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Central European Journal of Immunology
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vol. 32

Lung diseases in children with primary immunodeficiency

Wiesława Karnas-Kalemba
Barbara Basiewicz-Worsztynowicz
Bożena Polańska
Aleksandra Lewandowicz-Uszyńska
Adam Jankowski

(Centr Eur J Immunol 2007; 32 (1): 1-4)
Online publish date: 2007/04/16
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Immunological disorders predispose to multiple changes in the pulmonary tissue [1, 2]. Within developing organs of children with primary immunodeficiency, susceptible to
a range of diseases, interstitial lung tissue disorder can develop [3].
Children with primary antibody deficiency suffer from recurrent rhinitis, sinusitis, tonsillitis, bronchitis and pneumonias. Frequent complications, such as bronchiectasis, interstitial lung damage, fibrosis, lymphoma are common. Most primary immunological deficiencies are detected during infancy. In severe untreatable cases a child undergo prolonged suffering followed by death. Of the total number of children with primary immunological disorder 3.1% have common variable immunodeficiency (CVID), where as 12.9% suffer with subclasses IgG deficiency and 12% with IgA deficiency [4, 5]. CVID is usually detected when a child is over 10 years old. Until recently the origin of CVID and cause of autoimmunological diseases within 20% of patients with CVID is uncertain [6].
The clinical course of lung diseases and following symptoms are non-specific. Changes in pneumonia can appear in dysfunctional lungs (restrictive changes of ventilation in pulmonary function tests, decrease in DLCO and low resting PaO2) in some cases there are no clinical symptoms. X-ray of the chest may be clear when a disease is presently active or when a child is in good state of health, lung X-rays may revealed interstitial changes [1, 7]. Computed tomography (CT) is used for final diagnosis [8] but a lung biopsy may also be necessary. In this case specimens of lung tissue are removed for further histopathological and/or immunohistochemical tests. Inflammation of the pulmonary interstitium reveal histologic features, that may in worst cases lead to alveolar structures derangement with varying degrees of fibrosis [1, 9].
The report presents the findings in our 3 patients with severe primary immunodeficiency and lung disease.

Case reports

1. The first patient, NJ, a 15-year-old girl, was admitted to our hospital in 2003. Prior to this for a 2 year period she suffered from recurrent pneumonia, spending most of that time in hospital. From infancy she suffered from recurrent respiratory and urinary tract infections. She had two incidents of autoimmune haemolytic anaemia and idiopathic thrombocytopenia between 1995 and 1998. During her physical examination bilateral crackles in the lung bases and hepatosplenomegaly were detected. Initial investigations showed leukopenia (2.5 x 109/l), thrombocytopenia (68 x 109/l), hypogammaglobulinemia with IgG (1,81 g/l) and low subclasses (IgG1, IgG2, IgG4) serum levels, undetectable IgA, low CH50 also decreased T-cell proliferation to mitogens (PHA and ConA). Further to this she was diagnosed with CVID. The viral, bacterial and fungal infections were excluded. The chest X-ray and computed tomography examination showed extensive diffuse infiltrates along with enlarged lymph nodes of the mediastinum. The surgical lung biopsy was performed. Benign lymfoproliferative disorder was diagnosed using histopathology and immunohistochemistry (figure 1). The patient was given intravenous infusions of immunoglobin (IVIG) (0,2 g/kg every three weeks) and prednison beginning with
a preliminary dose of 50 mg/day. Any side effects were observed. Abnormalities in the lungs disappeared and both in spleen and liver reduced in size. The IgG and IgA deficiencys remain. For now, she is stable continuing IVIG treatment.
2. The second patient, TK, a 14-year-old girl, had medical history of recurrent respiratory tract infections and idiopathic thrombocytopenia. Splenectomy was performed during the 9th year of her life. At the age of 14 while hospitalized for pneumonia, X-rays showed diffuse interstitial inflammation. A high-resolution computed tomography (HRCT) scan of the chest revealed the following: bilateral diffuse disseminated densities, centrilobular nodules, reticular pattern, bronchiectasies and hilar lymphodenopathy
(figure 2). A surgical lung biopsy was performed and extrinsic allergic alveolitis was recognised. She was found to have hypogammaglobulinemia and was referred to our center in 2001 for evaluation of an immunological disorder. A physical examination showed lymphadenopathy. Her white blood cell count was 23.1 x 109/l, platelets of 627 x 109/l, CRP 12.3 mg/l. Serum immunoglobulin levels at the time were low (IgG of 2,04 g/l, undetectable IgA) and her T-helper cell count was 30%. From the course of the disease and laboratory tests she was diagnosed with CVID. The viral, bacterial and fungal infections were excluded. She received IVIG (0,2 g/kg every three weeks) along with prednisone until remission. Side effect including diabetes, osteoporosis and hypertension were observed during therapy. Two years later, in 2003, we observed a relapse of the disease. HRTC scans of the lungs revealed progression of bilateral nodular infiltrates and ground glass opacity. Pulmonary function tests also showed a restrictive pattern. She was treated with azathioprine (150 mg/day) along with prednisone (beginning with a dose of 40 mg/day) and also IVIG. Currently her pulmonary function tests are normal, she is receiving immunoglobulin replacement therapy, azathioprine (50 mg/day) and her health has improved.
3. The third patient, PA, a 9-year-old boy, was suffering from recurrent respiratory tract infections. This onset occurred during the first 6 month of his life, during teething. At the age of 2 he was suffering with the following: severe suppurative, ulcerative gingivitis with inflammatory oedema, bleeding gums, sore oral cavity and weight
loss. Initial laboratory investigations showed haemoglobin 9.3 g/dl, platelets of 425 x 109/l, white blood cells
count was 8.9 x 109/l with neutrophenia (0,07 x 109/l). Laryngotracheoscopy and aesophagoscopy showed the oedema of laryngeal mucous and tracheal mucous.
We collected Actinomyces israeli from the oral cavity [5]. Laboratory results indicated the following: udetectable IgA (in serum and saliva), low concentration of serum IgG levels (2,37 g/l with low subclasses IgG1 i IgG3), decreased numbers of CD4+ (29%), CD8+ (15%) subpopulations of lymphocytes. As for now he is receiving IVIG (0,2 g/kg every three weeks). At age 7, bibasilar rales and cracles appeared during lung auscultation. In spite of the treatment auscultatory changes remained for many weeks. The viral, bacterial and fungal infections were excluded. CT was required as the X-ray failed to reveal the ongoing problem. The HRCT detected the following: ground glass attenuation, bronchial dilatation, thickening of the walls along central and peripheral airways and enlargement of left hilar lymph node (figure 3). Currently the boy is awaiting a lung biopsy. During this period he receives immunoglobulin replacement therapy.


