A case of Bruton’s disease presenting with recurrent pneumonia

doi:10.4236/crcm.2013.26091

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Vol.2, No.6, 338-340 (2013) Case Reports in Clinical Medicine

http://dx.doi.org/10.4236/crcm.2013.26091

A case of Bruton’s disease presenting with recurrent

pneumonia

Fatih Akin1*, Saltuk Bugra Boke1, Ece Selma Solak1, Cengizhan Kılıcaslan1, Sukru Arslan2

1Department of Pediatrics, Konya Education and Research Hospital, Konya, Turkey;

*Corresponding Author: drfatihakin@gmail.com

2Department of Pediatric Nephrology, Konya Ed ucation and Research Hospital, Ko nya, Turkey

Received 9 July 2013; revised 3 August 2013; accepted 10 August 2013

permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

X-linked agammaglobulinemia also known as

Bruton’s disease, is a humoral immunodeficien-

cy disease characterized by recurrent bacterial

infections due to lo w levels or absence of serum

immunoglobulins. It has been shown to be caus-

ed by mutations in the gene encoding Bruton

tyrosine kinase. Although bacterial infections

typically begins 6 - 9 months after birth when

maternal IgG is reduced below the protective

level, the diagnosis is established before 5 years

of age. Here we report a case with Bruton’s

disease and recurrent pneumonia that is typical

of the late diagnosed disease. This report sug-

gests the importance of evaluating patients w ith

recurrent infections for immunodeficiency dis-

eases.

Keywords: X-Linked Agammaglobulin emia;

Recurrent Pneumonia; Immunodeficie ncy

1. INTRODUCTION

X-linked agammaglobulinemia (XLA) also called as a

Bruton’s disease, is a humoral immunodeficiency disease

described by Bruton in 1952 [1]. It is characterized by

recurrent bacterial infections due to low levels or ab-

sence of serum immunoglobulins. It has been shown to

be caused by mutations in the gene encoding Bruton’s

tyrosine kinase (Btk). The incidence of XLA is reported

to be around 1/200,000 male births [2].

The onset of recurrent bacterial infections typically

begins 6 - 9 months after birth when maternal IgG is re-

duced below the protective level. Although th e diagnosis

of immunodeficiency is established before the age of 5

years, with a careful clinical awareness the diagnosis can

be made in the first year of the life [1].

Pneumonia is inflammation of the parenchyma of the

lungs. It is fairly common especially in d eveloping coun-

tries and is a substantial cause of childhood morbidity

and mortality. Recurrent pneumonia is usually defined as

two or more episodes of pneumonia in a year, or 3 epi-

sodes in any time period [3,4].

Here we report a case with Bruton’s disease and re-

current pneumonia that is typical of the late diagnosed

disease. This report suggests the importance of evaluat-

ing patients with recurrent infections for immunodefi-

ciency diseases.

2. CASE REPORT

A seven-year-old boy was referred with fever, cough-

ing and fatigue. He had received ampisillin-sulbactam

and clarythromycine with the diagnosis of pneumonia

and acute otitis media for three days at a lo cal hospital. It

was learned that he had previously been hospitalised for

pneumonia for five times, had bilateral otitis media

which was treatment-resistant for the last two years and

had been suffering from upper air way infection 8 - 10

times per year. The first hospitalization for pneumonia

was at the age of 15-month-old. He was the first child of

non-consanguineous parents and had a healthy three-

year-old brother and ten-month-old sister. He was born

3200 gr at term with normal delivery. There was no fam-

ily history of immundeficiencies.

On physical examination, weekness and pallor was

remarkable. His weight was under the 3rd percentile. The

body temperature was 36.8˚C. He had a blood pressure

of 100/60 mmHg and pulse rate of 98/min. Bilateral pu-

rulent otorrhea was observed on ear examination. Bilat-

eral diminished breath sounds with rales were detected

by auscultation of the lungs. There were no palpable

lymph nodes and tonsillar tissue was hypoplasic.

