|Year : 2014 | Volume
| Issue : 2 | Page : 98-102
Clinical and radiological properties of common variable immunodeficiency patients: Case series
Ayse Aktas1, Zeynep Akcali2, Serdar Tarhan3
1 Department of Internal Medicine, Division of Allergy and Immunology, School of Medicine, Celal Bayar University, Manisa, Turkey
2 Department of Internal Medicine, School of Medicine, Celal Bayar University, Manisa, Turkey
3 Department of Radiodiagnostic, School of Medicine, Celal Bayar University, Manisa, Turkey
|Date of Web Publication||15-Sep-2014|
Department of Internal Medicine, Division of Allergy and Immunology, School of Medicine, Celal Bayar University, Manisa
Source of Support: None, Conflict of Interest: None
This study includes three cases with common variable immunodeficiency and bronchiectasis who have several respiratory symptoms and recurrent airway infections for long-term. The pulmonary function tests and findings of high-resolution computed tomography have been presented and discussed with literature.
Keywords: Bronchiectasis, common variable immunodeficiency, high-resolution computed tomography, pulmonary function tests
|How to cite this article:|
Aktas A, Akcali Z, Tarhan S. Clinical and radiological properties of common variable immunodeficiency patients: Case series. Indian J Allergy Asthma Immunol 2014;28:98-102
|How to cite this URL:|
Aktas A, Akcali Z, Tarhan S. Clinical and radiological properties of common variable immunodeficiency patients: Case series. Indian J Allergy Asthma Immunol [serial online] 2014 [cited 2020 Jan 20];28:98-102. Available from: http://www.ijaai.in/text.asp?2014/28/2/98/140790
| Introduction|| |
Common variable immunodeficiency (CVID) is the second most common primary immunologic disorder that is characterized by decreased levels of serum immunoglobulin G (IgG), IgA, and/or IgM antibody productions. In this disease, variable incidences of autoimmune diseases, splenomegaly, granulomatous infiltration, malignancies, and recurrent airway infections have been observed. ,,, Recurrent airway infections, especially pneumonia, may lead to widespread bronchiectasis. The incidence of autoimmune diseases has also increased due to T-cell and macrophage/monocyte abnormalities in these patients. , In this article, several clinical and radiological findings in respiratory systems of three cases with CVID have been presented.
| Case reports|| |
A 24-year-old male patient was admitted with the complaints of persistent cough and sputum. He had been suffering from frequent upper and lower respiratory tract infections since his childhood. He had been operated due to sinusitis and nasal polyposis 2 months ago. He was diagnosed with bronchiectasis 4 years ago. He was producing sputum between 5 and 10 cc a day, which was sometimes purulent. In addition, he had some constitutional symptoms such as fatigue, night sweats and weakness. He has recently completed a 1 week course of antibiotherapy. There was no family history of immunological disorder, autoimmune or malignant disease and social history was negative for alcohol and smoking.
Blood pressure was 110/70 mmHg, heart rate was 80 beats/min, and body temperature was normal. There was no hepatosplenomegaly or lymphadenopathy. Pulmonary examination showed bilateral crackles and inspiratory-expiratory wheezing with auscultation of back and the front side of the chest. Purified protein derivative (PPD) test was negative.
White blood cell (WBC) 10,700 cells/mm 3 with polymorphonuclear leukocytes (PMNL) 68%, lymphocytes 22.7%, monocytes 5.5%, eosinophils 2.3%, basophils 0.6% and platelet counts were in normal ranges. Serum electrolytes, liver and renal function tests were normal. Anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies and human immunodeficiency virus (HIV) antibodies were negative. Hepatitis B and C markers were also negative. Ig tests showed low IgG = 145 (700-1600 mg/dL), IgA = 23 (70-400 mg/dL), IgM = 16 (40-230 mg/dL), IgG1 = 63 (200-1150 mg/dL), IgG2 = 10 (100-550 mg/dL), IgG3 = 13 (15-120 mg/dL), IgG = 4 (0-125 mg/dL) levels [Table 1].
