CLINICAL OBSERVATIONS

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

F. J. J. HALBERTSMA1, C. NEELEMAN1, C. M. WEEMAES2 & M. van DEUREN3

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 asplenism—patient education, antibiotic prophylaxis and vaccination—are welldefined, controversy remains as to how to differentiate hyposplenism from functional asplenism.

Conclusion: Based on the present observations, we define a patient as functionally asplenic—and therefore at risk for life-threatening infections—when 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 0.2–5% and

a mortality over 50% [1–5]. Often, the absence of a

normal functioning spleen is known from the patient’s

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

difficult.

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: f.halbertsma@ic.umcn.nl

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

Acta Pædiatrica, 2005; 94: 369–383

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 normal

spleens in two younger, healthy brothers.

Discussion

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

advised.

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

association)

� 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 in

83%, and abnormal Doppler-flow patterns (no flow

or only hilar flow) in 88% [11]. However, the spleen

significantly decreases in size at elderly age with

retaining its function [12]. Thus, ultrasound with

Doppler-flow imaging alone can not establish or

exclude the diagnosis of functional asplenia.

In our opinion, a hyposplenic patient is to be

considered as functionally asplenic if, next to a small

spleen, splenic blood flow is compromised or Howell-

Jolly bodies are found in the blood smear as well.

Regarding the serious risk of infection in case of

functional asplenia, frequent follow-up of hyposplenic

patients is advised in order to monitor eventual

degeneration of the spleen.

For the management of a patient with asplenia, well-

defined guidelines are formulated regarding education,

vaccination and chemoprophylaxis [13,14]. With the

recent development of (T-cell-dependent) conjugate

vaccines, attention has shifted from chemoprophylaxis

to vaccination. It should be noted, however, that the

coverage of the currently available pneumococcal

conjugate vaccines (PCV) in Europe is significantly

lower than in the Unites States. It is to be expected

that, with the appearance of an 11- or 13-valent PCV,

the coverage will be increased sufficiently. Still, it

should be stressed that even if PCV is combined with

23-valent pneumococcal polysaccharide vaccine, no

complete protection against overwhelming pneumo-

coccal infection can be achieved. Therefore, depending

on the local pneumococcal antibiotic susceptibility,

we advocate chemoprophylaxis for children below

the age of 6 y, being more susceptible to infections

and more difficult to diagnose. As older children and

adolescents are known to show decreased medication

compliance and are able to recognize the onset of

infectious disease, stand-by antibiotics for this group

of patients are a good alternative. Amoxicillin or

penicillin in northern Europe is still the first choice;

however, as there has been a substantial increase in

penicillin- and macrolide-resistant pneumococcal

strains worldwide during the last decades, with rates

well over 50% in southern Europe, prophylaxis

should be carefully adjusted according to regional

susceptibility.

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Clinical observations 371