In a number of cases, who have primary immunodeficiency, inflammatory infiltrates in lung tissue can occur [10]. The disease is usually long-lasting, with periods of exacerbation [11]. Prognosis is uncertain in both primary immunological disorder, as well as interstitial lung diseases [11, 12]. Diagnosing pulmonary changes in children often requires surgery lung biopsy [13]. This can be a life threatening procedure in children who have immunological disorder. However, using histological examination specimens of lung tissue enable appropriate diagnosis and administration of treatment, until lung disease remission.
It is important that diagnosis is given early to minimize lung damage. Therapy is concentrated towards reducing inflammatory response to prevent possible fibrosis. Administrating adequate treatment limits spread of the disease hence improving the patients’ quality of life [14, 15]. In the case of first patient, treatment was administered enabling the patient to return to normal active life. Currently the girl attends school, meets her friends and takes part in social life of her peers. Since IVIG therapy was administered, the second patient only suffers from sporadic respiratory infections. However, this treatment did not protect her from exacerbation. Although the third patient has been receiving immunoglobulin replacement therapy since the age of 2, changes in the lungs appeared at the age of 7. In both cases (patient 2 and 3) developed interstitial lung diseases, although immunoglobulin replacement had been administered throughout many years. Our findings are consistant with that of other authors about progression of pulmonary changes occuring in patients who received an adequate immunoglobulin replacement therapy [16]. Most studies indicate that prognosis improved under immunoglobulin replacement therapy, when coexists with CVID [17].
There was an inadequate reference material after thorough research into this disease. The mechanisms of pathogenesis, promote lung disorders, pathways of disease regulation, or molecular basis are all still unclear [9]. Thorough investigations and research still must to be carried out. The long-term benefits of the treatment have not been revealed. It is possible, that patients who were diagnosed with lung disorders during childhood may develop further problems in later life. The effects of applied treatment on the evolution and spread of disease in adulthood are unknown.
It is essential to use critical monitoring to determine disease activity. Reliable non-invasive clinical markers allow to detecting any early symptoms of the disease furthers development or any relapse. There is no pathognomonic laboratory criteria for the diagnosis. It would be logical for the pediatricians and pulmonologists to cooperate, share data, files new methods and results. In summary, as more patients are identified, it may be possible to understand the relationship between therapy and regression of these two uncommon diseases. Every effort to recognize the immunological defect responsible for the dual presentation of primary immunological disorder and lung diseases will prevent irreversible structural lung damage.


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Copyright: © 2007 Polish Society of Experimental and Clinical Immunology This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
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