Flattening was detected in the gamma-band by protein electrophoresis. Thyroid function tests and thyroid autoantibodies were in normal ranges. The CD4 + and CD8 + T-cell counts were 22% (34-77), CD8 42% (17-54), respectively, with a ratio of: 0.5.
According to the spirometry findings; the forced expiratory volume 1 s (FEV 1 ) was 3.65 L (89%), the forced vital capacity (FVC) was 4.74 L (99%). The FEV 1 /FVC ratio was 77%. No obstruction was found according to FEV 1 and FVC; however, it was found according to FEV 1 /FVC ratio. The diffusion capacity of the lung for carbon monoxide (DLCO) was 24.8 mL/mmHg/min (74%) [Table 1].
The high-resolution computed tomography (HRCT) scan showed bronchial wall thickening on both lungs [Figure 1]a, parallel linear fibrotic opacities on the front of the left lung [Figure 1]b, reticulo-nodular densities, signet ring sign of bronchiectasis on the front, back and inferior lobes of both lungs [Figure 1]c.
|Figure 1: Signet ring sign of bronchiectasis (Figure 1a), bronchial wall thickening, parallel linear fibrotic opacities (Figure 1b), reticulo-nodular densities (Figure 1c)|
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A 28-year-old nonsmoker female patient was referred to our clinic for the assessment of asthma. She had persistent cough, frequent upper and lower respiratory infections since her childhood. She was producing sputum between 10 and 15 cc a day that was purulent most of the time. She had bronchiectasis, erythema nodosum, and arthralgia for 7 years. She usually had symptoms such as fatigue, flu like symptoms and joint pain. She had been using nonsteroidal anti-inflammatory agents. She had the history of surgery due to sinusitis 5 years ago and operation due to nasal polyposis 2 months ago. Social history was negative for alcohol and smoking and family history was unremarkable.
She had normal heart sounds, heart rate of 88 bpm, and blood pressure of 110/70 mmHg. Pulmonary examination demonstrated crackles and inspiratory and expiratory wheezing on both sides with auscultation from front side of the chest. There was no hepatosplenomegaly or lymphadenopathy. PPD test was negative.
Laboratory examinations showed WBC 12,250 cells/mm 3 with PMNL 83%, lymphocytes 10%, eosinophils 1%, basophils 0.1%, and platelets 333,000/mm 3 . The Ig levels were detected as: IgG = 364 (700-1600 mg/dL), IgA = 6 (70-400 mg/dL), IgM = 15 (40-230 mg/dL), IgG1 = 265 (200-1150 mg/dL), IgG2 = 46 (100-550 mg/dL), IgG3 = 29 (15-120 mg/dL), IgG4 = 6 (0-125 mg/dL) [Table 1]. Sputum culture yielded normal flora bacteria.
Flattening in the gamma-band was observed with protein electrophoresis. Hepatitis B and C markers, anti-HIV, ANA, and anti-DNA (−) were negative. Thyroid function tests and thyroid autoantibodies were within normal ranges. The CD4 + and CD8 + T-cell counts were 41.2% (34-77), CD8 24.2% (17-54), respectively, with a ratio of: 1.7.
According to the spirometry findings the FEV 1 was 2.68 L (89%), the FVC was 3.91 L (113%). The FEV 1 /FVC ratio was 69%. No sign of obstruction was detected according to the FEV 1 and FVC 1 ; however, it was found according to FEV 1 /FVC ratio. The DLCO was 14.1 mL/mmHg/min (53%) [Table 1].
