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Abstract
Williams-Campbell syndrome (WCS) is a rare congenital disorder characterised by the absence of cartilage in sub-segmental bronchi, leading to bronchiectasis. We report a case of a late adolescence male presenting with chronic respiratory symptoms initially misdiagnosed as asthma, later confirmed to have WCS following detailed evaluation. This case highlights the importance of considering WCS in the differential diagnosis of unexplained bronchiectasis and emphasises the role of advanced imaging techniques in its diagnosis.
- Respiratory medicine
- Lung function
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Background
Williams-Campbell syndrome (WCS) is an underdiagnosed congenital cause of bronchiectasis. It is associated with the absence of cartilage in the bronchial tree, leading to airway collapse and recurrent respiratory infections. Early and accurate diagnosis is crucial to manage and prevent disease progression, but it is often overlooked due to its rarity and the broad differential diagnosis of bronchiectasis. This case report aims to raise awareness about WCS and the diagnostic challenges associated with it.
Case presentation
A male farmer in his late adolescence, a resident of rural Bihar, India, with no known co-morbidities, was well till 6 years of age, when he started to develop a cough with whitish sputum initially, non-blood tinged, gradually progressive, and more during morning hours for about 10 years. He also complained of progressive dyspnoea, exertional in nature, not associated with cyanosis, wheezing, palpitations or chest pain. No history of fever, weight loss or loss of appetite was found. In family history, he gave a significant history of contact tuberculosis, from both his parents who were treated for pulmonary tuberculosis. Moreover, his siblings (both elder brothers) also manifested similar respiratory complaints and on examination were found to have clubbing. He also gave a history of recurrent childhood infections, which settled with intermittent usage of inhalational steroids. He gave a history of cattle exposure also (goats and cows). A birth history of childhood pneumonia after 15 days of birth was also given by the family, and he had improved after a course of antibiotics for over 2 weeks. There were no details of 2D echocardiography being done at that time.
On examination, his build was average, with no pallor, icterus, cyanosis, lymphadenopathy or oedema. He had third-degree clubbing, which was bilateral, multi-digital, painless, drumstick angulation, with a positive fluctuation test. His blood pressure was 110/70 mm Hg, respiratory rate 13/min with a regular breathing pattern, pulse rate 78/min, regularly regular. His father and elder brothers also had clubbing on examination.
On systemic examination, the chest was symmetrical, resonant on percussion with inspiratory crackles present in axillary, infra-axillary, infra-scapular and mammary areas.
Investigations
Initial labs revealed Hb-16.1 g/L, TLC- 13.66 thous/cumm and platelets- 417 thous/cumm. Renal function test revealed creatinine-0.63 mg/dl, Na/K- 142/4.29 meq/l. The liver function test was within normal limits.
Inflammatory markers including ESR were normal and CRP was 11 (positive). Since he had a history of exposure to tuberculosis, the Mantoux test and TB Quantiferon Gold were done, which were found to be negative. Sputum gram stain revealed occasional gram-negative bacilli, KOH, AFB, Mycobacterium tuberculosis Gene-Xpert and routine cultures were negative. The aspergillus antigen test was negative. Aspergillus IgG/IgM/IgE assays were negative. HIV antibody/P24 antigen, HbsAg, anti-HCV IgM were all negative.
Autoimmune and vasculitic workup revealed C anti-neutrophilic cytoplasmic antibodies (ANCA) and P ANCA were negative. Serum ACE level was 28 µg/l. RA factor was negative. His Alpha-1 antitrypsin assays were normal. The sweat chloride test for cystic fibrosis came out to be normal. Anti-neutrophilic antibodies (ANA) and ANA profile were negative.
His T-cell assay showed reduced CD4 memory cells. A 2D echo was done, which revealed type 1 diastolic dysfunction of the left ventricles with an ejection fraction of 65%.
Radiological examination in the form of a CT thorax revealed diffuse central bronchiectasis in bilateral lung fields with relative sparing of the superior segment of the right upper lobe and left upper lobe lung parenchyma with air trapping at places (figure 1). CT paranasal sinus was also done which showed evidence of nasal spur on the right side with mild mucosal thickening involving bilateral sphenoid sinuses, glio-encephalomalacic changes in the right basi-frontal region with pneumosinus dilatans of the right frontal sinus. CT’s abdomen was normal.
CT thorax showing diffuse central bronchiectasis with air trapping, sparing the superior segments of the upper lobes.
Differential diagnosis
The differential diagnosis included cystic fibrosis, primary ciliary dyskinesia, Young’s syndrome and Mounier-Kuhn syndrome. These were ruled out based on normal sweat chloride test, absence of sinusitis and situs inversus, and lack of tracheomalacia on imaging.
Treatment
During hospitalisation, the patient was treated with antibiotics (cefoperazone and sulbactam), steroids, and nebulisers. This treatment regimen led to significant improvement, and the patient was discharged in a stable condition.
