Autoimmune pulmonary alveolar proteinosis developed during treatment for systemic sclerosis: a case report

BMC Pulm Med. 2025 Jan 21;25(1):32. doi: 10.1186/s12890-025-03489-0.

Abstract

Background: Reports of autoimmune diseases coexisting with autoimmune pulmonary alveolar proteinosis (autoimmune PAP; APAP) are extremely rare. APAP coexisting with autoimmune diseases may often be misdiagnosed as connective tissue disease-associated interstitial lung disease (ILD). Here, we describe a rare case of a patient with systemic sclerosis who was diagnosed with APAP after the exacerbation of lung opacities during treatment with immunosuppressive agents.

Case presentation: A 72-year-old woman was diagnosed with systemic sclerosis (SSc) at the age of 68, and initiated treatment with prednisolone (PSL). At the age of 70, she was diagnosed with ILD associated with SSc. Despite intravenous cyclophosphamide (IVCY), no improvement was observed. A significant elevation of Krebs von den Lungen-6 (KL-6) and a crazy-paving pattern on chest computed tomography (CT) are observed. Bronchoscopy showed milky white bronchoalveolar lavage fluid (BALF) and histology of periodic acid-Schiff (PAS) stain-positive eosinophilic granular material. Serum anti granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies were measured, and the result was positive, leading to the diagnosis of APAP.

Conclusion: In patients with interstitial lung shadows who do not improve with immunosuppressive treatment, PAP is one of the differential diagnoses that should be considered. All physicians should be aware that the appropriate diagnosis of PAP and the measurement of serum anti-GM-CSF antibodies will critically affect patient outcomes.

Keywords: Anti-GM-CSF antibodies; Autoimmune diseases; Autoimmune pulmonary alveolar proteinosis; Sargramostim inhalation.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Autoimmune Diseases* / diagnosis
  • Autoimmune Diseases* / drug therapy
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoscopy
  • Cyclophosphamide / therapeutic use
  • Diagnosis, Differential
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Humans
  • Immunosuppressive Agents* / adverse effects
  • Immunosuppressive Agents* / therapeutic use
  • Lung Diseases, Interstitial / diagnosis
  • Lung Diseases, Interstitial / drug therapy
  • Lung Diseases, Interstitial / etiology
  • Prednisolone / administration & dosage
  • Prednisolone / therapeutic use
  • Pulmonary Alveolar Proteinosis* / diagnosis
  • Pulmonary Alveolar Proteinosis* / etiology
  • Scleroderma, Systemic* / complications
  • Scleroderma, Systemic* / diagnosis
  • Scleroderma, Systemic* / drug therapy
  • Tomography, X-Ray Computed*

Substances

  • Immunosuppressive Agents
  • Cyclophosphamide
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Prednisolone

Supplementary concepts

  • Pulmonary Alveolar Proteinosis, Acquired