Case report
Year :
2024 |
Month :
October
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Volume :
13 |
Issue :
4 |
Page :
PC05 - PC08 |
Full Version
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Pulmonary Alveolar Proteinosis in a Three-month-old Infant: An Unusual Case Report
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A Saranya, K Chandramouleeswari, M Dougul Regis 1. Postgraduate Student, Institute of Pathology, Madras Medical College, Chennai, Tamil Nadu, India.
2. Professor, Department of Pathology, Institute of Child Health and Hospital for Children, Madras Medial College, Chennai, Tamil Nadu, India.
3. Assistant Professor, Department of Pathology, Institute of Child Health and Hospital for Children, Madras Medial College, Chennai, Tamil Nadu, India.
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Correspondence
Address :
A Saranya, K Chandramouleeswari, M Dougul Regis, Dr. M Dougul Regis,
Assistant Professor, Department of Pathology, Institute of Child Health and Hospital for Children, Madras Medial College, Chennai-600003, Tamil Nadu, India.
E-mail: dougulregis@gmail.com
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| ABSTRACT |  | : Pulmonary Alveolar Proteinosis (PAP) is an unusual diffuse lung disease characterised by the alveolar accumulation of phospholipoprotein material, with a peak incidence in the 3rd to 4th decades of life and a male predominance. However, it has also been described in children. The recorded prevalence is 0.1 per 100,000 individuals. The major clinicopathogenetic subtypes include the autoimmune (idiopathic) form, which is associated with Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) autoantibodies, the secondary form and the congenital form (associated with surfactant gene mutations). Common presenting features include dyspnoea, cough, low-grade fever, inspiratory crackles and digital clubbing. Pulmonary function tests typically show restrictive ventilatory defects. Herein, the authors present a case of a three-month-old male infant who presented with cough, dyspnoea and failure to thrive over the past 10 days. X-rays revealed a bilateral reticular pattern with non homogeneous opacities. Computed Tomography (CT) of the chest showed features consistent with interstitial lung disease. High-resolution Computed Tomography (HRCT) demonstrated a crazy-paving appearance, suggestive of interstitial lung disease or a surfactant-related genetic disorder. Bronchial Alveolar Lavage (BAL) yielded milky fluid. Characteristic microscopic findings on lung biopsy included the filling of terminal bronchioles and alveolar spaces with deep pink granular Periodic Acid Schiff (PAS)-positive eosinophilic material, while the alveolar architecture remained preserved. Patients with minimal symptoms are managed conservatively, whereas those with hypoxaemia require a more aggressive approach. Whole Lung Lavage (WLL) is the safest and most effective form of treatment. To date, there have been 240 case reports and 410 case series documented in the literature. This is the first case of PAP reported in the study institution. The authors present this case report here due to its rarity and diagnostic significance. |
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Keywords
: Alveolar proteinosis, Respiratory failure, Therapeutic lavage |
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DOI and Others
: DOI: 10.7860/NJLM/2024/73055.2887
Date of Submission: May 23, 2024
Date of Peer Review: Jun 14, 2024
Date of Acceptance: Jul 18, 2024
Date of Publishing: Oct 01, 2024
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was informed consent obtained from the subjects involved in the study? No
• For any images presented appropriate consent has been obtained from the subjects. NA
PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: May 24, 2024
• Manual Googling: Jul 04, 2024
• iThenticate Software: Jul 17, 2024 (11%)
Etymology: Author Origin
Emendations: 6 |
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Case Report |
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A full-term male child, born via caesarean section, presented at the age of three months with cough, rapid breathing, mild fever and failure to thrive over the past 10 days. He is the firstborn male baby, delivered at 37 weeks gestation, with a birth weight of 2.5 kg. On examination, tachycardia and tachypnoea were noted, along with bilateral inspiratory stridor over the suprasternal, superior and inferior clavicular regions. These symptoms persisted despite treatment with antibiotics and he required oxygen, with an SpO2 of 89% in room air.
The chest X-ray, repeated on multiple occasions, showed hyperinflated lung fields with a bilateral reticular pattern (Table/Fig 1). The CT chest showed segmental hyperinflation with interstitial thickening, suggestive of childhood interstitial lung disease. The HRCT thorax demonstrated a crazy pavement appearance, suggestive of interstitial lung disease or a surfactant-related genetic disorder (Table/Fig 2). BAL yielded large amounts of milky white fluid, raising suspicion for PAP (Table/Fig 3). A biopsy of the lower lobe of the left lung was performed.
Microscopic Features
Cytology-BAL: The moderately cellular smear shows predominantly alveolar macrophages (75%), neutrophils (15%) and lymphocytes (10%) in a background of red blood cells and thick proteinaceous material (Table/Fig 4). The special stain PAS highlights the blotchy pink proteinaceous material (Table/Fig 5).
Lung biopsy: The section shows lung parenchyma with alveolar spaces of varying sizes filled with amorphous eosinophilic material (Table/Fig 6). Fibrosis is observed, along with a few haemosiderin-laden macrophages. The special stain PAS positive shows the amorphous eosinophilic material in the intra-alveolar spaces (Table/Fig 7). A diagnosis of PAP was made. The patient was started on antibiotics (inj. piperacillin+tazobactam). The baby was intubated, but the health condition deteriorated and the patient succumbed to death.
