X-linked agammaglobulinemia (XLA) is usually presented with clinical manifestations of bacterial respiratory and/or gastrointestinal infections below the age of 1 year, when the maternal IgG through placenta disappears from the circulation of the baby. Here, we describe an infant with XLA, who presented with interstitial pneumonia suggestive of Pneumocystis jiroveci (formerly Pneumocystis carinii) infection.

1 Patient report

A 3-month-old boy was admitted to Mie Hospital because of a long-standing cough, tachypnea and cyanosis. Physical examination showed a weight of 5.8 kg, temperature of 36.3°C, pulse of 170/min, respiration rate of 68/min, oxygen saturation on room air of 60%, respiratory retraction, and abnormal lung auscultation, but there was no lymphadenopathy. Chest radiology showed alveo-interstitial pneumonia (Fig. 1a), and chest computed tomography demonstrated diffuse ground-glass opacities (Fig. 1b). Laboratory tests showed a white blood count of 15,500/µl with 31.9% neutrophils and 54.4% lymphocytes, along with C-reactive protein of 0.02 mg/dl. The patient needed supplement oxygen, but did not require mechanical ventilation. He was first suspected of viral or Chlamydia pneumonia, and clarythromycin was administered but there was no improvement. Serum IgM against Chlamydia trachomatis and cytomegalovirus were negative. The patient’s serum IgG, IgA and IgM levels were 108, 0 and 15 mg/dl, respectively, and the peripheral B cells were absent, suggesting an XLA despite the lack of a family history. With parental consent, the patient was diagnosed as having XLA based on a missense mutation (Arg28His) in the Bruton’s tyrosine kinase (BTK) gene. The responses to phytohemagglutinin and concanavalin A are 56900 and 30900 cpm (control 141 cpm), respectively. Although T cell number and function were normal, he was suspected to have Pneumocystis jiroveci pneumonia. An elevated level of β-d glucan of >300 pg/ml (normal value <20) and KL-6 of 8750 U/ml (normal value, <500), suggested interstitial pneumonia caused by Pneumocystis jiroveci; however, polymerase chain reaction of sputum showed a negative result of Pneumocystis jiroveci. This may have been due to inadequate collection of sputum. He was treated with administration of sulfamethoxazole-trimethoprim (ST) and intravenous immunoglobulin (IVIG), with clinical improvement. The patient is currently well with IVIG replacement therapy and prophylactic administration of ST (Fig. 2).

Fig. 1
figure 1

Radiological findings in the patient. a Chest radiograph demonstrated bilateral perihilar opacities. b Computed tomography demonstrated diffuse ground-glass opacities in both lungs

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Fig. 2
figure 2

BTK mutational analysis. DNA sequences of the exon 2 of the BTK gene in the patient and a control are shown. Arrows indicate position 215 in which the patient demonstrates a G to A mutation, indicating an amino acid substitution of Arg28His

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2 Discussion

Interstitial pneumonia is caused by many organisms such as cytomegalovirus, adenovirus, fungus, and Pneumocystis jiroveci. An infant with interstitial pneumonia may be suspected of having an immunocompromised host with T cell deficiency, although there may have been Pneumocystis jiroveci pneumonia even in immunocompetent infants [1, 2]. XLA is a humoral immunodeficiency resulting from a block in early B cell development, and it is clinically characterized by recurrent bacterial infections [3]. Although XLA patients sometimes demonstrate enteroviral infections, they usually show a normal response to viral and fungus infections because of normal T cell functions. However, 3 XLA patients with Pneumocystis jiroveci pneumonia have been reported [4–6]. One of these three was an adult receiving immunosuppressive therapy, but 2 patients were infants as in our case. It has recently been reported that Toll-like receptor signaling is impaired in XLA [7, 8] and that may be associated with the development of Pneumocystis jiroveci infection in XLA patients. Prophylactic administration of ST as well as IVIG replacement therapy would be recommended for the treatment of XLA patients.