Outcome and follow-up
The patient was stable at discharge and advised regular follow-up. He was educated on recognising symptoms of exacerbation and the importance of adherence to the treatment regimen. Further genetic counselling was recommended due to the familial nature of the condition.
Discussion
Broad airways, with diminishing ciliary functions to clear off secretions, make these passages nidus of infections and are the prime pathology of bronchiectasis.1 2 There could be a spectrum of causes, particularly congenital, as in our case, due to the presence of congenital clubbing and a history of recurrent infections in siblings of this individual. Congenital causes include cystic fibrosis, Young syndrome, Kartagener’s syndrome, alpha 1 antitrypsin deficiency, Mounier-Kuhn syndrome and WCS.3 Thorough workup for cystic fibrosis and alpha 1 antitrypsin deficiency had came out to be negative in this patient. No history of recurrent sinus infection or infertility ruled out Young’s and Kartagener’s syndrome. A three-dimensional CT scan revealed central bronchiectasis in this patient without any tracheomalacia as in the case of Mounier-Kuhn syndrome, which helped us to clinch the diagnosis of exclusion as WCS in this individual.
In 1960, Williams and Campbell made a breakthrough contribution to the field of pulmonology by reporting 5 cases of bronchiectasis in young children with the involvement of segmental bronchi cartilage plates.4 Pathology of the syndrome is due to the abnormality of the cartilaginous plates surrounding the bronchus. On attempting biopsies as described by Williams and Campbell, the bronchial walls tend to protrude out, even after fixation with formalin, being known as ‘flabby’.4 Evidence supporting familial or genetic aetiology can be reported in the year 1976, when two siblings were found to have respiratory discomfort immediately after birth and were found to have uniformity in cartilaginous defects on bronchogram.5 WCS is a seldom reported entity comprising reduced or absent cartilage in the bronchial wall, which makes them collapsible, leading to bronchiectasis and susceptibility to infections. Most commonly, clubbing also appears in these patients due to bronchiectasis and bouts of infective recurrences.6
In the case of a 62-year-old non-smoker female presenting with complaints of shortness of breath, productive cough and fever, she showed hyper-expansion of the lungs and bronchiectasis of the distal bronchi on CT. The pulmonary function tests showed an obstructive pattern. She was worked up extensively for cystic fibrosis and allergic broncho-pulmonary aspergillosis, but all her tests came back negative. Based on radiologic identification of bronchiectasis with sacculations, she was diagnosed as WCS and improved with antibiotics, chest physiotherapy and supportive treatments.7 Another case of middle-aged male patient presenting with respiratory distress for 5 years, on evaluation was found to have central bronchiectasis on HRCT of the chest and showed significant improvement with antibiotics and supportive care, but was referred for lung transplantation later on.8 A case report from Texas of a 31-year-old male admitted for respiratory failure and cor pulmonale in Texas who had a history of similar recurrent episodes of bronchiolitis in siblings too. This individual, along with his siblings, was misdiagnosed as a dysfunctional variant of alpha 1 antitrypsin deficiency. Later on, he was confirmed as a case of WCS by histopathology, which revealed the absence of cartilage at the air passages.9
CT scan has become an important diagnostic modality for WCS, using biphasic respiratory imaging, which showed inspiratory distension of bronchiectatic bronchi and complete collapse of these segments during the expiration phase, pointing out towards absence or reduced cartilage. Nowadays, a three-dimensional reconstruction of CT, extensively popular as virtual bronchoscopy, allows one to visualise deficient cartilage rings.10 However, patterns like central bronchiectasis on CT are suggestive of allergic aspergillosis. The upper lobe is predominantly involved in cystic fibrosis. If the lower lobe along with the central lung is bronchiectatic, one must think of primary ciliary dyskinetic disorders.11 Treatment of WCS includes prophylaxis using antibiotics, and treatment which can be used to relieve symptoms like the use of bronchodilators, and physiotherapy of the chest. Severe cases might also require a lung transplant or lobectomy.12
Patient’s perspective
When I first started experiencing breathing difficulties and a persistent cough, I thought it was just a lingering cold or maybe asthma, as the doctors initially said. I had been dealing with these symptoms for years, but they kept getting worse despite the treatments I was given. It was a relief when the doctors finally figured out what was causing my symptoms – something called Williams-Campbell syndrome, which I had never heard of before. Although it was a shock to learn that I had a rare condition, it was also a relief to have a diagnosis that made sense of everything I had been going through. I’m hopeful that with the right care and regular follow-ups, I’ll be able to live a normal life again.
Learning points
Williams-Campbell syndrome (WCS) should be included in the differential diagnosis of congenital bronchiectasis, especially in the presence of a family history.
Early diagnosis and management can significantly improve outcomes and prevent disease progression.
Advanced imaging techniques, such as CT bronchoscopy, are valuable in the diagnosis of WCS, avoiding the need for invasive procedures like lung biopsies.
Ethics statements
Patient consent for publication
Footnotes
Contributors PK has formulated the concept of manuscript. SN, VT and SS have drafted the manuscript. VT is the guarantor.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.