The HRCT scan showed bronchiectasis, increased pneumonic infiltration and alveolar density localized on the middle lobe and lingula [Figure 2]a and b, bronchial wall thickening was also observed on both side [Figure 2]a-c.
|Figure 2: Bronchiectasis localized on the middle lobe and lingula (Figure 2 a,b), localized pneumonic infiltration and alveolar density and bronchial wall thickening (Figure 2 -a,b,c)|
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A 43-year-old nonsmoker female patient was admitted to our clinic with a persistent productive cough for several years. She had been treated unsuccessfully with antibiotics. She had the complaint of frequent upper and lower respiratory infections for 4 years. She had chronic dyspnea for approximately 4 years that have caused restriction in her ability to perform daily activities. She explained that she had bronchiectasis for 4 years, recurrent cough and sinus infections. She was producing sputum between 10 and 15 cc a day which was sometimes less, but purulent most of the time. She usually had symptoms such as cough, sputum with fever, besides fatigue. She was diagnosed with bronchiectasis by pulmonary specialist. She had a surgery history for exudative otitis media. There was no significant family history. Social history was negative for alcohol and smoking.
Blood pressure was 110/60 mmHg, heart rate was 100 beats/min. Body temperature was 37.5°C. Pulmonary examination showed bilateral cracle, especially on the front side of the chest with scattered rhonchi. There was no hepatomegaly and no splenomegaly. PPD test was negative.
Complete blood count revealed WBC 3940 cells/cm 3 with PMNL 64%, lymphocytes 22%, eosinophils 4%, basophils 1% and platelets 212,000/mm 3 . HIV screening test was negative. Ig levels were significantly reduced. The Ig levels were detected as: IgG = 356 (700-1600 mg/dL), IgA = 23.1 (70-400 mg/dL), IgM = 54.5 (40-230 mg/dL), IgG1 = 222 (200-1150 mg/dL), IgG3 = 6.23 (15-120 mg/dL), IgG = 6.9 (0-125 mg/dL). Sputum culture yielded nucleotide-binding fold. The CD4 + and CD8 + T-cell counts were 35% (34-77), CD8 38% (17-54), respectively, with a ratio of: 0.9 [Table 1].
The spirometry findings demonstrated the FEV 1 was 2.33 L (98%), the FVC was 2.97 L (107%). The FEV 1 /FVC ratio was 78%. No obstruction was found, while mild restrictive pattern was present. The DLCO was 18.2 mL/mmHg/min (79%) [Table 1].
The thorax computerized tomography scan showed bronchiectasis on the left lower lobe and pneumonic consolidation on the right lower lobe with reticulo-nodulary density [Figure 3] and [Figure 4]. The clinical and radiological properties of our patients have been presented on [Figure 1],[Figure 2],[Figure 3] and [Figure 4].
|Figure 3: Bronchiectasis on the left lower lobe (a), and reticulo-nodulary dencity (b)|
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|Figure 4: Pneumonic consolidation on the right lower lobe with reticulo-nodulary dencity|
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| Discussion|| |
We presented three patients with CVID who have bronchiectasis due to frequent respiratory infections. It has been shown that decreased serum levels of Igs in these patients and also pneumonic infiltration on HRCT has been observed as a finding of active infection in two of our patients.
Although there have been a number of investigations about the nature of CVID since it was first recognized in 1953 the cause of this disorder remains unclear.  The onset of disease can occur at any age, but mostly in the second or third decade of life.  The ages of our patients were 24, 28, and 43 at the time of diagnosis. The diagnostic delay of this disease has been seen in children and adults in both gender equally. The increased median delay in diagnosis in our patients is more than 20 years for two patients. Two patients had infections involving both the upper and lower respiratory tracts since their childhood and third patient had some constitutional and respiratory symptoms for 4 years.
Common variable immunodeficiency has been seen sporadically in the most of the patients. The effect of genetic factors presents in only 5% of the patients.  It was evaluated as sporadic because our patients had no family histories. The cause of morbidity is due to acute or chronic respiratory infections and respiratory failure as its sequence. Acute or chronic respiratory disease or malignancy may result with death as well.