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Discussion |
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The PAP is extremely uncommon in the paediatric age group; only a few cases have been documented in the literature (1),(2). The disease has a polymorphic manifestation and several underlying causes, including autoimmune, acquired, idiopathic and genetic (familial) factors (3). GM-CSF autoantibodies, changes in genes encoding surfactant proteins, associations with cancers, inhalation of chemicals and infections are the pathophysiological factors of PAP (Table/Fig 8). In comparison to other literature case series, most children had a history of fever, cough, progressive dyspnoea and tachypnoea (4),(5), as well as other manifestations like weight loss, haemoptysis and chest pain (6). However, due to the non specific symptomatology and variability in disease severity, the diagnosis of PAP can often be delayed or missed by physicians (7).
Previous literature has shown that there is an average delay of 4.5 months between the onset of symptoms and the diagnosis of PAP in patients. In some cases, like the one discussed in this article, the delay can be even longer. In the present case study, there was a delay of 1.5 months between the first clinical manifestations and the provisional diagnosis. This delay can be attributed to the complex clinical course of the disease, as well as limited access to diagnostic modalities (8). In resource-limited healthcare settings like India, the diagnosis of PAP may be delayed or overlooked due to the lack of diagnostic and treatment facilities, especially in rural and marginalised areas. This can result in late or undetected cases of PAP (9).
One of the key challenges in diagnosing PAP in such settings is the scarcity of diagnostic techniques, such as Bronchoalveolar Lavage (BAL) fluid examination and genetic work-up. This scarcity can make it difficult for both physicians and pathologists to accurately identify and treat PAP patients. Additionally, the characteristic radiological appearance of PAP, which includes bilateral, symmetric and perihilar airspace consolidation in a batwing distribution, may not always be evident in resource-limited settings (10). In some cases, the radiological findings may suggest non homogeneous opacities, which have been noted in previous studies of PAP. Overall, the limited access to diagnostic tools and treatment facilities in resource-limited healthcare settings can pose significant challenges in the timely diagnosis and management of PAP. Efforts to improve access to these resources and raise awareness about the condition are crucial in addressing this issue (11).
While the most common presentation of PAP is a crazy-paving pattern in imaging studies, there have also been reported cases with interstitial and nodular patterns. Routine haematological and biochemical investigations may not always be specific in the diagnosis of PAP, but they provide clues to an underlying cause. One of the characteristic bedside findings in PAP is the presence of opaque, milky BAL fluid. The BAL fluid is often rich in foamy alveolar macrophages and acellular proteinaceous debris (12).
Microscopically, the lung biopsy shows that the hallmark of the process is the accumulation of an amorphous eosinophilic (but sometimes basophilic) PAS-positive material of predominantly phospholipid nature in the alveolar lumina, associated with a minimal infiltrate of lymphocytes, macrophages and desquamated pneumocytes. The airspace exudate is usually affiliated with only mild interstitial abnormalities, including a lymphocytic infiltrate with minimal associated fibrosis (13). In patients with underlying haematological disorders or those who are otherwise immunocompromised, alveolar proteinosis may be associated with infections such as nocardiosis, pneumocystis, histoplasmosis, cryptococcosis, aspergillosis, tuberculosis, or cytomegalovirus, making the appropriate use of special stains and other microbiologic assays mandatory in this context (14).
Whole Lung Lavage (WLL) has emerged as a convenient and effective method of treating patients with late-onset PAP in the paediatric age group. This procedure has shown promising results in managing this rare disease, providing hope and relief to patients and their families (15).
Correction of GM-CSF deficiency using exogenous GM-CSF is an alternative therapy for patients with PAP. Combining systemic treatment with GM-CSF and local treatment through whole-lung lavage has shown to enhance the effectiveness of both methods. This innovative approach is paving the way for novel therapies in the treatment of PAP, as the medical community continues to expand its understanding of this rare disease through research and literature (16).
Based on imaging, the differential diagnosis includes pulmonary oedema, Pneumocystis jirovecii pneumonia, pulmonary amyloidosis, acute silicosis, alveolar mucinosis and pulmonary haemorrhage (Table/Fig 9) (17). Published cases are tabulated in (Table/Fig 10) (2),(3),(7),(8),(9),(10),(12),(13),(18). Various differential diagnosis have been documented in the literature based on overlapping clinical and histomorphological features, making it important to rule out these conditions.
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Conclusion |
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It is essential to emphasise the importance of early and accurate diagnosis through clinical evaluation, imaging and histopathological examination. Therapeutic approaches may include WLL, immunomodulatory therapies and, in some cases, lung transplantation. Understanding the underlying genetic or environmental factors is crucial for guiding treatment and improving outcomes for paediatric patients with PAP. It is important for paediatricians and pathologists to be aware of the symptoms and diagnostic challenges associated with PAP. Early recognition and prompt diagnosis are critical for improving outcomes for patients with this condition. By understanding the potential delays in diagnosis and treatment, physicians can work towards better management of PAP and ultimately improve the quality of life for those affected by this rare condition.
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TABLES AND FIGURES |  |
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