A 73-year-old-man was admitted by a local physician with dyspnea on exertion that had begun 2 months earlier. He was diagnosed with interstitial pneumonia, thrombocythemia, hepatic cirrhosis, and diabetes. He was referred to a hematologist for the thrombocythemia. He came from Nagasaki, an area in Japan in which HTLV-1 is prevalent. The hematologist diagnosed him as an HTLV-1 carrier with myeloproliferative disorder (essential thrombocythemia). He was then referred to our pulmonary outpatient clinic for interstitial pneumonia. Fine crackles were heard at the base of the bilateral lungs. He had a family history of interstitial pneumonia, as his brother and sister had both died of interstitial pneumonia, but the etiology of those interstitial pneumonia cases was not identified. Chest X-ray showed bilateral ground-grass opacity (GGO) in both of the lower lung fields (Fig. 1). Chest CT showed bronchovascular bundle-dominant reticular shadows and GGO in the bilateral lung field (Fig. 2, 7a). His percutaneous oxygen saturation in room air was 97% with a Modified British Medical Research Council (mMRC) grade two, and the findings on the pulmonary function test and 6-minute walk test (6MWT) were normal (Table 1). There were no positive data for collagen disease (Table 1). Given that the CT findings were inconsistent with the UIP pattern, we performed video-assisted thoracoscopic surgery (VATS) to confirm a diagnosis of interstitial pneumonia. Lung tissue was obtained by VATS from three parts of the lung (right S3, right S6, and right S8) (Fig. 2). The pathological findings of right S3 and right S6 were similar, and the primary lesions were organizing pneumonia like-lesions and usual interstitial pneumonia (UIP) like-lesions. In contrast, the primary lesions of right S8 were fibrotic non-specific interstitial pneumonia (f-NSIP)-like lesions (Fig. 3, 4). Taken together, the lung specimens revealed various interstitial pneumonia patterns, including UIP like-lesions, f-NSIP-like lesions, and organizing pneumonia-like lesions that were diagnosed as unclassifiable interstitial pneumonia.
Since HTLV-1 was not detected in the plasma or lung tissue, the patient was diagnosed with IIP. Given that some of these lesions showed a UIP pattern, the patient was administered pirfenidone at 1,800 mg/day. The CT findings and the dyspnea on exertion subsequently improved (Fig. 7b); however, the KL-6 and SP-D increased slightly (Fig. 6, clinical course). Gastrointestinal symptoms and depression developed as side effects 3 months after the initiation of pirfenidone at 1,800 mg/day. We reduced the pirfenidone dose to 1,200 mg/day and continued its administration. The symptom of dyspnea on exertion, the percutaneous oxygen saturation in room air, and the findings on the pulmonary function did not progress (Table 2); however, the CT findings of bronchovascular bundle-dominant reticular shadows and GGO had deteriorated 6 months after the initiation of the pirfenidone treatment (Fig. 7c).
We performed transbronchial lung biopsy (TBLB) and bronchoalveolar lavage (BAL) to rule out the infiltration of leukemic cells or lymphocytic interstitial pneumonia. TBLB specimens and cytology of the bronchoalveolar lavage fluid (BALF) showed no leukemic cells (Fig. 5). However, in the BALF, the percentage of lymphocyte was elevated (37%) and the findings for the HTLV-1 proviral pX gene were positive (Table 2). These results suggested the exacerbation of HABA-associated interstitial pneumonitis. Previous studies have reported the effectiveness of steroids in the treatment of HABA; however, we were concerned about the deterioration of the existing diabetes. We therefore increased the dose of erythromycin, which had been administered for viscous sputum two months earlier, from 200 mg/day to 400 mg/day. The GGO, KL-6, and SP-D improved after combined therapy with pirfenidone and erythromycin (Figure 6, 7).
This combined therapy with pirfenidone at 1,200 mg/day and erythromycin at 400 mg/day has been continued in this patient for more than 2 years, with no progression of the dyspnea on exertion or abnormalities on chest CT thus far.
The chest HRCT findings. (a) Before being treated, basal and bronchovascular bundle-dominant reticular shadows and GGO were shown.