malignancy

    & Functional/hyposplenism

    HbSS/Sickle-cell anaemia Portal hypertension Storage diseases (Amyloidosis, M. Gaucher) Iatrogenic (radiotherapy)

    370 Clinical observations

  • When to consider a hyposplenic patient as func-

    tionally asplenic remains controversial. For normal

    humoral and cellular immunological activity, only a

    few grams of splenic tissue are sufficient, but for an

    adequate filtering function in the defence against

    encapsulated micro-organisms more splenic tissue is

    probably required [10]. Still, the size of the spleen does

    not correlate well with its immunological function.

    In functionally asplenic patients, Gorg et al. found a

    small spleen (less than 7r3 cm) on ultrasound in83%, and abnormal Doppler-flow patterns (no flow