A 67-year-old woman with fever and cough was referred to a general hospital. A chest computed tomography (CT) scan revealed mediastinal lymphadenopathy and ground glass opacities in both lung fields. Initial blood examinations revealed a white blood cell (WBC) count of 11700/muL and an eosinophil count of 2925/muL. Cellular analysis of the bronchoalveolar lavage fluid (BALF) revealed 12.5% eosinophils. Histological findings from transbronchial lung biopsy (TBLB) specimens showed eosinophilic infiltration (5 cells/high-powered field [HPF]) (Fig. 1a). The patient was initially diagnosed with eosinophilic pneumonia, and oral prednisolone (PSL) was started at 30 mg/day. Thereafter, the ground glass opacities partially disappeared, and PSL was reduced to 10 mg/day. However, infiltrative opacities started appearing in the right middle lobe and the left lingula segment in chest CT. The patient was referred to our department for further examination.
Her medical history included steroid diabetes mellitus, surgery for extra-uterine pregnancy at the age of 30 years, and retinal detachment surgery at the age of 53. She had smoked four cigarettes a day for 20 years. She was receiving PSL 10 mg/day (prescribed for EP by the previous doctor), famotidine 20 mg/day, carbocysteine 1500 mg/day, and insulin lispro (8 U/day) for steroid diabetes mellitus. Her body temperature was 35.9  C and her oxygen saturation was 98% on room air. Fine crackles were heard in the bilateral lower lungs, without wheezing. Superficial lymph nodes and submandibular glands were not palpable. She had no obvious symptoms of dry eyes, dry mouth, eruption, or numbness in the extremities.
Laboratory data on admission were as follows: C-reactive protein (CRP), 17.8 mg/dL (normal range, < 0.30 mg/dL); WBC count of 10100/muL (eosinophil count of 0/muL); IL-6, 35.9 pg/mL (normal range, < 4.0); IgE, 237 IU/mL (normal range, < 170); IgG, 3916 mg/dL (normal range, 870-1700); IgG4, 435 mg/dL (normal range, 4.5-117); KL-6, 573 U/mL (normal range, < 500); RF, 110 IU/mL (normal range, < 15); ANA, titer 1/80; MPO-ANCA < 1.0 IU/mL; ACE 7.1 IU/L (normal range, 8.3-21.4). She had negative findings for human immunodeficiency virus antibodies and human herpesvirus 8 on polymerase chain reaction tests. Arterial blood gas analysis on room air yielded the following findings: partial pressure of oxygen, 79 mmHg; partial pressure of carbon dioxide, 36 mmHg; pH 7.47.
A chest CT scan showed swelling of the mediastinal lymph nodes, centrilobular granular nodules, ground glass opacity, thickening of the interlobular septa predominantly in the lower lung, and invasive opacity in the right middle lobe and the left lingula segment (Fig. 2). Gallium scintigraphy showed accumulation in the lower lungs, but not in the submandibular or lacrimal glands (Fig. 3). An abdominal CT scan did not show any abnormal findings in the structure of the pancreas or other abdominal organs.
MCD was suspected on the basis of clinical features such as the steroid-refractory nature of the condition, chest CT findings, polyclonal hypergammaglobulinemia, thrombocytosis (platelet count of 61.9 x 104/muL), anemia (hemoglobin, 9.1 g/dL), high IL-6 and CRP levels, and normal ANA, ACE, and MPO-ANCA levels. Bronchoscopy was therefore performed again and cellular analysis of BALF from the right B3 yielded the following findings: neutrophils, 2.0%; lymphocytes, 7.1%; eosinophils, 0.4%; macrophages, 90.6%; and CD4+/CD8+ ratio, 0.51. No pathogen was cultured and TBLB specimens showed mild alveolitis with fibrosis, and alveolar macrophage proliferation. A lower paratracheal right lymph node (#4R LN) specimen obtained by endobronchial ultrasound-guided transbronchial needle aspirate showed IgG4-positive plasma cell infiltration, with an IgG4+ to IgG+ plasma cell ratio of 12.9% (17/132 cells).
Since histological diagnosis could not be confirmed by lung and lymph node specimens, thoracoscopic surgical biopsy samples were obtained from the right S10 lung and #4R LN. In the right S10 specimen, patchy plasma cell-dominant inflammatory cell infiltration was apparent, but interstitial fibrosis or eosinophilic infiltration was not observed (Fig. 1d). In the #4R LN specimen, an atrophic germinal center and plasma cell proliferation in the follicle center were observed, but obliterative phlebitis, dense fibrosis, or eosinophilic infiltration were not apparent. IgG4+ plasma cells were observed in both the #4R LN and right S10 specimens (Fig. 1b and c), and the IgG4+/IgG+ plasma cell ratio was 36.4% (242/665 cells) in the #4R LN and 24.1% (123/510 cells) in the right S10, neither of which met the Comprehensive Diagnostic Criteria for IgG4-RD (IgG4+/IgG+ plasma cell ratio > 40%).
Taken together, we concluded that the clinical and histological findings of the patient were consistent with those of MCD. Since PSL monotherapy (at 10 mg/day) was not effective, we implemented administration of tocilizumab (8 mg/kg q2w) in addition to PSL, and the fever and cough disappeared. In the chest CT scan, the ground glass opacities in the left lower lobe and the consolidation in the left lingula segment and the right middle lobe improved partially (Fig. 4). Thereafter, tocilizumab administration was continued and the dose of PSL was successfully reduced until no further administration was required.
In chest computed tomography scans performed after 3 months of tocilizumab and prednisolone therapy, ground glass opacities in the lower lobe, on both sides, and consolidation in the left lingula segment and the right middle lobe were improved.