Laboratory tests were as follows: white blood cells,

3850/mL (neutrophils 88% and lymphocytes 12%); he-

F. Akin et al. / Case Reports in Clinical Medicine 2 (201 3) 338-340 339

moglobulin, 8 g/dL; platelets, 357 × 103/mL; sedimenta-

tion rate, 98 mm/s; CRP, 115 mg/L, serum immunog-

lobulin (Ig)G, IgA and IgM levels, 145 (normal range:

340 - 1200), 26 (30 - 230), and 29 (40 - 200) mg/dL,

respectively. Markedly reduced levels of B cells (CD 19+

cells) in the peripheral circulation (0.06%) were observed

by flow cytometric analysis. Biochemical and urine ana l y-

sis were within normal levels. Antibodies against viral

pathogens including cytomegalovirus, herpes simplex

virus, rubella, toxoplasma, parvovirus B19 and hepatitis

A, B, C viruses were negative. The results of the cu ltures

of blood, sputum, throat and urine were also negative.

His chest radiography and computed tomography find-

ings revealed bilateral infiltrations, consolidations and a

small amount of left pleural effusion (Figure 1). Sweat

testing and mutation analysis were negative for cystic

fibrosis. Echocardiographic examination for congenital

heart diseases was normal.

After admission to the hospital cefoperazone/sulbac-

tame and teicoplanin were started in travenously. The his-

tory of recurrent pneumonias requiring hospitalization

and recurrent otitis media, h ypogammaglobu lin emia with

the deficiency of CD19 B cells, absence of palpable lymph

nodes and hypoplasic tonsils suggested that our patient

had XLA. On the third day of the hospitalization intra-

venous immunoglobulin (IVIG) 2 gr/kg was given in two

days. On the fourteenth day of admission the patient was

totally recovered and discharged with a treatment sched-

ule of monthly gammaglobulin injections in dosages of

0.4 gr/kg.

3. DISCUSSION

Almost 60% of patients with XLA are diagnosed when

they develop a severe infection. The most common in-

fections seen in XLA patients include recurrent pneu-

monia, empyema, sinusitis, recurrent otitis, sepsis, re-

current meningitis or septic arthritis [1,5,6]. Although

bacterial infections typically begins 6 - 9 months after

birth when maternal IgG is reduced below the protective

level, the diagnosis of XLA is established before 5 years

of age [1]. Present case is a late diagnosed one at the ag e

of seven years old.

Recurrent pneumonia is defined as two or more epi-

Figure 1. Chest radiography and computed tomography show-

ing bilateral infiltrations and consolidations.

sodes of pneumonia in a year, or 3 or more ever [3,4].

Patients with re current pneumonia sho uld be evaluated for

underlying diseases including asthma, congenital heart

disease, gastroesophageal reflux, foreign body aspiration,

structural anomalies, cystic fibrosis and immunodefi-

ciency. Owayed et al. and Lodha et al. reported that 10%

and 15.7% of the patients with recurrent pneumonia had

an underlying disease of immunodeficiency, respectively

[3,4]. A study conducted in Turkey demonstrated that

10% of 71 cases with recurrent pneumonia had immu-

nodeficiency [7]. Chun et al. reported that 68.4% and

31.4% of 19 patients with XLA had pneumonia and acute

otitis media leading to hospitalization [5]. Our case also

had a history of recurrent pneumonia and treatment-re-

sistant otitis media suggesting the necessity of evaluating

patients with recurrent infections for immunodeficiency

diseases.

XLA is a rare genetic disorder in which the develop-

ment of B cells is arrested during differentiation. The

gene responsible for this order was identified in 1993 as

Btk [8]. Althoug h ear ly diagnosis h as be en made possible

by genetic analysis o f th e Btk, id en tifyin g mutatio n is no t

absolutely necessary for the diagnosis [5]. Wang et al.

reported that Btk gene mutation was not identified from

4 of the 16 patients with XLA [8]. The history of recur-

rent pneumonias requiring hospitalization and recurrent

otitis media, hypogammaglobulinemia with the defi-

ciency of CD19 B cells, absence of palpable lymph no des

and hypoplasic tonsils suggested the diagnosis of XLA in

our patient.

In conclusion, pneumonia is one of the most common

reasons for referral to pediatric physicians. Our case em-

phasises that patients with recurrent pneumonia should be

evaluated carefully for immunodeficiency diseases, be-

cause delay in diagnosis and treatment can result in se-

vere illness or death.

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