It has been reported that a vast majority of patients with CVID suffered from frequent acute upper respiratory tract infections, chronic sinusitis and recurrent otitis media. ,, Our two patients had been operated due to nasal polyposis and the other one had been operated due to recurrent otitis media and all of them frequently had the symptoms of lower and upper respiratory infections. Recurrent lower respiratory infections may result with structural damage in the form of bronchiectasis and pulmonary structural damage can be seen in CVID however the reason of which is not clear. ,, Not only infections but also noninfectious pulmonary manifestations have often been visualized on HRCT.  HRCT abnormalities were present with bronchial wall thickening in all of the patients. Gharagozlou et al. showed that bronchial wall thickening was more frequent than bronchiectasis, while others have found the opposite. , Bronchial wall thickening and bronchiectasis were also detected in our patients. Thickening of the bronchial wall as a determinant of airflow obstruction has previously been reported in studies on bronchiectasis in non-CVID patients.  Bronchial wall thickening can probably be regarded as inflammatory changes extending from the large airways to the periphery, including the alveoli. As a result of bronchial wall thickening low DLCO occurs. This could explain the relationship between bronchial wall thickening and low DLCO. Airway obstruction findings was not detected in pulmonary functions tests; however, they have impaired gas diffusion. The interstitial lung involvement may lead to reduced lung volumes and gas diffusion.  Only the first patient had some interstitial findings on HRCT. Gregersen et al. showed that the occurrence of mucus plugging, air trapping and bronchial wall thickening were related to decreased FEV 1 /FVC.  The ratios of FEV 1 /FVC were slightly decreased in our patients.
Autoimmune disorders are correlated in approximately 20% of cases with CVID.  One of our patients had rheumatoid arthritis in the follow-up; although, detailed examination and evaluation demonstrated, nonspecific arthritis. The autoimmunity may be due to the lack of immunologic regulatory mechanisms or ineffective clearance of antigens; ,, and also several types of arthritis, a sarcoid-like syndrome with noncaseating granulomata, frequent incidence of herpes zoster have been seen in comparison to the general population.  However, none of these conditions were diagnosed in our patients.
IgG levels reduced by >2 standard deviations below the mean for age. In addition, it has been observed that either IgA or IgM level has been included as part of the diagnostic criteria by some authors. Peripheral B-cell numbers can be either normal or reduced.  Ricardo et al. showed that, serum IgA levels have reduced in most of patients and also reduced IgM levels have been observed in half of them.  Serum IgA, IgG, IgM levels and also the levels of IgG subgroups had been reduced in all of our patients. T-cell numbers and functions are also reduced in some patients.  PPD reflects the delayed cell mediated immunity. The (−) PPD in these patients indicate a defect in T-cell function and therefore it supports CVID diagnosis and it was (−) in our cases.
CD8 + lymphocyte counts are high in 25-30% cases. CD4 + lymphocyte counts are normal or reduced, CD4/CD8 rates can be low. There are impairments in T-cell receptors on B-cells in some of the patients.  CD4 + counts were low in our first and second patients, CD8 + counts and the ratio of CD4 + /CD8 + rates were low in all of our patients.
| Conclusion|| |
In our three adult CVID patients, we could not detect airway obstruction and ventilatory restriction except impaired gas diffusion. Early identification of CVID before the development of serious infections is of utmost important for prognosis. A good evaluation of family history and clinical presentation of the patient are important for early diagnosis of the disorder. Detailed tests for definitive diagnosis should be performed and interpreted in collaboration with a clinical immunologist. The main form of treatment in CVID patients is intravenous Ig (IVIg) replacement. It must be used at the dose of 400-800 mg/kg for every 3-4 weeks. The goals of the treatment are to decrease the incidence of infection and to prevent bronchiectasis and decreased pulmonary function. The optimal Ig, antibiotic treatments or prophylactic antibiotic doses and bronchodilator therapy should be individualized for each patient. In our patients, after starting IVIg therapy, respiratory and some constitutional symptoms had ameliorated.
| Acknowledgments|| |
We thank Prof. Seyhun Kursat, MD for help with the English version of this manuscript.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]