Case ReportImages in Rheumatology

Development of Pulmonary Alveolar Proteinosis in a Patient With Adult-Onset Still Disease Treated With Tocilizumab

Yuhei Ito, Hiroki Nakahara and Ayako Nakajima
The Journal of Rheumatology February 2023, 50 (2) 288-289; DOI: https://doi.org/10.3899/jrheum.220128

We report a patient with systemic adult-onset Still disease (AOSD) who developed anti–granulocyte-macrophage colony-stimulating factor (GM-CSF)–positive pulmonary alveolar proteinosis (PAP) while using tocilizumab (TCZ), diagnosed by milky white bronchoalveolar lavage fluid (BALF; Figure 1). To our knowledge, this is the first case of PAP in AOSD.

Figure 1.
Figure 1.

Bronchoalveolar lavage findings: the recovered liquid gradually became white and turbid. F: fraction.

A 65-year-old woman with fever, typical eruption, liver dysfunction, lymphadenopathy, sore throat, and arthralgia was diagnosed with AOSD. She had no abnormalities on chest computed tomography (CT). Treatment with prednisolone (PSL; 30 mg/day) and methotrexate (MTX; 10 mg/week) resulted in remission. When PSL was tapered to 12.5 mg/day 6 months later, AOSD recurred. MTX was changed to intravenous TCZ, and AOSD successfully subsided.

Six months after the initiation of TCZ, she developed a mild cough and dyspnea on exertion. A crazy-paving pattern on chest CT (Figure 2), a milky appearance of BALF, and positive serum anti–GM-CSF antibody (115 U/mL) led to the diagnosis of PAP. TCZ was discontinued, but AOSD and PAP did not worsen.

Figure 2.
Figure 2.

Chest computed tomography showing diffuse ground-glass opacities along with thickened interlobular septa, consistent with crazy-paving appearance.

Very few cases of PAP have been reported in adult patients with other connective tissue diseases.1-3 Lung lesions, most of which are PAP, have been reported more recently in young patients with systemic juvenile idiopathic arthritis (sJIA) exposed to interleukin (IL)-1 or IL-6 inhibitors.4 Paradoxical reactions have been reported in 0.6% of patients with rheumatoid arthritis receiving TCZ in a French registry5; thus, we infer that anti-GM-CSF antibody might have developed in this adult patient with AOSD, the adult form of sJIA. Clinicians should be aware of the possible development of PAP while administering TCZ in patients with AOSD.

Footnotes

  • The authors declare no conflicts of interest relevant to this article.

    The Institutional Review Board of Mie University Hospital has deemed that an ethical review is not required for case reports. We obtained written consent to report the case described in this paper.

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