Medicine
October 9, 2026 · via Europe PMC
Secondary pulmonary alveolar proteinosis mimicking progression of interstitial lung disease during treatment for adult-onset still's disease: An autopsy case report.
Yamane T, Fujita T, Onoe A, Ichikawa C
AI summary — for doctors, generated from the abstract only
In a patient on immunosuppression for ILD, a steeply rising KL-6 and worsening opacities turned out to be secondary alveolar proteinosis with myelodysplasia, found only at autopsy.
What was studied
An autopsy case report of a 68-year-old woman with adult-onset Still's disease-associated interstitial lung disease whose respiratory function worsened during immunosuppressive therapy including a JAK inhibitor.
Key findings
- KL-6 climbed to 19,333 IU/L and new ground-glass opacities appeared despite control of systemic inflammation.
- Repeated bronchoscopies showed organizing pneumonia, and anti-GM-CSF antibodies were negative, so the diagnosis was missed during life.
- Autopsy confirmed secondary PAP and myelodysplastic syndrome; she died of respiratory failure.
Clinical relevance
Not all deterioration in CTD-ILD is disease progression, and escalating immunosuppression may be wrong if another process such as PAP is present.
Who should care
Limitations
A single case where the diagnosis was only retrospective, so the abstract cannot tell how often such a pattern would help earlier recognition.
When KL-6 keeps rising markedly in CTD-ILD on immunosuppression, reconsider the diagnosis (including PAP and haematological disease) before escalating therapy.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
RATIONALE
Secondary pulmonary alveolar proteinosis (sPAP) is a rare disorder caused by impaired surfactant clearance due to alveolar macrophage dysfunction and is often associated with hematologic disorders or immunosuppressive therapy. In patients with connective tissue disease-associated interstitial lung disease (CTD-ILD), worsening respiratory findings are frequently interpreted as progression of the underlying ILD, which may delay recognition of sPAP, particularly when anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies are negative. In the present case, preexisting ILD and repeated bronchoscopic findings of organizing pneumonia further obscured the development of sPAP, making the diagnosis particularly challenging.
PATIENT CONCERNS
A 68-year-old woman with adult-onset Still's disease (AOSD)-associated ILD developed progressive respiratory deterioration during immunosuppressive therapy. Despite apparent control of AOSD-related systemic inflammation, serum Krebs von den Lungen-6 (KL-6) levels increased markedly, and new diffuse ground-glass opacities appeared on chest computed tomography.
DIAGNOSES
Repeated bronchoscopic examinations demonstrated organizing pneumonia without features suggestive of PAP, supporting the interpretation of progressive CTD-ILD. However, KL-6 levels progressively increased to 19,333 IU per liter despite treatment, raising suspicion of PAP. Anti-GM-CSF antibody testing was negative, and a definitive diagnosis could not be established during life. Autopsy ultimately revealed sPAP with periodic acid-Schiff-positive intra-alveolar material and myelodysplastic syndrome (MDS). Hematologic abnormalities had initially been attributed to systemic inflammation, and subsequent bone marrow examination showed MDS-like dysplasia without establishing a definitive diagnosis of MDS.
INTERVENTIONS
The patient received escalating immunosuppressive therapies, including a Janus kinase inhibitor, under the assumption of progressive CTD-ILD, with the aim of minimizing glucocorticoid exposure.
OUTCOMES
Respiratory failure progressed despite treatment, and bronchoscopy was not feasible in the terminal stage. The patient died of respiratory failure. Postmortem examination confirmed sPAP and MDS.
LESSONS
In patients with CTD-ILD receiving immunosuppressive therapy, marked and progressive elevation of KL-6 should prompt reconsideration of the diagnosis, even when bronchoscopy does not demonstrate PAP and anti-GM-CSF antibodies are negative. Early recognition is essential to avoid inappropriate intensification of immunosuppression and further impairment of alveolar macrophage function.
DOI
10.1097/MD.0000000000051085
PMID
42854068
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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